@article {pmid42832167, year = {2026}, author = {Cheong, KX and Wu, F and Hoang, QV and Lai, JS and Zhang, Y and Htoon, HM and Ohno-Matsui, K and Lamoureux, EL and Saw, SM and Gupta, P}, title = {Prevalence, Associations, and Visual Impact of Myopic Macular Degeneration in a Multi-ethnic Older Population in Singapore: The PIONEER Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42832167}, issn = {2193-8245}, support = {Clinician Scientist Award (NMRC-CSA-SI #JRNMRR140601 and JRNMRR197001)//National Medical Research Council/ ; }, abstract = {INTRODUCTION: This study assessed the prevalence, associations, and dietary pattern of myopic macular degeneration (MMD), and its effect on vision among older adults in Singapore.<br><br>METHODS: Community-dwelling adults aged &#x2265;&#xa0;60&#xa0;years in the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER) study underwent examinations, including spherical equivalent (SE), axial length (AL), best-corrected visual acuity (BCVA), contrast sensitivity (CS), and fundus photography. Dietary intake was assessed using a validated 110-item interviewer-administered food frequency questionnaire. Dietary patterns were generated by applying exploratory factor analysis. MMD was graded using the meta-analyses of pathologic myopia classification. Associations with MMD were evaluated using multivariable&#xa0;logistic regression, and the impact of MMD on visual outcomes using multivariable linear regression, with SE and AL modelled separately.<br><br>RESULTS: Among 1643 phakic participants (mean age 70.6&#x2009;&#xb1;&#x2009;7.6&#xa0;years), the age-standardised MMD prevalence was 5.1% (95% confidence interval [CI] 4.0-6.2%), rising from 3.1% (60-65&#xa0;years) across consecutive 5-year brackets (5.6%, 5.9%, 8.0%, 9.8%) to 13.1% (&#x2265;&#x2009;85&#xa0;years). Among high myopes aged &#x2265;&#x2009;75&#xa0;years, MMD prevalence approached 80-100%. Multivariable analyses confirmed that more myopic SE, longer AL, and older age were associated with MMD (all p&#x2009;<&#x2009;0.001). MMD was associated with worse BCVA and CS, with adjusted differences ranging from 0.05 to 0.10&#xa0;logMAR and -&#x2009;0.10 to -&#x2009;0.15&#xa0;logCS (all p&#x2009;<&#x2009;0.05). Dietary patterns were not associated with MMD.<br><br>CONCLUSION: MMD poses a substantial public health burden among older Singaporeans, presenting as a near-inevitable complication in older high myopes that drives significant visual impairment in distance acuity and contrast sensitivity. The strong structural and age associations, alongside the absence of a dietary association, highlight the need for primary prevention and structural monitoring in high-risk myopic populations.}, }
@article {pmid42832168, year = {2026}, author = {Fricker, J and Sejournet, L and Prange, J and Andre, J and Calvet, R and Rougane, V and Gouze, S and Oudard, M and Ancel, A and Kodjikian, A and Nicoara, S and Desmangles, P and Mathis, T and Kodjikian, L}, title = {Early Real-World Outcomes of Intravitreal Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration in France: A Retrospective Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42832168}, issn = {2193-8245}, abstract = {INTRODUCTION: The aim of this work is to evaluate the early real-world effectiveness, anatomical outcomes, and safety of intravitreal aflibercept 8 mg in neovascular aged-related macular degeneration (nAMD) eyes.<br><br>METHODS: This retrospective single-center study included consecutive nAMD eyes treated with at least one aflibercept 8-mg injection between January 2025 and January 2026 in France. Primary outcomes were treatment interval extension and macular drying. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central macula thickness (CMT), OCT biomarkers, and safety. Subgroup analyses were performed according to treatment status, responder profile, and prior anti-VEGF generation. In addition, baseline predictive factors associated with treatment interval extension, achievement of an interval &#x2265; 12&#xa0;weeks, and dry macular status were evaluated. A sensitivity analysis was performed in eyes with &#x2265; 6&#xa0;months of follow-up.<br><br>RESULTS: A total of 338 eyes from 267 patients were included (82 treatment-na&#xef;ve and 256 switched eyes), with a mean follow-up duration of 5.5 &#xb1; 3.3&#xa0;months. In switched eyes, the mean treatment interval increased by +1.8 &#xb1; 2.4&#xa0;weeks (p&#xa0;< 0.001), with significant gains in good responders (+&#x2009;2.7&#xa0;weeks), frequent flyers (+&#x2009;0.7&#xa0;weeks), and poor responders (+&#x2009;1.8&#xa0;weeks) (all p&#xa0;< 0.001). Dry macula rates increased from 39.6% to 70.7% (p&#xa0;< 0.001). Among treatment-na&#xef;ve eyes, 74.4% achieved a dry macula at the last visit and 97.4% at the 4-week interval following induction. In eyes with &#x2265; 6&#xa0;months of follow-up, the interval increased by +1.6&#xa0;weeks and remained significant (p&#xa0;< 0.001). OCT biomarkers significantly decreased during follow-up (p&#xa0;< 0.001), while BCVA remained stable.<br><br>CONCLUSIONS: Early real-world use of aflibercept 8&#xa0;mg was associated with improved anatomical outcomes and extended treatment intervals in treatment-na&#xef;ve and previously treated nAMD eyes, while maintaining stable BCVA and a favorable safety profile. These findings support its potential to reduce treatment burden in routine clinical practice.}, }
@article {pmid42832170, year = {2026}, author = {Osmanov, &#x130; and Hazir, B and Altay, Y and Ekici, U}, title = {Early Intraocular Pressure Changes After Laparoscopic Sleeve Gastrectomy: A Prospective Comparative Study.}, journal = {Obesity surgery}, volume = {}, number = {}, pages = {}, pmid = {42832170}, issn = {1708-0428}, abstract = {PURPOSE: Obesity is a serious health problem worldwide and is associated with several ocular conditions, including glaucoma, cataract, and age-related macular degeneration. Elevated intraocular pressure (IOP) is a well-established and modifiable risk factor for glaucomatous optic neuropathy. This study aimed to evaluate early changes in IOP following laparoscopic sleeve gastrectomy and to examine their relationship with weight loss. A secondary exploratory aim was to describe whether postoperative improvement in hypertension or diabetes mellitus was accompanied by additional changes in IOP.<br><br>METHODS: This prospective comparative study included 82 patients who underwent laparoscopic sleeve gastrectomy between 2024 and 2025 and completed the predefined 6-month follow-up, together with 82 prospectively enrolled age- and sex-comparable non-obese control participants serving as a reference cohort. The control cohort was used to contextualize IOP values in non-obese individuals and was not designed to isolate the independent effects of surgical stress, weight loss, or metabolic improvement. Ophthalmologic evaluations, including IOP measurement, were performed at baseline and at 6 months according to the study protocol, whereas systemic comorbidity outcomes were ascertained from routine clinical follow-up records at 6 months. For correlation analyses, right- and left-eye IOP values were evaluated separately, whereas mean IOP values were used for patient-level analyses. Changes in IOP were assessed before and after surgery, and correlations between changes in body mass index (BMI) and IOP were examined. Subgroup observations according to postoperative improvement in hypertension and diabetes mellitus were considered exploratory.<br><br>RESULTS: The mean age was 37.4&#x2009;&#xb1;&#x2009;9.2 years in the sleeve gastrectomy group and 39.6&#x2009;&#xb1;&#x2009;9.6 years in the control group. The surgical group included 36 men and 46 women, and the control group included 43 men and 39 women. No significant differences were observed between the groups in age or sex distribution. Six months after surgery, BMI and body weight decreased significantly (both p&#x2009;<&#x2009;0.001). Mean IOP decreased significantly after sleeve gastrectomy, with a mean change of approximately&#x2009;-&#x2009;3.0 mmHg (p&#x2009;<&#x2009;0.001). Baseline mean IOP was significantly higher in the sleeve gastrectomy group than in controls (p&#x2009;=&#x2009;0.012). At 6 months, mean IOP in the sleeve gastrectomy group had decreased to 12.8&#x2009;&#xb1;&#x2009;2.2 mmHg compared with 13.3&#x2009;&#xb1;&#x2009;3.5 mmHg in controls (p&#x2009;=&#x2009;0.038). Significant positive correlations were observed between reductions in BMI and decreases in IOP in both the right eye (r&#x2009;=&#x2009;0.545, p&#x2009;<&#x2009;0.001) and left eye (r&#x2009;=&#x2009;0.489, p&#x2009;<&#x2009;0.001). Exploratory subgroup observations suggested a greater IOP reduction in patients with postoperative improvement in hypertension, whereas improvement in diabetes mellitus did not appear to confer an additional short-term effect.<br><br>CONCLUSIONS: Laparoscopic sleeve gastrectomy was associated with a significant short-term reduction in intraocular pressure in obese patients, and greater BMI reduction was associated with greater IOP reduction. Postoperative improvement in hypertension may also be associated with a greater decrease in IOP; however, this finding should be interpreted cautiously because the subgroup observations were exploratory. Larger prospective controlled studies are needed to clarify the independent contributions of weight loss, metabolic improvement, and surgery-related factors.}, }
@article {pmid42834106, year = {2026}, author = {Scholand, LE and Sørensen, TL}, title = {Real-world durability of faricimab in treatment-naïve nAMD patients: outcomes of an observe-and-plan regimen.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42834106}, issn = {1435-702X}, abstract = {BACKGROUND: This study aimed to evaluate the long-term durability and treatment-free intervals of treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with faricimab under an observe-and-plan (O&amp;P) regimen in a real-world setting.<br><br>METHODS: This retrospective, single-center cohort study included 410 treatment-na&#xef;ve eyes with active nAMD. All eyes received an initial loading phase consisting of three monthly intravitreal injections of faricimab. At the first post-loading visit, patients were assigned to either the "pause group" or the "continue group" based on the presence of a dry macula. The primary outcomes included changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and treatment-free interval duration.<br><br>RESULTS: Post-loading, mean BCVA improved by +&#x2009;3.6 letters (p&#x2009;<&#x2009;0.001) while mean CRT decreased by 122.8&#xa0;&#x3bc;m (p&#x2009;<&#x2009;0.001). Overall, 68.5% of eyes (n&#x2009;=&#x2009;281) achieved a dry macula and transitioned to the pause group. Within this group, the median treatment-free interval was 6.0 months (mean 7.1&#x2009;&#xb1;&#x2009;4.6 months), with 18.1% of patients remaining stable for >&#x2009;52 weeks without the need for re-treatment. Baseline CRT was identified as a significant predictor of treatment extension. It was found to be significantly higher in the "continue group" than in the "pause group" (449.2&#x2009;&#xb1;&#x2009;148.9 vs. 403.8&#x2009;&#xb1;&#x2009;118.0&#xa0;&#x3bc;m; p&#x2009;<&#x2009;0.001). Age, sex, and baseline BCVA did not affect the duration of the treatment-free interval.<br><br>CONCLUSIONS: Faricimab demonstrates strong real-world efficacy, enabling immediate extension of treatment intervals under an O&amp;P regimen. Baseline CRT is an important anatomical biomarker that helps tailor treatment regimens to individuals and reduce treatment burden.}, }
@article {pmid42834336, year = {2026}, author = {Heloterä, H}, title = {Insights into the modulation of age-related macular degeneration: Molecular and systems-level perspectives.}, journal = {Acta ophthalmologica}, volume = {104 Suppl 293}, number = {Suppl 293}, pages = {S4-S35}, pmid = {42834336}, issn = {1755-3768}, support = {//Mary och Georg C. Ehrnrooths Stiftelse/ ; //Aarne Koskelon S&#xe4;&#xe4;ti&#xf6;/ ; //Suomen silm&#xe4;- ja kudospankkis&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Humans ; Disease Progression ; Tomography, Optical Coherence/methods ; Female ; Male ; Fluorescein Angiography/methods ; Aged ; *Wet Macular Degeneration/diagnosis/genetics ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; }, abstract = {In developed countries, age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population. Understanding of its pathogenesis is limited and the number of patients is predicted to continue rising. AMD is classified into two main forms: dry and neovascular AMD (dAMD and nAMD, respectively). Dry AMD is the most prevalent form (80-90%) of AMD cases and has no approved treatment in Europe. Neovascular AMD (10-20% of AMD cases) is treated with frequent intravitreal injections with medicines intervening with vascular growth, but unfortunately, treatment is not curative and only a portion of patients respond to the current treatments. Increasing number of patients will create a challenge to the healthcare system and will underline the need to find either novel, more durable treatment options or ways to intervene with the disease course already in its early stages and prevent or delay disease escalation. Thus, understanding factors behind development of the disease and treatment response is important. Currently, the information on the factors influencing the progression and incidence of the disease is fragmented and does not provide sufficient tools for individualised patient care. In this study, our aim was to create a deeper understanding of factors modulating development and progression of AMD. By analysing data from nAMD patients treated in Kuopio University Hospital, we were able to identify that heavy smoking and high BMI increase the probability for earlier emergence of nAMD, while the presence of intraretinal fluid (IRF) resulted in a fast-progressing disease. We also observed a relationship between IRF and the appearance of subretinal drusenoid deposits, HRF and retinal atrophy. Thus, we observed that IRF plays a role in the escalation of the disease towards non-reversible changes in retinal anatomy. By analysing serum RNA profile of nAMD patients, we observed that the RNA profile of nAMD patients corresponds with anatomical changes observed in the retinal fluid compartments as well as atrophic changes in retinal layers. Especially, thioredoxin-related transmembrane protein 4 (TMX4) was identified as a protein whose function during AMD development should be evaluated more in detail in the future. Moreover, long-term follow-up of women living in the North Savo region revealed the role of systemic components during AMD progression and showed that people with long-term corticosteroid and immunosuppressant use have an increased risk for developing AMD. Our results highlight that further research on how systemic components behind corticosteroid and immunosuppressant use modulate AMD progression is needed. Thus, results of this study build more evidence from factors modulating AMD development and progression. Giving guidance to future analyses in a situation where comprehensive understanding from factors influencing AMD progression and development are lacking.}, }
@article {pmid42837224, year = {2026}, author = {Debourdeau, E and Harboun, D and Gabrielle, PH and Hashimoto, Y and Chamard, C and Michon, F and Wolff, B and Torres-Villaros, H and Giocanti-Auregan, A and Gillies, M and Creuzot-Garcher, C and Daien, V}, title = {Intravitreal faricimab in patients with nAMD: French data from the Fight Retinal Blindness! Registry.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70251}, pmid = {42837224}, issn = {1755-3768}, abstract = {PURPOSE: To assess real-world outcomes of intravitreal faricimab in French patients with neovascular age-related macular degeneration (nAMD) previously treated with vascular endothelial growth factor (VEGF) inhibitors using data from the Fight Retinal Blindness! (FRB!) Registry.<br><br>METHODS: Retrospective analysis of prospectively collected FRB! Registry data (November 2023-March 2026) on eyes switched to faricimab from other VEGF inhibitors.<br><br>PRIMARY ENDPOINT: change in injection interval at 12&#x2009;months. Secondary endpoints: macular neovascularization (MNV) inactivation, visual acuity (VA), injections, switch-off, safety. Mixed-effects models assessed baseline predictors of interval change and loading-dose effect on MNV inactivation.<br><br>RESULTS: We included 222 eyes (169 patients; mean [SD] age 81.4 [7.8] years; VA 64.6 [19.3] letters; interval 5.9 [3.5] weeks; 26.2 prior injections); 143 (64.4%) were 12-month completers. Mean interval increased from 6.0 to 8.4&#x2009;weeks (p&#x2009;<&#x2009;0.001), with a greater gain in inactive (&#x394; +4.0&#x2009;weeks) than active eyes (&#x394; +1.7&#x2009;weeks; p&#x2009;=&#x2009;0.033). VA remained stable (&#x394; -0.8 letters; p&#x2009;=&#x2009;0.28). Inactive MNV rose from 36% to 60% (p&#x2009;<&#x2009;0.001); 50% of active eyes achieved inactivation. After adjustment, MNV activity at switch was the only predictor of interval reduction (vs. inactive: SRFl only, &#x3b2;&#x2009;=&#x2009;-2.8&#x2009;weeks, p&#x2009;=&#x2009;0.015; IRF/haemorrhage, &#x3b2;&#x2009;=&#x2009;-2.4&#x2009;weeks, p&#x2009;=&#x2009;0.020). A loading dose was not associated with interval extension (p&#x2009;=&#x2009;0.59) or MNV inactivation (p&#x2009;=&#x2009;0.50). Intraocular inflammation occurred in 5 eyes (2.3%).<br><br>CONCLUSION: Macular neovascularization (MNV) inactivation and modest interval extension were observed in active eyes; inactive eyes showed a larger interval extension. Loading dose was not associated with better outcomes in this observational cohort. Safety was acceptable.}, }
@article {pmid42829723, year = {2026}, author = {Gong, W and Shakarchi, FF and Cooley, A and Gad El Sayed, MZ and Abboud, I and Shakarchi, Z and Shelby, CL and Coleman Iii, WT and LoBue, SA}, title = {Epidemiology and Associated Ocular Conditions of Visual Impairment in the United States: A Decade of Data from TriNetX US Network.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {633951}, pmid = {42829723}, issn = {1177-5467}, abstract = {PURPOSE: To characterize the demographic profile, within-cohort prevalence of associated ocular conditions, and trends in the incidence and prevalence of visual impairment in the United States using a large, real-world clinical database.<br><br>METHODS: We conducted a retrospective cohort study utilizing the TriNetX US Collaborative Network. Patients with visual impairment and associated ocular conditions potentially contributing to visual impairment were identified using ICD-10 codes between January 1, 2014 and January 1, 2026. Demographic characteristics, within-cohort prevalence of associated ocular conditions, and annual incidence and prevalence within the network were analyzed.<br><br>RESULTS: A total of 805,428 patients with visual impairment were identified. The mean current age was 55.3 &#xb1; 26.0 years, with slightly more females (52.93%). Most patients were White (61.68%), followed by Black or African American (20.92%) and Hispanic or Latino (11.54%). Cataract (18.5%), glaucoma (13.9%), age-related macular degeneration (9.7%), and diabetic retinopathy (6.6%) were the most frequently observed associated ocular conditions in our cohort. Between 2014 and 2025, the annual incidence of visual impairment increased significantly from 124.56 to 212.69 per 100,000 persons (P < 0.001). Prevalence increased from 471.56 to 1433.70 per 100,000 persons (P < 0.001).<br><br>CONCLUSION: Visual impairment affected a broad demographic spectrum, with cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy being the leading associated ocular conditions. Network-based incidence and prevalence increased over the decade, reflecting both true epidemiologic trends and network expansion. These findings highlight the importance of targeted screening, early detection, and timely treatment, particularly among high-risk and underserved populations.}, }
@article {pmid42831058, year = {2026}, author = {Levitan, B and Pepio, AM and Garg, S and Tran, N and Krucien, N and Csaky, K and Aragon, M and Irony, I and Montague, A and Whitty, JA and Thomas, C}, title = {US Patients' Preferences for Geographic Atrophy Treatment.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {642703}, pmid = {42831058}, issn = {1177-5467}, abstract = {PURPOSE: Two complement inhibitors are currently used for treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and other treatments are in development. We surveyed people with GA to better understand how efficacy, risks, and intravitreal injection frequency impact their treatment preferences.<br><br>METHODS: We used a mixed-methods approach (including qualitative research, pretesting interviews, and clinical expert and patient input) to design an online preference elicitation survey accessible to people with visual impairment. Preferences of US-based adults with GA were elicited with multi-dimensional thresholding. Participants ranked the included treatment characteristics and completed four sets of trade-off exercises (with two to three questions per exercise) containing two characteristics per question. The relative importance of treatment characteristics and participants' willingness to trade-off between characteristics were evaluated.<br><br>RESULTS: Participants (N=77; mean age 69.3 years; 32.5% GA treatment-experienced) often preferred treatment over no treatment, ranging from 57% preferring treatment for the "worst" assessed treatment to 99% for the "best" assessed. Participants' decisions were most influenced by extending the time until they were unable to read (relative importance: 32%) or time to see half as far (27%), followed by injection frequency (16%) and reducing risks of developing wet AMD (14%) and eye inflammation (12%). Most participants (86%) preferred a one-time intravitreal injection (vs every other month or every month). Within an 18-month time treatment timeframe, on average, participants were willing to accept higher risks for increased efficacy (eg a 35% higher risk of eye inflammation or 29% higher risk of wet AMD for a treatment that increases efficacy from 1 to 4 years longer to read and to see half as far). All else equal, participants were willing to accept higher risks for a one-time injection over monthly injections (eg 14% higher risk of eye inflammation or 12% higher risk of wet AMD).<br><br>CONCLUSIONS: Most participants preferred the "worst" treatment profile over no treatment, highlighting a potential unmet need for GA treatment. Treatment choices were most influenced by efficacy, particularly prolonging the time until they are unable to read. Participants were willing to tolerate significantly higher risks for their preferred injection frequency. Shared treatment decision-making is encouraged to ensure alignment with patients' individual preferences.}, }
@article {pmid42826319, year = {2026}, author = {Wu, Y and Jiao, Z and Liu, Y and Zhou, Y and Li, H and Chen, X and Liu, G}, title = {Association between oxidative balance score and prevalent age-related macular degeneration in US adults: A cross-sectional NHANES 2005-2008 study.}, journal = {Medicine}, volume = {105}, number = {40}, pages = {e50973}, pmid = {42826319}, issn = {1536-5964}, support = {2021ZQNZD012//Fujian Major Research Grants for Young and Middle-aged Health Professionals/ ; X2022018-SP//Special Project of Fujian University of Traditional Chinese Medicine/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology/metabolism ; United States/epidemiology ; Cross-Sectional Studies ; Female ; Nutrition Surveys ; Prevalence ; Middle Aged ; Male ; *Oxidative Stress/physiology ; Aged ; Adult ; Life Style ; Risk Factors ; Diet ; }, abstract = {The association between oxidative balance score (OBS) and age-related macular degeneration (AMD) in US adults currently remains unknown. This research aimed to explore the specific association between OBS and AMD. OBS was acquired based on dietary and lifestyle factors, including 16 nutrients and 4 lifestyle components. Weighted logistic regressions were used to explore the associations between OBS and the prevalence of AMD. Subgroup analyses and interaction tests were conducted to understand the relationships across different populations. Furthermore, linear or nonlinear correlations were assessed by spline smoothing and threshold effect analyses. A total of 2408 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES) in the United States. This research demonstrated a negative association between OBS and AMD; an increase in OBS may reduce the AMD prevalence. Specifically, lifestyle OBS showed the most consistent inverse association with AMD. Higher lifestyle OBS was associated with lower odds of prevalent AMD, while total and dietary OBS showed directionally inverse but non-significant associations after full adjustment. This negative association varied significantly across different subgroups, with more pronounced effects observed in younger or unmarried individuals, non-Hispanic Black races, and those with diabetes or hyperlipidemia within each stratum. Specifically, it was found that this association effect of OBS with AMD was observably greater in people aged 40 to 49 years [OR = 1.05 (0.91, 1.21), P for interaction = 0.0191], unmarried people [OR = 1.38 (0.83, 2.30), P for interaction = 0.0125], non-Hispanic Black [OR = 1.16 (0.90, 1.49), P for interaction = 0.0215], patients with diabetes [OR = 1.25 (1.01, 1.56), P for interaction = 0.0228], and people without hyperlipidemia [OR = 1.67 (1.23, 2.28), P for interaction = 0.0338]. Furthermore, no statistical evidence of nonlinear association was identified using spline smoothing. There exists a possible negative association between OBS and AMD in US adults. OBS is associated with AMD prevalence.}, }
@article {pmid42827124, year = {2026}, author = {Daniele, P and Goodchild, C and Ahmed, E and Bisoukis, A and Salvatore, S}, title = {Three-year real-world outcomes of faricimab in pretreated eyes with treatment-resistant neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42827124}, issn = {1476-5454}, }
@article {pmid42828615, year = {2026}, author = {Hashiya, N and Maruko, I and Tanaka, K and Honjo, J and Miyara, Y and Watanabe, Y and Maruko, R and Nakai, A and Wakatsuki, Y and Itagaki, K and Maehira, M and Terao, N and Kataoka, K and Okada, AA and Koizumi, H and Mukai, R and Sekiryu, T and Mori, R and Iida, T and , }, title = {Correction: Six-month outcomes with a reduced two-injection induction (2+TAE) regimen of aflibercept 8 mg in treatment-naive neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10384-026-01418-0}, pmid = {42828615}, issn = {1613-2246}, }
@article {pmid42824051, year = {2026}, author = {Vidal-Oliver, L and Terheyden, J and Behning, C and Basten, V and Kornau, M and Schlößer, L and Luhmann, UFO and Moll, KP and Zakaria, N and Leal, S and Schmid, M and Valckenberg, SS and Holz, F and Finger, RP and Saßmannshausen, M and , }, title = {Cuticular Drusen and the Risk of Progression to Late Age-Related Macular Degeneration: A MACUSTAR Study Report.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101375}, pmid = {42824051}, issn = {2666-9145}, abstract = {PURPOSE: To analyze the prevalence of cuticular drusen (CD) and their relationship with other structural biomarkers in the progression to late age-related macular degeneration (AMD) within the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801).<br><br>DESIGN: Longitudinal European multicenter cohort study.<br><br>SUBJECTS: 585 study participants at a mean age of 72.1 &#xb1; 7.0 years with intermediate age-related macular degeneration (iAMD) at baseline visit.<br><br>METHODS: Using multimodal imaging, study eyes with iAMD were graded at baseline visit for CD and other AMD-associated biomarkers, including retinal pigment epithelium-drusencomplex (RPEDC) volume, reticular pseudodrusen (RPD), hyper-reflective foci (HRF), and pigmentary abnormalities (PA). We analyzed the prevalence of structural biomarkers according to CD status. Multivariable time-discrete hazard models were used to assess the association of CD alongside RPEDC volume, RPD, HRF, and PA on the progression to late-stage AMD within a 4-year follow-up period.<br><br>MAIN OUTCOME MEASURES: Hazard ratio (HR) of progression from intermediate to late-stage AMD.<br><br>RESULTS: At baseline, 15.9% of iAMD eyes (93/585 participants; age 71.0 &#xb1; 7.2 years) presented with CD, with the following phenotype distribution: type 1, 45.2%; type 2, 32.2%; and type 3, 22.6%. RPD was less prevalent in eyes with CD (11.8%) compared to eyes without (29.9%), whereas other structural biomarkers were comparably prevalent between individuals with and without CD. Progression to late AMD occurred in 6% of eyes with CD (n = 6) and 16.0% without CD (n = 78). CD alone did not significantly modify the risk of AMD progression (HR = 0.49; 95% confidence interval [CI], 0.21&#x2011;1.12; P = 0.09). However, coexisting CD and RPD showed the highest risk (HR, 5.9; 95% CI, 1.1-31.5; P < 0.04), exceeding RPD alone (HR, 3.5; 95% CI, 2.3-5.5; P < 0.0001) or RPEDC volume (HR, 1.3; 95% CI, 1.1-1.5; P = 0.01). The presence of HRF and PA on top of CD did not significantly impact the risk of progression beyond the presence of HRF or PA alone. Over time, CD showed coalescence (37.6%), resorption (19.4%), and pigmentary changes (28.0%).<br><br>CONCLUSIONS: In iAMD, CD alone does not significantly modify the risk of progression to late AMD in the absence of RPD. However, when CD and RPD coexist, the risk of progression to late AMD is increased. Further investigations, including genetic analyses, are needed to better understand the mechanisms underlying this association.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42824271, year = {2026}, author = {O Kozhevnikova, S and Nikulich, IF and Derbeneva, AS and Devyatkin, VA and Kolosova, NG and Fursova, AZ}, title = {The APOE ε2 allele is associated with risk of neovascular age-related macular degeneration in a Russian cohort.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {30}, number = {5}, pages = {824-829}, doi = {10.18699/vjgb-26-83}, pmid = {42824271}, issn = {2500-0462}, abstract = {The APOE ε2 allele is associated with risk of neovascular age-related macular degeneration in a Russian cohort.}, }
@article {pmid42824725, year = {2026}, author = {Larsen, PP and Delyfer, MN and Korobelnik, JF and Delcourt, C and Merle, BMJ}, title = {Plasma Vitamin D and Intermediate Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101364}, pmid = {42824725}, issn = {2666-9145}, abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, with limited options to prevent disease progression. Vitamin D may influence AMD pathogenesis through anti-inflammatory, antioxidative, and antiangiogenic effects. This study aims to investigate the association between deseasonalized plasma 25-hydroxyvitamin D [25(OH)D] levels and the risk of incident AMD, as well as longitudinal changes in macular layer thickness in an elderly population.<br><br>DESIGN: Population-based cohort study.<br><br>PARTICIPANTS: Seven hundred eyes from 429 participants aged &#x2265;65 years from the ALIENOR Study, followed up over 18 years.<br><br>METHODS: Baseline deseasonalized plasma 25(OH)D levels were measured and categorized as sufficient (&#x2265;50 nmol/l), insufficient (25-49 nmol/l), or deficient (<25 nmol/l). Cox proportional hazards models adjusted for demographic, lifestyle, and clinical covariates were used to estimate the risk of incident AMD. Longitudinal linear mixed-effects models assessed changes in outer retinal layer thicknesses derived from OCT imaging.<br><br>MAIN OUTCOME MEASURES: Incident intermediate and advanced AMD based on fundus color photographs and OCT.<br><br>RESULTS: The mean baseline deseasonalized plasma 25(OH)D level was 37.9 &#xb1; 14.9 nmol/l. Vitamin D deficiency (<25 nmol/l) was significantly associated with increased risk of incident intermediate AMD compared to sufficient levels (&#x2265;50 nmol/l, hazard ratio [HR] = 2.34; 95% confidence interval [CI]: 1.19-4.61; P = 0.01), while insufficiency (25-49 nmol/l) showed a borderline increased risk (HR = 1.74; 95% CI: 0.98-3.08; P = 0.06). No significant associations were observed with advanced AMD. Vitamin D-deficient participants also experienced a significant increase in retinal pigment epithelium-Bruch membrane (RPE-BM) complex thickness over time (&#x3b2; = 0.07 &#x3bc;m/year; 95% CI: 0.01-0.13; P = 0.02), while other outer retinal layers showed no significant change.<br><br>CONCLUSIONS: Low deseasonalized plasma 25(OH)D levels were associated with a higher risk of developing intermediate AMD and progressive thickening of the RPE-BM complex, a key retinal structure implicated in AMD pathogenesis. These findings support an association hypothesis and highlight vitamin D status as a candidate modifiable factor worthy of further investigation.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42825629, year = {2026}, author = {Jonas, JB and Jonas, RA and Wang, YX and Panda-Jonas, S}, title = {Association Between Extrafoveal Paravascular Retinoschisis and Central Retinal Vessel Trunk Dragging in High Myopia.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {12}, pages = {7}, doi = {10.1167/iovs.67.12.7}, pmid = {42825629}, issn = {1552-5783}, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinoschisis/epidemiology/etiology/physiopathology/diagnosis ; *Retinal Vessels/pathology/physiopathology ; Female ; Male ; Prevalence ; Aged ; Middle Aged ; Aged, 80 and over ; *Myopia, Degenerative/complications/physiopathology ; Optic Disk/pathology ; Fovea Centralis ; Cross-Sectional Studies ; Visual Acuity ; }, abstract = {PURPOSE: To assess occurrence and associations of myopic extrafoveal paravascular retinoschisis (EPR).<br><br>METHODS: Using optical coherence tomographic images of the optic disc and macula, taken in the population-based Beijing Eye Study, we assessed prevalence and associations of parapapillary retinoschisis.<br><br>RESULTS: The study included 3336 individuals (3336 eyes) with a mean age of 64.2 &#xb1; 9.6 years (range, 50-93) and a mean axial length of 23.4 &#xb1; 1.2 mm (range, 20.16-30.88). EPR prevalence (34/3336, 1.0%; 95% confidence interval [CI], 0.6-1.4) increased from 1/3046 (0.03%) to 8/173 (4.6%; 95% CI, 1-8), 4/74 (5.4%; 95% CI, 0-11), 10/25 (40%; 95% CI, 19-61), and 11/18 (61%; 95% CI, 36-86) with axial lengths of &#x2264;25.0 mm, 25.01 to 26.0 mm, 26.01 to 27.0 mm, 27.01 to 28.0 mm, and >28.0 mm, respectively. Higher EPR prevalence was associated (multivariable analysis) with higher prevalence of central retinal vessel trunk dragging (CRVTD) (odds ratio [OR] = 8.81; 95% CI, 3.02-25.7; P < 0.001) and longer axial length (OR = 2.97; 95% CI, 2.27-3.89; P < 0.001; Nagelkerke R2 = 0.55), or alternatively with longer fovea-optic disc center distance (OR = 2.79; 95% CI, 1.55-5.03; P < 0.001). In a nonlinear manner, EPR prevalence increased steeply beyond an axial length of 25.5 mm and a fovea-disc center distance of 5.5 mm. These relationships were complemented by univariate associations between EPR prevalence and temporal retinal vessel straightening, smaller angle kappa, higher myopic macular degeneration stage and prevalence, and larger parapapillary beta zone and gamma zone.<br><br>CONCLUSIONS: EPR was a common feature in eyes with severe/high axial myopia and was mainly associated with CRVTD and longer axial length or fovea-disc center distance. As a hypothesis, EPR, contrary to myopic foveoschisis, may be due to a stretching of the temporal large retinal vessels in highly myopic eyes, related to the fovea-disc distance elongation.}, }
@article {pmid42822746, year = {2026}, author = {Simmerly, CM and Islam, MA and Williamson, AP and Corbin, EA}, title = {Spatio-temporal Mechanosensitive Phagocytic Response of Retinal Pigment Epithelial Cells to Reversible Changes in Substrate Stiffness.}, journal = {Acta biomaterialia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.actbio.2026.09.053}, pmid = {42822746}, issn = {1878-7568}, abstract = {In aging and diseased retina, Bruch's membrane (BrM) stiffens heterogeneously, impairing phagocytic clearance of photoreceptor outer segments by the overlying retinal pigment epithelial (RPE) monolayer and contributing to retinal degeneration. While substrate stiffness is known to influence RPE phagocytosis, conventional assays lack the spatial resolution to capture how mechanical cues coordinate behavior across the monolayer over time. Here, dynamic magnetorheological elastomer (MRE) substrates are combined with an automated machine-learning image-analysis pipeline to simultaneously quantify particle engagement kinetics, cell morphology, and spatial organization at single-cell resolution. This combination enables spatiotemporal observation of RPE mechanosensitivity inaccessible to population-level assays. Substrate stiffness shaped particle engagement kinetics, modulating engagement rate and maximum particle capacity. Soft substrates additionally increased cell area and eccentricity, suggesting stiffness-dependent cytoskeletal remodeling. Strikingly, cells with increased levels of particle engagement form spatially localized clusters whose organization was sensitive to substrate stiffness, revealing that mechanical cues coordinate engagement behavior at the tissue level rather than acting on cells independently. This work reveals how dynamic BrM stiffening drives coupled changes in particle engagement kinetics, cell morphology, and spatial coordination, highlighting the tissue-level complexity of RPE mechanosensitivity. Together, these findings reframe RPE particle engagement as a spatially coordinated, mechanosensitive process, providing new insight into how dynamic alterations in extracellular mechanical environments regulate cellular function. STATEMENT OF SIGNIFICANCE: The retinal pigment epithelium (RPE) clears cellular debris daily to maintain vision, a process that falters as the underlying tissue stiffens with age, a hallmark of macular degeneration. Existing tools capture only population averages on static surfaces, obscuring both the timing and spatial organization of the response. This study combines dynamically tunable substrates with automated machine-learning image analysis to quantify receptor-mediated particle engagement at single-cell resolution across time and space. Mechanical transitions, not stiffness magnitude alone, accelerate engagement rate while reducing total capacity. Cell shape predicts particle engagement activity in a stiffness-dependent manner, and highly active cells cluster spatially in patterns governed by the mechanical environment. These findings reframe RPE dysfunction as a spatially coordinated, mechanosensitive process with direct implications for early AMD.}, }
@article {pmid42818647, year = {2026}, author = {Jensen, RD and Mullin, NK and Mulfaul, K and Miller, JEB and Navratil, E and Voigt, AP and Scheetz, T and Wiley, LA and Stone, E and Tucker, B and Mullins, R}, title = {Transcriptomic Characterization of Terminal Complement Complex-bound Cells in Human Choroid Using Single-Cell RNA Sequencing.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.09.05.749603}, pmid = {42818647}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD) is among the leading causes of blindness worldwide. Early AMD is characterized by dysfunction in the choroid, including early dropout of endothelial cells and increased deposition of the complement cascade's membrane attack complex (MAC) in the choriocapillaris. In this study, we used a single-cell RNA sequencing-based approach with barcoded antibodies to measure abundance of the MAC and other surface proteins at single cell resolution on RPE/choroid samples from four aged human donor eyes. We included antibodies to detect the MAC, CD34, CD45, and complement regulators CD55 and CD59, in addition to control antibodies. Our analysis of these data revealed cell clusters with expected gene expression profiles and antibody-based detection of CD34 and CD45 congruent with transcriptome-based cell identity. We also detected surface complement regulators CD55 and CD59 across a wide variety of cell types. Across endothelial cells, surface CD55 and CD59 appeared more abundant on venous clusters, and abundance of each was correlated with expression of a third complement regulator, clusterin (CLU). The MAC was detected on a variety of cell types, but was most abundant on the surface of cells in the macrophage family, smooth muscle cells, and pericytes. We confirmed these findings by identifying MAC deposition on choriocapillaris pericytes using immunohistochemistry for MAC, endothelial, and pericyte markers. Ultimately, these data showcase a valuable new approach to analyze gene expression and surface complement in human donor eyes, and provide novel insight into patterns of MAC deposition and complement protection in the aging human choroid.}, }
@article {pmid42819474, year = {2026}, author = {Zhao, X and Cheng, T and Zhang, W and Gu, X and Zhao, Q and Chen, Y and Meng, L and Zhang, J and Qiu, B and Li, L and Cheng, S and Wang, Z and Wang, C and Wang, Y and Yang, Z and Shi, Z and Guo, Y and Liu, S and Chen, Y}, title = {Dissecting the angiogenic mechanism of pachychoroid polypoidal choroidal vasculopathy.}, journal = {iMeta}, volume = {}, number = {}, pages = {e70176}, pmid = {42819474}, issn = {2770-596X}, abstract = {Polypoidal choroidal vasculopathy (PCV) is a distinct variant of neovascular age-related macular degeneration (AMD) and a major cause of vision loss in older adults, yet its pathogenesis remains poorly understood. Pachychoroid PCV is a subtype characterized by poor treatment response, minimal typical AMD features, and dilated choroidal vessels. Using a multicenter PCV cohort, we conducted plasma multi-omics analyses and identified enrichment of fluid shear stress and atherosclerosis (FSS-AS) signaling pathways in this subtype. The pachychoroid phenotype, together with FSS-AS enrichment, implicated altered choroidal hemodynamics in its pathogenesis. By inducing choroidal circulatory hypertension (CCH) in mice, we recapitulated, for the first time, the hallmark ocular lesions of pachychoroid PCV. Single-cell sequencing identified the cellular origin of these angiogenic lesions and implicated endothelin-1 (EDN1) as a key effector. Alleviating choroidal hypertension, reducing EDN1 expression, or pharmacologically blocking the endothelin receptor A (EDNRA, the receptor for EDN1), prevented lesion formation. In vitro, disturbed fluid shear stress upregulated EDN1 in choroidal endothelial cells and promoted pathological remodeling and angiogenesis through EDNRA. Collectively, our findings define a pathogenic cascade wherein CCH induces abnormal hemodynamics (disrupted fluid shear stress) and drives angiogenesis via the EDN1/EDNRA axis, offering mechanistic insight and identifying a potential therapeutic target for pachychoroid PCV.}, }
@article {pmid42815670, year = {2026}, author = {Schulz, A and Al-Nawaiseh, S and Wakili, P and Krötz, C and Germann, A and Farese, G and Burri, C and von Briesen, H and Claaßen, C and Schmidt, S and Weber, A and Southan, A and Borchers, K and Szurman, P and Stanzel, BV}, title = {Subretinal integration of a vascular endothelial growth factor slow-release gelatin functionalized cell carrier for retinal pigment epithelium cell therapy.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {154685}, doi = {10.1016/j.ijbiomac.2026.154685}, pmid = {42815670}, issn = {1879-0003}, abstract = {PURPOSE: Replacement of retinal pigment epithelium (RPE) with a cell-based therapeutic represents a potential treatment strategy for age-related macular degeneration (AMD). To improve subretinal integration via angiogenesis, RPE cell carrier transplants were equipped with gelatin for vascular endothelial growth factor (VEGF) release after implantation.<br><br>METHODS: Gelatin coatings were applied to the basal side of polyethylene terephthalate (PET) membranes using doctor blading, dip coating, or pipetting to optimize film thickness and reproducibility. Human fetal RPE (hfRPE) cells were cultured on treated PET and monitored for morphology, pigmentation, transepithelial resistance, polarization, and expression of RPE-relevant proteins by immunofluorescence. PET/gelatin loaded w/or w/o VEGF, or PET/gelatin/VEGF carriers with hfRPE were subretinally implanted for 6&#x202f;weeks into pigmented rabbits onto RPE wounds. Subretinal integration was assessed using optical coherence tomography (OCT), fluorescein angiography (FA), indocyanine green angiography (ICGA), and histological and immunofluorescence staining.<br><br>RESULTS: Reproducible gelatin films were formed by pipetting a defined volume of solution, depending on concentration and gelatin type. In vitro, gelatin coating promoted hfRPE cell growth, monolayer formation, pigmentation, and tight junction development. Polarized secretion of VEGF and pigment epithelium-derived factor (PEDF) was maintained and bestrophin, ezrin and RPE65 showed a qualitatively more homogeneous distribution in gelatin treated hfRPE cells compared to controls. Six weeks after implantation, the hfRPE layer appeared largely intact as judged by a double layered OCT hyperreflectivity, and vascular channel-like structures were observed in the subimplant space.<br><br>CONCLUSIONS: Integration of RPE grafts into the subretinal space is promoted by PET carriers coated with VEGF-loaded gelatin.}, }
@article {pmid42815674, year = {2026}, author = {Li, D and Hu, S and Wu, M}, title = {Comment on "Cost-Effectiveness of Photobiomodulation for Intermediate Dry Age-Related Macular Degeneration: A Model-Based Analysis Using the LIGHTSITE III 24-Month Trial".}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.08.051}, pmid = {42815674}, issn = {1879-1891}, }
@article {pmid42815678, year = {2026}, author = {Tian, M and Bu, W and Cheng, X and Shen, Z and Fei, Y and Jiang, L and Sun, M and Wang, Z and Xiao, J and Cheng, D and Zhao, X}, title = {Integrating epidemiology and mechanistic studies links PFAS exposure to ocular diseases and implicates PFOS-associated glaucoma risk through the PI3K/Akt-MMP3 axis.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {218}, number = {}, pages = {116416}, doi = {10.1016/j.fct.2026.116416}, pmid = {42815678}, issn = {1873-6351}, abstract = {Perfluoroalkyl substances (PFAS) pose health risks, but their association with glaucoma, cataracts, and age-related macular degeneration remains uncertain. First, a cross-sectional analysis of NHANES (2005-2008) was performed using multiple logistic regression and mixture models, including weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR), to examine single and mixed PFAS exposures in relation to ocular diseases. Second, Mendelian randomization was applied to further explore the PFOS-glaucoma association. Third, network toxicology and in vitro experiments were employed to generate mechanistic hypotheses. Cross-sectional results suggested positive associations between PFOS and glaucoma, and between PFNA and cataracts. Sex-stratified analyses revealed positive associations of PFOS with glaucoma in females, and in males, of PFDA with glaucoma and PFNA with cataracts. Mixture models suggested that PFOS may be a driving factor for glaucoma risk. Sensitivity analyses yielded results generally consistent with the primary findings. Mendelian randomization supported a positive PFOS-glaucoma association. Network toxicology and in vitro experiments indicated that PFOS activates PI3K/Akt signaling and reduces MMP3 expression. LY294002 treatment partly restored MMP3 expression, supporting a role for PI3K/Akt signaling in this response. These results suggest that the PI3K/Akt-MMP3 axis may be involved in PFOS-induced extracellular matrix changes in trabecular meshwork cells.}, }
@article {pmid42818173, year = {2026}, author = {Pandey, NB and Mirando, AC and Almeida, DRP and Dang, S and Lally, DR and Bridges, WZ and Campochiaro, PA and Popel, AS and Green, JJ}, title = {A Single Suprachoroidal Injection of AXT107 (Gersizangitide), a Multimodal, Long-Acting Integrin-Disrupting Peptide, in Patients with Neovascular Age-Related Macular Degeneration: Results of the Phase 1/2a DISCOVER Trial.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.09.19.26363031}, pmid = {42818173}, abstract = {PURPOSE: To evaluate the safety, tolerability, and preliminary bioactivity of a single suprachoroidal injection of AXT107 (Gersizangitide), a multimodal integrin-disrupting peptide that acts on both the VEGFA pathway and angiopoietin-Tie2 pathway, in eyes with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Phase 1/2a, open-label, dose-escalation clinical trial.<br><br>PARTICIPANTS: Fifteen subjects with active nAMD, including 11 treatment-experienced partial responders to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and 4 treatment-na&#xef;ve subjects; 14 eyes met the protocol-specified baseline imaging criterion and were included in efficacy analyses.<br><br>METHODS: Study eyes received a single suprachoroidal injection of AXT107 microparticles at doses of 0.125, 0.25, or 0.5 mg and were followed for 40 weeks. Protocol-specified rescue intravitreal anti-VEGF treatment was permitted from week 12 based on protocol-specified best-corrected visual acuity (BCVA) or central subfield thickness (CST) criteria; anti-VEGF treatment before Week 12 was investigator-initiated. Primary outcomes were ocular and systemic safety through week 40; secondary outcomes included change in CST, change in BCVA, and time to first protocol-specified rescue injection.<br><br>MAIN OUTCOME MEASURES: Incidence of ocular and systemic adverse events, intraocular pressure (IOP), CST, BCVA, and time to first protocol-specified rescue injection.<br><br>RESULTS: Twenty subjects were screened and 15 enrolled across 4 U.S. sites; 3 eyes received 0.125 mg, 3 received 0.25 mg, and 9 received 0.5 mg of AXT107. No serious adverse events related to AXT107 occurred, and no cases of endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or clinically significant intraocular inflammation were observed through week 40. No clinically meaningful intraocular pressure (IOP) elevations occurred at any dose, and no subject required chronic IOP-lowering therapy. Among the 14 eligible eyes included in efficacy analyses, 2 treatment-experienced eyes, Eyes 08 and 09, completed 40 weeks without protocol-specified anti-VEGF rescue, and 1 treatment-experienced eye, Eye 10, first received protocol-specified rescue at Week 36. At the last on-treatment visit, BCVA changes ranged from +15 to -31 ETDRS letters; 3 eyes gained &#x2265;5 letters, 3 gained &#x2265;10 letters, and 1 gained &#x2265;15 letters. Among the 14 eligible eyes, anatomical improvements in CST were observed in at least 1 eye in each dose cohort. The most durable responses were seen in treatment-experienced eyes receiving 0.5 mg (median durability of 36 weeks), whereas treatment-na&#xef;ve 0.5-mg eyes showed more variable courses and generally earlier protocol-specified rescue in this small cohort.<br><br>CONCLUSIONS: In this first-in-human study, a single suprachoroidal injection of AXT107 up to 0.5 mg was well tolerated through Week 40, with no drug-related serious adverse events, no clinically significant intraocular inflammation, and no sustained IOP elevations. After a single suprachoroidal AXT107 injection, 2 eyes completed 40 weeks without protocol-specified rescue anti-VEGF treatment, and 1 additional eye received its first protocol-specified rescue treatment at Week 36. The exploratory observation that durability appeared greatest in treatment-experienced eyes supports further controlled study of AXT107, particularly in treatment-experienced nAMD populations.}, }
@article {pmid42818498, year = {2026}, author = {Cui, B and Bex, P}, title = {Central Vision Loss Alters Internal Emotion Representations: Evidence from a Generative Genetic Algorithm Paradigm.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.10.23.683781}, pmid = {42818498}, issn = {2692-8205}, abstract = {Central vision loss (CVL) from age-related macular degeneration (AMD) profoundly impacts daily life. While much research focuses on visual discrimination and reading, understanding how CVL affects emotional perception remains unexplored. We adapted the genetic-algorithm face paradigm introduced by Carlisi et al. (2021) and extended by Binetti et al. (2022), combining it with a three-dimensional morphable face model, to investigate how healthy young, healthy older, and CVL-affected individuals internally represent facial emotions. Participants evolved faces they perceived to best express 13 distinct emotions (or 4 for the older healthy group). Using a three-cohort design, we separated age effects from CVL-specific effects. Results revealed four significant group differences: Awe Convergence (H = 10.97, p = 0.001), Shame Intensity (H = 10.04, p = 0.005), Interest Range (H = 6.35, p = 0.016), and Interest Stability (H = 4.86, p = 0.026). Additionally, cosine similarity analysis in 199-dimensional face space showed cohorts use fundamentally different facial feature configurations (mean cosine ≈0.006 for YNG vs CVL), suggesting CVL may reorganize emotion representations rather than simply scaling them. These preliminary findings raise questions about whether all emotions require uniform amplification in CVL and point toward the potential value of selective rehabilitation over broad caricaturing approaches.}, }
@article {pmid42810674, year = {2026}, author = {Berni, A and Rosenfeld, PJ and Bacherini, D and Chakravarthy, U and Chaudary, V and Reibaldi, M and Shen, M and Ting, DSW and Trivizki, O and Viggiano, P and Zur, D and Sadda, S and Borrelli, E}, title = {From Intermediate AMD to Geographic Atrophy: Biomarkers, Endpoints, and a Roadmap for Next-Generation Clinical Trials.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101532}, doi = {10.1016/j.preteyeres.2026.101532}, pmid = {42810674}, issn = {1873-1635}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible legal blindness worldwide. Treatments exist for late-stage AMD, but none exists for the intermediate stage (iAMD), which precedes significant vision loss. A therapy tested in iAMD would aim to prevent or slow progression to late-stage disease, meaning geographic atrophy or exudative neovascular AMD. The difficulty is that iAMD can persist for five years or longer before it progresses, whereas a trial must reach an answer within approximately two years. Such a trial therefore has to do two things at once: enroll the eyes most likely to progress within that window, and measure an endpoint that moves when progression slows. This review identifies the enrichment and endpoint criteria that make this possible. An enrichment biomarker must predict progression, be reproducibly measured, and be deployable across sites within two years. Optical coherence tomography (OCT) is the best instrument for this purpose because it is well tolerated, quantitative, and already available wherever iAMD trials are run. A single OCT acquisition can measure drusen area and volume, photoreceptor band integrity, hyperreflective foci, calcified drusen, and reticular pseudodrusen. For the endpoint, the onset and growth of large hypertransmission defects and the progressive loss of the outer retinal bands provide continuous structural measures that can be paired with microperimetry to capture function. Drawing on natural history data to model progression and statistical power, we propose a configurable trial design in which OCT both enriches for high-risk eyes and supplies the endpoint.}, }
@article {pmid42810675, year = {2026}, author = {Jin, K and Zhao, K and Agrawal, R and Ying, GS and Grzybowski, A}, title = {Artificial intelligence for clinical decision-making in retinal disorders: From screening and diagnosis to treatment and longitudinal management.}, journal = {Progress in retinal and eye research}, volume = {115}, number = {}, pages = {101533}, doi = {10.1016/j.preteyeres.2026.101533}, pmid = {42810675}, issn = {1873-1635}, abstract = {Artificial intelligence (AI) in retinal imaging has expanded from image classification to multimodal interpretation, longitudinal prediction, and clinically oriented decision support. This narrative review focuses on four complementary clinical settings: diabetic retinopathy (DR) screening and referral, diabetic macular edema (DME) treatment assessment, neovascular age-related macular degeneration (nAMD) retreatment and longitudinal monitoring, and inherited retinal disease (IRD) diagnosis, genotype-phenotype support, progression modeling, and trial enrichment. We organize the evidence around disease-specific decision points, relevant data modalities, and the requirements for multimodal and longitudinal integration. Evidence is strongest for DR screening, supported by prospective and real-world validation, whereas treatment-oriented applications in DME and nAMD and multimodal diagnostic or prognostic applications in IRDs remain less consistently validated. We highlight the gap between model performance and clinical utility and propose a cautious translational roadmap emphasizing external validation, calibration, uncertainty handling, workflow integration, prospective evaluation, and accountable deployment.}, }
@article {pmid42812627, year = {2026}, author = {Achuck, K and Soares, R and Solish, D and Popovic, M and Felfeli, T and Muni, R and Shah, C and Baskin, D and Hsu, J and Garg, S}, title = {Effect of Topical Bromfenac 0.09% on Pain Following Intravitreal Antivascular Endothelial Growth Factor Injections.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261464998}, pmid = {42812627}, issn = {2474-1272}, abstract = {PURPOSE: To evaluate the effect of topical bromfenac 0.09% on pain following intravitreal (IVT) injection of antivascular endothelial growth factor (anti-VEGF) medications in patients diagnosed as having choroidal neovascularization secondary to age-related macular degeneration or other etiologies, diabetic macular edema, diabetic retinopathy, or macular edema associated with retinal vein occlusion.<br><br>METHODS: A total of 78 adult patients scheduled to receive bilateral anti-VEGF IVT injections were randomized to receive topical bromfenac 0.09% in 1 eye and artificial tears in the fellow eye (control) immediately before the anti-VEGF treatment at 2 academic institutions from March 2021 to June 2022. Pain was evaluated using the Wong-Baker FACES Pain Rating Scale (score range, 0-10) and the Short-Form McGill Pain Questionnaire (score range, 0-5) at baseline (preinjection) and 5 minutes, 6 hours, and 24 hours following injection. Wilcoxon signed-rank sum test was used for statistical comparisons.<br><br>RESULTS: In total, 156 eyes were analyzed. Mean baseline pain scores were similar between the bromfenac 0.09% and control groups. Five minutes after injection, eyes randomized to receive bromfenac 0.09% had significantly less pain compared with control eyes receiving artificial tears, on both the Wong-Baker FACES scale (mean raw score, 2.29 vs 2.79; P = .0275) and the McGill Pain Questionnaire (mean raw score, 1.13 vs 2.36; P = .0135). No significant difference in pain scores was noted at 6 hours or 24 hours post-IVT injection.<br><br>CONCLUSIONS: Bromfenac 0.09% solution administered to the study eye before IVT anti-VEGF injection reduced pain 5 minutes after injection in comparison with artificial tears. There was no difference in pain between the 2 groups at 6 hours or 24 hours post-IVT injection.}, }
@article {pmid42814127, year = {2026}, author = {Scrivens, B and Daniele, P and Papazacharia, A and Donia, A and Bailey, C and Maghsoudlou, P and Salvatore, S}, title = {Eighteen-month real-world outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration: a UK single-centre experience.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42814127}, issn = {1435-702X}, abstract = {PURPOSE: Intravitreal aflibercept 8 mg was developed to extend treatment intervals and reduce injection burden in neovascular age-related macular degeneration (nAMD). We evaluated visual, anatomical, and durability outcomes over 18 months in routine clinical practice.<br><br>METHODS: This retrospective observational study included 102 eyes of 95 treatment-na&#xef;ve nAMD patients commencing aflibercept 8&#xa0;mg at a UK tertiary centre. All eyes received three loading injections followed by a treat-and-extend protocol. Best-recorded visual acuity (BRVA), central subfield thickness (CST), intraretinal fluid (IRF), subretinal fluid (SRF), and macular haemorrhage were assessed at baseline, post-loading, 12 months, and 18 months. Linear and generalised mixed-effects models were applied.<br><br>RESULTS: Mean patient age was 81.1&#x2009;&#xb1;&#x2009;6.5 years; 68.4% were female. Mean BRVA was 62.5&#x2009;&#xb1;&#x2009;12.4 letters at baseline, 67.5&#x2009;&#xb1;&#x2009;13.7 post-loading, 66.8&#x2009;&#xb1;&#x2009;15.3 at 12 months (n&#x2009;=&#x2009;102), and 65.5&#x2009;&#xb1;&#x2009;18.5 letters at 18 months (n&#x2009;=&#x2009;73). Mean CST was 317.1&#x2009;&#xb1;&#x2009;95.4&#xa0;&#x3bc;m at baseline, 237.9&#x2009;&#xb1;&#x2009;45.2&#xa0;&#x3bc;m post-loading, 236.3&#x2009;&#xb1;&#x2009;51.7&#xa0;&#x3bc;m at 12 months, and 220.6&#x2009;&#xb1;&#x2009;32.2&#xa0;&#x3bc;m at 18 months (n&#x2009;=&#x2009;73). At 12 months, 51.9% of eyes achieved treatment intervals of &#x2265;&#x2009;12 weeks, increasing to 73.9% at 18 months. No cases of endophthalmitis were recorded.<br><br>CONCLUSION: Aflibercept 8&#xa0;mg achieved sustained visual acuity, significant anatomical improvement, and progressively extended treatment intervals over 18 months in treatment-na&#xef;ve nAMD within routine clinical practice, supporting its effectiveness in reducing treatment burden without compromising disease control.}, }
@article {pmid42814727, year = {2026}, author = {Ghadimi, M and Begum, H and Zeraatkar, D and Ma, J and Sivaprasad, S and Borrelli, E and Kaiser, P and Steel, DH and Wong, TY and Guymer, R and Wykoff, CC and Chaudhary, V}, title = {OphthoEvidence Report: Comparative effects of treatments for geographic atrophy secondary to age-related macular degeneration: A protocol for a living systematic review and network meta-analysis.}, journal = {PloS one}, volume = {21}, number = {9}, pages = {e0358699}, pmid = {42814727}, issn = {1932-6203}, mesh = {Humans ; *Geographic Atrophy/therapy/etiology ; *Macular Degeneration/complications ; Network Meta-Analysis as Topic ; Quality of Life ; Systematic Reviews as Topic ; Visual Acuity ; }, abstract = {BACKGROUND: Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), leads to legal blindness in approximately 16% of affected individuals within 6 years. Numerous trials have evaluated interventions to slow GA progression, and many studies are ongoing. However, the comparative benefits and harms of treatments within this rapidly evolving therapeutic landscape have not yet been systematically synthesized.<br><br>OBJECTIVES: To present a protocol for a living systematic review and network meta-analysis (NMA) addressing the effects of available interventions for the management of GA.<br><br>METHODS: We systematically searched Medline, EMBASE, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov from inception for randomized controlled trials comparing any pharmacologic or non-pharmacologic treatment versus another, placebo, sham, or standard care in adults with unilateral or bilateral GA secondary to AMD. Paired reviewers will independently screen studies, extract data, and assess risk of bias. Outcomes of interest include best-corrected visual acuity (BCVA), untransformed and square root-transformed total GA lesion area, vision-related quality of life, low luminance BCVA, reading speed, mean macular sensitivity, adverse events leading to discontinuation, macular neovascularization, need for rescue treatment, ischemic optic neuropathy, serious ocular adverse events, and serious non-ocular adverse events. For each outcome, if feasible, we will conduct frequentist random-effects NMAs. We will assess the certainty of evidence and interpret findings using the GRADE approach. To maintain this review as a living systematic review, we will conduct updates every six months.<br><br>DISCUSSION: This review will provide a comprehensive, trustworthy, and up-to-date summary of evidence on treatments for GA secondary to AMD.<br><br>REGISTRATION: Open Science Framework (https://doi.org/10.17605/OSF.IO/W4JHR).}, }
@article {pmid42806246, year = {2026}, author = {Cruz, MJ and Limaye, S and Christopher, M}, title = {Current Trends in AI and Eye Disease Diagnostics.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {}, number = {}, pages = {}, pmid = {42806246}, issn = {1475-1313}, support = {OT2OD032644/OD/NIH HHS/United States ; OT2OD032644/OD/NIH HHS/United States ; OT2OD032644/OD/NIH HHS/United States ; }, abstract = {PURPOSE: Artificial intelligence (AI) has rapidly advanced as an approach for ophthalmic disease detection, driven by the widespread use of high-dimensional imaging modalities (e.g., optical coherence tomography). This review summarises the machine learning and AI approaches for disease detection in ophthalmology and discusses emerging paradigms and highlights key challenges impacting clinical translation.<br><br>RECENT FINDINGS: AI-based systems have demonstrated suitably high diagnostic performance across major ophthalmic diseases, including diabetic retinopathy (DR), diabetic macular oedema, glaucoma, age-related macular degeneration and retinopathy of prematurity. Several tools have even received regulatory approval for commercial DR screening. More recently, foundation models trained using self-supervised learning have enabled more generalisable and data-efficient disease detection across datasets and imaging modalities. In parallel, multimodal large language model systems are emerging that integrate imaging and clinical data to support more comprehensive diagnostic workflows. Early agentic AI systems extend this paradigm further by coordinating multiple models to perform disease detection, provide clinical decision support and generate reports. AI-based disease detection in ophthalmology has achieved substantial technical progress but only limited translation into routine clinical practice. Key barriers include technical, clinical, ethical, economic and regulatory concerns. Future efforts should prioritise prospective evaluation in real-world settings, addressing model transparency and bias and alignment with clinical and regulatory requirements. With continued advances, AI has the potential to expand access to care, improve diagnostic accuracy and reduce the global burden of vision loss.}, }
@article {pmid42807675, year = {2026}, author = {Rák, T and Jin, Y and Chen, M and Csutak, A}, title = {The therapeutic potential of medicinal mushrooms in ophthalmology: from ethnomycology to evidence-based applications.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1887133}, pmid = {42807675}, issn = {1663-9812}, abstract = {Medicinal mushrooms have long been used in traditional medical systems, yet their ophthalmic relevance has only recently been explored. This narrative review provides, to our knowledge, an integrative mapping of medicinal mushroom-derived bioactive compounds in ophthalmology, with particular emphasis on their level of evidence across different ocular diseases. A structured search of PubMed, Scopus, Google Scholar and ScienceDirect (2001-2026) was conducted to identify experimental, clinical, and mechanistic studies addressing antioxidant, anti-inflammatory, immunomodulatory, neuroprotective and antifibrotic pathways in ocular tissues. The findings reveal a marked heterogeneity in evidence levels. A limited subset of fungal-derived compounds - primarily antimicrobial and immunomodulatory agents such as β-lactam antibiotics, cyclosporine A, and mycophenolate mofetil - are supported by high-level clinical evidence (Level 1), while emerging evidence (Level 2) is available for compounds such as Isaria cicadae in dry eye disease and Ganoderma lucidum in age-related macular degeneration. In contrast, the majority of medicinal mushrooms - including Pleurotus spp., Hericium erinaceus, Wolfiporia extensa, and Polyporus umbellatus - remain supported mainly by preclinical studies and traditional use (Level 5 evidence). Experimental data indicate that mushroom-derived polysaccharides and triterpenoids can modulate oxidative stress, inflammation, intraocular pressure, fibrosis, and neuronal survival. Additional compounds demonstrate potential in glaucoma, cataract, and retinal disorders through multitarget mechanisms. Overall, medicinal mushrooms represent a promising but still under-validated therapeutic resource in ophthalmology. The observed disparity between traditional use, experimental evidence, and clinical validation highlights a significant translational gap, underscoring the need for standardized formulations and well-designed clinical trials to enable evidence-based integration into ophthalmic practice.}, }
@article {pmid42808622, year = {2026}, author = {Eymard, P}, title = {[Anti-VEGF treatment in age related macular degeneration].}, journal = {La Revue du praticien}, volume = {76}, number = {7}, pages = {703-706}, pmid = {42808622}, issn = {2101-017X}, mesh = {Humans ; *Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bevacizumab/therapeutic use ; Ranibizumab ; }, abstract = {Intravitreal anti-VEGF (Vascular Endothelial Growth Factor) injections have transformed the prognosis of exudative age-related macular degeneration (AMD) over the past two decades. They are effective in stabilizing the disease, despite the cost of regular injections and follow-up examinations. The advent of biosimilars and second-generation molecules (which allow for longer average treatment intervals) would help to reduce the cost of these therapies. While these treatments have significantly reduced visual impairment due to wet-AMD, they continue to represent a major economic challenge.}, }
@article {pmid42809677, year = {2026}, author = {Guzel, A and Devebacak, A}, title = {Bilateral Vortex Keratopathy in a Patient Receiving Long-Term Ribociclib Therapy.}, journal = {Eye &amp; contact lens}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICL.0000000000001312}, pmid = {42809677}, issn = {1542-233X}, abstract = {We report a case of bilateral vortex keratopathy associated with long-term ribociclib therapy in a 67-year-old woman with metastatic breast cancer. The corneal deposits were identified during routine ophthalmic examination after 4 years of continuous treatment. Slit-lamp biomicroscopy revealed bilateral whorl-like epithelial deposits with a subtle morphological appearance compared with classic amiodarone-associated cornea verticillata. The patient had no history of tamoxifen, amiodarone, or chloroquine use, and there were no clinical features suggestive of Fabry disease. The combined severity of the bilateral cortical cataracts and macular changes associated with dry age-related macular degeneration was considered sufficient to explain the reduced visual acuity, whereas the subtle corneal deposits were not considered visually significant. The patient remained asymptomatic, and systemic therapy was continued without modification. This case suggests that ribociclib-associated vortex keratopathy may be detected after prolonged exposure and remain clinically silent at presentation, highlighting the importance of careful clinical assessment to avoid unnecessary interruption of essential oncologic treatment.}, }
@article {pmid42810526, year = {2026}, author = {Xue, CC and Li, H and Wang, S and Fan, Q and Yu, M and Chee, ML and Li-Gao, R and Willems van Dijk, K and Khor, CC and Tan, ACS and Wong, TY and Cheng, CY}, title = {Cholesteryl Ester Transfer Protein Inhibition and Risk of Age-Related Macular Degeneration.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.09.027}, pmid = {42810526}, issn = {1549-4713}, abstract = {PURPOSE: Cholesteryl ester transfer protein (CETP) inhibitors have shown cardiovascular benefits, but genetically proxied CETP inhibition may increase age-related macular degeneration (AMD) risk. We evaluated this association in European- and East Asian-ancestry populations.<br><br>DESIGN: Drug-target Mendelian randomization (MR) and observational genetic association analyses in the UK Biobank and the Singapore Epidemiology of Eye Diseases (SEED) study.<br><br>PARTICIPANTS: 457,242 UK Biobank participants without AMD at baseline and 7,058 SEED participants.<br><br>METHODS: In drug-target MR, CETP inhibition was instrumented using a CETP protein quantitative trait locus (pQTL) instrument in Europeans and a high-density lipoprotein (HDL)-weighted CETP-region instrument in East Asians. Outcomes included advanced and early AMD in Europeans and exudative AMD, typical neovascular AMD (nAMD), and polypoidal choroidal vasculopathy (PCV) in East Asians. In observational analyses, a CETP pQTL score was evaluated against incident AMD in the UK Biobank, and an HDL-weighted CETP genetic score against prevalent AMD in SEED.<br><br>MAIN OUTCOME MEASURES: Risk of AMD RESULTS: In drug-target MR, greater genetically proxied CETP inhibition was associated with higher risks of advanced AMD (OR, 1.45; 95% CI, 1.25, 1.67) and early AMD (OR, 1.29; 95% CI, 1.19, 1.41) in Europeans, and exudative AMD (OR, 3.14; 95% CI, 2.16, 4.57), typical nAMD (OR, 2.84; 95% CI, 1.69, 4.79), and PCV (OR, 3.18; 95% CI, 2.05, 4.93) in East Asians (all P<0.001). In UK Biobank, each 1-SD decrease in the CETP pQTL score, representing greater genetically proxied CETP inhibition, was associated with higher incident AMD risk (HR,1.03; 95% CI, 1.01, 1.06; P=0.008). In SEED, the HDL-weighted CETP genetic score showed a U-shaped association with prevalent early AMD. Compared with the midrange group, higher odds were observed in the highest decile, representing greater genetically proxied CETP inhibition (OR, 1.74; 95% CI, 1.07, 2.72; P=0.019), and the lowest tertile, representing weaker inhibition (OR, 1.50; 95% CI, 1.13, 1.99; P=0.005).<br><br>CONCLUSIONS: Greater genetically proxied CETP inhibition was associated with higher AMD risk across genetic analyses in European- and East Asian-ancestry populations. These findings raise a potential retinal safety signal requiring validation in clinical trials and longitudinal observational studies in clinical practice.}, }
@article {pmid42810652, year = {2026}, author = {Perina, ML and Calcagno, D and Sbardella, D and Deodato, D and Distefano, A and Tuccitto, N and Oliveri, V and Schlotter, F and Faller, P and Grasso, G}, title = {The chemical oxidation of albumin affects its capability to bind amyloid beta 1-40 peptide and to inhibit its aggregation.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {154678}, doi = {10.1016/j.ijbiomac.2026.154678}, pmid = {42810652}, issn = {1879-0003}, abstract = {Human Serum Albumin (HSA) is the most abundant protein in the human body, exerting vital antioxidant and carrier functions. Beyond its systemic roles, HSA is clinically employed as a therapeutic tear supplement to restore the ocular surface proteome in severe dry eye and corneal diseases. However, the functional integrity of HSA is frequently compromised by oxidative stress, a hallmark of several neurodegenerative proteinopathies. While elevated levels of oxidised HSA have been documented in the blood and cerebrospinal fluid of Alzheimer's Disease patients, similar oxidative modifications are implicated in the pathogenesis of glaucoma and Age-related Macular Degeneration, where amyloid-beta (Aβ) peptides deposition and impaired protein clearance drive disease progression. Despite these clinical correlations, the specific impact of oxidative damage on the ability of HSA to chaperone and interact with Aβ peptides remains poorly understood. In this work, we applied several different experimental techniques to study the effect of oxidation on HSA conformation and oligomeric state when Chloramine T (CT) and hydrogen peroxide in Metal Catalysed Oxidation (MCO) are employed. ThT aggregation studies confirmed that the two different oxidised forms of HSA affect Aβ1-40 fibrillation differently. In addition, SPR interaction studies between the two differently oxidised forms of HSA and Aβ1-40 allowed us to prove that CT and MCO induce two different oxidative damages on HSA, which in turn induce lower binding capability towards Aβ1-40. Our results indicate a possible explanation for the role of oxidised HSA in the development and progression of brain and retinal neurodegeneration characterized by accumulation of Aβ.}, }
@article {pmid42798467, year = {2026}, author = {Vijayan, M and Veerapu, G and J S, N}, title = {A two-stage deep learning framework with progressive feature fusion and attention mechanisms for multi-class retinal disease classification.}, journal = {Frontiers in artificial intelligence}, volume = {9}, number = {}, pages = {1925302}, pmid = {42798467}, issn = {2624-8212}, abstract = {Accurate and efficient automated analysis of Optical Coherence Tomography (OCT) images is critical for large-scale retinal disease screening. However, current deep learning models often fail to simultaneously achieve high classification accuracy, practical computational feasibility, and interpretability. To deal with these problems, this paper presents a deep learning framework on YOLOv11 for eight-class retinal disease classification optimized using a two-stage optimization strategy. The proposed architecture incorporates a Progressive Spatial Fusion (PSF) module to hierarchically integrate multi-scale feature representations, followed by a Squeeze-and-Excitation (SE)-based dual-attention refinement mechanism that refines disease-discriminative features prior to classification. Evaluated on the OCT-C8 dataset, the proposed model achieves 98.00% accuracy, precision, recall, and F1-score, together with 99.70% specificity, while achieving perfect classification performance for the Age-related Macular Degeneration (AMD), Central Serous Retinopathy (CSR), Diabetic Retinopathy (DR), and Macular Hole (MH) classes. Grad-CAM visualizations provide qualitative insights into image regions influencing model predictions and show correspondence with disease-associated structural patterns reported in OCT literature. These results show that the proposed framework provides a good trade-off between classification performance, computational requirements and interpretability and shows potential for automated OCT-based retinal disease screening support.}, }
@article {pmid42799897, year = {2026}, author = {Yadav, A and Phogat, J and Yadav, M and Bhardwaj, A and Panghal, V and Goel, S and Verma, M and Sharma, S and Singh, M and Kumar, R and Tanwar, M}, title = {A case-control study on IL-8 gene polymorphisms and serum IL-8 levels in patients with age-related macular degeneration in India.}, journal = {Human genetics}, volume = {145}, number = {1}, pages = {}, pmid = {42799897}, issn = {1432-1203}, support = {09 /382(0244)/20 19- EM R-I//Council for scientific and industrial research, New Delhi, India/ ; }, mesh = {Humans ; *Interleukin-8/genetics/blood ; Male ; Case-Control Studies ; Female ; India ; *Polymorphism, Single Nucleotide ; Aged ; *Macular Degeneration/genetics/blood ; Middle Aged ; Genetic Predisposition to Disease ; Genotype ; Gene Frequency ; Alleles ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, with inflammatory and genetic factors contributing to its development. This study examined the association of IL-8 polymorphisms (rs4073, rs2227306, rs2227543) and serum IL-8 levels in a North Indian AMD cohort. A case-control study involving 160 AMD patients and 100 controls was performed. AMD was confirmed through detailed clinical evaluation and diagnostic imaging. Genomic DNA was extracted and genotyped using PCR followed by Sanger sequencing, and serum IL-8 concentrations were determined by ELISA. Statistical analyses were conducted using SPSS v22.0 and SNPstats. AMD patients exhibited significantly higher serum IL-8 levels than control (p < 0.001). ANCOVA adjusting for age and smoking confirmed elevated IL-8 in AMD (adjusted mean: 63.52 pg/ml vs. 41.23 pg/ml in controls; p < 0.001), with higher levels in wet AMD than dry AMD (67.75 pg/ml vs. 54.32 pg/ml; p = 0.043). The IL-8 rs4073 AA genotype and A allele were more frequent in AMD patients (p = 0.006 and p = 0.011, respectively). Multivariate logistic regression showed strong associations between rs4073 AA genotype and AMD risk under codominant (adjusted OR = 2.68; 95% CI: 1.17-6.15; p = 0.025), recessive (adjusted OR = 2.68; 95% CI: 1.27-5.67; p = 0.0067), and log-additive (adjusted OR = 1.50; 95% CI: 1.02-2.20; p = 0.036) models. No significant associations were observed for rs2227306 or rs2227543. Among all participants, AA carriers had significantly higher serum IL-8 levels than TT and AT genotypes (p = 0.018 and p < 0.001). The IL-8 rs4073 AA genotype and elevated serum IL-8 levels may serve as potential markers for AMD susceptibility in the North Indian population.}, }
@article {pmid42800655, year = {2026}, author = {Wei, Y and Morobeid, H and Daynes, K and Lee, S and Ansari, G and Bredehorst, J and Mireles, J and Nelson, R and Eakins, RT and Brown, T and Pfau, M and Zhang, Y and Schmitz-Valckenberg, S and Fleckenstein, M}, title = {Structure-function associations in eyes with Early Atrophic Age-related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.09.029}, pmid = {42800655}, issn = {1879-1891}, support = {R01 EY034965/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To characterize baseline structure-function relationships in eyes with early atrophic age-related macular degeneration (AMD) and to identify functional outcomes that best reflect structural disease burden.<br><br>DESIGN: Cross-sectional study PARTICIPANTS: A total of 87 eyes from 87 participants enrolled in the ongoing prospective observational study of early atrophic AMD (ClinicalTrials.gov NCT05959005), with incomplete or complete retinal pigment epithelium and outer retinal atrophy and total atrophic lesion size &#x2264; 1.27 mm&#xb2; METHODS: Structural metrics derived from multimodal imaging included fundus autofluorescence (FAF)-defined geographic atrophy (GA) lesion size (total and targeted), targeted hypertransmission size, and distance to the fovea (DTF) from the lesion border. Structure-function relationships were evaluated using correlations and univariable linear regressions with multiple-comparison adjustment.<br><br>MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), Moorfields Acuity Test (MAT), reading acuity and reading speed, and mesopic and dark-adapted (DA) cyan fundus-controlled perimetry (FCP) using fixed and lesion-targeted macular patterns.<br><br>RESULTS: Lesion size-based structural metrics showed the strongest associations with FCP outcomes. In eyes with FAF-defined GA (n&#x202f;=&#x202f;38), each doubling of targeted GA lesion size was associated with a 3.55 dB decrease in mean targeted mesopic sensitivity and 3.65 dB in mean targeted DA sensitivity (all P < 0.001). Similarly, doubling of targeted hypertransmission size (n&#x202f;=&#x202f;81) was associated with decreases of 1.65 dB and 1.97 dB in mean targeted mesopic and DA sensitivities, respectively (both P < 0.001; correlations up to &#x3c1;&#x202f;=&#x202f;-0.66). In contrast, central visual and reading outcomes were primarily associated with lesion topography. Greater DTF was associated with better BCVA, LLVA, and MAT (approximately 4 to 5 letters per mm) and improved reading acuity (-0.11 logRAD per mm; all adjusted P < 0.05), whereas lesion size-based metrics showed no consistent significant association with these outcomes.<br><br>CONCLUSIONS: In early atrophic AMD, lesion size and hypertransmission extent are closely linked to localized FCP sensitivity loss, whereas central visual acuity and reading outcomes are determined by lesion proximity to the fovea. This domain-specific separation supports targeted FCP as a sensitive endpoint for detecting structure-related functional change in early atrophic AMD.}, }
@article {pmid42800947, year = {2026}, author = {Mallepally, A and Lam, M and Mittal, E and Mahmoudzadeh, R and Salabati, M and Randolph, J}, title = {Comparative Analysis of Systemic Complications of Antivascular Endothelial Growth Factor Therapies in Retinal Diseases.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261484033}, pmid = {42800947}, issn = {2474-1272}, abstract = {Purpose: To compare the systemic safety profiles of antivascular endothelial growth factor (anti-VEGF) agents using a large real-world dataset. Methods: The TriNetX Research Network database was used to identify adults with macular edema secondary to diabetes, retinal vein occlusion, or age-related macular degeneration who received bevacizumab, ranibizumab, or aflibercept (2012-2022) or faricimab (2022-2024). The bevacizumab cohort was matched with the other cohorts using propensity score matching to account for demographic characteristics and comorbidities. Outcomes included stroke, venous thromboembolism, myocardial infarction, hypertension, brain hemorrhage, and renal function. Results: In the propensity score-matched cohorts comparing outcomes between bevacizumab and aflibercept (each n = 9538), bevacizumab was associated with higher mean blood urea nitrogen level (28.07 mg/dL vs 26.89 mg/dL; P = .017), higher mean serum creatinine level (1.86 mg/dL vs 1.72 mg/dL; P = .004), and lower mean estimated glomerular filtration rate (55.64 mL/min vs 58.01 mL/min; P = .003) at 1 to 6 months' follow-up. Compared with the faricimab cohort, the bevacizumab cohort (each n = 3500) showed increased risk of stroke (risk ratio [RR], 1.71, 95% CI, 1.19-2.48), venous thromboembolism (RR, 1.80, 95% CI, 1.11-2.93), myocardial infarction (RR, 1.72, 95% CI, 1.19-2.49), and hypertension (RR, 1.47, 95% CI, 1.19-1.83) within 2 years of follow-up. No significant differences were found between the bevacizumab and ranibizumab cohorts (each n = 2211). Conclusions: Bevacizumab may confer an increased risk of cardiovascular events and differences in renal function parameters compared with aflibercept and faricimab, but not ranibizumab. This underscores the importance of tailoring anti-VEGF therapy to patient-specific profiles, particularly in patients with underlying cardiovascular and renal comorbidities. Further studies in lower-comorbidity populations are needed to clarify these associations.}, }
@article {pmid42803434, year = {2026}, author = {Remolí-Sargues, L and Monferrer-Adsuara, C and Castro-Navarro, V and López-Salvador, B and Francés-Muñoz, E and López-Sánchez, E and Montero-Hernández, J}, title = {Comparison of Choroidal Vascularity Index Between Type 1 and Type 2 Macular Neovascularization Before and After Anti-VEGF Therapy.}, journal = {Seminars in ophthalmology}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/08820538.2026.2740663}, pmid = {42803434}, issn = {1744-5205}, abstract = {PURPOSE: To compare choroidal structural features and visual and anatomical outcomes between type 1 and type 2 macular neovascularization (MNV) at baseline and following anti-vascular endothelial growth factor (anti-VEGF) therapy.<br><br>METHODS: This retrospective study included 56 eyes of 44 patients with treatment-na&#xef;ve neovascular age-related macular degeneration treated with intravitreal anti-VEGF. Choroidal vascularity index (CVI), best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (CST), and macular fluid status were assessed at baseline and the final follow-up visit.<br><br>RESULTS: At baseline, CMT was significantly lower in type 1 than in type 2 MNV (p 0.047), whereas CVI did not differ significantly between groups (p 0.091). At the final visit, CVI also showed no significant difference between subtypes. BCVA improved and CMT decreased descriptively in both groups, whereas CST decreased and CVI remained essentially stable. After adjustment for baseline values and actual follow-up duration, no significant differences were found between subtypes in final BCVA, CMT, CST, CVI, or macular fluid status (all p&#x2009;>&#x2009;.05).<br><br>CONCLUSION: No significant differences in CVI were found between type 1 and type 2 MNV at baseline or final follow-up, and longitudinal changes were comparable between subtypes. These findings do not support a predominant role of choroidal vascularity in distinguishing MNV subtypes. As retinal pigment epithelium integrity was not assessed, its potential contribution remains unclear. Larger prospective studies with standardized treatment protocols are needed to clarify the mechanisms underlying different MNV growth patterns.}, }
@article {pmid42804165, year = {2026}, author = {Arsoudi, V and Chontos, T and Voutsas, S and Petrou, P and Tyrlis, K and Karavidas, I and Kandarakis, SA and Chondrou, S and Diamanti, S and Angelidis, CD and Georgalas, I}, title = {Lipoprotein and apolipoprotein levels in age-related macular degeneration: A meta-analysis.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261492347}, doi = {10.1177/11206721261492347}, pmid = {42804165}, issn = {1724-6016}, abstract = {PurposeDrusen, the hallmark of AMD, are lipoprotein-rich particles. However, the role of systemic lipid metabolism in their formation remains controversial. This meta-analysis explored the association between ApoA1, ApoA2, ApoB and Lp(a) serum levels and AMD.MethodsWe systematically searched MEDLINE, Cochrane Library, EMBASE and Scopus for relevant studies. WMD meta-analyses were performed for ApoA1 and ApoB, whereas SMD meta-analyses were conducted for ApoA2 and Lp(a) serum levels in AMD patients vs healthy controls.ResultsA total of 11 studies with 5,084 subjects for ApoA1, 4,179 for ApoB, 3,177 for ApoA2 and 3,228 for Lp(a) were included. No significant differences were observed between AMD patients (all subtypes) and controls for serum ApoA1 (WMD = 0.29 mg/dL, -3.75 to 4.32, p = 0.89), ApoB (WMD = -2.16 mg/dL, -5.67 to 1.34, p = 0.23), or Lp(a) (g: -0.14, -0.54 to 0.27, p = 0.50). ApoA2 was significantly different (g = 0.2, 0.07 to 0.34, p = 0.003). In severe AMD (geographic atrophy, neovascular AMD), meta-analysis revealed no significant difference for ApoA1 (WMD = -2.68 mg/dL, -8.87 to 3.52, p = 0.4) or ApoB (WMD = -0.42 mg/dL, -6.20 to 5.32, p = 0.89).ConclusionThis meta-analysis discovered no meaningful association between systemic levels of ApoA1, ApoB, or Lp(a) and the presence or severity of AMD. Despite a significant change in ApoA2, utilizing a Reference Change Value based interpretation, we conclude that observed differences in analyzed markers represent physiological and analytical noise rather than true biological change. Our findings suggest that systemic ApoA1, ApoB, and Lp(a) levels are not elevated in individuals with AMD, though the potential role of ApoA2 warrants further investigation.}, }
@article {pmid42804496, year = {2026}, author = {Ouyang, Q and Zhou, H and Ji, C and Jiang, H and Zhao, L and Pan, Y and Xiang, S and Hu, X}, title = {Dioscin attenuates D‑galactose‑induced retinal pigment epithelium senescence and epithelial-mesenchymal transition via the TGF‑β2/PI3K/Akt/β‑catenin pathway.}, journal = {PloS one}, volume = {21}, number = {9}, pages = {e0359423}, pmid = {42804496}, issn = {1932-6203}, mesh = {Animals ; *Diosgenin/analogs &amp; derivatives/pharmacology ; *Epithelial-Mesenchymal Transition/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; beta Catenin/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; *Galactose/pharmacology ; *Transforming Growth Factor beta2/metabolism ; Humans ; Mice ; *Signal Transduction/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; *Cellular Senescence/drug effects ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Macular Degeneration/metabolism/drug therapy/pathology ; Cell Line ; Saponins ; }, abstract = {PURPOSE: This study aimed to evaluate the protective effects of Dioscin in an age-related macular degeneration (AMD) -like model and to explore its potential therapeutic mechanisms.<br><br>METHODS: The therapeutic potential of Dioscin for AMD was investigated using D-galactose-induced senescence models in ARPE-19 cells (an in vitro preliminary screening model) and C57BL/6J mice using RT-qPCR, western blotting, immunofluorescence, and SA-&#x3b2;-gal staining. Bioinformatic analysis and molecular docking identified TGF-&#x3b2;2 as a computationally predicted potential target of Dioscin in AMD. Key mechanisms involving TGF-&#x3b2;2 and the PI3K/Akt/&#x3b2;-catenin signaling pathway were assessed in vitro using RT-qPCR, western blotting.<br><br>RESULTS: In D-galactose-induced senescence models, Dioscin significantly alleviated RPE senescence and EMT. Single-cell transcriptome analysis revealed that TGF-&#x3b2;2 is highly expressed in choroidal vascular endothelial cells of AMD patients. Mechanistically, computational predictions (molecular docking and dynamics simulations) identified TGF-&#x3b2;2 as a computationally predicted potential target of Dioscin, and experimental data showed that Dioscin suppressed D-galactose-induced activation of the TGF-&#x3b2;2/PI3K/Akt/&#x3b2;-catenin pathway in RPE cells, suggesting a potential paracrine regulatory mechanism.<br><br>CONCLUSION: Dioscin alleviates RPE senescence and EMT through suppression of the TGF-&#x3b2;2/PI3K/Akt/&#x3b2;-catenin pathway. Single-cell transcriptomics reveals that TGF-&#x3b2;2 is specifically upregulated in choroidal vascular endothelial cells in AMD, suggesting a paracrine mechanism linking vascular pathology to RPE dysfunction. These findings suggest that Dioscin may have potential value in mitigating RPE senescence and EMT in an AMD&#x2011;like model, although further validation in more clinically relevant AMD models is required.}, }
@article {pmid42805085, year = {2026}, author = {Castro-Fernández, DC and Cañizo-Outeiriño, A and Martínez, AL and Cuartero-Martinez, A and Rodríguez-Martínez, L and González-Barcia, M and Fernández-Rodríguez, MI and Rodríguez-Cid, MJ and Abraldes, MJ and Almuiña-Varela, P and Mera-Yáñez, MP and de Domingo, B and Gil-Martínez, M and Méndez-Cepeda, MDP and Pazos-González, B and Goméz-Ulla, F and Loza, MI and Ortea, I and Brea, J and Mateos, J and Fernández-Ferreiro, A}, title = {The oxidative and carbonyl stress axis in anti-vascular endothelial growth factor-refractory neovascular age-related macular degeneration: Implications for therapeutic repurposing.}, journal = {European journal of medicinal chemistry}, volume = {320}, number = {}, pages = {119361}, doi = {10.1016/j.ejmech.2026.119361}, pmid = {42805085}, issn = {1768-3254}, abstract = {BACKGROUND AND PURPOSE: Neovascular age-related macular degeneration is a leading cause of irreversible blindness, and approximately 25% of patients respond inadequately to intravitreal anti-VEGF therapy, representing a major unmet clinical need. We aimed to identify repurposable therapeutic alternatives by anchoring a phenotypic screen in the molecular signature of inadequate responders.<br><br>EXPERIMENTAL APPROACH: The molecular phenotype of the disease was characterised by data-independent acquisition proteomic profiling of peripheral blood mononuclear cells from patients with an inadequate anti-VEGF response and from controls. Guided by this signature, the Prestwick Chemical Library (1160 approved compounds) was screened in ARPE-19 retinal pigment epithelial cells exposed to cigarette smoke extract. Cytoprotection was assessed by a primary viability assay and examined further by orthogonal high-content imaging of intracellular reactive oxygen species and by concentration-range evaluation.<br><br>KEY RESULTS: Baseline profiling showed increased thiol-reductase, lipid-peroxidation, platelet and immune-redox pathways, together with reduced high-density-lipoprotein-associated antioxidant components. Dual angiopoietin-2/VEGF inhibition partially reversed these changes, with oxidative and carbonyl stress emerging as a prominent axis. The single-replicate primary screen performed robustly and recovered 29 primary hits, including established antioxidants, which attenuated intracellular reactive oxygen species in the orthogonal assay. Of six candidates advanced to concentration-range evaluation, todralazine produced the most consistent and pronounced protective effect.<br><br>CONCLUSION AND IMPLICATIONS: These preliminary findings nominate todralazine, a hydrazinophthalazine structurally related to known carbonyl-scavenging agents, as a repurposable candidate requiring mechanistic and translational validation, and illustrate the value of anchoring phenotypic screens in disease-relevant molecular signatures.}, }
@article {pmid42794533, year = {2026}, author = {Wen, L and Li, F and Liu, Y and Zhang, K and Mao, A and Liu, L and Lv, X and Geng, L and Yu, F and Feng, L and Kan, H}, title = {Integrative Proteogenomics and Single-Cell Transcriptomics Prioritize Candidate Causal Proteins and Therapeutic Targets in Age-Related Macular Degeneration.}, journal = {International journal of molecular sciences}, volume = {27}, number = {18}, pages = {}, pmid = {42794533}, issn = {1422-0067}, support = {82500499//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Macular Degeneration/genetics/metabolism ; Animals ; Genome-Wide Association Study ; Mice ; Quantitative Trait Loci ; *Proteogenomics/methods ; Single-Cell Analysis/methods ; *Transcriptome ; Single-Cell Gene Expression Analysis ; Retinal Pigment Epithelium/metabolism ; Polymorphism, Single Nucleotide ; Gene Expression Profiling ; }, abstract = {Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment, yet identifying effector proteins and tissue-specific mechanisms underlying genome-wide association study (GWAS) loci remains challenging. This study aimed to systematically prioritize candidate causal circulating proteins and delineate their cellular and transcriptional dynamics in AMD. We integrated plasma protein quantitative trait loci (pQTL) summary statistics from the UK Biobank Pharma Proteomics Project (UKB-PPP; N=53,022) with FinnGen AMD GWAS data using proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) with the HEIDI test, and Bayesian colocalization analysis. Prioritized candidates were mapped across human and murine retinal single-cell/single-nucleus RNA sequencing atlases. Transcriptional responsiveness was validated in an independent clinical microarray dataset (GSE103060) and in human retinal pigment epithelial cells (ARPE-19) via in vitro inflammatory stimulation and RT-qPCR. Target tractability was assessed using pharmacological databases. Multi-stage genetic screening prioritized five candidate proteins stratified into two confidence tiers: three Tier 1 causal drivers supported by colocalization (PP4 > 0.80)-including risk factors CSF2, IL20RB, and WARS1 (also known as WARS)-alongside two Tier 2 candidates supported by SMR and HEIDI, comprising risk factor PILRA and inversely associated metabolic factor ACADSB. Retinal transcriptomic mapping localized PILRA specifically to microglia, ACADSB to inner retinal neurons, and WARS1 to photoreceptors, RPE, and vascular compartments, while IL20RB and CSF2 exhibited low baseline expression. In independent validation cohorts, IL20RB and WARS1 were significantly up-regulated in choroidal neovascularization (CNV) membrane-derived RPE from patients with AMD (p<0.01). Exposure of ARPE-19 cells to TNF-α markedly induced mRNA levels of IL20RB (P=0.0025) and WARS1 (p<0.0001). Dual normalization against ACTB as a secondary internal reference yielded consistent significant induction. Pathway enrichment highlighted cytokine-driven receptor cascades (JAK-STAT signaling) and mitochondrial substrate catabolism (branched-chain amino acid and fatty acid metabolism). Drug-target profiling identified small molecules and nutraceuticals interacting with ACADSB, CSF2, and WARS1. By combining large-scale plasma proteomic genetics with single-cell mapping and experimental validation, this study identifies a prioritized set of candidate causal proteins linking neuroimmune activation, vascular remodeling, and mitochondrial bioenergetics in AMD, providing candidate entry points for mechanistic and therapeutic exploration.}, }
@article {pmid42794693, year = {2026}, author = {Angel, I and Periyasamy, K and Gladnikoff, M and Joseph, B and Mayer, R and Aminov, E}, title = {Targeted Intracellular Metal Modulation Attenuates Oxidative Stress and Preserves Retinal Integrity and Function in a Zebrafish Model of Mitochondrial Dysfunction and Age-Related Retinal Degeneration.}, journal = {International journal of molecular sciences}, volume = {27}, number = {18}, pages = {}, pmid = {42794693}, issn = {1422-0067}, mesh = {Animals ; *Oxidative Stress/drug effects ; Zebrafish ; *Mitochondria/metabolism/drug effects/pathology ; Disease Models, Animal ; Humans ; *Retinal Degeneration/metabolism/pathology/drug therapy ; *Retina/metabolism/pathology/drug effects ; Retinal Pigment Epithelium/metabolism/drug effects ; Iron/metabolism ; Zinc/metabolism ; Reactive Oxygen Species/metabolism ; Epigenesis, Genetic/drug effects ; Macular Degeneration/metabolism ; *Metals/metabolism ; }, abstract = {Retinal degeneration is associated with mitochondrial dysfunction, oxidative stress, and disruption of metal homeostasis within the retinal pigment epithelium (RPE). Dysregulation of redox-active metals has been implicated in age-related macular degeneration (AMD), but whether targeted intracellular metal modulation preserves retinal structure and function remains incompletely understood. This study explores the effect of metal ion modulation on retinal structure and visual function. Telomir-Zn, a Zinc-based intracellular metal modulator, depletes labile Fe[2+], potently inhibits multiple JmjC KDMs, and induces epigenetic reprogramming. In a zebrafish model combining impaired DNA repair with accelerated mitochondrial oxidative stress and progressive retinal degeneration (Sen57^wrn-/-^ND6^-/+^), Telomir-Zn reduced oxidative stress, preserved retinal architecture, improved visual behaviors, and partially normalized telomeric content and CpG methylation patterns. Complementary studies in human ARPE-19 RPE cells showed attenuation of iron/copper-induced ROS and calcium dysregulation, with reciprocal zinc accumulation and labile Fe[2+] depletion. These findings suggest that targeted metal modulation and multi-KDM inhibition may be a novel strategy to mitigate oxidative-epigenetic stress to preserve retinal structure/function in degenerative disease, supporting further investigation and development for AMD.}, }
@article {pmid42795729, year = {2026}, author = {Ruiz-Moreno, JM and Bernal-Morales, C and Esteban-Floría, O and Rodríguez-de-la-Rúa, E and Remolí-Sargues, L and Borras-Blasco, J and Gómez-Benlloch, A and Cilveti, E and Valsero-Franco, S and Arriola-Naharro, C and García-Lunar, P and Kaminski-Santamaría, S and Muñoz-Molina, B and García-Layana, A}, title = {From Trials to Treatment: Current Evidence Supporting Faricimab Use in nAMD and DME.}, journal = {Journal of clinical medicine}, volume = {15}, number = {18}, pages = {}, pmid = {42795729}, issn = {2077-0383}, support = {//Roche Farma S.A./ ; }, abstract = {Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are leading causes of visual impairment and require long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy. However, treatment burden and suboptimal real-world outcomes remain major challenges. Faricimab is a bispecific monoclonal antibody that simultaneously inhibits VEGF-A and angiopoietin-2 (Ang-2), a key mediator of vascular destabilization, leakage and inflammation, offering a novel dual-pathway approach aimed at improving efficacy and durability. This narrative review summarizes evidence from pivotal clinical trials and recent real-world studies evaluating the efficacy, durability, and safety of faricimab in patients with nAMD and DME. Real-world evidence from international cohorts and emerging data from Spanish routine clinical practice largely corroborate previous findings, showing anatomical improvements, stable or improved visual outcomes, and reduced treatment burden in treatment-naïve and previously treated eyes. Overall, the evidence reviewed indicates that faricimab is an effective and well-tolerated therapeutic option that may help address unmet needs in the long-term management of nAMD and DME. Importantly, data from real-world clinical practice are consistent with findings from pivotal trials, supporting the translation of faricimab's outcomes into routine care.}, }
@article {pmid42798083, year = {2026}, author = {Wang, L and Lu, Y and Tang, H}, title = {Knowledge, attitudes, and practices regarding age-related macular degeneration among adults aged 30 years and above: A cross-sectional study.}, journal = {Medicine}, volume = {105}, number = {39}, pages = {e50700}, doi = {10.1097/MD.0000000000050700}, pmid = {42798083}, issn = {1536-5964}, support = {SWFZ23-C-95//Research Project of the Sichuan Provincial Primary Health Development Research Center/ ; }, mesh = {Humans ; *Health Knowledge, Attitudes, Practice ; Cross-Sectional Studies ; Female ; Male ; *Macular Degeneration/psychology/epidemiology ; Adult ; Middle Aged ; Surveys and Questionnaires ; Aged ; China/epidemiology ; Risk Factors ; Aged, 80 and over ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment. Although modifiable risk factors accumulate early in life, current research predominantly focuses on older adults. This study aimed to assess the levels of knowledge, attitudes, and practices regarding AMD among adults aged 30 years and above in Nanchong, Sichuan Province, China. A cross-sectional study was conducted between November 2023 and August 2024 at Nanchong Central Hospital among adults aged 30 years and above, employing a validated and self-designed questionnaire (Cronbach's α = 0.838). The survey collected demographic data and measured scores for knowledge, attitudes, and practices. Participants were recruited through convenience sampling from outpatients in the ophthalmology department. The study included 424 participants, with 48 (11.32%) diagnosed with AMD. The mean knowledge, attitude, and practice scores were 5.41 ± 5.20 (range = 0-22), 32.43 ± 4.15 (range = 9-45), and 20.74 ± 5.01 (range = 7-35), respectively. Significant positive correlations were observed between knowledge and attitude (r = 0.423, P < .001), knowledge and practice (r = 0.576, P < .001), and attitude and practice (r = 0.492, P < .001). Mediation analysis indicated that knowledge exerted significant direct effects on attitude (β = 0.435, P = .020) and practice (β = 0.719, P = .012). Attitude also showed a significant direct effect on practice (β = 0.360, P = .004). In addition, a significant indirect effect of knowledge on practice through attitude was observed (β = 0.156, P = .005), confirming the mediating role of attitude. Overall, the participants demonstrated low levels of AMD knowledge, moderately positive attitudes, and inactive practices. These findings underscore the need to move beyond simply increasing AMD awareness toward promoting sustained preventive eye health behaviors among adults aged 30 years and above. Integrating practical risk-reduction guidance and appropriate eye-care practices into public health education may help facilitate earlier recognition of AMD risk and more proactive eye health management.}, }
@article {pmid42793711, year = {2026}, author = {Amine, R and Mizuno, M and Matar, K and Indurkar, A and Simoes, P and Hu, M and Downes, RA and Talcott, KE and Reese, JL and Ehlers, JP}, title = {The Structure-Function Link of Ellipsoid Zone Integrity and Outer Retinal Features with Visual Acuity in Dry AMD.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {18}, pages = {}, pmid = {42793711}, issn = {2075-4418}, abstract = {Background/Objectives: The purpose of this study was to evaluate associations between quantitative ellipsoid zone (EZ) integrity metrics derived from spectral-domain OCT (SD-OCT) and visual outcomes, including clinically meaningful visual acuity (VA) loss, in dry age-related macular degeneration (AMD). Methods: This single-center retrospective image-analysis cohort included 351 eyes from 351 patients with intermediate AMD or atrophic changes. Macular SD-OCT scans were analyzed using a certified-reader-validated machine learning-based segmentation platform to delineate the EZ, retinal pigment epithelium (RPE), and Bruch's membrane (BM). EZ metrics included EZ-RPE thickness (i.e., outer segment thickness) and EZ attenuation, defined as partial attenuation (EZ-RPE thickness of ≤20 µm, abnormal outer segment thinning)) or total attenuation/loss (0 µm). Drusen volume was quantified from the RPE-BM compartment. VA was converted to ETDRS letters. Associations between baseline OCT metrics and baseline VA, Year 2 VA, and ≥15-letter VA loss were assessed using nonparametric testing, linear regression, and ANCOVA. Results: Greater EZ-RPE thickness and lower EZ attenuation were associated with better baseline VA (all p < 0.001), and EZ metrics remained significant in cross-sectional regression models. Among 188 eyes with Year 2 follow-up, 38 (20%) experienced ≥15-letter VA loss. These eyes had significantly lower baseline EZ-RPE thickness (i.e., abnormal outer segment thinning) and greater EZ attenuation than eyes without such loss (all p < 0.001). In ANCOVA models, EZ metrics remained associated with Year 2 VA (all p < 0.001), whereas drusen volume was not. Conclusions: Quantitative EZ integrity metrics were associated with cross-sectional and longitudinal visual outcomes in dry AMD. EZ-RPE thickness and EZ attenuation may serve as clinically relevant OCT biomarkers reflecting photoreceptor integrity and risk of meaningful VA loss.}, }
@article {pmid42783204, year = {2026}, author = {Salvetat, ML and Pellegrini, F and Zeppieri, M and Capobianco, M and Avitabile, A and Cannizaro, L and Gagliano, G and Cappellani, F and Gagliano, C}, title = {Iontophoresis Drug Delivery to the Macula of Lutein for Age Related Macular Degeneration.}, journal = {Diseases (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {42783204}, issn = {2079-9721}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) represents a leading cause of irreversible vision loss worldwide, driven by intricate interactions among oxidative stress, low-degree chronic inflammation, and macular pigment depletion in aging retinas. Lutein, a component of the macular pigment, has attracted significant attention in AMD management for its antioxidant and blue-light filtering properties. Its oral supplementation, however, although showing potential in slowing AMD progression, requires daily intake and results in variable macular absorption. Trans-scleral iontophoresis (TSI) is a non-invasive technique using low-intensity electric currents to deliver charged molecules into biological tissues and represents an innovative method to deliver lutein into the retina.<br><br>METHODS: The present narrative review synthesizes and discusses the results of lutein supplementation in AMD patients; the ocular iontophoresis basal principles, efficacy, safety and limitations in treating different ophthalmic pathologies; and the evolving clinical evidence supporting lutein TSI in the AMD management.<br><br>RESULTS: Ex-vivo studies have shown that lutein TSI may provide efficient, localized, rapid, and sustained retinal supplementation of macular pigment, overcoming oral intake limitations. Recent preliminary clinical studies have demonstrated that this technique is well-tolerated and effective in enhancing macular pigment optical density and improving some visual functions in AMD patients.<br><br>CONCLUSIONS: Ex-vivo and pilot clinical studies highlight the capacity of TSI to deliver lutein inside the retina, overcoming physiological barriers that may limit the efficacy of lutein oral administration. The demonstration of the efficacy of the procedure in preserving/improving visual functions and delaying disease progression in AMD patients requires further long-term randomized controlled clinical studies.}, }
@article {pmid42784432, year = {2026}, author = {Chang, JT and Chien, HW and Lee, TY and Wang, K and Huang, CH}, title = {Real-World Outcomes of Faricimab Versus Aflibercept in Treatment-Naïve Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.}, journal = {Seminars in ophthalmology}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/08820538.2026.2735013}, pmid = {42784432}, issn = {1744-5205}, abstract = {PURPOSE: To compare the real-world early outcomes of faricimab versus aflibercept 2 mg in Asian patients with treatment-naïve neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), focusing on retinal pigment epithelial detachment (RPED) reduction.<br><br>METHODS: This retrospective study included treatment-na&#xef;ve nAMD or PCV eyes with baseline RPED receiving three consecutive monthly loading injections of aflibercept or faricimab. Best-corrected visual acuity, central macular thickness (CMT), intraretinal or subretinal fluid, maximum RPED height, and RPED improvement ratio were assessed at baseline and after treatment. RPED was classified as fibrovascular or serous/mixed by optical coherence tomography.<br><br>RESULTS: Fifty-eight eyes were included: 27 treated with faricimab and 31 with aflibercept. Both aflibercept and faricimab had significantly reduced CMT (-99.7&#x2009;&#xb1;&#x2009;101.2 and -129.6&#x2009;&#xb1;&#x2009;109.3&#x2009;&#x3bc;m; both p&#x2009;<&#x2009;.001) and maximum RPED height (-99.4&#x2009;&#xb1;&#x2009;205.6 and -151.4&#x2009;&#xb1;&#x2009;183.5&#x2009;&#x3bc;m; p&#x2009;=&#x2009;.011 and <0.001, respectively). In the fibrovascular RPED subgroup, the RPED improvement ratio was significantly greater with faricimab (35.6% vs. 16.5%; p&#x2009;=&#x2009;.029). Serous component resolution was also more frequent with faricimab (100% vs 61.5%; p&#x2009;=&#x2009;.045).<br><br>CONCLUSIONS: Both treatments improved retinal anatomy, while faricimab produced greater fibrovascular RPED height reduction and more complete serous component resolution.}, }
@article {pmid42786857, year = {2026}, author = {Shahsuvaryan, ML}, title = {Metformin as an Emerging Candidate for Diabetic Retinopathy, Agerelated Macular Degeneration and Glaucoma Pharmacotherapy: Evidence and Perspectives.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328519947260917114932}, pmid = {42786857}, issn = {2772-4336}, abstract = {Varying degrees of visual impairment up to complete blindness are widespread and represent a public health problem with a highly demarсated escalation. Currently, the leading causes of blindness are Diabetic Retinopathy (DR), Age-Related Macular Degeneration (AMD), and glaucoma, with an obvious exponential enlargement of vulnerable population groups as a result of urbanization followed by lifestyle changes and growth of the aging population. Management of these diseases is still challenging. The development of intraocular therapy with antiangiogenics or Vascular Endothelial Growth Factor inhibitors (anti-VEGF) opens a new avenue in eye disease treatment; however, despite these advances, new concerns are raised. DR, AMD, and glaucoma represent diseases with bilateral involvement, which underscores a need for oral systemic preventive therapy targeting both eyes simultaneously, as a cost-effectively optimized approach. At the same time, there is a need for a multi-target drug with preventive and therapeutic potential not only for eye diseases, but also for systemic diseases in patients with multimorbidity. Continued research has the potential to enhance druggability of the leading causes of blindness. A growing body of evidence suggests that metformin, as a drug with multimodal activity, has good preventive and therapeutic potential, opening a new avenue in ocular pharmacotherapy.}, }
@article {pmid42787462, year = {2026}, author = {Guymer, RH and Wu, Z and Gao, SS and Zhang, M and Steffen, V and Chen, C and Zhang, J and Litts, KM and Chang, MC and Elstrott, J and Yaspan, B and Datta, S and Willis, JR and Liu, L and Chen, H and , }, title = {HONU: A Multicenter, Prospective, Observational Study of the Progression of Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101320}, pmid = {42787462}, issn = {2666-9145}, abstract = {PURPOSE: Large and lengthy clinical trials are currently required to study the efficacy of interventions aiming to slow the progression of the early stages of age-related macular degeneration (AMD). To enable the design of more feasible trials, an observational study HONU aims to comprehensively study eyes with intermediate AMD (iAMD) to explore novel clinical endpoints and patient enrichment strategies.<br><br>DESIGN: Prospective, multicenter, international observational study.<br><br>PARTICIPANTS: Four hundred patients, whose study eye is required to have large drusen and pigmentary change, but without evidence of any atrophic changes other than incomplete retinal pigment epithelium and outer retinal atrophy. The nonstudy eye is required to have some evidence of atrophy.<br><br>METHODS: Patients are assessed every 12 weeks for up to 36 months, with standard opthalmic examinations and multimodal retinal imaging as well as a range of novel visual functional tests. Patient-reported outcomes and biomarker samples are also collected. Structural changes on multimodal imaging are evaluated longitudinally and their relationship with visual function parameters analyzed. Exploratory interim analyses are planned.<br><br>MAIN OUTCOME MEASURES: The rates of conversion from baseline high risk iAMD to more advanced atrophic AMD stages, and the rate of ellipsoid zone loss.<br><br>RESULTS: Recruitment commenced in May 2022 and 400 patients were enrolled by August 2024, allowing for up to 3 years follow-up. Enrollment occurred at 72 sites across 6 countries. The median age of the patients at baseline was 75 years, ranging from 50 to 93 years. The cohort is predominantly female, making up 69% of patients, and 95% identified as White.<br><br>CONCLUSIONS: HONU will provide critical and robust natural history data on AMD progression in patients with high-risk iAMD in the study eye. Potential novel earlier clinical trial endpoints and enrichment strategy for high-risk patients will be determined. Knowledge gained will inform design and feasibility of early interventional studies aiming to slow progression to vision-threatening late AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42787488, year = {2026}, author = {Maass, KF and Maia, M and Gune, S and Chang, MC}, title = {Pharmacodynamics of Free VEGF After Treatment with the Port Delivery Platform with Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101367}, pmid = {42787488}, issn = {2666-9145}, abstract = {OBJECTIVE: To evaluate the pharmacodynamics of aqueous humor (AH) free VEGF concentrations after treatment with the Port Delivery Platform with ranibizumab (PDS) in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Pharmacokinetic and pharmacodynamic analyses from the phase III Archway (NCT03677934) and phase II Ladder (NCT02510794) trials.<br><br>PARTICIPANTS: Patients with treatment-responsive nAMD.<br><br>METHODS: In Archway, patients received PDS 100 mg/mL with refills every 24 weeks (Q24W) or intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W) for 96 weeks. In Ladder, patients received PDS 10, 40, or 100 mg/mL with refills based on protocol-defined criteria or intravitreal ranibizumab 0.5 mg Q4W. Aqueous humor samples were collected throughout the trials (PDS arms only in Ladder) in a subset of patients.<br><br>MAIN OUTCOME MEASURES: Aqueous humor ranibizumab and free VEGF concentrations.<br><br>RESULTS: Archway analyses included 1149 AH samples from 215 patients. Ladder analyses included 109 AH samples from 47 patients. Aqueous humor ranibizumab concentrations after treatment with the PDS were consistent with the PDS implant release rate. Median AH free VEGF concentrations at randomization (on average 3 weeks after intravitreal ranibizumab injection) were 8.46 and 7.26 pg/mL in the PDS 100 mg/mL and intravitreal ranibizumab Q4W arms, respectively. Throughout the trial, AH free VEGF concentrations remained suppressed in both arms relative to previously reported values from treatment-na&#xef;ve patients, and AH free VEGF concentrations 24 weeks after treatment with PDS 100 mg/mL Q24W were similar to or lower than those 4 weeks after treatment with intravitreal ranibizumab. In Ladder, analysis of limited samples suggests there was a tendency for a delayed loss of AH free VEGF suppression with increasing ranibizumab dose. Below AH ranibizumab concentrations of &#x223c;10[6] pg/mL, there was a negative correlation between AH free VEGF and AH ranibizumab concentration. There were no correlations between AH free VEGF concentrations and clinical outcomes in either arm, including change from baseline in best-corrected visual acuity and central subfield thickness at week 96.<br><br>CONCLUSIONS: These findings demonstrate that PDS 100 mg/mL Q24W suppresses AH free VEGF throughout the entire 24-week refill-exchange interval and to an extent similar to that at 4 weeks after intravitreal ranibizumab.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42788443, year = {2026}, author = {Safarpour Lima, B and Sayanjali, S and Shoham-Hazon, N}, title = {Stem Cell-Based Strategies for Retinal Cell Restoration.}, journal = {Biotechnology journal}, volume = {21}, number = {9}, pages = {e70311}, doi = {10.1002/biot.70311}, pmid = {42788443}, issn = {1860-7314}, mesh = {Humans ; *Stem Cell Transplantation/methods ; Animals ; *Stem Cells/cytology ; *Retina/cytology ; *Retinal Degeneration/therapy ; }, abstract = {Retinal degenerative diseases, including age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and inherited retinal dystrophies, are among the leading causes of irreversible vision loss and blindness worldwide. Current treatments primarily slow disease progression and are unable to restore lost retinal cells or visual function, highlighting the need for regenerative therapeutic strategies. Stem cell-based therapies have emerged as a promising approach for retinal repair through multiple mechanisms, including retinal cell replacement, stimulation of endogenous regeneration, cellular reprogramming, immunomodulation, and paracrine signaling. This narrative review provides a comprehensive overview of the major stem cell sources investigated for retinal regeneration. In addition, the roles of extracellular vesicles and retinal organoids as emerging therapeutic platforms are discussed. Particular emphasis is placed on comparing the biological rationale, therapeutic potential, current preclinical and clinical evidence, and translational readiness of each approach. Despite encouraging progress, several challenges continue to limit routine clinical application, including poor survival and integration of transplanted cells, immune rejection, tumorigenicity, genomic instability, variability in differentiation efficiency, manufacturing standardization, and long-term safety. Continued advances in stem cell biology, tissue engineering, gene editing, and clinical trial design are expected to accelerate the development of safe and effective regenerative therapies for retinal diseases.}, }
@article {pmid42788989, year = {2026}, author = {Kushwah, N and Liu, CH and Bora, K and Maurya, M and Pavlovich, MC and Fu, Z and Kamenecka, TM and Sun, Y and Solt, LA and Chen, J}, title = {Myeloid deficiency of RORα exacerbates lipid dysregulation and laser-induced choroidal neovascularization.}, journal = {Angiogenesis}, volume = {29}, number = {4}, pages = {}, pmid = {42788989}, issn = {1573-7209}, mesh = {Animals ; *Nuclear Receptor Subfamily 1, Group F, Member 1/deficiency/metabolism/genetics ; *Choroidal Neovascularization/metabolism/pathology/genetics/etiology ; *Lipid Metabolism ; *Lasers/adverse effects ; Macrophages/metabolism/pathology ; PPAR gamma/metabolism/genetics ; Mice ; *Myeloid Cells/metabolism/pathology ; Mice, Knockout ; Microglia/metabolism/pathology ; Inflammation/pathology ; }, abstract = {Dysregulated lipid and cholesterol metabolism is implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss. Retinoic acid receptor-related orphan receptor alpha (RORα) is a lipid-sensing nuclear receptor genetically associated with neovascular AMD. We investigated the role of RORα in regulating AMD-like pathologies and laser-induced choroidal neovascularization (CNV) through mediating myeloid cell lipid homeostasis and function. Both systemic (Rora[sg/sg]) and myeloid-specific (Rora[fl/fl];LysMCre) RORα deficient mice exhibited fundus lesions with aging, and exacerbated CNV with chronic subretinal inflammation, with subretinal accumulation of lipid-laden activated microglia/macrophages, and increased levels of pro-inflammatory cytokines. RORα-deficient macrophages showed enhanced lipid droplet formation and upregulation of peroxisome proliferator-activated receptor gamma (PPARγ), a lipogenic RORα target gene. Pharmacological inhibition of RORα in cultured macrophage recapitulated the effects of RORα deficiency on lipid enrichment and inflammation, whereas PPARγ inhibition in RORα deficient mice partially reversed the effects on laser-induced CNV, lipid accumulation and inflammation. Additionally, migratory chemokine receptors, including CX3CR1 and CD47, were downregulated in RORα-deficient myeloid cells, contributing to impaired elimination of inflammatory cells from the subretinal space. These findings identify RORα as a critical transcriptional regulator that links lipid dysregulation to persistent subretinal inflammation and pathological CNV highly relevant in AMD.}, }
@article {pmid42790816, year = {2026}, author = {Ha, J and Choi, YH and Lee, D and Choi, J and Seo, W and Lee, G and Nam, D and Thakur, S and Yoo, TK and Hwang, S}, title = {A multi-label deep learning system for simultaneous detection of nine fundus conditions.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100379}, doi = {10.1016/j.apjo.2026.100379}, pmid = {42790816}, issn = {2162-0989}, abstract = {PURPOSE: To develop and validate a deep learning model for simultaneous detection of nine fundus conditions from a single color fundus photograph.<br><br>METHODS: A development dataset of 236,242 color fundus images was assembled from 17 heterogeneous sources and partitioned at the patient level into training (70%), tuning (10%), and internal validation (20%) sets; 5-fold cross-validation was applied on the training set. Nine target conditions were labeled using standardized or photographic criteria: diabetic retinopathy (DR), age-related macular degeneration (AMD), myopic macular degeneration (MMD), glaucoma suspect (GS), epiretinal membrane (ERM), retinal vascular occlusion (VO), media opacity, retinal hemorrhages, and any retinal disorder (composite). A multitask ConvNeXt architecture was trained end-to-end, with operating thresholds pre-specified via Youden's index on the tuning set. External validation was performed on an independent cohort of 4,055 images from an East Asian health-screening center, excluded from model development.<br><br>RESULTS: On internal validation (N = 47,229), AUROCs ranged from 0.943 (AMD) to 0.989 (VO), with sensitivity of 88.1%-97.1% and NPV &#x2265;98.8% for eight of nine conditions. On independent external validation (N = 4,055), AUROCs ranged from 0.894 (retinal disorder) to 0.983 (MMD), with NPV &#x2265;95.6% for eight of nine conditions, including 99.3% for DR, 99.9% for VO, and 99.8% for MMD.<br><br>CONCLUSIONS: This study presents a validated, criteria-anchored multi-label fundus triage framework capable of simultaneously screening for nine conditions from a single fundus photograph, with performance maintained on external validation at a source-excluded health-screening site within the same national health-screening system.}, }
@article {pmid42791521, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Xue, J and Jonas, RA and Wang, YX}, title = {Shallow and bullous retinal pigment epithelium elevations in age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42791521}, issn = {1471-2415}, mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; Male ; Tomography, Optical Coherence/methods ; Female ; Prevalence ; Middle Aged ; Aged ; *Macular Degeneration/epidemiology/diagnosis/complications ; *Retinal Detachment/epidemiology/diagnosis ; }, abstract = {OBJECTIVE: To assess prevalence and associations of shallow retinal pigment epithelium (RPE) elevations (RPEEs) and bullous RPE detachments (RPEDs).<br><br>METHODS: Macular optical coherence tomographic images taken in the population-based Beijing Eye Study were examined for the presence of RPEEs/RPEDs.<br><br>RESULTS: In the study cohort of 953 eyes (mean age:63.3&#x2009;&#xb1;&#x2009;9.3years), RPEE/RPED prevalence increased from 0/376 (0%) in the normal group and 0/373 (0%) in the group with early AMD stage, to 33/199 (16.6%;95%CI:11.4,21.8) and 1/5 (20.0%;95%CI:0.0,75.5) in intermediate and late AMD, respectively. In intermediate AMD, prevalences of RPEEs and RPEDs were 30/199 (15.1%;95%CI:10.0,20.2) and 9/199 (4.5%;95%CI:1.5,7.5), respectively. Higher total RPEE/RPED prevalence was associated with higher AMD stage (OR:55.3;95%CI:14.4,327;P&#x2009;<&#x2009;0.001), higher drusen number (OR:1,05;95%%CI:1.02,1.07;P&#x2009;<&#x2009;0.001), lower prevalence of external limiting membrane defects (OR:0.19;95%CI:0.05,0.57;P&#x2009;=&#x2009;0.003), in addition to male sex (OR:11.0;95%CI:3.37,45.5;P&#x2009;<&#x2009;0.001) and higher serum concentration of triglycerides (OR:1.48;95%CI:1.20,1.89;P&#x2009;<&#x2009;0.001). RPEE/RPED prevalence was not significantly associated with choroidal thickness as a whole (P&#x2009;=&#x2009;0.55) or separated in a large-vessel choroidal layer (P&#x2009;=&#x2009;0.86), medium-sized vessel layer (P&#x2009;=&#x2009;0.66) or small-vessel layer (P&#x2009;=&#x2009;0.24), prevalence (P&#x2009;=&#x2009;0.97) and location of any intraretinal hyperreflective foci, and prevalence of reticular pseudodrusen (P&#x2009;=&#x2009;0.57).<br><br>CONCLUSIONS: Any RPEE/RPED, RPEEs and RPEDs were found in 16.6%, 15.1% and 4.5% of eyes with intermediate AMD, respectively, with a higher RPEE/RPED prevalence correlating with higher drusen number, lower prevalence of external limiting membrane defects and higher serum concentration of triglycerides. The statistical independence of RPEEs/RPEDs from the prevalences of reticular pseudodrusen and intraretinal hyperreflective foci point to differences in their etiologies.}, }
@article {pmid42792179, year = {2026}, author = {Krekora, J and Drożdż, J and Blasiak, J and Kaarniranta, K}, title = {From Retina to Vasculature: Oxidative Stress as a Common Mechanistic Link Between Age-Related Macular Degeneration and Cardiovascular Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/antiox15091140}, pmid = {42792179}, issn = {2076-3921}, abstract = {Increasing epidemiological and experimental evidence suggests that age-related macular degeneration (AMD) and cardiovascular disease (CVD) share multiple pathogenic mechanisms. Among these, oxidative stress has emerged as one of the most plausible links connecting retinal degeneration and cardiovascular pathology. Excessive production of reactive oxygen and nitrogen species, combined with declining antioxidant defenses, contributes to lipid peroxidation, mitochondrial dysfunction, chronic inflammation, complement activation, cellular senescence, and impaired cellular stress responses in both the retina and the vascular system. Notably, drusen (AMD) and atherosclerotic plaques (CVD) share several molecular constituents. Therefore, AMD and CVD may represent tissue-specific manifestations of broader age-related disturbances in redox homeostasis and inflammatory regulation. Nevertheless, the coexistence of AMD and CVD is incomplete, suggesting that genetic susceptibility, tissue-specific responses to oxidative stress, biological aging, and mechanisms of cellular resilience influence disease expression. In this review, we summarize current evidence linking AMD and CVD, examine oxidative stress-driven molecular pathways common to both disorders, discuss emerging biomarkers and therapeutic targets, and highlight important unresolved questions regarding disease heterogeneity and causal relationships. A better understanding of the shared mechanisms underlying AMD and CVD may facilitate the development of integrated preventive strategies, improved risk stratification, and more personalized therapeutic approaches for age-related diseases.}, }
@article {pmid42793059, year = {2026}, author = {Fang, YL and Hsu, YJ and Sung, CH and Kung, CC and Shiu, SR and Hung, CY and Chen, MJ and Chang, DC and Liang, IC and Hung, CF}, title = {Cynarin Alleviates Sodium Iodate-Induced Retinal Pigment Epithelium Injury by Regulating Oxidative Stress and Inflammation.}, journal = {Biomolecules}, volume = {16}, number = {9}, pages = {}, doi = {10.3390/biom16091227}, pmid = {42793059}, issn = {2218-273X}, support = {111-SHK-FJU-02//Shin Kong WHS Memorial Hospital/ ; TSGH_D_113127//Tri-Service General Hospital/ ; }, mesh = {*Iodates/toxicity ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology/injuries ; Animals ; Humans ; Mice ; *Inflammation/drug therapy/metabolism/chemically induced/pathology ; NF-kappa B/metabolism ; Cell Survival/drug effects ; Mice, Inbred C57BL ; Cell Line ; Macular Degeneration/drug therapy/chemically induced/metabolism ; *Pyrans/pharmacology ; Cytokines/metabolism ; Signal Transduction/drug effects ; }, abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and is strongly driven by oxidative stress and inflammation. This study investigated the protective effects of cynarin against sodium iodate (NaIO3)-induced retinal pigment epithelium (RPE) injury, focusing on the MAPK and NF-κB signaling pathways. Materials and Methods: Human ARPE-19 cells were exposed to NaIO3, and cell viability was assessed by the MTT assay. Protein expression of MAPK components (p38, JNK, ERK) and the NF-κB pathway was analyzed by Western blotting, and pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) mRNA expression was measured by RT-qPCR. In vivo, NaIO3-induced retinal degeneration in C57BL/6 mice was treated with cynarin (3 or 10 mg/kg) for seven days, and retinal changes were evaluated by fundus photography, fluorescein angiography, and OCT. Results: Cynarin preserved ARPE-19 cell viability without cytotoxicity. It significantly attenuated NaIO3-induced p38 and JNK phosphorylation, IκB degradation, and NF-κB activation while downregulating IL-1β, IL-6, and TNF-α expression. In vivo, cynarin reduced drusen-like lesions, hyperfluorescent abnormalities, and retinal thinning, and dose-dependently suppressed ocular pro-inflammatory cytokines. Conclusions: Cynarin protects against oxidative stress-induced retinal degeneration by suppressing MAPK and NF-κB inflammatory signaling, representing a promising therapeutic candidate for preventing or delaying NaIO3-induced dry AMD-like retinal injury.}, }
@article {pmid42776856, year = {2026}, author = {Rizzo, S and Sasso, P and Nepita, I and Francione, G and Caputo, CG and Ferrara, M and Feo, A and Savastano, A and Vidal-Aroca, F and Belousov, V and Romano, MR}, title = {First-in-Human Implantation of an Add-On Dual Intraocular System Combining a Standard IOL and the SING-IMT™ Telescope: Optical Simulation, Preclinical Validation, and Clinical Feasibility.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000005023}, pmid = {42776856}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate a dual-implant system combining a capsular-bag monofocal intraocular lens with a sulcus-implanted small-incision new-generation implantable miniature telescope (SING-IMT).<br><br>METHODS: Optical simulations quantified retinal spot size, modulation transfer function (MTF), and tolerance to misalignment. Preclinical porcine experiments evaluated surgical feasibility, anatomical stability, and early safety. First-in-human (FiH) implantation assessed surgical outcomes, anterior segment behaviour using ultrasound biomicroscopy and optical coherence tomography, functional vision, and safety over 6 months.<br><br>RESULTS: Optical modelling demonstrated that the dual-implant configuration maintained retinal image quality within the rehabilitative regime for advanced AMD, with root-mean-square retinal spot radii of 18.7 &#xb5;m (0&#xb0;) and 20.4 &#xb5;m (2.5&#xb0;), below the estimated retinal sampling limit (&#x223c;49 &#xb5;m), consistent with an expected visual acuity improvement of approximately 2 Snellen lines. Decentration up to 0.5 mm was optically well tolerated, whereas tilt produced rapid mid-frequency contrast loss. In vivo porcine studies confirmed stable sulcus seating without disruption of the capsular-bag IOL or anterior segment structures. FiH implantation was completed without intraoperative complications. At 6 months, distance visual acuity improved from 20/200 to 20/125, near acuity from 56 to 15 Colenbrander units, and reading speed from non-assessable preoperatively to 20 words/min, with no device-related adverse events.<br><br>CONCLUSION: This integrated evaluation supports the feasibility and short-term safety of sulcus-based SING-IMT implantation as a minimally invasive intraocular magnification strategy for selected pseudophakic patients with advanced AMD.}, }
@article {pmid42777504, year = {2026}, author = {Liu, J and Hu, J and Li, Y and Hu, N and Wang, Y and Chang, B and Guo, Y and Li, X and Zhang, Q and Ming, Y and Lin, C and Ji, H and Yang, Z and Tang, J}, title = {Corrigendum to "Microneedle-Mediated Biomimetic Nanoparticles for Targeted Antioxidant and Anti-Inflammatory Therapy in AgeRelated Macular Degeneration" [J. Control. Release 384(2025) 113908]".}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {399}, number = {Pt A}, pages = {115369}, doi = {10.1016/j.jconrel.2026.115369}, pmid = {42777504}, issn = {1873-4995}, }
@article {pmid42777948, year = {2026}, author = {Teo, KYC and George, LM and Forouhari, A and Fu, DJ and Sivaprasad, S and Fenner, B and Esmaeelpour, M and Herrmann, R and Cheung, CMG}, title = {Predictors of Geographic Atrophy Growth and Visual Decline in a longitudinal Asian cohort.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.09.020}, pmid = {42777948}, issn = {2468-6530}, abstract = {PURPOSE: To characterize GA growth and visual outcomes in Asian eyes with geographic atrophy (GA) secondary to age-related macular degeneration and to evaluate the incremental prognostic value of deep learning-derived optical coherence tomography (OCT) biomarkers.<br><br>DESIGN: Prospective longitudinal observational cohort study.<br><br>PARTICIPANTS: One hundred fifty-five eyes of 139 patients with GA and 12-month follow-up.<br><br>METHODS: Participants underwent baseline and month-12 multimodal imaging with fundus autofluorescence (FAF) and spectral-domain OCT. GA area was quantified on FAF. A validated deep learning algorithm segmented retinal pigment epithelium layer loss (RPEL), photoreceptor degeneration (PRD), hypertransmission (HTR), and retinal pigment epithelium and outer retinal atrophy (RORA). Layer-specific excess metrics beyond RORA were derived. Multivariable mixed-effects models were constructed to identify predictors of GA growth and month-12 best-corrected visual acuity (VA), with nested models assessing incremental value beyond conventional demographic and imaging features.<br><br>MAIN OUTCOME MEASURES: Twelve-month change in GA area and month-12 VA.<br><br>RESULTS: Mean baseline GA area was 3.89&#xb1;4.24 mm[2] and increased by 0.83&#xb1;0.92 mm[2] at month 12 (P<0.01). In lesions with baseline area &#x2265;2.5mm[2], one year growth rate was 1.32 &#xb1; 0.96 mm[2]. Baseline GA area, multifocality, and subretinal drusenoid deposits (SDD) were independently associated with faster growth. When analysed by baseline GA area, SDD were associated with increased growth in eyes with smaller baseline GA area (<2.5mm[2]). PRD-RORA excess was independently associated with GA growth and provided incremental predictive value beyond conventional predictors (&#x394;R[2]=0.02, P=0.04). Predictors differed by baseline lesion size. Mean VA decreased minimally from 0.68&#xb1;0.56 at baseline to 0.72&#xb1;0.57 logMAR at 1-year (P<0.01). Central 1-mm OCT occupancy measures provided greater explanatory value for month-12 VA than 6-mm OCT occupancy.<br><br>CONCLUSIONS: Photoreceptor degeneration extending beyond established atrophy provided modest incremental prognostic information beyond conventional features evaluated. Central 1-mm OCT features showed limited association with month-12 VA and may serve as complementary structural correlates of visual function.}, }
@article {pmid42778294, year = {2026}, author = {Bantounou, MA and Emfietzoglou, M and Baroutis, KG and Starr, MR and Miller, JW and Vavvas, DG}, title = {Sustained proton-pump inhibitor exposure and incident age-related macular degeneration: a new-user, population-based cohort study.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {3}, pages = {}, doi = {10.1136/bmjophth-2026-002935}, pmid = {42778294}, issn = {2397-3269}, mesh = {Humans ; *Proton Pump Inhibitors/adverse effects ; Aged ; Female ; Retrospective Studies ; *Macular Degeneration/epidemiology/chemically induced/diagnosis ; Incidence ; Male ; Middle Aged ; Aged, 80 and over ; Risk Factors ; }, abstract = {OBJECTIVE: Proton-pump inhibitors (PPIs) may disrupt lysosomal acidification, a pathway implicated in age-related macular degeneration (AMD) pathogenesis. We evaluated whether sustained PPI exposure increased the risk of incident AMD in older adults aged ≥60 years.<br><br>METHODS AND ANALYSIS: This retrospective observational cohort study included adults aged &#x2265;60 years with sustained PPI exposure, matched 1:1 to unexposed controls on demographics, overall health, healthcare utilisation, cardiometabolic factors. Participants were identified from electronic health records. Sustained PPI exposure was defined as &#x2265;2 years of cumulative use within 3 years of the first prescription. Fine-Gray models treating death as a competing event estimated subdistribution hazard ratios (sHRs) for AMD within 10 years; cause-specific Cox models provided complementary HRs. Analyses included histamine H2-receptor antagonists (H2-antagonists) as a negative exposure control and active comparator.<br><br>RESULTS: Incident AMD occurred in 814/49 796 PPI exposed participants (1.64%) and 668/49 796 controls (1.34%) (overall sHR=1.24, 95%&#x2009;CI 1.12 to 1.38; p<0.001; HR=1.25, 95%&#x2009;CI 1.13 to 1.38, p<0.001). Proportional sHRs were non-constant; sHRs were 1.09 (95%&#x2009;CI 0.91 to 1.29) before 2.5 years and 1.33 (95%&#x2009;CI 1.17 to 1.51)&#x2009;thereafter. For non-exudative AMD, 640 PPI exposed (1.29%) and 510 unexposed (1.02%) participants developed disease (overall sHR=1.28, 95%&#x2009;CI 1.14 to 1.44; p<0.001, HR=1.29, 95%&#x2009;CI 1.14 to 1.44, p<0.001). Among those with non-exudative AMD, 190/2503 PPI-exposed participants (7.59%) and 179/2503 controls (7.15%) progressed to exudative AMD (sHR and HR=1.03, 95%&#x2009;CI 0.84 to 1.26; p=0.802&#x2009;and p=0.801, respectively). No association was observed between H2-antagonists and AMD (sHR=1.02, 95%&#x2009;CI 0.88 to 1.19; p=0.784; HR=1.03, 95%&#x2009;CI 0.88 to 1.20, p=0.729). Results were consistent in the active-comparator analysis (reciprocal overall sHR=1.24, 95%&#x2009;CI 1.04 to 1.48; p=0.016; HR=1.25, 95%&#x2009;CI 1.05 to 1.49, p=0.012).<br><br>CONCLUSION: Sustained PPI exposure was associated with a modestly higher AMD risk, whereas no association was observed with H2-antagonists. The consistency of the active-comparator findings supports the potential specificity of this association and warrants further investigation to determine its clinical implications.}, }
@article {pmid42779760, year = {2026}, author = {Shautsova, V and Butt, E and Bhuckory, M and Vu, LM and Pham-Howard, D and Mamchik, V and Galambos, L and An, J and Shin, A and Mathieson, K and Kamins, T and Palanker, D}, title = {Electrodeposited Biocompatible Coatings for 3D Electrodes on Retinal Prostheses.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.09.06.749620}, pmid = {42779760}, issn = {2692-8205}, abstract = {Photovoltaic subretinal prosthesis, PRIMA, provides central vision to patients blinded by age-related macular degeneration, with acuity matching the 100 μm pixel size. Further miniaturization requires pillar electrodes to position the stimulating surfaces closer to the inner retinal neurons. While such structures can be electroplated in gold and coated on their tops with SIROF, the exposed gold sidewalls are not biocompatible. Sputtering or atomic layer deposition of protective coatings are unsuitable for selectively passivating the pillar structures without also coating the photosensitive regions and return electrodes of the implant. Here, we present a strategy for biocompatible coating of pillar sidewalls while preserving surrounding implant functionality. The approach combines non-critical photoresist lithography to protect planar return electrodes with electrodeposition of TiO2 or Pt onto gold pillar sidewalls. In-vivo studies demonstrated that both TiO2 and Pt coatings are biocompatible and prevent adverse reactions of the retinal tissue to gold. Since specific capacitance of electroplated TiO2 (25 μF/cm[2]) is much lower than that of Pt (240 μF/cm [2]), the former better limits the current from the side walls and ensures that charge injection occurs predominantly through the pillar tops coated with SIROF (∼6 mF/cm[2]). Electrodeposition, combined with noncritical photolithography provides a scalable wafer-level solution for fabrication of biocompatible three-dimensional electro-neural interfaces, addressing a critical bottleneck in bioelectronics.}, }
@article {pmid42783183, year = {2026}, author = {Tam, HM and Wang, SY and Sun, YS and Lo, KY}, title = {A Microfluidic Gradient Platform for High-Throughput Evaluation of Blue-Light-Induced Oxidative Stress and Antioxidant Protection in Retinal Pigment Epithelial Cells.}, journal = {Biosensors}, volume = {16}, number = {9}, pages = {}, pmid = {42783183}, issn = {2079-6374}, support = {NSTC 114-2112-M-030-004-//National Science and Technology Council/ ; NSTC 112-2313-B-002-049-MY3//National Science and Technology Council/ ; NSTC 114-2313-B-002-012-MY3//National Science and Technology Council/ ; }, mesh = {Blue Light ; Humans ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Oxidative Stress/radiation effects/drug effects ; *Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Cell Line ; *Microfluidics ; Epithelial Cells ; }, abstract = {The retinal pigment epithelium (RPE) is a monolayer of cells located between retinal photoreceptors and the choroid, playing a critical role in maintaining visual function by protecting the retina and supporting photoreceptor metabolism. Damage to RPE cells can lead to visual disorders, including macular degeneration. Chronic exposure to high-energy blue light has been shown to elevate intracellular reactive oxygen species (ROS) in RPE cells, causing oxidative stress and cellular damage. In this study, a microfluidic platform incorporating a gradient-generating structure was developed to establish controllable and stable gradients of blue light intensity and chemical concentrations. This platform was used to investigate the effects of varying blue light intensities and antioxidant concentrations on oxidative stress in human RPE cells ARPE-19. Cells cultured within the microfluidic channels were exposed to different blue light intensities in combination with chemical treatments. Results demonstrated that ROS production increased with higher blue light intensity, whereas higher antioxidant concentrations effectively reduced ROS accumulation, supporting the ability of these antioxidants to attenuate blue-light-induced intracellular oxidative stress. The present microfluidic device enables simultaneous evaluation of multiple conditions within a single experiment, reducing reagent consumption and enhancing experimental efficiency. This in vitro microfluidic platform integrates chemical and light gradients to assess retinal oxidative damage and antioxidant effects, offering significant potential for ophthalmic drug screening and investigations of retinal protective mechanisms.}, }
@article {pmid42776232, year = {2026}, author = {Ach, T and von der Emde, L}, title = {[Ophthalmological care of senior citizens in residential nursing facilities : Care gaps, the TOVIS study and ways to an improved ophthalmological care].}, journal = {Zeitschrift fur Gerontologie und Geriatrie}, volume = {}, number = {}, pages = {}, pmid = {42776232}, issn = {1435-1269}, abstract = {BACKGROUND: Around 800,000 older people live in approximately 16,500 nursing and old people's homes in Germany and this number will continue to rise due to demographic change. Visual impairment and eye diseases in need of treatment are among the most common yet most neglected health problems in this vulnerable population. This article summarizes the current state of ophthalmological care for nursing home residents in Germany, the barriers involved and the potential contribution of novel tele-ophthalmological care models to closing this care gap.<br><br>MATERIAL AND METHODS: Narrative review based on a&#xa0;selective literature search (PubMed, Google Scholar, professional society documents) on ophthalmological care of institutionalized older people with particular focus on the German OVIS and S&#xc4;VIP studies, the international literature on prevalence and care models in nursing homes and both published reports on the TOVIS study (TeleOphthalmologische Versorgung In Seniorenheimen).<br><br>RESULTS: The OVIS study (2017; n&#x202f;=&#x2009;600; 32&#xa0;homes) found an ophthalmological result requiring treatment in 61% of residents, most frequently cataract (53%), age-related macular degeneration (AMD, 39%) and glaucoma (11% suspected); the last ophthalmologist visit occurred on average 4 years earlier. Comparable deficits are described across numerous other countries. The TOVIS pilot study (2023; n&#x202f;=&#x2009;109 of 139 enrolled residents) tested a&#xa0;telemedical shared-eye-care model in which trained nonmedical personnel performed on-site examinations while ophthalmologists provided remote assessment. A vision-relevant cataract was found in 48.5%, typical AMD lesions in 34.1% and inadequately fitted eyeglasses in 60.6%; only 31.2% of the examined residents were aware of their diagnosis. At 6&#x2011;month follow-up only&#xa0;14 of 52 residents (26.9%) with a&#xa0;referral recommendation actually attended a&#xa0;specialist appointment, despite over 80% rating the tele-examination positively.<br><br>CONCLUSION: Ophthalmological care in German nursing homes has been insufficient for years, a&#xa0;pattern that is consistently mirrored across numerous other healthcare systems in the international literature. Tele-ophthalmological shared-eye-care models such as TOVIS are feasible and well accepted but do not by themselves solve the aftercare problem. A&#xa0;substantial gap remains between diagnosis and actual specialist treatment, which requires structured appointment management, transport and accompaniment solutions and closer collaboration between nursing staff, primary care and ophthalmology.}, }
@article {pmid42776254, year = {2026}, author = {Quarta, A and Sivaprasad, S and Wong, TY and Lanzetta, P and Wykoff, CC and Mastropasqua, R and Sadda, SR}, title = {Ranibizumab port delivery system for neovascular age-related macular degeneration: Current evidence and surgical considerations.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42776254}, issn = {1435-702X}, abstract = {PURPOSE: To review the engineering principles, pharmacokinetics, clinical evidence, surgical considerations, safety profile, and emerging real-world implications of the ranibizumab Port Delivery System (PDS) as a sustained intraocular drug-delivery platform for neovascular age-related macular degeneration.<br><br>METHODS: A systematic literature search was conducted to identify peer-reviewed publications addressing implant engineering, molecular compatibility, pharmacokinetics, phase 1-3 trials (LADDER, ARCHWAY, PORTAL), extension studies, perioperative management, safety outcomes, health-economic analyses, and patient-reported outcomes related to the ranibizumab PDS.<br><br>RESULTS: Phase 2 and 3 trials demonstrated that PDS delivering ranibizumab 100&#xa0;mg/mL with fixed 24-week refill intervals achieved visual and anatomic outcomes noninferior to monthly intravitreal injections, with approximately 95% of patients not requiring supplemental treatment before scheduled refills. Pharmacokinetic studies confirmed sustained intraocular drug exposure within the therapeutic window of monthly dosing. Long-term extension data support durability through multi-year follow-up. The distinct safety profile features implant- and conjunctival interface events, including conjunctival erosion, vitreous hemorrhage, and device-associated endophthalmitis, underscoring the importance of surgical technique and postoperative surveillance. Economic analyses indicate cost parity with branded anti-VEGF agents under high injection frequencies, while patient-reported outcomes consistently demonstrate strong preference for sustained delivery. In ARCHWAY, mean BCVA change averaged over Weeks 36/40 was +&#x2009;0.2 letters with PDS versus +&#x2009;0.5 letters with monthly ranibizumab, and 98.4% of PDS-treated eyes required no supplemental injections in the first 24-week interval; across later intervals, approximately 95% avoided supplemental treatment before scheduled refill.<br><br>CONCLUSIONS: The ranibizumab PDS establishes sustained intraocular anti-VEGF delivery as a viable alternative to anti-VEGF injections especially in patients requiring frequent dosing. Its long-term role will depend on optimization of surgical workflows, management of implant-specific risks, integration of monitoring strategies, and ongoing refinement of device design to support scalable, durable retinal care.}, }
@article {pmid42776803, year = {2026}, author = {Pařilová, T and Hejsek, L and Hodačová, L}, title = {Discordance Between Eye-Specific Clinical Outcomes and Patient-Reported Visual Function After Faricimab Treatment for Neovascular Age-Related Macular Degeneration: A Two-Case Report.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {42776803}, issn = {2411-5150}, support = {Cooperatio, research area HEAS//Charles University/ ; Cooperatio, research area SURG//Charles University/ ; SVV-2025-260776//Ministry of Education Youth and Sports/ ; }, abstract = {Neovascular age-related macular degeneration is a retinal disease of older adults causing central vision loss associated with macular neovascularization. Treatment response is commonly evaluated using visual acuity and retinal morphology. These measures may not fully reflect patient-perceived benefit. We report two older adults with neovascular age-related macular degeneration treated with faricimab who demonstrated discordance between clinical and patient-reported outcomes. In the first case, best-corrected visual acuity changed from 20/200 to 20/180 and central retinal thickness decreased from 480 to 389 µm, whereas the National Eye Institute Visual Function Questionnaire-25 score increased from 33.87 to 60.99 and the exploratory ordinal colour-vividness rating was 25 at baseline and 100 at follow-up. In the second case, best-corrected visual acuity improved from 20/100 to 20/45 and central retinal thickness decreased from 341 to 186 µm, whereas the National Eye Institute Visual Function Questionnaire-25 score declined from 67.08 to 33.17 and the exploratory ordinal colour-vividness rating was 75 at baseline and 25 at follow-up. Changes in patient-reported visual functioning may not always parallel conventional clinical outcomes, while the contrasting exploratory colour-vividness ratings observed in these two cases warrant further investigation.}, }
@article {pmid42776804, year = {2026}, author = {Gandhi, S and Balas, M and Curtis, R and Zhou, TE and Jin, YP and Yan, P}, title = {Global Ophthalmology Research Output Relative to Disease Burden and National Income, 2011-2021.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {42776804}, issn = {2411-5150}, abstract = {PURPOSE: To characterize ophthalmology research output relative to disease burden and national economic capacity after accounting for population size.<br><br>METHODS: We analyzed Scopus publications, Global Burden of Disease disability-adjusted life years (DALYs), and World Bank economic and population data from 2011 to 2021. Negative binomial and Gamma models evaluated publication volume and positive citation-weighted impact, adjusting for DALYs, gross domestic product (GDP) per capita, population, disease category, and publication year.<br><br>RESULTS: Refractive disorders accounted for 45.4% of DALYs and 23.2% of publication volume; cataract, 44.7% and 29.8%; glaucoma, 5.2% and 30.6%; and age-related macular degeneration, 3.8% and 15.2%. High-income countries accounted for 11.8% of burden, 67.2% of publication volume, and 74.2% of citation-weighted impact; lower-middle-income countries accounted for 49.1%, 7.9%, and 6.8%, respectively. DALYs were not independently associated with publication volume (adjusted count ratio [aCR], 0.99; 95% confidence interval [CI], 0.98-1.01; p = 0.278), whereas GDP per capita (aCR, 4.47) and population (aCR, 13.99) were strongly associated (both p < 0.001). For positive citation-weighted impact, DALYs had a small association (adjusted ratio of means [aRM], 1.05), whereas GDP per capita (aRM, 2.86) and population (aRM, 4.96) were strongly associated (all p < 0.001).<br><br>CONCLUSIONS: After accounting for population size, absolute disease burden was not independently associated with publication volume, whereas national economic capacity remained strongly associated with both outcomes. These patterns should inform research and service-delivery priorities.}, }
@article {pmid42769031, year = {2026}, author = {Liu, W and Hu, Q and Wu, P and Wang, D and Peng, Z and Liu, Z and Chen, X}, title = {Cellular Biological Basis and Novel Breakthroughs in the Pathogenesis of Myopia - A Narrative Review.}, journal = {International journal of general medicine}, volume = {19}, number = {}, pages = {633540}, pmid = {42769031}, issn = {1178-7074}, abstract = {Myopia has evolved into a severe global public health concern, exhibiting an epidemiological trend of earlier onset and higher refractive errors particularly among adolescents. Complications induced by high myopia, such as retinal detachment and macular degeneration, pose grave threats to visual health. This paper is a narrative review. It summarizes advances in the cell biology of myopia, elucidates the mechanisms underlying myopia mediated by multiple intraocular cell types, interprets several interactive regulatory pathways, and reviews biomarkers, targeted interventions and detection technologies. Different from previous reviews, this paper links retinal light signaling, intraocular cross‑tissue communication and scleral remodeling, with a focus on corneal biomechanics and the crosstalk between immunity and aging. It establishes an integrated analytical framework of "retinal phototransduction - trans-tissue cellular communication - scleral matrix remodeling", from which three core mechanistic conclusions are drawn: 1) Myopia is a sterile, chronic low-grade inflammation driven by coordinated dysfunction of multiple ocular tissue cells; cellular senescence and localized inflammation form a positive feedback loop that continuously fuels excessive axial elongation. 2) Retinal glial cells and retinal pigment epithelium serve as relays for visual growth signals. Abnormal defocus disrupts their secretion of cytokines, breaking the homeostasis of scleral collagen synthesis and degradation. 3) The hypoxic microenvironment of the choroid can amplify scleral remodeling and exacerbate myopia progression. Integrating the multilayered signaling regulatory network formed by cells of the cornea, retina and sclera helps clarify the complete pathological logic underlying multicellular synergistic pathogenesis of myopia. It provides mechanistic evidence for the clinical development of an early myopia warning system, tissue-specific targeted pharmaceuticals and stratified individualized prevention and control regimens, and facilitates the shift of myopia intervention from conventional empirical management to a novel precision diagnosis and treatment paradigm grounded in cellular and molecular characteristics.}, }
@article {pmid42769495, year = {2026}, author = {Moosa, A and Wang, JJ and DeAngelis, MM and Zhang, SX}, title = {The MTRNR2L gene family and age-related macular degeneration.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1925795}, pmid = {42769495}, issn = {1664-3224}, mesh = {Humans ; *Macular Degeneration/genetics/metabolism/pathology ; Animals ; Retinal Pigment Epithelium/metabolism/pathology ; Oxidative Stress ; Multigene Family ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in aging adults, yet no FDA-approved therapies exist for early and intermediate disease. Multiple interconnected pathways, including mitochondrial dysfunction, oxidative stress, and inflammation, contribute to retinal pigment epithelium (RPE) degeneration in AMD, highlighting the need for developing new cytoprotective strategies. The MTRNR2L gene family, comprising nuclear paralogs of mitochondrial-derived peptide humanin, has emerged as a potential regulator of these pathways. Humanin has demonstrated anti-apoptotic, anti-inflammatory, and mitochondrial-stabilizing effects across multiple cell types, including the RPE. Recent transcriptomic and single-cell RNA-sequencing (scRNA-seq) analyses indicate that MTRNR2L genes are upregulated in a variety of human diseases associated with cellular stress response, inflammation, angiogenesis, and neurodegeneration. These findings suggest that MTRNR2L genes participate in coordinated stress-adaptive programs and may mirror humanin's cytoprotective and immunomodulating actions. This review summarizes recent research advances and highlights key gaps for understanding the roles of the MTRNR2L family in RPE protection and AMD progression.}, }
@article {pmid42770020, year = {2026}, author = {Chen, Z and Bach, B and Zhang, H and Wahle, A and Han, IC and Boldt, HC and Russell, SR and Sonka, M and Sohn, EH}, title = {Retinal fluid segmentation in real-world OCT imaging of neovascular AMD using hybrid deep learning and graph-based optimization.}, journal = {Biomedical optics express}, volume = {17}, number = {9}, pages = {4834-4853}, pmid = {42770020}, issn = {2156-7085}, abstract = {Accurate segmentation and quantification of retinal fluid in optical coherence tomography (OCT) images are important for assessing disease activity and treatment response in neovascular age-related macular degeneration (nvAMD). Yet, manual delineation of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) is labor-intensive and subject to inter-grader variability. We developed a hybrid framework for robust retinal fluid segmentation in clinical-grade longitudinal OCT, combining anatomically constrained retinal-region extraction using Deep LOGISMOS with nnU-Net-based 2-D and 3-D fluid segmentation. To improve adaptation to heterogeneous clinical data while reducing annotation burden, an iterative expert-guided labeling strategy was used, starting with 70 RETOUCH OCT scans and 100 scans from subjects with macular neovascularization at the University of Iowa and expanding to a final aggregated training set of 291 scans. The method was validated on a held-out test set of 50 OCT volumes from 50 nvAMD subjects, with a subset of 20 volumes independently annotated by a second expert for inter-observer analysis. It was further applied to a longitudinal dataset of 14,500 Heidelberg Spectralis macular OCT scans from 221 independent subjects. The ensemble model achieved Dice similarity coefficients (%) of 89.5±11.7 for IRF, 88.0±10.7 for SRF, and 82.0±13.0 for PED against the primary expert annotations, with performance approaching expert-level agreement. In longitudinal inference, our developed framework supports robust large-scale quantification of fluid burden and spatial extent across heterogeneous scan protocols and extended follow-up. The artificial intelligence-based approach has the potential to enable scalable and clinically meaningful longitudinal analysis of retinal fluid in nvAMD.}, }
@article {pmid42770042, year = {2026}, author = {Kucharczuk, J and Kasprzak, H and Tuchowska-Celej, M and Gawęcki, M}, title = {Incidence and Clinical Course of Intraocular Inflammation Following Pharmacy-Compounded Intravitreal Aflibercept 8mg for Neovascular AMD: A Real-World Cohort Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {643475}, pmid = {42770042}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the incidence and clinical course of intraocular inflammation (IOI) after intravitreal aflibercept 8 mg (Eylea 8 mg - E8) injection in patients with neovascular age-related macular degeneration (nAMD) in Poland.<br><br>PATIENTS AND METHODS: This retrospective study included 867 eyes of 867 patients (591 female, 276 male) with nAMD treated with E8 at the 10[th] Military Hospital in Bydgoszcz between January and December 2025. Of these, 655 patients were switched from other intravitreal agents and 212 were treatment-na&#xef;ve. A total of 3441 E8 injections were administered before IOI onset, with two full 0.07mL (8mg) doses withdrawn from each single-use vial through pharmacy compounding. IOI severity was graded using the Standardization of Uveitis Nomenclature (SUN) criteria, and clinical course and outcomes were analyzed over 6 months of follow-up.<br><br>RESULTS: IOI occurred in 20 patients, corresponding to an incidence of 2.31% per eye/patient and 0.58% per injection. Symptoms appeared a mean of 3.3 &#xb1; 1.9 days after injection, with decreased visual acuity (BCVA dropped from 0.22 &#xb1; 0.10 to 0.58 &#xb1; 0.45 logMAR, p=0.0005). All cases were managed with topical corticosteroids, 16/20 additionally received sub-Tenon triamcinolone, and 6 required oral prednisolone; 1 patient required pars plana vitrectomy. Nineteen patients resolved on medical therapy alone, while one patient required surgical intervention (pars plana vitrectomy) to achieve resolution. No retinal vasculitis occurred, and central retinal thickness remained stable during follow-up.<br><br>CONCLUSION: In this first Polish cohort study, the incidence of IOI after E8 injection (2.31% per eye/patient) was higher than reported in registration trials, though episodes were generally mild and self-limited, without long-term visual impact. These findings may help inform clinical monitoring for patients receiving E8 for nAMD.}, }
@article {pmid42770455, year = {2026}, author = {Chinthaginjala, H and E, B and Thriveni, A and Vardhan, KV and Sai Kumar, M and Repollu, M}, title = {Exosomes in Ophthalmology: Bridging Physiological Barriers for Precision Ocular Drug Delivery.}, journal = {Current drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113894501468995260904090347}, pmid = {42770455}, issn = {1873-5592}, abstract = {INTRODUCTION: Eye disorders such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis persist as prominent contributors to visual impairment on a global scale. Conventional ocular drug delivery systems face a range of physiological hurdles, including tear film clearance, epithelium absorption, conjunctival absorption, and the formidable blood-retinal barrier. These challenges culminate in suboptimal ocular bioavailability, frequently compelling healthcare providers to resort to invasive drug administration methods.<br><br>METHODS: This review systematically evaluates recent literature focusing on exosome-based ocular drug delivery systems. Published preclinical and clinical studies were identified through structured searches of PubMed, Scopus, and Web of Science using the keywords "exosomes", "extracellular vesicles", "ocular drug delivery", "retina", and "ophthalmology". The search covered studies published between 2000 and 2025 to understand exosome biology, isolation and characterization techniques, drug-loading strategies, and their ability to overcome ocular physiological barriers.<br><br>RESULTS: Exosomes are naturally occurring extracellular vesicles enriched with proteins, lipids, and nucleic acids, exhibiting excellent biocompatibility and intrinsic targeting capabilities. Evidence from preclinical studies demonstrates their ability to traverse ocular barriers and enhance drug retention and bioavailability. Emerging clinical investigations highlight their therapeutic promise in retinal and anterior segment disorders.<br><br>DISCUSSION: Compared with synthetic nanocarriers, exosomes offer superior biological stability, reduced immunogenicity, and enhanced tissue penetration. However, challenges related to largescale production, standardization, storage stability, immunological safety, and regulatory approval remain critical barriers to clinical translation.<br><br>CONCLUSION: Exosome-based ocular drug delivery represents a promising precision medicine strategy that addresses long-standing limitations of conventional ophthalmic therapies. Continued advances in formulation optimization, scalable manufacturing, and regulatory frameworks are expected to accelerate their clinical and commercial translation for patient-centered eye care.}, }
@article {pmid42770919, year = {2026}, author = {Chew, EY and Ying, GS and Vitale, S}, title = {Does Cataract Surgery Accelerate the Progression to Late Age-related Macular Degeneration?.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.08.036}, pmid = {42770919}, issn = {1549-4713}, }
@article {pmid42771471, year = {2026}, author = {Park, S and Galdamez, A and Temme, W and Bradley, A and Le, M and Chea, L and Stevenson, E and Gradilla, Y and Lee, EJ and Lin, JH}, title = {Ceapin-A7 Suppresses UPR Signaling and Mitigates Retinal Neovascularization in Vldlr[-/-] Mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {18}, pages = {e72300}, doi = {10.1096/fj.202603175R}, pmid = {42771471}, issn = {1530-6860}, support = {P30EY026877//National Institutes of Health (NIH)/ ; R01EY027735//National Institutes of Health (NIH)/ ; R01NS088485//National Institutes of Health (NIH)/ ; I01RX001240/VA/VA/United States ; }, mesh = {Animals ; *Retinal Neovascularization/metabolism/drug therapy/pathology ; *Receptors, LDL/genetics ; Mice ; *Unfolded Protein Response/drug effects ; Activating Transcription Factor 6/metabolism/antagonists &amp; inhibitors/genetics ; *Signal Transduction/drug effects ; Mice, Knockout ; Mice, Inbred C57BL ; Retina/metabolism ; }, abstract = {Pathological neovascularization drives blinding retinal diseases, including diabetic retinopathy, retinopathy of prematurity, and neovascular age-related macular degeneration. Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling are key mechanisms underlying neovascularization. Mice lacking the UPR regulator Activating Transcription Factor 6 (ATF6) show normal retinal vasculature yet are resistant to pathologic neovascularization, suggesting that ATF6 inhibition may mitigate retinal damage and vision loss from aberrant retinal angiogenesis. We tested Ceapin-A7, a selective ATF6 inhibitor, in Vldlr[-/-] mice, a genetic model of retinal neovascularization. Intravitreal Ceapin-A7 reduced ectopic vascular projections into the outer retina and significantly increased scotopic b-wave amplitude, while a-wave and photopic responses showed no significant difference between groups. Single-nucleus RNA sequencing revealed suppressed ATF6/UPR gene programs and angiogenic pathways in retinal endothelial cells and reduced Müller cell gliosis. These findings demonstrate that pharmacologic ATF6 inhibition mitigates retinal neovascularization in Vldlr[-/-] mice and identifies ATF6/UPR as a therapeutic target for neovascular retinal diseases.}, }
@article {pmid42772557, year = {2026}, author = {Subrahmanian, SM and Sunilkumar, S and Budakoti, S and Yerlikaya, EI and Toro, AL and Barber, AJ and Dennis, MD}, title = {Regulation of Müller glial reprogramming by the stress response protein REDD1 and its limitations in preventing retinal degeneration.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {113583}, doi = {10.1016/j.jbc.2026.113583}, pmid = {42772557}, issn = {1083-351X}, abstract = {Studies here investigated the role of the stress-response protein regulated in development and DNA damage response 1 (REDD1) in Müller glial reprogramming in response to sodium iodate (NaIO3)-induced retinal degeneration. We previously demonstrated that global REDD1 deletion protected mice from NaIO3-induced retinal damage. NaIO3 promoted Müller glial remodeling, characterized by increased levels of glial fibrillary acidic protein (GFAP) and the horizontal orientation of Müller glial processes that localized to areas of retinal degeneration. NaIO3 increased TGF-β1 and mesenchymal gene expression in the retina, including upregulation of N-Cadherin in Müller glia. Retinal gliosis and mesenchymal markers were reduced in the retina of REDD1-deficient mice as compared to wild-type mice after NaIO3 administration, but this was likely secondary to retinal protection. TGF-β signaling was also investigated in human MIO-M1 Müller cell cultures. TGF-β1 increased REDD1 and the expression of gliosis and mesenchymal markers in wild-type Müller cells, and REDD1 deletion reduced TGF-β1-induced mesenchymal marker expression. REDD1 and its downstream effector GSK3β were required for TGF-β1-induced Smad2 linker domain phosphorylation and mesenchymal marker expression. To investigate the role of REDD1-dependent Müller glial reprogramming in retinal protection, NaIO3 was administered to Müller-glia specific REDD1 knockout mice. Müller glia-specific REDD1 deletion attenuated Müller cell remodeling; however, NaIO3-induced retinal damage was similar in Müller glia-specific REDD1 knockout and floxed control mice and visual function was only modestly preserved. The findings support the role of REDD1-dependent signaling in Müller cell reprogramming and implicate a critical role for REDD1 in cells beyond Müller glia in pathological retinal degeneration.}, }
@article {pmid42774045, year = {2026}, author = {Esser, E and Kuhrt, H and Ziemssen, F and Hollborn, M}, title = {Toll-like receptor 9 in retinal pigment epithelial cells: Expression, function and the role of TGF-β1.}, journal = {Molecular vision}, volume = {32}, number = {}, pages = {210-230}, pmid = {42774045}, issn = {1090-0535}, mesh = {*Retinal Pigment Epithelium/metabolism/cytology/drug effects ; Humans ; *Toll-Like Receptor 9/genetics/metabolism/agonists ; *Transforming Growth Factor beta1/metabolism/pharmacology ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Cell Hypoxia/drug effects ; Cobalt/pharmacology ; *Epithelial Cells/metabolism/drug effects/cytology ; Signal Transduction/drug effects ; Cell Survival/drug effects ; Gene Expression Regulation/drug effects ; Cell Line ; Toll-Like Receptor Agonists ; Cellular Senescence/drug effects ; RNA, Messenger/genetics/metabolism ; }, abstract = {PURPOSE: Inflammatory processes in the aged retina may be exacerbated by systemic infection with viruses and bacteria, potentially aggravating age-related macular degeneration (AMD). Toll-like receptors (TLR) are key mediators in detecting pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs). This study aimed to investigate TLR gene expression in cultured retinal pigment epithelial (RPE) cells, focusing particularly on TLR9.<br><br>METHODS: TLR gene expression was assessed using semiquantitative qPCR, while protein expression was evaluated through western blotting, immunocytochemistry, and ELISA. Hypoxic conditions were simulated using CoCl2 or by incubation in a 0.1% O2 atmosphere. RPE cell proliferation and viability were examined using bromodeoxyuridine (BrdU) and MTT assays. Cell necrosis and apoptosis were analyzed with a cellular DNA fragmentation ELISA.<br><br>RESULTS: Among the TLRs analyzed, TLR9 showed the most pronounced upregulation under hypoxic conditions. TLR9 protein expression was similarly induced by CoCl2 as well as in a 0.1% O2 atmosphere. Hypoxia increased the protein levels of &#x3b3;H2A.X, a marker for DNA damage and cellular senescence. The TLR9 agonist ODN 1826 induced the gene expression of downstream signaling molecules (MYD88, IRF7, RELA), inflammatory factors (IFNA, COX2), and MMP9 as well as the secretion of TGF-&#x3b2;1. These effects were reversed by TLR9 inhibitors (ODN 2088 and ODN INH-18). Transforming growth factor (TGF)-&#x3b2;1 significantly suppressed the TLR9 expression at both the mRNA and protein levels. This suppressive effect was reversed at the RNA level by inhibiting components of the TGF-&#x3b2;1 signaling pathway, including activin receptor-like kinase (ALK), Smad3, p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphatidylinositol 3-kinase (PI3K) under hypoxic conditions.<br><br>CONCLUSIONS: TLR9 activation under hypoxic conditions initiates pro-inflammatory pathways in RPE cells. In the aging retina, viral and bacterial infections and/or DAMPs may further amplify these responses, worsening retinal degeneration. TGF-&#x3b2;1 may exert protective, anti-inflammatory effects by downregulating TLR9 expression.}, }
@article {pmid42774060, year = {2026}, author = {Dohl, J and Zaw, NL and Nguyen, J and Burns, G and Park, B and Atilano, S and Schneider, K and Chwa, M and Kenney, MC}, title = {Assessing mitochondrial phenotypes in a cybrid model of dry age-related macular degeneration.}, journal = {Molecular vision}, volume = {32}, number = {}, pages = {196-208}, pmid = {42774060}, issn = {1090-0535}, mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; DNA, Mitochondrial/genetics/metabolism ; Phenotype ; Retinal Pigment Epithelium/metabolism/pathology ; *Geographic Atrophy/metabolism/pathology/genetics ; *Hybrid Cells/metabolism/pathology ; Membrane Potential, Mitochondrial ; Oxygen Consumption ; Cell Line ; Blood Platelets/metabolism/pathology ; Mitochondrial Proteins/metabolism/genetics ; Reactive Oxygen Species/metabolism ; *Macular Degeneration/metabolism/pathology/genetics ; }, abstract = {PURPOSE: Dry age-related macular degeneration (DAMD) is the leading cause of vision loss in developed countries, yet there are no FDA-approved treatments currently available. Mitochondria play a significant role in the pathology of DAMD; the retinal pigment epithelium cells of patients with DAMD exhibit mitochondrial dysfunction, elevated levels of mitochondrial DNA lesions, and increased mitochondrial reactive oxygen species. Investigations into the mitochondrial contributions to DAMD are complex as human tissue is challenging to acquire, and animal models do not fully recapitulate disease phenotypes. Cytoplasmic hybrid (cybrid) cells, formed by depleting the mitochondria of an immortalized cell line and fusing with patient platelets, are a possible model for mitochondrial studies on DAMD. This study evaluates if cybrid models of DAMD recapitulate the mitochondrial hallmarks of the disease, including mitochondrial dysfunction, decreased mitochondrial protein levels, lipid accumulation, and mitochondrial DNA lesions.<br><br>METHODS: The mitochondrial functions of five healthy and five DAMD cybrid cell lines were compared based on mitochondrial oxygen consumption rates, membrane potential, and protein expression. Secondary factors of mitochondrial dysfunction, including lipid accumulation and mitochondrial DNA stress response, were also examined.<br><br>RESULTS: Compared to healthy control cybrid lines, we found no alterations in bioenergetics, protein levels, and lipid accumulation in DAMD cybrid lines. Mitochondrial DNA stress responses were aberrant in DAMD cybrids compared to healthy controls, suggesting some conserved mitochondrial dysfunction.<br><br>CONCLUSIONS: Taken together, this study suggests that these DAMD cybrids do not fully recapitulate DAMD mitochondrial pathology, though this is limited to the study population of males with the H mtDNA haplogroup. However, there may be a niche for cybrid cell lines in investigating mitochondrial DNA phenotypes in patients with DAMD. This is likely because DAMD is a multifactorial disease, dependent upon an individual's genetics and the retinal microenvironment.}, }
@article {pmid42774544, year = {2026}, author = {Crincoli, E and Borrelli, E and Savastano, MC and Catania, F and Carlà, MM and Bacherini, D and Caporossi, T and Scampoli, A and Giannuzzi, F and Rizzo, C and Vallino, V and Boscia, G and Savastano, A and Reibaldi, M and Rizzo, S}, title = {Differential Remodeling of the Macular Neovascular Network under Different Anti-VEGF Agents in Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101336}, pmid = {42774544}, issn = {2666-9145}, abstract = {PURPOSE: To compare treatment-induced changes in OCT B-scan and OCT angiography (OCTA)-derived characteristics of the macular neovascular (MNV) network among different anti-VEGF agents in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Multicenter retrospective observational cohort study.<br><br>SUBJECTS: A total of 120 eyes from 102 patients with nAMD treated with ranibizumab 0.5 mg every 4 weeks (n = 30), aflibercept 2.0 mg every 4 weeks (n = 30), aflibercept 8.0 mg every 12 weeks (n = 30), or faricimab 6.0 mg every 8 weeks (n = 30) in a treat-and-extend regimen.<br><br>METHODS: Eyes with good-quality OCT B-scan and OCTA acquisitions at baseline and 1-year follow-up were included. OCT B-scan variables included pigment epithelium detachment (PED) height, PED homogeneity, and presence of intraretinal cystoid lesions and hyperreflective foci. OCT angiography variables included greatest linear diameter (GLD), MNV area, vessel density (VD), vessel length density (VLD), and VD index (VDI).<br><br>MAIN OUTCOME MEASURES: Between-group differences in OCT B-scan and OCTA parameters at 1-year follow-up, adjusted for baseline values and clinical covariates using multivariable regression with cluster-robust standard errors.<br><br>RESULTS: Baseline characteristics were comparable across groups. Significant between-group differences were observed at 1 year for GLD (P = 0.003), MNV area (P = 0.001), VD (P < 0.001), VLD (P = 0.002), and VDI (P < 0.001). Faricimab-treated eyes consistently showed the lowest adjusted 1-year values for all OCTA endpoints, with a mean VDI of 1.150 &#xb1; 0.07 compared with 1.453 &#xb1; 0.05 for ranibizumab, 1.334 &#xb1; 0.06 for aflibercept 2 mg, and 1.231 &#xb1; 0.06 for aflibercept 8 mg. Structural OCT outcomes differed significantly for PED height (P = 0.001) and PED homogeneity (P = 0.007), with faricimab showing the lowest PED height and highest homogeneity. No significant differences were observed for qualitative variables.<br><br>CONCLUSIONS: Dual VEGF-A/angiopoietin-2 inhibition with faricimab induces greater anatomical remodeling of the MNV network compared with VEGF-A inhibition alone, with a distinct pattern characterized by preferential impact on larger-caliber vessels. These findings suggest that targeting the angiopoietin-2 pathway extends the morphological effects of anti-VEGF therapy beyond peripheral capillary pruning. Long-term studies are needed to determine whether deeper anatomical suppression translates into improved clinical outcomes or influences the trajectory of macular atrophy.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42775094, year = {2026}, author = {Futterknecht, S and Pfau, M and Hall, U and Gabrani, C and Anders, P and Ansari, G and Traber, GL and Scholl, HP and Feltgen, N and Herzog, M and Garobbio, SA and Pfau, K}, title = {Spatial-Frequency-Dependent Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101351}, pmid = {42775094}, issn = {2666-9145}, abstract = {OBJECTIVE: To evaluate spatial-frequency-dependent differences in contrast sensitivity across early and intermediate age-related macular degeneration (eAMD and iAMD) and explore the discriminative value of visual function metrics beyond age.<br><br>DESIGN: Cross-sectional observational study.<br><br>SUBJECTS: Ninety-six participants from the Multimodal Assessment of Visual Function in Intermediate AMD study, including 49 controls, 14 participants with eAMD, and 33 with iAMD.<br><br>METHODS: Contrast sensitivity was assessed using the quick contrast sensitivity function method at six spatial frequencies from 1 to 18 cycles per degree, with derivation of contrast acuity and area under the log contrast sensitivity function (AULCSF). Additional visual function measures included microperimetry mean sensitivity, best-corrected visual acuity, and low-luminance visual acuity. Linear mixed-effects models evaluated associations between AMD stage, spatial frequency, and contrast sensitivity after adjustment for age- and lens-related covariates. Secondary analyses assessed the discriminative performance of visual function metrics using receiver operating characteristic analyses.<br><br>MAIN OUTCOME MEASURES: Contrast sensitivity across spatial frequencies and discriminative performance of visual function metrics.<br><br>RESULTS: In age- and lens-adjusted mixed-effects models, contrast sensitivity differed significantly by AMD stage (P < 0.001), with a significant AMD stage &#xd7; spatial frequency interaction (P = 0.035). Compared with controls, iAMD showed lower adjusted contrast sensitivity across most spatial frequencies, whereas eAMD differences were most pronounced at intermediate spatial frequencies. Discriminative analyses showed stronger separation of controls from iAMD than from eAMD. Microperimetry mean sensitivity provided the highest numerical discrimination for control versus iAMD and eAMD versus iAMD, whereas high-frequency contrast sensitivity and AULCSF performed best for control versus eAMD. Incremental gains beyond age- and lens-related covariates were modest for eAMD but larger for iAMD and for distinguishing eAMD from iAMD.<br><br>CONCLUSIONS: Contrast sensitivity differences in AMD are spatial-frequency-dependent and vary by disease stage after adjustment for age and lens-related covariates. Quick contrast sensitivity function-derived metrics showed modest incremental discrimination for eAMD, whereas microperimetry mean sensitivity and selected low-frequency contrast sensitivity measures better distinguished iAMD from controls and eAMD. These findings support spatial-frequency-resolved functional testing as an exploratory measure for AMD characterization; larger, age- and lens-balanced longitudinal cohorts are needed to determine prognostic utility.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42775100, year = {2026}, author = {Basile, M and Valentini, I and Calosci, EM and Sciomenta, I and Di Brino, E and Rumi, F and Barca, F and De Angelis, L and Savastano, A and Francione, G and Sasso, P and Toro Mario, D and Giglio, R and Rizzo, S}, title = {Cost-Effectiveness of the Smaller-Incision New Generation Implantable Miniature Telescope for Late-Stage Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101357}, pmid = {42775100}, issn = {2666-9145}, abstract = {OBJECTIVE: To assess the cost-effectiveness of the smaller-incision new-generation implantable miniature telescope (SING IMT) versus conventional standard care (CSC) from the Italian National Health Service (NHS) and societal perspectives.<br><br>DESIGN: Model-based cost-utility analysis.<br><br>SUBJECTS: A simulated cohort of patients with bilateral late-/end-stage age-related macular degeneration (AMD), based on a prospective multicenter study population (mean age, 76 years) eligible for SING IMT, compared with a clinically comparable cohort receiving CSC.<br><br>METHODS: A cohort Markov model with quarterly cycles and a lifetime horizon evaluated monocular SING IMT implantation, structured 6-month postoperative low-vision rehabilitation, and scheduled ophthalmologic follow-up. Costs included device acquisition, surgery, rehabilitation, follow-up, wet AMD treatment and monitoring, visual impairment and blindness, and adverse-event management. Costs and outcomes were discounted at 3% annually. Deterministic and probabilistic sensitivity analyses assessed uncertainty.<br><br>MAIN OUTCOME MEASURES: Incremental costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-utility ratio, and net monetary benefit (NMB) at a &#x20ac;40,000/QALY willingness-to-pay threshold.<br><br>RESULTS: In the deterministic base case, SING IMT provided 1.59 additional LYs and 1.27 additional QALYs versus CSC. From the NHS perspective, its incremental cost was &#x20ac;21,760.60, yielding incremental cost-effectiveness ratios of &#x20ac;13,712.33 per LY and &#x20ac;17,137.15 per QALY gained; incremental NMB was &#x20ac;29,031.05. Including societal blindness-related costs, SING IMT reduced total per-patient costs (&#x20ac;35,446.33 vs &#x20ac;74,035.45; difference, -&#x20ac;38,589.12), primarily through lower lifetime blindness costs. Thus, from the combined NHS and societal perspective, SING IMT was dominant, with an incremental NMB of &#x20ac;89,380.77. Results were robust in sensitivity analyses; baseline age was the main source of variability, whereas surgical time, visit frequency, and unit costs had marginal effects.<br><br>CONCLUSIONS: For appropriately selected Italian patients with late-stage AMD, SING IMT is expected to be cost-effective versus CSC, providing clinically meaningful gains in quality-adjusted survival. It is cost-effective but not cost-saving from the NHS perspective alone and becomes dominant when societal costs are included, owing mainly to avoided blindness-related expenditure. Findings are specific to the Italian health care context.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42775202, year = {2026}, author = {Chen, X and Ji, J and Yao, J and Chen, P and Zhang, J and Liu, L and Wen, X}, title = {The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1893953}, pmid = {42775202}, issn = {2296-634X}, abstract = {Extracellular purinergic signaling, mediated by nucleotides such as adenosine triphosphate (ATP) and adenosine, is a critical regulator of retinal homeostasis. Within the retina, this signaling pathway is indispensable for maintaining physiological functions. Dysregulation of extracellular purine balance is a key driver of retinal pathophysiology, contributing to inflammation, pathological angiogenesis, and neurodegeneration in diseases like diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and retinopathy of prematurity (ROP). The hydrolysis of extracellular ATP to adenosine, primarily orchestrated by the sequential actions of NTPDase1/ENTPD1 (CD39) and ecto-5'-nucleotidase/NT5E (CD73), represents a fundamental mechanism for calibrating purinergic signals and shifting the microenvironment from pro-inflammatory to anti-inflammatory and protective. CD39 and CD73 are pivotal enzymes in regulating retinal purinergic equilibrium. Despite their well-characterized roles in tumor biology and cerebral pathophysiology, the expression, physiological functions, and pathological implications of CD39/CD73 in the retina remain understudied and lack systematic synthesis. This review synthesizes current understanding of the roles of CD39 and CD73 in retinal physiology and pathology, with a focus on their implications in DR, AMD, glaucoma, and ROP. Critically, this review provides the first systematic integration of their layer-specific spatial compartmentalization, context-dependent functional duality, and emerging metabolic roles in photoreceptor homeostasis. We also discuss emerging therapeutic strategies that target this pathway, addressing the growing need for translational research to preserve vision.}, }
@article {pmid42763047, year = {2026}, author = {Yang, L and Li, Z}, title = {A New Omics View of Retinal Aging: Cell-Type Vulnerability, Spatial Niches, and Disease Susceptibility.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111243}, doi = {10.1016/j.exer.2026.111243}, pmid = {42763047}, issn = {1096-0007}, abstract = {Classical accounts of retinal aging emphasize oxidative, mitochondrial, inflammatory, vascular, proteostatic, and retinal pigment epithelium (RPE)-centered mechanisms. Omics studies now confirm and refine this non-uniformity, showing that aging-associated signals vary by cell type, anatomical niche, molecular layer, and functional reserve. Direct evidence from single-cell and single-nucleus transcriptomics is strong for lineage- and subtype-specific aging programs in neural retina, RPE, glia, vascular cells, and choroidal immune populations. Spatial omics can generate and test localization hypotheses across anatomically defined foveolar/foveal, parafoveal, perifoveal, peripheral, vascular, glial, optic nerve head, and RPE-Bruch's membrane-choroid niches, but direct spatial-omics evidence for normal human retinal aging remains sparse. Proteomic, metabolic, lipidomic, epigenomic, and imaging mass spectrometry data help determine whether transcriptional aging states translate into altered protein turnover, metabolic reserve, lipid handling, chromatin state, and inflammatory memory. AI-derived retinal age clocks provide population-scale imaging phenotypes, but color fundus photography alone is poorly depth-resolved; biological interpretation requires optical coherence tomography (OCT), visual function, biomarkers, destructive cell-type-resolved or spatially resolved tissue data, and longitudinal imaging or functional data. We integrate these findings into a multi-scale model in which normal retinal aging may lower resilience thresholds in defined cells and niches, thereby contributing to susceptibility to age-related macular degeneration, glaucoma, diabetic retinopathy, and inherited retinal degeneration. We also outline minimum standards for retinal aging omics, including anatomically specified sampling, donor metadata, evidence-source class interpretation, spatial validation, perturbation or rescue testing, and measurable endpoints of retinal resilience and visual function.}, }
@article {pmid42763542, year = {2026}, author = {Aljied, R and Saggu, S and Chaudhary, V and Pigeyre, M and Griffith, LE and Raina, P}, title = {Multivariable Prognostic Models for Age-Related Macular Degeneration: A Systematic Review.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {9231744}, pmid = {42763542}, issn = {2090-004X}, abstract = {BACKGROUND: Prognostic prediction models for age-related macular degeneration (AMD) are proliferating, driven by machine learning applied to retinal imaging. Although the methodological limitations of clinical prediction models are well recognized in general, AMD-specific multivariable prognostic models, as distinct from diagnostic or image-classification models, have not been appraised against contemporary prediction-model standards, with integrated assessment of outcome definitions, prediction horizons, calibration, validation design, and risk of bias.<br><br>OBJECTIVE: To systematically identify and critically appraise multivariable prognostic models predicting progression from non-late to late AMD and to determine whether quantitative synthesis was appropriate, with emphasis on model design, predictors, performance reporting, validation, and risk of bias.<br><br>METHODS: We searched PubMed/MEDLINE, and Embase from inception to April 2022, updated to December 2024, for studies developing, validating, or evaluating multivariable prognostic models for progression to late AMD. We extracted study population, outcomes, prediction horizons, predictors, modeling methods, performance measures, and validation approach and assessed risk of bias with PROBAST. Given substantial heterogeneity, findings were synthesized narratively in accordance with a prespecified conditional analysis plan (PROSPERO CRD42022323522).<br><br>RESULTS: Twenty studies were included. Models were derived from a small number of recurring cohorts, notably AREDS and HARBOR, of predominantly European ancestry; this limited population diversity was one of several constraints, alongside heterogeneous outcome definitions, infrequent calibration, and uncommon external validation. Approaches ranged from regression-based risk scores to deep learning applied to fundus photography, optical coherence tomography, or multimodal data. Because outcome definitions varied (composite late AMD, neovascular or exudative conversion, geographic atrophy or other atrophic endpoints, and treatment-initiation proxies), the observed AUC/c-statistic range (&#x223c;0.65-0.97) reflects differing prediction tasks rather than directly comparable performance. Calibration was addressed in six studies (30%), and fewer still met our definition of quantitative calibration. Imaging features and age were the most consistently retained predictors, and measures beyond discrimination were rare. Overfitting could not be excluded in several studies, as event counts, candidate-predictor numbers, use of shrinkage, and internal-validation procedures were incompletely reported. Ten of 20 studies were at low overall risk of bias, but calibration and external validation were uncommon across the evidence base as a whole.<br><br>CONCLUSIONS: Prognostic models for AMD progression are methodologically diverse but are drawn from few, homogeneous cohorts, with limited calibration and external validation, features that constrain interpretation of reported performance and transportability to routine, more diverse practice. Progress will depend less on new algorithms than on staged, feasible validation: prespecified outcomes and horizons, robust internal validation, routine calibration, and temporal or geographic validation with recalibration before clinical use. Until then, existing models should be regarded as exploratory rather than clinically actionable.}, }
@article {pmid42763736, year = {2026}, author = {Chakraborty, D and Sinha, TK and Biswas, RK and Maiti, A and Barman, MJ and Bhattacharya, R and Boral, S and Das, A}, title = {Real-World Analysis of Switching Between Ranibizumab Biosimilars: Safety and Results - a Multicenter Retrospective Observational Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {624886}, pmid = {42763736}, issn = {1177-5467}, abstract = {PURPOSE: To describe disease-specific visual, anatomical, treatment-exposure, and documented safety outcomes over 24 weeks among eyes undergoing availability-driven switching between ranibizumab biosimilars in routine retinal practice in India.<br><br>METHODS: This multicenter retrospective observational cohort study reviewed records from January to December 2024. Baseline was the index-switch visit, before administration of the substituted ranibizumab biosimilar. Only one eye per patient was included; when both eyes were eligible, the right eye was selected by convention. Eligible eyes had at least one documented availability-driven biosimilar-to-biosimilar switch and complete 24-week follow-up. Outcomes were summarized descriptively because there was no non-switch comparator group.<br><br>RESULTS: Of 742 screened eyes, 595 eyes from 595 patients met the inclusion criteria and received 1625 intravitreal ranibizumab biosimilar injections over 24&#xa0;weeks (mean, 2.73 injections per eye). One switch was recorded in 466 eyes (78.3%) and two switches in 129 eyes (21.7%). Mean BCVA improved from 0.57 logMAR at baseline to 0.26 at 12&#xa0;weeks and 0.32 at 24&#xa0;weeks; the early visual improvement therefore attenuated modestly by week 24 but remained better than baseline. Mean central macular thickness decreased from 490.4 micrometers at baseline to 273.6 micrometers at 24&#xa0;weeks. At final follow-up, 369 eyes (62.0%) gained at least two lines and 488 eyes (82.0%) maintained or improved vision. No endophthalmitis, retinal detachment, or treatment-related systemic adverse event was documented in the available clinical records.<br><br>CONCLUSION: Eyes exposed to availability-driven switching between ranibizumab biosimilars showed favorable short-term visual and anatomical outcomes over 24&#xa0;weeks. Because this retrospective study lacked a non-switch comparator and protocol-mandated safety or immunogenicity surveillance, it cannot establish an effect attributable to switching, comparative safety, equivalence, or formal interchangeability.}, }
@article {pmid42765048, year = {2026}, author = {Kang, MJ and LaBarre, N and Karo, M and Soong, R and Vida, TA}, title = {Illuminating Risk: An Ecological Analysis of Artificial Light at Night and Childhood Myopia Using State-Level US Data.}, journal = {Risk management and healthcare policy}, volume = {19}, number = {}, pages = {628850}, pmid = {42765048}, issn = {1179-1594}, abstract = {PURPOSE: Childhood myopia is a growing global health concern, associated with serious vision complications later in life, including retinal detachment and myopic macular degeneration. While behavioral factors such as screen time and reduced outdoor exposure have been studied, the potential contribution of environmental light pollution, particularly artificial light at night (ALAN), remains underexplored at the population level.<br><br>METHODS: We analyzed 2019 data from 46 US states to examine the association between ALAN and the prevalence of childhood myopia (ages 0-17). VIIRS satellite-derived nighttime radiance was used as a proxy for outdoor ambient lighting. Using generalized additive modeling (GAM), we examined nonlinear associations while adjusting for behavioral (screen time, insufficient sleep) and structural (Medicaid coverage, uninsured children, vision screening, optometrist density, urbanization) factors. Multicollinearity was assessed using Spearman correlation and variance inflation factors.<br><br>RESULTS: The final GAM explained 65.3% of the deviance in childhood myopia prevalence (adjusted R[2] = 0.509). Higher ALAN was significantly associated with higher myopia prevalence (F = 8.39, p = 0.0068). Screen time showed a nonlinear relationship, whereas sleep deprivation showed an unexpected inverse association, potentially reflecting detection disparities. Medicaid coverage showed a U-shaped association, with both low and high coverage associated with higher prevalence. Vision screening rates were positively associated with myopia prevalence, likely reflecting improved detection. Urbanization, optometrist density, and the number of Asian children were not statistically significant.<br><br>CONCLUSION: ALAN is a population-level correlate of childhood myopia in the US. Although not indicative of individual-level risk, its association warrants further ecological investigation and may merit consideration in environmental health and urban planning discussions. These findings highlight the multifactorial nature of pediatric refractive error and the value of integrating environmental exposure data into public health vision surveillance. Further individual-level research is needed to assess causal mechanisms.}, }
@article {pmid42765882, year = {2026}, author = {Tsukui, L and Miyata, M and Hata, M and Ooto, S and Tamura, H and Otsuka, A and Shirakami, M and Ueda-Arakawa, N and Miyake, M and Takahashi, A and Kadomoto, S and Muraoka, Y and Tsujikawa, A}, title = {ACUTE NEUROSENSORY RETINAL THINNING AND SHORT-TERM VISUAL OUTCOMES IN MASSIVE SUBMACULAR HEMORRHAGE: A LONGITUDINAL ANALYSIS FROM PRE-ONSET TO POST-DISPLACEMENT WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000005014}, pmid = {42765882}, issn = {1539-2864}, abstract = {PURPOSE: To investigate longitudinal visual and structural changes from pre-onset to 1 month postoperatively in eyes with massive submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) treated with subretinal tissue plasminogen activator (tPA) injection and to identify prognostic factors for visual outcomes.<br><br>METHODS: This retrospective observational study reviewed the medical records of consecutive eyes with massive SMH secondary to nAMD treated with pars plana vitrectomy with subretinal tPA injection and pneumatic displacement. We assessed best-corrected visual acuity (BCVA) and foveal sensory retinal thickness (FSRT) at pre-onset, preoperative, and 1-month postoperative time points.<br><br>RESULTS: Among 74 consecutive eyes treated with subretinal tPA injection for massive SMH, we analyzed 20 eyes with available pre-onset data. FSRT decreased significantly from 193.5 &#xb1; 101.4 &#x3bc;m at pre-onset to 107.0 &#xb1; 59.0 &#x3bc;m at 1 month postoperatively (P < 0.001). BCVA change negatively correlated with FSRT change (r = -0.56, P = 0.01). Univariable analysis showed that pre-onset BCVA significantly correlated with 1-month BCVA (r = 0.45, P = 0.049). At pre-onset, persistent fluid and pigment epithelial detachment were present in 65% and 15%, respectively.<br><br>CONCLUSIONS: Massive SMH causes acute and profound neurosensory retinal thinning, and pre-onset neuronal integrity may be a key determinant of visual outcomes. Because surgery cannot reverse this immediate damage, preventing hemorrhage by maintaining a strictly fluid-free macula may be an important proactive strategy.}, }
@article {pmid42767442, year = {2026}, author = {Luthert, PJ and Faes, L and Foss, AJ and Fu, DJ and Hill, LJ and Huang, R and Kiel, C and Lee, WH and Matei,  and Mirams, GR and Misson, G and Montesano, G and Niederer, S and Paraoan, L and Roberts, PA and Sivaprasad, S and Whitmore, SS and Zouache, MA and ,  and Bloomfield, PS}, title = {The Virtual Eye: An Integrative Multiscale Framework for Mechanistic Modelling of Ocular Physiology and Disease.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101529}, doi = {10.1016/j.preteyeres.2026.101529}, pmid = {42767442}, issn = {1873-1635}, abstract = {The Virtual Eye initiative described here seeks to build a versatile and integrative in silico platform, 'The Virtual Eye' that can capture and simulate the biology, physiology and function of the human eye, from molecular interactions to organ-level behaviour, in both healthy and diseased states. This effort has the potential to substantially deepen our understanding of the visual process, clarify the mechanistic basis of ocular diseases across multiple spatial and temporal scales, and support the development of therapeutic strategies for both common and rare eye conditions. A coordinated undertaking among biologists, biophysicists, clinicians, mathematicians and engineers has led to the development of a shared roadmap and collaborative investigations into foundational challenges, including for instance retinal vascular flow and the progression of geographic atrophy lesions in age-related macular degeneration (AMD). Here, we present an initial framework for advancing the Virtual Eye and define core models required to ensure its coherent development and expansion. This framework is rooted in current knowledge of biological mechanisms and integrated with mathematical representation, with the initial ambition of simulating a defined period of healthy function using a range of stimuli and experiments representing the natural world. We identify nine core modelling tasks that capture the healthy physiology of the eye and outline seven disease processes representing perturbations of normal function. Together, these components could form the first iteration of the Virtual Eye conceptual framework and roadmap for building it, enabling controlled experimental manipulation of a simulated system designed to generate realistic and biologically meaningful behaviours.}, }
@article {pmid42767615, year = {2026}, author = {Balas, M and Mihalache, A and Jhaveri, A and Kaleem, S and Popovic, MM and Kertes, PJ and Muni, RH}, title = {Congestive heart failure and other cardiac adverse events after intravitreal anti-VEGF therapy: a systematic review and meta-analysis.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.08.033}, pmid = {42767615}, issn = {1715-3360}, abstract = {OBJECTIVE: To evaluate congestive heart failure (CHF) and other cardiac adverse events (AEs) after intravitreal anti-vascular endothelial growth factor (VEGF) therapy for retinal vascular disease and compare risks across agents.<br><br>DESIGN: A systematic review and meta-analysis.<br><br>METHODS: Registered review (PROSPERO CRD42022302658) searched Ovid MEDLINE, Embase, and the Cochrane Library from January 2005 to February 2024 for randomized controlled trials (RCTs) of intravitreal anti-VEGF therapy for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. Eligible trials compared an anti-VEGF agent with sham or another anti-VEGF agent and reported CHF (primary outcome) or other cardiac AEs (secondary outcomes: arrhythmias, heart failure/cardiomyopathy, inflammatory heart disease, ischemic heart disease, or valvular heart disease). Risk of bias was assessed with RoB 2, certainty with GRADE, and random-effects models generated risk ratios (RRs) with 95% confidence intervals (CIs).<br><br>RESULTS: Fourteen reports describing 20 trials (11,803 eyes; mean age 71 &#xb1; 12 years; 53% female) were included. CHF was uncommon overall: aflibercept 2.0% (84/4172), ranibizumab 2.2% (25/1158), faricimab 2.3% (44/1926), brolucizumab 2.5% (40/1612), and sham 3.8% (20/524). Ranibizumab did not differ from sham for CHF (RR&#x202f;=&#x202f;1.53, 95% CI 0.46-5.06), whereas aflibercept was associated with higher CHF risk versus sham in 2 trials (RR&#x202f;=&#x202f;2.08, 95% CI: 1.03-4.23). No significant CHF differences were detected between aflibercept and brolucizumab, faricimab, or ranibizumab. Other cardiac events were similar across agents.<br><br>CONCLUSIONS: CHF and other AEs after intravitreal anti-VEGF therapy were uncommon in RCTs and comparable across agents. The aflibercept-sham CHF signal was based on limited evidence and should be interpreted cautiously.}, }
@article {pmid42767752, year = {2026}, author = {Miao, H and Tang, L and Lyu, X and Wu, L}, title = {Treatment burden and adherence in adults receiving long-term anti-VEGF intravitreal injections for retinal disease: a qualitative evidence synthesis protocol.}, journal = {BMJ open}, volume = {16}, number = {9}, pages = {e125908}, doi = {10.1136/bmjopen-2026-125908}, pmid = {42767752}, issn = {2044-6055}, mesh = {Humans ; Intravitreal Injections ; Systematic Reviews as Topic ; Qualitative Research ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Research Design ; *Retinal Diseases/drug therapy ; Macular Degeneration/drug therapy ; *Medication Adherence/psychology ; Cost of Illness ; Adult ; }, abstract = {INTRODUCTION: Retinal diseases such as neovascular age-related macular degeneration and diabetic macular oedema are leading causes of irreversible vision loss and require intravitreal anti-vascular endothelial growth factor (VEGF) injections over many years. Repeated treatment imposes physical, psychological, social and financial burdens and is associated with reduced adherence and poorer real-world outcomes. Existing research is largely quantitative and does not explain, from patients' perspectives, why people persist with, struggle against or discontinue burdensome treatment. This review will identify, appraise and synthesise qualitative studies to understand the burden of long-term anti-VEGF therapy, how it shapes adherence and the implications for patient-centred nursing care, shared decision-making and injection-service design.<br><br>METHODS AND ANALYSIS: This protocol is reported in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P); the completed synthesis will be reported following Enhancing Transparency in Reporting the Synthesis of Qualitative Research. We will use Thomas and Harden's three-stage thematic synthesis and the Population, Phenomenon of Interest, Context and Study design framework. Eligible studies are primary qualitative studies and independently extractable qualitative components of mixed-methods studies involving adults (&#x2265;18 years) receiving long-term anti-VEGF therapy for retinal disease, irrespective of publication language. Initial searches of nine databases (PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, CNKI, Wanfang Data and SinoMed) were conducted from inception between 31 May and 2 June 2026 and will be updated before completion of the review. Citation tracking and thesis-repository searches will supplement the database searches. Two reviewers will independently screen records, extract data and appraise quality using the Joanna Briggs Institute checklist, with disagreements resolved by a third reviewer. Confidence in each finding will be assessed using Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research.<br><br>ETHICS AND DISSEMINATION: Ethical approval is not required because the review uses published data. Six to eight patients, with up to two family advisers, will help interpret preliminary themes and develop a plain-language summary. Findings will be disseminated through peer-reviewed publication and conference presentation.<br><br>PROSPERO REGISTRATION NUMBER: CRD420261405614.}, }
@article {pmid42768077, year = {2026}, author = {Bilbao-Malavé, V and de la Puente, M and Ochoa-Tejada, L and Irigoyen Bañegil, C and Anduaga-Beramendi, A and Fraga de la Viesca, M and Llorente-González, S and Sáenz de Viteri, M and Hernández, M and Heras-Mulero, H and Arias-Barquet, L and García-Layana, A and Recalde, S and González-Zamora, J}, title = {Association between choroidal structure and retinal fluid location in type 1 neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42768077}, issn = {1476-5454}, abstract = {OBJECTIVES: To correlate choroidal structure parameters with the presence and amount of subretinal fluid (SRF) and intraretinal fluid (IRF) in treatment-naïve neovascular age-related macular degeneration (nAMD) patients with type 1 macular neovascularisation (MNV).<br><br>METHODS: A retrospective study reviewed clinical records of 96 patients diagnosed with nAMD between 2015 and 2022. Optical coherence tomography (OCT) scans were analysed for choroidal thickness, choroidal vascularity index (CVI), and large choroidal vessel index (LCVI) using ImageJ software with automated binarisation. SRF was manually quantified using embedded OCT tools, and IRF volume was measured using an artificial intelligence-based platform. Patients with type 1 MNV (n&#x2009;=&#x2009;56) were included for fluid-choroidal correlations. Statistical analyses included t-tests, Mann-Whitney U tests, and Spearman correlations (p&#x2009;<&#x2009;0.05).<br><br>RESULTS: In type 1 MNV eyes, SRF presence was associated with greater choroidal thickness (p&#x2009;=&#x2009;0.03), and SRF area correlated positively with choroidal thickness (p&#x2009;=&#x2009;0.02) and foveal LCVI (p&#x2009;=&#x2009;0.004). Maximum SRF height correlated with foveal LCVI (p&#x2009;=&#x2009;0.007). IRF presence was linked to reduced choroidal thickness (p&#x2009;=&#x2009;0.0008), and IRF volume inversely correlated with choroidal thickness (p&#x2009;=&#x2009;0.01) and macular LCVI (p&#x2009;=&#x2009;0.002). No significant choroidal changes were observed pre-MNV or compared to fellow eyes.<br><br>CONCLUSIONS: In treatment-na&#xef;ve type 1 MNV, choroidal thickness and LCVI exhibit opposite associations with subretinal and intraretinal fluid, emphasising distinct pathophysiological mechanisms: choroidal venous overload may be associated with SRF accumulation, while choroidal thinning may be implicated in IRF formation. These findings may help generate hypothesis regarding variability in anti-VEGF treatment response and suggest that choroidal characteristics warrant further investigation as potential biomarkers for future individualised management strategies.}, }
@article {pmid42768326, year = {2026}, author = {Karasu, B and Yılmaz Tuğan, B and Kesim, E and Özen, S}, title = {Rapid choroidal neovascularization after non-flap internal limiting membrane peeling for macular hole in a patient with AMD: a case report and literature review.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42768326}, issn = {1471-2415}, mesh = {Humans ; *Retinal Perforations/surgery/diagnosis/complications ; Female ; Aged ; *Choroidal Neovascularization/etiology/diagnosis ; *Vitrectomy/adverse effects ; Visual Acuity ; Tomography, Optical Coherence ; *Macular Degeneration/complications ; *Basement Membrane/surgery ; *Epiretinal Membrane/surgery ; *Postoperative Complications ; Fluorescein Angiography ; }, abstract = {BACKGROUND: Choroidal neovascularization (CNV) following macular hole (MH) surgery is a rare complication. While the exact pathogenesis remains unclear, previous reports in the literature suggest that it can occur in patients with pre-existing age-related macular degeneration (AMD) or macular drusen. In this report, we present a case that highlights the potential biomechanical triggers of this complication in an eye with AMD.<br><br>CASE PRESENTATION: We report the case of a 70-year-old female patient with AMD who presented with a full-thickness macular hole (FTMH). She underwent an uncomplicated 25-gauge pars plana vitrectomy with brilliant blue G-assisted internal limiting membrane (ILM) peeling and perfluoropropane gas tamponade. Notably, the ILM flap technique was not utilized; only standard, non-flap peeling without intraoperative complications was performed. Just 6 weeks postoperatively, the patient experienced a sudden decline in visual acuity due to the rapid development of CNV at the border of the ILM peeled-off area. Intravitreal aflibercept treatment was subsequently planned.<br><br>CONCLUSIONS: This case suggests that, in eyes with underlying AMD, CNV may develop rapidly after standard ILM peeling even without an ILM flap technique. Biomechanical stress related to ILM removal, potentially involving macular displacement and mechanical stress on M&#xfc;ller cells, may be a possible contributing factor, but causality cannot be established from a single case. Physicians should maintain high vigilance for this vision-threatening complication during the early postoperative period after MH surgery.}, }
@article {pmid42757636, year = {2026}, author = {Goodrich, Z and Schneider, J}, title = {Zinc-associated Copper Deficiency Myelopathy: A Case Report.}, journal = {Clinical neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1097/WNF.0000000000000701}, pmid = {42757636}, issn = {1537-162X}, abstract = {OBJECTIVE: Copper deficiency myelopathy is an uncommon but potentially reversible neurologic disorder characterized by sensory ataxia, gait impairment, and dorsal column dysfunction. Acquired copper deficiency most commonly results from malabsorption, prior gastrointestinal surgery, or excess zinc exposure. Zinc induces intestinal metallothionein, which preferentially binds copper and reduces its systemic absorption, potentially leading to hypocupremia and neurologic dysfunction. Although zinc-containing nutritional supplements are widely used, clinically significant neurologic complications remain rare.<br><br>METHODS: A retrospective review of the patient's medical history was performed in addition to a comprehensive literature review.<br><br>RESULTS: A 70-year-old woman receiving long-term zinc-containing PreserVision AREDS 2 supplementation for age-related macular degeneration presented with 6 months of progressive paresthesia, gait instability, and frequent falls. Neurologic examination demonstrated bilateral sensory deficits and weakness, while magnetic resonance imaging revealed dorsal column T2 hyperintensity. Laboratory evaluation showed undetectable serum copper, mildly elevated serum zinc, normocytic anemia, hypokalemia, and concurrent thiamine deficiency. Zinc-containing supplementation was discontinued, and the patient received copper and thiamine replacement. Over the following two months, serum copper normalized, and she experienced substantial neurologic recovery with restoration of independent ambulation.<br><br>CONCLUSIONS: This report describes a case of copper deficiency myelopathy in a patient receiving long-term high-dose zinc supplementation in the setting of multiple nutritional abnormalities. It highlights the importance of including copper deficiency in the differential diagnosis of patients receiving zinc-containing supplements who present with progressive myelopathy. It is intended to be hypothesis-generating and suggests that individual susceptibility and concurrent nutritional factors may contribute to the development of zinc-associated copper deficiency.}, }
@article {pmid42757924, year = {2026}, author = {Borchert, GA and Ferreira, LAF and Raji, S and Yu, J and Segovia, M and MacLaren, RE and Downes, SM and Cehajic-Kapetanovic, J and Xue, K and De Silva, SR}, title = {Apolipoprotein E2/2 (APOE2/2) Genotype Is Associated With Reduced Choroidal Thickness.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {11}, pages = {38}, doi = {10.1167/iovs.67.11.38}, pmid = {42757924}, issn = {1552-5783}, mesh = {Humans ; Female ; *Apolipoprotein E2/genetics ; Male ; Genotype ; Middle Aged ; *Choroid/pathology ; Tomography, Optical Coherence/methods ; Prospective Studies ; *Macular Degeneration/genetics ; Visual Acuity/physiology ; Aged ; Apolipoprotein E3/genetics ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of visual impairment in individuals >50 years. The APOE2 allele has been associated with increased AMD risk compared to the common APOE3 allele. However, the retinal phenotype of APOE2/2 individuals has not been characterized. This study aimed to compare the macular structure and function of APOE2/2 versus APOE3/3 homozygous individuals.<br><br>METHODS: Age- and sex-matched participants with APOE2/2 and APOE3/3 genotypes were prospectively recruited from the Oxford Biobank. Phenotyping included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), microperimetry, refractive error, multimodal retinal imaging, fasting lipid profile, and EPIC-Norfolk food frequency questionnaires. A linear mixed model of paired eye measurements with a subject-specific random intercept was applied, including age, sex, smoking status and refractive error as covariates. Findings were compared to similar UK Biobank cohorts.<br><br>RESULTS: 24 participants were recruited: 12 APOE2/2 and 12 APOE3/3 (mean age 60.5 &#xb1; 5.7 (standard deviation) years, female/male 1:1; 87.5% non-smokers). Serum triglycerides were significantly higher in APOE2/2 participants (1.8 vs. 1.03 mM, P = 0.010). A novel finding of reduced choroidal thickness was found in APOE2/2 compared to APOE3/3 participants after multivariate analysis controlling for age, sex, smoking status and refractive error (estimated difference 57.8 &#xb5;m, P = 0.02). Optical coherence tomography segmentation showed a trend toward reduced retinal thickness in APOE2/2 compared to APOE3/3 participants, but did not reach statistical significance. No differences in BCVA, LLVA, or retinal sensitivity were detected. Diet and background AMD genetic risk were comparable.<br><br>CONCLUSIONS: We report a novel genotype-phenotype association of reduced choroidal thickness in individuals homozygous for APOE2/2 compared with normative APOE3/3 controls.}, }
@article {pmid42759221, year = {2026}, author = {Neau, J and Turpin, A and Rajendrabose, D and Haneef, R and Soltani, O and Dilange, L and Couasnard, A and Bodaghi, B and Baudouin, C and Tubach, F and Guillo, S and Dechartres, A}, title = {Algorithms for the identification of ophthalmic diseases in medico-administrative databases: A systematic review.}, journal = {Journal of epidemiology and population health}, volume = {74}, number = {5}, pages = {203788}, doi = {10.1016/j.jeph.2026.203788}, pmid = {42759221}, issn = {2950-4333}, abstract = {CONTEXT: Medico-administrative databases (MADs) are increasingly used in comparative effectiveness research.<br><br>OBJECTIVE: To conduct a systematic review of algorithms used for the identification of key ophthalmic diseases in MADs: age-related macular degeneration (AMD), diabetic retinopathy (DR)/ diabetic macular edema (DME), glaucoma, cataract and uveitis.<br><br>METHODS: We searched PubMed between June 30, 2016, and August 6, 2024, using keywords related to MADs and the ophthalmic diseases of interest. Two reviewers independently selected studies and extracted data.<br><br>RESULTS: From the 1719 references identified, 315 were selected describing a total of 523 algorithms. Approximately half of the study objectives were related to the identification of factors associated with the onset of ophthalmic diseases, exacerbation, or hospitalization (48%, n = 151). Only 2% (n = 6) focused exclusively on the development and/or validation of algorithms. Most studies were from Taiwan (36%, n = 113), Korea (27%, n = 84) and the United States (20%, n = 64). From the 523 algorithms, a validation was mentioned for 47 (9%). After regrouping close algorithms, 433 different algorithms were identified concerning glaucoma (34%, n = 146), DR/DME (26%, n = 114), AMD (18%, n = 80), cataract (11%, n = 47) and uveitis (11%, n = 46). About half of these algorithms used diagnosis codes only (58%, n = 251), while others combined diagnosis codes and procedures (16%, n = 69), or diagnosis codes and drugs (12%, n = 50).<br><br>CONCLUSION: This systematic review showed heterogeneity between algorithms used to identify the same pathology, raising the question of which ones are more appropriate to use in a particular context. Moreover, most algorithms were not validated despite the potential impact on study results.}, }
@article {pmid42759378, year = {2026}, author = {Piloni-Parreira, R and Barbosa, MS and Neves, LL and Santana, HL and Rodrigues, JMRDS and Tavares, RS and Isaac, DLC and Pereira de Ávila, M}, title = {Ophthalmological and epidemiological profiles of Brazilian patients with philadelphia-negative Myeloproliferative neoplasms.}, journal = {Hematology, transfusion and cell therapy}, volume = {48}, number = {4}, pages = {106536}, doi = {10.1016/j.htct.2026.106536}, pmid = {42759378}, issn = {2531-1387}, abstract = {INTRODUCTION: Philadelphia-negative myeloproliferative neoplasms comprise a rare and biologically heterogeneous spectrum of hematopoietic stem cell malignancies. According to established clinicopathological criteria, these entities are principally categorized as polycythemia vera, essential thrombocythemia, or primary myelofibrosis. Ophthalmic manifestations are common in hematological diseases, yet they remain under-researched in this patient population.<br><br>METHODS: The purpose of this study is to analyze the ophthalmological and epidemiological profile of patients, describing ocular findings of Philadelphia-negative Myeloproliferative Neoplasms. Twenty-one individuals (forty-two eyes) with a Philadelphia-negative myeloproliferative neoplasm had their medical records selected, analyzed and relevant data collected. They were subsequently subjected to a complete ophthalmological evaluation, with assessment of visual acuity, biomicroscopy and fundoscopy employing wide-field color retinography and wide-field fundus autofluorescence examinations.<br><br>RESULTS: The mean age of participants was approximately 60 years, with a white demographic predominance and no sex bias. Most patients achieved early clinical diagnosis and effective disease control, with a high frequency harboring the JAK2 V617F mutation. Patients reported no subjective complaints of low visual acuity, and posterior segment involvement was sparse. Retinal hemorrhages were uncommon, occurring predominantly in polycythemia vera due to hyperviscosity or microvascular thrombosis in the absence of confounding ocular or systemic conditions. Fundoscopic lesions were mostly driven by comorbid diagnoses, specifically age-related macular degeneration (19.4%) and hypertensive retinopathy (9.5%).<br><br>CONCLUSION: Brazilian patients with well-controlled Ph-NMPs and early diagnosis rarely exhibit primary retinal complications or subjective low visual acuity. Retinal manifestations, particularly hemorrhages, are infrequent despite high rates of the JAK2 V617F mutation. Ocular findings in this population are more commonly driven by concurrent systemic or degenerative conditions, notably age-related macular degeneration.}, }
@article {pmid42759656, year = {2026}, author = {Jeong, YD and Jeon, S and Shin, W and Park, S and Park, T and Kim, TH and Smith, L and Rahmati, M and Yang, JM and Yon, DK}, title = {Global burden of age-related macular degeneration, with forecast up to 2050: a modelling study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.09.019}, pmid = {42759656}, issn = {2468-6530}, abstract = {TOPIC: We aimed to estimate the prevalence of age-related macular degeneration (AMD) using a single standardized classification and provide comparable global, regional, and national burden estimates from 1990 to 2050.<br><br>CLINICAL RELEVANCE: Owing to the marked heterogeneity in AMD classification criteria across the included studies, there remains a need to delineate the burden of AMD using a unified and standardized classification system.<br><br>METHODS: Following registration (CRD420251067039), a search was conducted in PubMed/MEDLINE, Embase, CINAHL, and Google Scholar. Eligible epidemiological studies reporting AMD prevalence were included, and extracted prevalence data were harmonized according to the Beckman classification. An expectation-maximization algorithm was applied to disaggregate data into early, intermediate, geographic atrophy (GA), and neovascular AMD (nAMD). Prevalence was modeled for 204 countries and territories using DisMod-MR, with projections to 2050 using a hybrid machine learning approach, including scenario analyses of tobacco reduction and increased physical activity. Estimates were stratified by clinical stage and ethnicity with 95% uncertainty intervals (UIs). Prevalence of AMD stratified by clinical stage (early, intermediate, geographic atrophy [GA], and neovascular AMD [nAMD]), age, sex, and ethnicity across 204 countries from 1990 to 2021, with projections and risk-reduction scenarios through 2050.<br><br>RESULTS: In 2021, the global prevalence of AMD across all stages was 10.03% (95% UI, 8.30-12.06); early AMD, 5.40% (4.72-6.14); intermediate AMD, 4.01% (3.41-4.66); GA, 0.32% (0.26-0.39); and nAMD, 0.31% (0.26-0.36). Prevalence increased from 1990 to 2021, whereas age-standardized rates declined. AMD prevalence rose sharply with age, with no significant sex differences in early or intermediate AMD. GA prevalence was highest among Hispanic populations, and nAMD among European populations. Projections indicate continued increases through 2050, with reductions under tobacco reduction and increased physical activity scenarios.<br><br>CONCLUSIONS: This study provides the first global, regional, and national prevalence estimates of AMD stratified by the Beckman classification, offering evidence to inform clinical practice and health policy.}, }
@article {pmid42755766, year = {2026}, author = {Guo, W and Wan, J and Zhang, F and Wu, X and Hong, Y and Wang, Z and Bian, W}, title = {Effect of a mobile application-based whole-course nutrition management intervention in patients with age-related macular degeneration: a randomized controlled trial.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1855870}, pmid = {42755766}, issn = {2296-2565}, mesh = {Humans ; *Macular Degeneration/diet therapy ; Female ; Male ; Aged ; *Mobile Applications ; Quality of Life ; Aged, 80 and over ; Nutritional Status ; Middle Aged ; Visual Acuity ; *Nutrition Therapy/methods ; }, abstract = {AIMS AND OBJECTIVES: Evaluate the effect of the application (APP)-based AIM-AMD (Assessment, Introduction, Management, and App-based Maintenance Dynamically) nutrition management model in patients with age-related macular degeneration (AMD).<br><br>BACKGROUND: Nutritional intervention are one of the only ways to prevent the development of AMD and slow its progression. However, poor compliance with patient nutritional management leads to ineffective nutritional supplementation outcomes.<br><br>DESIGN: A randomised controlled trial was conducted from October 2023-January 2024 and performed according to the CONSORT guidelines.<br><br>METHODS: A total of 140 participants were randomly assigned to the intervention or control group. The intervention was administered three times per week for a period of 3&#x202f;months. The intervention group was adopted with APP-based AIM-AMD nutrition management + routine nursing, while the control group was adopted with routine nursing. Comparison was conducted on the effects of different programs on AMD patient nutrient intake, nutrition knowledge, vision-related quality of life, self-efficacy and best-corrected visual acuity (BCVA) at the beginning and at the end of the intervention (Clinical Trials.gov: ChiCTR2200063978).<br><br>RESULTS: The results indicated that the intake of energy, zinc, copper, calcium, vitamin C, vitamin E and lutein was significantly higher in the intervention group than in the control group (p&#x202f;<&#x202f;0.001). The intake of protein was significantly higher in the intervention group than in the control group (p&#x202f;<&#x202f;0.01), whereas the intake of fat was significantly lower in the intervention group (p&#x202f;<&#x202f;0.001). However, there were no significant differences in the intakes of iron, vitamin A, vitamin D, or folic acid between the intervention and control group. Vision-related quality of life, nutritional knowledge and self-efficacy scores of intervention group were higher than that of control group (p&#x202f;<&#x202f;0.001). The BCVA of the intervention group did not differ significantly from that of the control group (p&#x202f;>&#x202f;0.05).<br><br>CONCLUSION: Our research demonstrates that the APP-based AIM-AMD nutrition management model offers patients comprehensive, accurate, and personalized guidance on dietary management.<br><br>The results of this study demonstrate that the AIM-AMD nutritional management model holds demonstrable clinical value in the nutritional management process of patients with AMD.<br><br>CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=175931, Identifier ChiCTR2200063978.}, }
@article {pmid42756394, year = {2026}, author = {Li, Z and Zhao, T and Ye, L and Li, R and Tian, H and Liao, R and Huang, L}, title = {Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate NaIO3-Induced Dry AMD by Delivering miR-486-3p to Inhibit Lipocalin-2-Mediated Ferroptosis.}, journal = {MedComm}, volume = {7}, number = {10}, pages = {e71000}, pmid = {42756394}, issn = {2688-2663}, abstract = {Dry age-related macular degeneration (AMD), affecting over 196 million people globally, represents the leading cause of irreversible blindness with limited disease-modifying therapies. The disease is characterized by progressive retinal pigment epithelium (RPE) degeneration driven by ferroptosis, an iron-dependent form of regulated cell death. While mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) show therapeutic promise, their mechanisms in counteracting RPE ferroptosis remain unexplored. Here, we prove that human umbilical cord MSC-derived EVs (hucMSC-EVs) significantly attenuate NaIO3-induced retinal degeneration, preserving retinal structure and improving visual function in mice. Transcriptomic profiling identified Lipocalin-2 (Lcn2) as a key ferroptosis-related target. MSC-EVs administration markedly downregulated Lcn2 and upregulated Gpx4 in NaIO3-induced models, demonstrating potent ferroptosis suppression. Furthermore, AAV-mediated Lcn2 overexpression induced AMD-like retinal pathology, which was effectively attenuated by subsequent MSC-EVs treatment. Small RNA sequencing reveals miR-486-3p as the key factor in the MSC-EVs, and dual-luciferase reporter assays confirm its direct binding to the Lcn2 3'UTR. Functional validation demonstrates that miR-486-3p agomir recapitulates the effects of MSC-EVs, including preservation of retinal structure and improvement of electrophysiological responses. Our findings establish a novel strategy where hucMSC-EVs deliver miR-486-3p to suppress Lcn2-mediated ferroptosis, offering a potential treatment for dry AMD.}, }
@article {pmid42754690, year = {2026}, author = {Faes, L and Kubravi, S and Spooner, K and Thottarath, S and Sivaprasad, S and Fu, DJ and , }, title = {Macular neovascularisation subtype determines visual consequences of early fibro-atrophic remodelling in neovascular AMD: PRECISE study report 11.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42754690}, issn = {1476-5454}, abstract = {PURPOSE: To evaluate whether baseline well-delineated hyperreflective material (wdHRM) is associated with short-term visual outcome in treatment-naïve neovascular age-related macular degeneration (nAMD), whether this association differs by macular neovascularisation (MNV) subtype, and how wdHRM relates to atrophy-related OCT biomarkers.<br><br>METHODS: Multicentre observational analysis of 2036 treatment-na&#xef;ve eyes (PRECISE cohort) completing three monthly aflibercept 2&#x2009;mg injections. Best-corrected visual acuity (BCVA) at Visit 4 (V4) was modelled against baseline wdHRM using adjusted multivariable linear regression. Secondary analyses assessed subtype interaction and eye-level association with atrophy-related OCT biomarkers.<br><br>RESULTS: Mean BCVA improved from 58.0 to 62.6 letters by V4. Baseline wdHRM was present in 14.6% of eyes, and foveal-involving wdHRM independently predicted lower V4 BCVA (&#x3b2; =-6.60 letters, 95%confidence interval [CI]-8.18 to -5.02; p&#x2009;<&#x2009;0.001). Foveal-involving baseline choroidal hypertransmission (HTM) showed a stronger adverse association (&#x3b2; =-8.98, 95%CI-10.97 to -6.98; p&#x2009;<&#x2009;0.001). The wdHRM association differed by subtype (interaction p&#x2009;=&#x2009;0.016), with adjusted BCVA reductions of -10.6 letters in Type 3 MNV, -4.8 in Type 2/mixed MNV, -4.1 in Type 1 MNV, and -1.0 in polypoidal choroidal vasculopathy. By V4, wdHRM increased to 21.0% and was associated with HTM and greater outer retinal disruption.<br><br>CONCLUSIONS: In treatment-na&#xef;ve nAMD, baseline wdHRM is independently associated with poorer short-term visual outcome, particularly in Type 3 MNV. Short-term visual outcome should be interpreted in relation to both fibrosis-related and atrophy-related OCT biomarkers.}, }
@article {pmid42747171, year = {2026}, author = {Bikbov, MM and Kazakbaeva, GM and Gilemzianova, LI and Panda-Jonas, S and Holz, FG and Jonas, JB}, title = {Safety of intravitreally applied epidermal growth factor receptor antibody panitumumab.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70235}, pmid = {42747171}, issn = {1755-3768}, abstract = {PURPOSE: To examine the safety of the epidermal growth factor (EGF) receptor antibody panitumumab intravitreally applied in patients with myopic macular degeneration (MMD) or neovascular age-related macular degeneration (AMD).<br><br>METHODS: Patients with MMD stage 4 underwent repeated intravitreal panitumumab injections in escalating doses, and patients with neovascular AMD received combined intravitreal ranibizumab/panitumumab injections, with single ranibizumab injections applied in between.<br><br>RESULTS: The study included 28 patients. In the first cohort, 11 highly myopic patients with MMD stage 4 (age: 66.8&#x2009;&#xb1;&#x2009;6.3&#x2009;years) received intravitreal panitumumab injections in doses of 0.6&#x2009;mg (4 eyes; 1 &#xd7;&#x2009;1 injection, 3 &#xd7;&#x2009;2 Injections), 1.2&#x2009;mg (4 eyes; 1 &#xd7;&#x2009;1 injection; 2 &#xd7;&#x2009;2 injections; 1 &#xd7;&#x2009;3 injections) and 1.8&#x2009;mg (3 eyes; 1 &#xd7;&#x2009;1 injection, 2 &#xd7;&#x2009;2 injections), respectively, in intervals of 3.6&#x2009;&#xb1;&#x2009;1.8&#x2009;months (first to second injection), and 4.7&#x2009;months (second to third injection). At 3.7&#x2009;&#xb1;&#x2009;0.4&#x2009;years (median: 3.6&#x2009;years; range: 3.5-4.7&#x2009;years) after the first injection, ten patients were re-examined, with no change in axial length (30.6&#x2009;&#xb1;&#x2009;1.0 vs. 30.7&#x2009;&#xb1;&#x2009;1.3; p&#x2009;=&#x2009;0.66). A second cohort included 17 eyes with neovascular AMD and receiving bimonthly combined panitumumab/ranibizumab (1.2&#x2009;mg/0.5&#x2009;mg) injections (mean: 2.4&#x2009;&#xb1;&#x2009;0.5 injections). The mean follow-up period was 11.0&#x2009;&#xb1;&#x2009;1.0&#x2009;months (median: 11&#x2009;months; range: 6-14&#x2009;months). In none of the eyes of the first and second cohort, treatment-related systemic or intraocular adverse events were noted. Ocular side effects were hyposphagmata at the injection sites. Signs of intraocular inflammation were not detected in any eye. The morphology of the optic nerve head did not change significantly, nor did the IOP (14.5&#x2009;&#xb1;&#x2009;4.3&#x2009;mmHg vs. 13.5&#x2009;&#xb1;&#x2009;1.5&#x2009;mmHg; p&#x2009;=&#x2009;0.30).<br><br>CONCLUSIONS: Repeated intravitreal panitumumab applications in various doses, single or combined with ranibizumab, were not associated with severe ocular or systemic side effects.}, }
@article {pmid42749023, year = {2026}, author = {Sakai, D and Hirami, Y and Takagi, S and Yamamoto, M and Totani, K and Yamanari, M and Fujihara, M and Sugita, S and Maeda, T and Takahashi, M and Mandai, M and Kurimoto, Y}, title = {Ten-Year Survival of First-in-Human Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Sheet Transplantation.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.09.005}, pmid = {42749023}, issn = {2468-6530}, abstract = {PURPOSE: This study aimed to report the 10-year follow-up results of the first-in-human study of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet transplantation, with a focus on long-term graft persistence assessed using multimodal imaging, including polarization-sensitive optical coherence tomography (PS-OCT)-based melanin evaluation.<br><br>DESIGN: Follow-up of a single patient PARTICIPANT: A patient with neovascular age-related macular degeneration METHODS: Autologous iPSC-derived RPE sheets were transplanted into the subretinal space in 2014.<br><br>MAIN OUTCOME MEASURES: Engraftment of the transplanted RPE sheet and preservation of the host retinal structure were evaluated using multimodal imaging, including color fundus photography, spectral-domain (SD)-OCT and PS-OCT, and near-infrared autofluorescence (NIRAF), throughout the post-transplantation period.<br><br>RESULTS: The patient was aged 88 years at the 10-year post-transplantation follow-up. There was stable anatomic appearance of the persistent subretinal pigmentation on color fundus photography. SD-OCT revealed the preservation of the outer nuclear layer over the graft. Choroidal thickness analysis indicated sustained structural preservation beneath the graft. PS-OCT demonstrated persistent depolarization signals of the RPE layer, which were separated from the overlying retina and corresponded to the pigmented area observed on color fundus photography. The combination of high polarimetric entropy on PS-OCT and low-to-iso-autofluorescence on NIRAF further delineated the grafted area, distinguishing it from healthy and atrophic regions.<br><br>CONCLUSIONS: Sustained preservation of the overlying neurosensory retina and underlying choroid, in conjunction with long-term pigment persistence, provides important evidence of the safety and structural stability of iPSC-based cell therapy. These findings support the potential of this approach for broader clinical application in regenerative medicine.}, }
@article {pmid42749828, year = {2026}, author = {Lim, AY and Fox, S and Mahendra, S and Nugawela, M and Seeberan, R and Barnes, A and Amalfitano, F and Sivaprasad, S and Mahroo, OA}, title = {Visual impairment certifications in England over 16 years: annual numbers attributable to age-related macular degeneration, glaucoma, diabetes and hereditary eye disease.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42749828}, issn = {1476-5454}, }
@article {pmid42749868, year = {2026}, author = {Cagini, C and Messina, M and Fiore, T and Chiruzzi, ML and Frenguelli, M and Crescenzi, L and Poddi, M}, title = {Short-term adjunctive use of a liposomal tear substitute after repeated intravitreal therapy: a randomized pilot study.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42749868}, issn = {1573-2630}, mesh = {Humans ; Pilot Projects ; Female ; Male ; Intravitreal Injections ; Liposomes ; Middle Aged ; *Dry Eye Syndromes/drug therapy/diagnosis/prevention &amp; control/etiology ; Angiogenesis Inhibitors/administration &amp; dosage ; Ophthalmic Solutions/administration &amp; dosage ; Aged ; Follow-Up Studies ; *Lubricant Eye Drops/administration &amp; dosage ; *Macular Degeneration/drug therapy ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Time Factors ; Aged, 80 and over ; Prospective Studies ; Tears ; }, abstract = {PURPOSE: This pilot study investigates the efficacy of a liposomal ophthalmic solution containing cross-linked hyaluronic acid, trehalose, and stearylamine in reducing the occurrence of dry eye-like signs and symptoms in patients undergoing repeated intravitreal treatment.<br><br>METHODS: Participants aged over 50&#xa0;years old were randomly assigned to receive either standard therapy alone (Group 1) or standard therapy with additional eye drops (Group 2). Examinations included TBUT, Schirmer's test, fluorescein staining, the Ocular Surface Disease Index (OSDI), and the 5-item Dry Eye Questionnaire (DEQ-5) at baseline and day 15, with a 30-day telephone follow-up for OSDI reassessment.<br><br>RESULTS: Ninety patients with age-related macular degeneration or other retinal diseases requiring anti-VEGF (vascular endothelial growth factor) treatment were enrolled in the study. In Group 1, which comprised 20 males and 25 females, DEQ-5 scores did not exhibit any significant change between V0 and V1 (10.89 &#xb1; 2.71 to 10.57 &#xb1; 2.60, p = 0.173), while Group 2, composed of 18 males and 27 females, demonstrated a considerable reduction in DEQ-5 values (9.28 &#xb1; 3.24 to 8.00 &#xb1; 3.64, p < 0.0001). OSDI scores in Group 1 showed no relevant change between V0 and V1 (p = 0.497), whereas in Group 2 they improved significantly (p < 0.0001). Additionally, Group 2 had notable enhancements in TBUT and Schirmer tests (p < 0.0001), while Group 1 experienced a significant decrease in TBUT values alone (p = 0.026).<br><br>CONCLUSION: Chronic intravitreal therapy contributes to significant ocular surface impairment, which can be effectively mitigated by the administration of a tear substitute alongside the standard treatment.}, }
@article {pmid42751623, year = {2026}, author = {Makhdoum, H and Alharbi, A and Alhazmi, S and Alrehaili, A and Afandi, R and Aljohani, G and Alharbi, K}, title = {Understanding anti-vascular endothelial growth factor medications: chemical properties, costs, and side effects.}, journal = {Journal of medicine and life}, volume = {19}, number = {7}, pages = {503-510}, pmid = {42751623}, issn = {1844-3117}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/adverse effects/therapeutic use/economics/pharmacology ; Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use/adverse effects ; Ranibizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor ; }, abstract = {Vascular endothelial growth factor (VEGF) is an important driver of abnormal retinal neovascularization and increased vascular permeability. VEGF overexpression is associated with a number of retinal conditions, such as diabetic macular edema (DME), and neovascular age-related macular degeneration (nAMD). Anti-VEGF treatments have been the most common for these conditions and have improved vision by reducing abnormal blood vessel formation and leakage. This narrative review addressed the fact that the pharmacological properties, safety profiles, and cost-effectiveness of the currently marketed anti-VEGF intravitreal agents (i.e. bevacizumab, ranibizumab, aflibercept, brolucizumab, pegaptanib, and recently faricimab) differ and therefore, each of these agents, have their own unique molecular structure, target specificity, duration of action in the eye, and systemic circulation, each of which will affect the dosing intervals and treatment burden as well as the safety and adverse events associated with each drug. Aflibercept is a high-binding-affinity decoy receptor and is therefore distinct from faricimab, which is a dual-action (VEGF-A and angiopoietin-2) inhibitor. By contrast, ranibizumab, bevacizumab, brolucizumab, and pegaptanib are anti-angiogenic agents with different VEGF blockade profiles, which ultimately lead to distinct clinical outcomes and pharmacokinetic profiles. While anti-VEGF therapies are highly effective, the outcomes regarding safety, efficacy, and cost depend heavily on the study design and reflect the actual treatment paradigm and continuum of care within the healthcare system. The various attributes of agents should help personalize a patient's treatment approach while also addressing potential challenges related to the safety, efficacy, and longevity of treatment for retinal diseases.}, }
@article {pmid42752553, year = {2026}, author = {Osorio, DL and Kumar, A and Choi, A and Sodhi, I and Guo, C and Montaner, S}, title = {Angiopoietin-Like 4 Induces Upregulation of VEGF and sVCAM1 Through JNK/c-Jun and JAK2/STAT5 Signaling Pathways.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {11}, pages = {36}, doi = {10.1167/iovs.67.11.36}, pmid = {42752553}, issn = {1552-5783}, mesh = {Animals ; *Vascular Endothelial Growth Factor A/genetics/biosynthesis/metabolism ; *Angiopoietin-Like Protein 4 ; Mice ; Up-Regulation ; *Janus Kinase 2/metabolism ; Mice, Inbred C57BL ; Signal Transduction ; *Vascular Cell Adhesion Molecule-1/genetics/biosynthesis/metabolism ; *STAT5 Transcription Factor/metabolism ; Blotting, Western ; Cells, Cultured ; Disease Models, Animal ; *Angiopoietins/pharmacology ; }, abstract = {PURPOSE: Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine regulating angiogenesis, vascular permeability, and inflammation that is elevated, along with vascular endothelial growth factor (VEGF), in multiple ocular neovascular disorders, including ischemic retinopathies and neovascular age-related macular degeneration. However, the downstream signaling pathways that contribute to the effects of ANGPTL4 in ocular disease remain unclear.<br><br>METHODS: A phospho-kinase Proteome Profiler array was used to map pathways activated by recombinant ANGPTL4 in immortalized murine retinal endothelial cells (iRECs). Candidate signaling routes were assessed using pharmacologic inhibition and siRNA-mediated knockdown to define their roles in ANGPTL4-driven angiogenesis and effector upregulation. Findings were validated following intraocular ANGPTL4 delivery in C57BL/6J mice.<br><br>RESULTS: ANGPTL4 robustly activated the c-Jun N-terminal kinase (JNK)/c-Jun and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) axes in iRECs, a signature recapitulated in neurosensory retina in vivo. Inhibition of either pathway significantly reduced ANGPTL4-induced angiogenesis, identifying these pathways as critical effectors of ANGPTL4 signaling. ANGPTL4 induced secretion of VEGF, soluble vascular cell adhesion molecule 1 (sVCAM1), T-cell immunoglobulin and mucin domain 1 (TIM-1), and proliferin; however, only VEGF and sVCAM1 depended on JNK/c-Jun and JAK2/STAT5.<br><br>CONCLUSIONS: ANGPTL4 functions as a signaling hub that integrates different cues to activate JNK/c-Jun and JAK2/STAT5 and upregulate the expression of key pathogenic proteins including VEGF and sVCAM1. This work establishes these cascades as previously unrecognized effectors of ANGPTL4 signaling in the retina and brings important insight into the critical role that ANGPTL4 plays in neovascular retinal disease.}, }
@article {pmid42753030, year = {2026}, author = {Jang, B and Oh, R and Lee, TH and Yoon, CK and Choi, HJ and Choi, J and Kim, YG and Bae, K}, title = {Deep learning-derived retinal age gap and its associations with lifestyle, systemic, and ocular health in a health screening cohort.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {42753030}, issn = {2509-2723}, abstract = {Individuals of the same chronological age differ in biological aging, and scalable, noninvasive markers are needed. The deep learning-derived retinal age gap (RAG) is a promising measure of retinal aging, but its associations with real-world health determinants remain unclear. We developed a multi-task model to predict retinal age using 29,530 fundus images from 7535 participants in a health screening cohort and evaluated RAG in cohort A for lifestyle, socioeconomic, and systemic factors (n = 5606) and cohort B for ocular diseases (n = 1810). The bias-corrected multi-task model trained on mixed data achieved the best performance, with a mean absolute error of 2.656 years and a Pearson correlation of 0.921 in cohort A and 2.529 years and 0.938 in cohort B. Higher RAG was significantly associated with smoking (ex-smokers, β = +0.46 years; current smokers, β = +0.50 years) and with clinical diabetes (+2.52 years); both survived false discovery rate (FDR) and Bonferroni correction, and the diabetes association persisted across all sequential covariate-adjustment sets. Married participants had lower RAG (β = -0.46 years), significant after FDR correction only. Hypertension and hyperlipidemia were not associated with RAG. In cohort B, RAG was significantly higher in eyes with age-related macular degeneration (β = +0.60 years) and cataract (β = +1.86 years) than in normal controls, both surviving corrections. RAG, an imaging-derived age-prediction residual, is therefore associated with lifestyle, systemic, and ocular health. Whether it reflects biological aging requires longitudinal validation against established aging biomarkers; at present, RAG suits population-level characterization better than individual-level risk stratification.}, }
@article {pmid42753946, year = {2026}, author = {Ong, AY and Struvyen, RR and Merle, DA and Mendez, K and Ashourizadeh, H and Mukherjee, S and Lima-Cabrita, A and Chang, J and Wu, D and Pundlik, S and Vavvas, DG and Kim, IK and Miller, JW and Wu, Z and Keane, PA and Miller, JB and Husain, D and Lains, I}, title = {Association of reticular pseudodrusen burden and dark adaptation in non-advanced age-related macular degeneration: a cross-sectional and longitudinal study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.09.003}, pmid = {42753946}, issn = {2468-6530}, abstract = {PURPOSE: Dark adaptation (DA) has emerged as a potential functional outcome for assessing age-related macular degeneration (AMD). While reticular pseudodrusen (RPD) have been linked to poorer DA, most studies to date have focused on qualitative RPD presence/absence or comprised small cross-sectional cohorts. This work aimed to assess how automated quantification of RPD area and volume relates to rod-mediated DA and its longitudinal decline in non-advanced AMD.<br><br>DESIGN: Prospective cross-sectional and longitudinal study.<br><br>PARTICIPANTS: Patients with non-advanced AMD and controls, all aged above 50, from the Massachusetts Eye and Ear AMD Biomarkers Study.<br><br>METHODS: All subjects underwent baseline multimodal retinal imaging and DA testing with a 20-minute extended protocol (AdaptDx, MacuLogix). Rod intercept time (RIT) and area under the dark adaptation curve (AUDAC) were calculated. A deep learning algorithm was employed to quantify RPD en face area (mm[2]) and volume (mm[3]), which were square- and cube-root transformed respectively for analysis. RPD extent within the DA testing locus was also measured. Linear mixed-effect models evaluated the relationship of RPD burden with DA metrics, accounting for age, sex, smoking, classic drusen volume and inter-eye correlation.<br><br>MAIN OUTCOME MEASURES: Association between RPD burden and dark adaptation (RIT and AUDAC) on a cross-sectional and longitudinal basis RESULTS: We included 545 eyes (52 early AMD, 285 intermediate AMD, 208 controls) from 310 patients (mean 69.6&#xb1;7.4 years). 128 (23.5%) had RPD. Greater RPD en-face area and volume were associated with prolonged RIT (&#x3b2; 1.59, p=0.002 and &#x3b2; 9.29, p=9.78 x 10[-5] respectively) and higher AUDAC (&#x3b2; 0.032, p=2.15 x 10[-4] and &#x3b2; 0.166, p=5.88x10[-5] respectively). Overall macular RPD burden, rather than local density at the DA testing locus, was independently associated with worse AUDAC (&#x3b2; 0.005, p=0.001). In longitudinal analyses (n=204 eyes, mean 2.8&#xb1;1.8 years), RPD presence (&#x3b2; 0.011, p=0.0067), en face area (&#x3b2; 0.012, p=4.48 x 10[-4]), and volume (&#x3b2; 0.054, p=2.11 x 10[-4]) were all significantly associated with a faster rate of AUDAC decline over time, and were predictive of AUDAC at any subsequent visit (&#x3b2; 0.048, p=6.72 x 10[-5] and &#x3b2; 0.198, p=2.02 x 10[-4]).<br><br>CONCLUSIONS: Quantitative RPD burden is independently associated with impaired rod-mediated DA and with subsequent functional decline, supporting its value as a prognostic structural biomarker for risk stratification and progression monitoring in non-advanced AMD.}, }
@article {pmid42745211, year = {2026}, author = {Bora, RA and Aher, P and Magdum, RA and Jagdish, R}, title = {Low Vision Intervention in Individuals with Age-related Macular Degeneration.}, journal = {Annals of African medicine}, volume = {25}, number = {6}, pages = {1400-1404}, doi = {10.4103/aam.aam_329_25}, pmid = {42745211}, issn = {0975-5764}, mesh = {Humans ; *Visual Acuity/physiology ; Female ; *Quality of Life ; *Macular Degeneration/rehabilitation/complications ; Aged ; Prospective Studies ; Male ; *Vision, Low/rehabilitation/etiology ; Activities of Daily Living ; Treatment Outcome ; Middle Aged ; Aged, 80 and over ; Surveys and Questionnaires ; Contrast Sensitivity ; Reading ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Low vision interventions (LVIs) aim to enhance residual visual function and promote independence. This study aimed to evaluate the clinical and functional outcomes of structured LVIs on visual performance, daily functioning, and quality of life in individuals with AMD.<br><br>METHODS: A prospective interventional study was conducted over 1 year at Dr. D. Y. Patil Medical College, Hospital, and Research Centre in Pune. Eighty-four participants with confirmed AMD and low vision were enrolled and assessed at baseline, 3 months, and 6 months postintervention. The rehabilitation program included optical, nonoptical, and electronic assistive devices, along with specialized visual training. Primary outcomes included best corrected visual acuity (BCVA), contrast sensitivity, and reading speed. Secondary outcomes were assessed using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and the modified Barthel index, evaluating self-reported visual function and independence in daily activities.<br><br>RESULTS: Of the 84 participants, 78 completed the full follow-up. Statistically significant improvements were observed in BCVA (mean gain: 0.17 logMAR), reading speed (mean increase: 18.8 words/min), and contrast sensitivity (mean gain: 0.22 units). The NEI VFQ-25 composite score improved by an average of 17.3 points, with marked enhancement in near-vision tasks and social engagement. Functional ability, as measured by the Modified Barthel Index, also showed meaningful improvement. No device-related complications were reported, and more than 85% of participants adhered to their prescribed rehabilitation plans.<br><br>CONCLUSIONS: Structured low vision rehabilitation leads to significant improvements in visual performance, functional independence, and perceived quality of life among patients with AMD. These findings support the integration of LVIs into standard ophthalmic care protocols for elderly individuals with low vision.}, }
@article {pmid42745735, year = {2026}, author = {Samanta, A and Krambeer, C and Flowers, A and Porter, M}, title = {Selective laser trabeculoplasty for anti-VEGF associated intraocular pressure elevation in steroid-naïve eyes.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1675048}, pmid = {42745735}, issn = {2674-0826}, abstract = {PURPOSE: Selective Laser Trabeculoplasty (SLT) is utilized in cases of primary and certain secondary open-angle glaucoma to decrease intraocular pressure (IOP). SLT effectiveness has been demonstrated in patients with increased IOP secondary to intraocular steroids. In addition to intravitreal steroids, intravitreal anti-vascular endothelial growth factor (VEGF) injections are commonly used in patients with diabetic retinopathy and age-related macular degeneration. Some patients receiving anti-VEGF injections experience increases in IOP. No studies have evaluated the effectiveness of SLT for anti-VEGF-associated glaucoma.<br><br>METHODS: This was a retrospective, single-center study. Anti-VEGF-associated IOP increase was defined as an eye receiving at least one anti-VEGF intravitreal injection prior to SLT. IOP and the number of pressure-lowering drops were measured at 3-, 6-, 9-, and 12-month post-SLT follow-up appointments. Outcomes included changes in IOP, and the number of IOP-lowering drops prescribed.<br><br>RESULTS: Twenty-three eyes from 18 patients were included in this study. The IOP was 18.26 &#xb1; 3.33 with 2.6 &#xb1; 1. drops prescribed at baseline. Two eyes required repeat SLT. Over the study period, IOP was reduced by 3 to 4.5&#xa0;mm Hg, with all p-values <0.001. Eight eyes in the study were drop-na&#xef;ve (no IOP-lowering drops prescribed prior to SLT). Of these, 6/8 (75%) remained drop-free at the end of the observation period. At their final clinic visit, 78.3% of patients were controlled on SLT without further surgical or medical intervention.<br><br>CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate the long-term effectiveness of SLT in anti-VEGF-associated open-angle glaucoma in steroid-na&#xef;ve eyes.}, }
@article {pmid42745817, year = {2026}, author = {Dutta, AK and Aljarallah, NA and Wahab Sait, AR}, title = {VG-RETFound: a hybrid retinal AI framework for early vision impairment screening through vessel-graph learning and cross-modal fusion.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1905129}, pmid = {42745817}, issn = {2296-858X}, abstract = {INTRODUCTION: Vision impairment caused by retinal diseases stands out as one of the significant sources of irreversible blindness, highlighting the importance of developing robust automated screening tools to detect eye diseases at an early stage. Despite the promising results of recent deep learning approaches to the automatic classification of retinal images, most existing solutions focus on image-based representations and do not consider the importance of vascular topology. To overcome the limitations, this study proposes VG-RETFound - a hybrid framework based on a retinal foundation model and graph-based vascular-topology modeling that can be used to classify multiple retinal categories and detect vision impairment.<br><br>METHODS: The authors use RETFound-a retinal foundation model-pretrained on a vast number of retinal images, as well as the Graph Attention Network (GAT), to learn vascular topology features by representing retinal vessels as graphs. The presented approach employs a cross-modal multi-head attention fusion method to integrate features from both modalities in real time. To evaluate the efficiency of VG-RETFound, experiments were conducted using the RFMiD and ODIR-5 K datasets for model training and testing across six retinal categories: Normal, Diabetic Retinopathy, Pathological Myopia, Age-related Macular Degeneration, Hypertensive Retinopathy, and Other Retinal Diseases.<br><br>RESULTS: The accuracy of 96.39%, F1-score of 95.84%, MCC of 94.87%, and Kappa of 94.71% were attained on an internal test dataset, while cross-dataset external validation on the BRSET dataset revealed accuracy of 94.81%, F1-score of 94.25%, MCC of 93.09%, and Kappa of 92.94%.<br><br>DISCUSSION: These findings demonstrate that integrating retinal foundation models with anatomically informed vessel-topology learning significantly improves classification accuracy, interpretability, and generalization, highlighting the potential of VG-RETFound as a tool for large-scale vision impairment. screening and retinal disease diagnosis.}, }
@article {pmid42745920, year = {2026}, author = {Liu, X and Liu, H and Wang, L and Zhao, J and Xie, X and Jiang, L and Zhao, CA}, title = {Preclinical evaluation of AL-001, a gene therapy for wet age-related macular degeneration.}, journal = {Frontiers in genetics}, volume = {17}, number = {}, pages = {1836684}, pmid = {42745920}, issn = {1664-8021}, abstract = {BACKGROUND: Frequent intravitreal administration of antivascular endothelial growth factor Vascular endothelial growth factor agents remains a major limitation in the management of wet age-related macular degeneration (wAMD). This study evaluated whether suprachoroidal delivery of an engineered recombinant adeno-associated viral (rAAV)-aflibercept vector could achieve sustained, targeted expression with improved efficacy and safety compared with intravitreal administration.<br><br>METHODS: AL-001, an engineered rAAV vector expressing aflibercept, was developed and characterized. Its expression profile was first assessed in New Zealand white rabbits following suprachoroidal space (SCS) injection. Efficacy, pharmacokinetics, and safety were then evaluated in a nonhuman primate model of laser-induced choroidal neovascularization (CNV), comparing SCS and intravitreal (IVT) administration routes.<br><br>RESULTS: AL-001 efficiently expressed aflibercept in relevant ocular cells in vitro. In rabbits, SCS administration produced sustained aflibercept levels in ocular tissues. In the nonhuman primate CNV model, a single SCS injection of AL-001 showed favorable efficacy to IVT injection and a notable mild inflammatory response. At week 4, grade IV lesion incidence was 0% (0/48) after SCS administration versus 14.3% (6/42) after IVT administration (absolute difference, -14.3 percentage points; 95% CI, 3.7%-27.8%; P = 0.0258). Throughout follow-up, mean leakage area and grade IV lesion incidence remained 0 with SCS, versus IVT peaks of approximately 0.3&#xa0;mm[2] and 33.0%, respectively, declining to 0.03&#xa0;mm[2] and 2.0% by day 100. Both the medium and high doses decreased pathological vascular leakage and subretinal hyperreflective material. Vector administration preceded laser-induced CNV modeling, demonstrating that sustained intraocular aflibercept expression in the retina and choroid provided durable antiangiogenic protection. Pharmacokinetic analysis confirmed distinct ocular exposure profiles between routes, with viral genomes confined predominantly to the injected eye and no significant systemic accumulation. AL-001 was well tolerated, without sustained intraocular pressure elevation or severe ocular inflammation, and only mild-to-moderate treatment-emergent adverse events. Low pre-existing anti-AAV2 immunity and time-dependent neutralizing antibody responses postdosing, informing a translational model for patient stratification and redosing feasibility.<br><br>CONCLUSION: Suprachoroidal administration of AL-001 is well tolerated and provides durable, targeted aflibercept expression with pronounced antiangiogenic efficacy. These results support AL-001 as a promising, long-acting therapeutic candidate for wAMD.}, }
@article {pmid42746219, year = {2026}, author = {Samaiya, PK and Agrawal, A and Kesharwani, S and Sathe, R and Prajapati, SK and Majumdar, S}, title = {Microbiota-mitochondria axis in neurodegenerative disorders and retinal dysfunction: mechanisms and emerging therapeutic opportunities.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1889898}, pmid = {42746219}, issn = {1663-9812}, abstract = {The gut microbiota crucial role in maintaining host metabolism, immune homeostasis, intestinal integrity, and mitochondrial function. Emerging evidence suggests that dysregulation of the microbiota-mitochondria axis represents one of the key mechanisms linking gut dysbiosis to the development of neurodegenerative and ocular diseases. The dysbiosis causes disruptions in mitochondrial physiology due to lower levels of short-chain fatty acids, increased intestinal permeability, endotoxemia, oxidative stress, and inflammation. These mechanisms contribute to the pathogenesis of Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, and central serous chorioretinopathy. Environmental factors such as unhealthy dietary patterns, excessive antibiotic use, and prolonged exposure to artificial blue light may exacerbate dysbiosis and further disrupt mitochondrial homeostasis, thereby contributing to disease progression. We also elaborated the emerging therapeutic strategies targeting both the gut microbiota and mitochondrial function, including next-generation probiotics, postbiotics, dietary interventions, mitochondria-targeted antioxidants, NAD[+] precursors, and precision medicine approaches. Collectively, current evidence represents the microbiota-mitochondria axis as a one of the promising mechanistic and therapeutic targets for neurodegenerative and ocular diseases. However, most therapeutic evidence discussed in this review is derived from preclinical studies, with relatively limited clinical validation. Future well-designed longitudinal studies and randomized clinical trials are essential to establish efficacy, safety, and translational applicability in humans.}, }
@article {pmid42746273, year = {2026}, author = {Chou, Z and Saade, C}, title = {Bilateral Choroidal Neovascular Membranes in a Patient With a C1QTNF5 Mutation Managed With Long-Term Anti-VEGF Therapy and PRN Protocol: A Case Report.}, journal = {Case reports in ophthalmological medicine}, volume = {2026}, number = {}, pages = {6047720}, pmid = {42746273}, issn = {2090-6722}, abstract = {Choroidal neovascular membranes (CNVM) are abnormal vascular complexes that can cause serious visual morbidity if untreated. They can be induced by the C1QTNF5 mutation, which disrupts retinal pigment epithelium (RPE) adhesion and leads to progressive sub-RPE deposit accumulation. Due to its overlapping clinical presentation with age-related macular degeneration (AMD), C1QTNF5-associated CNVM is often misdiagnosed. Early recognition of atypical CNVM clinical presentations is essential to prompt genetic testing and initiate personalized antivascular endothelial growth factor (anti-VEGF) therapy. We report a 57-year-old male with a history of pontine stroke and strabismus surgery who presented with bilateral submacular hemorrhages and visual distortion. Given the atypical bilateral presentation and absence of drusen, genetic testing was performed. A pathogenic C1QTNF5 mutation with a p. Asn22Lys variant was identified. Treatment was initiated with intravitreal bevacizumab (IVA) injection and switched to aflibercept (IVE). After 2 years of tailored injection intervals based on optical coherence tomography (OCT) and visual acuity, the patient achieved visual acuity of 20/25 in both eyes with complete or near-complete resolution of subretinal fluid. A pro re nata (PRN) protocol was then initiated, and vision remained stable at the 4-year follow-up. This case highlights the importance of considering inherited retinal disease in atypical CNVM presentations. Early diagnosis, genetic testing, and individualized, imaging-driven anti-VEGF therapy can lead to long-term stability and favorable visual outcomes in patients with C1QTNF5-associated CNVM. Although causality cannot be established from a single case, concurrent glaucoma findings support the need for comprehensive ocular surveillance in patients with C1QTNF5 mutations.}, }
@article {pmid42740461, year = {2026}, author = {Ørskov, M and Cehofski, LJ and Faber, C and Forte, P and Hansen, MS and Muttuvelu, DV and Niazi, S and Schou, MG and Shekho, N and Reiter, GS and Utheim, TP and Vergmann, AS and Subhi, Y}, title = {Accelerated biological ageing is associated with a large drusen burden.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70237}, pmid = {42740461}, issn = {1755-3768}, abstract = {PURPOSE: To investigate the association between accelerated biological ageing, measured by Phenotypic Age (PhenoAge) and PhenoAge Acceleration (PhenoAgeAccel), and features of early and intermediate age-related macular degeneration (AMD) in a population-based cohort.<br><br>METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey. Biological age was estimated using the PhenoAge algorithm, a composite of routine blood biomarkers and chronological age, and PhenoAgeAccel was defined as the residual from regression of PhenoAge on chronological age. Retinal outcomes were drusen &#x2265;500&#x2009;&#x3bc;m (primary outcome), drusen &#x2265;125&#x2009;&#x3bc;m and pigmentary abnormalities. Associations were evaluated using logistic regression adjusted for biological sex, race/ethnicity, smoking, body mass index and diabetes.<br><br>RESULTS: A total of 5322 participants were included (mean age 59.4&#x2009;&#xb1;&#x2009;12.4&#x2009;years; 50.4% female). Drusen &#x2265;500&#x2009;&#x3bc;m were present in 4.1%, drusen &#x2265;125&#x2009;&#x3bc;m in 10.2% and pigmentary abnormalities in 5.6%. PhenoAgeAccel >&#x2009;+&#x2009;3&#x2009;years was associated with higher odds of drusen &#x2265;500&#x2009;&#x3bc;m (OR: 1.56, 95%CI: 1.07-2.27, p&#x2009;=&#x2009;0.022), whereas no association was observed for <-3&#x2009;years. Each 1-year increase in PhenoAgeAccel was associated with higher odds of drusen &#x2265;500&#x2009;&#x3bc;m (OR: 1.02, 95%CI: 1.00-1.04, p&#x2009;=&#x2009;0.022). PhenoAgeAccel >&#x2009;+&#x2009;3&#x2009;years was also associated with drusen &#x2265;125&#x2009;&#x3bc;m (OR: 1.29, 95%CI: 1.00-1.65, p&#x2009;=&#x2009;0.049), but not with pigmentary abnormalities.<br><br>CONCLUSION: Accelerated biological ageing was associated with increased drusen burden, but not pigmentary abnormalities, suggesting that early structural features of AMD may reflect broader systemic ageing processes.}, }
@article {pmid42741500, year = {2026}, author = {Cui, X and Zhao, Q and Hui, J and Han, Z and Yu-Wai-Man, P and Han, Q}, title = {Decoding the Bone-Eye Axis: Machine Learning for Age-Related Macular Degeneration Risk Prediction.}, journal = {Cyborg and bionic systems (Washington, D.C.)}, volume = {7}, number = {}, pages = {0676}, pmid = {42741500}, issn = {2692-7632}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, yet systemic determinants of its risk remain incompletely understood. Bone mineral density (BMD), a marker of skeletal and biological aging, may reflect shared pathways linking systemic and retinal degeneration. We investigated the association between BMD and AMD using a multilayered framework integrating epidemiological analyses, Mendelian randomization (MR), proteomic and metabolomic profiling, machine learning, and an experimental low-BMD model. Across 3 cohorts, including UK Biobank, National Health and Nutrition Examination Survey, and a hospital-based Tianjin cohort, lower BMD was consistently associated with higher AMD risk, although AMD ascertainment and BMD measurement differed across cohorts. Two-sample MR analyses provided supportive genetic evidence consistent with a modest potential contribution of higher BMD to lower AMD risk, while sensitivity analyses did not indicate strong evidence of reverse causality. Machine learning models identified BMD as a recurrent predictive contributor alongside age, but its incremental clinical utility requires formal evaluation using models with and without BMD. UK Biobank proteomic and metabolomic analyses revealed overlapping molecular signatures involving extracellular matrix remodeling, lipid transport, amino acid metabolism, and inflammatory pathways. Two-step MR prioritized circulating proteins including granzyme A, collagen type II alpha 1 chain, and NEL-like protein 1 as candidate molecular intermediates rather than established mechanistic mediators. In a glucocorticoid-induced low-BMD rat model, retinal alterations relevant to degeneration, including outer retinal thinning, vascular narrowing, and delayed visual-spatial performance, were observed, but these findings should not be interpreted as direct validation of AMD pathology. Overall, these findings support an association between lower BMD and AMD risk and suggest that BMD may act as an accessible marker of systemic aging processes related to retinal vulnerability.}, }
@article {pmid42741679, year = {2026}, author = {Kang, J and Park, K and Choi, S and Han, S and Hwang, BE and Lee, JH and Jang, M and Chung, EK and Cho, H and Heo, Y and Han, S}, title = {Phase I Randomized Study of SCAI-005 Ophthalmic Solution: Safety, Tolerability, and Pharmacokinetics in Healthy Korean Adults.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101358}, pmid = {42741679}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of SCAI-005-a topical ophthalmic solution of axitinib for neovascular age-related macular degeneration (AMD), a VEGF receptor tyrosine kinase inhibitor-following single and multiple ascending doses (SAD and MAD) in healthy Korean adults.<br><br>DESIGN: Randomized, double-masked, placebo-controlled, single- and multiple-ascending-dose phase I study.<br><br>SUBJECTS: Forty-eight healthy Korean adults were randomized 3:1 (active:placebo) into six cohorts across SAD (0.04% as a single drop, 0.08% as a single drop, and 0.08% as two drops) and MAD (0.04% 1 drop three times daily (TID), 0.08% 1-drop TID, and 0.08% two-drop TID for 7 days) groups.<br><br>METHODS: SCAI-005 or placebo was administered topically to 1 eye per subject. Serial blood samples were collected for systemic PK analysis using noncompartmental analysis. Safety was assessed through treatment-emergent adverse events (TEAEs), ophthalmic examinations, vital signs, electrocardiography, and clinical laboratory tests.<br><br>MAIN OUTCOME MEASURES: Primary outcomes were safety and tolerability. Secondary outcomes included systemic PK parameters (Cmax and AUClast) and dose proportionality.<br><br>RESULTS: Forty-seven of 48 subjects (97.9%) completed the study. TEAEs were reported in 7 subjects (14.6%), with no obvious dose-dependent trend in this small sample. All treatment-related TEAEs were grade 1 in severity. No clinically significant changes were observed in ophthalmic assessments. SCAI-005 was rapidly absorbed following topical administration, with day 8 postdose peak systemic concentrations (Cmax) approximately 66- to 282-fold lower than the reported steady-state Cmax for oral axitinib 5 mg twice daily. Because predose trough concentrations were below the assay limit in most subjects, formal steady state could not be confirmed; repeated-dose parameters are therefore reported as day 8 postdose descriptive PK parameters. In the dose proportionality analysis, Cmax findings were broadly consistent with dose proportionality in both SAD and MAD cohorts. AUClast slope estimates were above unity in both cohorts (1.64-1.69) with confidence intervals not including unity.<br><br>CONCLUSIONS: Topical SCAI-005 was generally well tolerated in this small first-in-human study in healthy Korean adults, producing low systemic axitinib exposure and no obvious short-term safety signal. These findings will require confirmation in phase II studies enrolling the target neovascular AMD population.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42742484, year = {2026}, author = {Li, Y and Xiao, F and Liu, Z and Zhang, Y and Yu, J and Chen, Y and Pan, H and Xu, N and Sheng, F and Han, H and Fu, Q and Zhang, S and Gao, J and Tao, W and Yao, K and Kong, N}, title = {Cornea-Penetrating Nanodrug Co-Delivering VEGF-Silencing siRNA and Lutein for Treating Age-Related Macular Degeneration.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e74994}, doi = {10.1002/adma.74994}, pmid = {42742484}, issn = {1521-4095}, support = {52503205//National Natural Science Foundation of China/ ; 82572387//National Natural Science Foundation of China/ ; U24A20705//Regional Innovation Development Joint Fund of the National Natural Science Foundation of China/ ; 2024ZY01057//Central Guidance for Local Scientific and Technological Development Funding Program/ ; LQN25B020004//Zhejiang Provincial Natural Science Foundation of China/ ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, driven by oxidative stress, chronic inflammation, and pathological choroidal neovascularization (CNV). Although intravitreal anti-vascular endothelial growth factor (VEGF) therapies remain the current clinical standard, their invasive nature and requirement for long-term repeated injections present substantial risks and patient burden, underscoring an urgent need for noninvasive therapeutic alternatives. Here, we develop a noninvasive, cornea-penetrating nanodrug based on chitosan-modified lipid-polymer hybrid nanoparticles (LPNPs) for co-delivery of lutein and VEGF-silencing siRNA (Chi@Lu/si NPs) to treat AMD. The structurally stabilized nanoparticles overcome the intrinsic instability of siRNA and the poor solubility of lutein, while the chitosan coating confers strong mucoadhesion and transient modulation of epithelial tight junctions, enabling a 3.3-fold enhancement in trans-epithelial transport across the ocular surface. Once delivered to the posterior segment, lutein effectively scavenges excessive reactive oxygen species and suppresses inflammatory cascades, whereas siRNA-VEGF achieves precise VEGF gene silencing, collectively interrupting the pathological cycle driving CNV progression. In a laser-induced CNV mouse model, topical administration of Chi@Lu/si NPs twice daily exerted potent inhibitory effects on neovascularization, with therapeutic efficacy comparable to that of intravitreal bevacizumab, reducing CNV lesion thickness to 58.9% of pre-treatment levels while maintaining excellent ocular biocompatibility.}, }
@article {pmid42743220, year = {2026}, author = {Lo, C and Jackson, ML}, title = {Clinical characteristics and microperimetry of patients with myopic maculopathy referred to vision rehabilitation compared to age related macular degeneration.}, journal = {PloS one}, volume = {21}, number = {9}, pages = {e0356824}, pmid = {42743220}, issn = {1932-6203}, mesh = {Humans ; *Macular Degeneration/rehabilitation/physiopathology/diagnosis/complications ; Female ; Aged ; Male ; Retrospective Studies ; Aged, 80 and over ; Visual Acuity ; Visual Field Tests ; Middle Aged ; *Myopia/rehabilitation/physiopathology/complications ; }, abstract = {Myopic maculopathy (MM) is a progressive degenerative change of the retina and choroid associated with high myopia leading to central vision loss. The burden of MM is anticipated to increase due to the rising prevalence of myopia globally. Patients with MM are often referred for vision rehabilitation (VR) to help adapt to visual impairment. VR aims to allow patients to continue performing tasks and remain safe despite vision loss, typically through training with optical devices, assistive technology, or new strategies. This study compares the presenting clinical characteristics and VR process of patients with MM to patients with age-related macular degeneration (AMD), the latter being the most common diagnosis of patients referred for VR. This retrospective chart review included 32 consecutive patients with MM and 32 randomly selected patients with AMD referred for VR. Only patients with visual acuity in either eye better than 20/200 were included to represent the early stage of both disease processes. Available microperimetry data were collected for all eyes with a visual acuity better than 20/200 and graded for the presence of scotomas by two independent reviewers. Patients with MM were significantly younger (p < 0.0001) than those with AMD (mean age 68.0 vs 81.6 years respectively). Reported priority goals for vision rehabilitation showed a significant trend: patients with MM and moderate acuity prioritized daily living tasks more frequently (67%, p = 0.0045) than patients with AMD. At good acuity (>20/50), dense paracentral scotomas trended towards being more prevalent amongst patients with MM compared to moderate acuity (between 20/50 and 20/200) where central scotomas were more prevalent amongst patients with AMD. Patients with early MM have unique characteristics at presentation for VR compared to patients with AMD. It is important for providers to be aware of the visual challenges faced by younger patients with paracentral scotomas, which may warrant VR referral even when visual acuity is good.}, }
@article {pmid42743257, year = {2026}, author = {Park, D and Oh, R and Baek, J and Bae, K}, title = {Evaluating an AI-assisted triage workflow for retinal diseases.}, journal = {PLOS digital health}, volume = {5}, number = {9}, pages = {e0001700}, pmid = {42743257}, issn = {2767-3170}, abstract = {The clinical value of artificial intelligence (AI) in fundus photography depends on workflow efficiency as well as diagnostic performance. We evaluated an AI-assisted negative-screening workflow for diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD) using 6,904 color fundus photographs independently graded by three retina specialists. In this workflow, AI-negative images were classified as negative without ophthalmologist review, whereas AI-positive images were referred for human interpretation. For each reader-disease pair, the reference standard was agreement between the other two readers; discordant cases were excluded (DR, 1.2%-2.3%; RVO, 0.3%-0.6%; AMD, 6.1%-11.6%). The workflow reduced direct ophthalmologist review to 7.3%-8.0% of images for DR, 11.7%-11.9% for RVO, and 13.5%-16.8% for AMD. For DR, sensitivity decreased significantly (0.9168 to 0.8838; difference, -0.0330; 95% confidence interval [CI], -0.0495 to -0.0165; p < 0.001), whereas specificity did not change significantly (0.9961 to 0.9983; p = 0.183). For RVO, sensitivity was unchanged (0.9807) and specificity did not change significantly (0.9985 to 0.9988; p = 0.320). For AMD, sensitivity decreased significantly (0.8570 to 0.8445; difference, -0.0124; 95% CI, -0.0215 to -0.0033; p = 0.008), whereas specificity did not change significantly (0.9685 to 0.9843; p = 0.324). In an exploratory image-level analysis for at least one target disease, review decreased to 27.7%-30.1%; sensitivity changed from 0.9122 to 0.9039 (difference, -0.0083; 95% CI, -0.0131 to -0.0035; p < 0.001) and specificity from 0.9659 to 0.9804 (p = 0.334). AI-assisted negative-screening can reduce ophthalmologist workload across multiple retinal diseases, but with disease-specific safety trade-offs: because AI-negative images are not reviewed, reduced sensitivity for DR and AMD means a small proportion of true-positive cases would go undetected, potentially delaying diagnosis and treatment for sight-threatening disease. These results support disease-specific implementation strategies that balance workload reduction against missed positive cases.}, }
@article {pmid42744112, year = {2026}, author = {Lu, X and Li, B and Sun, B and Fan, S and Chen, N and Chu, Y}, title = {Targeting the choroidal neovascularization microenvironment: new perspectives in nanotherapeutic strategies.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {}, number = {}, pages = {115238}, doi = {10.1016/j.ejpb.2026.115238}, pmid = {42744112}, issn = {1873-3441}, abstract = {Choroidal neovascularization (CNV) is a key pathological mechanism underlying irreversible vision loss in diseases such as age-related macular degeneration (AMD). Although anti-vascular endothelial growth factor (VEGF) therapies effectively inhibit angiogenesis, they are limited by the need for frequent injections, the tendency to induce resistance, and their inability to reverse the complex pathological microenvironment driving CNV. Research indicates that the initiation and progression of CNV are cooperatively driven by the local microenvironment, particularly through the interplay of oxidative stress, hypoxia, and inflammatory networks. In recent years, the emergence of nanotechnology has provided unprecedented tools for precise modulation of this microenvironment. This review systematically delineates the mechanisms of CNV formation, with a focused analysis on the core interplay between oxidative stress, hypoxia, and inflammation. We provide an in-depth exploration of advanced nano-therapeutic strategies designed to multi-target angiogenic pathways, dynamically manipulate reactive oxygen species, disrupt hypoxia-driven feedback loops, reprogram the immunoinflammatory network, and restore defective cellular autophagy. This review aims to provide a theoretical foundation and forward-looking perspective for developing next-generation microenvironment-targeted therapies capable of intervening in CNV.}, }
@article {pmid42744754, year = {2026}, author = {Mahato, S and Daniele, E and Lewallen, CF and Sharma, R and Bharti, K}, title = {The Biology and Cell Engineering of Retinal Pigment Epithelium Cell Transplantation: Developing a Living Drug.}, journal = {Annual review of vision science}, volume = {12}, number = {1}, pages = {99-126}, doi = {10.1146/annurev-vision-110725-100948}, pmid = {42744754}, issn = {2374-4650}, mesh = {Humans ; *Retinal Pigment Epithelium/cytology/transplantation ; *Macular Degeneration/therapy/physiopathology ; Animals ; *Cell Engineering/methods ; *Stem Cell Transplantation/methods ; Cell Differentiation/physiology ; Induced Pluripotent Stem Cells/transplantation/cytology ; }, abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease that causes progressive vision loss, with retinal pigment epithelium (RPE) atrophy representing a key initiating event. The RPE monolayer plays a crucial role in maintaining photoreceptor and choriocapillaris health and function. In advanced AMD stages, degeneration extends to the photoreceptors and choriocapillaris, likely as a consequence of preceding RPE atrophy. Existing treatment modalities aim to slow disease progression rather than restore degenerated cells and improve visual function. Pluripotent stem cell-derived RPE cell replacement therapy has emerged as a promising approach for restoring native retinal structure and visual function. This review provides an overview of RPE biology and function, clinical-grade manufacturing of RPE transplants, quality control considerations, and the use of scaffolds to improve delivery and integration. We also summarize preclinical and clinical studies that assess the safety, efficacy, and translational potential of RPE transplantation for AMD and other retinal degenerative conditions.}, }
@article {pmid42744769, year = {2026}, author = {Muttuvelu, DV and Cehofski, LJ and Faber, C and Falk, MK and Giannaccare, G and Grauslund, J and Hansen, MS and Huemer, J and Keane, PA and Kiruparajan, LP and Larsen, MB and Peto, T and Qin, V and Søndergaard, CB and Taloni, A and Torp-Pedersen, TE and Subhi, Y and Rasmussen, MLR}, title = {Referral patterns after nationwide implementation of OCT-enabled teleophthalmology in optometrist stores in Denmark.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261488973}, doi = {10.1177/11206721261488973}, pmid = {42744769}, issn = {1724-6016}, abstract = {PurposeTo evaluate changes in opportunistic eye examination and referral patterns after nationwide implementation of Optical coherence tomography (OCT) within an optometrist-based teleophthalmology pathway.MethodsThis nationwide multi-period observational study included 1,220,082 individuals examined across 79 Danish optometrist stores between March 2022 and May 2025. Data were analyzed across three periods: before OCT, during implementation, and after full implementation. Outcomes included referral rates to teleophthalmology, diagnostic patterns, and referrals to public healthcare.ResultsMonthly referrals to teleophthalmology increased from 703 before OCT to 2,359 after implementation. Detection of macular diseases increased markedly, including central serous chorioretinopathy, epiretinal membrane, macular hole, and neovascular age-related macular degeneration. Referrals to public healthcare rose from 0.55% to 1.74%, with stable acute referrals but substantial increases in subacute (+178%) and routine (+292%) referrals.ConclusionsNationwide implementation of OCT within an optometrist-based teleophthalmology pathway was associated with increased teleophthalmology submissions, increased detection of selected retinal and optic-nerve conditions, and redistribution of public healthcare referrals towards subacute and routine priorities. These findings should be interpreted as changes within an integrated care model combining OCT imaging, standardized optometrist acquisition, consultant ophthalmologist review, and structured teleophthalmology triage, rather than as the isolated effect of OCT.}, }
@article {pmid42744950, year = {2026}, author = {Pu, J and Hao, X and Zhuang, X and Chen, X and Gan, Y and He, G and Su, Y and He, Y and Li, M and Wen, F}, title = {Geometric and concavity characteristics as diagnostic markers for differentiating nAMD-related MNV from pachychoroid neovascularisation.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42744950}, issn = {1476-5454}, abstract = {PURPOSE: To investigate morphometric differences in macular neovascularisation (MNV) outer contours between neovascular age-related macular degeneration (nAMD) and pachychoroid neovasculopathy (PNV) using quantitative optical coherence tomography angiography (OCTA) analysis.<br><br>METHODS: This retrospective cross-sectional study enrolled treatment-na&#xef;ve patients with newly diagnosed MNV, classified into nAMD and PNV groups. The nAMD group was further subdivided into Type 1 MNV, Type 2 MNV, and polypoidal choroidal vasculopathy (PCV). A semi-automated pipeline integrating FIJI-based contour extraction and custom Python algorithms quantitatively analysed four MNV morphometric domains: geometric parameters, shape descriptors, concavity features, and orientation.<br><br>RESULTS: Eighty-nine eyes (89 patients) were included (64 nAMD, 25 PNV). PNV patients were significantly younger (P&#x2009;<&#x2009;0.001) with better visual acuity (P&#x2009;=&#x2009;0.026), longer symptom duration (P&#x2009;<&#x2009;0.001), and greater subfoveal choroidal thickness (P&#x2009;<&#x2009;0.001). nAMD-related MNV exhibited significantly larger geometric dimensions (all P&#x2009;<&#x2009;0.05) and deeper marginal indentations (maximum: 0.41&#x2009;&#xb1;&#x2009;0.33 vs. 0.21&#x2009;&#xb1;&#x2009;0.14&#x2009;mm, P&#x2009;=&#x2009;0.009; mean: 0.17&#x2009;&#xb1;&#x2009;0.12 vs. 0.10&#x2009;&#xb1;&#x2009;0.06&#x2009;mm, P&#x2009;=&#x2009;0.002) compared to PNV. These differences were more pronounced between PCV and PNV (all P&#x2009;<&#x2009;0.001). ROC analysis demonstrated moderate discriminative performance for nAMD versus PNV (AUC&#x2009;=&#x2009;0.711 and 0.723) and good performance for PCV versus PNV (AUC&#x2009;=&#x2009;0.778 and 0.840) using equivalent diameter and mean concavity depth.<br><br>CONCLUSION: Outer contour morphometry effectively differentiates MNV aetiologies, with nAMD (particularly PCV) showing larger, more lobulated patterns than PNV's compact configurations, likely reflecting distinct pathophysiological mechanisms.}, }
@article {pmid42726725, year = {2026}, author = {Shirakami, M and Miyata, M and Hata, M and Ooto, S and Tamura, H and Otsuka, A and Tsukui, L and Ueda-Arakawa, N and Miyake, M and Takahashi, A and Kadomoto, S and Muraoka, Y and Tsujikawa, A}, title = {Two-dose aflibercept 8 mg versus three-dose aflibercept 2 mg loading for treatment-naïve neovascular age-related macular degeneration.}, journal = {PloS one}, volume = {21}, number = {9}, pages = {e0349947}, pmid = {42726725}, issn = {1932-6203}, mesh = {*Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Humans ; Retrospective Studies ; Female ; Male ; Visual Acuity/drug effects ; *Macular Degeneration/drug therapy/pathology ; Intravitreal Injections ; Aged ; Aged, 80 and over ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Dose-Response Relationship, Drug ; }, abstract = {This retrospective study compared the short-term efficacy of a two-dose intravitreal aflibercept (IVA) 8-mg loading regimen (2024-2025) with a conventional three-dose IVA 2-mg regimen (2013-2014) for treatment-naïve neovascular age-related macular degeneration (nAMD). Using 1:1 propensity score matching for age, sex, nAMD subtype, and baseline visual acuity, we evaluated 31 eyes per group. The primary endpoint was the proportion of eyes achieving a fluid-free center subfield one month after completing the respective loading phase (at 2 and 3 months from baseline, respectively). The fluid-free proportion was numerically higher in the 8-mg group (90.3%; 95% confidence interval [CI], 74.2-98.0%) than in the 2-mg group (80.6%; 95% CI, 62.5-92.5%); however, the difference was not statistically significant (P = 0.28). Both regimens yielded significant reductions in central retinal thickness, central choroidal thickness, and pigment epithelial detachment height, with no significant between-group differences. Within the 8-mg group, baseline intraretinal fluid strongly correlated with one-month visual acuity (r = 0.61, P < 0.001). These exploratory findings suggest that a reduced two-dose aflibercept 8-mg loading regimen provided short-term anatomical outcomes that did not differ significantly from the standard three-dose 2-mg regimen. This shortened loading phase potentially reduces the initial treatment burden. Further prospective studies should validate these preliminary outcomes.}, }
@article {pmid42726829, year = {2026}, author = {Kolot, NM and Shargorodska, IV and Ivaniuta, PP and Kovalov, IA and Averyanova, OS}, title = {Factors assoсiated with ocular structural changes inherent to pseudoexfoliation syndrome among Ukrainian patients.}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {54}, number = {4}, pages = {472-477}, doi = {10.36740/Merkur202604114}, pmid = {42726829}, issn = {1426-9686}, mesh = {Humans ; *Exfoliation Syndrome/pathology/complications/epidemiology ; Aged, 80 and over ; Female ; Male ; Middle Aged ; Aged ; Ukraine/epidemiology ; Adult ; Adolescent ; Young Adult ; Risk Factors ; }, abstract = {OBJECTIVE: Aim: To identify factors associated with ocular structural changes inherent to PEX among Ukrainian patients.<br><br>PATIENTS AND METHODS: Materials and &#x41c;ethods: The study was based on a clinical examination of 56 patients (112 eyes) aged 14 to 88 years. The main group included 39 patients (78 eyes) with ocular structural changes confirming the diagnosis of PEX: 14 patients (28 eyes) and 25 patients (50 eyes) with uni- and bilateral lateral involvement, respectively. The control group consisted of 17 patients (34 eyes) without any signs of PEX. The follow-up period was 5 years.<br><br>RESULTS: Results: The findings of the study support the concept of PEX as a systemic fibrillopathy, accompanied by a significant association with chronic coronary syndrome (64%), joint pathology (72%), diabetes mellitus (40%), and central nervous system (56%) disorders compared with the control group. Environmental factors, particularly urbanization (52%) and increased radiation background (64%), are likely additional contributors to disease development. The study demonstrated that bilateral PEX is accompanied by changes in eye structures: pronounced trabecular pigmentation (48%), a critical decrease in corneal endothelial cell density (80%), progression of age-related macular degeneration (40-44%), and the development of posterior subcapsular cataract (96%). In contrast, patients with unilateral PEX demonstrated a significantly higher long-term risk of nuclear cataract progression.<br><br>CONCLUSION: Conclusions: Managing patients with PEX necessitates a comprehensive multidisciplinary approach in view of the associated comorbidities and contributing factors. The clinical course of unilateral PEX is strongly linked to exposure to exogenous triggers (urbanization, increased background radiation, and tobacco smoking). The absolute majority of eyes with bilateral PEX showed biomechanical weakness of the sclera and cornea.}, }
@article {pmid42727684, year = {2026}, author = {Shen, M and Lam, WZ and Berni, A and Herrera, G and El-Mulki, OS and Badla, O and Herrera, E and Liu, J and Cheng, Y and Kastner, J and Trivizki, O and Meng, D and Patel, P and Kumar, S and Zhang, Y and Le, VH and O'Brien, RC and Nicola, MD and Yehoshua, Z and Dubovy, SR and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Two-Year Experience with Intravitreal Pegcetacoplan for the Treatment of Geographic Atrophy in Clinical Practice.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.09.011}, pmid = {42727684}, issn = {1879-1891}, abstract = {PURPOSE: To report the 2-year experience of using intravitreal pegcetacoplan for the treatment of geographic atrophy (GA) in age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective interventional case series.<br><br>METHODS: Eyes with symptomatic GA secondary to AMD were treated with 15mg of intravitreal pegcetacoplan and participated in an ongoing prospective swept-source optical coherence tomography angiography (SS-OCTA) imaging study. All eyes underwent SS-OCTA imaging before and during pegcetacoplan therapy to assess for GA lesion size, the presence of non-exudative macular neovascularization (MNV), and the onset of exudation. The growth rate of GA and best-corrected visual acuity (BCVA) were assessed for all eyes treated for 2 years.<br><br>RESULTS: From April 12, 2023 to December 8, 2025, 77 eyes from 58 patients continued pegcetacoplan treatment for 2 years. Eyes received an average of 18&#xb1;3 injections with an interval of 1.3 months between injections. For the 72 eyes with 2 years of follow-up and measurable GA, the square-root (sqrt) GA growth rate after pegcetacoplan treatment was 0.22&#xb1;0.12 mm/year. Of the 72 eyes, 71 eyes either decreased further in their sqrt GA growth rate or remained the same in the second year, while 1 eye had an increase in the sqrt GA growth rate. This eye also received concomitant anti-VEGF therapy due to exudative MNV. Of these 72 eyes, 49 eyes had prior annual visits before treatment. In these eyes, the annual sqrt GA growth rate was 0.33&#xb1;0.21 mm/year before pegcetacoplan and 0.19&#xb1;0.11 mm/year after 2 years, resulting in a 41% decrease in the growth rate (p<0.001). There were no significant differences in GA growth rates between foveal and non-foveal GA (all p&#x2265;0.99). The mean BCVA declined from 63&#xb1;14 to 55&#xb1;16 letters over 2 years (p<0.001), with no significant difference between foveal and non-foveal GA (p=0.14). Positive correlations were found between the sqrt GA growth rates prior to treatment and the percent growth inhibition over both 1 year (r=0.33, p=0.02) and 2 years of treatment (r=0.40, p=0.007).<br><br>CONCLUSIONS: Pegcetacoplan therapy reduced the growth rate of GA by about 41% over 2 years and continued to show accumulated efficacy during the second year.}, }
@article {pmid42728439, year = {2026}, author = {Golebka, JP and Josan, AS and Mi, H and Mole, G and Aslam, SA and MacLaren, RE and Cehajic-Kapetanovic, J}, title = {Comparison of current treatment strategies for AMD-related submacular haemorrhage: Real-world outcomes.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42728439}, issn = {1435-702X}, abstract = {PURPOSE: Comparison of available treatment modalities for neovascular AMD-related submacular haemorrhage including robot-assisted subretinal drug delivery.<br><br>METHODS: Single centre, long-term, retrospective analysis of patients treated for nAMD-related submacular haemorrhage. For each treatment group, outcomes assessed included haemorrhage resolution and best corrected visual acuity (BCVA) change with sub-analyses by haemorrhage size.<br><br>RESULTS: We identified 55 patients with classic nAMD-related submacular haemorrhage. We observed a preference for the surgical approach injecting subretinal TPA (manual or robotic) with intravitreal anti-VEGF and pneumatic displacement (30 cases: 8:10:12 ratio of small:medium:large haemorrhage), over intravitreal TPA/anti-VEGF/pneumatic displacement (13 cases: 4:5:4) or intravitreal anti-VEGF alone (12 cases 8:4:0). Subretinal TPA led to significant decrease in haemorrhage size by month 1 compared to intravitreal TPA or anti-VEGF monotherapy (p&#x2009;<&#x2009;0.0001, Tukey test) with most cases resolving by 12&#xa0;months irrespective of the treatment group. Mean BCVA change over 12&#xa0;months was not significantly different between treatment groups, although by 12&#xa0;months&#x2009;+&#x2009;15 letter gain was observed post subretinal TPA,&#x2009;+&#x2009;11 after intravitreal TPA and -7 letters loss after anti-VEGF monotherapy. A higher proportion of patients in the surgical group (53% subretinal and 69% intravitreal TPA) were associated with BCVA improvement, or stabilisation (33% and 15% respectively), while anti-VEGF alone led to more frequent BCVA deteriorations (50% of cases). Robot-assisted TPA injection showed comparable result to the manual technique.<br><br>CONCLUSIONS: Subretinal TPA approach, manual and robotic, resulted most effective clearance of submacular haemorrhage in the early post-operative phase, with some potential clinical benefit for longer term visual function.}, }
@article {pmid42732817, year = {2026}, author = {Fujimoto, S and Kokame, GT and Kawasaki, R and Hara, C and Omizo, JN and Nishida, K}, title = {Variations in the clinical characteristics of geographic atrophy among Caucasians, Japanese Americans in Hawaii, and Japanese in Japan.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100372}, doi = {10.1016/j.apjo.2026.100372}, pmid = {42732817}, issn = {2162-0989}, abstract = {PURPOSE: To compare clinical characteristics of geographic atrophy (GA) among Caucasians in Hawaii (C-A), Japanese Americans in Hawaii (J-A), and Japanese in Japan (J-J).<br><br>DESIGN: Retrospective study.<br><br>METHODS: Consecutive patients with GA were recruited from single institutions in Hawaii and Japan, and GA areas within 6&#xd7;6mm&#xb2; OCT scan area were measured on near-infrared images obtained at the latest visit. Ethnic differences in GA-related characteristics were assessed using mixed-effects models adjusted for age and sex. All values are means.<br><br>RESULTS: A total of 125 eyes from 91 patients were included: 51 eyes of 36 C-A (58% men), 36 eyes of 26 J-A (35% men), and 38 eyes of 29 J-J (69% men). Bilateral GA was more frequent in C-A (72%) than in J-J (34%, P < 0.01), while J-A (50%) did not differ from either group. The number of GA foci was greater in C-A (2.8) than in J-A (1.9, P < 0.05) and J-J (1.5, P < 0.01). GA area was significantly larger in C-A (10.3mm&#xb2;) than in J-J (8.8mm&#xb2;, P < 0.05), with J-A (6.0mm&#xb2;) intermediate. Subfoveal choroidal thickness (SFCT) was thinner in C-A (83.3&#xb5;m) than in J-A (140.8&#xb5;m, P < 0.001) and J-J (165.3&#xb5;m, P < 0.0001).<br><br>CONCLUSIONS: The number of GA foci and SFCT differed between J-J and C-A as well as between J-A and C-A, suggesting genetic differences. In contrast, significant differences in GA area and bilaterality were observed only between J-J and C-A. The intermediate values in J-A may reflect environmental influences. Further studies are warranted.}, }
@article {pmid42733609, year = {2026}, author = {Piedrahita, MA and Arias-Ortiz, WA and Acosta Cadavid, CP and Cadena Galvis, E and Peña, FY}, title = {Patient-Reported Quality of Life and Treatment Experiences Among Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept in Colombia: A Qualitative Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {626968}, pmid = {42733609}, issn = {1177-5467}, abstract = {PURPOSE: To explore the experiences and perceptions of patients with neovascular age-related macular degeneration (AMD) receiving anti-VEGF therapy and understand how treatment influences their quality of life.<br><br>PATIENTS AND METHODS: A qualitative study informed by a phenomenological perspective and employing a hybrid deductive-inductive thematic analysis was conducted at an ophthalmologic center in Medell&#xed;n, Colombia. Fourteen patients with confirmed AMD undergoing intravitreal aflibercept treatment participated in semi-structured telephone interviews. Participants were selected through purposive sampling until meaning saturation was achieved, defined as the point at which no new experiential themes emerged. Interviews were transcribed verbatim and analyzed using a hybrid deductive-inductive thematic analysis guided by the Felce and Perry quality-of-life framework, supported by ATLAS.ti v24.<br><br>RESULTS: Patients described AMD as a condition strongly associated with fear, uncertainty, and emotional distress, particularly related to progressive visual loss and blindness. Intravitreal injections were initially perceived as invasive and anxiety-provoking; however, over time many participants associated treatment with hope, visual stability, and preservation of independence. Family support, religious beliefs, and trust in the treating ophthalmologist emerged as important factors for emotional coping and treatment adherence. Participants also reported subjective improvement in daily activities such as reading, mobility, self-care, and social interaction. Nevertheless, some continued to experience limitations related to transportation, dependence on others, and social isolation. Concerns about continuity of care and access to medication were frequently expressed.<br><br>CONCLUSION: Quality of life in patients with AMD receiving anti-VEGF therapy extends beyond visual outcomes alone and is deeply influenced by emotional, social, and functional factors. Although treatment generated fear and discomfort at the beginning, it also represented an opportunity to maintain autonomy and social participation. These findings highlight the importance of patient-centered care strategies that integrate psychosocial support, clear communication, and continuous access to treatment.}, }
@article {pmid42734305, year = {2026}, author = {Ehrenzeller, C and Cancian, G and Kostin, V and Peyla, A and Ansari, G and Paris, A and Grimaldi, G and Pfau, M and Menghini, M}, title = {Clinical Surrogate Endpoints in Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Findings From a Two-Year Natural History Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {11}, pages = {24}, pmid = {42734305}, issn = {1552-5783}, mesh = {Humans ; Female ; Tomography, Optical Coherence/methods ; Male ; Middle Aged ; Visual Acuity/physiology ; Aged ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology ; Retinal Drusen/physiopathology ; Visual Field Tests ; *Corneal Dystrophies, Hereditary/physiopathology/diagnosis ; Disease Progression ; Visual Fields/physiology ; Multimodal Imaging ; *Retinal Dystrophies/physiopathology/diagnosis ; Optic Disk Drusen/congenital ; }, abstract = {PURPOSE: Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy is a rare, inherited retinal dystrophy characterized by drusen formation and early vision loss. Its phenotypical similarities with dry age-related macular degeneration (AMD) make Malattia Leventinese a valuable monogenetic disease model for AMD. Identifying sensitive outcome measures is crucial for clinical trials. This study quantifies retinal pigment epithelium and drusen complex (RPEDC) increase and retinal layer degeneration using fully automated segmentation for multimodal imaging analysis, and investigates structural thresholds associated with functional decline through pointwise correlation.<br><br>METHODS: This multicenter cohort study included 25 patients (15 women and 10 men; median age = 60 years, interquartile range [IQR] = 51-73 years) with genetically confirmed Malattia Leventinese. Participants underwent multimodal imaging, including spectral-domain optical coherence tomography (SD-OCT), ultrawide fundus retinography and fundus autofluorescence (FAF), and mesopic and two-color scotopic microperimetry. Changes in retinal layer thicknesses and retinal sensitivity were assessed over 2 years using linear mixed-effects models, and structure-function breakpoints were estimated with piecewise models.<br><br>RESULTS: RPEDC thickness increased (+2.24&#xa0;&#xb5;m/y), whereas photoreceptor inner segments (-0.70&#xa0;&#xb5;m/y) and outer nuclear layer (-1.95&#xa0;&#xb5;m/y) thicknesses, in addition to choroidal thickness (-10.83&#xa0;&#xb5;m/y), decreased with disease progression. Total retinal thickness remained stable. Scotopic sensitivity declined over time, with -0.40 decibel (dB)/year at 505 nm and -0.37 dB/year at 627 nm, whereas mesopic sensitivity remained stable. Function decreased most in early disease stages, with the onset of drusen accumulation.<br><br>CONCLUSIONS: In Malattia Leventinese, the total retinal thickness remains unchanged because the RPEDC increase offsets the thinning of outer retinal layers. Only scotopic function decreases significantly with progression and before the age of 55 years. Mesopic function may serve to track later stages. These findings support the outer nuclear layer and photoreceptor inner segment thicknesses as key structural endpoints and scotopic sensitivity as an early functional outcome measure for monitoring disease progression in ongoing and future clinical trials.}, }
@article {pmid42734658, year = {2026}, author = {Maeda, K and Machida, A and Murakami, R and Akiyama, F and Miyagi, S and Oishi, A}, title = {Fellow-eye retinal age gap and high injection burden over four years in neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42734658}, issn = {1435-702X}, support = {22K09793//Japan Society for the Promotion of Science/ ; 25K20183//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: To evaluate whether fellow-eye retinal age gap (RAG), estimated using a deep learning model, is associated with long-term intravitreal injection burden in treatment-naive neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective cohort study included 80 patients with treatment-naive nAMD followed for &#x2265;&#x2009;4 years after initiating anti-vascular endothelial growth factor therapy. Retinal age was estimated from fellow-eye fundus photographs using the publicly available Japan Ocular Imaging Registry model, and raw RAG was calculated as retinal age minus chronological age. Univariable analyses assessed associations of retinal age metrics with baseline ocular parameters, whereas univariable and multivariable analyses assessed their associations with 4-year injection burden.<br><br>RESULTS: Median chronological age, retinal age, and raw RAG were 67.6, 68.9, and 1.33 years, respectively. Retinal age correlated with baseline best-corrected visual acuity and central retinal thickness, while raw RAG correlated with central choroidal thickness. Neither raw nor age-corrected RAG was associated with total injection number in the count analysis. In an exploratory threshold-based analysis, the &#x2265;&#x2009;24-injection group had higher raw RAG than the <&#x2009;24-injection group (4.19 vs. 0.66 years, P&#x2009;=&#x2009;0.039), and higher raw RAG was associated with requiring&#x2009;&#x2265;&#x2009;24 injections (OR 1.11 per 1-year increase; 95% CI, 1.01-1.22; P&#x2009;=&#x2009;0.029). However, this association was attenuated after age correction and was not replicated at alternative thresholds.<br><br>CONCLUSION: Higher raw fellow-eye RAG was associated with the &#x2265;&#x2009;24-injection threshold; the association was attenuated after age correction and nonsignificant in alternative-threshold and count analyses. Further studies should evaluate RAG as a fundus-based candidate marker of sustained high treatment burden.}, }
@article {pmid42736398, year = {2026}, author = {Bousamri, A}, title = {Comment on: 'Aflibercept 8 mg in neovascular age-related macular degeneration and diabetic macular oedema'.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42736398}, issn = {1476-5454}, }
@article {pmid42736891, year = {2026}, author = {Öncül, H and Dağ, U and Alakuş, MF}, title = {Regular AREDS2 Supplement Use in Age-Related Macular Degeneration: Factors Associated with Supplementation, Medication Adherence, and Patient-Reported Barriers.}, journal = {Healthcare (Basel, Switzerland)}, volume = {14}, number = {17}, pages = {}, pmid = {42736891}, issn = {2227-9032}, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment, and AREDS2-based nutritional supplementation is recommended for clinically eligible patients to reduce the risk of disease progression. However, successful implementation depends on regular supplement use and sustained adherence. This study investigated demographic, socioeconomic, clinical, and physician-related factors associated with regular AREDS2 supplement use and evaluated medication adherence, physician counseling, and patient-reported barriers among clinically eligible patients with AMD. Methods: In this single-center cross-sectional study, 389 patients with intermediate AMD or advanced AMD in one eye who fulfilled the indications for AREDS2 supplementation were enrolled. Participants reporting occasional supplement use were excluded. A structured interviewer-administered questionnaire was used to collect demographic, socioeconomic, and clinical data, together with information on physician recommendation, medication adherence, patient knowledge, and perceived barriers to supplementation. Factors associated with regular AREDS2 supplement use were evaluated using univariable and multivariable logistic regression analyses, whereas adherence patterns and patient-reported barriers were analyzed descriptively. Results: Of the 389 participants, 273 (70.2%) reported regular AREDS2 supplement use, whereas 116 (29.8%) were non-users. Multivariable analysis showed that younger age, educational attainment, and physician recommendation were independently associated with regular supplement use (adjusted OR for physician recommendation, 5.38; 95% CI, 2.68-10.81; p < 0.001). Among regular users, 53.5% met the study-defined criteria for good medication adherence. The most frequently reported barriers among non-users were financial burden, limited supplement availability, polypharmacy, and insufficient knowledge regarding AREDS2 supplementation. Conclusions: Regular AREDS2 supplement use among clinically eligible patients with AMD was associated with demographic, educational, and physician-related factors, whereas long-term adherence remained suboptimal despite substantial uptake. These findings emphasize the importance of effective physician counseling, structured patient education, and interventions addressing socioeconomic barriers to improve the real-world implementation of evidence-based nutritional supplementation in AMD.}, }
@article {pmid42737684, year = {2026}, author = {Panos, GD and Empeslidis, T and Amaxilati, E and Tsiropoulos, GN and Topouzis, N and Konstas, PAG and Chatzimichail, E and Gatzioufas, Z and Amoaku, W}, title = {Molecular Determinants of Intravitreal Anti-VEGF Durability: Drug Architecture, Intraocular Pharmacokinetics, Target Biology and Treatment Resistance.}, journal = {International journal of molecular sciences}, volume = {27}, number = {17}, pages = {}, pmid = {42737684}, issn = {1422-0067}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage/therapeutic use/pharmacology ; Intravitreal Injections ; Animals ; Drug Resistance ; *Macular Degeneration/drug therapy/metabolism ; Eye/metabolism/drug effects ; Macular Edema/drug therapy/metabolism ; Ranibizumab/pharmacokinetics/therapeutic use ; }, abstract = {Intravitreal inhibition of vascular endothelial growth factor (VEGF) has transformed the management of neovascular age-related macular degeneration, diabetic macular oedema and macular oedema secondary to retinal vein occlusion, but frequent monitoring and retreatment remain major burdens. Ocular half-life is often used as shorthand for durability, although the clinical interval is produced by a wider molecular and biological system. This narrative review examines how dose, molecular format, hydrodynamic size, binding affinity, valency, ligand spectrum, target turnover, tissue distribution and delivery architecture determine the time for which an eye remains controlled. Human ocular pharmacokinetic and pharmacodynamic evidence is interpreted according to compartment, assay and model provenance, with particular attention to the distinction between drug elimination, free-ligand suppression, anatomical control and protocol-assigned treatment interval. Trial evidence for ranibizumab, aflibercept, conbercept, brolucizumab and faricimab shows that extended dosing can arise from greater starting exposure, altered binding architecture or pathway expansion without a proportionate change in intrinsic ocular half-life. Patient phenotype and retreatment rules further modify the observed interval. Refillable reservoirs, biodegradable depots and ocular gene therapy change the governing kinetics from bolus elimination to controlled release or sustained local production, thereby increasing the importance of reversibility and cumulative safety. We propose that durability be defined as a time-to-threshold phenotype integrating active target-site exposure, biological demand, anatomical recurrence, all treatment-related procedures and safety. Standardised estimands, longitudinal human ocular sampling, spatial exposure methods and externally validated mechanism-informed models are needed to make molecular durability comparable and clinically actionable.}, }
@article {pmid42738828, year = {2026}, author = {Mehta, P and Moore, E and Dash, A and Shukla, S}, title = {Liposomal Drug Delivery in Ocular Therapy: Strategies for Enhancing Corneal Penetration and Bioavailability.}, journal = {Cells}, volume = {15}, number = {17}, pages = {}, pmid = {42738828}, issn = {2073-4409}, mesh = {Humans ; *Liposomes/chemistry ; Biological Availability ; *Drug Delivery Systems/methods ; *Cornea/metabolism/drug effects ; Animals ; Administration, Ophthalmic ; *Eye Diseases/drug therapy ; Ophthalmic Solutions ; }, abstract = {Vision impairment affects approximately 2.2 billion people worldwide, with glaucoma, age-related macular degeneration, fungal keratitis, and diabetic retinopathy among the leading causes of preventable blindness. Effective pharmacotherapy remains severely constrained by the eye's multilayered barrier architecture. Tear film, the corneal epithelium, the blood-aqueous barrier, and the blood-retinal barrier collectively restrict conventional topical drug bioavailability to less than 5% of the administered dose. Liposomal drug delivery systems have emerged as a clinically translatable platform capable of overcoming these barriers through targeted surface modification. This review provides a brief introduction to ocular barriers to drug delivery and transport and critically examines numerous surface-modification strategies applied to liposomal carriers to enhance corneal permeation and ocular bioavailability of drugs. It highlights the advantages and disadvantages of each modification strategy, as well as the convergent mechanism of liposomal surface modification in overcoming ocular barriers, and provides a comparative analysis of different surface-modification strategies of liposomes in terms of safety, efficacy and corneal retention. Additionally, it describes challenges associated with liposomal ophthalmic formulations in industrial scaling up. The review also sheds light on some FDA-approved liposomal ophthalmic products, active clinical trials on liposomal formulations, and relevant patents, demonstrating the potential benefits of liposomal drug delivery in the treatment of ocular disorders.}, }
@article {pmid42739139, year = {2026}, author = {Baek, J and Oh, R and Park, D and Bae, K}, title = {Evaluating Artificial Intelligence as a First-Pass Reader in Fundus Photograph Screening: A Multireader Workflow Validation Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {17}, pages = {}, pmid = {42739139}, issn = {2075-4418}, support = {SNUH 0620242810//VUNO Inc/ ; KMI20260230//2026 research program of the Korea Medical Institute/ ; }, abstract = {Background/Objectives: Double reading with arbitration improves diagnostic reliability in fundus screening but requires repeated human interpretation. Whether artificial intelligence (AI) can serve as a first-pass decision source within this workflow, and whether this applies consistently across retinal diseases with differing inter-reader agreement, remains unclear. Methods: In this retrospective study, 6904 color fundus photographs from 2593 patients at a tertiary screening center were analyzed for age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Three retina specialists independently labeled each image, and an AI system provided binary classifications at a prespecified operating threshold targeting 0.99-sensitivity. In AI-human double reading, the AI and one reader independently interpreted each image, and a second reader arbitrated discordant cases; this was compared with conventional human-human double reading. Three reader combinations were evaluated per disease. Results: AI-human reading required 1.02-1.11 human reads per image versus 2.00-2.10 for human-human reading. For DR and RVO, human-human reading yielded sensitivities of 0.974 and 0.982 and specificities of 0.999 and 1.000, respectively. Across AI-human combinations, sensitivity and specificity did not differ significantly from human-human reading (all p ≥ 0.05; specificity differences ≤0.001). For AMD (human-human sensitivity 0.845, specificity 1.000), AI-human sensitivity varied: two combinations were higher (0.916 and 0.950; both p < 0.001) and one comparable (0.842; p = 0.742). AMD specificity remained ≥0.978. Conclusions: AI-human reading halved human reading volume without significant loss for DR and RVO; AMD varied by configuration. AI use within double-reading workflows should account for disease-specific inter-reader agreement, reader composition, and operating threshold. This was a single-center, retrospective study, prospective external validation in a multicenter setting is warranted before clinical implementation.}, }
@article {pmid42739742, year = {2026}, author = {Sato, T}, title = {The Eight-Chop Technique in Nonagenarian Patients: Real-World Intraoperative and Postoperative Outcomes.}, journal = {Journal of clinical medicine}, volume = {15}, number = {17}, pages = {}, pmid = {42739742}, issn = {2077-0383}, abstract = {Objectives: To describe intraoperative and postoperative outcomes of the Eight-Chop Technique in elderly patients, with particular attention to nonagenarian patients undergoing cataract surgery. Methods: This retrospective study included consecutive eligible eyes undergoing Eight-Chop phacoemulsification and posterior chamber intraocular lens implantation at a single clinic. Eyes were stratified by age at surgery into 70-79 years, 80-89 years, and ≥90 years groups. Sixty eyes were included in each younger group, and all 49 eligible nonagenarian eyes were included. Eyes were not intentionally excluded from the younger groups because of poor pupillary dilation, zonular weakness, white cataract, pseudoexfoliation, glaucoma, age-related macular degeneration, or advanced nuclear grade. Preoperative characteristics, intraoperative parameters, best-corrected visual acuity (BCVA), intraocular pressure, and corneal endothelial cell density (CECD) were evaluated. Linear mixed-effects models accounted for fellow-eye correlation. Results: A total of 169 eyes were analyzed. The ≥90-year cohort had greater baseline complexity; intraoperative differences were descriptive, with the highest operative time, phacoemulsification time, aspiration time, cumulative dissipated energy, and irrigation fluid volume (all p < 0.001). Postoperative BCVA improved from baseline in all groups. Mean CECD loss at 19 weeks was -1.3 ± 5.7%, -0.7 ± 5.7%, and 3.5 ± 9.2% in the 70-79-, 80-89-, and ≥90-year groups, respectively. No serious intraoperative complications occurred. Conclusions: The Eight-Chop Technique was used across elderly age groups, including nonagenarian patients. Observed age-group differences represent associations in this retrospective dataset and do not establish causal age effects or comparative superiority, safety, or endothelial protection of the technique.}, }
@article {pmid42739837, year = {2026}, author = {Kook, K and Park, D and Lee, G and Ji, YS}, title = {Time to Exudative Recurrence After Complete Fluid Resolution Following Anti-VEGF Loading in Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {17}, pages = {}, pmid = {42739837}, issn = {2077-0383}, abstract = {Background/Objectives: The timing of exudative recurrence after complete fluid resolution following anti-vascular endothelial growth factor (anti-VEGF) loading in neovascular age-related macular degeneration (nAMD) is unpredictable. We prespecified two questions: whether the speed of fluid resolution during loading, or the baseline pigment epithelial detachment (PED) type, predict recurrence timing. Methods: We retrospectively analyzed 72 treatment-naïve nAMD eyes that achieved complete resolution of subretinal fluid (SRF) and intraretinal fluid (IRF) after three monthly loading injections, then observed them under a pro re nata strategy. Time from the post-loading dry-confirmation visit to first detected recurrence was analyzed with Kaplan-Meier and Cox models; baseline variables with univariable p < 0.10 were entered into a multivariable model. Results: Recurrence was detected in 58 eyes (80.6%); median recurrence-free survival was 139 days (95% CI, 118-158). Resolution of SRF or IRF by one month was not significantly associated with recurrence timing (p = 0.586 and 0.054). Fibrovascular PED was associated with earlier detected recurrence compared with non-fibrovascular PED (adjusted hazard ratio 2.40, 95% CI, 1.17-4.92; p = 0.017; median 130 vs. 602 days). Eyes with fibrovascular PED were monitored more frequently, but the association persisted in an interval-censored sensitivity analysis (adjusted HR 2.71, 95% CI, 1.32-5.60). Conclusions: The speed of fluid resolution was not significantly associated with recurrence timing, whereas fibrovascular PED was associated with earlier detected recurrence and may represent a candidate prognostic marker requiring prospective validation.}, }
@article {pmid42739959, year = {2026}, author = {Sun, X and Lin, W and Yuan, C and Xu, J and Luo, Y}, title = {Self-Supervised OCT Representation Learning with Local Dimensionality Regularization for Automated Retinal Disease Diagnosis.}, journal = {Sensors (Basel, Switzerland)}, volume = {26}, number = {17}, pages = {}, pmid = {42739959}, issn = {1424-8220}, support = {2023YFC3402800//National Key Research and Development Program of China/ ; 62501292//National Natural Science Foundation of China/ ; BK2023200//Jiangsu Province Science and Technology Department/ ; 24KJB520020//Natural Science Research of Jiangsu Higher Education Institutions of China/ ; }, mesh = {*Tomography, Optical Coherence/methods ; Humans ; Representation Machine Learning ; *Retinal Diseases/diagnostic imaging/diagnosis ; Retina/diagnostic imaging ; Algorithms ; Supervised Machine Learning ; Image Processing, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging/diagnosis ; Diabetic Retinopathy ; }, abstract = {Optical coherence tomography (OCT) is a high-resolution and non-contact optical imaging and sensing modality that provides depth-resolved cross-sectional visualization of retinal microstructures. It plays an important role in the assessment of retinal diseases, including age-related macular degeneration (AMD) and diabetic macular edema (DME). However, automated OCT image classification commonly relies on fully supervised models that require large-scale expert annotations, which are costly and time-consuming because of the complex layered anatomy and subtle pathological patterns present in retinal OCT images. To reduce annotation dependence, this study proposes a self-supervised representation learning framework with local dimensionality regularization for retinal OCT image classification. The proposed method estimates the local intrinsic dimensionality of learned representations and incorporates it into an asymptotic Fisher-Rao regularization objective to mitigate local dimensional degeneration and preserve fine-grained structural information. Logarithmic scaling and geometric averaging are further introduced to reduce sensitivity to outliers and improve optimization stability. Experiments on three independent OCT datasets achieved classification accuracies of 94.35%, 92.48%, and 92.56%, respectively, demonstrating competitive performance compared with mainstream self-supervised methods. These results demonstrate that explicitly modeling local feature geometry can improve the discrimination of sensor-acquired OCT images while reducing reliance on manual annotations, providing an effective approach for intelligent analysis of biomedical optical imaging data.}, }
@article {pmid42723073, year = {2026}, author = {Tom, E and Gao, F and Franco, CN and Wong, A and Kemmerer, N and Wang, Z and Jairaman, A and Xu, Q and Zhuang, Y and Du, SW and Palczewska, G and Palczewski, K and Budin, I and Othy, S and Shi, X and Bonilha, VL and Schoeneberg, J and Wahlin, KJ and Albrecht, LV and Skowronska-Krawczyk, D}, title = {Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retinal aging.}, journal = {Molecular neurodegeneration}, volume = {21}, number = {1}, pages = {}, pmid = {42723073}, issn = {1750-1326}, mesh = {*Lysosomes/metabolism ; Animals ; *Aging/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; *Cell Membrane/metabolism ; Fatty Acid Elongases/metabolism ; Mice ; *Membrane Lipids/metabolism ; Acetyltransferases/metabolism ; Humans ; *Retina/metabolism ; }, abstract = {Age-associated remodeling of membrane lipid composition has been implicated in cellular dysfunction, yet the mechanisms linking lipid changes to membrane integrity and disease remain poorly defined. In the retinal pigment epithelium (RPE), lipid dysregulation is strongly associated with aging and age-related macular degeneration (AMD), a neurodegenerative disease of the central nervous system, but the causal pathways remain unclear. Here, we identify reduced activity of the lipid elongase ELOVL2 as a central driver of age-dependent membrane remodeling. Loss of ELOVL2-dependent polyunsaturated fatty acid (PUFA) elongation shifts plasma membrane lipid composition, leading to altered membrane biophysical properties and compromised membrane integrity. In response to this stress, RPE cells do not undergo apoptosis but instead activate a lysosome-dependent plasma membrane repair program that preserves barrier function under metabolic challenge. However, this adaptive response drives spatially polarized lysosomal exocytosis, promoting extracellular remodeling and accumulation of sub-RPE deposits associated with aging and AMD. Restoration of ELOVL2-derived lipid products reverses membrane abnormalities and suppresses lysosome-mediated remodeling phenotypes, demonstrating direct metabolic control of membrane homeostasis. Together, these findings define an ELOVL2-dependent lipid-lysosome axis that links PUFA elongation to plasma membrane integrity and reveals how compensatory repair mechanisms can contribute to tissue remodeling and disease progression in aging epithelia.}, }
@article {pmid42724764, year = {2026}, author = {Zhang, J and Feng, J and Song, J and Bi, H}, title = {The pathogenesis of müller cell glial-mesenchymal transition in retinal fibrosis-related eye diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1919772}, pmid = {42724764}, issn = {2296-634X}, abstract = {Retinal fibrosis represents an important pathological feature of several vision-threatening ocular diseases, including advanced diabetic retinopathy and neovascular age-related macular degeneration. Its progression may be associated with reactive changes in Müller glial cells and their acquisition of mesenchymal-like phenotypes. As the predominant glial population in the retina, Müller glial cells play crucial physiological roles in maintaining retinal homeostasis. However, under pathological conditions, they can become reactive and acquire mesenchymal- or myofibroblast-like features through a process referred to as glial-mesenchymal transition (GMT), potentially contributing to fibrotic remodeling. This review systematically examines the molecular mechanisms associated with Müller cell GMT, including the regulatory involvement of the TGF-β and Notch signaling pathways, inflammatory mediators, and oxidative stress. It discusses the potential contribution of GMT to retinal fibrotic progression. Furthermore, this article synthesizes the potential pathological and therapeutic relevance of GMT in related ocular diseases and discusses experimental intervention strategies targeting Müller cell phenotypic remodeling. Understanding the regulatory network of Müller cell GMT may inform the development of future therapeutic approaches to prevent or attenuate retinal fibrosis.}, }
@article {pmid42725097, year = {2026}, author = {Mazinani, FSH and Ashtiani, MK and Moradmand, A and Satarian, L}, title = {RPE-derived extracellular matrix improves graft retention and photoreceptor preservation in preclinical models of retinal degeneration.}, journal = {Matrix biology plus}, volume = {32}, number = {}, pages = {100203}, pmid = {42725097}, issn = {2590-0285}, abstract = {INTRODUCTION: Human pluripotent stem cells-derived retinal pigment epithelium (hPSC-RPE) represent a promising therapeutic approach for macular degeneration. This study examines whether RPE-derived extracellular matrix (RPE-ECM), enhances survival and functional outcomes following hPSC-RPE suspension transplantation in a preclinical model of retinal degeneration.<br><br>METHODS: hPSC-RPE cells were cultured under three conditions: control, RPE-conditioned medium (RPE-CM), and RPE-ECM. In vitro, the cells were assessed for proliferation, monolayer organization, and gene expression. In vivo, GFP-labeled hPSC-RPE cells were co-transplanted with the corresponding treatments into the subretinal space of a mouse model of retinal degeneration. For functional assessment, the cells were injected into RCS rats, with visual acuity tracked over six months using optomotor response testing. Retinal morphometry was analyzed by immunohistology techniques to evaluate graft integration and structural rescue.<br><br>RESULTS: In vitro, culture of hPSC-RPE cells with RPE-ECM enhanced proliferation and promoted monolayer formation, and increased Nidogen expression. In vivo, co-transplantation with RPE-ECM significantly improved mice retinal graft integration (47.1% vs. 3.6% in control, P&#xa0;<&#xa0;0.001) and visual acuity over four months in RCS rats. RPE-derived ECM improved graft retention and photoreceptor preservation observed at 180&#xa0;days (P&#xa0;<&#xa0;0.001), with neuroprotective effects extending beyond the graft site to the contralateral retina.<br><br>CONCLUSION: These findings suggest that co-transplantation with RPE-ECM enhances the integration and function performance of hPSC-RPE cells and may represent a promising strategy to improve graft viability within the host retina. Nevertheless, this study has several limitations, including short-term assessment in animal models and the lack of detailed ECM compositional analysis. Further studies are required to elucidate the underlying mechanisms and to evaluate the long-term transplantation potential of this approach in clinical settings.}, }
@article {pmid42722145, year = {2026}, author = {Seol, A and Jeong, JS and Kim, JE and Song, HJ and Lim, SJ and Wang, SH and Ryu, YE and Kim, YR and Yun, W and An, BS and Hwang, DY}, title = {HepG2 cells-derived exosomes exacerbate blue light-induced AMD-like retinal degeneration in A2E-laden ARPE-19 cells and BALB/c mice.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111231}, doi = {10.1016/j.exer.2026.111231}, pmid = {42722145}, issn = {1096-0007}, abstract = {Exosomes derived from hepatic cells have emerged as important mediators of inter-organ communication and may contribute to retinal degeneration associated with age-related macular degeneration (AMD) through the liver-eye axis. However, their role in AMD pathogenesis remains poorly understood. In this study, we investigated whether HepG2 cell-derived exosomes (HG-EX) exacerbate AMD-like retinal degeneration using in vitro and in vivo AMD-mimicking models. ARPE-19 cells co-treated with N-retinylidene-N-retinylethanolamine (A2E) and blue light (BL), as well as BL-exposed BALB/c mice, were pretreated with HG-EX. In AMD-mimicking ARPE-19 cells, HG-EX pretreatment significantly increased intracellular reactive oxygen species (ROS) and nitric oxide (NO) production while suppressing the expression of superoxide dismutase (SOD) and nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, HG-EX altered inflammatory signaling by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, while enhancing inflammasome-related protein expression. Apoptosis-related proteins and pro-angiogenic factors were also markedly elevated following HG-EX treatment. In AMD-mimicking mice, HG-EX administration significantly increased the retinal expression of COX-2, B-cell lymphoma 2 (Bcl-2)/ Bcl-2-associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, accompanied by a reduction in the thickness of the outer segment (OS) and inner nuclear layer (INL). Collectively, these findings demonstrate that HG-EX exacerbate oxidative stress, inflammation, apoptosis, and angiogenesis in both cellular and animal models that recapitulate selected pathological features of AMD. Our results suggest that HG-EX may contribute to AMD-like retinal degeneration and warrant further investigation into their potential role in AMD pathogenesis.}, }
@article {pmid42721102, year = {2026}, author = {Lenhof, S and Mathis, T and Lepretre, N and Rencker, J and Kodjikian, L}, title = {Faricimab in previously treated nAMD: Real-World Outcomes of a No-Loading-Dose Switching Protocol.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1}, doi = {10.1159/oph/aeeag012}, pmid = {42721102}, issn = {1423-0267}, abstract = {INTRODUCTION: Evaluate efficacy, anatomical outcomes, and safety of switching to faricimab without a loading dose, using a standardized institutional switch protocol, in patients with previously treated neovascular age-related macular degeneration (nAMD) who achieved a maximum fluid-free interval of 8 weeks or less with aflibercept or ranibizumab.<br><br>METHODS: Retrospective, single-center cohort study conducted at Croix-Rousse Hospital, Lyon and included eyes with a maximum fluid-free interval of 8 weeks or less on aflibercept or ranibizumab, switched to faricimab between November 2023 and December 2024. Eyes were classified as Poor Responders (PR) or Frequent Flyers (FF) based on their prior anti-VEGF response. No loading dose was administered. Primary outcome was change in last intended treatment interval. Secondary outcomes included best-corrected visual acuity (BCVA), SD-OCT parameters, predictors of interval extension and safety.<br><br>RESULTS: 128 eyes were included. Before switching, mean (SD) treatment duration was 36.4 (21.9) months with a mean (SD) 28.2 (17.0) intravitreal injections. After switching, the median gain in the last intended interval was 2.7 [IQR 2.1-3.3] weeks (p<0.001). Subgroup analysis showed a median gain of 3.1 weeks in PR (p<0.001) and 2.4 weeks in FF (p<0.001). BCVA remains stable (p=0.37). Significant reductions were observed in CMT (p<0.001), SHRM (p=0.02), IRF (p<0.001), and SRF (p<0.001). Baseline characteristics were not associated with treatment interval extension. There was one case of anterior uveitis and vitritis, which resolved with topical corticosteroid treatment.<br><br>CONCLUSION: In previously treated nAMD patients, switching to faricimab without a loading dose achieved meaningful treatment interval extension, potentially reducing treatment burden without compromising efficacy.}, }
@article {pmid42717802, year = {2026}, author = {Freeman, WR and Vail, D and Ye, M and López, FJ and Robinson, MR and Huang, J and Hallak, JA}, title = {Real-World Dosing Intervals for Long-Acting Anti-VEGF Intravitreal Injection Therapies in nAMD and DME: Academy IRIS[®] Registry Analysis.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {}, number = {}, pages = {10807683261484815}, doi = {10.1177/10807683261484815}, pmid = {42717802}, issn = {1557-7732}, abstract = {PURPOSE: To determine real-world dosing intervals for long-acting intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).<br><br>METHODS: Retrospective observational cohort study in American Academy of Ophthalmology IRIS[&#xae;] Registry (Intelligent Research in Sight) patients with nAMD or DME treated with aflibercept 8 mg (aflibercept) or faricimab. Mean injection intervals during a &#x2264;24-month period beginning 3 or 4 months after the initial injection were evaluated and descriptively contrasted with those in phase 3 clinical trials.<br><br>RESULTS: The mean dosing interval was 5-8, 9-12, and &#x2265;13 weeks in 27.5%, 45.6%, and 25.8% of aflibercept-treated patients with nAMD (n = 40,065); 27.0%, 43.4%, and 28.3% of aflibercept-treated patients with DME (n = 13,045); 40.5%, 36.1%, and 20.8% of faricimab-treated patients with nAMD (n = 132,697); and 42.2%, 31.7%, and 22.5% of faricimab-treated patients with DME (n = 39,849). Dosing intervals were consistent between treatment-na&#xef;ve and previously treated patients. In aflibercept phase 3 studies, 77% (nAMD) and 89% (DME) of patients achieved a 16-week dosing interval. In faricimab phase 3 studies, 45% (nAMD) and 52% (DME) of patients achieved a 16-week dosing interval.<br><br>CONCLUSION: Extension of injection intervals to 16 weeks is greatly reduced in real-world experience compared with phase 3 clinical studies. This discrepancy could be explained by protocol-mandated restrictive rescue criteria used in the registration studies, allowing injection only after vision loss and significant fluid recurrence. Current longer-acting anti-VEGF medications offer an extension to only 5-12 weeks for most patients in the real world.}, }
@article {pmid42718898, year = {2026}, author = {Shen, LL and Rosenfeld, PJ and Beqiri, S and O'Brien, RC and Zhang, J and Chew, EY and Del Priore, LV and Stewart, JM}, title = {Intereye Correlation in Bilateral Geographic Atrophy: Morphology and Growth Rates in the Age-Related Eye Disease Study.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101353}, pmid = {42718898}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate intereye correlation in geographic atrophy (GA) lesion morphology, topography, and growth rates, and whether fellow eyes could improve trial efficiency as internal controls.<br><br>DESIGN: Secondary analysis of a multicenter, prospective, randomized controlled trial.<br><br>PARTICIPANTS: Age-Related Eye Disease Study participants with bilateral GA.<br><br>METHODS: Color fundus photographs were used to delineate GA lesions and measure area, perimeter, circularity index, focality, and lesion number. Intereye correlations were evaluated cross-sectionally and longitudinally for 3 GA growth rates (area, square root-transformed, and perimeter-adjusted growth rate). Longitudinal correlations used the first-to-last interval (mean, 5.5 years). Sample-size requirements for paired and unpaired designs were estimated through exploratory power analyses in eyes with 1-year follow-up.<br><br>MAIN OUTCOME MEASURES: Geographic atrophy size, morphology, topographic distribution, and growth rate.<br><br>RESULTS: In 226 eyes from 113 patients, moderate-to-strong associations were observed between fellow eyes for GA area (&#x3c1; = 0.63), perimeter (&#x3c1; = 0.69), circularity index (&#x3c1; = 0.56), and across all 4 quadrants (range, &#x3c1; = 0.51-0.61). Longitudinally, intereye associations were moderate-to-strong for GA area growth rates (&#x3c1; = 0.74), square root-transformed area growth rates (&#x3c1; = 0.62), and perimeter-adjusted growth rates (&#x3c1; = 0.60). These values reflect the first-to-last interval (mean, 5.5 years); over 1 year, correlations were markedly lower (&#x3c1; = 0.53, 0.40, 0.34). By baseline lesion size, intereye correlation was slightly higher for area growth rate in small lesions (&#x2264;0.9 disc areas [DAs]) but comparable between area- and perimeter-adjusted rates in larger lesions (>0.9 DA). In exploratory 1-year power analyses, a paired design with within-participant randomization of study and fellow eyes was associated with approximately 40% lower estimated sample-size requirements than an unpaired design (149 pairs vs. 250 eyes per arm for area growth rate); adding a perimeter-adjusted endpoint in lesions >0.9 DA reduced the estimate to 50 pairs per arm.<br><br>CONCLUSIONS: We observed moderate-to-strong inter-eye correlations in GA morphology, topography, and progression. For exploratory designs of local unilateral therapies, fellow eyes may serve as internal controls alongside square root-transformed or perimeter-adjusted endpoints, reducing sample sizes, particularly for lesions >0.9 DA. Because these analyses use color fundus photography rather than fundus autofluorescence, they are hypothesis-generating for modern trials. These correlations may also inform group-level counseling on fellow-eye progression.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42718940, year = {2026}, author = {Jaffe, GJ and Wykoff, CC and McCaleb, ML and Barrett, TD and Frazer-Abel, A and Norris, D and Luhmann, UFO and Cukras, C and Yin, L and Lomax, M and Fauser, S and Schneider, E and Brice, GT and , }, title = {GOLDEN: Efficacy and Safety of Complement Factor B Antisense, Sefaxersen, in Geographic Atrophy due to Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101340}, pmid = {42718940}, issn = {2666-9145}, abstract = {OBJECTIVE: To evaluate the efficacy and safety of sefaxersen, an investigational antisense oligonucleotide targeting complement factor B (FB), in slowing the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Randomized, double-masked, placebo-controlled, adaptive phase II clinical trial.<br><br>SUBJECTS: A total of 332 patients with GA secondary to AMD were enrolled, with 91% of treated patients completing the final study visit at 56 weeks.<br><br>METHODS: In stage 1, 58 patients received subcutaneous injections of 40, 70, or 100 mg sefaxersen or placebo monthly. An interim analysis for FB, pharmacokinetics, and safety was conducted when patients reached at least 13 weeks of treatment to select 2 doses for expansion. In stage 2, an additional 274 patients were randomized to 40 or 70 mg sefaxersen or placebo. Patients were stratified based on baseline GA size, baseline rate of GA growth, and presence/history of exudative choroidal neovascularization in the fellow eye. Geographic atrophy area was assessed by fundus autofluorescence imaging. Safety assessments included ocular and systemic adverse events, laboratory parameters, and vital signs.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was the rate of GA lesion growth from baseline to week 49. Prespecified endpoints included changes from baseline in best-corrected visual acuity, low-luminance visual acuity, systemic complement measures, and occurrence of treatment-related adverse events.<br><br>RESULTS: Sefaxersen did not significantly reduce the rate of GA growth versus placebo. Differences in adjusted mean GA rate of growth versus placebo were -0.25 mm[2] (-11.5%, P = 0.171) and -0.08 mm[2] (-3.8%, P = 0.647) for 40 and 70 mg groups, respectively. At steady state, a reduction in adjusted mean plasma FB levels (40 mg: -63% and 70 mg: -69%) led also to a reduction in alternative pathway activity (adjusted mean -22% and -34%, respectively). The safety profile, both ocular and nonocular, of sefaxersen was comparable to that of the placebo, with the most common adverse events being coronavirus disease 2019, urinary tract infections, and nasopharyngitis.<br><br>CONCLUSIONS: Sefaxersen reduced systemic FB levels and alternative pathway activity, but the effect on GA growth rate was not significant compared with placebo. The treatment was well tolerated with a safety profile consistent with previous studies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42718944, year = {2026}, author = {de Vries, VA and Lee, SS and Stuart, KV and Schulze, A and Hunter, ML and Hopf, S and Pfeiffer, N and Lingham, G and Luben, RN and Wang, YX and Haarman, AEG and Tedja, MS and Verhoeven, VJM and Jonas, JB and Schuster, AK and Khawaja, AP and Klaver, CCW and Mackey, DA and Ramdas, WD and , }, title = {A Comprehensive Assessment of the Shared Genetic Architecture between Myopia and Open-Angle Glaucoma.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101328}, pmid = {42718944}, issn = {2666-9145}, abstract = {OBJECTIVE: Individuals with high myopia have an increased prevalence of open-angle glaucoma (OAG). We aim to clarify the possibly shared genetic architecture of myopia and OAG, in particular in high myopes with myopic macular degeneration (MMD), where OAG screening is highly challenging.<br><br>DESIGN: Individual participant data meta-analysis of one-sample Mendelian randomization analyses and pleiotropic analysis under a composite null hypothesis.<br><br>PARTICIPANTS: A total of 34&#x2009;825 participants from 6 population-based cohort studies and 1 high myopia case-control study, including 708 OAG and 1953 high-myopia cases.<br><br>METHODS: First, we calculated and validated genetic risk scores (GRSs) for OAG and myopia in each cohort. We subsequently meta-analyzed linear and logistic regression models for the association of a myopia GRS with OAG, intraocular pressure (IOP), and vertical cup-to-disc ratio (VCDR), and the association of an OAG-GRS with high myopia, axial length, and spherical equivalent. We stratified the analysis of OAG in different stages of axial elongation, and in high myopes with or without MMD. Pleiotropic analysis under a composite null hypothesis was applied to genome-wide association study summary statistics.<br><br>MAIN OUTCOME MEASURES: Odds ratio (OR) of OAG and high myopia, and mean difference in IOP, VCDR, axial length, and spherical equivalent.<br><br>RESULTS: One standard deviation (SD) increase in myopia GRS was associated with an OR (95% CI) of 1.18 (1.09, 1.28) for OAG, a beta (95% CI) of 0.04 (0.00, 0.08) mmHg in IOP, and of 0.005 (0.003, 0.007) in VCDR. The OAG-GRS was not significantly associated with high myopia compared to emmetropes, but a 1 SD increase was associated with a beta (95% CI) of 0.05 (0.01, 0.08) mm in axial length and of -0.05 (-0.10, -0.00) diopters in spherical equivalent. One SD increase in OAG-GRS had a substantially larger effect on OAG in high myopes with MMD, with an OR (95% CI) of 3.83 (1.89, 7.78) compared to 1.55 (1.24, 1.94) in emmetropes. Finally, we identified 95 independent pleiotropic single-nucleotide polymorphisms (SNPs).<br><br>CONCLUSIONS: There is strong evidence for pleiotropy between myopia and OAG. Further research into the biological mechanisms of the identified pleiotropic SNPs is needed. An OAG-GRS might help to clinically estimate OAG risk, in particular in individuals with MMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42720289, year = {2026}, author = {Rani, T and Vyas, M and Rachna,  and Sai Charan, L and Vijayasimha, M}, title = {Comment on: Light Adjustable Lens Implantation with Cataract Surgery in Eyes with Macular Pathology.}, journal = {Journal of cataract and refractive surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/j.jcrs.0000000000002049}, pmid = {42720289}, issn = {1873-4502}, }
@article {pmid42720425, year = {2026}, author = {Hua, X and Hormel, TT and Wang, J and Flaxel, CJ and Bailey, ST and Hwang, TS and Jia, Y}, title = {Structural and Angiographic Assessment of the Nerve Fiber Layer in Age-Related Macular Degeneration and Diabetic Retinopathy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {11}, pages = {17}, doi = {10.1167/iovs.67.11.17}, pmid = {42720425}, issn = {1552-5783}, mesh = {Humans ; Female ; *Diabetic Retinopathy/diagnosis/pathology ; *Nerve Fibers/pathology ; Male ; Aged ; *Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/pathology ; *Retinal Ganglion Cells/pathology ; Tomography, Optical Coherence/methods ; Middle Aged ; *Retinal Vessels/pathology ; Aged, 80 and over ; *Optic Disk/pathology/blood supply ; }, abstract = {PURPOSE: The purpose of this study was to evaluate structural and microvascular alterations in the nerve fiber layer (NFL) in age-related macular degeneration (AMD) and diabetic retinopathy (DR).<br><br>METHODS: A total of 74 healthy controls, 101 patients with AMD, and 117 patients with DR were included. One eye per participant was imaged using a Solix OCTA device centered on the optic disc to measure NFL thickness and nerve fiber layer plexus (NFLP) vessel density (VD). For both parameters, we analyzed the independent associations of age, AMD, and DR; compared age-matched healthy controls with the AMD groups and with the DR groups; and evaluated correlations with age in healthy controls.<br><br>RESULTS: Multivariate analyses demonstrated that age was independently associated with both NFL thickness and NFLP VD, whereas AMD was not associated with either parameter and DR was associated only with NFLP VD. The associations of AMD and DR with these two parameters were also confirmed in age-matched analyses. Additionally, NFLP VD decreased significantly with increasing DR severity (P < 0.001). In healthy controls, age was significantly correlated with both NFL thickness (Spearman's &#x3c1; = -0.26, P = 0.026) and NFLP VD (&#x3c1; = -0.32, P = 0.006).<br><br>CONCLUSIONS: NFL thickness was associated with age, but not with AMD or DR. In contrast, DR was independently associated with reduced NFLP VD, which also significantly correlated with DR severity. These findings provide evidence supporting further investigation of NFLP VD in relation to DR, while accounting for age.}, }
@article {pmid42709274, year = {2026}, author = {Candan, O and Orman, G and Ünlü, N and Uney, G and Acar, DD and Burcu, A}, title = {Pre- and post-COVID-19 changes in retinal disease patterns in Türkiye: insights from a tertiary hospital.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42709274}, issn = {1573-2630}, mesh = {Humans ; *COVID-19/epidemiology ; Retrospective Studies ; Male ; *Tertiary Care Centers/statistics &amp; numerical data ; Middle Aged ; Prevalence ; Female ; Aged ; *Retinal Diseases/epidemiology/diagnosis ; *SARS-CoV-2 ; Adult ; Aged, 80 and over ; }, abstract = {PURPOSE: To estimate the prevalence of common retinal diseases in Türkiye during 2017-2023 and to characterize age and gender-specific differences.<br><br>METHODS: This retrospective, single-center, hospital-based study included 475,865 adults presenting to an ophthalmology outpatient clinic. The study period was divided into pre-pandemic (January 2017-March 2020), acute pandemic (March-June 2020), and post-pandemic (June 2020-July 2023) phases. Patient age, gender, diagnoses, and major complications were recorded. The primary outcomes were defined as changes in the prevalence of common retinal diseases and their complications before and after the pandemic.<br><br>RESULTS: Among 475,865 adults, 10,131 (2.13%) were diagnosed with a retinal disease. Age-related macular degeneration was the most prevalent disease, with prevalence increasing from 0.99% in the pre-pandemic period to 1.23% in the post-pandemic period (P < .001). Diabetic retinopathy was the second most common and remained stable across the pandemic periods (0.95% and 0.97%; P = .395). Diabetic macular edema (DME) exhibited a notable increase, particularly among patients aged &#x2265; 50&#xa0;years (from 16.68 to 26.72%; P < .001). Retinal vein occlusion (RVO) ranked third, with prevalence rising from 0.17% before the pandemic to 0.25% after (P < .001). The proportion of patients with DME secondary to RVO requiring injection increased from 38.2% in the pre-pandemic period to 43.8% in the post-pandemic period.<br><br>CONCLUSION: This large-scale longitudinal study demonstrated significant changes in the epidemiology of several retinal diseases across the pre- and post-pandemic periods in T&#xfc;rkiye. However, the mechanisms underlying these changes remain uncertain and need to be clarified through future multicenter population-based studies.}, }
@article {pmid42709378, year = {2026}, author = {Yang, X and Zhang, S and Wang, Y and Shi, J and Li, W and Lou, X and Yu, Y and Zhang, J and Sang, A}, title = {LAPTM5 correlates with RPE senescence and subretinal fibrosis through the LAPTM5-WWP2-OPTN mitophagy cascade and cGAS/STING activation in a D-galactose-induced aging model.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {42709378}, issn = {2509-2723}, support = {M2024045//Jiangsu Commission of Health/ ; K2024063//Jiangsu Commission of Health/ ; LKM2024040//Jiangsu Commission of Health/ ; MS2025005//Nantong Municipal Commission of Health and Family Planning/ ; 23ZH313//Nantong University/ ; }, abstract = {Retinal pigment epithelium (RPE) senescence acts as a core driver of subretinal fibrosis, a major irreversible pathological feature that exacerbates age-related macular degeneration (AMD). Mitophagy is essential for maintaining RPE homeostasis during aging. However, the upstream molecular mechanisms underlying mitophagy impairment in senescent RPE remain poorly defined. Here, we show that lysosomal-associated transmembrane protein 5 (LAPTM5) is significantly upregulated in human AMD specimens and D-galactose (D-gal)-induced aging mouse model, with its overexpression correlating with transcriptomic signatures of RPE senescence and fibrogenesis. Gain- and loss-of-function assays validate that LAPTM5 acts as an important regulator of RPE senescence and senescence-associated secretory phenotype (SASP) production. Mechanistically, LAPTM5 physically interacts with and promotes the lysosome-dependent degradation of WW domain-containing E3 ubiquitin protein ligase 2 (WWP2), which in turn diminishes optineurin (OPTN) polyubiquitination and ablates OPTN-mediated mitophagy. The resulting mitophagy deficiency is associated with cytoplasmic mitochondrial DNA leakage and sustained cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) innate immune activation, stimulating robust senescence-associated secretory phenotype (SASP) release that promotes RPE epithelial-mesenchymal transition (EMT) and exacerbates subretinal fibrotic scarring. Notably, AAV-mediated RPE-specific Laptm5 knockdown efficiently alleviates subretinal fibrotic lesions in the aged mouse model, while pharmacological STING inhibition with H-151 markedly attenuates EMT progression. Collectively, our findings identify a previously uncharacterized LAPTM5-WWP2-OPTN mitophagy cascade and reveal a new pathogenic circuit linking impaired mitophagy to RPE senescence and age-related retinal fibrosis, offering translational prospects for treating senescence-associated fibrotic diseases.}, }
@article {pmid42709406, year = {2026}, author = {Macchione, RM and Ottaiano-Poli, PA and Germano-Morrel, CS and Tomishige, KS and Kasahara, N}, title = {Vision-related quality of life in glaucoma and age-related macular degeneration patients from a middle-income country.}, journal = {International health}, volume = {}, number = {}, pages = {}, doi = {10.1093/inthealth/ihag089}, pmid = {42709406}, issn = {1876-3405}, support = {//ARVO/ ; }, abstract = {BACKGROUND: Vision-related quality of life (VRQoL)-vision's impact on one's social, emotional and economic well-being-has not been extensively studied in patients living in middle-income countries. The aim of this study was to compare the VRQoL among age-related macular degeneration (AMD), primary open-angle glaucoma (POAG) and normal subjects in Brazil.<br><br>METHODS: This was a case-control, cross-sectional study. Patients with AMD or POAG and normal controls underwent a complete eye examination; all participants answered the Brazilian-Portuguese version of the Visual Function Questionnaire 25 (VFQ-25). Each item was scored and an overall composite score was calculated and compared among groups with an analysis of variance test.<br><br>RESULTS: The sample included 60 patients with AMD, 64 with POAG and 60 controls. All groups were matched for age, gender, ethnic distribution and comorbidities. The VFQ-25 total score was lower in both AMD (50.6&#xb1;20.9) and POAG (61.8&#xb1;20.4) as compared with controls (89.2&#xb1;9.1, p<0.001); scores for AMD patients were lower than for POAG patients (p<0.001).<br><br>CONCLUSIONS: Brazilian patients with POAG, and especially AMD, presented significantly lower VRQoL scores, underscoring the need to improve the care of patients with visual impairment in Brazil.}, }
@article {pmid42709964, year = {2026}, author = {Wu, Y and Fu, DJ and Zhou, Y and Wagner, SK and Keane, PA}, title = {Performance, Failures, and Oversight of a Large Language Model Agent for Clinical Data Analysis: Evaluation Study.}, journal = {Journal of medical Internet research}, volume = {28}, number = {}, pages = {e99597}, pmid = {42709964}, issn = {1438-8871}, mesh = {*Large Language Models ; Humans ; *Data Analysis ; }, abstract = {BACKGROUND: Large language model (LLM) agents capable of generating and executing statistical code from natural language may broaden access to clinical data analysis, yet which pipeline stages they perform reliably and which require expert oversight remain poorly defined.<br><br>OBJECTIVE: This study aimed to evaluate the performance and systematic failure modes of an LLM agent across 5 stages of a clinical data analysis workflow.<br><br>METHODS: The publicly available dataset and R script (R Foundation for Statistical Computing) were drawn from a previously published study of 12-year outcomes in 7802 patients with eyes with neovascular age-related macular degeneration at Moorfields Eye Hospital. Participants were evaluated using an LLM agent (Claude; Anthropic) across 3 interaction modes (Chat, Code, and Cowork). It was asked to perform 3 levels of data analysis practice: prompt A, to generate research questions from raw data only; prompt B, to develop a statistical analysis plan (SAP) from a high-level clinical objective, then execute it; and prompt C, to execute an analysis given an investigator-drafted SAP. Each was replicated 3 times (27 total runs). Qualitative evaluation of research question thematic coverage (prompt A), SAP completeness against a reference checklist (prompt B), and evaluation of execution outputs against validated reference values and of result text and narrative summaries against execution logs (prompts B and C) was conducted.<br><br>RESULTS: The agent generated 18 clinically grounded questions spanning 7 domains; Cowork mode uniquely reached 3 thematic areas requiring data-driven methods. All 9 SAPs correctly identified the statistical framework. Kaplan-Meier estimates were near-identical across 17 completed runs. Systematic execution errors emerged: SAP quality did not predict code correctness, and within-mode errors propagated identically across independent repetitions. Result text accurately reflected execution logs in nearly all runs, though unit propagation and an undisclosed postcrash rerun were identified. Of 17 narrative summaries, 8 were fully satisfactory; 2 runs produced clinically meaningful errors.<br><br>CONCLUSIONS: LLM agents perform reliably for question generation and SAP drafting but require expert verification of formula composition, cohort boundary logic, and concordance computation before results are reported. Using an ophthalmology dataset as a controlled testbed, this study develops and applies an evaluation framework whose lessons are likely applicable across clinical specialties.}, }
@article {pmid42712725, year = {2026}, author = {Long, N and Si, M and Jiang, Y and Chen, F and Chen, B and Jiang, F and Pan, S and Chu, X and Wu, H}, title = {Bionic vision technologies: progress and perspectives on retinal prostheses and optogenetics for the treatment of advanced retinal degeneration.}, journal = {Frontiers in medical technology}, volume = {8}, number = {}, pages = {1898982}, pmid = {42712725}, issn = {2673-3129}, abstract = {Advanced degenerative retinal diseases [e.g., retinitis pigmentosa (RP) and age-related macular degeneration (AMD)] are characterized by irreversible photoreceptor loss, and conventional interventions rarely prevent progression to profound vision loss at advanced stages. Retinal prostheses and optogenetic therapies are two leading bionic strategies to bypass absent photoreceptors, yet both are limited by a shared "encoding-biointerface" bottleneck: converting external scenes into interpretable neural activity in surviving retinal circuits with adequate selectivity, safety margins, and long-term stability. This review critically compares the two approaches in spatial resolution, neural adaptation, and biosafety, while explicitly distinguishing clinical evidence from preclinical and proof-of-concept studies. Retinal prostheses provide near-term light perception and limited form vision but are constrained by current spread, non-selective pathway/axon recruitment, interface reactions, and cortical decoding burden. Optogenetic restoration offers cell-type-biased reactivation and potentially more physiological processing, but currently remains coupled to external light-delivery hardware and is limited by scattering, heterogeneous transduction, safety-limited irradiance, restricted dynamic range, and adeno-associated virus (AAV)-related inflammatory risk. We highlight emerging integrative directions, including opto-electronic hybrid interfaces, adaptive encoding, broadband subretinal nanomaterial-based photovoltaic nanoprostheses, and experimental acoustic modalities (e.g., focused ultrasound and sonogenetics), alongside ethical and accessibility considerations for translation.}, }
@article {pmid42713229, year = {2026}, author = {Ho, SC and Lee, IXY and Liu, C and Yu, M and Tan, HC and Tan, GSW and Liu, YC}, title = {Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms.}, journal = {Journal of pharmacy &amp; pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques}, volume = {29}, number = {}, pages = {16995}, pmid = {42713229}, issn = {1482-1826}, mesh = {Humans ; *Fenofibrate/therapeutic use/pharmacology/administration &amp; dosage ; Animals ; *Eye Diseases/drug therapy/metabolism ; *Hypolipidemic Agents/pharmacology/therapeutic use/administration &amp; dosage ; PPAR alpha/agonists/metabolism ; }, abstract = {Ophthalmic diseases are a growing global cause of visual impairment, driven by population aging and the rising prevalence of diabetes mellitus. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist widely used for dyslipidemia, has emerged as a candidate for therapeutic repurposing in ophthalmology. This narrative review synthesizes current preclinical and clinical evidence on fenofibrate across anterior and posterior segment diseases, including diabetic corneal neuropathy, diabetic keratopathy, dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, diabetic retinopathy, diabetic macular edema, neovascular age-related macular degeneration, and central retinal artery occlusion. Across ocular disease models, fenofibrate demonstrates neuroprotective, vascular stabilizing, and tissue-remodeling effects. These actions appear to involve modulation of shared pathogenic pathways, including PPARα-dependentregulation of inflammatory signaling, mitochondrial and lipid metabolism, and preservation of epithelial, endothelial, neuronal, and vascular integrity. Clinical evidence is strongest for diabetic retinopathy, where randomized trials support a potential adjunctive role in slowing progression and reducing interventions in patients with early-to-moderate disease. Preliminary clinical evidence for diabetic corneal neuropathy is promising but limited, whereas data for dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, neovascular age-related macular degeneration, and retinal ischemic injury remains preclinical. Emerging experimental ocular delivery strategies may improve local bioavailability while reducing systemic exposure. Overall, fenofibrate represents a biologically plausible adjunctive ophthalmic therapy, but further randomized trials, mechanistic studies, pharmacokinetic evaluation, and long-term safety assessments are required to define its therapeutic role beyond diabetic retinopathy.}, }
@article {pmid42714580, year = {2026}, author = {Hoffmann, S and Liegl, C and Stasik, I and Holz, FG and Liegl, R}, title = {One-year real-world data of intravitreal faricimab in patients with pre-treated neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42714580}, issn = {1435-702X}, abstract = {PURPOSE: To assess one-year real-world outcomes of faricimab therapy in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF agents and managed using a treat-and-extend (TAE) regimen.<br><br>METHODS: Patients with treatment-resistant nAMD were switched to faricimab. Functional and structural parameters, including best-corrected visual acuity (BCVA in logMAR), foveal centre point (FCP in &#xb5;m), central subfield retinal thickness (CSRT in &#xb5;m), and macular volume (MV in mm&#xb3;), were recorded over a one-year observation period.<br><br>RESULTS: Seventy eyes from 59 patients initiated faricimab therapy between September and December 2022; complete one-year data were available for 60 eyes, with a mean follow-up of 391&#x2009;&#xb1;&#x2009;20 days. Prior to switching, patients had received an average of 42.4&#x2009;&#xb1;&#x2009;25.2 anti-VEGF injections over 70.8&#x2009;&#xb1;&#x2009;45.4 months. Significant structural improvements were observed: FCP decreased from 359&#x2009;&#xb1;&#x2009;165&#xa0;&#x3bc;m to 283&#x2009;&#xb1;&#x2009;132&#xa0;&#x3bc;m, CSRT from 414&#x2009;&#xb1;&#x2009;153&#xa0;&#x3bc;m to 343&#x2009;&#xb1;&#x2009;116&#xa0;&#x3bc;m, and macular volume from 2.74&#x2009;&#xb1;&#x2009;0.67&#xa0;mm&#xb3; to 2.46&#x2009;&#xb1;&#x2009;0.49&#xa0;mm&#xb3; (all p&#x2009;<&#x2009;0.001). The mean injection interval increased from 5.8&#x2009;&#xb1;&#x2009;1.8 weeks to 8.2&#x2009;&#xb1;&#x2009;3.3 weeks (p&#x2009;<&#x2009;0.001), indicating improved disease control. BCVA remained stable (0.45&#x2009;&#xb1;&#x2009;0.37 logMAR vs. 0.44&#x2009;&#xb1;&#x2009;0.39 logMAR; p&#x2009;=&#x2009;0.35). At the end of follow-up, 37% of eyes achieved a completely dry macula with no residual intra-, subretinal, or sub-RPE fluid. Two eyes developed mild anterior chamber inflammation, which resolved fully under topical corticosteroids.<br><br>CONCLUSION: Switching to faricimab in recalcitrant, heavily pretreated nAMD may yield meaningful structural improvements while stabilizing visual acuity.}, }
@article {pmid42714745, year = {2026}, author = {Sugisawa, T and Nishi, Y and Imaizumi, H and Aoki, S and Miki, A and Kishi, M and Yamauchi, T and Nagasato, D and Ozawa, Y and Haruta, M and Kato, N and Matsubara, H and Yasukawa, T and Kato, A and Terasaki, H and Hirano, T and Iesato, Y and Tsujinaka, H and Murakami, T and Mitamura, Y and Wakuta, M and Kimura, K and Shimura, M and Gomi, F}, title = {Changes in demographics and treatment trends in neovascular age-related macular degeneration during the COVID-19 pandemic in Japan.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42714745}, issn = {1613-2246}, abstract = {PURPOSE: To elucidate changes in the management of neovascular age-related macular degeneration (nAMD) in Japan during the COVID-19 pandemic .<br><br>STUDY DESIGN: Retrospective cohort study.<br><br>METHODS: We conducted a multicenter retrospective cohort study of patients newly examined at 16 retina specialist facilities from January 2017 to March 2021. Baseline findings and 3-year follow-up data were compared between pre-pandemic (2017-February 2020) and post-pandemic (March 2020-March 2021) groups.<br><br>RESULTS: Analysis of 2271 patients with nAMD revealed a significant decrease in the number of patients examined at hospitals during the COVID-19 pandemic period (p = 0.011), along with a higher proportion of patients who had received treatment within the previous year at local clinics. Baseline ocular findings showed no significant differences between the pre- and post-pandemic groups. Loss to follow-up increased through the second year of the pandemic period (first year, p = 0.0012; second year, p = 0.023). No significant differences were observed during follow-up in visual acuity, central retinal thickness, or number of anti-vascular endothelial growth factor injections. However, in the post-pandemic period the frequency of photodynamic therapy tended to decrease, and examination visits decreased significantly (p = 0.0038).<br><br>CONCLUSION: The number of nAMD patients treated in hospitals was lower in the post-pandemic period, and the proportion managed initially in local clinics increased. Although baseline and follow-up characteristics remained largely similar, the use of photodynamic therapy and the number of follow-up visits declined. These findings suggest a shift in the initial nAMD management from hospitals to local clinics during the early post-pandemic period.}, }
@article {pmid42562649, year = {2026}, author = {Demirayak, P and Fleming, LL and Stewart, P and Chua, R and Visscher, KM}, title = {Increased Attentive Use Is Linked to More Idiosyncratic Functional Connections.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {46}, number = {36}, pages = {}, doi = {10.1523/JNEUROSCI.2178-25.2026}, pmid = {42562649}, issn = {1529-2401}, mesh = {Humans ; Female ; Male ; *Attention/physiology ; Adult ; Magnetic Resonance Imaging ; *Nerve Net/physiology/diagnostic imaging ; *Brain/physiology/diagnostic imaging ; Middle Aged ; Brain Mapping ; }, abstract = {Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brain's complexity, multiple network changes could each move the system toward optimality. Standard approaches examine each connection independently; these studies have often shown considerable interindividual variability and modest effects (Marek et al., 2022). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how "idiosyncratic" the pattern is. We examined how the idiosyncrasy of whole-brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (who use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person to person in healthy vision controls (14 females, 9 males). In a second set of analyses, we examined the brains of people with central vision loss (11 females, 10 males) who use a portion of peripheral vision [the preferred retinal locus (PRL)] more frequently for attention-demanding tasks in their daily lives. The cortical representation of the PRL exhibits more idiosyncratic connections, compared with a control brain region or compared with the same brain region in matched healthy vision controls. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole-brain connections.}, }
@article {pmid42705516, year = {2026}, author = {Kim, M and Park, Y and Choi, SW and Lee, EK and Park, UC and Park, KH and Yoon, CK}, title = {Reticular Pseudodrusen Subtypes and Their Interaction With Soft Drusen: Longitudinal Structure-Function Analysis.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.08.047}, pmid = {42705516}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate longitudinal structure-function relationships of reticular pseudodrusen (RPD) subtypes and their interaction with soft drusen (SD) on retinal sensitivity (RS) in intermediate age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: Forty-six eyes of 28 patients diagnosed with intermediate AMD or RPD who underwent microperimetry at two time points 6 to 12 months apart.<br><br>METHODS: RPD presence and subtype (dot or ribbon) and SD were assessed individually at each of 37 Early Treatment Diabetic Retinopathy Study grid test points on co-registered multimodal imaging. Linear mixed-effects models estimated baseline RS and its change by drusen composition, with test-point location as a fixed effect and adjustment for clinical covariates, plus baseline RS for the change analysis.<br><br>MAIN OUTCOME MEASURES: Change in RS over follow-up and baseline RS, according to drusen composition.<br><br>RESULTS: At baseline, ribbon-type RPD regions showed lower RS than lesion-free regions (mean difference 0.72 &#xb1; 0.24 dB, P&#x202f;=&#x202f;.002), whereas dot-type RPD did not differ (P&#x202f;=&#x202f;.120); SD was independently associated with reduced RS (P&#x202f;=&#x202f;.021). No baseline RPD subtype&#x202f;&#xd7;&#x202f;SD interaction was observed. Longitudinally, a significant interaction was found (P&#x202f;=&#x202f;.005): regions with both ribbon-type RPD and SD showed the greatest RS decline, whereas RPD subtypes did not differ without SD (all P > .9).<br><br>CONCLUSIONS: The functional impact of RPD varies by subtype and coexistence with SD. Ribbon-type RPD is associated with greater RS impairment, particularly when combined with SD, highlighting the importance of lesion phenotype in functional risk assessment.}, }
@article {pmid42706530, year = {2026}, author = {Ranabhat, S and Shakya, K and Bajgai, P and Singh, L and Shrestha, S and Agrawal, R}, title = {Retinal and choroidal morphometric analysis in fellow eye of unilateral wet age related macular degeneration using optical coherence tomography angiography.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42706530}, issn = {1471-2415}, mesh = {Humans ; Male ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/pathology ; Cross-Sectional Studies ; Female ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; *Wet Macular Degeneration/diagnosis/pathology/diagnostic imaging ; Middle Aged ; Fundus Oculi ; Visual Acuity ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) when associated with macular neovascularization can cause severe visual morbidity. This study aims to evaluate the retinal and choroidal microvascular alterations using optical coherence tomography angiography (OCTA) in eyes with unilateral wet age-related macular degeneration (AMD) termed as "affected eye" (AE) and compare it with their "fellow eyes" (FE).<br><br>METHODS: This cross-sectional study included 60 patients (120 eyes) with age over 50 years. Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexuses (SCP), deep capillary plexus (DCP) and avascular slab were assessed using OCTA. Enhanced depth imaging was used to evaluate subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI).<br><br>RESULTS: The mean age was 73.9&#x2009;&#xb1;&#x2009;9.54 years (51-89 years) with 51.7% male. Quantitative OCTA analysis showed no significant inter-eye differences in VD or PD in SCP or DCP (p&#x2009;>&#x2009;0.05). However, FAZ was significantly enlarged in AE compared with FE in SCP (0.91&#x2009;&#xb1;&#x2009;0.40 vs. 0.64&#x2009;&#xb1;&#x2009;0.20&#xa0;mm&#xb2;; p&#x2009;<&#x2009;0.001) and DCP (p&#x2009;<&#x2009;0.001). FAZ enlargement in the avascular slab was not statistically significant (p 0.20). Pattern I macular neovascularization (MNV) was significantly associated with the shape (p 0.026), presence of anastomoses (p 0.029), and overall activity scores (p 0.001). Inter-eye differences choroidal parameters were statistically significant for SFCT (p 0.019), haller layer (p 0.014) and CVI (p&#x2009;<&#x2009;0.001). AE status was significantly associated with age (p 0.04) smoking (p 0.01), and lens status (p 0.05).<br><br>CONCLUSION: FAZ enlargement demonstrated greater inter-eye separation and higher discriminatory performance compared than density-based OCTA parameters and may reflect localized microvascular or structural alteration in unilateral neovascular AMD. OCTA-based assessment of FE may aid in detecting early microvascular alterations and guiding timely intervention, which may be potentiated by retinal and choroidal vascular or structural remodeling.}, }
@article {pmid42709011, year = {2026}, author = {Blix, T and Løkken, JFT and Steffensen, LA and Sæther, EM and Husum, YS and Ødegaard, EM and Bragadottir, R and Moe, MC and Jørstad, &#xd8;K}, title = {Impact of faricimab and high-dose aflibercept on treatment demand in a tertiary ophthalmic centre in Norway.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70240}, pmid = {42709011}, issn = {1755-3768}, abstract = {PURPOSE: To evaluate the impact of introducing faricimab and high-dose aflibercept on intravitreal injection (IVI) demand and treatment costs for retinal diseases in a large tertiary retina centre.<br><br>METHODS: This retrospective longitudinal registry study included all anti-VEGF treatment episodes at Oslo University Hospital, Norway, between 2021 and 2025. Annual injection volumes, treatment patterns, and costs were assessed following the introduction of faricimab (2023) and high-dose aflibercept (2025). High-dose aflibercept was&#x2009;generally administered at 50&#x2009;&#x3bc;L (5.7&#x2009;mg). Costs components were estimated using a health-economic model.<br><br>RESULTS: A total of 142&#x2009;960 treatment episodes comprising 169&#x2009;700 IVIs in 7865 patients (mean age 75.5&#x2009;years, 56.6% female) were included. Macular degeneration was the most common diagnosis. Treated patients increased from 4148 in 2021 to 4982 in 2025. Injections increased from 31&#x2009;780 in 2021 to a peak of 35&#x2009;508 in 2024 before declining to 33&#x2009;696 in 2025, while mean injections per patient decreased from 7.7 to 6.8. Following its introduction in 2023, faricimab became the most used agent. Off-label bevacizumab proportion decreased from 50.6% in 2021 to 30.0% in 2025. Mean treatment cost per patient increased from NOK 38029 in 2021 to NOK 40187 in 2025 (+5.7%), while total treatment costs increased from NOK 158 million to NOK 200 million (+26.9%).<br><br>CONCLUSIONS: The introduction of faricimab and high-dose aflibercept was associated with reduced per-patient treatment intensity, while the treated population continued to increase. Longer-acting anti-VEGF drugs may reduce pressure on retinal services by lowering injection frequency; however, their introduction was associated with higher overall costs.}, }
@article {pmid42698447, year = {2026}, author = {Wan, Z and Chen, X and Gao, F and Shi, F and Dai, R and Peng, Q and Wei, Q}, title = {Faricimab in neovascular age-related macular degeneration: aqueous humor cytokine profiling and biomarker correlations.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1927909}, pmid = {42698447}, issn = {2296-858X}, abstract = {PURPOSE: To investigate aqueous humor cytokine profile changes in neovascular age-related macular degeneration (nAMD) patients before and after intravitreal faricimab injection, and their correlation with biomarkers.<br><br>METHODS: Twenty-three nAMD patients and 10 cataract controls were enrolled. Aqueous humor was collected from nAMD patients at baseline and 12&#x202f;weeks post-faricimab injection, and from controls during phacoemulsification. Twelve cytokines were quantified via multiplex bead-based immunoassay. OCTA measured central macular thickness (CMT) and retinal vessel density in nAMD eyes.<br><br>RESULTS: Baseline vascular endothelial growth factor (VEGF), Angiopoietin-2 (Ang-2) and HGF levels were higher in nAMD patients than controls. Post-treatment, VEGF and Ang-2 decreased below control levels, while hepatocyte growth factor (HGF) and interferon gamma protein 10 (IP-10) increased significantly. Reductions in Ang-2/VEGF correlated positively with decreased CMT and whole retinal thickness, with concurrent improvements in best-corrected visual acuity. Elevated IP-10 showed a correlative association with reduced superficial foveal vessel density.<br><br>CONCLUSION: Faricimab dual-blockades VEGF/Ang-2, reducing their aqueous levels, improving CMT/whole retinal thickness and visual acuity. However, post-treatment HGF/IP-10 upregulation indicates compensatory inflammatory-angiogenic remodeling. IP-10 may serve as a potential correlative biomarker linked to subclinical capillary rarefaction. Future studies should explore combined anti-IP-10 therapy or extended dosing intervals to preserve foveal vasculature while maintaining anti-leakage efficacy.}, }
@article {pmid42698711, year = {2026}, author = {Liu, Y and Li, Z and Ma, Y and Liu, Y}, title = {Targeting angiogenesis: advances in the design and engineered applications of nanobodies.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1912560}, pmid = {42698711}, issn = {1664-3224}, mesh = {Humans ; *Single-Domain Antibodies/therapeutic use/immunology/genetics/chemistry ; Animals ; *Neovascularization, Pathologic/immunology/drug therapy ; Neoplasms/immunology/therapy ; Protein Engineering ; *Angiogenesis Inhibitors/therapeutic use ; }, abstract = {Angiogenesis is a fundamental physiological process; however, its pathological dysregulation drives diseases such as solid tumors, wet age-related macular degeneration, and rheumatoid arthritis. Although clinically effective, conventional anti-angiogenic monoclonal antibodies are limited by poor tissue penetration, off-target toxicities, and susceptibility to compensatory resistance. This review systematically examines the structural advantages and engineering strategies of nanobodies (Nbs) targeting angiogenesis-related pathways. Advanced engineering approaches, such as AI-assisted humanization and multivalent assembly, effectively mitigate immunogenicity and extend serum half-life. Furthermore, multispecific designs can simultaneously block compensatory pathways to circumvent resistance. Moreover, preclinical studies indicate that integrating these molecules into site-specific nanobody-drug conjugates and targeted delivery vehicles may improve therapeutic precision and local drug accumulation; however, their long-term safety, manufacturability, and clinical benefit remain to be established. Functionalizing Nbs with radionuclides or fluorophores may enable the development of novel theranostic platforms that support real-time molecular imaging and image-guided surgery. In parallel, nanobody-based CAR-T (Nb-CAR-T) cells facilitate the targeted remodeling of the disease microenvironment. Ultimately, this review highlights the value of engineered Nbs as a highly programmable and transformative platform. By overcoming key limitations of conventional antibodies, engineered nanobodies open new avenues for precise, multi-dimensional interventions in solid tumors. Their potential in certain non-neoplastic angiogenic diseases is emerging but requires further validation.}, }
@article {pmid42700909, year = {2026}, author = {Zhang, X and Lin, Y and Cheng, J and Yan, M and Huang, Z and Ye, Y and Song, Y}, title = {Association Between Subretinal Hyperreflective Material and OCTA-Derived Macular Neovascularization Morphology in Treatment-Naive Neovascular Age-Related Macular Degeneration.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105645}, doi = {10.1016/j.pdpdt.2026.105645}, pmid = {42700909}, issn = {1873-1597}, abstract = {PURPOSE: To evaluate whether baseline subretinal hyperreflective material (SHRM) status is associated with optical coherence tomography angiography (OCTA)-derived macular neovascularization (MNV) vessel density, complexity, and ramification in treatment-naive neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective, single-center, cross-sectional imaging study included 89 eyes from 89 treatment-naive patients with nAMD. One eye per patient was included to avoid inter-eye correlation. SHRM was assessed on baseline structural optical coherence tomography (OCT). OCTA images were acquired using 6&#x202f;&#xd7;&#x202f;6 mm scans, and MNV lesions were manually delineated as regions of interest. The primary OCTA-derived parameters were MNV vessel density, fractal dimension, and branch points. Multivariable linear regression models were adjusted for age, sex, central macular thickness, and MNV type.<br><br>RESULTS: SHRM was present in 56 eyes (62.9%) and absent in 33 eyes (37.1%). Compared with SHRM-negative eyes, SHRM-positive eyes had worse baseline best-corrected visual acuity (BCVA) (P < 0.001), greater central macular thickness (P < 0.001), and higher frequencies of subretinal fluid, intraretinal fluid, and retinal hemorrhage. SHRM-positive eyes also showed higher MNV vessel density (0.262 vs. 0.196; P&#x202f;=&#x202f;0.017), fractal dimension (1.568 vs. 1.487; P&#x202f;=&#x202f;0.024), and branch points (140.5 vs. 91.0; P&#x202f;=&#x202f;0.035). After adjustment, SHRM remained associated with higher MNV vessel density (&#x3b2;&#x202f;=&#x202f;0.045; P&#x202f;=&#x202f;0.042), fractal dimension (&#x3b2;&#x202f;=&#x202f;0.077; P&#x202f;=&#x202f;0.029), and branch points (&#x3b2;&#x202f;=&#x202f;98.74; P&#x202f;=&#x202f;0.045).<br><br>CONCLUSIONS: These findings suggest that SHRM-positive status is associated with a denser, more complex, and more ramified OCTA-derived MNV vascular phenotype at baseline in treatment-naive nAMD.}, }
@article {pmid42701791, year = {2026}, author = {Chen, Z and Liu, J and Cheng, S and Xu, Q}, title = {The Evolving Burden of Age-Related Macular Degeneration in China (1990-2023): Insights from an Aging Society and the Anti-VEGF Era.}, journal = {Clinical epidemiology}, volume = {18}, number = {}, pages = {621990}, pmid = {42701791}, issn = {1179-1349}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. China bears the world's largest AMD burden. This study analyzes the evolving AMD burden in China (1990-2023) and the impact of anti-VEGF therapy.<br><br>METHODS: We analyzed data from the Global Burden of Disease (GBD) 2023 study using joinpoint regression, decomposition analysis, and Bayesian modeling. A supplementary meta-analysis of single-arm studies was conducted to assess anti-VEGF efficacy in Chinese patients.<br><br>RESULTS: From 1990 to 2023, China's age-standardized prevalence rate (ASPR) and disability-adjusted life year rate (ASDR) for AMD decreased by -0.67% and -1.48% annually, respectively. In 2023, China accounted for 35.82% of global cases and 30.25% of global DALYs. A supplementary meta-analysis of 13 single-arm observational studies showed a pooled efficacy rate of 74% for anti-VEGF drugs in China, albeit with substantial heterogeneity (I[2] = 93.07%), warranting cautious interpretation. The accelerated decline in ASDR after 2011 coincided temporally with the clinical introduction and subsequent insurance coverage of anti-VEGF therapy. Projections indicate a continued decline in burden through 2038.<br><br>CONCLUSION: Despite a declining age-standardized burden, China's absolute AMD burden remains substantial due to rapid population aging and other challenges. The temporal association between anti-VEGF therapy availability and the accelerated burden decline suggests a potential contribution of this treatment, though causality cannot be directly inferred from this ecological analysis. The observed trends likely reflect multiple factors, including improved healthcare access, early diagnosis, socioeconomic development, and anti-VEGF therapy. Comprehensive strategies focusing on prevention and equitable healthcare access are needed.}, }
@article {pmid42703379, year = {2026}, author = {Zeaiter, M and Jaber, H and Gharbi, K and Fernandes, SMB and Mchaik, J and Ahmed, M and Hassan, A and Hammoud, AA}, title = {Faricimab in the Treatment of Retinal Disease: A Narrative Review.}, journal = {Cureus}, volume = {18}, number = {8}, pages = {e114098}, pmid = {42703379}, issn = {2168-8184}, abstract = {Retinal and choroidal diseases, including diabetic macular edema, neovascular age-related macular degeneration, retinal vein occlusion, and polypoidal choroidal vasculopathy, remain a significant cause of visual impairment around the world, especially among elderly . Although anti-vascular endothelial growth factor (anti-VEGF) therapy remains the standard of care, it is limited by its side effect profile, resistance, and high injection burden. This underscores the need for a more optimal and possible replacement. Faricimab is an emerging bispecific antibody targeting VEGF-A and angiopoietin-2, addressing both angiogenesis and vascular permeability by modulating the tyrosine kinase with immunoglobulin-like domains-2 pathway. This literature review synthesizes information from preclinical studies and randomized controlled trials. It focuses on the molecular reasoning behind the use of faricimab and the safety profile compared with anti-VEGF monotherapy.}, }
@article {pmid42705337, year = {2026}, author = {Kim, DE and Kim, M and Im, M}, title = {Perceptual characteristics of scotomas modulate visual performance under simulated prosthetic vision.}, journal = {Journal of neural engineering}, volume = {}, number = {}, pages = {}, doi = {10.1088/1741-2552/aea36b}, pmid = {42705337}, issn = {1741-2552}, abstract = {Retinal prostheses aim to restore vision in patients blinded by photoreceptor degeneration, yet functional outcomes vary substantially across individuals. Scotomas-regions of reduced or absent visual sensitivity-are a defining feature of retinal degenerative diseases, but their perceptual status is often underappreciated in the design and evaluation of prosthetic vision. Here, we investigated how differences in scotoma perception influence perceptual visual task performance and perceptual representations. Approach. Psychophysical experiments were conducted using a virtual reality (VR) platform that simulated visual field deficits characteristic of retinal degeneration, including age-related macular degeneration (AMD). Two different scotoma conditions, perceptually filled-in (invisible) and solid black, were implemented in a head-mounted display (HMD) environment developed in Unity 3D Game Engine. Participants performed visual tasks while behavioral measures, including accuracy, response time, and eye-tracking metrics, were recorded and analyzed. Main Results. Despite identical visual inputs, task performance showed statistically significant differences depending on the perceptual characteristics (i.e., background-matching vs. black) of the simulated scotoma. Critically, the spatial-frequency performance cost on response time was abolished selectively under the black-scotoma-with-phosphene condition (χ[2](3) = 8.72, p = 0.033), whereas it remained significant under all invisible scotoma conditions, indicating that a perceptually distinct scotoma background enhances the detectability of phosphene signals. These differences were reflected corroborated by systematic divergences in gaze trajectory length and terminal fixation location across conditions. Significance. Our findings suggest that variability in scotoma perception constitutes an important, yet underexplored, factor contributing to inter-individual differences in the effectiveness of retinal prosthetic stimulation. Accounting for perceptual properties of scotomas may provide a framework for optimizing stimulation strategies and improving functional outcomes of future retinal prostheses.}, }
@article {pmid42697260, year = {2026}, author = {Pourbagherkhah, P and Jaldian, HB}, title = {Biomarkers for Detecting and Predicting Macular Neovascularization in Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography: A Systematic Review.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105637}, doi = {10.1016/j.pdpdt.2026.105637}, pmid = {42697260}, issn = {1873-1597}, abstract = {PURPOSE: This systematic review evaluates the role of optical coherence tomography angiography (OCTA)-based biomarkers in detecting and predicting macular neovascularization (MNV) in age-related macular degeneration (ARMD).<br><br>METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus and Google Scholar up to 20 May 2026, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed original cohort and cross-sectional studies reporting OCTA-derived quantitative and qualitative biomarkers associated with MNV.<br><br>RESULTS: A total of 203 articles were initially identified, with 11 studies meeting the eligibility criteria, comprising 642 eyes. Key OCTA biomarkers included vascular density, MNV area, total vessel length, and choroidal vascularity index, which demonstrated strong associations with disease activity and progression.<br><br>CONCLUSION: OCTA-derived biomarkers offer a non-invasive and effective means for detecting and monitoring MNV in ARMD. Despite current challenges in standardization and interpretation, integrating these biomarkers into clinical practice could improve early diagnosis and personalized treatment strategies.}, }
@article {pmid42697271, year = {2026}, author = {Kardo, H and Garweg, RA and Imbach, L and Garweg, JG}, title = {Longitudinal Changes in Inner Retinal Layers in Treatment-Naïve Neovascular AMD During Intravitreal Anti-VEGF Therapy.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.08.031}, pmid = {42697271}, issn = {2468-6530}, abstract = {PURPOSE: To investigate longitudinal changes in retinal nerve fiber layer (RNFL) and ganglion cell- inner plexiform layer (GC-IPL) thickness in treatment-naïve neovascular age-related macular degeneration (nAMD) under intravitreal anti-VEGF therapy (IVT), compared with untreated fellow eyes with dry AMD (dAMD).<br><br>DESIGN: Retrospective single-center cohort study.<br><br>SUBJECTS: Consecutive patients with treatment-na&#xef;ve nAMD receiving anti-VEGF therapy under a treat-and-extend regimen and a minimum follow-up of 24 months were included. Untreated fellow eyes with dAMD served as controls.<br><br>METHODS: RNFL and GC-IPL thickness were assessed longitudinally using spectral-domain optical coherence tomography and RetinAI analysis. Best-corrected visual acuity (BCVA) and structural retinal changes were evaluated over time. Linear mixed-effects models were used to assess factors associated with retinal layer changes.<br><br>MAIN OUTCOME MEASURES: Longitudinal changes in RNFL thickness, GC-IPL thickness, and BCVA.<br><br>RESULTS: In nAMD eyes, median RNFL thickness in the 3 mm ring zone decreased from 32.3 &#x3bc;m (30.1-35.4) at baseline to 30.9 &#x3bc;m (29.0-33.4; adjusted P < .001) after the loading phase and remained stable thereafter (all adjusted P > .05), with a similar pattern observed in fellow dAMD eyes. In contrast, GC-IPL thickness progressively declined in both groups. In nAMD eyes, median GC-IPL thickness decreased from 89.1 &#x3bc;m (81.9-94.9) at baseline to 85.1 &#x3bc;m (77.7-90.2) after loading (adjusted P < .001), followed by continued thinning throughout follow-up. BCVA in nAMD eyes improved after loading with a median gain of 4.8 ETDRS letters (0-10.2; adjusted P < .001), remained stable for up to 3 years, and gradually declined thereafter. Mixed-effects modeling showed RNFL thickness was associated with injection number, whereas GC-IPL loss was associated with age and follow-up duration, independent of injection number or sex.<br><br>CONCLUSIONS: The regression in RNFL and GC-IPL thickness during the loading phase in eyes with nAMD may reflect the resolution of pre-treatment swelling. RNFL thickness remained stable thereafter, while GC-IPL thickness and BCVA declined after loading similarly to fellow eyes with dAMD. According to the mixed-effects model, GC-IPL thinning appears linked to progression of the underlying degenerative process, whereas RNFL thickness appears comparatively preserved.}, }
@article {pmid42697425, year = {2026}, author = {Sun, X and Zhang, G and Feng, X and Hong, Z and Qu, Y and Li, M and Xia, Z and Xu, J and Bachwenkizi, J and Lam, H and Wang, Y and Honda, Y and Hashizume, M and Chen, R and Wu, Z and Ji, JS and Liang, D and Guo, Y and Kan, H and Jia, H and Wong, TY}, title = {Exposome for Ocular Diseases: From Exposure Evidence to Causality and Actionable Prevention.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101524}, doi = {10.1016/j.preteyeres.2026.101524}, pmid = {42697425}, issn = {1873-1635}, abstract = {The exposome, defined as the totality of external exposures individuals experience throughout the lifespan and the internal biological responses they trigger, is increasingly recognized as a major, modifiable determinant of health. The eye is uniquely vulnerable to exposome risk factors because it comprises an external interface directly exposed to the environment, a transparent lens highly sensitive to cumulative oxidative injury, and metabolically active retina prone to inflammation and vascular dysregulation. Research linking ocular diseases to air pollution, climate and weather factors, heavy metals, persistent organic pollutants, and emerging threats such as micro-/nanoplastics has expanded rapidly, yet the evidence remains fragmented and lacks systematic integration. In this review, we propose an anatomy-informed ocular exposome atlas along the visual axis to comprehensively evaluate evidence from clinical studies, pathological mechanisms, and intervention strategies across major disease groups-including ocular surface diseases, cataract, refractive errors, glaucoma, and retinal diseases. We further integrate cross-disease mechanistic pathways (oxidative stress, cellular responses, inflammation, immune reactions) and discuss causality. Finally, we identify priority research directions and provide actionable recommendations for prevention and policy.}, }
@article {pmid42696011, year = {2026}, author = {Kozlov, M and Sadeghi, E and Chhablani, J}, title = {Adoption patterns of anti-vascular endothelial growth factor therapies in retinal disease.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42696011}, issn = {1435-702X}, abstract = {PURPOSE: To characterize real-world adoption patterns of anti-vascular endothelial growth factor (anti-VEGF) therapies across retinal vascular diseases.<br><br>METHODS: This retrospective cohort study identified patients diagnosed with exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) within TriNetX. Monthly utilization of ranibizumab, bevacizumab, aflibercept, brolucizumab, and faricimab was measured across each indication. To provide absolute treatment context, we also determined the annual number of unique patients within each disease cohort with at least one documented exposure to any evaluated anti-VEGF agent.<br><br>RESULTS: The cohorts included 138,384 AMD patients, 322,865 DME patients, and 105,605 RVO patients. Aflibercept demonstrated sustained long-term utilization across all three indications, whereas faricimab showed rapid early uptake after its introduction. Ranibizumab utilization declined over time, while brolucizumab demonstrated limited and transient uptake. The annual number of patients receiving anti-VEGF treatment increased substantially over the observation period and reached 16,319 in AMD, 12,105 in DME, and 6,873 in RVO in 2023.<br><br>CONCLUSION: Real-world adoption of anti-VEGF therapies differs markedly across retinal diseases and agents. Aflibercept demonstrated sustained long-term use, while faricimab showed rapid early uptake. Changes in agent-specific utilization occurred alongside substantial growth in the absolute number of treated patients over the study period, underscoring the importance of interpreting drug-specific trajectories in the context of overall treatment activity.}, }
@article {pmid42690636, year = {2026}, author = {Chen, S and Li, Y and Xuan, M and Xiong, R and Tan, S and Wang, W}, title = {Longitudinal Trajectories of 3-Dimensional Eye Shape and Pathological Sequelae in High Myopia.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42690636}, issn = {2168-6173}, abstract = {IMPORTANCE: The highly myopic eye remodels in 3 dimensions, but the longitudinal trajectories of globe shape and their associations with sight-threatening outcomes remain poorly defined.<br><br>OBJECTIVE: To characterize 15-year 3-dimensional (3D) remodeling trajectories of highly myopic globes and examine their associations with baseline features and ocular outcomes.<br><br>This 15-year 3D magnetic resonance imaging (MRI) cohort substudy was nested within the Zhongshan High Myopia Cohort. Thirty participants (60 eyes) with bilateral high myopia (spherical equivalent refraction, -6.00 D or worse) randomly drawn from 95 participants imaged in September 2011 were rescanned in September 2025.<br><br>EXPOSURES: Orbital 3D MRI reconstructions were classified into 6 globe-shape categories. Paired classifications, global enlargement, and staphyloma status defined 5 remodeling patterns: quiescence, proportional expansion, focal emergence, focal progression, and shape transition.<br><br>MAIN OUTCOMES AND MEASURES: Distribution of remodeling patterns and their associations with myopic macular degeneration (MMD), myopic traction maculopathy (MTM), posterior staphyloma (PS), visual acuity, and visual field indices.<br><br>RESULTS: Among the 30 included participants, the mean (SD) age was 37.30 (15.89) years, and 16 (53.3%) participants were women. The 60 eyes were classified as quiescent (21 [35.0%]), proportional expansion (12 [20.0%]), focal emergence (14 [23.3%]), focal progression (6 [10.0%]), or shape transition (7 [11.7%]). No deformed eye reverted to spheroidal. Pattern distribution was associated with baseline age and contour: 10 of 12 eyes (83.3%) of individuals younger than 20 years underwent proportional expansion, whereas 13 of 24 eyes (54.2%) of individuals aged 40 years and older followed focal progression or shape transition. Eyes with focal emergence had the largest best-corrected visual acuity decline (0.26 logMAR) and mean deviation worsening (-3.50 dB), and eyes with shape transition had the largest pattern standard deviation increasing (1.95 dB). At similar axial elongation, eyes developing focal deformation had higher frequencies of MMD progression (91.7%; 95% CI, 74.2-97.7 vs 58.8%; 95% CI, 36.0-78.4; P&#x2009;=&#x2009;.02), incident or progressive PS (91.7%; 95% CI, 74.2-97.7 vs 17.6%; 95% CI, 6.2-41.0; P&#x2009;<&#x2009;.001), and MTM (58.3%; 95% CI, 38.8-75.5 vs 11.8%; 95% CI, 3.3-34.3; P&#x2009;=&#x2009;.003).<br><br>CONCLUSIONS AND RELEVANCE: Highly myopic globes followed age- and geometry-associated trajectories linked to outcomes beyond axial elongation. These 2-time-point findings potentially support 3D shape analysis as a candidate framework for individualized surveillance, pending prospective validation.}, }
@article {pmid42693542, year = {2026}, author = {Jung, W and Lee, JJ and Cho, Y and Min, KA and Yun, HY and Lee, S and Yang, J and Chae, JW}, title = {Determination of Human Effective Dose via Translational Ocular Modeling: Clinical Translation of a Novel Topical Agent Using PBPK.}, journal = {Clinical and translational science}, volume = {19}, number = {9}, pages = {e70717}, pmid = {42693542}, issn = {1752-8062}, support = {RS-2022-00155857//Korea Government/ ; RS-2023-00278597//Korea Government/ ; RS-2022-NR069643//Korea Government/ ; RS-2022-NR070856//Korea Government/ ; RS-2021-KE001333//Core Technology Development Project for Environmental Diseases Prevention and Management/ ; //Korea Ministry of Environment (MOE)/ ; //Korea Machine Learning Ledger Orchestration for Drug Discovery Project (K-MELLODDY)/ ; RS-2024-00460694//Ministry of Health &amp; Welfare and Ministry of Science and ICT, Republic of Korea/ ; 2710008763//Korea Institute of Toxicology (KIT) Research Program/ ; KK-2401-01//Korea Institute of Toxicology (KIT) Research Program/ ; //Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI)/ ; RS-2024-00336984//Ministry of Health &amp; Welfare, Republic of Korea/ ; RS-2025-02306055//Ministry of Health &amp; Welfare, Republic of Korea/ ; RS-2024-00434342//Korea Institute for Advancement of Technology (KIAT)/ ; //National Research Foundation of Korea (NRF)/ ; RS-2025-25397599//Ministry of Education/ ; //EyeBioKorea/ ; }, mesh = {Humans ; Animals ; Rabbits ; Mice ; *Models, Biological ; *Macular Degeneration/drug therapy ; Translational Research, Biomedical ; Dose-Response Relationship, Drug ; *Ophthalmic Solutions/administration &amp; dosage/pharmacokinetics ; Computer Simulation ; Tissue Distribution ; Species Specificity ; Male ; }, abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of vision loss, and human dose selection for ocular therapeutics remains a key translational challenge. We developed a physiologically based pharmacokinetic (PBPK) model for EB-203 to guide dose selection by translating preclinical ocular tissue exposure to human. PK data were obtained from mouse and rabbit studies and human plasma PK from a phase I trial. The model incorporated species-specific ocular physiology, drug permeability, and pharmacokinetics, and was implemented using an open-source PBPK modeling software (MoBi, version 12.2, Open Systems Pharmacology). Drug-specific model parameters were estimated using mouse and rabbit plasma and ocular tissue concentration data. Human plasma PK data from a Phase I clinical trial were then used to estimate human-specific systemic clearance, and human ocular tissue concentrations were subsequently predicted by the model. Simulated human retinal drug concentrations (AUC, Cmax, and Cavr) under multiple dosing regimens were evaluated against preclinical efficacy thresholds to determine the optimal dosing strategy. The model adequately described drug disposition across species, with most predicted PK parameters falling within a 2-fold error of the observed data. Simulations suggested that a 4% four-times-daily dosing regimen in humans achieves retinal exposure comparable to the efficacious mouse concentrations. No significant systemic accumulation was observed, indicating a favorable safety profile. This PBPK framework provides a practical approach for predicting human ocular drug exposure and can be adapted to other compounds or ocular indications in the absence of direct tissue sampling. These results support further clinical evaluation of EB-203 for the treatment of wAMD.}, }
@article {pmid42694158, year = {2026}, author = {Jin, E and Zhu, X and Li, S and Zhao, M and Miao, H and Qian, T}, title = {Short-term morphological and functional outcomes of intravitreal faricimab for chorioretinal disorders: a real-world study in a Chinese population.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1909782}, pmid = {42694158}, issn = {2296-858X}, abstract = {OBJECTIVE: To evaluate the real-world efficacy and safety of the bispecific antibody faricimab in Chinese patients with neocascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema secondary to retinal vascular occlusion (RVO-ME).<br><br>METHODS: This retrospective, single-center study included 63 patients (74 eyes: 47 nAMD, 19 DME, 8 RVO-ME); no subjects dropped out. Of the 74 eyes, 37.8% were treatment-na&#xef;ve and 62.2% were treatment-experienced. All eyes received intravitreal faricimab 6 mg in a three-dose loading regimen followed by pro re nata (PRN) retreatment. Best-corrected visual acuity (BCVA, ETDRS letters) and central macular thickness (CMT) were assessed at baseline, 1 month, 3 months, and final follow-up (mean follow-up, 23.9 &#xb1; 12.3 weeks). Subgroup analyses by prior treatment status were performed.<br><br>RESULTS: Faricimab was associated with anatomical and functional improvements. In nAMD, treatment-na&#xef;ve patients (n = 17) showed significant BCVA improvement (62.52 &#xb1; 5.80 to 71.05 &#xb1; 15.68 letters, P = 0.037) and CMT reduction (477.86 &#xb1; 189.45 to 324.19 &#xb1; 137.62 &#x3bc;m, P = 0.001) at final follow-up. Previously-treated nAMD patients (n = 30) showed only a transient CMT reduction at 3 months (P = 0.022) without sustained visual improvement. After the first injection, intraretinal fluid resolved in 90% of nAMD eyes that had IRF at baseline. After three loading doses, complete resolution of subretinal fluid and pigment epithelial detachment (PED) occurred in 66.7% and 31.3% of eyes, respectively. In DME, treatment-na&#xef;ve patients (n = 9) achieved early BCVA improvement at 1 month (P = 0.0273) and sustained benefit at final follow-up (P = 0.0180), whereas previously-treated patients (n = 10) showed delayed improvement at 3 months in both BCVA and CMT (P = 0.0117 and 0.0195). In RVO-ME, BCVA improved significantly at 3 months and final follow-up (P = 0.018 and 0.028), whereas CMT showed a nonsignificant decrease. No significant ocular or systemic adverse events were observed.<br><br>CONCLUSION: In this short-term real-world study comprising three exploratory disease-specific cohorts of Chinese patients, faricimab was associated with favorable anatomical and functional outcomes and was well tolerated, with the most pronounced benefit in treatment-na&#xef;ve nAMD eyes. Responses in DME and RVO-ME were more variable and appeared to be influenced by prior treatment history; these subgroup analyses were exploratory, and larger prospective studies are warranted.}, }
@article {pmid42684442, year = {2026}, author = {Bandello, F and Borrelli, E and De Falco, S and Invernizzi, A and Lanzetta, P and Lupidi, M and Midena, E and Ricci, F and , }, title = {Aflibercept 8 mg for diabetic macular edema and neovascular age-related macular degeneration: an italian expert consensus paper.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42684442}, issn = {1435-702X}, abstract = {PURPOSE: To provide consensus recommendations on the clinical use of aflibercept 8 mg in managing neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in the real-world setting.<br><br>METHODS: A modified Delphi study was undertaken, involving ophthalmologists from specialized centers in Italy, to gauge consensus on statements related to the use of aflibercept 8&#xa0;mg in nAMD and DME. Two initial rounds of online surveys were conducted, followed by 2 workshops to assess the clinical feasibility of selected statements and identify the behavioral drivers and barriers to their adoption in practice. Consensus was defined as &#x2265;&#x2009;75% agreement ('strongly agree' or 'somewhat agree').<br><br>RESULTS: Consensus was reached for 30 initial statements, following refinement and discussion. Of these, 12 statements were analyzed and discussed at the behavioral workshop. Statements covered clinical differentiation of aflibercept 2&#xa0;mg and 8&#xa0;mg, treatment initiation in aflibercept-na&#xef;ve patients, switching to aflibercept 8&#xa0;mg, optimal aflibercept 8&#xa0;mg maintenance, and safety considerations. There was expert group consensus that aflibercept 8&#xa0;mg represents a viable treatment option with an extended injection interval for patients with nAMD or DME, with the possibility of improving treatment adherence, and therefore outcomes. Experts also discussed practical considerations in Italy and offered evidence-based guidance.<br><br>CONCLUSION: Experts agreed that aflibercept 8&#xa0;mg is a treatment option for both nAMD and DME with the potential to improve treatment adherence. Although real-world data are limited, experts offered guidance on the management of nAMD and DME in the context of aflibercept 8&#xa0;mg.}, }
@article {pmid42685076, year = {2026}, author = {Cheng, FF and Mou, H and Liu, Z and Zhang, CJ and Zhuang, YY and Wu, Z and Wen, XR and Xue, A and Zhang, X and Yang, J and Jin, ZB}, title = {Genetic evidence and cross-species functional characterization implicate CNN2 in age-related macular degeneration susceptibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {36}, pages = {e2533682123}, doi = {10.1073/pnas.2533682123}, pmid = {42685076}, issn = {1091-6490}, support = {82125007//MOST | National Natural Science Foundation of China (NSFC)/ ; 92368206//MOST | National Natural Science Foundation of China (NSFC)/ ; CX23YZ14//Chinese Institutes for Medical Research/ ; BRWEP2024W172050100//Beijing Research Ward Excellence Program/ ; PWD&amp;RPP-MRI//Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes/ ; JYY2023-6//Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes/ ; U23A20165//MOST | National Natural Science Foundation of China (NSFC)/ ; 2024SSYS0032//"Pioneer" and "Leading Goose" R&amp;D Program of Zhejiang/ ; 2022SDXHDX0001//"Pioneer" and "Leading Goose" R&amp;D Program of Zhejiang/ ; }, mesh = {Animals ; *Genetic Predisposition to Disease ; *Macular Degeneration/genetics/pathology/metabolism ; Zebrafish ; Quantitative Trait Loci ; Genome-Wide Association Study ; Mice ; Humans ; Cytoskeletal Proteins/genetics/metabolism ; Disease Models, Animal ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the aging population globally. Although genome-wide association studies (GWAS) have identified many AMD susceptibility loci, the genes and mechanisms underlying many of these associations remain unresolved. Here, we integrated expression quantitative trait locus (eQTL) data with AMD GWAS to prioritize nine putative genes. Through in vivo screening in zebrafish, we demonstrated that the downregulation of cnn2 and sarm1 expression led to ocular structural abnormalities and visual functional impairment. Subsequent mouse model studies confirmed that Cnn2 deficiency affected photoreceptor structure and function, impaired contrast sensitivity, and caused abnormalities in cone cell immunostaining. Given that CNN2 is predominantly expressed in endothelial cells, we propose that endothelial dysfunction may cascade to impair photoreceptor function. Collectively, through in silico prioritization and cross-species functional characterization, we identify CNN2 as a candidate susceptibility gene in AMD pathogenesis, providing vital underlying mechanistic insights.}, }
@article {pmid42686244, year = {2026}, author = {Manikya, S and Vadhithala, V and Kumar, R and Nainwal, P}, title = {Re: Holz et al.: Adherence to intravitreal aflibercept in neovascular age-related macular degeneration: 24-month results from the ANDROMEDA Study (Ophthalmol. Retina. 2026;10:241-249).}, journal = {Ophthalmology. Retina}, volume = {10}, number = {9}, pages = {e81-e82}, doi = {10.1016/j.oret.2026.06.013}, pmid = {42686244}, issn = {2468-6530}, }
@article {pmid42687065, year = {2026}, author = {Attia, SA and Tse, AM and Ramirez, AD and Izadiar, M and Liu, Y and Guo, H and Albanese, A and Cohn, W and MacKay, AW and Seidler, PM and Kannan, R and Sreekumar, PG and MacKay, JA}, title = {αB-crystallin elastin-like polypeptides for sustained ocular drug delivery.}, journal = {Drug delivery and translational research}, volume = {}, number = {}, pages = {}, pmid = {42687065}, issn = {2190-3948}, abstract = {The unfolded protein response (UPR) has been mechanistically implicated in multiple ocular disorders, including age-related macular degeneration (AMD). Therapeutic intervention using an αB-crystallin-derived 'mini-cry' chaperone peptide has potential to restore proteostasis; however, its low molecular weight results in rapid ocular clearance. To prolong mini-cry's ocular effects, our team linked it with elastin-like polypeptides (ELPs). ELPs are thermoresponsive polymers that phase-separate into microscale coacervates. Provided ELPs do not interfere with biological activity, cry-ELPs could prolong intraocular retention and improve therapeutic effect. This study compares two cry-ELPs (cry-SI and cry-V96) designed to phase-separate following intravitreal administration. First, chaperone activity was assessed using tau protein aggregation assays, demonstrating that cry-V96 exhibited superior inhibition of tau seeding and fibril disaggregation. Second, modulation of the UPR was assessed in human retinal pigment epithelium cells using tunicamycin-induced stress. Both constructs suppressed PERK/ATF-4/CHOP signaling, with cry-V96 showing the most robust attenuation of ER stress. Third, cellular uptake and subcellular localization were analyzed by biochemical fractionation and Western blotting, revealing enhanced cellular uptake and association and stress-dependent nuclear localization of cry-ELPs, compared to controls. Fourth, the lead construct, cry-V96, was evaluated in vivo in rabbit eyes, where it formed a sustained intravitreal depot, exhibited prolonged retention, and showed no evidence of ocular toxicity by fluorescence imaging and optical coherence tomography (OCT). Finally, proteomic profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 59 proteins selectively enriched by cry-V96, implicating pathways involved in proteostasis, intracellular trafficking, and stress adaptation. Collectively, these findings establish cry-ELPs as multifunctional molecules that combine potent chaperone activity with sustained ocular delivery, providing a promising strategy for targeting UPR dysregulation in AMD and related degenerative diseases.}, }
@article {pmid42687870, year = {2026}, author = {Mandal, D and Roy, A and Chen, X and Zhong, JF and Kim, ES}, title = {Microfluidic platform for nanoliter qPCR of several retinal pigment epithelial (RPE) cells.}, journal = {Journal of micromechanics and microengineering : structures, devices, and systems}, volume = {36}, number = {9}, pages = {095001}, pmid = {42687870}, issn = {0960-1317}, abstract = {The clinical implant of stem cell-derived retinal pigment epithelium (RPE) monolayer for age-related macular degeneration requires rigorous validation of the monolayer's cellular maturity. Conventional bulk molecular assays lack the sensitivity to resolve cellular heterogeneity and are prone to damaging the RPE monolayer. This study developed and validated an automated nanoliter-scale microfluidic platform for single-cell transcriptomic quality control of engineered RPE monolayers. A compact polydimethylsiloxane -based microfluidic platform was developed to generate monodisperse 10 nL RPE cell cDNA droplets and 90 nL quantitative PCR (qPCR) reagent droplets using dual-focused-flow geometries. Deterministic droplet fusion was achieved via direct current electrocoalescence, enabling ∼100% merging efficiency. An auxiliary co-flow spacing mechanism was implemented to prevent secondary coalescence during downstream transport. Automated droplet collection into oil-filled 96-well plates was achieved through a custom two-dimensional gantry system, and droplet volume consistency was verified using a Python-based computer vision algorithm. Biological validation was conducted using H14 human embryonic stem cell-derived RPE cells targeting β-actin and lineage-specific markers MITF1, MITF2, PEDF, and PMEL17. The platform demonstrated stable generation and deterministic merging of nanoliter droplets, yielding uniform 100 nL reaction volumes suitable for qPCR analysis. Automated volumetric verification confirmed high droplet uniformity and reliability. Gene expression analysis revealed robust detection of housekeeping and lineage-specific genes at nanoliter scales. These findings demonstrated the feasibility of performing nanoliter-scale qPCR using the proposed microfluidic workflow. The workflow enabled reliable detection of extremely low quantities of nucleic acid using a widely available commercial qPCR platform, providing a practical and accessible approach for routine laboratory and translational research applications. The system-maintained assay sensitivity while significantly reducing reagent consumption and sample input. This automated microfluidic platform enabled reproducible, sample-efficient, single-cell transcriptomic validation of stem cell-derived RPE monolayers. By integrating droplet generation, deterministic merging, automated collection, and computational verification, the system addressed key limitations of bulk molecular quality control of RPE monolayers. This work established a scalable and cost-effective nanoliter qPCR framework for high-resolution molecular quality assurance of regenerative cell therapies.}, }
@article {pmid42687910, year = {2026}, author = {Swaroop, A and Marchal, C and Gaur, M and Kumari, A and Mohan, S and Brooks, M and Jaeger, C and Advani, J and Campello, L and English, M and Singh, N and Diaz, X}, title = {Enhanced chromatin compaction is associated with de novo expression of a nuclear microprotein, global loss of H3 acetylation and local transcriptional changes in retinal rod photoreceptors.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-10017071/v1}, pmid = {42687910}, issn = {2693-5015}, abstract = {We have limited understanding of how aging alters gene expression and remodels cellular architecture in post-mitotic neurons. The inverted nuclear organization of mouse rod photoreceptors provides a unique model to gain mechanistic insights into age-associated decline in neuronal function. We have generated and integrated multi-omic datasets including 3D-genome topology, histone modifications, chromatin accessibility, DNA methylation and transcriptome of rod photoreceptors from young- and aged-mice. We show that aging drives global chromatin compaction, with regional alterations enriched at active chromatin. Epigenomic and transcriptional changes broadly correlate with chromatin dynamics as validated by high resolution microscopy. We uncover a megabase-sized genomic region with multi-level alterations, including de novo transcription of Gm7239, which encodes a functional microprotein carrying histone acetyltransferase-inhibitor domain. Overexpression of Gm7239 is associated with global loss of histone H3 acetylation, highlighting a potential new axis of genomic regulation in aging. Finally, we identify multiple significant local transcriptional alterations in non-annotated regions and genes associated with age-related macular degeneration. Our studies link age-related chromatin landscape changes with gene expression that may influence rod function and vulnerability to diseases.}, }
@article {pmid42681078, year = {2026}, author = {Cheong, KX and Jiang, Y and Xu, X and Htoon, HM and Foo, LL and Lamoureux, EL and Hoang, QV and Lan, W and Saw, SM}, title = {Two-Year Fundus Progression in Highly Myopic Eyes in the Aier-SERI High Myopia Adult Cohort Study.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {}, number = {}, pages = {}, pmid = {42681078}, issn = {1475-1313}, support = {2024RC5002, 2023RC1079//Science and Technology Innovation Program of Hunan Province, China/ ; JRDUKY004900//Duke-NUS Distinguished Professorship grant/ ; }, abstract = {PURPOSE: To evaluate 2 year fundus progression and associated factors in adults in the Aier-SERI High Myopia cohort in Changsha, China.<br><br>METHODS: A total of 367 adult high myopes (spherical equivalent [SE]&#x2009;&#x2264;&#x2009;-5.0D) underwent baseline and 2 year assessments, including colour fundus photography graded by the Meta-analysis for Pathologic Myopia (META-PM) classification. Progression was defined as advancement to a higher category, enlargement of atrophy or development/worsening of plus lesions. Associations were analysed using multivariable generalised estimating equation (GEE) logistic regression adjusting for age, sex, SE or axial length (AL) and baseline META-PM category.<br><br>RESULTS: In this cohort (mean age: 45.2&#x2009;&#xb1;&#x2009;7.3 years), fundus progression occurred in 31/734 eyes (4.2%, 27 participants). Of 37 lesion changes in 31 eyes, the most frequent changes were enlargement of patchy atrophy (51.4%), followed by diffuse atrophy (16.2%) and lacquer crack extension (16.2%). Fuchs' spot expansion and category progression were less common (8.1% each). In GEE models, progression was associated with more myopic SE (per -1D, odds ratio [OR]: 1.21; 95% confidence interval [CI]: 1.14-1.29, p&#x2009;<&#x2009;0.001), longer AL (per 1-mm, OR: 1.96; 95% CI: 1.64-2.34, p&#x2009;<&#x2009;0.001) and older age (per year, OR: 1.06; 95% CI: 1.02-1.11, p&#x2009;<&#x2009;0.01). Eyes with baseline Category 3 lesions had markedly higher odds of progression (OR: 85.55; 95% CI: 25.07-291.93, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Over 2 years, fundus progression in adult highly myopes occurred mainly in those with advanced atrophy at baseline and was associated with greater myopia, longer AL and older age. Eyes of Categories 0-1 remained stable, suggesting a threshold for accelerated degeneration.}, }
@article {pmid42681693, year = {2026}, author = {Ruiz-Medrano, J and Zamorano, M and de Alboran, CM and Ruiz-Moreno, JM}, title = {Two-year real-world effectiveness of faricimab after treatment switch in neovascular age-related macular degeneration.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {42681693}, issn = {2056-9920}, abstract = {PURPOSE: To evaluate the 2-year real-world outcomes of switching to intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF agents and unable to extend treatment intervals (TI) beyond 12 weeks.<br><br>METHODS: Prospective cohort study including patients with nAMD managed under a treat-and-extend regimen who required frequent anti-VEGF injections (<&#x2009;12-week intervals) to maintain retinal dryness. Patients were switched to faricimab without a loading phase and followed for a minimum of 2 years. TI were extended in 4-week increments based on anatomical response. The primary outcome was change in TIl; secondary outcomes included change in best-corrected visual acuity (BCVA) and identification of predictors of response. "Optimal responders" were defined as eyes achieving&#x2009;&#x2265;&#x2009;8-week interval extension.<br><br>RESULTS: A total of 110 eyes from 97 patients were included (mean age 78.7&#x2009;&#xb1;&#x2009;9.8 years). Prior to switching, the mean TI was 6.18&#x2009;&#xb1;&#x2009;2.05 weeks, which increased significantly to 13.61&#x2009;&#xb1;&#x2009;5.62 weeks at the last follow-up visit (p&#x2009;<&#x2009;0.001). BCVA remained stable over 2 years (0.42&#x2009;&#xb1;&#x2009;0.24 vs. 0.43&#x2009;&#xb1;&#x2009;0.25; p&#x2009;=&#x2009;0.0117). At final follow-up, 68.2% of eyes achieved intervals&#x2009;&#x2265;&#x2009;12 weeks, 20.0% &#x2265;16 weeks, and 24.6% reached&#x2009;&#x2265;&#x2009;20-week intervals. Overall, 89.1% of eyes experienced interval extension. Optimal responders accounted for 47.3% of eyes and were significantly younger and had received fewer prior injections (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: Switching to faricimab in previous treated nAMD patients enabled meaningful extension of TI over 2 years while maintaining stable visual acuity. These findings support faricimab as an effective strategy to reduce treatment burden in patients who are difficult to extend with prior anti-VEGF therapies.}, }
@article {pmid42682018, year = {2026}, author = {Swan, J and Gagneux, P}, title = {Glycosylation of the retina.}, journal = {Biochemical Society transactions}, volume = {54}, number = {9}, pages = {1183-1192}, doi = {10.1042/BST20260004}, pmid = {42682018}, issn = {1470-8752}, support = {M2023003F//BrightFocus Foundation (BFF)/ ; }, mesh = {Glycosylation ; Humans ; *Retina/metabolism ; Animals ; Polysaccharides/metabolism ; Proteoglycans/metabolism ; Glycosphingolipids/metabolism ; Retinal Diseases/metabolism ; }, abstract = {Unlike the cornea and tear fluid, glycosylation within the retina remains remarkably underexplored. This review highlights the diverse roles of glycans in retinal development and vision, with a focus on major glycan classes, including glycosphingolipids (GSLs; glycans attached to lipids), N- and O-linked glycans on proteins, glycosaminoglycans (GAGs) on proteoglycans, O-mannosylated proteoglycans, and intracellular O-GlcNAcylation. Together, these components provide a comprehensive framework for understanding glycan-mediated processes in retinal biology. Current knowledge of the retinal glycosylation nanolandscape, primarily derived from lectin binding and anti-glycan antibody studies, is summarised. The review also examines the roles of altered glycosylation in immune regulation and retinal diseases such as retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy. Finally, key gaps in knowledge and priority areas for future research are discussed. The retina remains understudied with regard to the complex patterns of glycosylation. Alterations of these patterns could represent consequences or be driving pathology, given the well-established roles of glycan patterns in development and homeostasis in other tissues.}, }
@article {pmid42683940, year = {2026}, author = {Guo, CW and Zhao, AH and Kaelber, D and Singh, RP and Talcott, KE}, title = {Effect of Hormone Replacement Therapy on Risk of Age-related Macular Degeneration Among an Aggregate Health Record Cohort.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-9}, doi = {10.3928/23258160-20260813-03}, pmid = {42683940}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: Estrogen in hormone replacement therapy (HRT) exerts anti-inflammatory effects believed to oppose age-related macular degeneration (AMD) pathogenesis, but whether HRT can be protective against AMD is contested. The aim of the study was to evaluate the association between HRT use and the risk of development and progression of AMD in postmenopausal women.<br><br>PATIENTS AND METHODS: This was a retrospective cohort study utilizing ICD-10 codes for HRT usage and rates of AMD development and progression.<br><br>RESULTS: There was a decreased risk of developing AMD in patients more than 60 years of age at 5 years (RR 0.72, 95% CI: 0.63-0.82) and 8 years (0.68, 0.60-0.76) after HRT initiation. Patients more than 75 years of age also demonstrated a reduced risk of developing AMD after 5 years (0.70, 0.60-0.82) and 8 years (0.64, 0.56-0.74) of HRT use. Patients more than 75 years of age had a reduced risk of progression to exudative AMD at 8 years (0.66, 0.49-0.89) after HRT initiation.<br><br>CONCLUSION: HRT may be associated with a decreased risk of developing AMD, with continued effects at more chronic timepoints after HRT initiation.}, }
@article {pmid42676384, year = {2026}, author = {Wang, MH and Lee, SMY and Wang, Y and Alves, JC and Xie, R and He, Y and Hou, G and Fang, X and Yu, Y and Cai, X and Zheng, S and Liu, J and Cheang, C and Kuok, KI and Qin, S}, title = {Artificial intelligence for precision therapeutics in age-related macular degeneration: current advances, challenges, and future directions.}, journal = {Frontiers in artificial intelligence}, volume = {9}, number = {}, pages = {1822604}, pmid = {42676384}, issn = {2624-8212}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is characterized by substantial clinical, imaging, and molecular heterogeneity that complicates disease prediction and therapeutic management. Recent advances in artificial intelligence (AI) and precision therapeutics have created new opportunities for more individualized and data-driven AMD care. AI models trained on multimodal datasets-including fundus photography, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), genetic susceptibility loci (e.g., CFH, ARMS2/HTRA1, C3, CFI, and APOE), and longitudinal clinical information-have demonstrated promising capability in early disease detection, progression forecasting, biomarker identification, and prediction of treatment response. These developments align closely with emerging precision therapeutic strategies, including optimized anti-vascular endothelial growth factor (anti-VEGF) regimens, complement-targeted therapies, gene-based interventions, and stem cell-associated regenerative approaches. This review provides a translational overview of AI-enabled precision therapeutics in AMD, with emphasis on multimodal biomarker integration, individualized therapeutic stratification, longitudinal disease monitoring, and clinically interpretable AI systems. Importantly, we further propose a Five-Level Clinical Readiness and Translational Utility Framework for AI in AMD Precision Therapeutics, categorizing AI applications according to evidence strength, clinical maturity, validation status, interpretability, and real-world implementation potential. The framework distinguishes near-reference-standard imaging AI systems, advanced clinical decision-support tools, emerging multimodal precision therapeutic AI, supportive workflow-oriented AI systems, and currently limited or unsuitable AI applications. Despite substantial progress, important translational barriers remain, including limited external validation, retrospective study designs, dataset heterogeneity, domain shift, insufficient explainability, regulatory uncertainty, and challenges related to workflow integration and real-world clinical deployment. Future advances in multimodal longitudinal AI, explainable AI, federated learning, digital health platforms, and multi-omics integration may facilitate a transition from reactive disease management toward more proactive, predictive, and personalized ophthalmic care. Collectively, AI-enabled precision therapeutics may help establish a more scalable and clinically integrated framework for individualized AMD management and future precision ophthalmology.}, }
@article {pmid42676770, year = {2026}, author = {Verma, V and Gupta, S and Singh, P and Karkhur, S and Behera, PR}, title = {Global Patterns of Visual Disability and Low Vision Aid Prescription: A Systematic Review.}, journal = {Cureus}, volume = {18}, number = {7}, pages = {e113756}, pmid = {42676770}, issn = {2168-8184}, abstract = {Visual disability remains a major global public health challenge, particularly among individuals with irreversible ocular diseases where medical or surgical treatment cannot restore functional vision. Low-vision rehabilitation (LVR), including the prescription of low-vision aids (LVAs), plays a critical role in optimizing residual vision and improving quality of life; however, patterns of visual disability and LVA utilization vary widely across populations and healthcare settings. This systematic review was conducted in accordance with PRISMA 2020 guidelines to evaluate patterns of visual disability and the prescription, utilisation, and functional outcomes of low-vision aids across diverse patient populations. Electronic databases, including PubMed, Scopus, EMBASE, and the Cochrane Library, along with Google Scholar and citation tracking, were searched for studies published between 2000 and 2025. Observational studies, randomized or crossover trials, service audits, and rehabilitation reports assessing low-vision rehabilitation or assistive devices were included. Of 975 records identified, 19 studies met the inclusion criteria. Retinal diseases such as age-related macular degeneration, diabetic maculopathy, and inherited retinal dystrophies were the predominant causes of visual disability in adults, whereas congenital and developmental conditions were more common in pediatric populations. Optical LVAs, particularly high-add spectacles and magnifiers, were the most frequently prescribed devices, while electronic and wearable aids demonstrated superior task-specific performance but lower real-world uptake due to cost and usability barriers. Telerehabilitation showed functional outcomes comparable to in-clinic training. Overall, low-vision aids significantly improve functional outcomes across a wide spectrum of visual disabilities, and a multimodal, patient-centered rehabilitation model integrating optical, electronic, and tele-rehabilitation approaches is essential to enhance accessibility, service reach, and effectiveness.}, }
@article {pmid42676855, year = {2026}, author = {Xiang, Y and Kou, J and Cao, H and Zhang, Y and Cheng, H and Wang, T and Jiang, J and Pan, S and Kang, J and Ding, Y and Wan, W and Zheng, S and Li, M and Huang, X and Hu, K}, title = {Nano-drops of biomimetic macromolecular drugs based on macrophage membranes for targeted treatment of fundus diseases.}, journal = {Materials today. Bio}, volume = {40}, number = {}, pages = {103577}, pmid = {42676855}, issn = {2590-0064}, abstract = {Ocular fundus diseases-including age-related macular degeneration and diabetic retinopathy-are leading causes of irreversible vision loss worldwide. Current macromolecular therapies require frequent intravitreal injections, which increase patient burden and complication risks. To address these limitations, we engineered a macrophage membrane-biomimetic nanovesicle encapsulating ranibizumab (designated M@R) for noninvasive ocular delivery and selective targeting of inflammatory lesions in the posterior segment. In vitro studies demonstrated that M@R retained potent cytokine-scavenging activity against key pro-inflammatory mediators, and the macrophage membrane coating significantly enhanced transcytosis-mediated transport of ranibizumab across ocular epithelial barriers. Ex vivo and in vivo studies confirmed that M@R is capable of noninvasive traversal of ocular barriers, achieving targeted delivery to inflammatory lesions within the fundus. In a laser-induced choroidal neovascularization (CNV) mouse model, topical ocular administration of M@R significantly reduced both the area and thickness of CNV, attributable to its dual anti-inflammatory and anti-VEGF activities. Although multiple dosing was required to achieve therapeutic efficacy comparable to that of a single intravitreal ranibizumab injection, M@R exhibited markedly improved safety profiles, with no observable local ocular toxicity or systemic adverse effects following repeated administration. Collectively, these findings establish macrophage membrane-coated nanovesicles as a promising platform for barrier-penetrating, inflammation-targeted delivery of biologics in the treatment of fundus diseases.}, }
@article {pmid42676917, year = {2026}, author = {Shen, Y and Xu, X and Yang, Y and Song, Y and Liu, F and Zhao, F}, title = {The COPD-driven "lung-eye axis": mechanisms and clinical evidence of ocular disease.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1893979}, pmid = {42676917}, issn = {2296-858X}, abstract = {COPD is a chronic systemic disease marked by ongoing airflow obstruction, sustained inflammation, and increased oxidative stress, whose pathological impact extends far beyond the lungs. Growing data suggest that COPD impacts the eye via chronic systemic inflammation, intermittent or persistent hypoxia, oxidative stress, and endothelial dysfunction, establishing a cross-system pathological connection termed the "lung-eye axis." Evidence from clinical and experimental studies indicates potential associations between COPD and key ophthalmic conditions, such as dry eye disease, cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. The underlying mechanisms largely involve the retina and optic nerve, which rely heavily on oxygenation and microvascular homeostasis, highlighting them as prime ocular targets of COPD systemic effects. The application of noninvasive imaging, such as OCT and OCTA, offers quantitative and objective preliminary evidence for the lung-eye axis, indicating that ocular imaging could function as a surrogate marker of systemic disease burden in COPD. Despite being largely cross-sectional and methodologically constrained, the proposed "COPD-driven lung-eye axis" framework offers a cross-organ perspective for understanding the systemic characteristics of COPD. There is an urgent need for large, prospective, multicenter studies combining pulmonary function tests, blood gas measurements, inflammatory biomarker profiling, and multimodal ocular imaging to establish causal links and clinical utility, providing novel strategies for precision stratification and early intervention of COPD-related systemic complications.}, }
@article {pmid42677513, year = {2026}, author = {Li, Y and Li, B and Zou, D and Zeng, Z and Guo, B and Gong, W and Deng, K and Wang, Z and Zhou, H and Zhou, Y and Xu, X}, title = {Stereospecific Peptide-Polysaccharide Conjugates Enable Noninvasive Therapy of Neovascular Age-Related Macular Degeneration.}, journal = {Journal of the American Chemical Society}, volume = {148}, number = {33}, pages = {35467-35483}, doi = {10.1021/jacs.6c05947}, pmid = {42677513}, issn = {1520-5126}, support = {22077028//National Natural Science Foundation of China/ ; 22277023//National Natural Science Foundation of China/ ; 32000995//National Natural Science Foundation of China/ ; 82271110//National Natural Science Foundation of China/ ; 91956105//National Natural Science Foundation of China/ ; 2025JJ50628//Natural Science Foundation of Hunan Province/ ; 20255098//Scientific Research Project of the Hunan Provincial Health Commission/ ; 2025RC3064//Science and Technology Innovation Program of Hunan Province/ ; 2026JJ20024//Outstanding Young Scientists Program of the Natural Science Foundation of Hunan Province/ ; NA//?Furong Scholar? Distinguished Professor Program in Hunan Province/ ; NA//Flexibly Recruited High-End Talent Program of Yunnan Province/ ; SKY24078//Xiangjiang Public Welfare Foundation of Hunan Province/ ; }, mesh = {Animals ; *Peptides/chemistry/pharmacology/therapeutic use ; *Polysaccharides/chemistry/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy/pathology ; Mice ; Humans ; Stereoisomerism ; *Choroidal Neovascularization/drug therapy ; Cell Proliferation/drug effects ; }, abstract = {Therapeutic interventions for posterior segment ocular diseases, including neovascular age-related macular degeneration (nAMD), remain constrained by poor intraocular bioavailability and the need for repeated intravitreal injections. Here, we introduce a noninvasive therapeutic strategy based on stereospecific peptide-polysaccharide conjugates (PPC) for efficient nAMD treatment. A controllable synthetic strategy was established to generate stereospecific L-PPC and D-PPC, among which D-PPC displayed pronounced chirality-dependent bioactivity, characterized by high-affinity binding to integrin receptors and enhanced inhibition of endothelial/epithelial cell proliferation and migration. Following topical administration, D-PPC efficiently overcame ocular barriers and penetrated choroidal lesions while markedly suppressing pathological angiogenesis in a laser-induced choroidal neovascularization mouse model, comparable to that of intravitreal ranibizumab. We elucidated that stereospecific D-PPC modulates key molecular programs in vivo, including T-cell receptor signaling and cell adhesion molecule pathways. Notably, D-PPC exhibited no detectable ocular or systemic toxicity. This study establishes chirality-engineered peptide-polysaccharide conjugates as a noninvasive and effective therapeutic for posterior ocular diseases, providing a structural and mechanistic blueprint for future translational ophthalmic applications.}, }
@article {pmid42678546, year = {2026}, author = {Piszár, I and Buhl, A and Chronopoulos, A and Schloesser, L and Dicke, C and Eter, N and Zimmermann, JA and ,  and Finger, RP}, title = {[The oregis IVOM registry-Introduction of a registry for the systematic documentation of representative IVOM treatment data from routine treatment of macular diseases in Germany].}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42678546}, issn = {2731-7218}, abstract = {BACKGROUND: Intravitreal operative medication injection (IVOM) treatment in routine clinical practice often fails to achieve the treatment outcomes demonstrated in clinical trials. In Germany, comprehensive and representative real-world data on IVOM treatment (IVT) for macular diseases are still lacking.<br><br>OBJECTIVE: Against this background the oregis IVOM registry was established as a&#xa0;subregistry of the national oregis registry. The aim is the standardized collection and analysis of the course of IVOM treatment in the clinical routine in Germany, to evaluate long-term outcomes and identify potential areas for optimizing patient care. In this way participating ophthalmological centers can make an active contribution to the evidence-based development of IVOM treatment.<br><br>MATERIAL AND METHODS: The oregis IVOM registry is a&#xa0;prospective, noninterventional observational study. Medical routine care data of adult patients receiving IVOM treatment for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO) or choroidal neovascularization (CNV) are collected. Data acquisition is performed via web-based remote data entry into an electronic database using REDCap. Registry structure, datasets and data collection parameters are aligned with the international Fight Retinal Blindness! registry.<br><br>CONCLUSION: The oregis IVOM registry provides, for the first time, a&#xa0;nationwide structured platform for the systematic collection and evaluation of real-world IVT data in Germany. It closes an important evidence gap in health services research for IVOM treatment in Germany and enables regional and international comparisons as well as analyses of treatment adherence and real-world care.}, }
@article {pmid42680556, year = {2026}, author = {Gao, Q and Kuo, D and Amason, J and Lee, T and Rathinavelu, JK and Pajic, M and Hadziahmetovic, M}, title = {Modular multi-task deep learning framework for prediction of treatment initiation in neovascular age-related macular degeneration modular AI for NVAMD treatment initiation study-MANTIS.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328327}, pmid = {42680556}, issn = {1468-2079}, abstract = {PURPOSE: The purpose of this study is to develop a fully automated system for determining the optimal time to begin anti-vascular endothelial growth factor (anti-VEGF) treatment, based on retinal changes observed in optical coherence tomography (OCT) images and visual acuity (VA) scores.<br><br>METHODS: This retrospective study included two cohorts: patients with intermediate dry age-related macular degeneration (AMD) who did not progress to neovascular AMD (NVAMD) and those who progressed and received anti-VEGF treatment. Subjects had &#x2265;3 consecutive visits. Two tasks were defined: (1) develop a deep learning (DL) model to identify the need for anti-VEGF treatment and (2) estimate outer retina thickness (ORT) from Bruch's membrane to the outer plexiform layer as an imaging biomarker. A convolutional neural network extracted OCT features related to ORT, and two long short-term memory models were trained on separate datasets to address Task I and II treatments.<br><br>RESULTS: A total of 122&#x2009;patients (207 eyes) were included: 49 in dataset 1 (69 eyes; mean (SD) age 84 (8); 25 (51%) female) and 100 in dataset 2 (138 eyes; 82 (7); 54 (54%) female). Task I performance was evaluated by the model's alignment with clinical decisions on anti-VEGF initiation, and demonstrated area under the receiver operating curve of 0.73 (95% CI 0.59 to 0.87), area under the precision-recall curve of 0.51 (95% CI 0.35 to 0.66), an accuracy of 0.87 (95% CI 0.76 to 0.97), a precision of 0.73 (95% CI 0.59 to 0.87), a sensitivity of 0.69 (95% CI 0.54 to 0.83) and a specificity of 0.92 (95% CI 0.84 to 1.00). Task II achieved NMAE 0.12 (95% CI 0.04 to 0.20).<br><br>CONCLUSIONS: This DL framework provides a fully automated approach for determining optimal treatment timing, supporting earlier intervention to preserve VA in NVAMD patients.<br><br>TRANSITIONAL RELEVANCE: An accurate DL framework that can help with identifying the best time to initiate therapy for NVAMD.}, }
@article {pmid42669559, year = {2026}, author = {Telegina, DV and Kutlimetova, AO and Izyurov, AE and Kulikov, AV and Kolosova, NG}, title = {Age-Related Alterations in Retinal Monoamine Neuromodulation during AMD-Like Retinopathy Development in Rats.}, journal = {Biochemistry. Biokhimiia}, volume = {91}, number = {8}, pages = {1406-1416}, doi = {10.1134/S0006297926600870}, pmid = {42669559}, issn = {1608-3040}, mesh = {Animals ; *Retina/metabolism/pathology ; Rats ; *Aging/metabolism ; *Macular Degeneration/metabolism/pathology ; Rats, Wistar ; Monoamine Oxidase/metabolism ; *Biogenic Monoamines/metabolism ; Male ; Dopamine/metabolism ; Tyrosine 3-Monooxygenase/metabolism ; }, abstract = {Aging is the major risk factor for age-related macular degeneration (AMD), a leading cause of vision loss in aging populations. Increasing evidence suggests that alterations of neurotransmitter systems contribute to the pathogenesis of AMD. Although biogenic amines in the retina were first detected over 50 years ago, their age-related dynamics and role in AMD development are still poorly understood. Here, we compare age-related changes in the concentrations of norepinephrine, serotonin, dopamine, and their main metabolites in the retinas of senescence-accelerated OXYS rats that develop an AMD-like retinopathy and Wistar rats. We also assessed activities of monoamine oxidases (MAOs) and tyrosine hydroxylase and compared changes in these activities with transcriptome data on genes associated with biogenic amine pathways. The results revealed that in OXYS rats, retinal aging and progression of AMD-like retinopathy are primarily associated with alterations in the dopaminergic system. Specifically, dopamine and its main metabolite DOPAC were present in the retinas at higher levels than serotonin and 5-hydroxyindoleacetic acid. Furthermore, the development of retinopathy in OXYS rats was accompanied by elevated dopamine and DOPAC levels, decreased MAO activity, and changes in the expression of genes associated with the dopaminergic synapse signaling.}, }
@article {pmid42669560, year = {2026}, author = {Yakovleva, MA and Kostyukov, AA and Aronshtam, NL and Shilkrot, PM and Borzenok, SA and Kuzmin, VA and Feldman, TB and Dontsov, AE and Ostrovsky, MA}, title = {Age-Related Changes in bis-Retinoids of Lipofuscin Granules in Human Retinal Pigment Epithelium Cells.}, journal = {Biochemistry. Biokhimiia}, volume = {91}, number = {8}, pages = {1417-1431}, doi = {10.1134/S0006297926600985}, pmid = {42669560}, issn = {1608-3040}, mesh = {Humans ; *Lipofuscin/metabolism/chemistry ; *Retinal Pigment Epithelium/metabolism/cytology ; *Retinoids/metabolism/chemistry ; *Aging/metabolism ; Oxidation-Reduction ; Spectrometry, Fluorescence ; }, abstract = {Lipofuscin granules (LGs) in retinal pigment epithelium (RPE) cells contain bis-retinoids and their oxidation and degradation products, rendering them photo- and cytotoxic to intracellular structures. LGs are implicated in the pathogenesis of multiple visual pathologies, including age-related macular degeneration (AMD). They exhibit strong autofluorescence, which has led to the development of fundus autofluorescence (FAF) imaging as a non-invasive diagnostic method in ophthalmology. Spectral analysis of autofluorescence can expand the capabilities of this method, including for preclinical diagnostics, as pathological conditions are often associated with increased proportions of oxidized bis-retinoid derivatives that alter LG autofluorescence parameters. However, limited knowledge of age-dependent changes in LG bis-retinoid composition remains a key limitation. In this study, we combined fluorescence spectroscopy, confocal fluorescence microscopy, and fluorescence lifetime imaging (time-correlated single-photon counting) to demonstrate that, under physiological conditions, aging is accompanied by a progressive increase in the relative abundance of oxidation and degradation products of bis-retinoids in LGs. These findings provide an age-dependent baseline for distinguishing physiological and pathological states, thereby improving the potential of FAF imaging for early (preclinical) diagnosis.}, }
@article {pmid42671233, year = {2026}, author = {Rosito, A and Caranti, S and Verna, R}, title = {Comparison of adverse events of three anti-VEGF drugs for the treatment of age-related macular degeneration.}, journal = {The Malaysian journal of pathology}, volume = {48}, number = {2}, pages = {267-276}, pmid = {42671233}, issn = {0126-8635}, mesh = {Humans ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Ranibizumab/adverse effects/therapeutic use ; *Bevacizumab/adverse effects ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/adverse effects ; Pharmacovigilance ; }, abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible central vision loss among elderly individuals in developed countries. The neovascular form of AMD is currently treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, particularly ranibizumab, aflibercept, and bevacizumab. Although these therapies significantly improve visual outcomes, repeated intravitreal administration requires continuous monitoring of ocular and systemic adverse events. This review compares the safety profiles of the three principal anti-VEGF agents used for AMD treatment through analysis of pharmacovigilance data, regulatory reports, and major clinical trials. Particular attention is dedicated to ocular complications, systemic thromboembolic events, and the implications of off-label bevacizumab use. Current evidence suggests an overall comparable efficacy and safety profile among the three agents, although Bevacizumab requires stricter preparation and monitoring protocols because of its off-label use. Pharmacovigilance remains essential for identifying safety signals, supporting regulatory decisions, and optimising therapeutic strategies in ophthalmology.}, }
@article {pmid42671884, year = {2026}, author = {Karaca, I and Tezel, TH}, title = {Systemic Lupus Erythematosus Associated Drusen-like Deposits.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000005005}, pmid = {42671884}, issn = {1539-2864}, }
@article {pmid42672000, year = {2026}, author = {Forouhari, A and Cheung, CMG and Leng, LL and Gilead, N and Chakravarthy, U and Teo, KYC}, title = {Predicting risk of progression of early to late AMD in the aging eye through imaging and multimodal evaluation: PRIME study protocol.}, journal = {PloS one}, volume = {21}, number = {8}, pages = {e0355953}, pmid = {42672000}, issn = {1932-6203}, mesh = {Humans ; *Macular Degeneration/diagnostic imaging/pathology/diagnosis ; Disease Progression ; Tomography, Optical Coherence ; Female ; Prospective Studies ; Singapore ; Aged ; Male ; Middle Aged ; Longitudinal Studies ; *Multimodal Imaging ; *Aging/pathology ; Visual Acuity ; Risk Factors ; *Eye/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision impairment globally and demonstrates substantial variation regarding progression and clinical subtypes across populations. This paper describes the methodology of our study, designed to establish the natural history of AMD in Asian elderly and to identify predictors of progression from early signs of AMD to late AMD over a 5-year period.<br><br>METHODS: This prospective, longitudinal cohort study aims to recruit 1500 participants from community-based cohorts in Singapore, with a follow-up duration of 5 years. Eligible participants are adults aged 55 years or older without severe systemic illness that would preclude participation. At baseline, demographic data and medical history will be collected, and visual acuity will be assessed. A basic imaging protocol including color fundus photography (CFP), optical coherence tomography (OCT), and OCT angiography (OCTA) will be performed. Blood samples will be collected from consenting participants. Images will be graded for early signs of AMD, defined as the presence of pathological findings on CFP, OCT, or OCTA. Participants without early signs of AMD will undergo annual follow-up using the basic imaging protocol. Those with any pathological findings at baseline or during follow-up will undergo an enhanced imaging protocol every 6 months, including ultrawide-field fundus photography, fundus autofluorescence (FAF), OCT, and OCTA. All follow-up visits will be conducted at the Singapore Eye Research Institute (SERI). Multimodal imaging biomarkers will be integrated with clinical, demographic, genetic, and metabolomic data to assess the relative risk of progression and identify potential predictors. The study protocol has been approved by the SingHealth Centralised Institutional Review Board.<br><br>DISCUSSION: There is a paucity of data on the progression of AMD and optimal referral thresholds, particularly in Asian populations. This community-based cohort, representative of the general population, will generate one of the largest longitudinal datasets on AMD in Asia and aims to inform future screening strategies. Study registration number: ClinicalTrials.gov Identifier, NCT07653269.}, }
@article {pmid42674195, year = {2026}, author = {Zhang, S and Song, M and Feng, L and Kang, H and Zhao, H and He, J}, title = {Expression, Purification and Antioxidant Activity of Recombinant Human Vascular Endothelial Growth Factor B167 in Escherichia coli.}, journal = {Protein expression and purification}, volume = {}, number = {}, pages = {107001}, doi = {10.1016/j.pep.2026.107001}, pmid = {42674195}, issn = {1096-0279}, abstract = {Age-related macular degeneration (AMD) is a major cause of visual impairment in the elderly, with oxidative stress as its core pathogenesis. Herein, a prokaryotic expression system in Escherichia coli (E. coli) BL21 was developed to yield recombinant human vascular endothelial growth factor B 167(VEGFB167), after systematic optimization of expression and purification parameters, the antioxidant capacity of the target protein was experimentally verified. VEGFB167 was efficiently expressed as inclusion bodies. Following chromatographic purification, the protein purity attained 97% with a concentration of 1.4 mg/mL. Cellular functional assays revealed that VEGFB167 significantly reduced reactive oxygen species, malondialdehyde, and lactate dehydrogenase release, enhanced both superoxide dismutase activity and SOD1/SOD2 gene expression level, inhibited apoptosis, and promoted cell proliferation. These results support further development of VEGFB167 as a biotherapeutic candidate for oxidative injury-triggered illnesses exemplified by AMD.}, }
@article {pmid42674309, year = {2026}, author = {Sekáč, D and Faura, G and Eikenes, M and Josifovska, N and Petrovski, G and Ellederová, Z and Eide, L}, title = {Polarized Secretion of Mitochondrial DNA by Retinal Pigment Epithelial cells.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111225}, doi = {10.1016/j.exer.2026.111225}, pmid = {42674309}, issn = {1096-0007}, abstract = {Mitochondrial DNA (mtDNA) damage is strongly implicated in age-related macular degeneration (AMD), the most frequent cause of age-mediated visual impairment in developed countries. Here, we investigated and compared the fate of acutely induced oxidation damage in primary retinal pigment epithelial (RPE) cells. The individual RPE clones responded heterogeneously to hydrogen peroxide, both with respect to cell sensitivity and mtDNA damage formation. Peroxide-induced mtDNA damage in human RPE (hRPE) was fully repaired within 4 hours. In parallel, hRPE cells secreted mtDNA from both apical and basolateral surfaces (AP-mtDNA and BL-mtDNA, respectively) independent of peroxide exposure and that could not be explained by detached cells. Most mtDNA was released apically, and the quality of AP-mtDNA was comparable to that of intracellular mtDNA (c-mtDNA). In contrast, BL-mtDNA constituted only 3% of AP-mtDNA, and exhibited a 10-fold higher damage burden. The difference in mtDNA quality suggests a non-random selection of mtDNA molecules to be targeted for export in apical versus basolateral direction. To investigate this, we analyzed epigenetic marks (m.545 methylation) and SNPs (heteroplasmies) in extracellular and cellular mtDNA. We detected differences Extracellular mtDNA in general appeared to be more modified than c-mtDNA and that AP-mtDNA differs from BL-mtDNA, which is indicative of a targeted secretion. Porcine RPEs (pRPEs) from a minipig model of Huntington's Disease associated with impaired epithelial polarity (TgHD) displayed approximately 2-fold higher leakage of AP-mtDNA than control pRPEs, but lower than hRPEs. Together, our data imply that extracellular mtDNA originating from RPE shapes the outer retina and the implications for polar secretion are discussed.}, }
@article {pmid42675158, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis.}, journal = {Angiogenesis}, volume = {29}, number = {4}, pages = {}, pmid = {42675158}, issn = {1573-7209}, mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Retinal Neovascularization/therapy/genetics/metabolism ; *Capillary Permeability ; Translational Research, Biomedical ; Gene Therapy Agents ; }, abstract = {INTRODUCTION: Retinal diseases driven by pathological angiogenesis and vascular leakage, including neovascular age-related macular degeneration and diabetic retinopathy, impose substantial visual and treatment burdens because current anti-vascular endothelial growth factor (anti-VEGF) therapy requires repeated intravitreal administration. Ocular gene therapy can provide durable intraocular expression of therapeutic proteins and sustained pathway-level disease control.<br><br>METHODS: This systematic review and meta-analysis was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Scopus, Web of Science, ScienceDirect, and the Cochrane Library were searched from inception to April 21, 2026. Eligible studies included preclinical, in vitro, and clinical investigations of gene-based interventions targeting retinal angiogenesis, vascular permeability, or related anatomical and treatment-burden outcomes. Random-effects meta-analyses were performed using standardized mean differences (SMDs), mean differences (MDs), and logit event rates.<br><br>RESULTS: Twenty-five studies were included. Preclinical gene therapy significantly reduced pathological neovascularization, with a pooled standardized mean difference (SMD) of -1.16 (95% confidence interval [CI], -1.48 to -0.84; p < 0.001) and negligible heterogeneity (I&#xb2; = 0%). Vascular leakage was also significantly reduced across preclinical experimental studies, with a pooled mean difference (MD) of 0.215 (95% CI, 0.178-0.251; p&#x2009;<&#x2009;0.001; I[2]&#x2009;=&#x2009;0%) after directional harmonization. In clinical cohorts, ocular gene therapy significantly reduced central subfield thickness (CST) by -55.30 &#x3bc;m (95% CI, -72.58 to -38.03; p < 0.001) and was associated with reduced anti-vascular endothelial growth factor (anti-VEGF) treatment burden, with a pooled logit event rate of 0.62 (95% CI, 0.20-1.04; p = 0.0039), corresponding to a pooled proportion of approximately 65% of participants meeting study-specific criteria for reduced supplemental anti-VEGF use.<br><br>CONCLUSION: Ocular gene therapy shows strong preclinical anti-angiogenic and anti-permeability effects, with emerging clinical evidence of anatomical improvement and reduced anti-VEGF treatment burden in neovascular retinal disease cohorts. Larger disease-specific randomized trials are required to confirm long-term efficacy, safety, and patient selection.}, }
@article {pmid42675195, year = {2026}, author = {Mendo, I and Camacho, P and Cabral, D}, title = {Incidental subfoveal choroidal synphlebia in non-neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42675195}, issn = {1476-5454}, }
@article {pmid42675470, year = {2026}, author = {Hazra, D and Tomita, Y and Uchida, A and Kato, S and Nagai, N and Suzuki, M and Minami, S and Kunimi, H and Ban, N and Kurihara, T and Shinoda, H and Ozawa, Y and Negishi, K}, title = {Long-term visual outcomes and development of retinal pigment epithelial and outer retinal atrophy in neovascular age-related macular degeneration: a comparison of conventional and novel classifications.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42675470}, issn = {1471-2415}, support = {23K15938 and 25K12855//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; *Visual Acuity/physiology ; Female ; Tomography, Optical Coherence/methods ; Male ; Atrophy ; Aged ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/drug therapy/classification/physiopathology/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Retrospective Studies ; Intravitreal Injections ; Polypoidal Choroidal Vasculopathy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Photoreceptor Cell Outer Segment/pathology ; }, abstract = {BACKGROUND: Retinal pigment epithelial and outer retinal atrophy (RORA) and complete RORA (cRORA) are major determinants of long-term vision in neovascular age-related macular degeneration (nAMD), but their development across subtypes is poorly defined, especially in Asian populations, in whom pachychoroid-driven disease is common. We compared long-term visual outcomes and atrophy burden between the conventional and novel nAMD classifications.<br><br>METHODS: One hundred twenty eyes of 120 treatment-na&#xef;ve patients with nAMD followed at least six years were classified by conventional (typical nAMD [tAMD], polypoidal choroidal vasculopathy [PCV], retinal angiomatous proliferation [RAP]) and novel (drusen type, pachychoroid type, mixed type, other type) schemes. All eyes received three loading anti-VEGF injections followed by a pro re nata regimen. RORA within the central 1&#xa0;mm was graded on optical coherence tomography; lesions&#x2009;&#x2265;&#x2009;250&#xa0;&#x3bc;m were defined as cRORA. Visual acuity (VA) retention, atrophy prevalence, and VA around atrophy onset were assessed.<br><br>RESULTS: Mean age was 78.0&#x2009;&#xb1;&#x2009;9.2 years and overall VA retention was 71%. VA retention did not differ among conventional subtypes, but under the novel classification was significantly lower in the drusen type and higher in the pachychoroid type (P&#x2009;<&#x2009;0.01). VA declined significantly after both RORA and cRORA onset (both P&#x2009;<&#x2009;0.001). Final RORA/cRORA prevalence was 44.4%/29.6% in tAMD, 50.0%/28.3% in PCV, 83.3%/50.0% in RAP and 76.9%/61.5% in the drusen type, in which cRORA was highest (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: The novel classification distinguished long-term visual outcomes that the conventional classification did not: the drusen type showed the poorest VA retention and highest cRORA prevalence, whereas the pachychoroid type fared best.}, }
@article {pmid42667403, year = {2026}, author = {Hasegawa, T and Yagi, R and Fujita, H and Nishimaki, R and Asami, H and Orio, Y and Hiranuma, Y and Saima, Y and Taguchi, R and Tanaka, Y and Kaburaki, T and Kakehashi, A and Nakagawa, S}, title = {Bilateral choroidal thinning during unilateral aflibercept for neovascular age-related macular degeneration: 5-year mixed-effects analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42667403}, issn = {1435-702X}, support = {24K12750//Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS)/ ; 25K12854//Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS)/ ; }, abstract = {PURPOSE: To evaluate 5-year choroidal changes in eyes with unilateral neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVA) and to compare longitudinal changes among treated, fellow untreated, and control eyes using mixed-effects modeling.<br><br>METHODS: Sixteen patients with unilateral nAMD (16 treated and 16 fellow untreated eyes) and 20 age-matched and sex-matched control eyes were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), central choroidal thickness (CCT), and choroidal vascularity index (CVI) were assessed. Absolute and proportional CCT changes were analyzed. Annual rates of change were estimated using linear mixed-effects models.<br><br>RESULTS: Over 5 years, control eyes showed mild age-related choroidal thinning (-&#x2009;3.7&#xa0;&#x3bc;m/year). In contrast, CCT declined significantly faster in treated eyes (-&#x2009;11.5&#xa0;&#x3bc;m/year; p&#x2009;<&#x2009;0.01 vs. control); fellow untreated eyes also demonstrated accelerated thinning (-&#x2009;8.2&#xa0;&#x3bc;m/year; p&#x2009;<&#x2009;0.05 vs. control). Proportional analyses showed a similar graded pattern. BCVA worsened and CST decreased in treated eyes, while remaining stable in fellow eyes. CVI increased modestly and similarly in treated and fellow eyes (approximately&#x2009;+&#x2009;0.8%/year).<br><br>CONCLUSION: In this 5-year three-group longitudinal analysis, treated eyes showed the greatest annual reduction in CCT, fellow untreated eyes showed an intermediate reduction, and age-matched control eyes showed the smallest decline. The inclusion of a control group indicated that fellow-eye thinning exceeded that expected from physiological aging alone, supporting bilateral choroidal change during long-term unilateral IVA therapy.}, }
@article {pmid42668221, year = {2026}, author = {Holt, C and Neidert, C and Gedtal, M and Virgili, G and Hogg, R and Qureshi, R}, title = {Corrigendum to "Prognostic factors for age-related macular degeneration progression: An overview of systematic reviews" [Surv Ophthalmol 71(3) (2025): 759-773].}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.08.010}, pmid = {42668221}, issn = {1879-3304}, }
@article {pmid42668661, year = {2026}, author = {Beqiri, S and Herrera, G and Shen, M and Berni, A and El-Mulki, OS and Badla, O and Lam, W and Herrera, E and Ascioti, N and Moxam, J and Shuldiner, S and Boopathiraj, N and Cheng, Y and Le, VH and Trivizki, O and O'Brien, RC and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Symmetry in the Enlargement Rates of Large Hypertransmission Defects between Eyes in Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {10}, pages = {101333}, pmid = {42668661}, issn = {2666-9145}, abstract = {PURPOSE: The symmetry of macular atrophy growth rates between eyes of patients with bilateral nonexudative age-related macular degeneration (AMD) was assessed to determine if both eyes could be used in clinical trials to test therapies that might slow the growth of atrophy.<br><br>DESIGN: Retrospective review of prospectively collected swept-source OCT angiography images.<br><br>SUBJECTS: Patients with bilateral nonexudative AMD with &#x2265;1 large hypertransmission defect (hyperTD) in both eyes were included.<br><br>METHODS: All large hyperTDs, defined by a greatest linear dimension &#x2265;250 &#x3bc;m, were identified by 2 independent graders and annotated using a semiautomated algorithm. Growth rates were assessed using the area, square root (sqrt) area, and the perimeter-adjusted growth-rate strategies. Baseline lesion sizes were stratified using a size breakpoint of 0.9 disc area (DA). Intereye comparisons of annual hyperTD growth rates were performed. Power analyses were calculated to determine the sample sizes needed for different clinical trial designs.<br><br>MAIN OUTCOME MEASURES: Intereye concordance of growth rates was evaluated using Lin concordance correlation coefficients, and inter eye growth-rate agreement was evaluated using Bland-Altman analyses. Sample sizes for a 2-arm clinical trial design were calculated to detect a 30% reduction in growth rates in the treatment arm with 80% power and a 2-sided &#x3b1; = 0.05.<br><br>RESULTS: Sixty-four subjects (128 eyes) were followed for a mean of 4.2 &#xb1; 1.9 years, providing 942 annualized growth-rate intervals. Prior to stratification by baseline size of 0.9 DA, intereye concordance was high (rc = 0.76) for the total area growth rate, but lower for the sqrt and perimeter-adjusted growth rates (rc = 0.51, rc = 0.60, respectively). Upon stratification, lesions <0.9 DA showed low correlation (0.39-0.46) across the 3 growth rates, but lesions &#x2265;0.9 DA showed high correlation regardless of the transformation strategy (0.73-0.78).<br><br>CONCLUSIONS: High intereye concordance in hyperTD growth rates was observed for lesions &#x2265;0.9 DA using 3 different growth-rate strategies. Regardless of the growth-rate strategy used, recruitment of fellow eyes in a paired-eye study for localized treatments or both eyes for systemic treatments resulted in a marked reduction in sample sizes, with improved clinical trial efficiency.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42668898, year = {2026}, author = {Kurzawa-Akanbi, M and Haggarty, J and Hansohn, C and Patel, MT and Cree, AJ and Teo, P and Armstrong, M and Coles, N and Platt, M and Griffiths, H and Cordell, HJ and Khundakar, A and Goldberg Oppenheimer, P and Whitfield, P and Lotery, A and Urlaub, H and Mozaffari-Jovin, S and Lako, M}, title = {Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.}, journal = {Journal of extracellular biology}, volume = {5}, number = {9}, pages = {e70178}, pmid = {42668898}, issn = {2768-2811}, abstract = {Vision impairment caused by age-related macular degeneration (AMD) is a global health priority. Retinal pathology is driven by ageing and exacerbated by genetic and environmental risk factors. Peripheral blood circulation is increasingly recognised as a contributor to disease initiation and progression, and a source of biomarkers to support earlier diagnosis and personalised treatment strategies. Here, we performed an analysis of plasma-derived extracellular vesicle (EV)-enriched samples from 30 AMD and 30 controls. Proteomics identified significantly altered proteins in AMD, the majority of which were downregulated with a strong interaction network involving complement proteins and endopeptidase inhibitors. Importantly, many of the altered proteins are known AMD biomarker candidates and act in pathways affecting AMD: oxidative stress response, immune function and proteolysis dysregulation. Lipidomics revealed an increase in total sphingomyelin to ceramide ratio in AMD, indicating lipid metabolism defects. Raman spectroscopy complemented these findings by demonstrating protein and lipid oxidative modifications, alongside compositional abnormalities in AMD samples. Thus, AMD plasma EV-enriched samples carry a systemic signature of complement and coagulation dysregulation, impaired redox homeostasis, and altered sphingolipid metabolism, reflecting established mechanisms of AMD retinal pathology. These AMD-associated biochemical profiles form a promising source for developing new diagnostics and mechanistic insights for precision medicine.}, }
@article {pmid42669558, year = {2026}, author = {Pavlenko, TA and Chesnokova, NB and Lisovskaya, OA and Beznos, OV and Grigoryev, AV}, title = {Neuroprotective Effect of Subconjunctival Melatonin Injections in 6-Hydroxydopamine-Induced Neurotoxic Eye Damage.}, journal = {Biochemistry. Biokhimiia}, volume = {91}, number = {8}, pages = {1396-1405}, doi = {10.1134/S0006297925603880}, pmid = {42669558}, issn = {1608-3040}, mesh = {Animals ; *Melatonin/administration &amp; dosage/pharmacology/therapeutic use ; Rabbits ; *Neuroprotective Agents/administration &amp; dosage/pharmacology ; *Oxidopamine/toxicity ; Matrix Metalloproteinase 9/metabolism ; Male ; Retina/drug effects/metabolism/pathology ; Vitreous Body/metabolism/drug effects ; alpha-Macroglobulins/metabolism ; Intraocular Pressure/drug effects ; }, abstract = {The search for new effective methods of neuroprotection is relevant for the treatment of a wide range of common eye diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy. Using a rabbit model of neurotoxic eye damage induced by intravitreal injection of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), we studied the effect of subconjunctival injections of 0.1% melatonin solution on pathophysiological and biochemical processes in the eye. Administration of 6-OHDA caused destruction of the retinal pigment epithelium, narrowing of retinal vessels, hemorrhages, decrease in ocular blood flow, and intraocular pressure, as well as reduced activity of α2-macroglobulin and concentrations of matrix metalloproteinase-9 and angiotensin-converting enzyme in the aqueous humor, vitreous body, and retina. Subconjunctival melatonin injections over 9 days resulted in the 2-fold on average reduction of the area of retinal damage, and normalization of the minute volume of ocular blood flow and intraocular pressure. On day 14, an increase in the α2-macroglobulin activity in the aqueous humor (0.66 ± 0.19 vs. 0.49 ± 0.13 nmol/min per 1 mg protein) and vitreous body (0.50 ± 0.15 vs. 0.21 ± 0.07 nmol/min per 1 mg protein, p < 0.05) was observed, along with a decrease in the matrix metalloproteinase-9 concentration (118.4 ± 34.6 vs. 524.3 ± 163.2 ng/mg, p < 0.05) and angiotensin-converting enzyme concentration (371.0 ± 52.1 vs. 596.1 ± 171.5 ng/mg, p < 0.05) in the retina. This indicates reduction in the intensity of inflammation and vascular wall permeability. Melatonin could be considered a promising neuroprotective component in the complex therapy of retinal diseases.}, }
@article {pmid42656493, year = {2026}, author = {Mukwaya, A and Yin, Z and Yarcusko, R and Baldwin, G and Uddin, N and Venkat, H and Xue, Y and Van Arnam, NS and Kam, HT and Chen, DF and Krasemann, S and Lennikov, A and Margeta, MA}, title = {Assessing microglial phagocytosis of apoptotic neurons in vitro: a multimodal approach.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1813556}, pmid = {42656493}, issn = {1662-4548}, support = {R01 EY035312/EY/NEI NIH HHS/United States ; }, abstract = {Microglia are the resident immune cells of the central nervous system, responsible for defending against infections, responding to tissue damage, and maintaining homeostasis. Dysregulation of their phagocytic activity has been implicated in many neurodegenerative diseases of the brain and the eye, including Alzheimer's disease, multiple sclerosis, glaucoma, and age-related macular degeneration. Past work has shown that brain and retinal microglia switch to a disease-associated molecular phenotype (DAM) following phagocytosis of apoptotic neurons in vivo, but it is technically challenging to perform these assessments and isolate phagocytic cells for downstream analysis. Although several protocols exist for isolating and culturing microglia to evaluate their phagocytic activity in vitro, these approaches often fail to mimic the pathophysiology of neurodegeneration, where dysregulated phagocytosis of damaged or apoptotic neurons is a key feature. Here we describe a protocol for evaluating phosphatidylserine-mediated phagocytosis by primary mouse brain microglia in vitro. The procedure involves isolating primary mouse brain microglia, inducing apoptosis in a feeder neuronal cell line, labeling apoptotic cells with a fluorescent dye, feeding the labeled cells to the microglia, and analyzing phagocytosis using several complementary approaches. This protocol enables an accessible and high-throughput assessment of microglial phagocytic activity using a biologically relevant stimulus, offering improved insights into the regulation of this critical immune process in a disease-relevant context.}, }
@article {pmid42657322, year = {2026}, author = {Shen, LL and Bao, Y and Ying, GS and Keenan, TDL and Chew, EY and Vajzovic, L and Stewart, JM and Del Priore, LV}, title = {A Novel Pixel-Based Spatial Modeling Framework for Mapping At-Risk Retina in Geographic Atrophy Progression.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101330}, pmid = {42657322}, issn = {2666-9145}, support = {P30 EY002162/EY/NEI NIH HHS/United States ; P30 EY026878/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To develop a Pixel-based At-risk Retina Mapping (PARM) framework quantifying local geographic atrophy (GA) progression in nonexudative age-related macular degeneration and evaluate its predictive performance and statistical efficiency relative to conventional area-based measures.<br><br>DESIGN: Secondary analysis of a multicenter randomized controlled trial.<br><br>PARTICIPANTS: Eyes with GA from the Age-Related Eye Disease Study.<br><br>METHODS: Annual color fundus photographs were manually segmented, registered, and converted into 10-&#x3bc;m pixel grids. The perilesional "at-risk" zone was empirically defined as pixels with &#x2265;5% 1-year GA conversion probability. Within this zone, 1-year GA pixel involvement was modeled using a generalized additive model with random effects for eye and participant. Predictors included pixel-level measures (distances to GA border and foveal center) and 9 eye-level factors. Prediction accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Simulation-based power analyses compared sample size requirements between the PARM framework and conventional area-based measures for detecting a 30% treatment effect (odds ratio 0.70 for pixel conversion) at 80% power (2-sided &#x3b1; = 0.05).<br><br>MAIN OUTCOME MEASURES: One-year GA pixel involvement.<br><br>RESULTS: We included 239 eyes from 161 participants. Pixels within 500 &#x3bc;m of the GA border had &#x2265;5% 1-year conversion risk, defining the "at-risk" region. Shorter distance to the GA border and greater distance from the foveal center were independently associated with a higher 1-year risk of GA pixel involvement (P < 0.001); 9 eye-level factors did not improve model fit. The pixel-based model achieved an AUC of 0.875 (95% confidence interval [CI], 0.865-0.887), outperforming the eye-level model (AUC = 0.750, 95% CI, 0.740-0.768). Detecting a 30% treatment effect required 30 eyes per arm using the PARM framework, compared with 140 eyes for square-root-transformed area and 310 eyes for total GA area.<br><br>CONCLUSIONS: Pixel-based spatial modeling of GA progression within a 500-&#x3bc;m perilesional at-risk zone showed stronger predictive performance than conventional eye-level modeling and improved statistical efficiency relative to area-based measures in internal simulations by leveraging pixel-level distances to the GA border and foveal center. These findings support further evaluation of PARM framework for studying GA progression, with external validation required before clinical-trial implementation.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42658802, year = {2026}, author = {Kim, MS and Nam, S and Lee, J and Woo, SJ}, title = {Risk of intraocular hemorrhage among exudative age-related macular degeneration patients treated with different anti-VEGF agents.}, journal = {PloS one}, volume = {21}, number = {8}, pages = {e0356596}, pmid = {42658802}, issn = {1932-6203}, mesh = {Humans ; Male ; Female ; Ranibizumab/adverse effects/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Recombinant Fusion Proteins/adverse effects/therapeutic use ; Aged ; *Macular Degeneration/drug therapy/complications ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Eye Hemorrhage/epidemiology/chemically induced/etiology ; Middle Aged ; Risk Factors ; Aged, 80 and over ; Vitrectomy ; Republic of Korea/epidemiology ; Proportional Hazards Models ; Intravitreal Injections ; }, abstract = {BACKGROUND: Intraocular hemorrhage is a vision-threatening complication in patients with exudative age-related macular degeneration (AMD) receiving intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We aimed to compare the risk of intraocular hemorrhage requiring vitrectomy among patients with exudative AMD treated with ranibizumab, aflibercept, or brolucizumab.<br><br>METHODS AND FINDINGS: This nationwide retrospective cohort study used claims data from the Korean National Health Insurance Review and Assessment Service (May 2014-April 2023). Korean patients aged 40 years or older with newly diagnosed exudative AMD who initiated anti-VEGF therapy and had no history of intraocular hemorrhage were included. The primary outcome was intraocular hemorrhage requiring vitrectomy after anti-VEGF initiation. Time-to-event analyses using Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs; Kaplan-Meier curves showed cumulative incidence probability, and logistic regression provided complementary risk estimates. Among 75,812 patients, 1,128 (1.5%) experienced intraocular hemorrhage requiring vitrectomy. Compared with ranibizumab, the adjusted risk was higher with brolucizumab (HR, 1.83; 95% CI, 1.18-2.83; P&#x2009;=&#x2009;.007) and aflibercept (HR, 1.31; 95% CI, 1.14-1.49; P&#x2009;<&#x2009;.001). Logistic regression similarly showed higher odds with aflibercept versus ranibizumab (adjusted odds ratio, 1.32; 95% CI, 1.16-1.51; P&#x2009;<&#x2009;.001). Patients with hemorrhage received fewer anti-VEGF injections in the first year than those without hemorrhage (3.15&#x2009;&#xb1;&#x2009;1.87 vs 4.01&#x2009;&#xb1;&#x2009;1.85; P&#x2009;<&#x2009;.001).<br><br>CONCLUSION: In this large nationwide cohort, intraocular hemorrhage requiring vitrectomy after anti-VEGF therapy for exudative AMD was rare but occurred more frequently with brolucizumab and aflibercept than with ranibizumab. Although unlikely to be the primary determinant of anti-VEGF selection, these findings provide adjunctive safety information that may be considered when counseling and monitoring selected patients.}, }
@article {pmid42665201, year = {2026}, author = {Dhoot, DS and Singerman, LJ and Ferrone, PJ and Wykoff, CC and Goldberg, RA and Guymer, RH and Kim, EL and MacCumber, MW and Maia, A and Yu, S and Yemanyi, F and Coughlin, BA and Baumal, CR and Holz, FG and , }, title = {Early Versus Delayed Pegcetacoplan Treatment for Geographic Atrophy Secondary to Age-Related Macular Degeneration in OAKS, DERBY, and GALE.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.08.028}, pmid = {42665201}, issn = {1879-1891}, abstract = {PURPOSE: To report the efficacy of early versus delayed pegcetacoplan treatment in eyes with geographic atrophy (GA) secondary to age-related macular degeneration as well as the 48-month safety profile of pegcetacoplan.<br><br>DESIGN: Efficacy and safety data from the phase 3 GALE open-label extension (OLE) of the phase 3 OAKS and DERBY studies, representing up to 48 months of continuous pegcetacoplan treatment, were analyzed.<br><br>PARTICIPANTS: Eyes with nonsubfoveal or subfoveal GA receiving pegcetacoplan in OAKS and DERBY continued receiving pegcetacoplan at the same dosing regimen in GALE, and sham-observed eyes with nonsubfoveal or subfoveal GA in OAKS and DERBY crossed over to active treatment in GALE at the same dosing interval in those studies.<br><br>METHODS: The overall population included eyes with nonsubfoveal GA and eyes with subfoveal GA. Subgroup analyses were performed on data from eyes with nonsubfoveal GA and eyes with subfoveal GA. The early treatment group comprised eyes receiving pegcetacoplan for 48 months across the OAKS, DERBY, and GALE studies. The delayed treatment group included sham-observed eyes from OAKS and DERBY which crossed over at 24 months to receive pegcetacoplan treatment for 24 months in the GALE OLE.<br><br>MAIN OUTCOME MEASURES: GA area growth rate, amount of retinal tissue preserved, risk of progression to absolute scotoma, and safety.<br><br>RESULTS: In the overall population, 48 continuous months of pegcetacoplan treatment reduced GA area growth rate by up to 24% compared with projected sham, translating to 1.88 mm[2] of retinal tissue. Approximately three times more retinal tissue (up to 3.16 mm[2] with monthly treatment) was preserved in eyes with nonsubfoveal GA in the early treatment group compared with eyes in the nonsubfoveal GA delayed treatment group (1.11 mm[2]). Reduced risk of progression to absolute scotoma of all central 4 and 16 loci (32% and 43%, respectively) was observed in the overall population. GALE safety data were consistent with the findings of the OAKS and DERBY studies.<br><br>CONCLUSIONS: Pegcetacoplan demonstrated effectiveness in slowing GA progression and consistent safety over 48 months. Long-term anatomic and functional outcomes support the importance of early treatment to maximize the preservation of retinal tissue and function.}, }
@article {pmid42666667, year = {2026}, author = {Katan, M and Mróz, K and Pacwa, A and Lewin-Kowalik, J and Smędowski, A}, title = {Gap junction protein connexin 36 proteostatic mechanisms in photoreceptor cells subjected to excitotoxic stress.}, journal = {Acta biochimica Polonica}, volume = {73}, number = {}, pages = {16091}, pmid = {42666667}, issn = {1734-154X}, mesh = {Animals ; *Connexins/metabolism/genetics ; Mice ; Gap Junction delta-2 Protein ; Macrolides/pharmacology ; *N-Methylaspartate/pharmacology ; Proteasome Endopeptidase Complex/metabolism ; Proteotoxic Stress ; *Photoreceptor Cells, Vertebrate/metabolism/drug effects ; Cell Line ; Autophagy/drug effects ; }, abstract = {Connexin 36 (Cx36), a neuronal gap junction protein, is essential for retinal signal transmission but may also contribute to neurodegeneration by facilitating the spread of excitotoxic stress signals. This study aimed to examine the degradation pathway of Cx36 under stress conditions relevant to retinal disease. Using immortalized 661W murine photoreceptor cells transfected with GFP-tagged Cx36, we evaluated the effects of lysosomal inhibition (Bafilomycin A1) and excitotoxic stimulation (NMDA). Immunofluorescence revealed intracellular Cx36 accumulation following Bafilomycin and NMDA exposure, accompanied by increased expression of p62/SQSTM1 and PSMA1, suggesting impaired autophagic flux and a potential compensatory involvement of the proteasome. Elevated RAB11A levels suggested recruitment of endosomal recycling pathways. NMDA treatment was associated with increased ubiquitin accumulation, particularly in Cx36-overexpressing cells, indicating enhanced proteostatic stress under excitotoxic conditions. These findings highlight the stress-responsive behavior of Cx36 and suggest that connexin proteostasis may represent a potential target for future investigation in retinal neurodegeneration, including glaucoma and age-related macular degeneration. Immunofluorescence revealed intracellular accumulation of p62 and PSMA1 after Bafilomycin exposure with signal intensities increasing approximately 1.5-2-fold versus controls (n = 3, p < 0.05). These data are consistent with disrupted autophagic flux and suggest proteasome involvement, but do not constitute functional proof.}, }
@article {pmid42654271, year = {2026}, author = {Pieńczykowska, K and Bryl, A and Mrugacz, M}, title = {Obesity and Eye Diseases.}, journal = {Nutrients}, volume = {18}, number = {16}, pages = {}, pmid = {42654271}, issn = {2072-6643}, mesh = {Humans ; *Obesity/complications ; *Eye Diseases/etiology/epidemiology ; Risk Factors ; Macular Degeneration/etiology ; }, abstract = {Background: Obesity has become a major global public health challenge, affecting individuals across all age groups and contributing to a wide range of systemic disorders. Beyond its well-established associations with cardiovascular and metabolic diseases, obesity is increasingly recognized as a chronic inflammatory condition that influences the structure and function of multiple organs, including the eye. Methods: A comprehensive literature review was conducted between November 2025 and June 2026 using PubMed, Web of Science, and Google Scholar. Priority was given to recent studies evaluating the impact of obesity and obesity-related metabolic disturbances on ocular health. Results: Available evidence indicates that obesity is associated with an increased risk of several ophthalmic conditions, including age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, and retinal vein occlusion. Multiple anthropometric measures of adiposity have been positively associated with diabetic retinopathy risk. Although findings regarding glaucoma remain heterogeneous, metabolic syndrome and its components, particularly impaired glucose metabolism, appear to increase glaucoma susceptibility. Obesity has also been linked to dry eye disease through inflammatory and tear film alterations. Conclusions: Obesity exerts significant effects on ocular health through complex metabolic, inflammatory, and vascular pathways. Recognition of obesity as a modifiable risk factor for eye disease may facilitate earlier detection, targeted prevention strategies, and improved multidisciplinary management. Further longitudinal and mechanistic studies are needed to clarify causal relationships and determine whether effective obesity treatment can reduce the burden of vision-threatening ocular disorders.}, }
@article {pmid42655080, year = {2026}, author = {Gündüz, A and Ekici Gök, Z and Evren, &#xd6;}, title = {Effects of Intravitreal Anti-VEGF Therapy on Conjunctival Flora and Antibiotic Resistance in Age-Related Macular Degeneration.}, journal = {Microorganisms}, volume = {14}, number = {8}, pages = {}, pmid = {42655080}, issn = {2076-2607}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment among older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are widely used for neovascular AMD; however, their potential effects on the conjunctival microbiota remain poorly understood. This study evaluated the impact of intravitreal anti-VEGF therapy on conjunctival microbial composition and antimicrobial resistance patterns.<br><br>MATERIALS AND METHODS: Ninety patients with AMD were enrolled and assigned to three groups: bevacizumab-treated (n = 30), aflibercept-treated (n = 30), and untreated dry-type AMD controls (n = 30). Conjunctival swab samples were collected two months after the last injection in treated patients and during routine examination in controls. Bacterial identification and antimicrobial susceptibility testing were performed using automated microbiological systems.<br><br>RESULTS: Culture positivity rates were comparable among groups, although a lower growth rate was observed in the bevacizumab group (83.3%) than in the aflibercept and control groups (100% each). Staphylococcus epidermidis was significantly more prevalent in both treatment groups than in controls (p = 0.014). Most other bacterial species were detected more frequently in controls. Levofloxacin resistance among staphylococcal isolates was significantly higher in the aflibercept group (p = 0.007), whereas erythromycin and fusidic acid resistance were significantly higher in controls (p = 0.040 and p = 0.001, respectively). Resistance in treated eyes was predominantly associated with S. epidermidis and S. hominis.<br><br>CONCLUSIONS: Intravitreal anti-VEGF therapy may be associated with transient alterations in conjunctival microbiota composition and antimicrobial resistance patterns. These findings may have implications for infection prevention in patients undergoing repeated intravitreal injections.}, }
@article {pmid42656281, year = {2026}, author = {Chun, JM and Choy, S and Seok, JW and Kim, JD and Park, SR}, title = {Photobiomodulation in animal models of ophthalmic disease: protocol for systematic review and meta-analysis of morphological, visual function, and inflammatory outcomes.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1904150}, pmid = {42656281}, issn = {2296-858X}, abstract = {BACKGROUND: Despite accumulating preclinical evidence supporting the therapeutic efficacy of photobiomodulation (PBM) in ophthalmic disease models, the systematic evaluation and quantitative synthesis of these findings remain underexplored. This protocol aims to comprehensively synthesize existing studies by categorizing outcome measures into morphological, visual, and inflammatory domains according to ophthalmic pathology. The primary objective of this study is to evaluate the therapeutic efficacy of PBM for ophthalmic diseases and to consolidate the current body of preclinical evidence.<br><br>METHODS: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines. We will include controlled preclinical studies using animal models of four predefined ophthalmic conditions: age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and corneal injury. A systematic search will be conducted across relevant electronic databases without restrictions on publication date. Outcomes will be categorized into three domains, morphological, visual functional, and inflammatory, to evaluate the efficacy of PBM in ophthalmic diseases. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment using the SYRCLE tool. Where appropriate, meta-analyses will be conducted using random-effects models, with heterogeneity assessed using I[2] statistics. Subgroup and sensitivity analyses will be performed to explore sources of variability.<br><br>DISCUSSION: This systematic review aims to integrate and assess the quality of current evidence regarding PBM's efficacy across morphological, visual functional, and inflammatory outcomes. Findings will contribute to future trial designs and support the development of standardized protocols for PBM applications in ophthalmology.<br><br>https://www.crd.york.ac.uk/PROSPERO/view/CRD420251054002, PROSPERO CRD420251054002.}, }
@article {pmid42654113, year = {2026}, author = {Ma, Z and Zhang, D and Chen, X and Zhang, F}, title = {Kaempferol's Therapeutic Applications and Mechanistic Insights in Ocular Diseases: Current Progress, Challenges, and Translational Opportunities.}, journal = {Pharmaceutics}, volume = {18}, number = {8}, pages = {}, pmid = {42654113}, issn = {1999-4923}, abstract = {Kaempferol is a natural flavonol compound widely present in various single-herb remedies and compound formulations used for the treatment of ocular diseases. Despite its inherent pharmaceutical limitations, accumulating evidence indicates that kaempferol exerts broad protective effects against diverse ocular disorders through multiple biological pathways, highlighting its potential as a multi-target therapeutic candidate in ophthalmology. However, current evidence regarding kaempferol-based ophthalmic applications remains fragmented across different ocular diseases and mechanistic investigations, and a comprehensive evaluation of its therapeutic potential, translational challenges, and existing limitations is still lacking. This review systematically summarizes the research progress on kaempferol in the treatment of eye diseases, encompassing its source distribution, structural characteristics, ocular delivery strategies, disease spectrum coverage, molecular mechanisms, and safety profile. By critically evaluating currently available evidence, this review further identifies unresolved issues and translational barriers that hinder the clinical application of kaempferol in ophthalmology. Regarding delivery strategies, carriers such as gelatin nanoparticles, porous bovine serum albumin membranes, platelet-derived extracellular vesicles, and polyvinylpyrrolidone-based nanocomposites have preliminarily improved ocular surface retention and corneal permeability of kaempferol in models of corneal neovascularization and alkali burns. In terms of therapeutic indications, kaempferol has demonstrated protective effects in diverse experimental models, including age-related macular degeneration (AMD), diabetic retinopathy, diabetic cataract, dry eye disease, fungal keratitis, corneal transplant rejection, acute glaucoma, and retinoblastoma. At the mechanistic level, kaempferol exerts comprehensive pharmacological actions-anti-inflammatory, antioxidant, metabolic regulation, anti-angiogenic, and immunomodulatory-by modulating multiple signaling pathways, including MAPK, NF-κB, STAT1/IRF7, Nrf2/HO-1, VEGF/PI3K/Src/Akt/ERK, aldose reductase, estrogen-related receptor alpha (ERRα), and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Available safety assessments suggest that kaempferol exhibits a generally favorable safety profile across ocular, cellular, systemic, and genetic evaluations. Despite these advances, the clinical translation of kaempferol in ophthalmology remains limited by insufficient clinical and pharmacokinetic evidence, underdeveloped targeted delivery strategies, and a lack of integrated understanding of its molecular basis in ocular protection. By systematically integrating evidence from ocular disease models, molecular mechanisms, delivery strategies, and safety evaluations, this review bridges fragmented knowledge regarding kaempferol-based ophthalmic applications and provides an integrated framework for understanding its therapeutic potential and translational prospects. Overall, this review highlights kaempferol as a promising multi-target therapeutic candidate for ocular diseases and provides insights into its future translational development.}, }
@article {pmid42642015, year = {2026}, author = {Chen, X and Han, M and An, Y and Zhang, S and Liu, M and Wang, Y and Zhao, S and Wang, Z and Zhang, Y}, title = {Epigallocatechin gallate protects ARPE-19 cells in vitro and the retina in vivo by suppressing NF-κB p65-mediated ferroptosis.}, journal = {Experimental eye research}, volume = {272}, number = {}, pages = {111214}, doi = {10.1016/j.exer.2026.111214}, pmid = {42642015}, issn = {1096-0007}, abstract = {The accumulation of ferrous ions and resulting oxidative stress within the retinal pigment epithelium triggers ferroptosis, leading to photoreceptor degeneration in dry age-related macular degeneration (dAMD), which is a disease currently without effective therapy. As ferroptosis has been identified as a molecular target of epigallocatechin-3-gallate (EGCG) in other diseases, this study aimed to investigate the protective role of EGCG and its mechanism against ferroptosis in NaIO3-induced ARPE-19 cell and RPE injury. We observed that iron overload disrupts iron homeostasis in both cellular and animal models, leading to RPE damage via ferroptosis activation. In ARPE-19 cells, EGCG attenuated NaIO3-induced injury by reducing Fe[2+], MDA, and LDH levels, increasing GSH content, and upregulating SLC7A11 and GPX4 expression, effects which were equivalent to those produced by Fer-1. Mechanistically, EGCG exerted its anti-ferroptotic effect by binding strongly to NF-κB p65 and inhibiting its activation, consistent with the effects of the NF-κB inhibitor QNZ and NF-κB p65 silencing. In a dAMD model, EGCG administration suppressed ferroptosis, downregulated NF-κB p65 expression, and ameliorated RPE damage. In conclusion, these findings suggest that EGCG alleviates RPE damage associated with NF-κB p65-mediated ferroptosis, providing new insights into AMD pathogenesis and a promising therapeutic strategy.}, }
@article {pmid42642221, year = {2026}, author = {Jiang, Y and Cheong, KX and Hu, Z and Foo, LL and Zhou, Y and Tang, X and Pan, W and Chen, Z and Saw, SM and Hoang, QV and Yang, Z and Lan, W}, title = {Association between retinal/choroidal vascularity and macular sensitivity in myopic macular degeneration: Aier-SERI high myopia adult cohort study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328323}, pmid = {42642221}, issn = {1468-2079}, abstract = {PURPOSE: To investigate the associations between retinal/choroidal vascular parameters and macular sensitivity (MS) in adults with myopic macular degeneration (MMD).<br><br>METHODS: This cross-sectional study included a total of 439 eyes from 253 participants of the Aier-SERI high myopia cohort in Changsha, central China. MS was evaluated using the microperimetry (MP-3). Retinal and choroidal vascular parameters, including superficial vascular density (SVD), deep vascular density (DVD), choriocapillaris perfusion area (CCPA) and choroidal vascularity index (CVI), were quantified using swept-source optical coherence tomography angiography (SS-OCTA). Differences in MS across MMD severity categories were analysed via one-way analysis of variance, and relationships between retinal/choroidal vascular parameters and MS were evaluated using multivariable linear regression models with generalised estimating equations to account for inter-eye correlations.<br><br>RESULTS: Participants had an average age of 44.6&#xb1;6.6 years with a mean spherical equivalent (SE) of -9.1&#xb1;4.1 D and axial length (AL) of 27.2&#xb1;1.8&#x2009;mm. MS, SVD, DVD and CVI in different regions decreased with increasing severity of MMD (all P values <0.05), but CCPA not (p>0.05). In multivariate models, factors related to reduced MS included older age (&#x3b2;=-0.074, p=0.007), longer AL (&#x3b2;=-0.388, p<0.001), increasing severity of MMD (&#x3b2;&#x2264;-0.677, all p<0.05), lower SVD (&#x3b2;=0.077, p=0.022), lower DVD (&#x3b2;=0.069, p=0.019) and lower CVI (&#x3b2;=3.083, p=0.015). CVI demonstrated significantly greater discriminatory power for MS impairment compared with SVD and DVD in different regions (all P values <0.05).<br><br>CONCLUSION: Reduced MS is associated with more severe MMD, older age, longer AL, lower SVD, lower DVD and lower CVI. Among retinal/choroidal vascular biomarkers, CVI exhibits superior diagnostic utility for identifying MS impairment in MMD, highlighting the choroid's potential role as a sensitive indicator of visual function.}, }
@article {pmid42642671, year = {2026}, author = {Chang, W}, title = {Early anatomical rescue after switching to aflibercept 8 mg in faricimab-refractory neovascular AMD.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42642671}, issn = {1573-2630}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; *Visual Acuity ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; Male ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Aged ; *Drug Substitution ; Fluorescein Angiography/methods ; Follow-Up Studies ; Treatment Outcome ; Dose-Response Relationship, Drug ; Aged, 80 and over ; Time Factors ; *Macula Lutea/pathology ; Fundus Oculi ; Bridge Therapy ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate early anatomical outcomes after switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) refractory to faricimab.<br><br>METHODS: This retrospective study included 32 eyes of 31 patients with nAMD who were switched from faricimab to aflibercept 8&#xa0;mg due to persistent or recurrent fluid. Main outcome measures included central subfield thickness (CST), best-corrected visual acuity (BCVA), and proportion of eyes achieving fluid-free macula at weeks 8 and 16. Subgroup analyses were performed based on diagnosis (PCV vs non-PCV) and prior treatment history.<br><br>RESULTS: Mean CST decreased significantly from 374.0 &#xb1; 88.3&#xa0;&#x3bc;m at the time of switch to 324.6 &#xb1; 80.6&#xa0;&#x3bc;m at week 8 (p = 0.003) and 321.4 &#xb1; 84.0&#xa0;&#x3bc;m at week 16 (p = 0.002). Fluid-free rate increased from 18.8 to 43.8% at week 8 and 46.9% at week 16. Mean BCVA remained stable throughout. Both PCV (n=12) and non-PCV (n=20) subgroups showed significant CST reduction. Eyes treatment-na&#xef;ve before faricimab and those treatment-experienced before faricimab demonstrated comparable responses. No serious adverse events were observed.<br><br>CONCLUSIONS: Switching to aflibercept 8&#xa0;mg resulted in rapid and significant anatomical improvement in faricimab-refractory nAMD, with most improvement occurring by week 8. The treatment was effective across diagnostic subtypes including PCV and regardless of prior treatment burden. Although early anatomical improvement was observed, the long-term durability of this response remains unknown and warrants further study.}, }
@article {pmid42643214, year = {2026}, author = {Toral, MA and Ng, B and Velez, G and Yang, J and Tsang, SH and Bassuk, AG and Mahajan, VB}, title = {Persistent Cytotoxic Immune Signaling in Anti-VEGF-Treated Neovascular Age-Related Macular Degeneration.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.06.26350115}, pmid = {42643214}, abstract = {PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard of care for neovascular age-related macular degeneration (AMD), yet many patients exhibit persistent retinal degeneration, fibrosis, and incomplete therapeutic response. The molecular pathways underlying this incomplete response remain poorly understood. We sought to identify VEGF-independent signaling pathways active in the vitreous of anti-VEGF-treated AMD patients.<br><br>METHODS: We performed multiplex antibody-based proteomic profiling of 1,000 human proteins in vitreous samples from patients with neovascular AMD receiving anti-VEGF therapy (n=8) and comparative controls (n=6). Differential protein expression was assessed using one-way ANOVA, followed by gene ontology and pathway enrichment analyses. Drug-target relationships were evaluated to identify potential opportunities for therapeutic repositioning.<br><br>RESULTS: We identified 107 differentially expressed proteins (p<0.05), including key regulators of immune signaling, angiogenesis, and metabolism. Notably, multiple components of cytotoxic lymphocyte pathways were dysregulated, including IL-21R, SIGLEC-7, CTLA4, and IL-2-associated signaling. Enrichment analyses revealed significant activation of pathways related to T-cell activation, interleukin signaling, and leukocyte-mediated cytotoxicity. These immune signatures persisted despite suppression of VEGF signaling. Several clinically available immunomodulatory agents-including abatacept, sirolimus, and dupilumab-targeted pathways identified in this dataset.<br><br>CONCLUSIONS: Anti-VEGF-treated neovascular AMD exhibits persistent cytotoxic immune signaling in the vitreous, suggesting that VEGF-independent immune mechanisms may contribute to ongoing retinal damage and incomplete therapeutic response. These findings provide a rationale for combination therapeutic strategies targeting both angiogenic and immune pathways in AMD.}, }
@article {pmid42643435, year = {2026}, author = {Bellanda, V and Bala, S and Castilho S Barbosa, G and Mohan, N and Schulgit, MJ and Babiuch, AS and Yuan, A and Sastry, A and Talcott, KE and McOwen, D and Igrec, F and Srivastava, SK and Sharma, S and Schachat, AP and Mammo, DA}, title = {Initial Impact of Loss of Copay Assistance From a National Nonprofit Fund on Outcomes of Retinal Disease.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261477369}, pmid = {42643435}, issn = {2474-1272}, abstract = {PURPOSE: Many patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or retinal vein occlusion who have lost copay assistance from the DBA Good Days national charity fund have been forced to switch treatment from branded intravitreal antivascular endothelial growth factor (anti-VEGF) therapy to bevacizumab. This study sought to characterize the short-term impact of these changes on clinical outcomes.<br><br>METHODS: This retrospective study included 89 eyes of 69 patients with nAMD, DME, or retinal vein occlusion who transitioned from receiving branded anti-VEGF therapy (aflibercept 2.0 mg or 8.0 mg; faricimab) to bevacizumab. The primary endpoint was changes from baseline in central subfield thickness (CST) after 1, 2, and 3 injections. Secondary endpoints included changes in best-corrected visual acuity (BCVA), intraocular pressure, intraretinal fluid, subretinal fluid, pigment epithelial detachment, injection intervals, predictors of poor outcome (BCVA loss of &#x2265;15 Early Treatment Diabetic Retinopathy Study letters or CST increase of &#x2265;50 &#xb5;m), and switchback to branded therapy.<br><br>RESULTS: From baseline to after the third bevacizumab injection, the CST increased from a mean (&#xb1;SD) 228.7 &#xb1; 52.3 &#xb5;m to 271.3 &#xb1; 40.0 &#xb5;m in the overall cohort (P = .004), and from 224.1 &#xb1; 50.6 &#xb5;m to 268.6 &#xb1; 38.5 &#xb5;m among nAMD eyes (P = .007). The injection interval decreased from a median 8.6 weeks (interquartile range [IQR], 7.0-10.9 weeks) preswitch to 7.5 weeks (IQR, 5.3-9.5 weeks) after 3 injections (P < .001). Fourteen eyes (15.7%) met the criteria for poor outcome, and 15 (16.9%) were switched back to branded therapy. Worsening intraretinal fluid was an early indicator of suboptimal response, and shorter preswitch injection intervals were a predictor of switching back to branded therapy.<br><br>CONCLUSIONS: Switching from branded anti-VEGF therapy to bevacizumab was associated with anatomic worsening and shorter injection intervals. Shorter preswitch intervals and early postswitch intraretinal fluid changes may help identify patients at risk for poor outcomes.}, }
@article {pmid42644681, year = {2026}, author = {El Majdoubi El Idrissi, K and Pastore, MR and Mehanna, CJ and Miere, A and Souied, EH}, title = {Large Pigment Epithelial Detachments Associated With Type 1 Macular Neovascularization: Do Swept-Source OCT Angiography Devices Detect the Same Thing?.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {8}, pages = {25}, doi = {10.1167/tvst.15.8.25}, pmid = {42644681}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/instrumentation/methods ; *Retinal Detachment/diagnostic imaging/diagnosis/etiology ; Prospective Studies ; *Fluorescein Angiography/instrumentation/methods ; Female ; Male ; Aged ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Retinal Neovascularization/diagnostic imaging/complications ; Aged, 80 and over ; Sensitivity and Specificity ; }, abstract = {PURPOSE: Large pigment epithelial detachments (PEDs) compromise automated swept-source optical coherence tomography angiography (SS-OCTA) segmentation, leading to false-negative type 1 macular neovascularization (MNV) in neovascular age-related macular degeneration. We compared the diagnostic sensitivity of two SS-OCTA platforms from different generations to assess whether technological advances offset segmentation limitations.<br><br>METHODS: This was a prospective comparative study of 82 eyes with type 1 MNV and PED height &#x2265; 250&#xa0;&#xb5;m. Each eye underwent dual SS-OCTA imaging with a first-generation 1050-nm (100-kHz) system and a next-generation 1060-nm (400-kHz) system. Two masked readers evaluated automated versus manually adjusted segmentation slabs across PED height categories.<br><br>RESULTS: On the 1050-nm system, detection improved from 22.0% with automated segmentation to 81.7% after manual adjustment (P < 0.001). The 1060-nm system showed higher automated detection (68.3%), with a modest increase to 75.6% after manual segmentation. Stratified analysis showed superior automated performance of the 1060-nm device in shallow PEDs, whereas intermediate PEDs were most challenging for both systems. In very large PEDs, manual segmentation yielded similar detection rates on both devices.<br><br>CONCLUSIONS: Detection of type 1 MNV beneath large PEDs is significantly device dependent. Although next-generation SS-OCTA systems improve automated detection, manual segmentation remains crucial for optimal sensitivity and accuracy. Device-specific protocols integrating routine manual review are warranted to avoid false-negative findings and treatment delays.<br><br>TRANSLATIONAL RELEVANCE: Manual segmentation remains essential to prevent false-negative detection of type 1 MNV beneath large PEDs, even with next-generation SS-OCTA devices. This has direct implications for diagnostic protocols and treatment decisions in nAMD.}, }
@article {pmid42648703, year = {2026}, author = {Huang, RS and Naidu, SC and Mihalache, A and Xie, JS and Popovic, MM and Kertes, PJ and Sarraf, D and Sadda, SR and Muni, RH and Kohly, RP}, title = {Predictors of loss to follow-up in neovascular age-related macular degeneration.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.08.006}, pmid = {42648703}, issn = {1715-3360}, abstract = {OBJECTIVE: To investigate the demographic, clinical, and treatment-related risk factors associated with being lost to follow-up (LTFU) among patients with neovascular age-related macular degeneration (nAMD) receiving antivascular endothelial growth factor (anti-VEGF) intravitreal injections (IVIs).<br><br>METHODS: We conducted a multicentre retrospective cohort study of patients with nAMD treated with anti-VEGF IVIs in Toronto, Ontario, from January 2012 to December 2021. LTFU was defined as the absence of an ophthalmic visit within 1 year of the last retinal specialist appointment. Univariable and multivariable logistic regression analyses were conducted to examine associations between demographic, clinical, and treatment-related factors and becoming LTFU.<br><br>RESULTS: Among 2556 patients with nAMD, 527 (21%) were LTFU over a mean follow-up of 65.5 &#xb1; 15.2 months. In multivariable analysis, male sex (OR&#x202f;=&#x202f;1.40; p < .001), greater travel distance (>200 km; OR&#x202f;=&#x202f;2.51; p < .001), and multiple systemic comorbidities (&#x2265;3; OR&#x202f;=&#x202f;1.39; p&#x202f;=&#x202f;.01) were associated with higher odds of LTFU. Compared with White patients, Black (OR&#x202f;=&#x202f;2.07; p < .001) and Hispanic patients (OR&#x202f;=&#x202f;1.70; p < .001) had increased odds of LTFU. In contrast, age &#x2265;90 years (OR&#x202f;=&#x202f;0.53; p < .001), worse baseline visual acuity (>20/200; OR&#x202f;=&#x202f;0.72; p&#x202f;=&#x202f;.03), pseudophakia (OR&#x202f;=&#x202f;0.80; p&#x202f;=&#x202f;.04), bilateral disease (OR&#x202f;=&#x202f;0.72; p&#x202f;=&#x202f;.01), and higher first-year anti-VEGF injection burden (OR&#x202f;=&#x202f;0.55; p < .001) were associated with lower odds of LTFU.<br><br>CONCLUSIONS: Male sex, Black or Hispanic race/ethnicity, multiple systemic comorbidities, and greater travel distance were associated with increased odds of becoming LTFU, while older age, worse baseline visual acuity, pseudophakia, bilateral disease, and higher IVI burden were protective factors. These findings can inform the development of targeted retention strategies for high-risk patients.}, }
@article {pmid42649279, year = {2026}, author = {Ying, Y and Li, R and Huang, J and Hou, J and Huang, P and Chen, M and Wang, J and Huang, A and Wang, J and Chen, K and Gao, X and Liang, H and Deng, Y and Chen, Y and Tian, M and Yu, H and Lai, M and Chi, K}, title = {Association of cardiovascular-kidney-metabolic syndrome with blinding eye diseases: insights from a UK Biobank cohort analysis.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42649279}, issn = {1476-5454}, support = {U24A20707, 82271125, 82301260, 82301205//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024T170185//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome's overall impact on major blinding eye diseases remains unclear.<br><br>METHODS: We included participants from the UK Biobank. Baseline CKM syndrome at study entry was classified into five stages according to the American Heart Association criteria. We calculated the absolute incidence rates of cataract, glaucoma, and age-related macular degeneration (AMD) across CKM stages. The associations between CKM syndrome and these eye diseases were examined using Cox proportional hazards models, with further sensitivity and subgroup analyses conducted to assess robustness.<br><br>RESULTS: During more than 10 years of follow-up, 50,894 cataract events, 11,518 glaucoma events, and 8708 AMD events were documented. The absolute incidence rates of cataract, glaucoma, and AMD differed across baseline CKM stages, with the highest rates observed at stage 3. Compared with stage 0, stage 3 CKM syndrome demonstrated the largest effect size estimates for cataract (HR 2.25 [95% CI 2.10-2.41]), glaucoma (HR 1.76 [1.51-2.05]), and AMD (HR 2.08 [1.76-2.46]).<br><br>CONCLUSIONS: Baseline CKM syndrome was closely associated with the risk of major blinding eye diseases.}, }
@article {pmid42650298, year = {2026}, author = {Toro, MD and Avitabile, A and Amato, R and Rusciano, D and Gagliano, C}, title = {Photobiomodulation for Photoreceptor Rescue in Retinal Disease: Mitochondrial, Redox, Vascular, and Translational Perspectives-A Narrative Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/antiox15081034}, pmid = {42650298}, issn = {2076-3921}, abstract = {Photoreceptors work in a biologically demanding compartment of the eye. They consume large amounts of energy, receive continuous light and oxygen, and renew outer-segment membranes enriched in polyunsaturated lipids. These conditions are necessary for vision, but they also make the outer retina poorly tolerant to persistent mitochondrial dysfunction and oxidative stress. Photobiomodulation (PBM), mainly based on red and near-infrared light, has been investigated as a way to support retinal cells that are functionally impaired but not yet irreversibly lost. The field has also acquired new clinical relevance after the 2024 De Novo marketing authorization by the United States Food and Drug Administration (FDA) of the Valeda Light Delivery System for dry age-related macular degeneration (AMD). This narrative review examines the mitochondrial, redox, inflammatory, and neurovascular mechanisms proposed for PBM, and discusses preclinical and clinical evidence across nonexudative AMD, inherited retinal degeneration, diabetic retinal disease, and light-induced damage. Current findings are encouraging, but devices, doses, schedules, endpoints, and sponsorship patterns differ substantially among studies. PBM therefore deserves further investigation, especially in early or intermediate disease, but its clinical use should remain linked to tested protocols, rigorous safety monitoring, and biomarkers of residual retinal functional reserve.}, }
@article {pmid42652099, year = {2026}, author = {Zeng, J and Zhang, J and Schulz, J and Arafah, ADB and Lee, S and Yam, M and Shen, Y and Zhou, F and Zhang, T and Gillies, MC and Zhu, L}, title = {Region-Specific Proteomic Profiles of Extracellular Vesicles (EVs) Derived from Human Macular and Peripheral RPE-Choroid Explants.}, journal = {Biomedicines}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/biomedicines14081715}, pmid = {42652099}, issn = {2227-9059}, support = {N/A//Sydney Nano Institute Kickstarter funding/ ; GNT2020950//National Health and Medical Research Council/ ; GNT1195021//National Health and Medical Research Council/ ; DE230100837//Australian Research Council/ ; }, abstract = {Background: Regional heterogeneity of the macula and peripheral retinas contributes to the differences in retinal physiology, metabolic demand and susceptibility to macular diseases such as age-related macular degeneration (AMD), diabetic macular oedema (DME) and Macular telangiectasia type 2 (MacTel). Extracellular vesicles (EVs) released from the retinal pigment epithelium (RPE)-choroid are increasingly recognised as mediators of extracellular communication and correlate with the molecular biological states of their tissue of origin. However, regional variation in EV composition in human RPE-Choroid tissues remains poorly characterised. Methods: Human macular and peripheral RPE-choroid explants from non-diseased donor eyes (n = 4) were cultured ex vivo using a transwell system. EV and EV-depleted conditioned media were collected by differential ultracentrifugation, respectively. EVs were characterised by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Proteomic profiling was performed using LC-MS/MS followed by multivariate, pathway, and differential expression analyses. Results: TEM and NTA confirmed the presence of vesicle-like particles in a 119-140 nm size range, indicating small EVs in both regions. Proteomic analysis demonstrated a region-associated separation between the macular and peripheral samples in both EV proteome and EV-depleted soluble secretome datasets. GO enrichment analysis revealed that macular EV proteomes were enriched for wound healing, cell-substrate adhesion, and focal adhesion-related terms with a high abundance of integrin and annexin family members, whereas peripheral EV proteomes were enriched for retinoid- and vitamin-binding terms. In the EV-depleted soluble secretome, macular-enriched proteins were associated with actin binding and extracellular matrix-related terms, while peripheral-enriched proteins were correlated with RNA localisation and nuclear compartment terms. Comparative analysis identified EV-specific, secretome-specific, and shared extracellular protein pools. Several EV-specific markers and membrane proteins such as annexins and integrins, showed a relatively high enrichment in macular EV proteomes, whereas CD63 is more abundant in peripheral EV proteomes. In contrast, EV-depleted soluble secretome contains cytokine- and ligand-associated proteins, including MIF, SPP1, and IL6, which may suggest that EVs and soluble secreted proteins represent partially distinct extracellular signalling compartments. Conclusions: Human macular and peripheral RPE-choroid explants released secretory proteins in a regional differentiated manner, supported by PLS-DA and GO enrichment analyses of both EV proteomes and EV-depleted soluble secretome. Further analysis of the EV proteomes may show that such differences were also able to be reflected in protein categories such as EV-specific markers, mitochondrial and membrane proteins. These findings provide a foundation for future investigations into the role of EV-mediated communication in macular diseases and may support the development of region-specific extracellular biomarkers and therapeutic targets.}, }
@article {pmid42652191, year = {2026}, author = {Chong, V}, title = {The Biochemical and Genetic Architecture of Geographic Atrophy: The Role of the FHL-1/CFH Axis and the Paradigm of RNA Interference Therapeutics.}, journal = {Biomedicines}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/biomedicines14081809}, pmid = {42652191}, issn = {2227-9059}, abstract = {Geographic atrophy (GA) represents the advanced, non-neovascular (dry) form of age-related macular degeneration (AMD), a chronic, progressive, and currently irreversible neurodegenerative disease of the retina. The clinical consequences of GA are severe; it is characterized by the insidious, expanding loss of the retinal pigment epithelium (RPE), the overlying photoreceptors, and the underlying choriocapillaris. This state of complete RPE and outer retinal atrophy (cRORA) permanently destroys the neural architecture required for high-acuity central vision. For decades, the pathophysiological etiology of geographic atrophy was framed principally in terms of cumulative oxidative stress, lipid peroxidation, and cellular senescence. However, the foundational understanding of AMD pathophysiology changed substantially following the landmark genomic discoveries published in 2005. Multiple independent genome-wide association studies (GWAS) linked specific single-nucleotide polymorphisms in the CFH gene to a substantially increased risk of developing AMD. The CFH gene encodes Complement Factor H (FH) and its alternative splice variant, Factor H-like protein 1 (FHL-1), which are the primary soluble regulators of the alternative complement pathway. This genetic discovery established GA not merely as a disease of metabolic wear-and-tear, but fundamentally as an immunologic disorder driven by the chronic dysregulation of the innate immune system. With the rapid emergence and clinical validation of targeted gene-silencing technologies, particularly small interfering RNA (siRNA) and antisense oligonucleotides, there is substantial scientific and pharmaceutical interest in modulating the complement cascade at the post-transcriptional level. This narrative review examines the structural biology, spatial partitioning, and pathophysiological roles of the FHL-1/CFH axis in GA focusing on the possibilities of using siRNA as a new potential therapy for GA.}, }
@article {pmid42652879, year = {2026}, author = {Eggarter, V and Ruscitti, L and Ascioti, N and Bonanata, M and Peyla, A and Simona, F and Menghini, M and Grimaldi, G}, title = {Artificial Intelligence-Assisted Analysis of Retinal Pigment Epithelium Tears in Patients with Neovascular Age-Related Macular Degeneration Treated with Aflibercept (2 mg and 8 mg) and Faricimab: A Single-Centre Retrospective Case Series.}, journal = {Journal of clinical medicine}, volume = {15}, number = {16}, pages = {}, doi = {10.3390/jcm15166478}, pmid = {42652879}, issn = {2077-0383}, abstract = {Purpose: We aimed to describe retinal pigment epithelium (RPE) tears in patients with neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED), focusing on OCT features and AI-assisted image analysis. Methods: This retrospective case series included patients with neovascular AMD and PED who developed RPE tears between 2020 and 2025 after treatment with intravitreal aflibercept (2 mg or 8 mg) or faricimab. Multimodal imaging, including spectral-domain OCT and infrared imaging, was reviewed. PED morphology, fluid characteristics, RPE denudation, timing of RPE tear, and visual outcomes were analyzed using manual grading and AI-assisted software. Results: Among 375 PED-bearing eyes, 11 eyes of 11 patients developed an RPE tear (2.9%), of which 10 (90.9%) were temporally associated with anti-VEGF treatment. Rates were similar across agents-2.7% (aflibercept 2 mg), 3.0% (aflibercept 8 mg) and 2.4% (faricimab)-with no significant difference. Eight eyes (72.7%) were treatment-naïve and one tear (9.1%) occurred spontaneously after hemorrhage without recent injection. Among treatment-associated tears, 30% followed the first and 50% the second injection (mean 2.1 injections), detected a mean of 44 ± 30 days after the last injection. Mean baseline PED height was 594.8 ± 239.2 μm and median AI-derived PED volume was 2922 nL. Mean RPE-denudation area at detection was 5.25 ± 3.87 mm[2], remaining stable in 7 of 9 evaluable eyes. Visual acuity was stable or improved in seven eyes; four lost ≥15 ETDRS letters. Conclusions: RPE tears were an uncommon, predominantly early complication occurring in eyes with large PEDs, with no excess risk from second-generation agents. AI-assisted OCT may aid anatomical characterisation, and most eyes retained vision with continued therapy.}, }
@article {pmid42652894, year = {2026}, author = {Macha, N and Yu, M}, title = {Full-Field Stimulus Threshold: A Key Functional Outcome Measure in Retinal Diseases and Clinical Trials.}, journal = {Journal of clinical medicine}, volume = {15}, number = {16}, pages = {}, doi = {10.3390/jcm15166492}, pmid = {42652894}, issn = {2077-0383}, support = {EY025585/EY/NEI NIH HHS/United States ; }, abstract = {Full-field stimulus threshold (FST) testing is a psychophysical method used to assess global retinal function, particularly in patients with severe visual impairment where conventional perimetry is unreliable. This review explores the development, clinical protocols, and applications of FST in retinal diseases, with a focus on its role in inherited retinal dystrophies (IRDs) such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). FST has emerged as a key functional outcome measure in clinical trials, particularly in evaluating novel gene therapies for IRDs. Its fixation-independent nature and ability to detect residual visual function make it valuable for assessing disease progression and treatment efficacy. However, challenges remain regarding standardization and test variability. Ongoing efforts seek to standardize and optimize FST protocols and establish it as a standardized metric in both clinical and research settings.}, }
@article {pmid42653456, year = {2026}, author = {Song, YS and Wang, S and Darjatmoko, SR and Sheibani, N and Sorenson, CM}, title = {Bcl-2-Dependent Persistence of Mononuclear Phagocytes Promotes Ocular Fibrosis.}, journal = {International journal of molecular sciences}, volume = {27}, number = {16}, pages = {}, doi = {10.3390/ijms27167455}, pmid = {42653456}, issn = {1422-0067}, support = {Unrestricted award to the Department of Ophthalmology and Visual Sciences//Research to Prevent Blindness/ ; Endoument Funds//Retina Research Foundation/ ; AMD Research Award//Edward N. &amp; Della L. Thome Memorial Foundation/ ; AMD Research Award//Carl Marshall and Mildred Almen Reeves Foundation/ ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Fibrosis ; *Proto-Oncogene Proteins c-bcl-2/metabolism/genetics ; *Choroidal Neovascularization/pathology/metabolism/etiology ; Macrophages/metabolism/pathology ; Disease Models, Animal ; *Phagocytes/metabolism/pathology ; Mice, Inbred C57BL ; }, abstract = {Ocular diseases, such as neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR), have a fibrotic component that negatively impacts vision. Unfortunately, few treatments are available to mitigate fibrosis in the eye. The clearance of inflammatory cells proceeds, at least in part, through the intrinsic cell death pathway in which Bcl-2 family members play integral roles. Here, we assessed the influence of Bcl-2 expression in mononuclear phagocytes (MP) on the engagement and clearance of inflammatory cells, choroidal neovascularization (CNV), and subsequent subretinal fibrosis in a mouse laser-induced CNV model. Lack of Bcl-2 expression in MP (Bcl-2[MP] mice) decreased neutrophil (Gr1[+]) and microglia (Iba1[+]) presence without impacting M1 (CD80[+]) and M2 (CD206[+]) macrophage presence, CNV, or fibrosis during the first 2 weeks following laser photocoagulation. Later, after inflammation dampens, decreased later-stage fibrosis and CNV were noted in Bcl-2[MP] mice, which were accompanied by increased presence of M2 macrophages (CD206[+]). However, how these increased levels of CD206[+] M2 macrophages in the absence of Bcl-2 contribute to decreased CNV and fibrosis remains unknown. To address whether Bcl-2 expression affects other forms of ocular fibrosis, we utilized the dispase PVR model. Bcl-2[MP] mice, or treatment of wild-type mice with Bcl-2 inhibitors, significantly decreased fibrosis in the PVR model. Furthermore, Bcl-2 inhibitors mitigated CNV and fibrosis (collagen I-defined) in wild-type mice during laser photocoagulation. Thus, inhibition of Bcl-2 activity prevents the late-stage clearance of CD206[+] M2 macrophages during nAMD and PVR, mitigating ocular neovascularization and fibrosis.}, }
@article {pmid42653812, year = {2026}, author = {Panos, GD}, title = {Faricimab 6 mg Versus Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Protocol-Standardised In Silico Study.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {8}, pages = {}, doi = {10.3390/ph19081316}, pmid = {42653812}, issn = {1424-8247}, abstract = {Background: Faricimab 6 mg and aflibercept 8 mg permit extended treatment intervals in neovascular age-related macular degeneration (nAMD), but their pivotal programmes used different loading and maintenance schedules. This study compared treatment burden under the same loading and treat-and-extend protocol and included an exploratory longitudinal analysis of published aggregate visual and anatomical outcomes. Methods: Treatment-specific Dirichlet distributions represented persistent Q8W, Q12W and Q16W capability. Both treatments received injections at weeks 0, 4, 8 and 16, followed by identical four-week extensions from Q8W to Q16W. The primary analysis comprised 30,000 evidence draws, 100,000 paired virtual eyes, a 1.5-million-pair scenario grid and a nested five-million-pair probabilistic analysis. Exploratory multilevel meta-regressions estimated BCVA and change in retinal thickness through week 52; IRF, SRF and complete retinal dryness were analysed separately. Results: Mean injections with faricimab and aflibercept 8 mg were 7.255 and 7.212 at week 52 and 11.522 and 11.144 at week 104. The nested 104-week difference was -0.393 injection (95% uncertainty interval -0.682 to -0.107), but broad source-weight uncertainty included no difference and credible source analyses changed the direction of the contrast. Exploratory week-52 BCVA gains were 5.65 and 6.29 letters, respectively; the difference was 0.64 letter (95% uncertainty interval -1.41 to 2.70) and should be interpreted in the context of three aflibercept 8 mg study families. The expanded retinal-thickness sensitivity model estimated changes of -171.8 and -147.2 micrometres, while the between-treatment direction varied in the three-dose-only analysis. Complete retinal dryness was projected in 57.0% and 69.0% of eyes, respectively, based on three study families per treatment. Conclusions: Use of the same protocol predicted essentially equal one-year burden and a small two-year fixed-weight difference that varied across source choices. The exploratory longitudinal projections, informed by three independent aflibercept 8 mg study families at one year, provide supportive context for the visual and anatomical findings but should be interpreted as hypothesis-generating rather than confirmatory.}, }
@article {pmid42640665, year = {2026}, author = {Hung, CH and Chang, TW}, title = {Comment on: "Impact of GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus on the Development and Progression of Age-Related Macular Degeneration".}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004994}, pmid = {42640665}, issn = {1539-2864}, }
@article {pmid42640689, year = {2026}, author = {Fragiotta, S and Freund, KB and Fernández-Avellaneda, P and Liakopoulos, S and Bijon, J and Moraes, RT and Dolz-Marco, R}, title = {Retinal pigment epithelium defects, sealed and unsealed: a lifecycle and disease agnostic terminology.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004991}, pmid = {42640689}, issn = {1539-2864}, abstract = {PURPOSE: To describe two recurrent phenotypes of retinal pigment epithelium (RPE) defects, sealed and unsealed, which may occur in various diseases.<br><br>METHODS: Medical records and multimodal imaging of 17 patients (70.3 &#xb1; 9.3 years) with RPE defects, including RPE apertures, RPE detachment (RPED) devoid of RPE, and serous maculopathy with the absence of RPE (SMARPE), were retrospectively analyzed. Proposed pathogenic mechanisms are presented, revising current terminology.<br><br>RESULTS: Eyes with RPE apertures (12/17, 70.6%) and SMARPE (1/17, 5.9%) presented RPE defects connecting the subretinal and sub-RPE spaces with subretinal fluid (SRF) and intact outer retina. These features are consistent with patent RPE defects, termed 'unsealed'. RPED devoid of RPE defects developed in &#xbe; eyes (75%) over a serous PED without collapse. The lesions occurred beneath a degenerated outer retina that adheres to the RPE defect without SRF, supporting the term 'sealed'.<br><br>CONCLUSIONS: RPE defects beneath a disrupted photoreceptor layer may become "sealed" by reactive M&#xfc;ller cell gliosis, preventing the occurrence of SRF. RPE defects with intact photoreceptors remain "unsealed", resulting in SRF accumulation. We propose "sealed" and "unsealed" as disease agnostic terms, which can be used for cases previously described as "RPE aperture," "SMARPE," and "RPED devoid of RPE".}, }
@article {pmid42640691, year = {2026}, author = {Kazantzis, D and Thottarath, S and Sheemar, A and Keskin, AM and Kubravi, HS and Sivaprasad, S and , }, title = {Incidence and associations of Retinal pigment epithelial (RPE) tear post-loading phase of aflibercept 2mg in Treatment Naïve Neovascular Age-Related Macular Degeneration (nAMD): PRECISE study report 10.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004985}, pmid = {42640691}, issn = {1539-2864}, abstract = {PURPOSE: To report the incidence of retinal pigment epithelial (RPE) tears following three monthly 2-mg aflibercept injections in treatment-naïve neovascular age-related macular degeneration (nAMD) and to identify associated risk factors.<br><br>METHODS: Treatment-na&#xef;ve patients aged &#x2265;50 years with nAMD and baseline visual acuity (VA) between 24 and 78 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters were included. RPE tears were diagnosed on optical coherence tomography (OCT) as a definite discontinuity of the RPE. Logistic regression using Generalized Estimating Equations (GEE) was performed to account for correlated eye data and identify factors associated with RPE tear development. Cluster bootstrap receiver operating characteristic (ROC) curve analysis assessed the predictive value of baseline pigment epithelial detachment (PED) height.<br><br>RESULTS: A total of 1,929 eyes were analyzed; 67 eyes (3.5%) developed an RPE tear after the aflibercept loading phase. Multivariable analysis adjusted for age, ethnicity, and sex showed that male sex, poorer baseline VA, increased central subfield thickness, hemorrhagic PED, increased PED height, presence of subretinal hyperreflective material (SHRM), and polypoidal choroidal vasculopathy (PCV) were associated with higher odds of RPE tear and that presence of drusen with decreased odds of RPE tear. ROC analysis demonstrated that a baseline PED height of 244 &#xb5;m optimally predicted RPE tear development with a sensitivity of 73.8% and a specificity of 73.6%.<br><br>CONCLUSION: RPE tears occurred in 3.5% of treatment-na&#xef;ve nAMD eyes after aflibercept loading phase. Several baseline clinical and imaging risk factors were identified to be significantly associated with RPE tear development.}, }
@article {pmid42640898, year = {2026}, author = {Fan, Z and Qin, Y and Chen, L and Yuan, J and Xiong, Z and Chen, X and Lai, S and Tham, YC and Sheng, B and Wang, X and Grzybowski, A and Lee, AY and Lee, CS and Cheung, CY and Liu, TYA and Wong, TY and Wang, YX}, title = {A decade of artificial intelligence research in ophthalmology: Global trends and transferable insights for medical AI.}, journal = {PLOS digital health}, volume = {5}, number = {8}, pages = {e0001347}, pmid = {42640898}, issn = {2767-3170}, abstract = {To characterize global trends in ophthalmic AI research from 2015-2025 and drive transferable insights into the broader evolution of AI in medicine, we conducted a systematic bibliometric analysis of original AI articles in ophthalmology indexed in the Web of Science Core Collection, Scopus, and Pubmed from 2015 to 2025. Publications were screened and categorized using an LLM-assisted pipeline with predefined labels, and agreement between LLM-assisted classifications and human grading was evaluated. We analyzed temporal trends and emergence patterns across study design, model architecture, disease focus, and data modalities. Among 12,911 included articles, annual publications increased at a compound annual growth rate of 39.7%, from 108 in 2015-3061 in 2025. Four key shifts were identified. Study design: Development studies (88.3%) dominated through the period, whereas evaluation studies (7.4%) began to emerge in 2019. Model architecture: Classical deep learning (71.8%) became the most prevailing approach from 2017, while foundation model studies (0.6%) increased sharply in 2024-2025. Disease focus: Diabetic retinopathy (32.9%), glaucoma (17.5%), and age-related macular degeneration (12.6%) remained the leading disease areas, while corneal diseases (7.0%), cataract (4.3%) and myopia (3.4%) emerged after 2019-2020 and grew rapidly. Data modalities: Among image-based modalities (84.1%), color fundus photography and retinal optical coherence tomography remained dominant but plateaued after 2019, whereas text-based modalities (5.5%) continued to rise after 2022. Over the past decade, ophthalmic AI research expanded rapidly and evolved from narrow image-based deep learning toward broader work spanning evaluation studies, foundation models, multimodal data integration, and a wider spectrum of eye diseases. These trajectories may extend beyond ophthalmology, offering broader insights into how medical AI matures toward clinical evaluation and translation.}, }
@article {pmid42641479, year = {2026}, author = {Giulivi, C and Villafuerte-Trisolini, C and Greenblatt, ZL and Dang, J and Tork, A and Mullah, R and Le, S and Min, A and Nair, M and Vorkapich, A and Tran, HA and Doyle, E and Law, A and O'Keefe, O and Wu, A and Shibata, B and Ripolles-Garcia, A and Thomasy, SM and Harris, RA and Chen, R and Liu, YA and Yiu, G}, title = {Adaptive and degenerative mitochondrial remodeling define distinct redox states in age-related macular degeneration.}, journal = {Redox biology}, volume = {96}, number = {}, pages = {104365}, doi = {10.1016/j.redox.2026.104365}, pmid = {42641479}, issn = {2213-2317}, abstract = {Age-related macular degeneration (AMD) is associated with mitochondrial dysfunction and oxidative stress, yet the relationship between mitochondrial remodeling, redox homeostasis, and disease progression remains poorly understood. Nonhuman primates (NHPs) develop spontaneous AMD-related phenotypes, including punctate deposits and soft drusen, providing a unique animal model to investigate mitochondrial pathology in the aging retinal pigment epithelium (RPE). We integrated quantitative mitochondrial ultrastructural profiling with flavoprotein fluorescence imaging, plasma metabolomics, and whole-exome sequencing to characterize mitochondrial and redox alterations in aged rhesus macaques with AMD-related lesions. Flavoprotein fluorescence imaging demonstrated increased metabolic heterogeneity in eyes with soft drusen, consistent with altered mitochondrial redox states and oxidative stress. Morphometric analysis identified distinct mitochondrial remodeling patterns across phenotypes. Normal aging was characterized by concentric cristae and type I paracrystalline inclusions. Eyes with punctate deposits exhibited increased mitochondrial fusion-associated morphology, hyperbranching, and type I paracrystalline inclusions, consistent with a stress-responsive mitochondrial remodeling pattern. In contrast, eyes with soft drusen exhibited reduced fusion-associated morphology, reduced structural complexity, and ultrastructural features consistent with mitochondrial deterioration. These ultrastructural patterns were accompanied by distinct plasma metabolomic signatures. Punctate deposits were associated with altered glycolytic, tricarboxylic acid cycle, and redox-buffering metabolites, consistent with differences in stress-responsive metabolism, whereas soft drusen exhibited metabolomic signatures consistent with altered redox homeostasis. Whole-exome sequencing identified a mitochondrial DNA variant, MT:9582G > A, in cytochrome c oxidase subunit III (COX3) associated with the drusen phenotype. Collectively, these findings identify distinct mitochondrial remodeling patterns associated with AMD-related phenotypes in aged rhesus macaques. The convergence of ultrastructural, imaging, metabolomic, and genetic analyses suggests that punctate deposits and soft drusen are associated with different mitochondrial and redox-related responses to chronic retinal stress. These findings provide a framework for future studies investigating mitochondrial biology and redox-driven mechanisms in AMD.}, }
@article {pmid42633835, year = {2026}, author = {Viggiano, P and Pignataro, MG and Termite, AC and Boscia, G and Savastano, A and Evangelista, F and Alessio, G and Boscia, F and Peto, T and Chakravarthy, U}, title = {Retinal Pigment Epithelial Detachment: Molecular Mechanisms, Multimodal Imaging Classification, and Clinical Management Across the Spectrum of Macular Disease.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101512}, doi = {10.1016/j.preteyeres.2026.101512}, pmid = {42633835}, issn = {1873-1635}, abstract = {Pigment epithelial detachment (PED) represents a critical structural finding across the spectrum of chorioretinal diseases, occurring in 63-80% of eyes with neovascular age-related macular degeneration and frequently in central serous chorioretinopathy, polypoidal choroidal vasculopathy, and inflammatory conditions. This review provides a comprehensive analysis of current multimodal imaging techniques in the diagnosis and management of PEDs. We examine the role of various imaging modalities including optical coherence tomography (OCT), OCT angiography (OCTA), en face OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), infrared imaging (IR), and fundus autofluorescence (FAF) in evaluating PEDs. Each imaging modality provides unique insights: OCT reveals characteristic structural changes and quantitative biomarkers (height, volume, prechoroidal cleft); OCTA demonstrates type 1-4 MNV localisation; en face OCT visualises internal architecture; FA shows leakage patterns; ICGA identifies choroidal hyperpermeability; IR assists RPE evaluation; and FAF highlights dysfunction patterns. The integration of these imaging techniques has enhanced our understanding of PED pathophysiology-hydrostatic imbalance, RPE pump failure, Bruch's alterations-and improved classification into drusenoid, serous, fibrovascular, and haemorrhagic subtypes. This review particularly emphasises how advanced OCT/OCTA has advanced our knowledge of PED natural history, treatment response (anti-VEGF/PDT), and complications (RPE tears). We also discuss future directions in AI-driven classification and imaging biomarkers for personalised therapeutic approaches. The synergistic use of multimodal imaging represents a cornerstone in PED management, enabling precise diagnosis, risk stratification, and tailored treatment strategies.}, }
@article {pmid42635473, year = {2026}, author = {Pilotto, E and Parolini, F and Edwards, MM and Midena, E and Midena, G}, title = {Hyperreflective Choroidal Foci Characterization Supports the Existence of Different Clinical Phenotypes of Geographic Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {56}, doi = {10.1167/iovs.67.10.56}, pmid = {42635473}, issn = {1552-5783}, mesh = {Humans ; *Geographic Atrophy/diagnosis/pathology ; Tomography, Optical Coherence/methods ; *Choroid/pathology ; Phenotype ; Female ; Retinal Pigment Epithelium/pathology ; Aged ; Male ; Fluorescein Angiography/methods ; Aged, 80 and over ; }, abstract = {PURPOSE: To characterize and quantify optical coherence tomography (OCT) hyperreflective choroidal foci (HCF) in geographic atrophy (GA) of age-related macular degeneration (AMD) and to assess their distribution across different GA phenotypes.<br><br>METHODS: Eyes with bilateral GA (B-GA) or unilateral GA (U-GA) with macular neovascularization in the fellow eye, as well as controls, were included. HCF were classified in different subtypes according to size (small, &#x2264;30&#xa0;&#xb5;m; large, >30&#xa0;&#xb5;m) and reflectivity (high or intermediate). Each subtype was also identified according to location (choriocapillaris vs. choroid). HCF counts were quantified within complete retinal pigment epithelium and outer retinal atrophy (cRORA), incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), and non-atrophic outer retinal alteration (noRORA). The comparison of HCF count between the GA groups and the controls was performed only in noRORA segments.<br><br>RESULTS: Seventy-seven eyes were enrolled (40 B-GA, 18 U-GA, and 19 controls). The extent of cRORA, iRORA, and noRORA regions did not differ between the two GA groups (P > 0.05 for all). In noRORA regions, both GA groups exhibited significantly higher HCF number compared to controls (P < 0.0001 for both). Total HCF count did not differ between the GA groups across all RORA regions (P > 0.05 for all). However, the analysis of HCF subtypes revealed significant differences. Small intermediate-reflectivity choriocapillaris HCF were significantly more numerous in U-GA eyes than in B-GA in cRORA and noRORA regions (P = 0.0006 and P = 0.006, respectively). Large high-reflectivity choriocapillaris HCF were significantly more numerous in B-GA eyes than in U-GA within cRORA regions (P = 0.025). In choroid, HCF subtypes did not differ between the two GA groups in the different RORA regions.<br><br>CONCLUSIONS: Although overall HCF burden was similar between the two GA phenotypes, significant distinct distribution of HCF subtypes was documented. Detailed HCF characterization provides new insights into GA heterogeneity, supporting the value of novel biomarkers in further characterizing different GA phenotypes.}, }
@article {pmid42636089, year = {2026}, author = {Sabaner, MC and Gunes, I and Anguita, R and van Dijk, EHC and Ferro Desideri, L and Cehofski, LJ and Ramtohul, P and Subhi, Y}, title = {Concurrent macular neovascularization in shallow irregular retinal pigment epithelium elevation phenotypes in age-related macular degeneration and chronic central serous chorioretinopathy: A systematic review and meta-analysis.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70226}, pmid = {42636089}, issn = {1755-3768}, support = {//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; }, abstract = {This systematic review and meta-analysis synthesized the reported frequency of concurrent macular neovascularization (MNV) among selected eyes with author-defined shallow irregular retinal pigment epithelium (RPE) elevations in age-related macular degeneration (AMD) and chronic central serous chorioretinopathy (CSC). Nine databases were searched on 3 May 2026 for observational studies assessing contemporaneous MNV in phenotype-positive eyes. Studies were classified according to phenotype definition, disease context, unit of analysis and MNV ascertainment directness. Principal quantitative syntheses were restricted to clinically comparable Tier 1 eye-level cohorts, while Tier 2 evidence was examined in a restricted sensitivity analysis. Random-effects meta-analysis of logit-transformed proportions was performed separately by disease, with binomial-normal generalized linear mixed models (GLMM) used as sensitivity analyses. Certainty was assessed using a GRADE-style framework, and the review was registered in PROSPERO (CRD420261384416). Twenty-two reports were included, comprising five AMD and 17 CSC reports. Three selected fellow-eye AMD cohorts contributed 160 double-layer sign (DLS)-positive eyes to the principal AMD analysis; the pooled frequency of contemporaneous MNV was 52% (95% confidence interval [CI], 19%-84%; I[2] = 72.52%). Five selected chronic CSC cohorts contributed 232 flat irregular pigment epithelial detachment (FIPED)-positive eyes to the principal CSC analysis; the pooled frequency was 43% (95% CI, 25%-63%; I[2] = 61.32%). A restricted Tier 1 plus Tier 2 CSC sensitivity analysis yielded 39% (95% CI, 23%-57%; I[2] = 77.89%). GLMM sensitivity analyses produced similar point estimates, although confidence and prediction intervals remained wide. Certainty of evidence was very low. In selected phenotype-positive cohorts, contemporaneous MNV was identified in approximately one-half of DLS-positive AMD eyes and two-fifths of FIPED-positive chronic CSC eyes, but the estimates were imprecise. These findings should not be interpreted as diagnostic, prognostic, population-prevalence or treatment thresholds. Structural OCT phenotypes should prompt disease-contextualized multimodal characterization rather than stand-alone inference of MNV activity or treatment need.}, }
@article {pmid42636893, year = {2026}, author = {Zhang, Y and Luan, F and Feng, J and Sun, W and Tao, Y}, title = {Dual-restricted AAV gene delivery via suprachoroidal administration mediates precision RPE SOCS3 restoration for dry age-related macular degeneration.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {}, number = {}, pages = {115289}, doi = {10.1016/j.jconrel.2026.115289}, pmid = {42636893}, issn = {1873-4995}, abstract = {Dry age-related macular degeneration (dAMD) is a leading cause of irreversible vision loss, driven by chronic oxidative stress and inflammation in the retinal pigment epithelium (RPE). Disruption of key negative regulators of the JAK-STAT pathway, particularly SOCS3, contributes to this oxidative-inflammatory cascade. To address this, we developed a dual-restricted ocular gene delivery platform that combines suprachoroidal administration with an RPE-specific Best1 promoter, enabling localized, durable, and cell-restricted SOCS3 expression. Comparative analysis showed that intravitreal injection poorly transduced the RPE, whereas suprachoroidal delivery improved AAV access to the RPE/outer retinal region, and the Best1 promoter further restricted expression to RPE cells, reducing neural retinal off-target expression. In vitro, SOCS3 restoration suppressed STAT3 activation, inflammatory cytokine release, reactive oxygen species accumulation, mitochondrial disruption, and barrier impairment. In vivo, the dual-restricted system achieved long-term, ocular-localized expression for at least six months, reducing microglial/macrophage activation, inflammation, oxidative stress, and apoptosis, thereby preserving outer retinal architecture. Ocular and systemic safety assessments detected no overt toxicity under the tested conditions. Together, these findings support suprachoroidal AAV-Best1-SOCS3 delivery as a dual-restricted platform for localized modulation of oxidative-inflammatory retinal degeneration and warrant further preclinical evaluation.}, }
@article {pmid42637139, year = {2026}, author = {Conforti, A and Cifuentes-González, C and Agrawal, KR and Agrawal, R}, title = {GLP-1 receptor agonists and ocular disease: Therapeutic promise, mechanistic insights and emerging safety signals.}, journal = {Drug discovery today}, volume = {}, number = {}, pages = {104786}, doi = {10.1016/j.drudis.2026.104786}, pmid = {42637139}, issn = {1878-5832}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity and are increasingly recognised for their pleiotropic effects beyond glycaemic control. Growing evidence suggests that these agents influence inflammatory, vascular and neuroprotective pathways relevant to ocular disease, creating opportunities for therapeutic repurposing while raising important questions regarding long-term ocular safety. This review crucially synthesises current mechanistic, preclinical and clinical evidence regarding the role of GLP-1 RAs across major ophthalmic conditions. Experimental studies consistently demonstrate anti-inflammatory, antioxidative and neurovascular-protective effects, particularly in diabetic retinopathy, whereas clinical studies suggest a potential benefit yet are limited by heterogeneous study designs and the absence of dedicated ophthalmic endpoints. We also examine emerging safety signals, including reported associations with nonarteritic anterior ischaemic optic neuropathy and neovascular age-related macular degeneration, highlighting the limitations of current observational evidence and the uncertainty surrounding causality. Finally, we discuss the translational potential of GLP-1 RAs in immune-mediated ocular diseases such as noninfectious uveitis and identify key priorities for future research. Because the clinical use of GLP-1 RAs continues to expand, carefully designed prospective studies integrating mechanistic insights with standardised ophthalmic outcomes will be essential to define both their therapeutic potential and long-term ocular safety.}, }
@article {pmid42637173, year = {2026}, author = {Fritsch, S and Wall, K and Vaisband, M and Hasenauer, J and Schwenzer, N and Jauch, AS and Holz, FG and Curcio, CA and Ach, T}, title = {Fluorescence lifetime imaging microscopy of pigmented cells in age-related macular degeneration.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111216}, doi = {10.1016/j.exer.2026.111216}, pmid = {42637173}, issn = {1096-0007}, abstract = {This study characterized fibrosis-associated pigment changes in neovascular age-related macular degeneration (nAMD) using fluorescence lifetime imaging microscopy (FLIM). Retinal cross sections from human donor eyes with nAMD (n = 5; mean age 91.5 ± 2.1 years) and control eyes without maculopathy (n = 5; 82.5 ± 0.7 years) were analyzed at λexc 488 nm and λexc 780 nm. In total, 116 regions of interest (50 μm width each) were assessed across the fovea, parafovea, and areas of subretinal fibrosis in nAMD eyes and compared with corresponding locations in controls. Fluorescence lifetimes (FLTs) were evaluated using a linear mixed-effects model across pigment in unremarkable retinal pigment epithelium (RPE), pigment in RPE above fibrosis, pigment within fibrosis, and pigment in the choroid. At λexc 488 nm, FLTs were significantly prolonged in RPE above fibrosis (0.54 ± 0.04 ns) compared with unremarkable RPE (0.49 ± 0.04 ns, linear mixed-effect model: p = 0.04). Pigment within fibrosis (0.51 ± 0.03 ns) showed similar lifetimes to unremarkable RPE (p = 0.58), while choroidal pigment exhibited markedly shorter lifetimes (0.23 ± 0.04 ns; p < 0.001). At λexc 780 nm, pigment within fibrosis displayed shorter lifetimes (0.27 ± 0.03 ns) than unremarkable RPE (0.34 ± 0.04 ns, p = 0.04), and choroidal pigment again showed the shortest values (0.11 ± 0.01 ns; p < 0.001). Dual-wavelength FLIM reveals distinct lifetime patterns at fibrotic locations consistent with an RPE origin of fibrosis-associated pigment in nAMD.}, }
@article {pmid42637174, year = {2026}, author = {Falcão, AS and Lopes-da-Silva, M and Antas, P and Escrevente, C and Pedro, M and Felgueiras, B and Caires, B and Coelho, R and Ferreira, IS and Santos, IP and Ciossek, T and Nicklin, P and Tenreiro, S and Seabra, MC}, title = {Enhancing lysosome function via TFEB activation reduces lipofuscin-like granules in the retinal pigment epithelium.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111215}, doi = {10.1016/j.exer.2026.111215}, pmid = {42637174}, issn = {1096-0007}, abstract = {Age-related macular degeneration (AMD) is the most common blinding disease in the western world and is currently incurable. Although the exact causes of AMD are not clear, the primary origin of pathology appears to be the aged retinal pigment epithelium (RPE) exhibiting signs of lysosomal dysfunction and oxidative damage. RPE is responsible for the daily digestion of photoreceptor outer segments (POS), imposing a heavy continuous burden on the lysosomal network. A cellular model of RPE lysosomal dysfunction can be achieved by feeding RPE with a single pulse of POS, leading to the accumulation of autofluorescence granules (AFG), similar to lipofuscin in vivo. Here we show that synchronous phagocytosis of POS leads to early transient mTOR activation followed by inhibition in late phagosome maturation. One of its substrates, the transcription factor EB (TFEB) increases during phagosome maturation albeit mostly in its inactive phosphorylated form. We questioned whether modulation of the mTOR/TFEB axis could improve POS clearance and hence reduce AFG load. Treatment of POS-fed cells after the appearance of AFGs with rapamycin, an mTORC1 inhibitor results in ∼30% reduction of AFG load. This effect is dependent on active lysosomal enzymes and induction of active dephosphorylated TFEB with consequent activation of GADD34 and lysosomal biogenesis. As a proof of concept, we show that overexpressing a constitutively active form of unphosphorylated TFEB dramatically reduces POS-dependent AFG accumulation. Overall, this study suggests that viral or pharmacological approaches activating the TFEB pathway in the RPE could be beneficial as cell-protective treatment of early/intermediate cases of AMD, acting to delay progression of the disease.}, }
@article {pmid42639196, year = {2026}, author = {Shehryar, T and Fazal, ZZ and Salam, AA and Varada, S and Jabran, F and Akram, MU}, title = {Why aren't we using AI in eye clinics? A systematic review of barriers and solutions in AI-based fundus image diagnostics for ocular diseases.}, journal = {International journal of ophthalmology}, volume = {19}, number = {9}, pages = {1809-1825}, pmid = {42639196}, issn = {2222-3959}, abstract = {Artificial intelligence (AI) has shown remarkable accuracy in the diagnosis of common ocular diseases such as diabetic retinopathy (DR), glaucoma, retinopathy of prematurity (ROP), and age-related macular degeneration (AMD), often matching or even outperforming expert clinicians. Despite these advancements, AI adoption in clinical settings remains limited due to key barriers. This systematic review evaluates 34 studies (2018-2025) highlighting AI's diagnostic performance (often >90% accuracy) while pointing out significant gaps in real-world deployment. We identify these persistent challenges through comprehensive analysis of current literature and propose actionable pathways to bridge the "last-mile gap" between research and clinical practice. This review pointed out three significant gaps in real-world deployment. These include 1) disjointed integration into clinical workflows, 2) lack of transparency in AI decision-making, and 3) poor generalizability across diverse populations. Our findings provide a framework for advancing AI implementation in ocular diagnostics to achieve equitable, scalable, and trustworthy solutions for global vision care.}, }
@article {pmid42639213, year = {2026}, author = {Zhang, NY and Kong, HQ and Liao, YQ and Pan, YJ and Sun, W and Xi, L and Yu, HH and Shi, YH}, title = {Targeting ferroptosis in ocular diseases: mechanisms, clinical implications, and therapeutic horizons.}, journal = {International journal of ophthalmology}, volume = {19}, number = {9}, pages = {1858-1877}, pmid = {42639213}, issn = {2222-3959}, abstract = {Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been increasingly implicated in selected ocular diseases, although its causal relevance varies across disease entities. The retina and retinal pigment epithelium are biologically susceptible to ferroptosis-related injury because of their high oxygen demand, abundant polyunsaturated lipids, mitochondrial activity, light exposure, and tightly regulated iron handling. This review summarizes core mechanisms of ocular ferroptosis, including iron uptake and export, glutathione-glutathione peroxidase 4 (GPX4)-dependent antioxidant defense, lipid peroxidation, mitochondrial dysfunction, neuroinflammation, and blood-retina barrier disruption. We discuss evidence from major degenerative, vascular, ischemic, hereditary, infectious, and immune-mediated retinal diseases, with particular attention to glaucoma, age-related macular degeneration, diabetic retinopathy, ocular toxoplasmosis, uveitis, retinal vasculitis, and inflammatory chorioretinopathy. We also evaluate ferroptosis-targeted therapeutic strategies, proposed operational criteria for defining ferroptosis in retinal disease, and candidate structural, functional, biochemical, and imaging endpoints for future translational studies. Current evidence supports ferroptosis as a context-dependent contributor to retinal injury rather than a uniform pathogenic mechanism. Future studies should integrate cell-type-resolved biomarkers, lipidomic and imaging readouts, functional rescue experiments, and clinically meaningful visual outcomes to clarify when ferroptosis modulation may support vision preservation.}, }
@article {pmid42639827, year = {2026}, author = {Neumeister, N and Auer, EA and Patnaik, JL and Palestine, AG and Lynch, AM}, title = {Chronic Hypertension and Conversion from Intermediate Age-Related Macular Degeneration (iAMD) to the Advanced Phenotypes.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/09286586.2026.2719736}, pmid = {42639827}, issn = {1744-5086}, abstract = {PURPOSE: To assess the relationship between chronic hypertension (cHTN) and progression from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) and neovascular AMD (NVAMD).<br><br>METHODS: We examined the records of iAMD patients recruited to the University of Colorado AMD Registry (July 2014 - June 2024). cHTN was self-reported at enrollment and confirmed by review of the Electronic Health Record (EHR). Number of prescribed antihypertensive medication classes was also collected. Conversion to GA and NVAMD was assessed through November 2024 with multi-modal imaging for each eye. Cox proportional hazards models with sandwich estimators were used to assess time to conversion.<br><br>RESULTS: We studied 900 eyes from 450 iAMD patients, of which 115 eyes (12.8%) converted to GA and 74 eyes (8.2%) converted to NVAMD. Neither measure of hypertension was associated with conversion to GA. In univariate analysis, patients with cHTN were at a 1.81 (95% CI: 1.06, 3.06, p&#x2009;=&#x2009;0.029) times greater risk of conversion to NVAMD and were at a 1.30 (95% CI: 1.05, 1.62, p&#x2009;=&#x2009;0.019) times greater risk of conversion to NVAMD for each additional antihypertensive medication class prescribed. In a body mass index (BMI) stratified analysis, the two measures of cHTN were associated with an elevated risk of conversion among overweight/obese patients (BMI&#x2009;&#x2265;&#x2009;25&#x2009;kg/m[2]) but not underweight/healthy patients (BMI&#x2009;<&#x2009;25&#x2009;kg/m[2]).<br><br>CONCLUSIONS: cHTN and antihypertensive medication class count were associated with conversion to NVAMD. BMI may be an effect modifier in the relationship between cHTN and progression from iAMD to NVAMD.}, }
@article {pmid42640154, year = {2026}, author = {Wang, J and Osada, H and Chen, S and Yamaguchi, S and Hayashi, K and Negishi, K and Kurihara, T and Ban, N}, title = {Nicotinamide Mononucleotide Attenuates Inflammatory Activation, Choroidal Neovascularization, and Lesion-Associated Remodeling.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {59}, doi = {10.1167/iovs.67.10.59}, pmid = {42640154}, issn = {1552-5783}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; Mice ; Mice, Inbred C57BL ; Disease Models, Animal ; Blotting, Western ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Choroid/pathology/metabolism/drug effects ; *Inflammation/drug therapy/metabolism ; Male ; Humans ; NF-kappa B/metabolism ; Cells, Cultured ; }, abstract = {PURPOSE: To evaluate the therapeutic potential of nicotinamide mononucleotide (NMN) for modulating the neurovascular inflammatory microenvironment and blunting tissue remodeling in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A laser-induced choroidal neovascularization (CNV) model was established in C57BL/6J mice, and CNV lesion size was quantified on RPE/choroid flat mounts. Immunostaining evaluated myeloid cell accumulation and fibrosis-associated remodeling. Quantitative RT-PCR and Western blotting assessed inflammatory/angiogenic gene expression and signaling activation in the retina and RPE/choroid. In vitro, lipopolysaccharide (LPS)-stimulated bEnd.3 and primary mouse RPE cells and TGF-&#x3b2;-stimulated THP-1-derived macrophage cells were used to model inflammatory and profibrotic responses.<br><br>RESULTS: NMN treatment significantly reduced CNV size in the laser-induced CNV model. This was accompanied by decreased myeloid cell accumulation within CNV lesions. NMN attenuated inflammatory and angiogenesis-related gene expression in the RPE/choroid and neural retina and reduced downstream signaling activation. In vitro, NMN suppressed LPS-induced inflammatory and proangiogenic responses in primary RPE cells and bEnd.3 endothelial cells and inhibited NF-&#x3ba;B activation. NMN further attenuated tissue remodeling, as shown by reduced collagen I-positive area under prolonged and delayed dosing regimens, together with decreased F4/80-positive area and &#x3b1;-smooth muscle actin-positive area within CNV lesions. In TGF-&#x3b2;-induced THP-1-derived macrophage cells, NMN suppressed profibrotic responses.<br><br>CONCLUSIONS: Our findings indicate that NMN reduces inflammatory signaling and alleviates the inflammatory microenvironment in CNV, accompanied by decreased angiogenesis-related gene expression and fibrosis-related remodeling. By attenuating inflammatory activation and tissue remodeling processes, NMN warrants further evaluation as an adjunctive approach to limit CNV progression and late-stage tissue remodeling in nAMD.}, }
@article {pmid42640156, year = {2026}, author = {Cicinelli, MV and Bianco, L and Antropoli, A and Bandello, F and Borrelli, E and Edwards, M}, title = {From Subretinal to Intraretinal Fluid in Type 1 Macular Neovascularization: A Clinicopathologic Disease Transition Model.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {57}, doi = {10.1167/iovs.67.10.57}, pmid = {42640156}, issn = {1552-5783}, mesh = {Humans ; *Subretinal Fluid/metabolism/diagnostic imaging ; Female ; Tomography, Optical Coherence/methods ; Male ; Retrospective Studies ; Visual Acuity/physiology ; Aged ; Aquaporin 4/metabolism ; *Retinal Neovascularization ; Fluorescein Angiography ; Aged, 80 and over ; *Wet Macular Degeneration/metabolism/diagnosis ; Immunohistochemistry ; Glial Fibrillary Acidic Protein/metabolism ; Follow-Up Studies ; Disease Progression ; }, abstract = {PURPOSE: To characterize the transition from subretinal fluid (SRF)-dominant to intraretinal fluid (IRF)-dominant exudation in type 1 macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD), using longitudinal optical coherence tomography (OCT) phenotyping and exploratory clinicopathologic correlation.<br><br>METHODS: Serial OCT volumes from eyes with type 1 MNV and baseline SRF without IRF were retrospectively reviewed to define the temporal sequence of subretinal hyperreflective material (SHRM) formation, external limiting membrane (ELM) disruption and descent, IRF emergence, and outer retinal remodeling. Time-dependent Cox regression identified predictors of IRF development, and linear mixed-effects models related structural transitions to visual acuity (VA). Exploratory immunohistochemistry for glial fibrillary acidic protein and aquaporin-4 (AQP4) was performed in a donor eye with nAMD.<br><br>RESULTS: Among 143 eyes (130 patients; median follow-up, 49.2 months [interquartile range, 28.2-90.8]), SHRM developed in 85 eyes (59%), ELM disruption or descent in 67 eyes (47%), and IRF in 44 eyes (31%). ELM alterations preceded IRF occurrence in 74% of eyes (hazard ratio, 12.94; 95% CI, 6.41-26.11). IRF onset was associated with worse VA (&#x3b2; = +0.07 logMAR; P < 0.001) and accelerated visual decline (time &#xd7; IRF interaction: &#x3b2; = +0.019 logMAR/year; P = 0.004). Histopathology demonstrated M&#xfc;ller cell extension beyond the ELM into fibrovascular tissue, reactive gliosis, and AQP4 redistribution, mirroring ELM descents and outer retinal adhesions observed on OCT.<br><br>CONCLUSIONS: In type 1 MNV, the shift to IRF-dominant exudation may reflect a structural disease state transition in which ELM disruption, M&#xfc;ller cell remodeling, and altered AQP4-mediated fluid transport are contributing mechanisms. These findings provide a possible clinicopathologic framework for developing outer retina-preserving therapeutic strategies in nAMD.}, }
@article {pmid42640395, year = {2026}, author = {Lin, L and Zhang, J and Xie, X}, title = {Exosomes in the treatment of age-related ophthalmic diseases: an updated review.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42640395}, issn = {1573-2630}, support = {XKTD2022005//Chengdu University of Traditional Chinese Medicine/ ; }, mesh = {Humans ; *Exosomes/physiology ; *Macular Degeneration/therapy ; *Dry Eye Syndromes/therapy ; *Drug Delivery Systems/methods ; *Cataract/therapy ; *Aging ; }, abstract = {Exosomes are nanoscale extracellular vesicles of endosomal origin that mediate intercellular communication by transferring bioactive cargo, including proteins, lipids, messenger RNAs, microRNAs, and other regulatory molecules. Through this process, they can modulate the biological functions of recipient cells. Age-related ophthalmic diseases, including age-related macular degeneration (AMD), dry eye disease (DED), and age-related cataract (ARC), are degenerative ocular conditions whose incidence increases with age and are associated with chronic inflammation, oxidative stress, dysregulated angiogenesis, tissue fibrosis, epithelial injury, and apoptosis. Diabetic retinopathy (DR), although not classically defined as an age-related ophthalmic disease, is also briefly discussed in this review as an age-associated metabolic retinal comorbidity. Existing clinical treatments have several limitations, including the need for repeated administration, variable therapeutic responses, and potential adverse effects. Because of their biocompatibility, low immunogenicity, modifiable cargo and potential for local delivery, exosomes are being investigated as therapeutic agents and drug delivery vehicles in ophthalmology. This review summarizes the biological characteristics of exosomes and their potential relevance to ophthalmic applications, reviews recent evidence on their roles and mechanisms in major age-related ophthalmic diseases, and discusses the current limitations and future directions of exosome-based therapeutic strategies.}, }
@article {pmid42640457, year = {2026}, author = {Marechal, V and Amoroso, F and Pacurariu, S and Capuano, V and Mehanna, CJ and Miere, A and Xompero, C and Semoun, O and Souied, EH}, title = {Real-world outcomes after switching to faricimab in treatment-resistant neovascular AMD: Short-term response and 12-month follow-up.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261478167}, doi = {10.1177/11206721261478167}, pmid = {42640457}, issn = {1724-6016}, abstract = {AimsTo assess the efficacy and safety of faricimab in neovascular age-related macular degeneration (nAMD) resistant to anti-VEGF therapies.MethodsThis retrospective study evaluated nAMD patients with persistent fluid despite anti-VEGF treatments (aflibercept or ranibizumab; mean injection interval of 4.63 ± 0.78 weeks), switched to faricimab and treated with three monthly injections. Data included demographics, baseline macular characteristics and prior treatments. Outcomes focused on anatomical changes (central macular thickness (CMT), pigment epithelial detachment (PED) height, fluid resolution), predictive factors for response, and fluid-free intervals.ResultsSeventy-five eyes from 64 patients (mean age 81.5 years) with predominantly type 1 macular neovascularization (84%) and extensive prior anti-VEGF exposure (mean 43.7 injections) were analyzed. Complete dryness was achieved in 58.67% of cases, with partial dryness in 28%. CMT and PED height showed significant reductions (p < 0.0001), while visual acuity remained stable throughout follow-up. In a selected subgroup of complete responders with at least 12-month follow-up (42/75 eyes), CMT reduction was maintained, but these longer-term findings should be interpreted cautiously because of potential selection bias. In cases with complete fluid resolution, the fluid-free interval averaged six weeks.ConclusionFaricimab offers notable anatomical improvements in nAMD resistant to anti-VEGF therapy, with stable visual acuity. In this heavily pretreated, treatment-resistant population, treatment intervals nevertheless remained short, averaging less than six weeks (5.34 ± 1.31 weeks), so the main benefit appears anatomical, with limited evidence for functional gain or reduced treatment burden.}, }
@article {pmid42640660, year = {2026}, author = {McLaughlin, SA and Bineshfar, N and Williams, BK}, title = {RE: Comment on: "Impact of GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus on the Development and Progression of Age-Related Macular Degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004995}, pmid = {42640660}, issn = {1539-2864}, }
@article {pmid42624227, year = {2026}, author = {Zhong, Y and Feng, M and Tawfeeq, RD and Cheng, J}, title = {Emerging Research Trends in the Application of Artificial Intelligence, LLMs, Machine Learning, and Deep Learning in Ophthalmic Diseases: A Bibliometric and Visual Analysis.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105628}, doi = {10.1016/j.pdpdt.2026.105628}, pmid = {42624227}, issn = {1873-1597}, abstract = {BACKGROUND: To examine global research activity in the application of artificial intelligence, large language models, machine learning, and deep learning in ophthalmic diseases from 2015 to 2025.<br><br>METHODS: The study retrieved relevant publications from the Web of Science Core Collection. Bibliometric indicators were analysed using VOSviewer, CiteSpace, and Bibliometrix. Annual publication numbers, citation distribution, countries, institutions, journals, co-cited journals, author productivity, co-authorship networks, keyword frequency, burst terms, and thematic clusters were assessed.<br><br>RESULTS: A total of 1,997 articles were included in this analysis based on the inclusion criteria. Annual publication numbers increased after 2018 and remained high from 2020 to 2025. The United States, China, and the United Kingdom showed the highest research output.The University of California System, the University of London and University College London were leading institutions in terms of publication output. The most common keywords included deep learning, optical coherence tomography, diabetic retinopathy, and macular degeneration. Citation burst analysis identified influential articles on diabetic retinopathy detection, optical coherence tomography biomarker analysis, and residual network models. Visual cluster analysis identified themes related to automated retinal imaging, diabetic retinopathy screening, fluid quantification models, multimodal image analysis, and recent studies using large language models.<br><br>CONCLUSION: Artificial intelligence and deep learning research in ophthalmology has increased significantly, with imaging-based studies contributing the highest output. Publications on LLM-based applications have also increased during recent years. This bibliometric analysis summarizes the distribution of publications, research themes, and methodological trends in ophthalmic artificial intelligence and provides a basis for future clinical and research applications.}, }
@article {pmid42624312, year = {2026}, author = {de Carlo Forest, TE and Mathias, MT and Grove, N and Manoharan, N and Cordaro, N and Beckwith, AD and Nebbia, G and McNamara, SM and Kalpathy-Cramer, J and Lynch, AM and Mandava, N}, title = {Describing Candidate Geographic Atrophy Phenotypes and Their Different Growth Parameters.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.08.023}, pmid = {42624312}, issn = {1879-1891}, abstract = {PURPOSE: Describe distinct candidate geographic atrophy (GA) phenotypes in age-related macular degeneration (AMD) and their different growth parameters.<br><br>DESIGN: Prospective cohort study.<br><br>METHOD: Patients with GA enrolled in the University of Colorado AMD Registry from 9/2014-9/2022, with follow-up through 4/2023 were included. Patients with &#x2265;five fundus autofluorescence (FAF) time points were included. Longitudinal FAFs for each patient's eye were reviewed by two graders for candidate GA phenotype: (1) unifocal foveal-involving, (2) large coalescing multifocal, (3) small numerous multifocal, as well as presence of a concomitant peripapillary component. Each FAF image was processed using an artificial intelligence (AI) based segmentation model to automatically delineate GA lesions and calculate lesion area, with manual review and adjustment performed by a vitreoretinal specialist. Square-root transformed (SQRT) growth rate was calculated per eye. Gompertz modelling of GA growth was performed to estimate each eye's maximum GA growth rate and maximum projected GA size. Linear regression using generalized estimating equations was used to estimate associations between phenotypes and measures of GA growth rate.<br><br>RESULTS: 81 eyes with GA from 48 patients were included. Average subject age was 80 years (SD: 8). Average baseline GA size was 6.4 mm[2] (SD:7.5). Eyes with a peripapillary component had faster modeled maximum GA growth rates (Beta 0.37; 95%CI:0.16,0.59; p<0.001) and higher predicted maximum GA size (Beta 0.24; 95%CI:0.10,0.38; p<0.001) in univariate analysis. After adjusting for presence of a peripapillary component, the large coalescing multifocal and small numerous multifocal phenotypes had larger predicted maximum GA sizes than the unifocal foveal-involving phenotype (Beta 0.10; 95%CI:0.03,0.18; p=0.009 and Beta 0.10; 95%CI:-0.00,0.21; p=0.059, respectively). The small numerous multifocal phenotype had faster SQRT and modeled maximum GA growth rates compared to the unifocal foveal-involving phenotype (Beta 0.09; 95%CI:0.03,0.16; p=0.005 and Beta 0.29; 95%CI:0.13,0.44; p<0.001, respectively), and the large coalescing multifocal phenotype had borderline faster SQRT growth rates than the unifocal foveal-involving phenotype (p=0.05). Further, the small numerous multifocal phenotype had marginally higher modeled maximum GA growth rates than the large coalescing multifocal phenotype (estimated marginal mean difference 0.200mm/yr; 95%CI:-0.00,0.40; p=0.054).<br><br>CONCLUSION: We describe three candidate GA phenotypes and their different growth parameters. The large coalescing multifocal and small numerous multifocal phenotypes had more severe growth trajectories, and presence of a peripapillary component portended more severe outcomes. This may have implications for clinical trial interpretation and clinical prognostication.}, }
@article {pmid42626053, year = {2026}, author = {Zeppieri, M and Capobianco, M and Visalli, F and Khouyyi, M and Musa, M and Avitabile, A and Leandro, I and Giglio, R and Tognetto, D and Gagliano, C and D'Esposito, F and Cappellani, F}, title = {Artificial intelligence in ophthalmology: From diagnostic accuracy to clinical application.}, journal = {World journal of methodology}, volume = {16}, number = {3}, pages = {115265}, pmid = {42626053}, issn = {2222-0682}, abstract = {Artificial intelligence in ophthalmology encounters a continual challenge: Systems proficient in picture classification seldom yield quantifiable enhancements in patient outcomes. The primary concern is the disparity between pixel-level performance metrics and their clinical significance. Primary obstacles encompass data bias, domain shift, and label noise, exacerbated by the lack of prospective, randomized deployment trials. The frequent disregard for patient-centered objectives, cost-effectiveness, and equity evaluations is significant. Rectifying these deficiencies necessitates stringent external validation, established decision criteria, and ongoing surveillance within actual clinical practices. Transparent reporting criteria and the deliberate incorporation of human-factors engineering are essential. Only by bridging this gap can algorithmic accuracy be converted into significant diagnostic precision for glaucoma, diabetic retinopathy, and macular conditions (specifically diabetic macular edema and age-related macular degeneration). This paper aims to assess the limits of using high-performing artificial intelligence systems in ocular image processing, which seldom lead to enhanced patient outcomes, and to delineate the scientific, clinical, and practical techniques required to close this gap.}, }
@article {pmid42626541, year = {2026}, author = {Xin, X and Zhao, X and Ling, F and Qin, L and Liu, X and Liu, C}, title = {CircMETTL3 Inhibits H2O2-Induced Senescence, Oxidative Stress, and DNA Damage in ARPE-19 Cells via miR-100/BMPR2 Axis.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {3194421}, pmid = {42626541}, issn = {2090-004X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common degenerative eye disease that eventually leads to irreversible vision loss. CircRNAs have received increasing attention for their regulatory role in AMD. In this study, whole transcriptome sequencing identified differentially expressed circRNA (circMETTL3) in AMD. Previous studies have unlocked the potential mechanism of circMETTL3 in cancer, but its role in AMD has not been studied.<br><br>METHODS: ARPE-19 cells treated with H2O2 were used as the AMD cell model. The senescence, oxidative stress, and DNA damage of ARPE-19 cells were determined by SA-&#x3b2;-gal staining, DCFH-DA staining, and IF assay. The levels of RPE-specific markers or mRNA levels were assessed using western blot assay. The potential mechanism of circMETTL3 was investigated by luciferase reporting assay and RIP assay.<br><br>RESULTS: CircMETTL3 was revealed to decrease in AMD cell models. The addition of circMETTL3 decreased SA-&#x3b2;-gal staining and ROS production and facilitated cell viability in H2O2-treated ARPE-19 cells. Moreover, &#x3b3;H2AX and KRT18 levels were suppressed, and TJP1, BEST1, and CTNNB1 protein levels were increased by circMETTL3 addition. In addition, circMETTL3 could bind to and negatively regulate miR-100. Overexpression of miR-100 exacerbated senescence, oxidative stress, and DNA damage in H2O2-treated ARPE-19 cells, which reversed the effects of circMETTL3. Furthermore, BMPR2 was targeted by miR-100. Overexpression of BMPR2 inhibited H2O2-induced cell damage in ARPE-19 cells, which reversed the effects of miR-100.<br><br>CONCLUSIONS: In sum, these findings demonstrated that the circMETTL3/miR-100/BMPR2 axis plays a vital regulatory role in AMD development.}, }
@article {pmid42627194, year = {2026}, author = {Pitsillidou, O and Petrou, P and Postma, MJ}, title = {Cost-neutral adoption of anti-VEGF therapies in neovascular age-related macular degeneration.}, journal = {Expert review of pharmacoeconomics &amp; outcomes research}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/14737167.2026.2717293}, pmid = {42627194}, issn = {1744-8379}, abstract = {OBJECTIVE: In therapeutic classes characterized by outcome equivalence, the decision problem shifts from incremental cost-effectiveness to cost-neutral pricing. This study formalizes a break-even pricing framework, translating real-world utilization and costs into cost-neutral price thresholds, using anti-VEGF therapies for neovascular age-related macular degeneration (nAMD) as a case study.<br><br>METHODS: A cost-minimization framework was applied from a public payer perspective in a single-payer system (Cyprus). Five anti-VEGF agents were evaluated over 3 years with 3.5% discounting. Injection frequencies were derived as weighted averages of treat-and-extend and pro re nata regimens from Phase 3/4 trials, with year 3 extrapolated from year 2. Break-even prices were defined as unit prices yielding equal discounted per-patient costs versus comparators. First-line thresholds used bevacizumab; second-line thresholds used a utilization-weighted comparator. Sensitivity analyses were conducted.<br><br>RESULTS: Bevacizumab defined the lowest-cost benchmark (&#x20ac;4,130). Cost-neutral first-line use of newer agents required price reductions of 84-98%. Under second-line utilization, several agents fell below break-even thresholds at list prices. Key drivers were acquisition price, injection frequency, and monitoring costs.<br><br>CONCLUSION: Break-even pricing generates explicit cost-neutral thresholds under outcome equivalence. While jurisdiction-specific, the framework is transferable and supports consistent pricing decisions in single-payer systems.}, }
@article {pmid42627258, year = {2026}, author = {Iglicki, M and Zur, D and Melamud, JI and Loewenstein, A}, title = {Biomarker-Guided Management in Vitreoretinal Diseases: Integrating Imaging, Pharmacotherapy, and Surgical Decision-Making-A Narrative Review.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004984}, pmid = {42627258}, issn = {1539-2864}, abstract = {PURPOSE: To synthesize current evidence on imaging biomarkers in vitreoretinal diseases and to review the potential for a biomarker-guided framework integrating imaging, pharmacotherapy, and surgical decision-making in contemporary clinical practice.<br><br>METHODS: This narrative review integrates published evidence and clinical insights on optical coherence tomography (OCT) and OCT angiography (OCTA)-derived biomarkers, focusing on their role in predicting disease behavior, therapeutic response, and surgical indications.<br><br>RESULTS: Key imaging biomarkers-including disorganization of the retinal inner layers (DRIL), hyperreflective foci (HRF), intraretinal and subretinal fluid patterns, and vascular perfusion changes-demonstrate significant value in stratifying disease phenotype and guiding management. Biomarker-based approaches enable differentiation between angiogenic and inflammatory patterns, supporting individualized therapeutic strategies. These include optimized use of anti-vascular endothelial growth factor therapy, corticosteroid-based treatments, and newer long-acting agents. In addition, imaging biomarkers play a central role in identifying surgical candidates and determining timing of intervention, particularly in tractional maculopathies and refractory disease.<br><br>CONCLUSION: A biomarker-guided approach provides a clinically actionable framework for personalized vitreoretinal care. The integration of multimodal imaging with pharmacologic and surgical decision-making represents a critical step toward precision medicine, with the potential to improve outcomes and reduce treatment burden.}, }
@article {pmid42623949, year = {2026}, author = {Xie, Y and He, P and Lv, J and Li, X and Zhou, X and Li, Z and Jiang, X and Zhang, L and Yu, Y and Chen, F}, title = {Antioxidant hydrogel eye drops for the effective management of dry age-related macular degeneration by enhancing SIRT1/Nrf2 signaling.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {161}, number = {}, pages = {158709}, doi = {10.1016/j.phymed.2026.158709}, pmid = {42623949}, issn = {1618-095X}, abstract = {BACKGROUND: Dry age-related macular degeneration (dAMD) is a major cause of irreversible vision loss, in which oxidative stress-induced retinal pigment epithelial injury plays a key role. Astragaloside IV (ASIV) has antioxidant potential but is limited by poor aqueous solubility and ocular bioavailability.<br><br>PURPOSE: To evaluate the retinal protective effects of an ASIV-loaded antioxidant hydrogel eye drop (ALG) in experimental dAMD.<br><br>METHODS: A NaIO&#x2083;-induced mouse model of dAMD was established. Retinal protection was evaluated using hematoxylin and eosin (H&amp;E) staining, immunofluorescence, ophthalmic imaging, and functional examinations. Cytocompatibility and cellular uptake were assessed in ARPE-19 cells.<br><br>RESULTS: ALG underwent a sol-gel transition at 35 &#xb0;C and displayed a markedly sustained release profile compared with free ASIV. In vivo, ALG reduced retinal ROS accumulation and increased retinal sirtuin 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. In addition, ALG exhibited favorable cytocompatibility. Compared with liposomes and eye drops, the liposome gel also showed greater uptake by ARPE-19 cells.<br><br>CONCLUSION: ALG attenuated oxidative stress-related retinal injury, and meanwhile retinal SIRT1 and Nrf2 expression increased. Therefore, ALG may exert therapeutic effects against dAMD in association with SIRT1/Nrf2 upregulation.}, }
@article {pmid42622344, year = {2026}, author = {Pandala, N and Haefeli, LM and Lang, M and Stone, EM and Mullins, RF and Tucker, BA and Han, IC}, title = {Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {8}, pages = {17}, doi = {10.1167/tvst.15.8.17}, pmid = {42622344}, issn = {2164-2591}, mesh = {Animals ; Rats, Sprague-Dawley ; *Disease Models, Animal ; *Choroid/injuries/pathology/drug effects ; Rats ; *Retinal Degeneration/pathology/therapy ; Iodates/toxicity ; Male ; Immunohistochemistry ; }, abstract = {PURPOSE: Loss of the choroid is an important pathophysiological step in retinal diseases ranging from age-related macular degeneration (AMD) to choroideremia. However, current models of choroidal injury, such as laser photocoagulation-induced injury, induce acute tissue damage that does not parallel the gradual loss seen in most retinal degenerations. As such, there remains a need for models of targeted choroidal injury to study mechanisms of disease and develop potential treatments.<br><br>METHODS: We report a targeted choroidal injury model using bioconjugated saporins (immunotoxins) against cluster of differentiation (CD) domains CD38 and CD105. To induce injury, 10&#xa0;&#xb5;L of bioconjugate solution or control (phosphate-buffered saline) was delivered via suprachoroidal injection in wild-type Sprague-Dawley (SD) and Sprague-Dawley Rag2/Il2rg (SRG; double-knockout) rats. The extent and severity of choroidal injury were compared with animals treated with sodium iodate administered via tail vein injections at 1, 2, and 3 weeks post-treatment using clinical imaging and immunohistochemistry.<br><br>RESULTS: Choroidal injury induced by either anti-CD38 or anti-CD105 immunotoxin was targeted to the choroid and localized to the sector of the injection, unlike global destruction induced by sodium iodate. Immunotoxin-induced vascular damage remained constant over 3 weeks, without choroidal neovascularization seen, whereas sodium iodate caused progressive and severe injury of the choroid and overlying retina.<br><br>CONCLUSIONS: Suprachoroidal injection of anti-CD38 and anti-CD105 immunotoxins can induce localized and durable choroidal injury in both wild-type and immunosuppressed rats.<br><br>TRANSLATIONAL RELEVANCE: Immunotoxin-based models of targeted choroidal injury may be useful for understanding pathophysiologic mechanisms and developing therapies in conditions involving choroidal cell death.}, }
@article {pmid42622722, year = {2026}, author = {Katabami, T and Ota, M and Saeki, Y and Yashiro, K and Aoki, S and Kitamoto, K and Terao, R and Azuma, K}, title = {Faricimab for treatment-naïve nAMD: 1- and 2-year outcomes and PS-OCT polarimetric entropy.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42622722}, issn = {1573-2630}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Visual Acuity ; Intravitreal Injections ; Female ; Male ; Aged ; Follow-Up Studies ; Time Factors ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Fluorescein Angiography/methods ; Fundus Oculi ; Entropy ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: To evaluate 1- and 2-year real-world outcomes of intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration (nAMD) and to explore factors associated with visual acuity change, including polarization-sensitive OCT (PS-OCT)-derived polarimetric entropy (PE).<br><br>METHODS: This retrospective single-center study included 27 treatment-na&#xef;ve nAMD eyes initiating faricimab; all eyes were evaluable at 1&#xa0;year (n = 27) and 18 at 2&#xa0;years (n = 18). BCVA (logMAR), central retinal thickness (CRT), PE, and entropy-defined HRF-like foci (HEF)-related metrics were assessed. Associations with &#x394;logMAR (post-pre) were examined using multivariable linear regression. Prespecified baseline-BCVA-adjusted and EZ-adjusted sensitivity models were additionally performed. EZ integrity was graded at the fovea and included in sensitivity analyses.<br><br>RESULTS: BCVA improved from 0.40&#x2009;&#xb1;&#x2009;0.28 to 0.20&#x2009;&#xb1;&#x2009;0.23 at 1&#xa0;year (P&#x2009;<&#x2009;0.0001). In the 2-year cohort, BCVA improved from 0.35&#x2009;&#xb1;&#x2009;0.28 to 0.15&#x2009;&#xb1;&#x2009;0.20 at 1&#xa0;year (P&#x2009;=&#x2009;0.0003) and 0.12&#x2009;&#xb1;&#x2009;0.17 at 2&#xa0;years (P&#x2009;=&#x2009;0.0004). CRT decreased from 337.5&#x2009;&#xb1;&#x2009;159.8 to 186.7&#x2009;&#xb1;&#x2009;47.3&#xa0;&#xb5;m at 1&#xa0;year (P&#x2009;<&#x2009;0.0001) and from 337.3&#x2009;&#xb1;&#x2009;185.9 to 185.1&#x2009;&#xb1;&#x2009;46.4&#xa0;&#xb5;m at 1&#xa0;year (P&#x2009;=&#x2009;0.0019) and 181.2&#x2009;&#xb1;&#x2009;60.9&#xa0;&#xb5;m at 2&#xa0;years (P&#x2009;<&#x2009;0.0001). Mean PE increased at 1&#xa0;year (0.44&#x2009;&#xb1;&#x2009;0.06 to 0.46&#x2009;&#xb1;&#x2009;0.05; P&#x2009;<&#x2009;0.0001) but not from baseline to 2&#xa0;years (P&#x2009;=&#x2009;0.81). In multivariable analyses, &#x394;PE was associated with 1-year &#x394;logMAR (&#x3b2;;&#x2009;-&#x2009;2.7 to -&#x2009;2.8; P&#x2009;&#x2264;&#x2009;0.01) together with MNV subtype, whereas at 2&#xa0;years the incremental association of &#x394;PE was attenuated in baseline-adjusted and EZ-adjusted sensitivity analyses in the 2-year completer cohort.<br><br>CONCLUSIONS: Faricimab treatment was associated with sustained functional and anatomical improvement in treatment-na&#xef;ve nAMD. PE change may serve as a complementary imaging marker associated with visual improvement, particularly at 1&#xa0;year, while longer-term associations warrant confirmation in larger cohorts.}, }
@article {pmid42623367, year = {2026}, author = {Do Song, Y and Kim, J and Jang, JH and Kim, Y and Oh, HK and Ji, MJ and Choi, M and Park, M and Kim, DW}, title = {Generation of dual mouse models of retinal degeneration with slow and rapid progression driven by ectopic RIP3 expression.}, journal = {PloS one}, volume = {21}, number = {8}, pages = {e0356284}, pmid = {42623367}, issn = {1932-6203}, mesh = {Animals ; *Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism ; Mice, Transgenic ; *Disease Models, Animal ; Mice ; *Retinal Degeneration/pathology/genetics/metabolism ; Disease Progression ; Retinal Pigment Epithelium/pathology/metabolism ; Humans ; }, abstract = {Dry age-related macular degeneration (AMD) is a leading cause of blindness, characterized by progressive loss of retinal pigment epithelium (RPE) and subsequent photoreceptor degeneration. Current experimental models, including sodium iodate-induced injury, fail to fully recapitulate the chronic, age-related progression of the human disease. Although RIP3-mediated necroptosis has been strongly implicated in RPE cell death, its direct contribution to retinal degeneration in vivo remains unclear. To address this limitation, we generated two RIP3 transgenic mouse lines with distinct patterns of RIP3 overexpression. While RIP3-Tg mice exhibit systemic RIP3 overexpression, RIP3-Tg-RPE mice display additional RPE-specific overexpression beyond the levels observed in RIP3-Tg mice. We then evaluated these transgenic lines, along with wild-type controls, for age-driven retinal degeneration by using optical coherence tomography (OCT), behavior-based visual function assays, and molecular profiling of inflammation and cell death. First, RIP3-Tg mice exhibited gradual retinal thinning, progressive visual decline, and sustained upregulation of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) over 6-15 months, recapitulating the slow progression of dry-AMD. Second, RIP3-Tg-RPE mice, which exhibit further RPE-specific increases in RIP3 expression, showed markedly accelerated retinal degeneration, with significant structural and functional deficits evident as early as 2 months of age. These findings indicate that ectopic RIP3 expression in the RPE contributes to inflammatory responses and subsequent retinal degeneration. Collectively, our results highlight RIP3 as a potential contributing factor in the progression of retinal degeneration and introduce biologically relevant transgenic models that capture both slow and accelerated disease progression. These models provide a valuable platform for investigating disease mechanisms and developing therapeutic strategies targeting necroptosis in dry-AMD.}, }
@article {pmid42623818, year = {2026}, author = {Dai, J and Zhou, X and Zeng, M and Sun, Z and Luo, W and He, Y and Peng, Q and Wu, Q}, title = {Standard Tea Intake Is Causally Associated with a Reduced Risk of Wet Age-Related Macular Degeneration: A Mendelian Randomization Study.}, journal = {Physiological genomics}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiolgenomics.00314.2025}, pmid = {42623818}, issn = {1531-2267}, support = {2023JJ40474//Youth Science Fund of Hunan Science Foundation/ ; 82004427//National Natural Science Foundation of China/ ; 2017TP1018//Key Laboratory of TCM Prevention and Treatment of Eye,Ear, Nose and Throat Diseases of Hunan Province/ ; 2018TP2008//Hunan Provincial Engineering Technology Research Center for TCM Prevention and Treatment of Eye, Ear, Nose and Throat Diseases and Visual Function Protection/ ; 2023SK4038//Hunan Clinical Medical Research Center of Ophthamology (TCM), China/ ; }, abstract = {Researchers have posited that increased consumption of tea and coffee may be associated with more favourable treatment outcomes in patients with age-related macular degeneration (AMD). However, there is no clear evidence regarding the causal associations. To delve deeper into this potential connection, scientists employed a rigorous method known as Mendelian randomization (MR). This technique was utilized to explore the causal impact of tea and coffee consumption on the development or progression of AMD. With the aim of investigating the cause-effect relationship between 16 tea and coffee consuming subtypes and 3 AMD, we designed a two-sample MR-study using comprehensive data from genome-wide association studies (GWAS). The major approach adopted was inverse variance weighting (IVW). Furthermore, we implemented complementary methods like the weighted median (WM), weighted mode, and MR-Egger to strengthen our findings. Sensitivity analyses, including MR-Egger, MR-PRESSO, leave-one-out, and Cochran's Q tests, were employed to validate results, explore heterogeneity and pleiotropy, and pinpoint potential biases. 268 instrumental variables were selected for MR analysis. The results showed that standard tea intake may be a protective factor for wet AMD (OR=0.7076, 95%CI=(0.5776 - 0.8668), P=8×10-4, PFDR=0.0402). Sensitivity analysis suggests that the results are robust. Our findings provide genetic evidence that standard tea intake is a protective factor against wet AMD, providing new insights into early risk stratification and prevention strategies for the disease.}, }
@article {pmid42609323, year = {2026}, author = {Singh Bhangu, J and Swarnkar, PK and Stewart, C and Rifat, M and Khalid, S and Al-Janabi, A and Awad, MH and Williams, GS}, title = {Faricimab versus Aflibercept for Discharge and Readmission in Neovascular Age-Related Macular Degeneration: A Lesion-Type Stratified, Real-World UK Analysis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {593566}, pmid = {42609323}, issn = {1177-5467}, abstract = {BACKGROUND: Anti-VEGF treatment improves outcomes in neovascular age-related macular degeneration (nAMD) management. No real-world data have compared discharge and readmission rates between Faricimab and Aflibercept 2mg, stratified by lesion type.<br><br>METHODS: A retrospective audit study of 1004 eyes in 912 patients diagnosed with nAMD. Patients received either Faricimab or Aflibercept 2mg. The outcomes assessed were central macular thickness CMT, best-corrected visual acuity BCVA, fluid resolution, discharge to community care defined as being asymptomatic for more than 6 months and then reviewed by optometrist, and readmission. Lesion types were classified into Type 1, Type 2, and Prepapillary. Statistical analysis used t-tests, chi-square, and appropriate nonparametric tests.<br><br>RESULTS: The demographic of the patients in this study consisted of 60.6% of women with participants being on average 76.9 years old. Type 1 lesions had a greater change from baseline CMT, and a greater change in BCVA than Type 2 lesions. Discharge rates from hospital and the average time to discharge from hospital was greater for Faricimab (84.1%, 378 days) compared with Aflibercept (69.5%, 1048 days, p < 0.0001). The number of eyes readmitted was lower for Faricimab (14.7% vs 29.1%) and was not different for lesion type (p = 0.96). The number of injections was not different amongst discharged patients and readmitted patients. In this retrospective cohort, service outcomes at discharge and readmission appeared to differ between Faricimab and aflibercept, whereas no clear differences were observed by lesion type.<br><br>CONCLUSION: In this real-world audit, treatment with Faricimab was associated with higher discharge rates, earlier discharge, and fewer readmissions compared with aflibercept, although these findings should be interpreted as observational associations rather than causal effects. Lesion type did not appear to be an independent predictor of these service outcomes within the limits of this analysis.}, }
@article {pmid42610095, year = {2026}, author = {Parmar, UPS and Singh, RB and Bhullar, S and Gupta, R and Gauba, A and Shayan, M and Rai, K and Ichhpujani, P}, title = {Nanotechnological Advances in Ocular Therapeutics: A Narrative Review of Drug Delivery Platforms, Clinical Applications, and Translational Challenges.}, journal = {Nanotechnology, science and applications}, volume = {19}, number = {}, pages = {611594}, pmid = {42610095}, issn = {1177-8903}, abstract = {PURPOSE: Nanotechnology-based ocular drug delivery systems offer a promising approach to overcoming the anatomical and physiological barriers that limit the efficacy of conventional ophthalmic formulations, where topical bioavailability typically remains below 5% owing to rapid nasolacrimal drainage, precorneal tear turnover, and corneal impermeability. This narrative review synthesises current evidence on nanocarrier design, delivery pathways, and disease-specific therapeutic applications, incorporating cross-platform comparison across six nanocarrier systems and explicit stratification of evidence by translational stage.<br><br>METHODS: A structured narrative review was conducted using OVID MEDLINE, Embase, Scopus, Web of Science, and PubMed from database inception to September 2025, supplemented by citation chaining and targeted Google Scholar searches. Data extraction focused on carrier architecture, drug-loading and release characteristics, delivery routes, mechanistic behaviour, therapeutic outcomes, and safety profiles. This review was conducted in accordance with the general principles for narrative reviews as described in the Scale for the Assessment of Narrative Review Articles (SANRA).<br><br>RESULTS: Key nanocarrier classes included liposomes, polymeric micelles, dendrimers, nanosuspensions, nanoemulsions, and chitosan- and protein-based nanoparticles. Compared with conventional formulations, these systems demonstrated improved corneal residence, enhanced mucoadhesion, increased transscleral diffusion, reduced dosing frequency, and sustained intraocular exposure. Clinically translated examples include cyclosporine A nanomicelle and nanoemulsion formulations, marketed as Cequa (0.09%), Restasis (0.05%), and Ikervis (0.1%), approved for dry eye disease, and a subconjunctival PLGA nanoparticle depot that achieved greater than 20% intraocular pressure reduction sustained over 90 days from a single injection in early clinical evaluation. Applications spanned anterior-segment disorders, including dry eye disease, conjunctivitis, infectious keratitis, ocular inflammation, and glaucoma, and posterior-segment diseases such as diabetic retinopathy, age-related macular degeneration, retinoblastoma, and retinopathy of prematurity.<br><br>CONCLUSION: Lipid-based and polymeric nanocarrier platforms are currently closest to clinical translation, with approved formulations and early-phase trial data supporting meaningful therapeutic advantages over conventional delivery. Realising the full potential of ocular nanomedicine will require addressing residual challenges in long-term ocular safety, manufacturing scalability, and regulatory compliance, particularly for posterior-segment applications, where non-invasive topical delivery remains largely at the preclinical stage.}, }
@article {pmid42611377, year = {2026}, author = {Yoo, HS and Yu, P and Zhou, C and Hosseini, A and Granville, DJ and Matsubara, JA}, title = {Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.}, journal = {Acta neuropathologica}, volume = {152}, number = {1}, pages = {}, pmid = {42611377}, issn = {1432-0533}, mesh = {Humans ; *Granzymes/metabolism ; Animals ; *Neurodegenerative Diseases/enzymology/metabolism/pathology ; *Neuroinflammatory Diseases/enzymology/metabolism/pathology ; }, abstract = {Neurodegenerative diseases are increasingly recognized as disorders shaped not only by intrinsic neuronal vulnerability, but also by chronic neuroinflammation mediated by maladaptive neuroimmune signaling. Granzymes, a family of serine proteases classically studied for their cytotoxic roles in anti-viral and anti-tumor immunity, are emerging as important mediators of central nervous system (CNS) pathology. In addition to their canonical intracellular functions, granzymes can act extracellularly to cleave the extracellular matrix (ECM), activate cell-surface receptors, disrupt epithelial barrier function, amplify inflammatory cascades, and alter glial and neuronal responses to injury. In this review, we synthesize current knowledge on the roles of Granzyme A (GzmA), Granzyme B (GzmB), Granzyme H (GzmH), and Granzyme K (GzmK) in neurodegeneration and neuroinflammation across diverse CNS disease and injury contexts, such as Alzheimer's disease (AD), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and age-related macular degeneration (AMD). GzmB is the most extensively characterized, with evidence supporting both intracellular neurotoxicity and extracellular pathogenic functions mediated through protease-activated receptor signaling, ECM cleavage, outer blood-retina barrier disruption, angiogenesis, fibrosis, and chronic inflammation. GzmA is implicated in tau proteolysis and structural destabilization of neurons and astrocytes, while GzmK has emerged as a context-dependent regulator of neuroinflammation through PAR-1 activation, microglial modulation, and complement cascade activation. GzmH remains the least understood but may contribute to nerve injury through mechanisms that are only beginning to be defined. We also discuss endogenous and pharmacological granzyme inhibition, highlighting the therapeutic promise of selective extracellular granzyme targeting, particularly for GzmB, while emphasizing the current lack of selective inhibitors for GzmA, GzmK, and GzmH. Collectively, these findings position granzymes as underappreciated neuroimmune effectors and potential therapeutic targets in neurodegenerative diseases and CNS injury.}, }
@article {pmid42612071, year = {2026}, author = {Mai, J and Liu, T and Yao, Y}, title = {lncRNAs and miRNAs in Exosome-Mediated Macrophage Polarization: Implications for Age-Related Macular Degeneration.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {233}, pages = {}, doi = {10.3791/71424}, pmid = {42612071}, issn = {1940-087X}, mesh = {*Exosomes/genetics/metabolism/immunology ; *Macrophages/immunology/metabolism/cytology ; Humans ; *Macular Degeneration/genetics/pathology/immunology/metabolism ; *MicroRNAs/genetics/immunology ; *RNA, Long Noncoding/genetics/immunology/metabolism ; Animals ; }, abstract = {Age-related macular degeneration (AMD) is a progressive and multifactorial retinal disease that represents a leading cause of irreversible vision loss among the elderly. Increasing evidence suggests that exosomes, small extracellular vesicles that mediate intercellular communication, play a critical role in regulating immune and angiogenic signaling in the retina. These vesicles transport diverse molecular cargo, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Recent studies highlight the importance of exosome-mediated ncRNA signaling in macrophage polarization, a key immunological process involved in AMD progression. Exosomal miRNAs and lncRNAs released from retinal pigment epithelium (RPE) cells, endothelial cells, and immune cells can regulate macrophage phenotypes and alter inflammatory and angiogenic pathways within the retina. Dysregulated ncRNAs, including miR-21, miR-23a, miR-150, and the lncRNA NEAT1, have been implicated in promoting macrophage-driven inflammation, lipid dysregulation, and pathological neovascularization. Through these mechanisms, exosomal ncRNAs contribute to the transition from early retinal stress and drusen formation to advanced forms of AMD characterized by geographic atrophy or choroidal neovascularization. In addition to their mechanistic role in disease progression, exosomal ncRNAs show promise as minimally invasive biomarkers for early diagnosis and monitoring of AMD. Their stability in biological fluids, such as plasma, aqueous humor, and vitreous fluid, suggests their potential use in liquid biopsy approaches. Moreover, engineered exosomes carrying therapeutic ncRNAs represent a promising strategy for modulating macrophage polarization and restoring retinal immune homeostasis. This review integrates current knowledge on the exosome-ncRNA-macrophage axis in AMD, highlighting its role in retinal immune regulation, disease progression, and therapeutic development. Understanding this emerging signaling network may provide new opportunities to develop precision diagnostic tools and targeted therapies to prevent or slow retinal degeneration in AMD.}, }
@article {pmid42612872, year = {2026}, author = {Gu, R and Hou, B and Hébert, M and Indurkar, A and Yang, Y and Chew, EY and Keenan, TDL and Lu, Z}, title = {Toward Multimodal Conversational AI for Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.08.010}, pmid = {42612872}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate OcularChat, an age-related macular degeneration (AMD)-specific multimodal large language model for interpreting color fundus photographs.<br><br>METHODS: A general-purpose multimodal large language model was fine-tuned using 705,850 simulated patient-physician dialogues paired with 46,167 AREDS images, then tested on separate AREDS and AREDS2 datasets.<br><br>RESULTS: In AREDS, OcularChat correctly classified advanced AMD, pigmentary abnormalities, and drusen size in 95.4%, 84.9%, and 67.8% of images, respectively. Retina specialists rated its responses more highly than those of the same model without fine-tuning.<br><br>CONCLUSIONS: OcularChat gives the potential to support clinician-supervised, interpretable AMD image review, research annotation, and education, requiring prospective validation before clinical deployment.}, }
@article {pmid42615798, year = {2026}, author = {Hughes, D and Larue, AEM and Taus, P and Markert, E and Bhattacharyya, D and Atlasi, Y and Neubauer, H and Xu, H and Chen, M}, title = {A Novel Ocular Fibrosis Signature for AMD Using the Two-Stage Laser-Induced Subretinal Fibrosis Mouse Model.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {49}, doi = {10.1167/iovs.67.10.49}, pmid = {42615798}, issn = {1552-5783}, mesh = {Animals ; Mice ; Fibrosis ; Disease Models, Animal ; *Retinal Pigment Epithelium/pathology/metabolism ; Humans ; Mice, Inbred C57BL ; Choroidal Neovascularization ; Choroid/pathology/metabolism ; *Macular Degeneration/genetics/pathology/metabolism ; Male ; }, abstract = {PURPOSE: Subretinal fibrosis is a major cause of irreversible vision loss in neovascular age-related macular degeneration (AMD), yet no effective antifibrotic therapies exist due to poorly defined molecular drivers. This study aimed to derive and validate a persistent ocular fibrosis signature using the two-stage laser-induced subretinal fibrosis mouse model and to assess its translational relevance in human AMD.<br><br>METHODS: RNA sequencing (RNA-seq) was performed on retinal pigment epithelium (RPE)/choroid tissues collected at days 3, 6, and 10 following the second laser injury in the two-stage model. A novel core fibrosis signature of 88 persistently upregulated genes was observed across all time points and cross-validated in an independent mouse dataset (GSE189555) and multiple human AMD RNA-seq datasets (GSE115828, GSE146887, GSE135092), including surgically extracted choroidal neovascularization (CNV) membranes and macular RPE/choroid samples. Key signature genes were further validated by immunofluorescence in human subretinal fibrotic and age-matched tissues.<br><br>RESULTS: The novel ocular fibrosis signature was enriched in epithelial-mesenchymal transition, complement activation, and inflammatory pathways and showed choroid-specific expression with minimal retinal involvement. Cross-validation on independent chronic mouse data and multiple human AMD datasets (peripheral retina, surgically extracted CNV membranes, and macular RPE/choroid) confirmed a progressive enrichment in advanced disease stages. Immunofluorescence in human fibrotic tissue validated key genes (tenascin C, tissue inhibitor of metalloproteinases 1, and apelin receptor) and showed colocalization with myofibroblast-like cells and microglia.<br><br>CONCLUSIONS: We identified a novel, persistent, choroid-specific ocular fibrosis signature with strong cross-species conservation, highlighting fibrogenic-associated drivers and providing a valuable translational tool to understand subretinal fibrosis development and targeted antifibrotic therapies in neovascular AMD.}, }
@article {pmid42615809, year = {2026}, author = {Sarwar, F and Kristoff, C and Kavoussi, S}, title = {Prevalence of Potentially Sight-Threatening Pathology Detected by Non-Mydriatic Fundus Photography in a National Diabetic Screening Platform.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-4}, doi = {10.3928/23258160-20260717-02}, pmid = {42615809}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: Hundreds, if not thousands, of non-mydriatic fundus images are acquired in primary care offices daily and uploaded for remote grading by ophthalmologists, retina specialists, and/or artificial intelligence. No prior studies of this magnitude have explored the yield of sight-threatening pathology identified on these platforms. The goal of this study is to report on the prevalence of potentially sight-threatening pathology during a 9-year experience with a single national telemedicine platform.<br><br>PATIENTS AND METHODS: This was a multicenter, non-interventional, non-masked, non-randomized, retrospective review of 1,190,754 consecutive gradable bilateral fundus exams obtained on non-mydriatic fundus cameras in the primary care setting and uploaded to a national platform. All images were interpreted by board-certified ophthalmologists and/or fellowship-trained retinal specialists.<br><br>RESULTS: In total, 44% of gradable exams were obtained on the Center Vue DRS camera, 38% on the Volk Pictor Plus, and the remainder on other cameras. Of these, 381,023 exams (32%) had evidence of pathology. Suspected moderate, severe, and proliferative diabetic retinopathy were present on 101,714 (9%), 23,988 (2%), and 30,515 (3%) exams, respectively. Macular edema was present on 27,712 exams (2%). Epiretinal membrane and age-related macular degeneration (total of exudative and dry) were present on 14,306 (1%) and 36,298 (3%) exams, respectively. Suspected glaucoma was present on 70,154 exams (6%). Papilledema, melanoma, posterior uveitis, and retinal detachment were reported in an "other pathology" category that included 116,762 exams (10%).<br><br>CONCLUSION: Routine non-mydriatic fundus screening in the primary care setting detects diabetic and non-diabetic pathology in approximately one-third of patients.}, }
@article {pmid42619175, year = {2026}, author = {Qu, L and Cai, Y}, title = {Drug Delivery Research Related to Posterior Segment Eye Diseases: A Bibliometric Analysis of Global Trends and Therapeutic Hotspots.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {}, number = {}, pages = {10807683261477884}, doi = {10.1177/10807683261477884}, pmid = {42619175}, issn = {1557-7732}, abstract = {PURPOSE: Drug delivery to the posterior segment remains constrained by ocular barriers, short intraocular residence, repeated administration, and safety concerns. We mapped the global research structure of drug delivery research related to posterior segment eye diseases and identified major contributors, knowledge foundations, and therapeutic hotspots.<br><br>METHODS: English-language articles and reviews published from 1999 to 2024 were retrieved from the Web of Science Core Collection using a predefined topic search combining drug-delivery and posterior segment terms. Bibliometrix, VOSviewer, and CiteSpace were used to analyze publication growth, contributors, journals, highly cited articles, cocited references, keyword co-occurrence, citation bursts, thematic evolution, and conceptual structure.<br><br>RESULTS: The dataset contained 4,055 publications and showed sustained growth, with a higher output phase after 2020. The United States and China were the leading national contributors, while the University of Helsinki, University of Eastern Finland, Johns Hopkins University, and Emory University were prominent institutional contributors. Keyword, burst, and thematic analyses indicated a shift from permeability, pharmacokinetics, and sustained-release platforms toward macular degeneration, anti-VEGF-related therapy, injection burden, nanoparticles, long-acting systems, and clinically oriented formulation strategies.<br><br>CONCLUSION: Research has shifted from barrier characterization, pharmacokinetics, and sustained-release platforms toward macular degeneration, anti-VEGF-related therapy, injection burden, long-acting systems, and clinically oriented formulation strategies. These bibliometric signals indicate research activity rather than clinical effectiveness.}, }
@article {pmid42620072, year = {2026}, author = {Moore, NC and Song, YE and Gulyayev, AV and Miskimen, K and Miron, P and Laux, RA and Lynn, A and Fuzzell, SL and Hochstetler, SD and Miller, D and Caywood, LJ and Clouse, JE and Herington, SD and Wang, P and Liu, Y and Dorfsman, DA and Vance, JM and Nittala, MG and Sadda, SR and Stambolian, D and Scott, WK and Pericak-Vance, MA and Haines, JL}, title = {Heritability of Age-Related Macular Degeneration in the Amish.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.08.04.26359695}, pmid = {42620072}, abstract = {PURPOSE: Age-related Macular Degeneration (AMD), a degenerative disease of aging, leads to central vision loss and has a strong genetic risk. Genetic heritability, used to quantify genetic influence on a trait, has mainly focused on twin study designs but these are vulnerable to bias. Studying relatives beyond twins is necessary to bring clarity to the genetic burden of AMD and help focus the search for additional genetic risk loci.<br><br>METHODS: Through both single nucleotide polymorphism (SNP) and pedigree-based heritability methods, the heritability of AMD was analyzed using relationship informed analyses of families from an Amish population (n = 525). AMD status was determined using the Beckman grading scale (285 controls and 240 cases). An estimate of genetic relatedness preceded SNP heritability estimation, whereas the pedigree heritability model utilized genealogical reports. Primary models were adjusted for age, sex, and population structure. A comparison of SNP- and pedigree-based models followed heritability estimation. Sensitivity models adjusting for all possible combinations of three known strong AMD genetic risk variants were constructed.<br><br>RESULTS: SNP heritability is 55% +/- 13% (p= 9.87e-06) and the pedigree heritability is 49% +/- 18% (p= 3.06e-04). The sensitivity analyses revealed that the estimates were robust to changes in the inclusion of AMD variants as covariates.<br><br>CONCLUSIONS: These heritability estimates support existing twin and SNP-based AMD heritability estimates and corroborate the substantial involvement of genetics in AMD. Adjusting for known AMD variants revealed that additional genetic contribution exists, supporting a large polygenic effect in AMD.}, }
@article {pmid42620344, year = {2026}, author = {Tao, D and Zhou, D and Wu, M and Xie, P and Zhang, Y and Bao, J}, title = {ADORA2A activation restores lysosomal function and photoreceptor outer segment degradation in stressed retinal pigment epithelium.}, journal = {Frontiers in physiology}, volume = {17}, number = {}, pages = {1866784}, pmid = {42620344}, issn = {1664-042X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) involves early retinal pigment epithelium (RPE) dysfunction and impaired processing of photoreceptor outer segments (POS). We investigated whether ADORA2A regulates post-ingestive POS handling and lysosomal recovery under AMD-relevant stress.<br><br>METHODS: A2E-stressed ARPE-19 cells, primary porcine RPE cells, and a sodium iodate-induced mouse model were studied. ADORA2A was activated with CGS21680 and inhibited with ZM241385. POS handling, LC3B/Rubicon association with POS, lysosomal function, Rubicon depletion, chronic stress phenotypes, and retinal protection were assessed.<br><br>RESULTS: A2E increased ADORA2A expression while preserving receptor-dependent cAMP responsiveness. CGS21680 had modest effects on early POS binding and uptake but enhanced post-ingestive POS clearance and rhodopsin degradation; these effects were attenuated by ZM241385 and ADORA2A knockdown. CGS21680 increased LC3B and Rubicon association with POS-containing structures, improved lysosomal acidification, and restored DQ Green BSA processing, Cathepsin D activity, and V-ATPase-associated assembly. Bafilomycin A1 increased LC3-II and p62 accumulation and impaired CGS21680-associated POS clearance, supporting lysosome-dependent turnover. Rubicon depletion attenuated CGS21680-associated improvements in POS clearance and lysosomal acidification. CGS21680 also reduced chronic stress-associated autofluorescence, oxidative stress, apoptosis, and junctional disruption. These protective effects were reproduced in primary RPE cells. In sodium iodate-injured mice, CGS21680 preserved outer retinal structure, reduced FITC-BSA leakage, improved electroretinographic responses, and was accompanied by increased CREB phosphorylation and recovery of Cathepsin D proteolytic competence.<br><br>CONCLUSION: ADORA2A activation promotes Rubicon-associated, lysosome-dependent LC3 processing of internalized POS and restores lysosomal degradative competence, supporting ADORA2A as a potential therapeutic target for early AMD.}, }
@article {pmid42620739, year = {2026}, author = {Hunt, PW and Sezgin, E and Olshen, AB and Murad, N and Ambayec, GC and Schneider, MF and Jabs, DA}, title = {Associations of Host Genetics and Plasma Proteomics with Incident Age-Related Macular Degeneration in Persons with AIDS.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101318}, pmid = {42620739}, issn = {2666-9145}, abstract = {OBJECTIVE: To evaluate whether common plasma proteomic pathways connect host genetic risk factors to incident age-related macular degeneration (AMD) in persons with AIDS.<br><br>DESIGN: Nested case-control study.<br><br>PARTICIPANTS: Subset of persons enrolled in the Longitudinal Study of Ocular Complications of AIDS.<br><br>METHODS: Baseline cryopreserved plasma specimens were assayed for inflammatory and cardiovascular proteins using the Olink Inflammation Explore Panels 1 to 2 and the Cardiometabolic Explore Panels 1 to 2. Age-related macular degeneration&#x2011;associated genetic variants were assessed using Applied Biosystems Taqman probes. Baseline proteomic profiles for 26 persons who subsequently developed incident intermediate-stage AMD after 5 to 10 years of follow-up and 49 controls without AMD matched for age, natal sex, race/ethnicity, and follow-up duration were compared. False discovery rate correction was performed with the Storey Q method, and both unsupervised gene ontology pathway enrichment and dedicated pathway analyses were performed. Age-related macular degeneration&#x2011;associated plasma protein levels were compared between AMD high-risk and AMD low-risk genotypes.<br><br>MAIN OUTCOME MEASURES: Incident intermediate-stage AMD.<br><br>RESULTS: 371 (26%) of 1448 evaluable plasma proteins were associated with incident AMD at the false discovery rate Q < 0.05 threshold. Hallmark pathways significantly enriched in incident AMD included inflammation, complement, and fatty acid metabolism pathways. Complement factor H, a complement activation regulating protein with a genetic association with AMD, levels appeared to be associated with AMD (adjusted odds ratio: 0.12 per 2-fold increase, P = 0.055). Several related proteins in the Hallmark complement pathway were strongly associated with AMD, 16 including CD46, platelet-derived growth factor &#x3b2;, chemokine ligand 1, and CCL5 (all Q < 0.05), which have been linked to AMD risk in genetic studies. Among cholesterol homeostasis-related genes, lipoprotein lipase was associated with a decreased risk of AMD (adjusted odds ratio: 0.18 per 2-fold increase, Q = 0.008). Participants with AMD high-risk genotypes had elevated levels of shared proteins in inflammatory, complement, and fatty acid metabolism pathways.<br><br>CONCLUSIONS: Levels of several plasma proteins linked to the complement pathway and cholesterol homeostasis, which have been linked to AMD risk in genetic studies, are associated with incident AMD in people with AIDS. Plasma levels of shared inflammatory proteins linked to several different genetic AMD risk factors predicted AMD risk, suggesting common immunologic mechanisms linking genetic risk factors for AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42621091, year = {2026}, author = {Mohammadi, SS and Sikora, H and Bisen, J and Kim, H and Drakopoulos, M and Nadel, A and Hamzeh, N and Bains, H and Lyon, AT and Mirza, RG}, title = {Functional and Anatomic Outcomes at 12 Months After Switching to Faricimab in Treatment-Recalcitrant Neovascular Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261472089}, pmid = {42621091}, issn = {2474-1272}, abstract = {Purpose: To evaluate functional and anatomic outcomes over 12 months in patients with recalcitrant neovascular age-related macular degeneration (nAMD) whose treatment was transitioned to faricimab. Methods: This retrospective observational study included 36 patients (41 eyes) with treatment-recalcitrant nAMD previously treated with bevacizumab, ranibizumab, or aflibercept. Patients received 4 monthly intravitreal faricimab injections followed by individualized treatment intervals. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) images, and swept-source OCT angiography images were assessed at baseline, 6 months, and 12 months. Anatomic features evaluated included intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), macular neovascularization (MNV), and geographic atrophy (GA). Results: Mean (±SD) BCVA remained stable over the 12-month period (baseline, 0.289 ± 0.350 logMAR; 12 months, 0.306 ± 0.394 logMAR; P = .41). Treatment intervals increased from a mean of 5.29 weeks prior to the switch to faricimab to 7.58 weeks afterward. Anatomically, the proportion of eyes without IRF or SRF improved from 34.14% at baseline to 74.68% at 12 months. A significant reduction in PED maximum height was observed at 6 months, along with decreases in mean PED height and volume. MNV metrics demonstrated a significant decline in vessel area density at 6 months (P = .031), although no sustained significant changes were observed at 12 months. GA size increased by a mean of 0.41 mm[2]/year over the study period (P = .026). Conclusions: Switching to faricimab in treatment-recalcitrant nAMD maintained visual acuity, improved anatomic outcomes, and significantly extended injection intervals. These findings underscore faricimab's efficacy in managing refractory nAMD cases.}, }
@article {pmid42621295, year = {2026}, author = {Mares, V and Sacu, S and Frank-Publig, S and Eidenberger, A and Fuchs, P and Coulibaly, LM and Baratsits, M and Faustmann, G and Gumpinger, M and Sükei, E and Bogunovic, H and Reiter, GS and Leingang, O and Miere, A and Creuzot-Garcher, C and Kodjikian, L and Gualino, V and Wolff, B and Scheschy, U and Schmidt-Erfurth, U}, title = {Early Structure-Function Correlates in Neovascular Age-Related Macular Degeneration Using Artificial Intelligence-Derived OCT Biomarkers.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101281}, pmid = {42621295}, issn = {2666-9145}, abstract = {PURPOSE: To correlate automated artificial intelligence-based retinal fluid quantification with ellipsoid zone (EZ) thickness and loss, macular neovascularization (MNV) type, and visual function.<br><br>DESIGN: This is a post hoc analysis of a prospective, real-world, multicenter clinical trial.<br><br>SUBJECTS: Patients with active neovascular age-related macular degeneration (nAMD) were included.<br><br>METHODS: Best-corrected visual acuity (BCVA), measured using the ETDRS chart, OCT, OCT angiography, and microperimetry, were collected by the same certified examiners. Subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) volumes for the central 1- and 6- mm areas were calculated at baseline using the Fluid Monitor (Retinsight) on Spectralis OCT (Heidelberg Engineering). An automated algorithm segmented EZ thickness and loss detectable after fluid resolution at month 1.<br><br>MAIN OUTCOME MEASURES: Fluid volumes were associated with MNV type, EZ thickness and loss, retinal sensitivity, and BCVA using univariate and multivariate regression models and Wilcoxon rank-sum tests with bootstrapped confidence intervals. Spearman correlation was used to analyze retinal sensitivity and EZ loss.<br><br>RESULTS: Two hundred ninety eyes from 290 consecutive patients with active MNV were included in the study at baseline. Macular neovascularization type 1 was the most prevalent in this cohort. Comparing MNV types, lower amounts of IRF were found in type 1 (all P < 0.001) and lower amounts of SRF for type 3 (all P < 0.05), in the central 1- and 6-mm areas. A decreased BCVA at month 1 was associated with IRF in the central 1 mm at baseline (-6.8 letters/100 nL; P < 0.001). Intraretinal fluid and PED volumes at baseline were correlated with EZ loss at month 1 in the central 6 mm. High fluid volumes of IRF, SRF, and PED in the central 1- and 6- mm areas also correlated with decreased mean retinal sensitivity (all P < 0.01). Ellipsoid zone loss in the central 1- and 6-mm area correlated with decreased retinal sensitivity (all P < 0.01).<br><br>CONCLUSION: Retinal fluid volumes in nAMD are triggered by MNV types and correlate with photoreceptor integrity and visual function, with the impact depending on the fluid compartment. Although fluid is central to disease monitoring, a more comprehensive approach to structural-functional assessment in nAMD is of interest.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42621341, year = {2026}, author = {Eandi, CM and Snyder, VC and Grieve, K and Gocho, K and Chaumette, C and Castro-Farias, D and Norberg, N and Eddy, G and Friberg, TR and Eller, AW and Dansingani, KK and Martel, JN and Chhablani, J and Sahel, JA and Paques, M and Rossi, EA}, title = {High-Resolution and Multimodal Structural Phenotyping of Intermediate and Advanced Non-Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101307}, pmid = {42621341}, issn = {2666-9145}, abstract = {PURPOSE: To characterize structural phenotypes in intermediate and advanced non-neovascular age-related macular degeneration (AMD) using flood-illumination adaptive optics (FIAO) and to explore their relationship with established multimodal imaging biomarkers, including OCT-based atrophy classifications.<br><br>DESIGN: Prospective, cross-sectional observational study.<br><br>SUBJECTS: A total of 208 eyes from 117 patients (mean age 74 years; 63% female) with intermediate AMD (iAMD) or geographic atrophy (GA) were enrolled. Eligible participants had visual acuity &#x2265;20/63, refractive error between -6 and +2 diopters, and sufficient media clarity for high-quality imaging.<br><br>METHODS: Participants underwent multimodal imaging, including color fundus photography, spectral-domain OCT, infrared reflectance, fundus autofluorescence, and FIAO. Structural phenotypes (drusen, subretinal drusenoid deposits, pigmentary changes, and GA margins) were assessed qualitatively across modalities. Flood-illumination adaptive optics features were compared with OCT-based atrophy classifications (incomplete and complete retinal pigment epithelium and outer retinal atrophy [iRORA and cRORA]) using descriptive analyses and cross-tabulation.<br><br>MAIN OUTCOME MEASURES: Prevalence and multimodal characteristics of AMD structural phenotypes, and their correspondence with FIAO features.<br><br>RESULTS: Drusen and pigmentary abnormalities were detected in the majority of eyes across modalities, with variability in prevalence depending on imaging technique. Flood-illumination adaptive optics identified drusen in 70% of eyes revealing a consistent reflectivity pattern of hyperreflective borders and hyporeflective centers. Hyporeflective clumps corresponding to pigmentary changes were always observed on FIAO, frequently localizing to areas of atrophy or transition zones. Distinct FIAO-defined GA border phenotypes were observed, including well-demarcated and indistinct margins. In descriptive cross-tabulation, well-demarcated FIAO borders were more frequently associated with OCT-defined cRORA, whereas indistinct or hyporeflective margins were with iRORA.<br><br>CONCLUSIONS: Flood-illumination adaptive optics provides high-resolution visualization of structural features in iAMD and GA, revealing distinct patterns of drusen, pigmentary changes, and atrophic margins. While certain FIAO features show qualitative correspondence with OCT-defined atrophy stages, these relationships remain descriptive. Further quantitative and longitudinal studies are needed to determine their clinical relevance and role in disease characterization.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42621407, year = {2026}, author = {Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Schwartz, R and Sacu, S and Bogunovic, H and Schmidt-Erfurth, U}, title = {Predictive Value of Perilesional Fundus Autofluorescence Patterns and OCT-Based Ellipsoid Zone/Retinal Pigment Epithelium Loss Ratios in Geographic Atrophy Growth Rates.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101306}, pmid = {42621407}, issn = {2666-9145}, abstract = {PURPOSE: To investigate the association between perilesional fundus autofluorescence (FAF) patterns and ellipsoid zone (EZ)/retinal pigment epithelium (RPE) loss ratio on OCT in geographic atrophy (GA) and their predictive value on disease progression and therapeutic response to pegcetacoplan.<br><br>DESIGN: Post hoc analysis of 2 prospective randomized controlled phase III clinical trials.<br><br>SUBJECTS: Patients with GA secondary to age-related macular degeneration.<br><br>METHODS: OCT and FAF images from the OAKS (NCT03525613) and DERBY (NCT03525600) trials, 2 phase III, randomized controlled clinical trials of intravitreal pegcetacoplan for the treatment of GA secondary to age-related macular degeneration, were analyzed. Retinal pigment epithelium and EZ loss were measured on OCT by previously validated deep learning-based algorithms. Perilesional FAF patterns were graded at a centralized reading center from the trials. Pooled study eyes and fellow eyes that met the inclusion/exclusion criteria were divided into 4 quartiles based on baseline EZ/RPE loss ratios on OCT. The distribution of FAF patterns between the quartiles was analyzed. The association between baseline FAF pattern and disease progression and therapeutic response to pegcetacoplan was investigated.<br><br>MAIN OUTCOME MEASURES: Distribution of FAF patterns between EZ/RPE loss ratio quartiles, mean change in FAF-based GA growth, RPE, and EZ loss on OCT.<br><br>RESULTS: Fundus autofluorescence and OCT gradings were available for 1317 study and fellow eyes from both trials pooled together. The focal pattern showed smaller ratios (P < 0.001), whereas the diffuse-trickling pattern was present in higher ratios (P = 0.005) at baseline. All other patterns showed no correlation with EZ/RPE loss ratios. There was an association of the focal and the diffuse-trickling pattern with FAF-based GA progression and OCT-based RPE loss, but not with OCT-based EZ loss. A greater treatment effect was identified in eyes with the diffuse-trickling pattern, which was present in a small number of eyes.<br><br>CONCLUSIONS: The focal and diffuse-trickling FAF patterns were associated with RPE loss; however, perilesional FAF patterns were not associated with photoreceptor degeneration. There was a greater treatment effect in eyes with the diffuse-trickling pattern, presenting with higher EZ/RPE loss ratios on OCT in a small subgroup.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42621660, year = {2026}, author = {Yao Jin, L and Selvam, EGP and Mei, Q and Luu, CD and Yap, YHY and Teh, DBL}, title = {Advancing Treatment of Degenerative Eye Diseases at the Nanoscale.}, journal = {Smart medicine}, volume = {5}, number = {4}, pages = {e70050}, pmid = {42621660}, issn = {2751-1871}, abstract = {Degenerative ocular diseases are characterized by a convergence of molecular perturbations, including oxidative stress, chronic inflammation, failure of proteostasis, mitochondrial dysfunction, abnormal angiogenic signaling, and biomechanical remodeling. The eye's unique architecture, sealed by the blood-retina barrier, presents formidable anatomical and cellular topological challenges to achieving long-term curative therapeutics. Nanotechnology offers an advantage in potential therapy: by utilizing carriers in the nanometer size range and leveraging on appropriate surface modifications, it can effectively overcome these physiological barriers for enhanced, controlled, and targeted treatment. Clinical and preclinical systems such as antioxidant nanoparticles, sustained release implants, anti-angiogenic nanoplatforms, multifunctional nanocomposites, and regenerative scaffolds illustrate how nanotechnology can overcome limitations in bioavailability, tissue penetration, and pathway specificity in degenerative ocular diseases. Diagnostic advances that include plasmonic contrast agents, quantum dots, graphene biosensors, smart contact lenses, and photothermal neuromodulators further demonstrate continuous molecular surveillance and responsive intervention. Emerging materials such as DNA origami and magnetoelectric nanosystems expand this capability by enabling direct modulation of transcriptional, metabolic, and neuroelectrical pathways. Together, these developments position nanotechnology as a powerful strategy for addressing the molecular origins of ocular degeneration while also highlighting ongoing challenges in long term safety, device stability, manufacturing reproducibility, and regulatory standardization.}, }
@article {pmid42608930, year = {2026}, author = {Kurysheva, NI and Maslova, EV}, title = {[Glaucoma and age-related macular degeneration: challenges and prospects for prevention and treatment of combined pathology. Part 1. Epidemiology and pathogenesis].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {4}, pages = {112-119}, doi = {10.17116/oftalma2026142041112}, pmid = {42608930}, issn = {0042-465X}, mesh = {Humans ; *Macular Degeneration/epidemiology/physiopathology/therapy/prevention &amp; control/diagnosis/etiology ; *Glaucoma/epidemiology/physiopathology/therapy/prevention &amp; control/diagnosis/complications ; Risk Factors ; }, abstract = {Glaucoma and age-related macular degeneration are the leading causes of irreversible vision loss in individuals over 60 years of age. This review consolidates current data on the epidemiology, shared genetic factors, and pathophysiological mechanisms underpinning their coexistence, and outlines prospects for personalized prevention and therapy. Common modifiable risk factors comprise cigarette smoking, arterial hypertension, and dyslipidemia. Chorioretinal hypoperfusion, mitochondrial dysfunction, activation of the NLRP3 inflammasome, and impaired glymphatic elimination of amyloid contribute to neurodegeneration both in the macula and in the optic nerve area. Treatment prospects include comprehensive vascular and neuroprotective regimens, targeted complement modulation, and the use of polygenic risk scores for patient stratification and longitudinal monitoring.}, }
@article {pmid42608931, year = {2026}, author = {Fursova, AZ and Vasilyeva, MA and Derbeneva, AS and Amir, IM and Tarasov, MS and Nikulich, IF and Karlash, YA and Agamian, ER}, title = {[The effect of angiogenesis inhibitor therapy on the risk of fibrosis formation in neovascular age-related macular degeneration and potential strategies for its prevention].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {4}, pages = {120-126}, doi = {10.17116/oftalma2026142041120}, pmid = {42608931}, issn = {0042-465X}, mesh = {Humans ; *Angiogenesis Inhibitors/pharmacology/administration &amp; dosage ; Fibrosis/prevention &amp; control ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy ; Angiopoietin-2/metabolism ; *Retina/pathology ; *Wet Macular Degeneration/drug therapy ; }, abstract = {Numerous randomized clinical trials and real-world clinical practice have demonstrated the effect of angiogenesis inhibitors (anti-VEGF agents) on the activity and growth of neovascular complexes in neovascular age-related macular degeneration (nAMD), with a proven reduction in the risk of macular fibrosis, the incidence of which decreased from 39-100% in the "pre-antiangiogenic era" to 20.4-61.4% after introduction of anti-VEGF therapy. The main factors determining the risk of subretinal fibrosis are disease activity, time of therapy initiation, treatment regimen, its regularity, and the type of drug. Variations in retinal thickness and the volatility of specific fluid compartments lead to an increase in the volume of subretinal hyperreflective material (SHRM) and prevent full restoration of the integrity of the ellipsoid zone. Extensive research into the role of angiopoietin-2 (Ang-2) in the development of fibrosis has shown that it acts not only as a cofactor of angiogenesis but also as an independent regulator of fibrogenesis through vascular destabilization with increased VEGF-mediated permeability and exudation, activation of macrophages and microglia with the production of TGF-β and CTGF, and cross-talk with classical fibrotic pathways. The synergism between Ang-2 and VEGF-A stimulates subretinal scarring and highlights the high potential of bispecific therapy for improving clinical outcomes in patients with nAMD. Compensatory activation of Ang-2 during anti-VEGF monotherapy may support tissue remodeling, contributing to the development of treatment resistance. Preclinical studies in models of choroidal neovascularization and clinical data on the effectiveness of faricimab 6 mg through dual Ang-2/VEGF-A inhibition have demonstrated not only superiority in controlling exudation and resolving retinal edema but also a targeted effect on preventing proliferation and the development of subretinal fibrosis, as confirmed by a significant reduction in the volume of SHRM - a key precursor to fibrotic changes.}, }
@article {pmid42601635, year = {2026}, author = {Chen, N and Liu, Y and Chen, Z and Xiang, Y and Yu, H}, title = {Integrative genomic and proteomic analyses identify candidate genetic loci and genetically supported proteins in age-related macular degeneration.}, journal = {Eye and vision (London, England)}, volume = {13}, number = {1}, pages = {}, pmid = {42601635}, issn = {2326-0254}, support = {8227041127//the launch fund of Guangdong Provincial People's Hospital for NSFC/ ; 82301205//National Natural Science Foundation of China/ ; 2023B1515120028//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2024T170185//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment; however, robust drug targets for primary prevention remain elusive. This study aimed to identify candidate genetic loci and putative genetically supported proteins for AMD through integrative genomics and proteomics.<br><br>METHODS: A genome-wide association study (GWAS) meta-analysis (28,543 cases and 1,072,092 controls) was performed to identify risk loci, followed by proteome-wide Mendelian randomization (MR), colocalization, and multi-omics summary-data-based MR with heterogeneity in dependent instruments (SMR-HEIDI) analyses to infer genetically supported proteins. Functional characterization included gene enrichment, single-cell RNA sequencing, mediation across 731 immunophenotypes, and a mouse knockout assessment. Druggability was evaluated using the Drug-Gene Interaction Database.<br><br>RESULTS: The GWAS meta-analysis identified 10 candidate genetic loci for AMD (including three previously reported and seven newly identified loci). Proteome-wide MR and colocalization analyses uncovered 23 genetically supported plasma proteins (11 risk and 12 protective factors). Multi-omics SMR-HEIDI analysis prioritized LAMC2 and PLTP as first-tier risk genes, which was consistently supported across protein, expression, and methylation levels. Single-cell RNA sequencing revealed cell-type-specific enrichment of key genes in monocytes and stromal/progenitor-like cells within AMD retinas, and subsequent mediation analysis identified specific immune traits, most notably regulatory T-cell subsets, as potential partial mediators of AMD risk. Druggability assessment identified 15 target genes, and bioinformatic enrichment nominated cyclophosphamide. Given the toxicity profile of cyclophosphamide, this computational finding serves strictly as a pathway indicator, reinforcing the broader therapeutic relevance of modulating the identified immune-related targets.<br><br>CONCLUSION: Our integrative analyses identified candidate genetic loci and genetically supported proteins for AMD, providing a foundation for translating genomic findings toward primary prevention. The exploratory nature of this study highlights the need to experimentally validate the proposed targets and underlying mechanisms.}, }
@article {pmid42601984, year = {2026}, author = {Lai, A and Issa, M and Ali, A and Pereira, A and Ali, AA and Chhablani, J and Yan, P}, title = {Aging-Related Choroidal Heterogeneity and Loss: An Investigative Global Human Choroidal Thickness Review (ARCHLIGHT Study).}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261457969}, pmid = {42601984}, issn = {2474-1272}, abstract = {PURPOSE: To synthesize current evidence on the pathophysiology, clinical relevance, and implications for age-related choroidal thinning.<br><br>METHODS: A systematic literature search of relevant publications was conducted across MEDLINE, Embase, and Cochrane Library, up to and including May 2024. Identified studies reported choroidal thickness changes with aging. Data on subfoveal choroidal thickness, choroidal vascularity index, and associated factors (ethnicity, systemic disease, axial length) were analyzed (PROSPERO ID: CRD420251041101).<br><br>RESULTS: Choroidal thickness declines with age, with ethnicity-specific rates ranging from -0.93 &#xb5;m/year in Spanish cohorts to -4.00 &#xb5;m/year in Chinese populations. Age-related choroidal thinning correlates with retinal and neurodegenerative pathologies, including glaucoma (nasal choroidal thinning >250 &#xb5;m in older adult patients), myopic maculopathy (subfoveal choroidal thickness <100 &#xb5;m in high myopia), and Alzheimer disease (subfoveal choroidal thickness 169 &#xb5;m vs 253 &#xb5;m in control patients). Enhanced depth imaging optical coherence tomography (OCT) and swept-source OCT reveal preferential vascular loss (choroidal vascularity index <30%) and stromal atrophy. Systemic risks, such as hypertension or smoking, accelerate choroidal thinning.<br><br>CONCLUSIONS: Age-related choroidal thinning exists on a continuum between physiologic aging and pathology, with implications for retinal and systemic health. Future prospective studies will help determine diagnostic thresholds (subfoveal choroidal thickness <200 &#xb5;m in nonmyopic adults >60 years or rapid thinning beyond ethnic normative values), management recommendations for high-risk cohorts (glaucoma, age-related macular degeneration, high myopia), and therapeutic considerations for monitoring of choroidal thickness changes from moderate- to low-certainty evidence.}, }
@article {pmid42602093, year = {2026}, author = {Taylor, CX and Reed, H and Talcott, KE and Singh, RP}, title = {Incidence and Recovery of 15-Letter Loss of Visual Acuity in Patients With Neovascular Age-Related Macular Degeneration on Antivascular Endothelial Growth Factor Therapy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261472092}, pmid = {42602093}, issn = {2474-1272}, abstract = {PURPOSE: To describe how 15-letter loss of visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) results in transient fluctuations in vision. In addition, to compare recoverability of letter loss in patients treated with antivascular endothelial growth factor (anti-VEGF) with untreated patients.<br><br>METHODS: Patients with previously untreated nAMD in the Comparisons of AMD Treatments Trials were assigned to transient and nontransient groups based on recovery of baseline best-corrected VA within 8 weeks. Magnitude of recoverable letter loss was modeled via linear regression.<br><br>RESULTS: Two hundred fifty-three of 1018 patients (25%) experienced 15-letter loss: 68 transient (7%) and 185 nontransient (18%). Two-year outcomes were better without 15-letter loss (+12 letters, 95% CI, 11-13, n = 772) compared with transient 15-letter loss (+0.4 letters, 95% CI, -4 to 5) and nontransient 15-letter loss (-14 letters, 95% CI, -17 to -12). Nontransient losses up to -2.5 letters were expected to be recoverable (95% CI, -6.0 to 1.0). Fifteen-letter loss was associated with smoking (P = .02) and poor nontransient outcomes with higher blood pressure (P = .04).<br><br>CONCLUSIONS: Patients experiencing transient and nontransient 15-letter loss differed significantly in outcomes. Nontransient losses were not expected to be recoverable. These findings may help guide the selection of measures in clinical trial design.}, }
@article {pmid42606042, year = {2026}, author = {Muth, DR and Venkataraman, AP and Dominguez-Vicent, A and Petrovski, G and Williams, PA and Quérat, L and Locri, F and Zweifel, SA and Kvanta, A}, title = {Regional growth kinetics of geographic atrophy in age-related macular degeneration with and without fovea-sparing.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70229}, pmid = {42606042}, issn = {1755-3768}, support = {//&#xd6;gonfonden, Sweden/ ; }, abstract = {PURPOSE: Fovea-sparing geographic atrophy (GA) patients retain near-normal central vision. To better understand GA progression in relation to the fovea, we performed a semi-automated image analysis of regional atrophy growth in a long-term GA natural-history cohort.<br><br>METHODS: Prospective-observational, single-centre-study (02/2013-07/2025) at the Division of Eye and Vision, Karolinska Institutet/St. Erik Eye Hospital, Stockholm, Sweden. Longitudinal square-root-transformed GA area and distance-growth rates [mm/year] in all retinal quadrants were calculated from fundus autofluorescence images. Eyes were stratified based on best-corrected visual acuity: fovea-sparing (&#x2265;65 ETDRS) and fovea-involving (<65 ETDRS).<br><br>RESULTS: 65 eyes (65 patients) presented fovea-sparing and 91 eyes (91 patients) fovea-involving. Median follow-up was 18&#x2009;months (range: 5-125). The fovea-involving group decreased in BCVA (Wilcoxon, p&#x2009;<&#x2009;0.001). Total area growth was faster for fovea-sparing than fovea-involving lesions: 0.34 vs. 0.26 (Mann-Whitney U, p&#x2009;=&#x2009;0.0019). The same was true for the superior, inferior, and temporal quadrants (Mann-Whitney U, all p&#x2009;<&#x2009;0.0472). Fovea-sparing lesions showed slower distance growth towards the fovea than outwards in all quadrants: superior 0.09 vs. 0.21; nasal 0.08 vs. 0.18; inferior 0.06 vs. 0.17; temporal 0.09 vs. 0.20 (Wilcoxon, all p&#x2009;<&#x2009;0.001). Lesions closer to the fovea (&#x2264;500&#x2009;&#x3bc;m) at baseline showed decreased regional growth towards the fovea. Outwards growth was not related to lesion location.<br><br>CONCLUSIONS: In this longitudinal cohort, fovea-sparing lesions showed faster total and regional growth than fovea-involving lesions, mainly caused by a faster outward expansion component. Location 500&#x2009;&#x3bc;m or closer to the fovea resulted in slower growth, which supports a foveal self-protecting mechanism. These are relevant findings for patients with fovea-sparing lesions.}, }
@article {pmid42607745, year = {2026}, author = {Futterknecht, S and Riedl, S and Mai, J and Arabi, S and Hall, U and Bogunovic, H and Fritsche, LG and Rueckert, D and Menten, MJ and Sacu, S and Schmidt-Erfurth, U and Sivaprasad, S and Lotery, A and Pfau, M}, title = {Lesion-Centered Functional Trajectories Reveal Early Retinal Sensitivity Decline in Intermediate AMD: PINNACLE Study Report 15.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.08.017}, pmid = {42607745}, issn = {1879-1891}, abstract = {PURPOSE: To characterize lesion-centered functional decline in intermediate age-related macular degeneration (iAMD), including measurement variability, spatial vulnerability, pre-detection functional changes, and lesion-specific sensitivity trajectories.<br><br>DESIGN: Longitudinal analysis of microperimetry from the prospective, multicenter PINNACLE study (NCT06682455).<br><br>PARTICIPANTS: Overall, 264 participants contributing 422 eyes were included. Focal event analyses included 338 OCT-defined events from 131 eyes of 113 participants.<br><br>METHODS: Participants underwent mesopic microperimetry using a standard 24-point grid. OCT-defined events triggered lesion-centered 5-point testing. Repeatability was assessed using linear mixed-effects models. Lesion-centered sensitivity trajectories were estimated using spatiotemporal generalized additive mixed models incorporating measured post-detection focal-grid data and spatially interpolated pre-detection standard-grid data. A secondary piecewise linear mixed-effects model quantified changes before and after event detection.<br><br>MAIN OUTCOME MEASURES: Point-wise microperimetry repeatability, sensitivity loss of &#x2265;7 dB, relative and absolute scotoma, and model-estimated lesion-centered sensitivity trajectories.<br><br>RESULTS: The point-wise coefficient of repeatability was 7.61 dB (95% confidence interval [CI], 7.58-7.64) for standard-grid testing and 13.00 dB (95% CI, 12.76-13.21) for lesion-centered testing. The 338 events comprised 240 ellipsoid zone/interdigitation zone loss events, 85 drusen-collapse events, and 13 subretinal-fluid events. Within 2 years, the risk of sensitivity loss of &#x2265;7 dB was lower at parafoveal (hazard ratio, 0.66; 95% CI, 0.51-0.84) and perifoveal locations (hazard ratio, 0.68; 95% CI, 0.53-0.87) than at foveal locations. Model-estimated sensitivity at ellipsoid zone/interdigitation zone loss sites declined before detection by 0.57 dB/year (95% CI, 0.25-0.89 dB/year) and continued after detection, reaching 0.94 dB/year (95% CI, 0.55-1.34 dB/year) during the late post-detection period. Drusen-collapse sites showed no clear longitudinal decline. Subretinal-fluid events showed an immediate loss of 2.18 dB (95% CI, 0.84-3.53), followed by early decline and possible later improvement. Matched control locations remained stable.<br><br>CONCLUSIONS: Localized functional decline in iAMD is characterized by measurement variability, central spatial vulnerability, and lesion-specific trajectories. Model-estimated sensitivity decline was most evident at sites of ellipsoid zone/interdigitation zone loss. These findings support structurally and spatially informed microperimetry endpoints while highlighting substantial measurement variability.}, }
@article {pmid42607856, year = {2026}, author = {Chou, SJ and Wang, CH and Tsai, PH and Hsiao, YJ and Ou-Yang, H and Fang, WC and Tsai, HY and Shia, KS and Song, JS and Wu, CH and Lee, N and Tsai, ML and Hwang, DK and Hsu, CC and Chen, SJ and Chiou, SH and Lin, TC and Yang, YP}, title = {Inhibition of CXCR4-Induced Angiogenesis to Block Choroidal Neovascularization and Restore Retinal Function in Age-Related Macular Degeneration by In Silico-Selected Small Molecules.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {179236}, doi = {10.1016/j.ejphar.2026.179236}, pmid = {42607856}, issn = {1879-0712}, abstract = {The chemokine receptor CXCR4 has been recognized as a pivotal mediator of cytokine-driven angiogenesis. Wet age-related macular degeneration (wet-AMD) is characterized by choroidal neovascularization (CNV) leading to vision loss. However, the current anti-VEGF therapy remains limited by recurrent CNV in refractory wet-AMD. Herein we developed small-molecule inhibitors targeting CXCR4-mediated neovascularization in wet-AMD. Employing computational molecular docking simulations for candidate screening, BPRCX807 exhibited superior binding affinity as a CXCR4 antagonist relative to other compounds tested. A laser-induced wet-AMD murine model was established, demonstrating subretinal CNV and upregulation of proteins implicated in CXCR4 signaling and angiogenesis. Retinal structural alterations and CNV-progression were monitored via real-time fluorescein angiography and optical coherence tomography (OCT), revealing that BPRCX807 treatment significantly attenuated angiogenesis compared to conventional anti-VEGF therapy. Retinal safety evaluation further indicated that BPRCX807 administration did not induce detectable retinal toxicity or structural abnormalities. Ex vivo choroid sprouting assays corroborated the reduction of vascular leakage and CNV-formation by BPRCX807. The visual-functional electroretinographic evaluations indicated that, while anti-VEGF agents produced modest functional improvements, BPRCX807 achieved superior restoration of retinal visual function. Notably, bioinformatic analyses supported that inhibition of CXCR4 signaling effectively suppressed VEGF-driven and cytokine-mediated angiogenic pathways. Finally, biomolecular simulations combined with predictive signaling-pathway analyses suggested that BPRCX807 modulates multiple VEGF-regulatory signaling cascades, thereby enhancing its inhibitory effects on VEGF expression and downstream angiogenesis. Collectively, these computational and experimental data demonstrate that BPRCX807 disrupts CXCR4 receptor interactions and suppresses angiogenic factor expression via inhibition of the CXCR4/p-AKT signaling pathway, representing a promising therapeutic approach for wet-AMD.}, }
@article {pmid42607929, year = {2026}, author = {Shmushkevich, SB and Bajrami, S and Grand, ZA and Tijerina, JD and Williams, BK and Rothman, AL}, title = {Risk of New Glaucoma Diagnosis and Surgery for Patients with Intravitreal Injections in the TriNetX Database.}, journal = {Ophthalmology. Glaucoma}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ogla.2026.08.002}, pmid = {42607929}, issn = {2589-4196}, abstract = {OBJECTIVE: To quantify the long-term risk of incident glaucoma and of undergoing glaucoma surgery associated with intravitreal injection therapy using a large electronic health record network.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: Patients with no prior glaucoma diagnosis in the TriNetX US Collaboration Network seen between 03/14/2006-03/14/2026 with either exudative age-related macular degeneration (AMD) and intravitreal injection or nonexudative AMD with no history of injection.<br><br>METHODS: Patients with exudative AMD who received intravitreal injections (Current Procedural Terminology 67028) were compared with patients with nonexudative AMD. Patients with retinal vascular occlusions, proliferative diabetic retinopathy, retinal ischemia, pseudoexfoliation syndrome or pigment dispersion syndrome were excluded. Cohorts were propensity score matched 1:1 for age, sex, race, ethnicity, and systemic comorbidities. Time-to-event analyses were performed, and effect estimates included risk ratios (RR), odds ratios (OR), and hazard ratios (HR).<br><br>MAIN OUTCOME MEASURES: New glaucoma diagnosis (International Classification of Diseases-10 H40) and glaucoma surgical interventions.<br><br>RESULTS: After exclusions and matching, each cohort contained 27,967 patients. Incident glaucoma occurred in 15.1% (4,218/27,967) of injection patients versus 12.9% (3,621/27,967) of controls (RR 1.17; OR 1.19; HR 1.08, p<0.001). Any glaucoma surgery occurred in 1.6% (435/27,967) of injection patients compared with 0.8% (236/27,967) of controls (RR 1.84; OR 1.86; HR 1.66, p<0.001). Patients with intravitreal injection were more likely to undergo glaucoma tube implantation (p<0.001), laser trabeculoplasty (p<0.001), cyclodestructive procedures (p=0.001), and trabeculectomy (p=0.03). Incisional angle surgery trended toward significance (p=0.054).<br><br>CONCLUSIONS: In a large cohort, intravitreal injection therapy for exudative AMD was associated with higher risks of incident glaucoma and glaucoma surgery compared with matched nonexudative AMD controls, corresponding to a number needed to harm of approximately 47 for incident glaucoma.}, }
@article {pmid42608919, year = {2026}, author = {Andreeva, IV and Stoyukhina, AS and Smolin, SA and Hamza, V}, title = {[Modern diagnostic possibilities for peripapillary neovascular membranes. Report 1. OCT diagnostic signs].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {4}, pages = {26-36}, doi = {10.17116/oftalma202614204126}, pmid = {42608919}, issn = {0042-465X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Neovascularization/diagnosis/etiology ; Diagnosis, Differential ; Fluorescein Angiography/methods ; Aged ; *Choroid/pathology/diagnostic imaging ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Middle Aged ; *Optic Disk/pathology ; }, abstract = {UNLABELLED: Peripapillary subretinal neovascular membranes (SRNVMs) develop due to neovascular age-related macular degeneration (nAMD), retinal angioid streaks, inflammatory diseases, congenital optic disc anomalies, and other causes. Diagnosis of peripapillary SRNVMs relies on multimodal imaging, with optical coherence tomography (OCT) being the main method.<br><br>OBJECTIVE: The study aimed to identify differential diagnostic signs of peripapillary SRNVMs of various etiologies according to OCT data.<br><br>MATERIALS AND METHODS: We examined 48 patients with active peripapillary SRNVMs. All patients underwent OCT, including OCT angiography. Quantitative and qualitative characteristics were evaluated.<br><br>RESULTS: In nAMD, peripapillary SRNVMs presented as fibrovascular retinal pigment epithelium (RPE) detachment (p=0.05), with a "double-layer" sign and drusen in one-third of cases (p=0.017). Subfoveal choroidal thickness in patients with nAMD did not differ significantly from the age-related norm (p=0.473 and p=0.384 for the study and fellow eyes, respectively); the inner choroidal surface had a smooth profile (p=0.033), and the Bruch membrane was preserved (p=0.033). In angioid streaks, OCT visualized a thin choroid with folding of the inner surface (p<0.0001) and ruptures of the Bruch membrane (p<0.0001). In the area of peripapillary SRNVM, choroidal thickness was lower than in patients with nAMD (p=0.024) and pachychoroid spectrum diseases (p<0.0001). In pachychoroid-related SRNVMs, choroidal thickness in the SRNVM area and subfoveally, both in the study and fellow eyes, significantly exceeded the values observed in SRNVMs of other etiologies (p<0.0001). RPE changes mainly presented as a shallow local detachment (p=0.02) with a saw-tooth contour and no defects. Subretinal hyperreflective material in the SRNVM area was also absent (p=0.02), but isolated subretinal fluid predominated in pachychoroid neovasculopathy (p=0.004), whereas a combination of subretinal and intraretinal fluid was more prevalent in chronic central serous chorioretinopathy.<br><br>CONCLUSION: To correctly determine the type of peripapillary SRNVM, it is necessary to pay primary attention to the condition of the choroid and Bruch membrane, the presence of drusen and subretinal hyperreflective material in the SRNVM area and subfoveally, presence of fluid in the SRNVM area, and the condition of the fellow eye.}, }
@article {pmid42599645, year = {2026}, author = {Salvatore, S and Harvey, J and Hughes, A and Gibson, L and Hopcroft, J and Swift, S and Marsterson, J and Bailey, C}, title = {Enhanced Macular Imaging Referral Pathway: Bridging Community Optometrists and Hospital Specialists for Smarter Eye Care.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42599645}, issn = {2193-8245}, abstract = {INTRODUCTION: Hospital eye services in England face sustained demand, with nearly 9 million outpatient appointments in 2023-2024. Teleophthalmology pathways that combine community-acquired imaging with hospital virtual review may reduce unnecessary face-to-face visits. We evaluated an enhanced macular imaging referral pathway linking community optometry optical coherence tomography (OCT) and colour fundus imaging with hospital-led teleophthalmology review.<br><br>METHODS: We performed a retrospective service evaluation of 376 consecutive adult macular referrals received at University Hospitals of Bristol and Weston, between July 2024 and March 2025. Community optometrists submitted bilateral macula-centred 45&#xb0; colour fundus photographs, bilateral OCT volume scans in digital imaging and communications in medicine (DICOM) format and clinical data via a secure platform. Referrals were reviewed by a consultant ophthalmologist or hospital optometrist within 1 working day. Under the previous pathway, all accepted referrals required an initial face-to-face hospital appointment. Primary outcomes were referral appropriateness, avoided hospital appointments and redirection to other sub-specialties; secondary outcomes were management decision and diagnostic category. Analyses were descriptive.<br><br>RESULTS: Median age was 74&#xa0;years (IQR 14); 54.3% were female. Overall, 327/376 referrals (87.0%, 95% CI 83.2-90.0) were appropriate for macular assessment. Of the referrals, 49 (13.0%) were inappropriate because of incomplete imaging (n&#x2009;=&#x2009;18, 4.7%) or redirection to another sub-specialty (n&#x2009;=&#x2009;31, 8.2%), most commonly vitreoretinal services (n&#x2009;=&#x2009;27, 7.2%). Among appropriate referrals, 241/327 (73.7%, 95% CI 68.7-78.2) avoided the mandatory first hospital visit required under the previous pathway. Management outcomes across the cohort were: neovascular age-related macular degeneration (nAMD) pathway, 17.1%; redirection, 6.1%; discharge to community, 10.2%; virtual follow-up, 15.3%; and face-to-face appointment, 51.2%. Mean time to treatment for nAMD was 8.6&#xa0;days (95% CI 6.0-11.2&#xa0;days).<br><br>CONCLUSIONS: This teleophthalmology-enabled macular referral pathway achieved high referral appropriateness and substantially reduced mandatory first-visit hospital appointments while supporting timely treatment for sight-threatening macular disease. The model appears scalable and may help National Health Service hospital eye services manage rising demand more efficiently.}, }
@article {pmid42600888, year = {2026}, author = {Huang, A and Ling, J and Gilead, N and Sherif, M and Teo, K and Lam, WC and Cheung, CMG}, title = {Variations in nAMD and PCV Phenotypes and Treatment Outcomes Across Singaporean, Canadian Asian, and Canadian Caucasian Populations.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.08.018}, pmid = {42600888}, issn = {1879-1891}, abstract = {PURPOSE: To compare the frequency of polypoidal choroidal vasculopathy (PCV) features, treatment patterns, and one-year outcomes across Singaporean Asian, Canadian Asian, and Canadian Caucasian populations with neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT)-based diagnostic criteria.<br><br>DESIGN: Retrospective, multicenter, comparative study.<br><br>PARTICIPANTS: A total of 327 treatment-na&#xef;ve patients with nAMD: 181 from Singapore National Eye Centre and 146 from Vancouver, Canada (89 Caucasian, 57 Asian).<br><br>METHODS: PCV was diagnosed using modified Asia-Pacific Ocular Imaging Society non-indocyanine green angiography OCT-based criteria (sharp-peaked pigment epithelial detachment and sub-retinal pigment epithelium ring-like lesion). Baseline OCT features, treatment patterns, and 12-month outcomes were compared across the three ethnic groups.<br><br>MAIN OUTCOME MEASURES: PCV prevalence, OCT-based morphological features, treatment patterns, and change in best-corrected visual acuity (BCVA) at 12 months.<br><br>RESULTS: PCV prevalence was similar between Singaporean Asian (42.5%) and Canadian Asian (42.1%) groups, both significantly higher than Canadian Caucasians (13.5%, P<0.01). OCT features in PCV eyes were consistent across ethnic groups, including macular predominance (79.2-83.3%), double-layer sign (83.3-93.5%), low soft drusen prevalence (4.2-8.3%), and subfoveal choroidal thickness >200 &#xb5;m. Treatment patterns differed: bevacizumab predominated in Canada (65.0-70.0% for PCV), while Singapore used varied agents with photodynamic therapy in 31.1%. At 12 months, BCVA improved in Singaporean PCV eyes (-0.22 logMAR, P<0.01). In typical nAMD, BCVA improved significantly across all three groups.<br><br>CONCLUSIONS: Ethnic differences in PCV prevalence persist regardless of geographic location, supporting a predominant genetic basis for PCV susceptibility. OCT-based PCV features are consistent across ethnicities, while treatment patterns vary substantially between healthcare systems. Non-invasive OCT-based diagnostic criteria enable reliable cross-ethnic PCV comparison when indocyanine green angiography is unavailable.}, }
@article {pmid42601611, year = {2026}, author = {Lin, Y and Zhang, X and Huang, Z and Ye, Y and Yan, M and Song, Y}, title = {Predictors of 1-year fibrosis in treatment-naïve neovascular age-related macular degeneration: the role of baseline OCTA-derived MNV vessel density.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42601611}, issn = {1471-2415}, support = {2025BSH070//the Postdoctoral Scientific Research Foundation, General Hospital of Central Theater Command/ ; 82471110//the National Natural Science Foundation of China General Program/ ; }, mesh = {Humans ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Fibrosis/diagnosis ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/therapeutic use ; Female ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis/pathology ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; Intravitreal Injections ; Visual Acuity ; Follow-Up Studies ; Fundus Oculi ; Aged, 80 and over ; ROC Curve ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macula Lutea/pathology ; }, abstract = {BACKGROUND: To investigate baseline and post-loading optical coherence tomography angiography (OCTA) characteristics associated with 1-year fibrosis in treatment-naïve neovascular age-related macular degeneration (nAMD), and to evaluate whether baseline clinical variables combined with OCTA-derived biomarkers could improve fibrosis prediction.<br><br>METHODS: This retrospective, single-center study included treatment-na&#xef;ve nAMD eyes with type 1 or type 2 macular neovascularization (MNV) that completed a 3&#x2009;+&#x2009;PRN anti-VEGF loading regimen and had at least 12 months of follow-up. High-quality OCTA images were required at baseline and at the post-loading visit, defined as within 1 week after completion of the three-injection anti-VEGF loading phase. OCTA quantitative parameters, including fractal dimension, branch points, endpoints, segments, and MNV vessel density, were measured within the manually delineated MNV region of interest. Baseline clinical and imaging characteristics were compared between fibrosis and non-fibrosis groups. Univariate and multivariable logistic regression analyses were performed to identify factors associated with 1-year fibrosis, and receiver operating characteristic (ROC) curves were used to assess predictive performance.<br><br>RESULTS: A total of 72 patients (88 eyes) were included, of which 31 eyes developed fibrosis at 1 year and 57 did not. Compared with the non-fibrosis group, eyes that developed fibrosis had worse baseline best-corrected visual acuity (BCVA), greater baseline central macular thickness (CMT), and a higher prevalence of subretinal hyperreflective material (SHRM), retinal hemorrhage, type 2/mixed MNV, high pigment epithelial detachment, and intraretinal fluid. At baseline, the fibrosis group showed significantly higher MNV vessel density, whereas MNV fractal dimension showed a borderline difference. At the post-loading visit, MNV fractal dimension, MNV branch points, MNV endpoints, MNV segments, and MNV vessel density were all significantly higher in the fibrosis group. However, within-group comparisons between baseline and the post-loading visit revealed no significant changes in OCTA parameters in either group. In multivariable analysis, baseline BCVA (OR 1.162, 95% CI 1.024-1.319; P&#x2009;=&#x2009;0.020), baseline CMT (OR 1.032, 95% CI 1.001-1.064; P&#x2009;=&#x2009;0.043), and baseline MNV vessel density (OR 1.073, 95% CI 1.009-1.142; P&#x2009;=&#x2009;0.025) remained independently associated with 1-year fibrosis, whereas SHRM did not. The combined model achieved the best predictive performance, with an area under the ROC curve of 0.787 (95% CI 0.688-0.874).<br><br>CONCLUSIONS: Eyes with treatment-na&#xef;ve nAMD that developed fibrosis within 1 year had worse baseline disease status and distinct OCTA microvascular characteristics. Baseline BCVA, baseline CMT, and baseline MNV vessel density were independently associated with fibrosis. Integrating conventional clinical and structural features with OCTA-derived MNV vessel density may provide complementary information for fibrosis risk stratification in nAMD.}, }
@article {pmid42598505, year = {2026}, author = {Alibrandi, S and Mordà, D and Scimone, C and D'Ascola, A and Aliquò, F and Abate, G and Pozzato, G and Scalinci, SZ and D'Angelo, R and Sidoti, A and Donato, L}, title = {Quantum molecular resonance and secretome synergistically unlocks a protective ceRNA axis in the human retinal pigment epithelium.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {3}, pages = {103034}, pmid = {42598505}, issn = {2162-2531}, abstract = {The retinal pigment epithelium (RPE) contributes to retinal homeostasis in part through non-coding RNA (ncRNA) regulatory networks, and its degeneration underlies blinding diseases. How physical and paracrine regenerative stimuli affect the RPE non-coding transcriptome remains unknown. We performed RNA-seq on ARPE-19 cells in a full-factorial design of four treatments (CTRL, QMR, a patient blood-derived secretome, and QMR+SECRETOME) two oxidative-stress states (basal and tert-butyl hydroperoxide [tBHP]-induced), and three time points (8, 24, 72 h). lncRNAs and circRNAs were sub-classified and mapped via GO enrichment and in silico ceRNA prediction. PCA identified QMR as the dominant driver of transcriptomic variance, priming ARPE-19 cells to integrate paracrine signals. Analysis across six factorial contrasts identified 105 modulated non-coding transcripts, including a pan-responsive antisense core (BASP1-AS1, SOD2-OT1) and condition-specific shifts in master lincRNAs (NEAT1, MALAT1). QMR+SECRETOME produced a distinct combinatorial transcriptomic signature. circASPH was exclusively upregulated by QMR, while circCRIM1 was preferentially hyperactivated by combinatorial treatment. ceRNA analysis predicted potential sponging of miR-29, miR-21, and miR-155, which may derepress BMP signaling and extracellular matrix remodeling. QMR reshapes the ARPE-19 non-coding transcriptome and enables a non-additive transcriptomic response to secretome co-treatment. The QMR-secretome-circRNA axis identifies candidate non-coding biomarkers and therapeutic targets for retinal regeneration.}, }
@article {pmid42598632, year = {2026}, author = {Chen, KM and Chen, KW and Patil, A and Diaconita, V and Chang, S and Suh, LH}, title = {OphthoChat: A HIPAA-Compliant, Artificial Intelligence-Driven Natural-Language Chatbot for Ophthalmic Electronic Medical Record Querying and Analysis.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101315}, pmid = {42598632}, issn = {2666-9145}, abstract = {PURPOSE: To introduce and evaluate OphthoChat, a Health Insurance Portability and Accountability Act-compliant, artificial intelligence (AI)‑powered natural language chatbot designed to enable clinicians to query ophthalmic electronic medical records (EMRs) using conversational language, without requiring coding experience.<br><br>DESIGN: Retrospective validation study using a clinical data set and clinician-authored queries.<br><br>PARTICIPANTS: The study included 500 adult patients seen at Columbia University Irving Medical Center between 2020 and 2025: 250 patients who received intravitreal injections for wet age-related macular degeneration and 250 patients who underwent cataract surgery.<br><br>METHODS: We processed >50 000 EMR artifacts, including progress notes, operative reports, imaging summaries, and optical character recognition&#x2011;converted scanned documents, into a vectorized database. OphthoChat used a retrieval-augmented generation architecture powered by GPT-4o to answer 1000 natural-language queries stratified by complexity (simple, intermediate, advanced). Each response was evaluated against a reference standard determined by dual clinician adjudication.<br><br>MAIN OUTCOME MEASURES: Primary metrics included response accuracy, sensitivity, specificity, and time-to-answer per query. Supporting chart citations were also assessed for traceability and rank.<br><br>RESULTS: OphthoChat achieved an overall accuracy of 96%, with a sensitivity of 93% and a specificity of 97%. Median time to answer a query was 35 seconds, an 11-fold speed improvement over manual chart review (6.6 minutes). Among correct responses, 97% of cited lines matched the reference standard, with a mean reciprocal rank of 0.92. Performance remained strong across all difficulty levels, including 91% accuracy on advanced narrative inference tasks. The system demonstrated robustness in processing complex chart histories while offering full traceability.<br><br>CONCLUSIONS: OphthoChat enables fast, accurate, and traceable chart review in ophthalmology through natural-language dialogue. By eliminating the need for technical setup or programming knowledge, it significantly lowers the barrier to AI adoption in clinical research and practice. OphthoChat's ability to synthesize complex EMR data across structured and unstructured formats offers a scalable solution for accelerating outcomes research, clinical decision-making, and cohort identification. Further development will focus on EMR integration and subspecialty expansion.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42599028, year = {2026}, author = {Zhao, H and Gao, B and Ding, N and Zhang, R and Zhou, W and Song, G and Li, H and Wu, H and Yang, Y and Shao, L and Dong, L and Wei, W}, title = {Aqueous Humor Proteomics Reveals the Molecular Basis for Differential Treatment Responses in nAMD and pmCNV.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {36}, doi = {10.1167/iovs.67.10.36}, pmid = {42599028}, issn = {1552-5783}, mesh = {Humans ; *Aqueous Humor/metabolism ; *Proteomics/methods ; Female ; Biomarkers/metabolism ; *Choroidal Neovascularization/metabolism/drug therapy ; Male ; *Wet Macular Degeneration/metabolism/drug therapy ; Aged ; *Eye Proteins/metabolism ; Angiogenesis Inhibitors/therapeutic use ; *Myopia/metabolism/complications ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Mass Spectrometry ; }, abstract = {PURPOSE: Choroidal neovascularization (CNV) causes vision loss in neovascular age-related macular degeneration (nAMD) and pathologic myopia-related CNV (pmCNV). Despite shared clinical features, they respond differently to treatment. This study compared aqueous humor (AH) proteomic profiles of nAMD and pmCNV to identify biomarkers and mechanisms of CNV formation.<br><br>METHODS: AH samples were collected from eyes with nAMD, pmCNV, age-related cataract controls, and pathologic myopia without CNV. Label-free data-independent acquisition (DIA) mass spectrometry was used for proteomic profiling. Differentially expressed proteins were identified using limma models adjusted for age, sex, and axial length. Functional enrichment analyses used Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. Stability-based feature selection, LightGBM modeling, and SHapley Additive exPlanations (SHAP) prioritized discriminative proteins; selected findings were evaluated in an independent nAMD-control Olink cohort.<br><br>RESULTS: DIA proteomics identified 3986 proteins, of which 3667 passed quality filtering. nAMD and pmCNV showed weakly correlated proteomic alterations (r2 = 0.061), with 385 nAMD-specific, 398 pmCNV-specific, and 100 shared altered proteins. nAMD was characterized by vascular endothelial growth factor (VEGF/VEGF receptor [VEGFR]) pathway activation and reduced glucose-metabolism-related proteins, whereas pmCNV showed extracellular matrix remodeling, platelet/coagulation activation, and downregulation of Slit/Robo-related neurovascular guidance pathways. The stability-selected LightGBM model using 33 proteins achieved a macro-average area under the curve (AUC) of 0.92. SHAP analysis highlighted VEGFR2 (KDR) and VEGFA as major nAMD-associated drivers, and Olink validation showed concordant expression trends for six selected proteins.<br><br>CONCLUSIONS: nAMD and pmCNV exhibit largely distinct AH proteomic signatures, supporting different molecular mechanisms of CNV formation and anti-VEGF responsiveness. AH proteomics may help prioritize subtype-specific candidate biomarkers, warranting further validation across independent cohorts.}, }
@article {pmid42599042, year = {2026}, author = {Veernala, I and Chan, KS and Congivaram, HTS and Cuamatzi-Castelan, AS and Rajesh, A and Gong, J and Ide, OC and Lavine, JA and , }, title = {The Role of Dopaminergic Agonists in Geographic Atrophy: Converging Evidence From Clinical and Experimental Data.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {8}, pages = {10}, doi = {10.1167/tvst.15.8.10}, pmid = {42599042}, issn = {2164-2591}, mesh = {Animals ; Mice ; *Geographic Atrophy/drug therapy/pathology/chemically induced ; *Levodopa/therapeutic use/pharmacology ; Retrospective Studies ; *Dopamine Agonists/therapeutic use/pharmacology ; Humans ; Male ; Disease Models, Animal ; Tomography, Optical Coherence ; Female ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/pathology/drug effects ; Aged ; Receptors, Dopamine D2/agonists ; }, abstract = {PURPOSE: Levodopa (L-DOPA) is an emerging drug repurposing candidate for age-related macular degeneration (AMD). Basic and clinical studies identify a potential role for L-DOPA to prevent and treat neovascular AMD. However, only one prior study has been performed in geographic atrophy (GA).<br><br>METHODS: We performed a retrospective cohort analysis from the Sight Outcomes Research Collaborative database, including eyes with a diagnosis of early- or intermediate-stage AMD in 1 eye. We compared eyes exposed to any dopamine agonist (DA), dopamine receptor D2 agonist, and L-DOPA with eyes with no DA exposure using propensity score matching and survival analysis with multivariable Cox proportional hazard models with new GA development as our primary outcome. Mice were treated with intraperitoneal NaIO3 to induce GA-like pathology. We compared L-DOPA with phosphate-buffered saline-treated controls in both pigmented and albino mice. We quantified retinal thickness by optical coherence tomography, and performed immunofluorescence to quantify choriocapillaris and retinal pigment epithelium density.<br><br>RESULTS: Any DA, dopamine receptor D2, and L-DOPA exposure were not associated with new-onset GA. NaIO3 treatment caused retinal thinning, choriocapillaris loss, and retinal pigment epithelium degeneration, which were not rescued by L-DOPA treatment in pigmented nor albino mice.<br><br>CONCLUSIONS: In both retrospective database analysis and preclinical models, DA had no effect upon GA pathology.<br><br>TRANSLATIONAL RELEVANCE: Further investigation of levodopa may be more appropriately directed toward neovascular age-related macular degeneration, rather than geographic atrophy, where preclinical, retrospective, epidemiologic, and prospective data suggest a benefit.}, }
@article {pmid42592127, year = {2026}, author = {Wei, Y and Zhao, K and Grzybowski, A and Jin, K}, title = {Federated learning for privacy-preserving ophthalmic artificial intelligence: clinical applications and translational challenges.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1904004}, pmid = {42592127}, issn = {2296-858X}, abstract = {Federated learning (FL) is increasingly relevant to ophthalmology because retinal photographs, optical coherence tomography (OCT), OCT angiography, visual fields, and linked clinical records are clinically valuable but difficult to pool across institutions. In this narrative review, we synthesize ophthalmology-focused FL literature across diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), pediatric retinal disease, multi-disease retinal diagnostics, and emerging ophthalmic platforms. Current evidence suggests that FL can support collaborative AI development without centralizing raw patient data, and selected studies show performance close to centralized training under controlled retrospective or multicenter experimental conditions. For example, multicenter glaucoma detection from volumetric OCT achieved an AUC of 0.92 with FL compared with 0.94 for centralized training. However, FL is privacy-enhancing rather than privacy-complete, and most ophthalmic FL systems have not yet undergone prospective clinical validation. Model updates may remain vulnerable to gradient inversion, membership inference, poisoning, site-level bias, and latent identity or attribute leakage. For eye-care networks, the main value of FL is therefore not simply algorithmic performance but a governance model for privacy-conscious collaboration. Prospective validation, interoperability, explainability, workflow integration, privacy auditing, and clear responsibility for monitoring are needed before FL-enabled ophthalmic AI can be deployed routinely.}, }
@article {pmid42593178, year = {2026}, author = {Zhu, M and Cui, L and Guo, Y and Tu, Y and Wang, Y and Zhou, W and Zhang, Y and Xie, L and Jin, H}, title = {LPA1-Induced EMT of Retinal Pigment Epithelial Cells Promotes Subretinal Fibrosis via USP1-Mediated Deubiquitination and Stabilization of ZEB1.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {34}, doi = {10.1167/iovs.67.10.34}, pmid = {42593178}, issn = {1552-5783}, mesh = {Animals ; *Zinc Finger E-box-Binding Homeobox 1/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; Fibrosis/metabolism ; *Epithelial-Mesenchymal Transition/physiology ; Mice, Inbred C57BL ; Blotting, Western ; Disease Models, Animal ; Ubiquitination ; *Ubiquitin-Specific Proteases/metabolism ; Cells, Cultured ; Cell Movement ; *Gene Expression Regulation ; }, abstract = {PURPOSE: Subretinal fibrosis (SRF) is a vision-threatening complication of neovascular age-related macular degeneration (nAMD), yet effective antifibrotic strategies remain limited. This study investigated the role of lysophosphatidic acid receptor 1 (LPA1), a fibrosis-associated G protein-coupled receptor, in SRF progression and evaluated its therapeutic potential.<br><br>METHODS: A two-stage laser injury model was used to induce SRF in C57BL/6J mice. LPA1 expression and its regulation of ubiquitin-specific peptidase 1 (USP1) and zinc finger E-box binding homeobox 1 (ZEB1) were assessed by western blotting and immunofluorescence. Retinal pigment epithelial (RPE) cell epithelial-mesenchymal transition (EMT) was evaluated by migration assays and fibrotic marker analysis. ZEB1 and USP1 loss-of-function experiments were performed to define their roles. Molecular docking and co-immunoprecipitation were used to examine USP1-mediated ZEB1 deubiquitination. The antifibrotic effects and the safety of LPA1 inhibition by BMS-986278 were assessed in vivo.<br><br>RESULTS: LPA1 was upregulated in laser-induced SRF and was associated with increased fibrotic marker expression. LPA1 overexpression promoted RPE EMT and migration through the USP1/ZEB1 axis. Mechanistically, LPA1 increased USP1 expression, which stabilized ZEB1 and promoted its nuclear translocation by reducing ZEB1 ubiquitination. USP1 inhibition attenuated LPA1-induced EMT and fibrosis, similar to ZEB1 silencing. In vivo, BMS-986278 suppressed EMT and reduced SRF severity, with a stronger inhibitory effect on fibrotic lesions than on neovascular lesions.<br><br>CONCLUSIONS: LPA1 promotes SRF by driving RPE EMT through USP1-mediated deubiquitination and stabilization of ZEB1. Targeting the LPA1/USP1/ZEB1 axis may provide a promising therapeutic strategy for nAMD-associated SRF.}, }
@article {pmid42593483, year = {2026}, author = {Reiter, GS and Loewenstein, A}, title = {Enriched trial designs and the patients left behind.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42593483}, issn = {1435-702X}, }
@article {pmid42593648, year = {2026}, author = {Baker, L and Rahhal, FM and Gilbert, CJ and Leng, T}, title = {Understanding the Geographic Atrophy Journey: Patient and Physician Perspectives to Inform Better Care.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42593648}, issn = {2193-8245}, support = {P30-EY026877/EY/NEI NIH HHS/United States ; }, abstract = {OBJECTIVES: Geographic atrophy (GA) can place substantial physical and emotional burdens on affected individuals, related to both the disease and its treatment. Here, we provide insights into the perspectives of a patient with GA and retina specialists around GA diagnosis, treatment, communication, and needs.<br><br>METHODS: Unstructured qualitative interviews were conducted with a patient author with GA and two retina specialist authors involved in the management of GA. The authors discussed early GA symptoms, its diagnosis and management, treatment experience, support, and education.<br><br>RESULTS: Several themes emerged. A GA diagnosis can be emotionally distressing and difficult for patients to accept. The reality is that although current treatments delay progression of further visual impairments, these therapies do not restore lost vision. Current GA treatments are associated with frequent clinic visits and intravitreal injections that can lead to discomfort and temporary visual disturbances, which are disruptive to daily life. Physicians also noted a lack of clinical endpoints for guiding optimal dosing. The importance of patient-physician communication in the management of GA was highlighted, focusing on an approach that incorporates the emotional and practical needs of patients. Physicians play a central role in ensuring treatment compliance to minimize further vision loss. Peer support is also invaluable for sharing experiences, treatment expectations, and reassurance. Finally, patient and provider suggestions for improving outcomes for people with GA were discussed, including access to patient-focused educational materials on GA and treatment, development of tangible endpoints in clinical trials, and facilitation of peer support. All authors supported the development of long-acting formulations, systemic medications, or optimally a cure, to reduce treatment burden.<br><br>CONCLUSIONS: GA and its treatment place a substantial burden on patients. Multiple opportunities remain to improve the experiences of people with GA and empower patients to understand their condition and treatment, which ultimately could improve their outcomes. Audio feature available for this article.}, }
@article {pmid42593649, year = {2026}, author = {Angers, S and Wykoff, CC and Antonetti, DA and Junge, HJ and Nudleman, E and Nagiel, A and Schlottmann, PG and D'Amico, DJ and Prenner, J and Guyer, DR and Miller, CG and Baker, K and Stephens, P and Henry, E and Rekers, H and Adamis, AP and Ng, YSE}, title = {Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42593649}, issn = {2193-8245}, abstract = {Breakdown of the blood-retinal barrier (BRB) is implicated in many blinding retinal diseases, including diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion. Anti-vascular endothelial growth factor (anti-VEGF) therapies or laser photocoagulation are currently the standard of care for retinal diseases that are characterized by breakdown of the vascular barrier function and vascular hyperpermeability. However, inadequate response to anti-VEGF therapy is seen in a substantial proportion of patients and laser photocoagulation does not restore vision loss and can lead to collateral damage of the retina. Thus, new therapeutic targets are needed. The β-catenin-dependent wingless-related integration site (Wnt) signaling pathway plays a critical role in inner BRB development and maintenance. There are several potential therapeutics for retinal vascular diseases targeting the Wnt/β-catenin pathway under investigation, including several in preclinical development and one (MK-3000; also known as Restoret and formerly EYE103) with early clinical trial results advancing to late-stage clinical development. In this narrative review we examine the role of Wnt/β-catenin signaling in inner BRB maintenance and in retinal vascular diseases, as well as the potential for Wnt pathway agonism as a therapeutic approach.}, }
@article {pmid42594967, year = {2026}, author = {Ferrara, S and Schloss, J}, title = {Does Crocus sativus (Saffron) Have an Influence or Effect on Ocular Health: A Systematic Literature Review.}, journal = {Journal of evidence-based integrative medicine}, volume = {31}, number = {}, pages = {2515690X261478846}, doi = {10.1177/2515690X261478846}, pmid = {42594967}, issn = {2515-690X}, mesh = {*Crocus/chemistry ; Humans ; Vitamin A/analogs &amp; derivatives ; Carotenoids/pharmacology ; *Eye Diseases/drug therapy ; *Plant Extracts/pharmacology ; }, abstract = {BackgroundCrocus sativus (Saffron) and its bioactive constituents, crocin and crocetin have gained attention for their neuroprotective and antioxidant properties in ocular health. This review synthesises clinical evidence from extracted studies evaluating their efficacy, safety and dosing across Age-related Macular Degeneration (AMD), Primary Open-Angle Glaucoma (POAG), Diabetic Macular Edema (DME), Central Serous Retinopathy (CSR), Stargardt Disease (STGD1) and Paediatric Myopia (PM).MethodologyA systematic literature review was undertaken assessing randomized trials, observational or cohort studies, case studies or series written in English between January 2015 to January 2025. Studies were identified using PubMed, AMED, CINHAL, ScienceDirect and Scopus as well as the grey literature.ResultsTen clinical trials were identified from 529 citations. Interventions involved oral supplementation of saffron (20-50mg/day), crocin (5-15mg/day) and crocetin (7.5mg/day) over durations ranging from 6 weeks to 12 months. Primary outcomes included visual acuity, retinal electrophysiology, intra-ocular pressure, macular thickness, and safety profiles.ConclusionSaffron, crocin and crocetin, demonstrate consistent efficacy and exceptional safety profiles across a range of ocular conditions. Saffron's dose-dependent therapeutic effects are a promising adjunctive therapy in ophthalmology. Further large-scale trials are warranted to confirm these findings and refine condition specific dosing.}, }
@article {pmid42597498, year = {2026}, author = {Miller, WP and Arevalo-Alquichire, S and Perez-Corredor, P and Lin, R and Upreti, A and Sanchez-Suarez, J and Vanderleest, TE and Marino, C and Spencer, D and Scribner, M and Vargas, J and Muriel-Torres, A and Hu, X and Adu-Rutledge, Y and Kaplan, BA and Barake, KW and Gunawan, AL and Vijikumar, A and Shrestha, R and Lennikov, A and Kim, LA and Arboleda-Velasquez, JF and Peterson, A and Agrawal, S and Vathipadiekal, V and Loya, C and O'Hare, M}, title = {Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {3}, pages = {103024}, pmid = {42597498}, issn = {2162-2531}, abstract = {Antisense oligonucleotides (ASOs) are RNA-targeting therapeutics with broad potential for genetically defined and complex ocular diseases. The eye is particularly well suited for ASO delivery because of its compartmentalized anatomy, accessibility, and capacity for sustained intraocular drug retention. Autosomal dominant drusen (ADD), an inherited retinal dystrophy characterized by early drusen formation and secondary choroidal neovascularization (CNV), is caused by the EFEMP1 R345W mutation. Mutant EFEMP1 accumulates within the retinal pigment epithelium (RPE) and extracellular matrix, contributing to disease pathology. EFEMP1 is also elevated in the serum and RPE/choroid of patients with age-related macular degeneration (AMD), although its functional role in AMD remains incompletely defined. Here, we developed a biallelic EFEMP1-targeted ASO that achieved potent knockdown and modulated disease-relevant pathways in iPSC-derived RPE, human microvascular retinal endothelial cells (HMRECs), ex vivo human choroidal explants, and in vivo mouse models. EFEMP1 protein levels were increased in AMD tissue, and ASO-mediated EFEMP1 knockdown reduced complement factor 3 (C3), suppressed HMREC proliferation and migration, and inhibited angiogenic sprouting in choroidal explants. These findings support EFEMP1 as a pathogenic regulator of retinal degeneration and vascular dysfunction and establish EFEMP1-directed ASOs as a promising therapeutic strategy for ADD and AMD.}, }
@article {pmid42598009, year = {2026}, author = {Abdalla Elsayed, MEA and MacLaren, RE}, title = {Quantification of Ocular Gene Therapy-Related Inflammation Using the VRMACS Grading System.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101316}, pmid = {42598009}, issn = {2666-9145}, abstract = {Retinal gene therapy has been shown to be a benefit in treating inherited retinal degenerations and may become the first line of treatment for patients with more common conditions such as age-related macular degeneration and diabetic retinopathy. A major limitation of ocular gene therapy is inflammation which has occurred in several clinical trials and may be the cause of dose limiting toxicity. Up until now it is been difficult to grade inflammation due to the small number of studies across many different centers. The absence of a standardized, reproducible system to grade retinal inflammation limits cross-study comparisons and consistent safety assessment. We synthesize evidence from published retinal gene therapy studies that report inflammatory outcomes and from our gene therapy center. Based on these findings, we propose a standardized grading framework-the vitritis, retinitis, microperimetry changes, fundus autofluorescence abnormalities, choroiditis, and subretinal infiltrates (VRMACS) score-to assess retinal inflammation over time using clinical examination and multimodal imaging. The system evaluates 6 domains: vitritis, retinitis, microperimetry changes, fundus autofluorescence abnormalities, choroiditis, and subretinal infiltrates. Grading allows for structured, longitudinal assessment of inflammatory severity after gene therapy. The VRMACS score provides a standardized grading system that may improve detection, quantification, and reporting of inflammation associated with subretinal ocular gene therapy. Standardized inflammation grading could support dose selection, guide prespecified stopping rules, and improve consistency in the interpretation of inflammation-related adverse events across early- and late-phase trials. From a regulatory perspective, adoption of this system may support consistent safety assessment across clinical trials and facilitate regulatory evaluation of inflammation-related adverse events. Clinically, VRMACS offers a practical tool for monitoring patients receiving retinal gene therapy and guiding timely intervention.}, }
@article {pmid42598079, year = {2026}, author = {Gui, C and Chen, X and Liu, H and Dong, J and Zhang, Q and Gao, Y and Peng, Q}, title = {Dynamic changes in aqueous humor cytokines and OCTA parameters during aflibercept loading in treatment-naive neovascular age-related macular degeneration.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1857826}, pmid = {42598079}, issn = {2296-858X}, abstract = {PURPOSE: To investigate dynamic changes in aqueous humor cytokines and retinal vessel density during aflibercept loading in treatment-naive neovascular age-related macular degeneration (nAMD), and to analyze their associations with visual improvement.<br><br>METHODS: This single-center retrospective clinical study included 20 treatment-naive patients with nAMD (20 eyes) and 20 patients with cataracts (20 eyes). In the nAMD group, aqueous humor samples were collected at baseline and at the time of the third intravitreal aflibercept injection, while samples from the cataract control group were obtained before surgery. Relevant aqueous humor cytokines were measured using the Bio-Plex suspension bead array system. In the nAMD group, best-corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) examinations were performed at baseline and at 1 and 2 months after treatment. Longitudinal changes in OCTA parameters were analyzed using mixed-effects models, followed by correlation analyses. According to the final BCVA outcome, eyes in the nAMD group were further classified into an obvious-improvement group and a non-obvious-improvement group for exploratory subgroup comparison.<br><br>RESULTS: Compared with the cataract control group, eyes with nAMD showed significant differences in baseline aqueous humor levels of Ang-2, HGF, VEGF-C, IP-10, HB-EGF, IL-8, and PlGF. During aflibercept loading, aqueous humor levels of Ang-2, HGF, and IP-10 increased, whereas IL-8 decreased. At month 2, the superficial parafoveal vessel density and the superficial and deep perifoveal vessel density decreased significantly compared with baseline, while BCVA improved significantly. Baseline Ang-2, bFGF, and IL-8 showed nominal exploratory associations with OCTA changes, but these associations did not remain significant after FDR correction. In subgroup analysis of the nAMD cohort, only the change in deep perifoveal vessel density differed significantly between the obvious-improvement group and the non-obvious-improvement group.<br><br>CONCLUSION: Treatment-naive nAMD eyes exhibited differential changes in aqueous humor cytokines during aflibercept loading, consistent with possible non-VEGF pathway involvement. Meanwhile, regional remodeling of retinal microcirculation was observed, and changes in deep perifoveal vessel density showed a trend consistent with short-term visual improvement.}, }
@article {pmid42582531, year = {2026}, author = {Narapareddy, M and Balakrishnan, N and Iqbal, MA}, title = {Retinal Pigment Epithelial Detachment Following Topical Travoprost Therapy.}, journal = {Journal of current glaucoma practice}, volume = {20}, number = {2}, pages = {102-105}, pmid = {42582531}, issn = {0974-0333}, abstract = {Prostaglandin analogs, including travoprost, are widely used to lower intraocular pressure in primary open-angle glaucoma. While generally safe, rare posterior segment changes have been reported. Retinal pigment epithelial detachment (RPED) associated with travoprost is uncommon and poorly documented. We report three patients who developed serous RPED shortly after initiating topical travoprost, none of whom had preexisting macular disease. Optical coherence tomography (OCT) confirmed the detachments, and complete anatomical and visual recovery occurred following discontinuation of travoprost and initiation of alternative glaucoma therapy. A clear temporal relationship was observed between drug initiation and RPED onset. The absence of clinical or OCT features suggestive of alternative diagnoses-such as central serous chorioretinopathy, age-related macular degeneration, or pachychoroid spectrum disorders-combined with consistent reversibility, suggests a possible association between travoprost and RPED. These findings emphasize the importance of early recognition and timely intervention, as RPED appears fully reversible when identified promptly, preventing potential persistent visual impairment.}, }
@article {pmid42584788, year = {2026}, author = {Lu, Y and Reschigna, A and Kynast, F and Yang, Z and Gerhardt, M and Kielkowski, P and Priglinger, S and Biel, M and Michalakis, S}, title = {Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis.}, journal = {Angiogenesis}, volume = {29}, number = {4}, pages = {}, pmid = {42584788}, issn = {1573-7209}, mesh = {Animals ; Two-Pore Channels ; Humans ; *Microglia/metabolism/pathology ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Lysosomes/metabolism ; *Signal Transduction ; *Calcium Channels/metabolism/genetics ; *Endothelial Cells/metabolism/pathology ; Mice ; Mice, Knockout ; }, abstract = {Pathological choroidal neovascularization underlies vision loss in neovascular age-related macular degeneration (nAMD), yet the molecular regulators coordinating vascular and immune components remain incompletely defined. Here, we investigated the role of the endolysosomal cation channel, two-pore channel 2 (TPC2) in choroidal angiogenesis. Loss of TPC2 in mice markedly reduced ex vivo choroidal sprouting, while pharmacological activation enhanced vascular growth. Mechanistically, Tpc2-deficiency led to downregulation of multiple microglia-derived pro-angiogenic factors and impaired the ability of the microglial secretome to stimulate neovascularization. In choroidal vascular cells, TPC2 loss attenuated NF-κB/MAPK signaling pathways. Tpc2-deficiency is also associated with lysosomal secretion of cathepsins, especially CTSD, resulting in decreased extracellular proteolytic activity and impaired paracrine regulation of angiogenesis. Extending these findings to human cells, TPC2 knockout in iPSC-derived endothelial cells impaired migration, tube formation, and CTSD activity in the secretome, mirroring the murine phenotype. Together, these results establish TPC2 as one of the regulators of lysosome-mediated choroidal angiogenesis, highlighting its potential as a therapeutic target in nAMD.}, }
@article {pmid42585000, year = {2026}, author = {Colasanti, JJ and Santeford, A and Lin, JB and Terao, R and Lee, TJ and Apte, RS}, title = {MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {33}, pages = {e2524037123}, doi = {10.1073/pnas.2524037123}, pmid = {42585000}, issn = {1091-6490}, support = {EY019287//HHS | National Institutes of Health (NIH)/ ; EY02687//HHS | National Institutes of Health (NIH)/ ; 1T32GM197740-1//HHS | National Institutes of Health (NIH)/ ; F30DK130282//HHS | National Institutes of Health (NIH)/ ; T32GM07200//HHS | National Institutes of Health (NIH)/ ; }, mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Kruppel-Like Transcription Factors/metabolism/genetics ; *Macular Degeneration/genetics/metabolism/pathology ; Mice ; Humans ; *Choroidal Neovascularization/genetics/metabolism/pathology ; *Receptors, CXCR4/metabolism/genetics ; *Chemokine CXCL12/metabolism/genetics ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; *Neovascularization, Pathologic/genetics/metabolism ; Male ; }, abstract = {Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is unclear. In an injury-induced murine CNV model, we found miR-34a promoted pathological angiogenesis, without altering expression of Vegfa or its receptor Kdr, the canonical regulators of CNV. Mechanistically, miR-34a directly targets and inhibits the transcription factor KLF2, thereby upregulating the proangiogenic factors CXCR4 and CXCL12. Finally, we show miR-34a exacerbates CNV in aged mice and is expressed in CNV lesions excised from wet AMD patients. These findings establish a causal link between the age-related miR-34a and neovascularization in AMD.}, }
@article {pmid42586246, year = {2026}, author = {Manjunatha, HJ and Mahalingappa, G and Varadaraju, SR and Manjunath, SH and Prashantha, K and Damle, A and Lee, C and Kumar, A}, title = {From Food to Function: Nutraceutical-Based Modulation of Mitochondrial, Inflammatory, and Epigenetic Networks in Retinal Neurodegeneration.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {103288}, doi = {10.1016/j.arr.2026.103288}, pmid = {42586246}, issn = {1872-9649}, abstract = {Retinal neurodegenerative diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and inherited retinal dystrophies, are major causes of irreversible vision loss worldwide. Although they originate from different causes, these disorders increasingly appear to share a network of cellular stress pathways, including impaired mitochondrial function, oxidative stress, endoplasmic reticulum proteostasis collapse, chronic neuroinflammation, epigenetic dysregulation, and activation of regulated cell death pathways. The interactions among these processes create an integrated stress network that gradually disrupts retinal homeostasis and promotes neuronal degeneration, which explains the failure of therapies targeting single molecular pathways. Nutraceutical compounds found in food are gaining interest as potential agents to support retinal health because many exhibit pleiotropic biological activities that influence mitochondrial function, inflammatory signaling, antioxidant defenses, and transcriptional regulation. Herein, we consolidate knowledge of the molecular mechanisms underlying retinal neurodegeneration and how major classes of nutraceuticals (polyphenols, carotenoids, omega-3 fatty acids, and metabolic modulators) may interact with these pathways. We also discuss key translational challenges in developing therapies, including poor bioavailability and differences between human phenotypes and model systems. Additionally, we highlight emerging concepts such as microbiome-dependent metabolism of nutraceuticals, personalized nutrition strategies, and advanced ocular drug-delivery technologies. Collectively, these findings support a systems-level framework in which selected nutraceuticals may influence multiple nodes of retinal stress biology, although clinical validation remains limited.}, }
@article {pmid42586515, year = {2026}, author = {Feo, A and Quarta, A and Ramtohul, P and Faes, L and Corradetti, G and Cabral, D and Butterfield, SD and Forte, P and Eshkoly-Lior, T and Popovic, MM and Romano, MR and Banaee, T and Agarwal, A and Freund, KB and Sadda, SR and Sarraf, D}, title = {Is extensive macular atrophy with pseudodrusen a variant of age-related macular degeneration? New insights from the first multiethnic, multicentreU.S. cohort.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.07.008}, pmid = {42586515}, issn = {1715-3360}, abstract = {OBJECTIVE: To characterize the long-term clinical and multimodal imaging (MMI) features of extensive macular atrophy with pseudodrusen (EMAP) in a U.S.<br><br>DESIGN: Multicentre retrospective case series.<br><br>PARTICIPANTS: Patients diagnosed with EMAP between 2015 and 2025.<br><br>METHODS: Clinical records and MMI-including colour fundus photography, fundus autofluorescence, OCT, and OCT angiography-were reviewed at baseline and last follow-up.<br><br>RESULTS: Fifteen patients (30 eyes) were included, with longitudinal MMI analysis available in 11 patients (22 eyes). Median age at referral was 72 years (range, 40-76 years), and median baseline visual acuity was 0.3 logMAR (20/40). All eyes demonstrated diffuse pseudodrusen-like deposits and retinal pigment epithelium-Bruch membrane separation consistent with basal laminar deposits. Four eyes (13.3%) showed no macular atrophy at baseline, suggesting an early disease stage (stage 0). Peripheral retinal degeneration was identified in approximately 50% of eyes, and macular neovascularization developed in 25%, including 2 eyes (6.7%) with type 3 macular neovascularization. Median visual acuity declined to 0.54 logMAR (20/70) at final follow-up (P < 0.001), and 27% met criteria for U.S. legal blindness. Disease progression was observed in 59% after a median follow-up of 47.5 months (range, 4-114 months).<br><br>CONCLUSIONS: EMAP may represent a high-risk variant of age-related macular degeneration characterized by rapid progression to geographic atrophy. Critical diagnostic features include pseudodrusen-like deposits and basal laminar deposits, whereas a vertical pattern of atrophy represents the typical outcome. Atrophy may be absent in early disease stages. Genetic validation and consideration for inclusion in future atrophic AMD interventional trials are warranted.}, }
@article {pmid42586882, year = {2026}, author = {Guang, X and Zhang, G and Wang, Y and Chai, H}, title = {Comment on "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.2026.08.005}, pmid = {42586882}, issn = {0929-6646}, }
@article {pmid42588090, year = {2026}, author = {Łapińska, J and Kasperczuk, K and Koba, A and Kiełczyńska, E and Forma, A and Dolar-Szczasny, J and Rejdak, R and Flieger, J and Teresiński, G and Baj, J}, title = {Bioactive Properties of Carotenoids in Ocular Diseases: Antioxidant, Anti-Inflammatory, and Neuroprotective Effects.}, journal = {Nutrients}, volume = {18}, number = {15}, pages = {}, doi = {10.3390/nu18152467}, pmid = {42588090}, issn = {2072-6643}, mesh = {Humans ; *Antioxidants/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Carotenoids/pharmacology/therapeutic use ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Eye Diseases/drug therapy ; Animals ; Oxidative Stress/drug effects ; Dietary Supplements ; }, abstract = {Ocular diseases are a significant public health problem worldwide and represent one of the leading causes of disability. The prevalence of visual impairment is steadily increasing, largely driven by the ageing population. Oxidative stress, chronic inflammation and neurodegenerative processes underlie the pathogenesis of many eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts, contributing to progressive vision loss and functional impairment. Carotenoids such as lutein, zeaxanthin, meso-zeaxanthin, β-carotene, lycopene, and astaxanthin exhibit multidirectional biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. These compounds are selectively accumulated in the tissues of the eye, especially in the retina and macula, where they neutralise reactive oxygen species, modulate inflammatory pathways, stabilise mitochondrial function and support the survival and function of retinal ganglion cells and photoreceptors. The aim of our review was to provide a comprehensive review of current data regarding the mechanisms of action of carotenoids and their potential clinical significance in the prevention and treatment of retinal, optic nerve, lens, and eye surface diseases, including dry eye syndrome and Meibomian gland dysfunction. We identified results of available experimental and clinical research and outlined that an adequate supply of carotenoids in the diet or in the form of supplementation may support the protection of eye structures against oxidative and inflammatory damage, improve visual performance and potentially slow disease progression. However, high-quality prospective clinical trials are necessary to conclusively assess their therapeutic efficacy and establish evidence-based recommendations for clinical practice.}, }
@article {pmid42589986, year = {2026}, author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S}, title = {Association of Vortex Vein Morphology with Punctate Hyperfluorescence on ICGA in Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {15}, pages = {}, doi = {10.3390/jcm15155882}, pmid = {42589986}, issn = {2077-0383}, abstract = {Background/Objectives: Punctate hyperfluorescence (PH) on indocyanine green angiography (ICGA) is frequently observed in pachychoroid disease. However, the spatial relationship between PH lesions and vortex vein abnormalities remains unclear. This study quantified PH distribution in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) and examined its association with vortex vein asymmetry and watershed-zone status. Methods: This retrospective observational study included 58 fellow eyes with PH from patients with unilateral nAMD. PH lesions were quantified on late-phase ICGA images using ImageJ software. Vortex vein distribution was classified as symmetric, superior-dominant, or inferior-dominant. Eyes were also classified by the presence of a horizontal watershed zone. PH distribution was compared by vortex vein morphology. Results: A watershed zone was absent in 14 eyes (24.1%). Vortex vein distribution was asymmetric in 27 eyes (46.6%), including 17 (29.3%) superior-dominant and 10 (17.2%) inferior-dominant. Overall, 3401 PH lesions were detected. Eyes without a watershed zone had significantly more PH lesions than those with a watershed zone (p = 0.002). The proportion of superior-region PH lesions differed significantly by vertical vortex vein predominance, with preferential distribution on the dominant side (p < 0.001). Although PH distribution did not differ significantly among the four quadrants overall, 30 eyes (51.7%) had >50% of PH lesions clustered in a single quadrant. Conclusions: PH lesions were preferentially distributed on the dominant side of vortex vein asymmetry, and eyes without a watershed zone had more PH lesions. These findings indicate that PH distribution and lesion burden are associated with vortex vein morphology and watershed-zone status and may reflect underlying alterations in choroidal venous drainage.}, }
@article {pmid42590230, year = {2026}, author = {Kashiwagi, K and Fukuba, S and Kasai, H and Fukuda, Y and Hosoda, S and Tanabe, N}, title = {Patient-Reported Visual Function and Vision-Related Quality of Life Across Ophthalmic Diseases: An Exploratory Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {15}, number = {15}, pages = {}, doi = {10.3390/jcm15156128}, pmid = {42590230}, issn = {2077-0383}, abstract = {Background/Objectives: Patient-reported outcomes (PROs) provide information on subjective visual function that is not fully captured by conventional clinical measures. This exploratory cross-sectional study evaluated item-level responses to an original 11-item questionnaire and their association with vision-related quality of life across ophthalmic diseases. Methods: A total of 262 participants, including patients with glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, cataract, and individuals with long-standing severe visual impairment, completed the questionnaire and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25). Associations with age, disease category, and better-eye visual acuity were examined using correlation analyses, multivariable regression, and ordinal logistic models. Results: Perceived change in vision after treatment or disease management (A6) showed the most consistent item-level associations. A6 remained associated with age after adjustment for disease category and visual acuity (β = -0.030, p < 0.001), whereas visual acuity was not associated with questionnaire domains. A6 was negatively correlated with the VFQ-25 composite score (r = -0.693, p < 0.001) and remained associated with this score in multivariable analysis (β = -0.230, p < 0.001). Conclusions: Item-level PRO responses varied across clinical backgrounds and were not adequately explained by visual acuity alone. These findings suggest that patient-perceived visual change after treatment or disease management may provide complementary information on vision-related quality of life. Further studies using validated instruments and disease-specific severity measures are needed.}, }
@article {pmid42576424, year = {2026}, author = {Kim, BK and Min, J and Park, SH and Shin, S and Yu, S and Park, JE and Kim, S and Park, W and Ko, J and Kwon, S}, title = {Inhibition of VEGF-Induced Angiogenesis and Vascular Leakage by Bicistronic Co-Expression of Aflibercept and COMP-Ang1.}, journal = {Advanced healthcare materials}, volume = {}, number = {}, pages = {e71568}, doi = {10.1002/adhm.71568}, pmid = {42576424}, issn = {2192-2659}, support = {//National Research Foundation of Korea/ ; RS-2026-25498717//Ministry of Science and ICT/ ; RS-2023-00218543//Ministry of Science and ICT/ ; RS-2024-00512240//Korean ARPA-H/ ; //Korea Health Industry Development Institute/ ; //Ministry of Health and Welfare/ ; }, abstract = {Current anti-VEGF monotherapies for neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR) are limited by incomplete therapeutic responses, drug resistance, and the high burden of frequent intravitreal injections (IVTs). Although extensive research is underway to improve therapeutic outcomes, there remains a critical need for more effective strategies. To address this limitation, a bicistronic rAAV8 vector, Afb/cAng1, was developed to co-express aflibercept (Afb) and COMP-Ang1 (cAng1), simultaneously inhibiting VEGF signaling and activating the Tie2 pathway. In vitro characterization using conditioned medium containing secreted Afb/cAng1 showed that the treatment effectively suppresses VEGF-induced VEGFR2 phosphorylation to below basal levels while robustly activating Tie2. Consequently, the conditioned medium significantly inhibited endothelial cell migration and tube formation, and restored VE-cadherin expression compromised by VEGF stimulation or hyperglycemic conditions. Afb/cAng1 in a 3D angiogenesis-on-a-chip model reduces neovascular area and vascular permeability, showing superior efficacy compared to Afb (Eylea). In vivo choroidal neovascularization (CNV) analysis confirmed dose-dependent anti-angiogenic efficacy of rAAV8-Afb/cAng1, comparable to that of Eylea. These findings highlight Afb/cAng1 as a dual-targeting gene therapy strategy that concurrently suppresses pathological angiogenesis and promotes vascular stabilization through coordinated VEGF inhibition and Tie2 activation in AMD and DR.}, }
@article {pmid42576929, year = {2026}, author = {Zheng, Z and Rong, G and Li, G and Zhai, Y and Liang, Y and Shi, M and Huang, J and Zhang, Y and Zhao, X and Zhuo, Q and Hong, J and Xia, W and Cheng, Y and Zhao, C}, title = {Supramolecular Nrf2-activating peptide nanotherapeutics enable deep retinal penetration and RPE targeting for dry age-related macular degeneration.}, journal = {Materials today. Bio}, volume = {40}, number = {}, pages = {103492}, pmid = {42576929}, issn = {2590-0064}, abstract = {Dry age-related macular degeneration (AMD) is a leading cause of blindness that currently lacks effective therapies. Restoring redox homeostasis in the retinal pigment epithelium (RPE) via the Keap1-Nrf2 axis offers a compelling precise therapeutic strategy. While peptide-based protein-protein interaction (PPI) inhibitors are highly specific for this axis, the delivery to the deep RPE layer remains a formidable challenge, typically restricted by electrostatic entrapment within the vitreous matrix or limited transretinal penetration. Herein, we developed a novel, mechanism-driven, supramolecular peptide nanotherapeutic (FNBP) engineered to bypass these barriers and reach the RPE layer. Driven by distinct fluorophilic self-assembly, FNBP spontaneously organizes into bio-inert nanostructures that evade vitreous adhesion and exhibit superior transretinal diffusivity and accumulation to the RPE layer. Upon RPE internalization, the assembly leverages its physicochemical properties to trigger efficient cytosolic release, allowing the payload to disrupt the Keap1-Nrf2 interaction, thereby enabling potent Nrf2 activation and restoring redox homeostasis. In a murine model of retinal degeneration, a single intravitreal injection provided sustained preservation of retinal integrity for 28 days, significantly outperforming conventional peptide formulations and clinical supplements. This work offers a precise, mechanism-based solution for RPE-targeted regulation therapies and establishes a paradigm for designing peptide nanotherapeutics that circumvent the intrinsic limitations of retinal drug delivery.}, }
@article {pmid42579492, year = {2026}, author = {Wang, S and Zhao, S and Daniels, A and Naaman, E and Gardner, A and Smith, LEH and Cepko, CL}, title = {AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {33}, pages = {e2616985123}, doi = {10.1073/pnas.2616985123}, pmid = {42579492}, issn = {1091-6490}, support = {NA//Howard Hughes Medical Institute (HHMI)/ ; }, mesh = {Animals ; *NF-E2-Related Factor 2/genetics/metabolism ; *Dependovirus/genetics ; *Oxidative Stress ; Mice ; *Choroid/blood supply/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/genetics/therapy ; Retinal Pigment Epithelium/metabolism/pathology ; Disease Models, Animal ; *Growth Differentiation Factor 15/metabolism/genetics ; *Retinal Vessels/metabolism/pathology ; }, abstract = {Oxidative stress is proposed to be a driver of age-related diseases. Age-related macular degeneration (AMD) is one such disease, where the retinal pigment epithelium (RPE) is affected early in the disease. Vasculature damage also occurs, sometimes preceding RPE damage. To model some aspects of dry AMD, we used the NaIO3 mouse model of oxidative damage. Disruption of the deep retinal vascular plexus, disorganization and death of capillaries within the choriocapillaris, and marked electroretinographic decline were observed. Adeno-associated virus (AAV) overexpressing the transcription factor, NRF2, which induces antioxidation enzymes and represses inflammation, was tested for protection of damage. The BEST1 promoter limited expression to the RPE. The RPE, photoreceptors, and vascular architecture in both retinal and choroidal compartments were protected. Conditioned medium from RPE-choroid explants, infected by AAV8/BEST1-NRF2, was sufficient to transfer partial protection in vivo, suggesting that NRF2 induces a protective secreted factor(s). Analysis of RNA-seq data nominated growth differentiation factor 15 (GDF15) as a candidate secreted mediator. Injection of recombinant GDF15 reproduced key protective phenotypes in vivo, whereas Gdf15 deficiency attenuated NRF2-mediated rescue. Pharmacologic inhibition of TGF-β receptor signaling diminished NRF2-induced protection, supporting involvement of this signaling pathway. In a laser-induced choroidal neovascularization model, intravitreal GDF15 injection reduced fluorescein leakage and lesion size. These findings support a model in which NRF2 activation in the RPE induces expression of GDF15, which is capable of protecting the RPE, photoreceptors, and the retinal and choroidal vasculature. NRF2 and GDF15 have therapeutic potential for ocular diseases, as well as for other diseases with vascular pathology.}, }
@article {pmid42579523, year = {2026}, author = {Kim, JH}, title = {Persistent subretinal fluid in neovascular AMD: clinical significance and implications for treatment.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14712598.2026.2718366}, pmid = {42579523}, issn = {1744-7682}, abstract = {INTRODUCTION: In neovascular age-related macular degeneration (AMD), complete resolution of retinal fluid has traditionally been regarded as the hallmark of successful treatment, yet accumulating evidence suggests that residual subretinal fluid (SRF) may not be uniformly harmful. In this report, the cumulative evidence supporting and qualifying an 'SRF-tolerating' treatment approach is summarized.<br><br>AREAS COVERED: Relevant articles were identified through a search of the PubMed/MEDLINE database until April 2026, using terms including 'subretinal fluid,' 'intraretinal fluid,' 'neovascular AMD,' and 'anti-vascular endothelial growth factor.' The report discusses post hoc analyses of major clinical trials (CATT, VIEW, HARBOR, ARIES, and In-Eye), the randomized FLUID study, real-world cohorts, and a recent meta-analysis, covering the association of residual SRF with visual acuity and macular atrophy, contrasting evidence linking large-volume, fluctuating, or prolonged SRF with poorer outcomes, and the distinct behavior of SRF in type 3 macular neovascularization.<br><br>EXPERT OPINION: The impact of persistent SRF on outcomes has not yet been fully established, and its clinical significance is likely to depend on its volume, location, stability, duration, and the underlying lesion subtype. An SRF-tolerating approach may be considered in selected patients, but strict monitoring of fluid status and visual acuity are required to prevent undertreatment.}, }
@article {pmid42579800, year = {2026}, author = {Shi, L and Cherukaraveedu, D and Cho, H and Ri, K and Zhou, L and Cao, Y and Kale, N and Xu, Z and Liyanage, W and Kannan, RM and Duh, EJ}, title = {Mononuclear phagocyte-specific cGAS/STING targeting suppresses experimental choroidal neovascularization.}, journal = {JCI insight}, volume = {11}, number = {15}, pages = {}, pmid = {42579800}, issn = {2379-3708}, mesh = {Animals ; *Choroidal Neovascularization/pathology/metabolism/drug therapy ; Mice ; STING Protein ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; *Membrane Proteins/metabolism/antagonists &amp; inhibitors ; *Nucleotidyltransferases/metabolism/antagonists &amp; inhibitors ; cGAS-STING Signaling Pathway ; Disease Models, Animal ; Mice, Inbred C57BL ; Macrophages/metabolism ; Humans ; Male ; Female ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of blindness and is characterized by pathologic angiogenesis, specifically choroidal neovascularization (CNV). Mononuclear phagocytes (MPs), including infiltrating systemic monocyte-derived macrophages and retinal microglia, play critical roles in promoting CNV. The cGAS/STING pathway is increasingly implicated in multiple neuronal and systemic diseases and recently in ocular neovascularization. Given its roles across multiple cell types and the absence of MP-targeted therapies, we investigated the MP-specific role of cGAS/STING and a strategy for its selective targeting. In the laser-induced CNV mouse model, cGAS/STING was predominantly expressed in MPs. To enable selective targeting, we used a hydroxyl dendrimer (HD) previously shown to target MPs. HD conjugated to Cy3 selectively localized to MPs in laser CNV. HD conjugated to the STING inhibitor SN-011 (HD-SN-011) effectively inhibited cGAS/STING activation in cultured MPs. In the laser-CNV model, HD-SN-011 significantly reduced CNV leakage and lesion size, both important clinical endpoints in nAMD. RiboTag profiling confirmed selective suppression of cGAS/STING signaling and inflammatory gene expression in MPs. Together, our results implicate the specific importance of MP cGAS/STING signaling in CNV and provide proof of concept for specific modulation of STING in MPs as a therapy for nAMD.}, }
@article {pmid42579803, year = {2026}, author = {Moza, H and Jansen, E and Zackery, O and Henry, T}, title = {Isolated Ocular Relapse Following Prolonged Remission in Primary Central Nervous System Lymphoma: A Case Report.}, journal = {Journal of investigative medicine high impact case reports}, volume = {14}, number = {}, pages = {23247096261475139}, pmid = {42579803}, issn = {2324-7096}, mesh = {Humans ; Female ; Aged ; Methotrexate/administration &amp; dosage/therapeutic use ; Rituximab/therapeutic use/administration &amp; dosage ; *Central Nervous System Neoplasms/drug therapy/pathology ; Remission Induction ; Magnetic Resonance Imaging ; Neoplasm Recurrence, Local ; *Eye Neoplasms/drug therapy/secondary ; }, abstract = {Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma most commonly involving the brain and leptomeninges. While high-dose methotrexate (HD-MTX)-based therapy has improved outcomes, relapse remains common and typically occurs within the CNS. Isolated ocular relapse after prolonged CNS remission is uncommon and diagnostically challenging. We report the case of a 78-year-old woman diagnosed in 2020 with PCSNL presenting with subacute constitutional and neurologic symptoms found to have a right frontal periventricular mass. She achieved complete radiographic remission following induction with HD-MTX and rituximab and remained free of CNS disease for nearly five years on serial surveillance imaging. Beginning in 2023, she developed progressive unilateral visual decline that was initially attributed to age-related macular degeneration, with repeatedly negative MRI studies of the brain and orbits. In 2025, further ophthalmologic evaluation with an ocular oncologist revealed vitreous and retinal involvement confirming isolated ocular relapse in the absence of systemic recurrence. She was retreated with HD-MTX and rituximab, resulting in clinical and fundoscopic improvement. This case highlights a rare pattern of delayed isolated ocular relapse following long-term remission in PCNSL. It underscores the limitations of neuroimaging in detecting ocular disease and emphasizes the importance of continued ophthalmologic surveillance with those specifically trained in ocular oncology in patients with persistent visual symptoms. Guideline-consistent systemic retreatment may provide effective disease control even in late relapse, particularly in patients with prior methotrexate sensitivity.}, }
@article {pmid42570770, year = {2026}, author = {Gu, X and Zhuang, A and Fan, J and Wen, X and Yang, L and Jia, R and Chai, P and Fan, X}, title = {Lactate signaling and lactylation in retina: From physiological Warburg effect to pathological metabolic reprogramming.}, journal = {Progress in retinal and eye research}, volume = {114}, number = {}, pages = {101509}, doi = {10.1016/j.preteyeres.2026.101509}, pmid = {42570770}, issn = {1873-1635}, abstract = {Lactate was once regarded merely as a byproduct of glycolysis, but is now recognized as a multifunctional metabolite that coordinates energy redistribution, intercellular communication, receptor-mediated signaling, and epigenetic regulation. In the retina, these functions are especially consequential because visual processing depends on a highly specialized and energetically demanding tissue, characterized by steep oxygen gradients, a dual vascular supply, and tightly integrated metabolic crosstalk among photoreceptors (PCs), Müller glia, the retinal pigment epithelium, vascular cells, and retinal ganglion cells. In this review, we synthesize current advances in lactate signaling and lactylation in the retina, and examine how their dysregulation contributes to neovascularization, inflammation, and neurodegeneration in disorders including diabetic retinopathy, age-related macular degeneration, autoimmune uveitis and glaucoma. Drawing from these metabolic insights, therapeutic interventions targeting lactate signaling and lactylation are discussed as potential approaches to mitigate retinal abnormalities. Collectively, this review highlights the central importance of lactate signaling and lactylation in retinal physiology and pathology, and provides a conceptual framework for developing metabolic interventions aimed at restoring retinal lactate homeostasis.}, }
@article {pmid42572660, year = {2026}, author = {Duculescu, AI and Pirvulescu, R and Geamanu, A and Firinciogullari, E and Toma, E and Alexandrescu, C and Stanca, HT}, title = {Optical Coherence Tomography Angiography in Age-Related Macular Degeneration.}, journal = {Romanian journal of ophthalmology}, volume = {70}, number = {2}, pages = {191-198}, pmid = {42572660}, issn = {2501-2533}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroid/blood supply ; *Macular Degeneration/diagnosis/physiopathology ; Fundus Oculi ; Disease Progression ; *Retinal Vessels/diagnostic imaging/pathology ; }, abstract = {OBJECTIVE: To review and synthesize current evidence regarding the importance of optical coherence tomography angiography (OCTA) in the assessment of choriocapillaris alterations and macular neovascularization (MNV) across the spectrum of age-related macular degeneration (AMD), focusing on disease progression and clinical implications.<br><br>METHODS: Selective review of the specialized literature, concentrating on both qualitative and quantitative OCTA analyses of the retinal and choroidal microvasculature in AMD. We focused on measures related to choriocapillaris flow deficits, the morphology and maturity of MNV, and their associations with structural changes like drusen, geographic atrophy, and exudative conditions. The review included findings from both spectral-domain and swept-source OCTA systems.<br><br>RESULTS: OCTA enables non-invasive, depth-resolved visualization of choriocapillaris and MNV alterations throughout the progression of AMD. In the early and intermediate stages of AMD, localized choriocapillaris flow deficits are often observed beneath drusen and around lesion areas. In more advanced stages, there is significant choriocapillaris damage, especially near geographic atrophy and macular neovascularization. Quantitative OCTA biomarkers, such as density and flow deficit percentage, show strong correlations with disease stage, progression risk, and treatment response. Additionally, the maturity patterns of MNV identified through OCTA seem to affect the integrity of the surrounding choriocapillaris and the dynamics of atrophy.<br><br>DISCUSSION: The reviewed studies support a close relationship between choriocapillaris dysfunction, the development of macular neovascularization, and the progression of AMD. These findings reinforce the concept that vascular alterations play a central role throughout the disease spectrum and highlight the potential of OCTA to provide biomarkers that may improve prognostic assessment and treatment monitoring. However, further standardization of imaging protocols and quantitative analysis methods is needed before these biomarkers can be fully integrated into routine clinical practice.<br><br>CONCLUSIONS: OCTA has become a crucial imaging tool for understanding microvascular changes in AMD. The quantitative evaluation of the choriocapillaris and detailed analysis of MNV morphology offer important insights into disease mechanisms, progression risk, and treatment monitoring. Incorporating OCTA-derived biomarkers into routine clinical practice could improve personalized management strategies for patients across the spectrum of AMD.}, }
@article {pmid42573803, year = {2026}, author = {Hu, L and Cao, H and Ma, X}, title = {Neovascular age-related macular degeneration trial innovation remains vascular endothelial growth factor-centred despite therapeutic diversification.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42573803}, issn = {1435-702X}, support = {81271022//National Natural Science Foundation of China/ ; }, }
@article {pmid42575302, year = {2026}, author = {Matar, K and Delaney, A and Indurkar, A and Amine, R and Budrevich, J and Tang, A and Hu, M and Yu, HJ and Reese, J and Srivastava, SK and Wykoff, CC and Ehlers, JP}, title = {Assessment of Ellipsoid Zone Integrity and Other Quantitative OCT Biomarkers for Intermediate AMD Progression to Atrophy.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.08.005}, pmid = {42575302}, issn = {1549-4713}, abstract = {PURPOSE: To evaluate the association between baseline optical coherence tomography (OCT) biomarkers and 2-year disease progression from intermediate age-related macular degeneration (iAMD) to advanced atrophic AMD, defined by OCT, with emphasis on ellipsoid zone (EZ) attenuation/loss and other quantitative structural features.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: 502 eyes with iAMD and no evidence of atrophy (i.e., RPE loss with associated outer retinal atrophy) or exudation at baseline, each with 2-year follow-up OCT imaging.<br><br>METHODS: Baseline and 2-year spectral-domain OCT scans were analyzed using a validated, machine learning-enhanced multilayer segmentation platform with subsequent certified reader review and correction. Quantitative OCT parameters included EZ-RPE thickness, partial and total EZ attenuation, drusen volume, hyperreflective foci (HRF) count, total RPE loss, and outer nuclear layer-RPE (ONL-RPE) thickness. Fully automated deep-learning models quantified hypertransmission and EZ at-risk (i.e., a model developed to identify areas of abnormal EZ-RPE thinning in the absence of RPE loss). A random forest classifier was trained using baseline features, with performance assessed using 5-fold stratified cross-validation.<br><br>MAIN OUTCOME MEASURES: Development of OCT-defined advanced atrophic AMD defined by total RPE loss with associated outer retinal atrophy with an area &#x2265;0.05 mm[2] (i.e., cRORA equivalent) at 2 years and baseline OCT biomarkers associated with progression.<br><br>RESULTS: Eyes that developed advanced atrophic AMD showed significantly greater partial and total EZ attenuation, reduced EZ-RPE and ONL-RPE thickness, higher drusen volume, and greater HRF counts than non-converters (all p<0.05). Deep-learning-derived EZ at-risk and hypertransmission metrics were also significantly higher in converters. The cross-validated predictive model incorporating all baseline features achieved a mean area-under-the-ROC curve (AUC) of 0.85 &#xb1; 0.02. EZ integrity metrics and HRF count ranked as the most influential predictors of progression.<br><br>CONCLUSIONS: Quantitative OCT biomarkers, particularly EZ integrity measures and HRF count, are strongly associated with 2-year progression to advanced atrophic AMD in iAMD. These findings support the role of quantitative EZ integrity metrics and hyperreflective foci features for early disease risk stratification and may inform the design of prevention-focused or early-intervention clinical trials aimed at delaying the onset of atrophic changes.}, }
@article {pmid42575959, year = {2026}, author = {Sun, G and Zeraatkar, D and Man, REK and Ghadimi, M and Pedro Lima, J and Sivaprasad, S and Borrelli, E and Steel, DH and Guymer, RH and Wong, TY and Wykoff, CC and Ma, J and Chaudhary, V}, title = {Correction: Vision-related quality of life in non-neovascular age-related macular degeneration: a protocol for systematic review and meta-analysis.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-026-04787-5}, pmid = {42575959}, issn = {1476-5454}, }
@article {pmid42576020, year = {2026}, author = {Lee, WA and Tsai, DH and Lai, EC}, title = {Real-world safety of aflibercept 8 mg in neovascular age-related macular degeneration.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {42576020}, issn = {1432-1912}, abstract = {Aflibercept 8 mg is a higher-dose intravitreal anti-vascular endothelial growth factor formulation developed to extend treatment intervals in neovascular age-related macular degeneration (nAMD). Although pivotal trial data have supported its ocular safety profile, real-world evidence regarding intraocular inflammation (IOI) after aflibercept 8 mg remains limited. This study evaluated the real-world patient-level risk of newly coded IOI following aflibercept 8 mg initiation among patients with nAMD in a large multi-institutional electronic health record network. We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network. Patients with nAMD who received aflibercept 8 mg were identified using RxNorm code 1,232,150 with a strength restriction of 114.3 mg/mL and were required to have a prior or concurrent diagnosis of unspecified macular degeneration, exudative age-related macular degeneration, or retinal neovascularization. The index date was defined as the first recorded administration of aflibercept 8 mg. Newly coded IOI was assessed from 1 to 365 days after the index date and defined as acute or subacute iridocyclitis, retinal vasculitis, unspecified iridocyclitis, or posterior cyclitis. Patients with any component IOI diagnosis before the outcome window were excluded from the risk analysis. The mean age was 77.7 ± 10.1 years; 59.6% of patients were female, and 83.4% were White. After excluding patients with pre-existing IOI, 1,670 patients were eligible for outcome analysis. During the 365-day follow-up, 29 patients had newly coded IOI, corresponding to an observed patient-level risk of 1.74% (95% CI, 1.17%-2.48%). The mean follow-up was 281.5 ± 124.6 days, with a median of 365 days and an interquartile range of 162 days. Kaplan-Meier analysis showed an IOI-free survival probability of 97.89% at 365 days, corresponding to a Kaplan-Meier-estimated cumulative incidence of 2.11% (95% CI, 1.47%-3.04%). The low frequency of newly coded IOI provides preliminary descriptive reassurance. However, the absence of an active comparator, potential outcome misclassification, and the limited event count preclude definitive conclusions regarding comparative ocular safety.}, }
@article {pmid42567877, year = {2026}, author = {Sivaprasad, S and Stewart, MW and Wykoff, CC and Eichenbaum, D and Korobelnik, JF and Lanzetta, P and Chaudhary, V and Cheung, CMG and Gale, R and Munk, MR and Sakamoto, T and Stahl, A and Zarranz-Ventura, J and Wong, TY and Holz, FG and Loewenstein, A}, title = {Aflibercept 8 mg in neovascular age-related macular degeneration and diabetic macular oedema: Translating clinical trials into clinical practice.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42567877}, issn = {1476-5454}, abstract = {Provide expert-informed guidance on the integration of aflibercept 8 mg into routine clinical care for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO), based on clinical trial and real-world evidence. Sixteen retina specialists ('experts') met during the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May 2025 to discuss the clinical use of aflibercept 8 mg. A post-meeting online platform was used to collect additional independent input. Agreement was captured using binary responses and categorised as: all agreed (100%), majority agreed (≥ 75%), most agreed (50-74%), or non-consensus (≤ 50%). All experts agreed that aflibercept 8 mg may be considered as a first-line treatment in treatment-naïve patients with nAMD and DMO, and switching to aflibercept 8 mg can be considered for previously treated patients. The majority of experts agreed that switching patients with well-controlled disease on shorter or intermediate dosing intervals may enable further interval extension while maintaining disease control, and switching patients with poorly controlled disease may optimise anatomical outcomes and improve stability. Most experts agreed that three initial monthly loading doses are appropriate in newly diagnosed patients. No consensus was reached on optimal dosing-decision strategies after switching in patients with poorly controlled disease, nor on the timing of initial interval modification during treatment initiation. These expert opinions, informed by available, emerging clinical evidence and real-world clinical experience, support aflibercept 8 mg as a first-line and switch option for nAMD and DMO, using personalised treatment approaches for both treatment-naïve and previously treated patients.}, }
@article {pmid42568574, year = {2026}, author = {Lewis-Luján, LM and Iloki Lewis, AP and Guerrero Magaña, DE and Alvarez Chavez, CR and Osadchuk, MA and Trushin, MV and Galvez Ruiz, JC and Vargas Durazo, JT and Perez Martinez, CJ and Trujillo López, S and Iloki-Assanga, SB}, title = {Marine nutraceuticals from Mexican Pacific Sargassum targeting oxidative stress and inflammation in age-related macular degeneration.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1888072}, pmid = {42568574}, issn = {2296-861X}, abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal neurodegenerative disease characterized by oxidative stress, chronic inflammation, retinal pigment epithelium (RPE) dysfunction, and progressive central vision loss. Marine-derived bioactive compounds from Mexican Pacific Sargassum species have emerged as promising nutraceutical candidates due to their antioxidant, anti-inflammatory, and cytoprotective properties. This narrative review critically examines the nutritional composition and pharmacologically relevant bioactive constituents of Mexican Pacific Sargassum, with emphasis on fucoxanthin, fucoidans, phlorotannins, and polyunsaturated fatty acids. Particular attention is given to their molecular mechanisms of action in AMD-related pathways, including modulation of oxidative stress, Nrf2/HO-1 signaling, NF-κB-mediated inflammation, VEGF-associated angiogenesis, mitochondrial dysfunction, and apoptosis in retinal cells. Current evidence from preclinical retinal models suggests that these compounds may exert protective effects against AMD progression through multipronged regulation of redox and inflammatory pathways. Additionally, major translational challenges related to bioavailability, extraction standardization, safety, and the absence of AMD-specific clinical trials are critically discussed. Overall, Mexican Pacific Sargassum represents a promising yet underexplored source of marine bioactives with potential applications in the development of nutraceutical strategies targeting retinal degeneration and AMD.}, }
@article {pmid42569289, year = {2026}, author = {Ehrenzeller, C and MacLaren, RE}, title = {Interactions Between Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101287}, pmid = {42569289}, issn = {2666-9145}, abstract = {CLINICAL RELEVANCE: Age-related macular degeneration (AMD) remains the leading cause of irreversible blindness in Western populations, with no approved therapies for the dry form characterized by drusen accumulation and retinal pigment epithelium atrophy. This review examines extracellular matrix alterations in Bruch's membrane by comparing healthy aging, AMD pathogenesis, and Doyne Honeycomb Retinal Dystrophy-a monogenic disorder that serves as a surrogate model for AMD due to similar phenotypic manifestations.<br><br>METHODS: We focus on the critical interactions between epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases-3, and complement factors. We explore their roles in extracellular matrix homeostasis disruption. In healthy aging, oxidative stress and inefficient waste removal drive gradual matrix remodeling and low-grade inflammation. Age-related macular degeneration results from polygenic risk variants in complement and extracellular matrix genes, combined with environmental stressors, leading to accelerated matrix dysfunction and chronic complement activation. In Doyne Honeycomb Retinal Dystrophy, the EFEMP1 R345W mutation causes rapid disease progression through impaired protein secretion, abnormal matrix accumulation, and complement dysregulation.<br><br>RESULTS: Our analysis reveals that EFEMP1-tissue inhibitor of metalloproteinases-3 complexation may represent a critical threshold in drusen formation across both conditions, AMD and Doyne Honeycomb Retinal Dystrophy.<br><br>CONCLUSION: While AMD pathogenesis unfolds over decades through cumulative insults, the EFEMP1 mutation compresses similar pathological changes into 30 to 40 years, suggesting this mutation acts as a major hazard for matrix homeostasis disruption. Understanding these shared mechanisms provides insights into therapeutic targets, including complement inhibition, MMP modulation, and EFEMP1-directed interventions. We propose continued investigation of Doyne Honeycomb Retinal Dystrophy as a valuable model for identifying AMD treatments.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42569388, year = {2026}, author = {Bodmer, NS and Guezelguen, M and Huber, L and Howell, J and Faes, L and Bachmann, LM and Fu, DJ and Spooner, K and Sivaprasad, S and Schmid, MK}, title = {Vision-Related Patient-Reported Outcomes in Randomized Controlled Trials of Age-Related Macular Degeneration: A Systematic Review.}, journal = {Ophthalmology science}, volume = {6}, number = {9}, pages = {101308}, pmid = {42569388}, issn = {2666-9145}, abstract = {TOPIC: This systematic review examined how vision-related patient-reported outcome measures (PROMs) were selected, operationalized, and reported at baseline in randomized controlled trials (RCTs) enrolling patients across the spectrum of age-related macular degeneration (AMD).<br><br>CLINICAL RELEVANCE: Age-related macular degeneration is a major cause of visual disability, and visual acuity alone does not fully capture its effects on everyday functioning and quality of life. Inconsistent selection and incomplete reporting of PROMs may limit interpretation, comparison across trials, and evidence synthesis.<br><br>METHODS: A systematic search of Medical Literature Analysis and Retrieval System Online, Embase, Web of Science Core Collection, and Scopus was conducted from database inception to September 27, 2023, supplemented by a targeted update for relevant 2024 and 2025 publications. Eligible studies were RCTs enrolling &#x2265;20 participants with AMD and reporting both baseline visual acuity and baseline vision-related PROM data. Data on PROM instrument selection, scoring, baseline distributions, laterality context, and subgroup reporting were extracted and synthesized descriptively.<br><br>RESULTS: Thirty-eight RCTs met the inclusion criteria, spanning early through late-stage AMD. Across included trials, 11 distinct PROM instruments were reported. The National Eye Institute Visual Function Questionnaire family predominated (78.9%), with the National Eye Institute Visual Function Questionnaire&#x2011;25 being the most commonly used version (n = 17). Baseline patient-reported functional status varied by disease stage: early and intermediate AMD cohorts reported higher scores (75.3-89.1), whereas trials enrolling neovascular AMD patients showed lower and more heterogeneous scores (59.1-77.9). Subscale and domain reporting was inconsistent, with many trials presenting only composite scores or a limited subset of subscales. Baseline PROM results were not reported by subgroup, preventing comparisons across patient populations. Reporting of visual function was incomplete with only 13% of studies reporting both better-seeing and worse-seeing eyes.<br><br>CONCLUSION: The interpretive value of PROMs in AMD trials is constrained by inconsistent baseline reporting and limited reporting of both-eye and binocular acuity needed to contextualize patient-level function. Enhanced consistency in stage-appropriate PROM selection and routine reporting of baseline distributions are essential to support patient-centered evaluation and evidence synthesis in AMD research.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42570084, year = {2026}, author = {Ahuja, AS and Vasu, P and Wagner, IV and Hwang, TS and Dorairaj, SK and Young, BK}, title = {Racial and ethnic disparities in faricimab injections: a propensity matched cohort study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42570084}, issn = {1435-702X}, abstract = {PURPOSE: To evaluate potential racial and ethnic disparities in the utilization of faricimab-svoa in the management of macular edema (ME) and neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A retrospective cohort study using the TriNetX database analyzed patients diagnosed with nAMD, type 2 diabetes with diabetic macular edema (DME), or retinal vein occlusion macular edema (RVO ME), grouped by Hispanic ethnicity, African American (AA) race, and non-Hispanic, non-AA controls. Propensity score matching was conducted for age, gender, diabetes mellitus, essential hypertension, obesity, ischemic heart disease, and atherosclerotic heart disease. The primary outcome was faricimab-svoa injection incidence at any time point after diagnosis. Odds ratios (ORs) were calculated between cohorts.<br><br>RESULTS: Of 49,568 AA patients (mean [SD] age at injection, 68.3 [14.4] years; 58.5% women) with a diagnosis of nAMD or ME, 55 received faricimab injection (OR 0.162; 95% CI, 0.122-0.215) compared to 338 in the control group of the same size. A similar relationship was noted for Hispanic patients (mean [SD] age at injection, 66.6 [13.5] years; 50.1% women) who received the injection (25 of 13,520) compared to non-Hispanic patients (91 of 13,520) (OR 0.273; 95% CI, 0.176-0.426).<br><br>CONCLUSION: Faricimab is underutilized in the management of ME and nAMD in patients with AA race and Hispanic ethnicity compared to propensity score matched controls.}, }
@article {pmid42567397, year = {2026}, author = {Wang, Y and Luo, T and Li, C and Zhou, L and Lin, H and Yang, MM}, title = {Cellular senescence in posterior segment neovascular diseases: A proposed feed-forward amplification model.}, journal = {Experimental eye research}, volume = {272}, number = {}, pages = {111189}, doi = {10.1016/j.exer.2026.111189}, pmid = {42567397}, issn = {1096-0007}, abstract = {Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR) continue to be significant contributors to permanent visual impairment. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has substantially improved disease management, recurrent neovascularization, persistent leakage, incomplete treatment response, subretinal fibrosis in nAMD, and fibrovascular membrane formation or tractional complications in PDR indicate that disease progression involves mechanisms beyond VEGF signaling alone. Cellular senescence-a stress-induced condition marked by persistent cell-cycle arrest, altered stress responses, and context-dependent senescence-associated secretory phenotype (SASP) activity-has been identified as a potential pathogenic amplifier in posterior-segment neovascular diseases. Chronic oxidative stress, hyperglycemia, hypoxia, metabolic dysfunction, and inflammation in the retina and choroid may induce senescence-associated or senescence-like remodeling in retinal pigment epithelial cells, Müller glia, endothelial cells, and pericytes. Nonetheless, conclusive evidence of bona fide cellular senescence in human ocular tissues remains scarce and varies markedly across cell types and disease contexts. This review integrates direct experimental evidence, marker-based observations, and inferred mechanistic insights to delineate a proposed, evidence-based senescence-associated feed-forward amplification model. In this model, chronic pathological stress may initiate or reinforce senescence-related programs, whereas SASP factors, extracellular vesicles, and immune microenvironment remodeling may further amplify angiogenic, inflammatory, vascular, and fibrotic dysfunction. Importantly, this model should be interpreted as a hypothesis-generating, non-exclusive framework rather than a fully established causal pathway. We also compare disease-specific features of nAMD and PDR, discuss methodological challenges in defining retinal senescence, and evaluate the translational potential and safety concerns of senolytics and SASP-modulating strategies as adjuncts to anti-VEGF therapy. Rather than presenting cellular senescence as a fully established causal driver, this review frames senescence-associated remodeling as a context-dependent, evidence-stratified amplifying component within this proposed feed-forward framework.}, }
@article {pmid42561799, year = {2026}, author = {Xu, Y and Xu, M and Qie, J and Yu, B and He, X and Zhou, Y and Zhang, L and Jin, Q and Ye, J and Han, H}, title = {A boronate-phenolic network nanoplatform carrying dimethyl itaconate for ameliorating neovascular age-related macular degeneration.}, journal = {Biomaterials}, volume = {337}, number = {}, pages = {124528}, doi = {10.1016/j.biomaterials.2026.124528}, pmid = {42561799}, issn = {1878-5905}, abstract = {Age-related macular degeneration (AMD), particularly its neovascular form driven by choroidal neovascularization (CNV), remains leading cause of irreversible blindness worldwide. Current anti-vascular endothelial growth factor (VEGF) therapy offers limited efficacy, indicating that monotherapies targeting the downstream VEGF pathway cannot meet clinical needs, thus highlighting the demand for upstream and multifunctional therapeutic strategies. In this study, a boronate-phenolic network was constructed by cross-linking antioxidant tannic acid (TA) with ((1,3,5-Triazine-2,4,6-triyl)tris(benzene-4,1-diyl))triboronic acid (TBPT), in the presence of polyethylene glycol (PEG) for stabilization. Anti-inflammatory dimethyl itaconate (DMI) was further encapsulated, resulting in DTTP nanoparticles. With this multifunctional design, DTTP effectively promoted ROS elimination and mitochondrial protection, reestablished glutathione homeostasis, and downregulated genes involved in pyroptotic and inflammatory pathways. In a laser-induced CNV mouse model, intravitreal DTTP exhibited robust therapeutic efficacy with a favorable safety profile, achieving a 71.8% reduction in neovascularization and a 57.4% reduction in vascular leakage, with aflibercept serving as a clinically relevant benchmark. Collectively, DTTP represents a promising multifunctional nanotherapeutic for the management of neovascular AMD (nAMD).}, }
@article {pmid42562233, year = {2026}, author = {Narayan, A and Issa, PC and Yusuf, IH and MacLaren, RE}, title = {CDHR1-associated retinal degeneration: Clinical phenotypes and therapeutic approaches.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101508}, doi = {10.1016/j.preteyeres.2026.101508}, pmid = {42562233}, issn = {1873-1635}, abstract = {CDHR1 is a recently identified cause of autosomal recessive retinal degeneration manifesting as three distinct clinical phenotypes: macular dystrophy, cone-rod dystrophy or retinitis pigmentosa. In this review, we summarise the discovery and characterisation of CDHR1, clinical phenotypes, natural history and therapeutic approaches including gene supplementation and CRISPR gene editing. CDHR1 is a non-classical cadherin that is highly expressed in cone and rod photoreceptors and is essential for the higher-order organisation of the functionally critical outer segments. Promising pre-clinical data show that AAV gene supplementation therapy delivered by subretinal injection can lead to long-term morphological, structural, functional and behavioural improvements in the Cdhr1 knockout mouse model. Notably, CDHR1 supplementation restored full-length photoreceptor outer segments that are usually shortened and disorganised in disease models and prolonged photoreceptor survival - key mechanisms for the functional and behavioural rescue effects that were observed. The disease is likely to be underdiagnosed because CDHR1-associated macular dystrophy - likely to be the most common disease phenotype - is most often caused by a 'silent' nucleotide substitution that has previously been overlooked by genetic testing. Since the macular dystrophy phenotype has phenotypic similarities to advanced dry age-related macular degeneration (AMD), misdiagnoses are common. CDHR1-associated macular dystrophy also shares phenotypic features with a variety of monogenic masquerades such as ABCA4, PRPH2 and GUCY2D-associated macular dystrophies; we present a flowchart to guide the clinical distinction of these disorders which is now critical for patients as their treatments diverge. AAV gene therapy may be beneficial across the CDHR1 disease spectrum - including those with hypomorphic variants associated with macular dystrophy or retinitis pigmentosa. The coding sequence fits into AAV and with the macular dystrophy phenotype, there is a large time window for potential intervention and a large treatable population. Hence clinical trials are anticipated. It is therefore important that patients with CDHR1-associated retinal degeneration are accurately phenotyped and genetically confirmed to support the application of CDHR1 gene therapy.}, }
@article {pmid42562278, year = {2026}, author = {Zhuang, X and Olivieri, C and Neri, G and Ricardi, F and Monici, G and Viggiano, P and Boscia, F and Pauleikhoff, D and Sadda, S and Sarraf, D and Staurenghi, G and Reibaldi, M and Borrelli, E}, title = {Macular atrophy in neovascular age-related macular degeneration: Prevalence, risk factors, imaging features, and clinical implications.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.08.002}, pmid = {42562278}, issn = {1879-3304}, abstract = {Macular atrophy (MA) is a major cause of long-term visual decline in neovascular age-related macular degeneration (nAMD), despite the ability of anti-vascular endothelial growth factor (anti-VEGF) therapy to control exudation. We summarize current evidence on the definition, epidemiology, risk factors, imaging features, and functional consequences of MA in nAMD. Optical coherence tomography (OCT) has improved the identification of atrophic changes and supports distinguishing complete retinal pigment epithelium and outer retinal atrophy from fibro-atrophy, a proposed OCT-based category in which outer retinal and RPE loss occur beneath hyperreflective or fibrotic tissue that makes choroidal hypertransmission absent or unassessable. In treated eyes, long-term studies show that MA becomes increasingly common over time and is a major factor limiting durable visual benefit, yet epidemiologic estimates remain difficult to compare because MA definitions, imaging modalities, lesion-size thresholds, and terminology varies substantially across studies. Important risk factors include older age, poor baseline visual acuity, type 3 macular neovascularization, intraretinal fluid, subretinal hyperreflective material, and early atrophic signs on baseline imaging, whereas type 1 neovascularization may be associated with slower atrophy progression. Once established, MA substantially affects visual function, not only reducing visual acuity, but also impairing reading speed and other visual functions. A major unresolved controversy is whether cumulative anti-VEGF exposure contributes independently to MA, rather than reflecting more severe or recurrent exudative disease. Future progress will depend on standardized definitions, multimodal imaging, and predictive models to guide personalized management and develop therapies targeting atrophy.}, }
@article {pmid42566331, year = {2026}, author = {Simond, B and Fenniri, I and Chirpaz, N and Elbany, S and Rocher, A and Gilli, C and Chacun, S and Voirin, N and Burillon, C and Matagrin, B and Dot, C}, title = {Evaluation of treatment interval extension and short-term stability after switching to faricimab in neovascular AMD, a mid-term observational study.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1}, doi = {10.1159/oph/aeeag007}, pmid = {42566331}, issn = {1423-0267}, abstract = {INTRODUCTION: The SHIFT-HB study (SwitcH Faricimab Treatment in High Burden patients) aimed to evaluate the anatomical and functional outcomes -and the short-term stability of extended dosing intervals- after switching to faricimab in high treatment burden (HB) neovascular age-related macular degeneration (nAMD) previously treated with first-generation anti-VEGF agents. The primary aim was to assess treatment interval changes after 6 intravitreal injections (IVI) and the persistence of interval gains between the 5th and 6th faricimab IVI.<br><br>METHODS: Single-center, retrospective real-world study (November 2023-November 2024; tertiary center Edouard Herriot Hospital, Lyon). Eligible eyes had nAMD requiring &#x2264;8-weeks intervals despite &#x2265;6 prior aflibercept or ranibizumab injections. After the switch, all eyes received &#x2265;6 faricimab IVIs under a proactive Treat-and-Extend regimen. Short-term stability was defined, among eyes with any interval gain, as a prescribed interval at V6 identical to or longer than that at realized at V5.<br><br>RESULTS: 190 eyes from 158 patients (mean age 81 &#xb1; 7.5 years; 57.9% female) were included. The mean pre-switch interval was 4.9 &#xb1; 1.2 weeks and increased to 6.7 weeks after 6 faricimab IVIs (p=5.85x10-20). Interval increased in 61.6% of eyes; among these, 45% gained &#x2265; 3 weeks (range +3 to +8). Short-term stability between V5 and V6 occurred in 82.3% of responders. The maximum interval was first achieved at V6 in 52.1% of responder eyes. Among eyes with paired baseline and V6 measurements, best corrected visual acuity remained stable (69.2 vs 71.2 ETDRS letters; p=0.67), while central retinal thickness (CRT) decreased (303.1&#x202f;&#xb5;m to 287.2&#x202f;&#xb5;m; p=9.98x10-4). Intraocular inflammation occurred in 7 eyes (3.7%; 0.61% of injections) and led to drug discontinuation.<br><br>CONCLUSION: In real world HB nAMD, switching to faricimab enabled a significant extension of injection intervals in nearly two-thirds of eyes while maintaining vision and improving OCT anatomy, supporting faricimab as a strategy to reduce treatment burden in this difficult to treat population.}, }
@article {pmid42566756, year = {2026}, author = {Sassi, H and Miere, A and Oubraham, H and Kaoudio, D and Ionita, D and El Filali, M and Bourroubey, A and Wang, X and Jung, C and Souied, E}, title = {OUTCOMES AND HEALING PROCESS OF RETINAL PIGMENT EPITHELIAL TEARS IN AMD PATIENTS: A 5-YEAR RETROSPECTIVE OBSERVATIONAL CASE SERIES.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004960}, pmid = {42566756}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the incidence of retinal pigment epithelium (RPE) remodeling after RPE tears in age-related macular degeneration (AMD) and assess its association with visual outcomes over a 5-year follow-up.<br><br>METHODS: This retrospective observational study reviewed AMD eyes with RPE tears and a minimum follow-up of 5 years. Changes in best-corrected visual acuity (BCVA) were recorded, and the presence and delay to development of tear-associated retinal pigment epithelial proliferation (TARP) were evaluated.<br><br>RESULTS: Twenty-six eyes from 23 patients were included. Mean age was 80.08 &#xb1; 6.67 years. Baseline BCVA was 0.83 &#xb1; 0.52 logMAR (Snellen equivalent 20/125), and final BCVA declined to 1.05 &#xb1; 0.54 logMAR (20/200) (p = 0.028). Mean follow-up was 6.25 &#xb1; 1.25 years. Both the greatest linear diameter and the area of RPE loss increased significantly from baseline to year 5 (p = 0.012 and p = 0.009, respectively). TARP was observed in 54.2% of eyes at 5 years, with a mean onset of 293 &#xb1; 258 days. Final BCVA was significantly worse in eyes with subretinal hemorrhage (p = 0.02), while the presence of TARP was not associated with visual outcome (p = 0.21). At 5 years, BCVA declined in both groups (with and without TARP), with no significant difference (p = 0.21).<br><br>CONCLUSIONS: Approximately half of the eyes with RPE tears developed TARP, typically within the first year. TARP did not confer a visual benefit. These findings suggest that anatomical remodeling of RPE tears may occur without translating into improved visual outcomes.}, }
@article {pmid42558742, year = {2026}, author = {Mou, H and Zhang, CJ}, title = {Association between frailty and incidence of AMD among middle-aged and older people: evidence from the UK Biobank.}, journal = {Frontiers in aging}, volume = {7}, number = {}, pages = {1838979}, pmid = {42558742}, issn = {2673-6217}, abstract = {BACKGROUND: To explore the association between age-related macular degeneration (AMD) and frailty and the link between frailty and neurological aging diseases in AMD patients.<br><br>METHODS: This study included 354,334 individuals aged &#x2265;40 years without AMD at baseline from the UK Biobank. Frailty was assessed using the Fried phenotype. Cox proportional hazard models were used to analyze the association between frailty and AMD incidence. Logistic regression models were used to examine the link between frailty and nervous system-related diseases among AMD patients.<br><br>RESULTS: Frailty was associated with AMD incidence (hazard ratio [HR] 1.36 [95% confidence interval [95% CI] 1.29-1.44] for prefrailty; HR 2.12 [95% CI 1.86-2.42] for frailty). All five frailty components were associated with AMD: weight loss (HR 1.11 [95% CI 1.03-1.20]), exhaustion (HR 1.13 [95% CI 1.03-1.23]), low physical activity (HR 1.12 [95% CI 1.01-1.23]), low grip strength (HR 1.23 [95% CI 1.14-1.32]), and slow walking pace (HR 1.23 [95% CI 1.12-1.35]). Additionally, among AMD patients, frailty was linked to neurodegenerative diseases (odds ratio [OR] 3.09 [95% CI 1.58-6.07]), neurovascular diseases (OR 3.77 [95% CI 2.16-6.60]), and mental diseases (OR 2.09 [95% CI 1.12-3.93]).<br><br>CONCLUSION: Frailty is a significant risk factor for AMD incidence, with all five components showing a positive association with AMD. Furthermore, frailty is linked to neural system-related diseases in AMD patients. Early detection and intervention for frailty may help prevent or delay AMD onset.}, }
@article {pmid42560008, year = {2026}, author = {Larsen, PP and Linard, M and Schweitzer, C and Delyfer, MN and Korobelnik, JF and Helmer, C and Delcourt, C}, title = {Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {14}, doi = {10.1167/iovs.67.10.14}, pmid = {42560008}, issn = {1552-5783}, mesh = {Humans ; *Macular Degeneration/etiology ; *Diabetic Retinopathy/etiology ; *Endotoxemia/complications ; Animals ; *Glaucoma/etiology ; Lipopolysaccharides ; Oxidative Stress ; }, abstract = {Lipopolysaccharide (LPS), a component of Gram-negative bacteria, is a potent activator of the innate immune system and has been implicated in the pathogenesis of eye diseases, including age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), and diabetic retinopathy (DR). LPS enters systemic circulation through bacterial lysis or active secretion, leading to endotoxemia-either acute or chronic. Chronic endotoxemia, often resulting from gut dysbiosis, may link microbial imbalances to eye diseases. Indeed, chronic LPS exposure may contribute to both systemic and local inflammation. Within the retina, it activates resident immune and structural cells triggering pro-inflammatory cytokine production, oxidative stress, complement cascade activation, and inflammasome activation. These immune cascades compromise blood-retinal barrier integrity, increase vascular leakage, and impair neuronal viability. LPS exposure can stimulate the secretion of pro-angiogenic factors, promoting the development of neovascularization within the retina. Furthermore, the aging retina may be particularly vulnerable to LPS-mediated damage due to an increased exposure to LPS (linked to microbial dysbiosis and alterations of both intestinal and blood-retinal barriers) as well as a reduced capacity for repair. Although direct human evidence remains limited, emerging experimental data support a mechanistic role for LPS in AMD, glaucoma, and DR. This review emphasizes that addressing the impact of chronic endotoxemia represents a promising avenue for both understanding and treating eye diseases. Continued investigation into the multifaceted roles of LPS may yield innovative biomarkers and therapeutic targets to slow or prevent neurodegenerative, vascular, and inflammatory processes underlying conditions such as AMD, glaucoma, and DR.}, }
@article {pmid42560501, year = {2026}, author = {Özkaya, D and Nazıroğlu, M}, title = {Psalmotoxin-1, a novel TRPM2 channel antagonist, reduces age-related macular degeneration-caused mitochondrial oxidative damage and apoptosis in human retinal pigment epithelial (ARPE-19) cells.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42560501}, issn = {1435-702X}, support = {2024-05//BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry LTD, Isparta, T&#xfc;rkiye/ ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) develops as a result of mitochondrial reactive oxygen species (mitROS) and apoptosis caused by increased Ca[2+] influx via the overstimulation of transient receptor potential melastatin 2 (TRPM2). Psalmotoxin-1 (PSTX) has acid-sensing ion channel (ASIC) inhibitor and antioxidant actions in several cells. PSTX has been shown to modulate hypoxia-induced oxidative cytotoxicity and cell death in mouse eye cells by inhibiting ASIC-mediated Ca[2+] influx; however, this mechanism does not apply to AMD. In this study, we investigated how PSTX inhibits TRPM2 to protect human retinal pigment epithelium - 19 (ARPE-19) cells against mitROS damage and apoptosis caused by sodium iodate (SoI).<br><br>MATERIALS AND METHODS: Control (CONT), 20 nM PSTX for 24&#xa0;h, 10 mM SoI for 24&#xa0;h, SoI&#x2009;+&#x2009;PSTX, and SoI&#x2009;+&#x2009;TRPM2 antagonist (25 &#xb5;M N-(p-amylcinnamoyl) anthranilic acid, ACA) groups were induced in the ARPE-19 cells.<br><br>RESULTS: The ADP-ribose-induced TRPM2 current density, Fe[2+], and H2O2-induced cytosolic Ca[2+] concentrations were elevated by the SoI treatment. Additionally, its treatment increased the markers of apoptosis, caspases (caspase-3, -8, and -&#x2009;9), oxidative stress, and mitochondrial membrane dysfunction while lowering glutathione (GSH), glutathione peroxidase (GSH-Px), and cell viability number. GSH, GSH-Px, and cell viability were enhanced, whereas oxidative stress and cell death indicators were decreased via TRPM2 inhibition by the treatments of PSTX and ACA.<br><br>CONCLUSION: The results of the preliminary study indicated that PSTX incubation blocked TRPM2-mediated Ca[2+] signaling, reducing AMD-induced mitochondrial oxidant injury and cell death. PSTX, a new TRPM2 antagonist, may be utilized to treat oxidative stress and aberrant Ca[2+] influx induced by AMD.}, }
@article {pmid42560951, year = {2026}, author = {, }, title = {Expression of Concern: Serum lipids mediate the association of per- and polyfluoroalkyl substances exposure and age-related macular degeneration.}, journal = {PloS one}, volume = {21}, number = {8}, pages = {e0355440}, pmid = {42560951}, issn = {1932-6203}, }
@article {pmid42549264, year = {2026}, author = {Yılmaz, AC and Mutlu, FM}, title = {Prevalence of Occult Macular Pathologies Detected by Optical Coherence Tomography in Patients Scheduled for Cataract Surgery.}, journal = {Beyoglu eye journal}, volume = {11}, number = {2}, pages = {95-102}, pmid = {42549264}, issn = {2587-0394}, abstract = {OBJECTIVES: To investigate the prevalence of macular pathologies detectable only by optical coherence tomography (OCT) and not suspected on fundoscopic examination before cataract surgery in a large series of Turkish patients and to determine associated risk factors.<br><br>METHODS: Medical records of patients who underwent cataract surgery, had normal fundoscopic findings during preoperative evaluation, and underwent macular OCT were retrospectively reviewed for demographic data, ophthalmological findings, and systemic examination results. Patients were divided into normal and abnormal OCT groups according to their macular OCT results. Patients in the abnormal OCT group were further analyzed for the prevalence of OCT-detected occult macular pathologies and associated risk factors.<br><br>RESULTS: Data from 1.091 eyes were included in the study. Macular pathology was detected on OCT in 9.2% of patients. Among these patients, 40 (40%) had age-related macular degeneration, 31 (31%) had epiretinal membrane, 11 (11%) had vitreomacular traction, 8 (8%) had lamellar macular hole, 5 (5%) had diabetic macular edema, and 5 (5%) had macular pseudohole. The mean age of patients with occult macular pathology was significantly higher than that of patients with normal OCT findings (p=0.001). 78.0% of patients with retinal pathology were 70 years of age or older. Advanced age was identified as the most important predictor of occult macular pathology (OR: 1.086, p=0.001).<br><br>CONCLUSION: Reliance solely on fundoscopic examination would result in approximately 1 in 10 eyes with occult macular pathology being overlooked. OCT screening should be considered prior to cataract surgery, particularly in elderly patients.}, }
@article {pmid42549279, year = {2026}, author = {Cheong, KX and Lan, W and Hoang, QV and Saw, SM}, title = {The prevalence, progression, and visual loss associated with myopic macular degeneration in Asia.}, journal = {Taiwan journal of ophthalmology}, volume = {16}, number = {2}, pages = {272-284}, pmid = {42549279}, issn = {2211-5072}, abstract = {This systematic review examines the epidemiology, natural history, and visual outcomes of myopic macular degeneration (MMD) in Asia. MMD is irreversible, may affect both eyes, and may occur during a person's productive years, making it a significant public health concern. Population-based studies report a wide variation in MMD prevalence, ranging from 0.24% in rural India to 4.5% in mainland China. MMD is etiologically heterogeneous, with its prevalence associated with a more negative spherical equivalent (SE), longer axial length (AL), older age, and a lower education level. The development of MMD is likely nonlinear, with the prevalence of MMD increasing markedly once specific thresholds in age (60-70 years), SE (-6 to - 7 diopters), and AL (about 26 mm) are exceeded. The 5-year, 6-year, and 12-year incidence of MMD is up to 1.1%, 1.2%, and 10.3% respectively. The 10-year progression rate of MMD may reach 35.5%, often involving the development or worsening of chorioretinal atrophy. MMD is associated with significant visual impairment (VI) and blindness, with a decrease in best corrected visual acuity (BCVA) ranging from one to 13 lines. Among individuals with MMD, up to 54.5% experience VI, and up to 14.9% develop blindness in the better eye. Up to 36.4%, 21.6%, 12.3%, and 4.5% of individuals with MMD have unilateral VI, bilateral VI, unilateral blindness, and bilateral blindness, respectively. BCVA loss increases with MMD severity. These findings underscore the urgent need for public health strategies to address the growing burden of MMD in Asia's aging and increasingly myopic populations.}, }
@article {pmid42549844, year = {2026}, author = {Yu, RMC and Oguz, G and Fu, NY and Shihabuddeen, WA and Cheung, C and Wang, X and Wong, TY and Cheung, CMG and Ramasamy, A and Yanagi, Y}, title = {Caveola and Its Resident Proteins, Caveolin-1 and -2, Play Critical Roles in the Pathogenesis of nAMD and PCV.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {10}, pages = {10}, doi = {10.1167/iovs.67.10.10}, pmid = {42549844}, issn = {1552-5783}, mesh = {Humans ; *Caveolin 1/genetics/physiology/biosynthesis ; *Polypoidal Choroidal Vasculopathy/metabolism/genetics ; *Caveolin 2/genetics/physiology/biosynthesis ; *Caveolae/metabolism ; Female ; Human Umbilical Vein Endothelial Cells/metabolism ; *Macular Degeneration/metabolism/genetics ; Male ; Gene Expression Regulation/physiology ; Cytokines/metabolism ; Monocytes/metabolism ; Leukocytes, Mononuclear/metabolism ; Aged ; }, abstract = {PURPOSE: The purpose of this study was to investigate cellular and molecular mechanisms underlying neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) via single-cell RNA sequencing (scRNA-seq), then focusing on caveolae-resident proteins based on identified negatively enriched caveolae via Gene Set Enrichment Analysis (GSEA).<br><br>METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with nAMD/PCV (n = 10) and healthy controls (n = 9) were collected. A total of 22,593 high-quality monocytes were analyzed for differentially expressed genes (DEGs) and GSEA. The key finding of negatively enriched caveola was recapitulated by in vitro mRNA transfections in THP-1 monocytes and human umbilical vein endothelial cells (HUVECs), followed by validation using qPCR. Functional assays and cytokine profiling were also performed.<br><br>RESULTS: A total of 122 significant pathways was identified from WikiPathways, Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology. GSEA revealed significant negative enrichment of caveola in classical monocytes of PCV (NES = -1.769, P = 0.001, q = 0.026). Cytokine/chemokine profiling revealed that Caveolin (CAV)1/2-overexpressing monocytes secreted markedly higher levels of several proinflammatory mediators, including IL-1&#x3b2;, IL-2, IL-8, IL-17, TNF-&#x3b1;, PDGF-BB, and MIP-1&#x3b1;/&#x3b2;. CAV1 or CAV2 overexpression in THP-1 cells increased monocyte adhesion but inhibited transendothelial migration. In HUVECs, their overexpression induced moderate cytokine profiles, including downregulation of RANTES (CCL5), IL-10, and VEGF, and upregulation of IL-6 and MIP-1&#x3b1;. CAV1/2 overexpression also significantly inhibited tube formation, whereas knockdown of CAV1 or CAV2 enhanced tube formation.<br><br>CONCLUSIONS: Caveolins appear to contribute to the pathogenesis of nAMD and PCV as modulators of inflammation and vascular function. Enhanced CAV1/2 expression in endothelial cells attenuates angiogenic activity, indicating a potential therapeutic strategy.}, }
@article {pmid42552269, year = {2026}, author = {Sumer, F and Toren, M and Asan, B and Solak, M and Coskuner, N and Ozkan, B and Karabas, VL and Demirel, S and Ozdemir, H}, title = {Comparative Evaluation of Deep Generative Models for Predicting 12-Month Neovascular AMD Progression Using OCT and Fundus Photography.}, journal = {Journal of imaging informatics in medicine}, volume = {}, number = {}, pages = {}, pmid = {42552269}, issn = {2948-2933}, abstract = {The purpose of this study is to systematically compare six deep generative models for predicting long-term anatomic progression of neovascular age-related macular degeneration (nAMD) from pretreatment retinal imaging. We retrospectively analyzed OCT and fundus images from 85 treatment-naïve eyes initiating anti-VEGF therapy for nAMD. Five GAN-based architectures (BiCycleGAN, CycleGAN, Pix2pixHD, CycleGAN-Turbo, Pix2pix-Turbo) and one diffusion-based model (Stable Diffusion Img2Img) were trained separately for each modality to generate synthetic projections at 3, 6, and 12 months. Quantitative performance was assessed using structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), mean squared error (MSE), and root mean squared error (RMSE). Clinical realism was evaluated through a visual Turing test by five blinded expert graders. Pix2pixHD consistently achieved the highest image-quality metrics across all models, modalities, and time points. For OCT, they are SSIM 0.84 and PSNR 27.2 dB (3 months) and SSIM 0.83 and PSNR 25.8 dB (12 months). For fundus photographs, they are SSIM 0.80 and PSNR 26.0 dB (3 months) and SSIM 0.80 and PSNR 24.7 dB (12 months). In the visual Turing test, experts correctly identified synthetic images in 58% of cases (chance level, 50%), with OCT images showing near-chance discriminability (52%) compared to fundus photographs (64%). This study provides the first systematic comparison of multiple generative architectures for long-term nAMD progression prediction. Pix2pixHD achieved the highest fidelity, generating synthetic images whose realism was frequently, though not reliably, distinguished by observers (58%, not significantly different from chance; p = 0.13), particularly for OCT. These findings support the potential of deep generative models for AI-driven decision support in personalized retinal care. This work bridges the gap between computational science and clinical ophthalmology by demonstrating that deep generative models can transform pretreatment retinal images into clinically realistic predictions of disease progression. By enabling visualization of anticipated anatomical outcomes before treatment initiation, these tools have the potential to transition nAMD management from reactive to proactive paradigms, supporting individualized patient counseling, risk stratification, and evidence-based treatment planning at the point of care.}, }
@article {pmid42552408, year = {2026}, author = {Zhuang, X and Ulla, L and Foti, C and Cariola, R and Neri, G and Olivieri, C and Parisi, G and Petrillo, F and Marolo, P and Reibaldi, M and Borrelli, E}, title = {Real-world comparative effectiveness of faricimab versus aflibercept 2 mg in treatment-naïve exudative neovascular AMD patients treated with a treat-and-extend regimen.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42552408}, issn = {1476-5454}, abstract = {PURPOSE: To compare the real-world effectiveness of faricimab versus aflibercept 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We analysed treatment-na&#xef;ve nAMD patients aged &#x2265;50 years initiating intravitreal anti-VEGF therapy between March 2024 and September 2024. Patients received either faricimab or aflibercept 2&#x2009;mg. Inverse probability of treatment weighting was used to minimise selection bias. Primary outcomes were best-corrected visual acuity (BCVA) changes from baseline to post-loading phase and 1-year follow-up. Secondary outcomes included anatomic resolution of intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal hyperreflective material (SHRM), treatment burden, and safety.<br><br>RESULTS: A total of 172 patients were included (86 faricimab, 86 aflibercept). Baseline characteristics were well-balanced between groups. The faricimab regimen was associated with greater BCVA improvement compared with aflibercept at post-loading phase (adjusted mean difference -0.075 logMAR; 95% confidence interval [CI], -0.130 to -0.020; P&#x2009;=&#x2009;0.008) and at 1 year (-0.073 logMAR; 95% CI, -0.128 to -0.018; P&#x2009;=&#x2009;0.011). Patients receiving faricimab achieved significantly higher rates of SRF resolution (odds ratio 2.446; 95% CI, 1.012 to 5.912; P&#x2009;=&#x2009;0.047). The faricimab group was associated with fewer injections from the post-loading phase to 1 year (median 3 vs. 4; P&#x2009;<&#x2009;0.001) and lower therapy switching rates (7.9% vs. 25.6%; P&#x2009;=&#x2009;0.003).<br><br>CONCLUSIONS: In treatment-na&#xef;ve nAMD patients, faricimab achieved greater visual acuity gains, enhanced anatomic outcomes, and reduced treatment burden compared with aflibercept. However, these findings should be interpreted in light of the non-randomised design, different loading regimens, and potential differences in early treatment exposure.}, }
@article {pmid42554417, year = {2026}, author = {Ford, LM and Occelli, LM and Enfield, ME and Benjamin, NA and Sun, K and Pasmanter, N and Petersen-Jones, SM}, title = {Functional and Structural Characterization of a Large Animal Model of RDH5-Associated Retinopathy.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {8}, pages = {2}, doi = {10.1167/tvst.15.8.2}, pmid = {42554417}, issn = {2164-2591}, mesh = {Animals ; Disease Models, Animal ; Cats ; *Alcohol Oxidoreductases/genetics/metabolism ; Electroretinography ; Tomography, Optical Coherence ; Ophthalmoscopy ; Retinal Cone Photoreceptor Cells ; Retinal Rod Photoreceptor Cells ; Immunohistochemistry ; Mutation, Missense ; Humans ; Retinal Diseases ; }, abstract = {PURPOSE: Inherited retinal diseases are a group of hereditary diseases that cause variable levels of blindness and affect a multitude of adults and children. One such disease is fundus albipunctatus (FA). FA is caused by autosomal recessive retinol dehydrogenase 5 (RDH5) mutations and results in rod dysfunction leading to night blindness and, in a subset of patients, macular degeneration (MD). We previously reported a spontaneous feline model of FA due to an RDH5 missense mutation. The affected cats showed rod dysfunction and a proportion developed degeneration of the area centralis (AC), equivalent to MD in humans.<br><br>METHODS: We used fundus confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging, six different electroretinography protocols, immunohistochemistry, and histology/transmission electron microscopy to further characterize this large-animal cat model.<br><br>RESULTS: In addition to rod dysfunction, cone recovery from intense stimulation was impaired. For RDH5-/- cats that developed AC degeneration, an initial elongation of rod outer segments with disorganization of the distal tips was initially detected in the AC and visual streak, suggestive of impaired shedding/phagocytosis. With progression, photoreceptors degenerated in the AC, matching the MD seen in some human patients.<br><br>CONCLUSIONS: The RDH5-/- cat model recapitulates features of both rod and cone dysfunction seen in human patients with RDH5 mutations.<br><br>TRANSLATIONAL RELEVANCE: The RDH5-/- cat model offers a unique opportunity to further understand the mechanisms of RDH5-associated retinopathies and to investigate potential therapeutic approaches.}, }
@article {pmid42555638, year = {2026}, author = {Liu, X and Tang, D and Zhang, J and Li, T and Huang, J and Qu, J and Ruan, Y and Chai, H and Chi, ZL}, title = {3D epigenomic landscape of the human retinal pigment epithelium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {32}, pages = {e2526200123}, doi = {10.1073/pnas.2526200123}, pmid = {42555638}, issn = {1091-6490}, support = {82271114//MOST | National Natural Science Foundation of China (NSFC)/ ; 32250710678//MOST | National Natural Science Foundation of China (NSFC)/ ; 32400426//MOST | National Natural Science Foundation of China (NSFC)/ ; LZ22H120001//MOST | NSFC | NSFC-Zhejiang Joint Fund | | Natural Science Foundation of Zhejiang Province (ZJNSF)/ ; KYYW202227//Wenzhou Medical University (WMU)/ ; YNZD1201901//Eye Hospital Wenzhou Medical University/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Epigenomics/methods ; Induced Pluripotent Stem Cells/metabolism/cytology ; Cell Differentiation ; Chromatin/metabolism/genetics ; Extracellular Matrix/metabolism ; Cell Line ; *Epigenesis, Genetic ; }, abstract = {The retinal pigment epithelium (RPE) is crucial for visual function, and its dysfunction contributes to retinal diseases such as age-related macular degeneration. Despite the translational potential of iPSC-derived RPE (iPSC-RPE) in cell replacement therapy, the functional visual gains achieved to date are modest. A key challenge is that the molecular and epigenomic signatures underlying functional RPE are yet to be fully elucidated. By integrating multiomics data, we systematically benchmarked the 3D epigenomic landscapes of primary human RPE (hRPE), iPSC-RPE, and the immortalized ARPE-19 cell line. Our analysis reveals that iPSC-RPE exhibits a mixed molecular state. iPSC-RPE recapitulates hRPE-like transcription and chromatin looping, but its histone modification states remain incompletely matured, and its chromatin accessibility and higher-order chromatin organization do not fully converge to hRPE. Furthermore, we found that hRPE exhibits strong extracellular matrix (ECM) organization driven by enhancer-mediated long-range chromatin interactions and enriched RUNX1 motifs, while iPSC-RPE retains key developmental-related transcriptional signatures, marked by factors such as HAND1, OTX2, and PAX6. These findings establish a multiomics benchmark for RPE maturity, pinpoint key regulatory nodes like ECM organization and RUNX1 for therapeutic targeting, and provide a roadmap for optimizing differentiation protocols and scaffold design in retinal regenerative medicine.}, }
@article {pmid42556322, year = {2026}, author = {Pizzato, HA and Bhattacharya, D}, title = {Guiding pluripotent stem cell therapies past the immune system.}, journal = {Stem cells translational medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.1093/stcltm/szag051}, pmid = {42556322}, issn = {2157-6580}, support = {R41AI191979/NH/NIH HHS/United States ; R41AI192172/NH/NIH HHS/United States ; }, mesh = {Humans ; *Pluripotent Stem Cells/immunology/transplantation ; Animals ; *Diabetes Mellitus, Type 1/therapy/immunology ; *Stem Cell Transplantation/methods ; *Graft Rejection/immunology/prevention &amp; control ; *Immune System ; }, abstract = {Pluripotent stem cell (PSC)-based therapies hold the potential to unlock cures for numerous diseases, including, but not limited to, Parkinson's disease, macular degeneration, heart failure, type 1 diabetes, and cancer. Yet as protocols to differentiate PSCs into therapeutically useful cell types have progressed rapidly, immunological rejection remains a major barrier that may limit the widespread use of such PSC-based therapies. In recent years, strategies to genetically modify PSCs to prevent immunological rejection of the downstream cell product have become a point of emphasis. Here, we provide an immunological perspective on these strategies, discussing the breadth of rejection mechanisms that have been uncovered through decades of research and the relative simplicity of designing PSC immune evasion strategies to circumvent these mechanisms. We focus in particular on how these strategies apply to the treatment of type 1 diabetes.}, }
@article {pmid42556705, year = {2026}, author = {Holekamp, NM and Ivanova, S}, title = {The Perfusion-Based Model of AMD: Moving Towards a Unifying Hypothesis.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101507}, doi = {10.1016/j.preteyeres.2026.101507}, pmid = {42556705}, issn = {1873-1635}, abstract = {Age-related macular degeneration (AMD) is a complex disease wherein age, genetics, and environment play a role. How each of these factors contribute to the overall disease initiation and progression remains largely unelucidated. A renewed examination of the existing literature regarding the blood supply to the outer retina may provide novel insights. Hypoxia in the retinal pigment epithelium (RPE) can produce features of AMD, including photoreceptor degeneration. In the macula, the choriocapillaris has unique features making it susceptible to hypoperfusion, producing low-grade ischemia and chronic tissue hypoxia. The choriocapillaris experiences vascular loss and decreased blood flow early in AMD. Genetic risk, when viewed through a new lens, points to vascular insult as central to AMD pathophysiology. Complement-related risk genes are active in the vasculature, from large tributary vessels to small vessels of the choriocapillaris. HtrA serine peptidase 1 (HTRA1) is associated with cerebral small vessel disease and localizes to the choriocapillaris in AMD. Ageing can be interpreted as inevitable atherosclerosis from large to small vessels of the cerebral system. Western diets, smoking, and a rising prevalence of metabolic syndrome in people over age 60 are confirmed to accelerate both atherosclerosis and AMD. A perfusion-based model for complement-related, soft drusen-associated AMD is proposed while also explaining a second phenotype of non-complement related subretinal drusenoid deposit-associated AMD. Common to both phenotypes of AMD is chronic hypoperfusion causing decreased oxygen exchange and waste removal at the neurovascular unit of the choriocapillaris, RPE, and photoreceptors. Understanding AMD as an end-organ vascular disease may move us towards a unifying hypothesis.}, }
@article {pmid42556869, year = {2026}, author = {Wilkinson, E and Beresford, S and Mushtaq, B and Salvatore, S and Sivaprasad, S and Brown, K and Carter, JS and Singh, J and Schrire, T and Chase, TJG}, title = {Optimising the patient pathway for macular conditions requiring intravitreal injections.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {3}, pages = {}, doi = {10.1136/bmjophth-2025-002663}, pmid = {42556869}, issn = {2397-3269}, mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retinal Vein Occlusion/drug therapy ; Macular Edema/drug therapy ; *Macular Degeneration/drug therapy ; *Critical Pathways ; }, abstract = {Macular disease is the leading cause of vision loss in the United Kingdom, affecting nearly 1.5 million people. Vascular endothelial growth factor (VEGF) has a major role in the onset and progression of vision-threatening macular conditions such as neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion. Anti-VEGF treatments, given by intravitreal injection, can prevent vision loss and may improve vision but must be started quickly before sight loss is irreversible. Informed by an observational study using Hospital Episode Statistics and the Emergency Care Data Set in England and a Costed Integrated Patient Scenario, we identify issues within the current pathway in England. Our key recommendations to optimise care and improve patient outcomes include: (1) increasing public awareness of macular disease to reduce late presentation; (2) ensuring the right patients are seen in the right place at the right time by improving quality and priority of optometrist referrals and by specialists directing patients with conditions such as diabetes and hypertension to community optometrists in the first instance; (3) planning for current and future demand and capacity using innovative solutions to manage expected increases in medical retina conditions and (4) ensuring patient-centred care. Our evidence should encourage National Health Service organisations at all levels to review macular disease pathways to address immediate issues and plan for the future. A shift in care delivery is needed, embracing scalable sustainable solutions, earlier diagnosis and treatment, improved access to more durable therapies, wider adoption of digital technologies and care closer to home.}, }
@article {pmid42557039, year = {2026}, author = {Lin, Z and Wang, S and You, R and Wang, L and Abdullahi, MA and Du, W and Xu, X and Lu, F and Zhang, S and Liang, Y}, title = {Integrating opportunistic ocular diseases screening into general health examination in Chinese: a multicentre study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329267}, pmid = {42557039}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: Cost-effective screening models for ocular diseases in large populations remain a critical challenge for blindness prevention. Our preliminary study demonstrated the feasibility of opportunistic glaucoma screening integrated into general health examinations. This study aimed to evaluate the efficacy of this model for fundus disease screening in a multicentre, large-sample Chinese population.<br><br>METHODS: This study was conducted in five health examination centres from four provinces of China. Chinese participants aged &#x2265;18 years undergoing routine health examinations were invited to complete bilateral presenting visual acuity and non-mydriatic fundus photography. Fundus photography was assessed by two experienced graders. Proportion of fundus diseases/changes were calculated. Costs for the screening were also assessed.<br><br>RESULTS: A total of 63&#x2009;935 eligible participants (age 45.4&#xb1;14.0 years, 51.3% men) were enrolled. The top five diseases/changes were non-macular drusen (8.80%), macular degeneration (6.30%), glaucoma suspect (5.54%), epiretinal membrane (3.92%) and diabetic retinopathy (3.89%). The proportion of low vision and blindness in the total population was 5.85% and 0.15%, respectively. The top five diseases/changes with vision impairment were retinitis pigmentosa (18.18%), myopic retinopathy (16.52%), macular hole (11.76%), non-glaucomatous optic neuropathy (7.25%) and glaucomatous optic neuropathy (6.37%). The unit cost of screening a single case and an ocular disease suspect was US$22.2 (US$15.7 to US$26.7) and US$83.2 (US$58.7 to US$99.9), respectively.<br><br>CONCLUSIONS: This health examination centre-based screening model is feasible, effective and affordable for detecting multiple fundus diseases in large populations. As the model is promoted and its coverage expands, screening costs may be further reduced.}, }
@article {pmid42557420, year = {2026}, author = {Velez-Montoya, R and Cruz-Gonzalez, A and Pedraza-Rivera, G and García-Albisua, AM and Ureña-Tejeda, KM and Rosales-Díaz, R and Lucero-De la Rosa, X and Pineda-Pérez, JE and Hernández-Castellanos, S and Guevara-Flores, K and Ramirez-Estudillo, A and Campos-Wolter, CI and Marte-Ramirez, VA and Ledesma-Gil, G and Navas, A and González-Cortés, JH and Mohamed-Noriega, K and Ramos-Betancourt, N}, title = {Ocular surface and meibomian gland changes following repeated exposure to 5% povidone-iodine during intravitreal injections.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42557420}, issn = {1476-5454}, abstract = {BACKGROUND: To evaluate the impact of repeated exposure to 5 percent povidone iodine on meibomian gland atrophy in eyes receiving intravitreal injections.<br><br>METHODS: Patients undergoing intravitreal injections with a standardised protocol that included 5% povidone-iodine instillation in one eye were prospectively enroled. Eligible patients had received their last injection within the previous 12 weeks. Patients were stratified according to the number of prior injections. Those with systemic conditions or medications affecting ocular surface parameters were excluded. Assessments included Keratograph 5&#x2009;M meibography, slit lamp examination, and Schirmer testing at baseline, one hour, and seven days after injection. Meibomian gland atrophy was quantified using ImageJ software. Statistical analysis included repeated-measures ANOVA, regression modelling, and interobserver agreement.<br><br>RESULTS: A total of 143 patients with a mean age of 69 years were included. Age-related macular degeneration was the predominant diagnosis, and treat and extend was the most common protocol. In the study eye, tear meniscus height, bulbar hyperaemia, and Schirmer scores increased, while tear breakup time decreased at one hour post-injection. These changes were most evident in patients with fewer than five or more than thirteen prior injections and resolved by day seven. Meibography revealed reduced gland atrophy, especially in the inferior eyelid. Regression analysis showed a small but significant inverse association between injection number and gland atrophy.<br><br>CONCLUSIONS: Patients with more intravitreal injections and greater exposure to 5% povidone-iodine showed less meibomian gland atrophy, particularly in the inferior eyelid, along with improved ocular surface parameters.}, }
@article {pmid42558051, year = {2026}, author = {Mohapatra, D and Corson, TW}, title = {Diagnostic and therapeutic potential of carbon nanodots for ocular disease.}, journal = {Nanomedicine (London, England)}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/17435889.2026.2712542}, pmid = {42558051}, issn = {1748-6963}, abstract = {Conventional therapeutics (eye drops, injectables, ointments, gels) for ocular diseases face several challenges, including low ocular permeability, rapid clearance, low bioavailability, and off-target effects due to complex anatomical barriers and physiological ocular events. Nanomedicine can avoid some challenges of conventional delivery systems by offering prolonged ocular retention, site-specific targeted drug delivery, low toxicity, improved bioavailability, and therapeutic activity. Further, theranostic nanomedicines offer the advantages of diagnostic and therapeutic features during treatment. Carbon dots (CDs), also known as carbon nanodots (CNDs) or carbon quantum dots (CQDs), are ultra-low-sized, zero-dimensional nanomaterials with a diameter below 10 nm, and have received attention due to their excellent fluorescence, tunable emission, biocompatibility, aqueous solubility, surface functionalization ability, stability, safety, and cost-effectiveness. A growing number of studies explore the therapeutic, diagnostic, or theranostic use of CDs for ocular applications, demonstrating real-time monitoring of disease progression and treatment efficacy in ocular disease models. CDs have been explored for ocular drug delivery, fluorescent angiography, ocular bioimaging, and treatment in models of various ocular diseases, including bacterial keratitis, glaucoma, vitreous opacification, and neovascular age-related macular degeneration (nAMD). In this special report, the potential of CDs for ophthalmic applications is reviewed based on publications over the last decade.}, }
@article {pmid42546222, year = {2026}, author = {Pyatova, Y and Zhang, B and Misawa, M and Markowitz, SN and Sen, A and Appel, L and Cheung, K and Nasir, P and Tchao, D and Garcia-Giler, E and Daibert-Nido, M and Reber, M}, title = {A Visual Telerehabilitation Program in Virtual Reality for Age-Related Macular Degeneration: Randomized Feasibility and Proof-of-Concept Trial.}, journal = {JMIR rehabilitation and assistive technologies}, volume = {13}, number = {}, pages = {e87596}, pmid = {42546222}, issn = {2369-2529}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) causes progressive central vision loss in older adults. Low-vision rehabilitation can improve functional vision by training the use of a preferred retinal locus, commonly through clinic-based biofeedback training (BFT). However, repeated supervised rehabilitation is burdensome, and functional gains may be difficult to sustain without home practice. Stand-alone virtual reality (VR) may enable home-based, remotely monitored visual stimulation, but feasibility, safety, and usability in older adults with AMD remain insufficiently characterized.<br><br>OBJECTIVE: This study aimed to evaluate the feasibility and safety of adding home-based VR 3D single-object tracking (3D-SOT-VR) to conventional BFT in older adults with dry AMD in a parallel, randomized, single-blind (to assessors), controlled, formative trial and to generate exploratory functional hypotheses for a future trial.<br><br>METHODS: Adults with dry AMD were recruited at the Low Vision Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada, from September 2021 to October 2023. Participants were randomized to BFT once weekly for 4 weeks (BFT group) or BFT plus home-based 3D-SOT-VR (BFT-VR group) every other day for 4 weeks. Experimental intervention consisted of tracking a single object among distractors moving at different speeds in a 3D virtual space in a VR headset. Primary feasibility and safety outcomes included recruitment, adoption, adherence, compliance, intervention completion, remote data transfer, usability, and VR-induced symptoms and effects. Secondary outcomes included visual acuity, contrast sensitivity, fixation stability, retinal sensitivity, reading speed, and low-vision quality of life. Exploratory outcomes assessed performance at 3D-SOT-VR and usage. Analyses were descriptive and exploratory, with CIs and denominators reported to reflect limited precision and missingness.<br><br>RESULTS: Fourteen individuals were randomized (BFT, n=6; BFT-VR, n=8), below the planned sample size of 32. Recruitment was not achieved because of COVID-19-related interruptions and reduced onsite access. Eleven individuals were analyzed for the primary outcome (BFT n=6, BFT-VR n=5). Intervention completion was 100% in the BFT arm and 75% in the BFT-VR arm, below the prespecified BFT-VR threshold. Among participants who used VR, adherence to scheduled home sessions was acceptable, completed VR-session files were transmitted without loss, and no participant met the predefined cybersickness stopping rule. One BFT-VR participant discontinued because headset weight caused neck fatigue. Group-level visual outcomes did not provide significant effectiveness. Reading speed showed a clinically meaningful individual-level improvement in the BFT-VR arm and correlated with VR-task performance. The findings were not clearly durable at follow-up.<br><br>CONCLUSIONS: This pilot study provides formative evidence that clinic-based BFT combined with home-based, remotely monitored VR visual stimulation can be implemented safely in older adults with dry AMD, while identifying major contextual feasibility barriers. The intervention is innovative because it extends low-vision rehabilitation into the home using a connected device and objective performance monitoring. Recruitment, retention, missing data handling, and sustainability of functional gains must be addressed before effectiveness testing.}, }
@article {pmid42546865, year = {2026}, author = {Jonas, JB and Jonas, RA and Wang, YX and Panda-Jonas, S}, title = {Central Retinal Vessel Trunk Dragging in Highly Myopic Eyes.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.058}, pmid = {42546865}, issn = {1879-1891}, abstract = {PURPOSE: To assess occurrence and associations of central retinal vessel trunk (CRVT) dragging.<br><br>DESIGN: Retrospective, population-based cohort study.<br><br>METHODS: Using optical coherence tomographic images of the optic disc and macula, taken in the participants of the Beijing Eye Study, we assessed the prevalence of CRVT-dragging, defined as an optic disc tissue prominence at the inferior, superior and nasal, but not the temporal, optic disc border.<br><br>RESULTS: The study included 3336 individuals (3336 eyes) (mean age:64.2&#xb1;9.6 years; axial length:23.4&#xb1;1.2mm (range:20.16-30.88mm). CRVT dragging prevalence increased from 0/3046 (0%) to 9/173 (5.2%;95%CI:2,9), 9/74 (12.2%;95%CI:5,20), 6/25 (24.0%;95%CI:6,42) and to 13/18 (72.2%;95%CI:49,95) in eyes with an axial length of &#x2264;25.0mm, 25.01mm-26.0mm, 26.01mm-27.0mm, 27.01mm-28.0mm, and >28.0mm, respectively. Higher CRVT dragging prevalence was associated (multivariable analysis) with longer optic disc-fovea distance (OR:5.82;95%CI:2.23,15.2;P<0.001) and higher prevalence of parapapillary retinoschisis (OR:8.61;95%CI:2.43,30.5;P<0.001), with adjusting for longer axial length (OR:1.95;95%CI:1.25,3.05;P=0.003) and older age (OR:1.08;95%CI:1.02,1.14;P=0.008). In eyes with an axial length of &#x2265;25.0 mm, CRVT dragging prevalence increased 5.69-fold (95% CI:2.30,14.1) for each mm increase in fovea-disc distance. These relationships were complemented by univariate associations between CRVT dragging prevalence and temporal retinal vessel straightening, smaller angle kappa, higher myopic macular degeneration stage and prevalence, and larger parapapillary beta zone and gamma zone.<br><br>CONCLUSIONS: CRVT-dragging as a common feature in highly myopic eyes may etiologically be explained by the myopic axial elongation-related increase in the fovea-disc distance. Influencing the three-dimensional appearance of the optic nerve head, CRVT dragging may be of importance for the morphological diagnosis of optic neuropathies in highly myopic eyes.}, }
@article {pmid42547533, year = {2026}, author = {Chauhan, MZ and Muayad, J and Karimaghaei, C and Karimaghaei, S and Sallam, AB}, title = {Large-scale analysis of risk factors for developing retinal vein occlusion in the fellow eye.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42547533}, issn = {1476-5454}, abstract = {BACKGROUND/OBJECTIVES: The main objective was to elucidate the associations for developing a fellow-eye retinal vein occlusion (RVO) after a patient experiences a first-time unilateral RVO event.<br><br>SUBJECTS/METHODS: Large, multicenter, retrospective study using the global TriNetX database. We included patients newly diagnosed with unilateral RVO from 1 January 2015 to 1 January 2025. We estimated the incidence of fellow-eye RVO using Kaplan-Meier survival analysis, compared baseline demographic and medical characteristics between groups with and without progression to bilateral RVO and calculated hazard ratios with 95% confidence intervals for fellow-eye RVO based on various systemic and ocular comorbidities.<br><br>RESULTS: 437 of 22,969 patients (1.90%) developed RVO in the fellow eye. Patients with fellow-eye RVO had higher rates of primary open-angle glaucoma (POAG; 22% vs. 17%, p&#x2009;=&#x2009;0.006), dry age-related macular degeneration (AMD; 15% vs. 12%, p&#x2009;=&#x2009;0.008) and anemia (39% vs. 31%, p&#x2009;=&#x2009;0.0001). They also were more likely to self-identify as Black/African American (21% vs. 17%, p&#x2009;=&#x2009;0.03) and less likely to be White (50% vs. 58%, p&#x2009;=&#x2009;0.0008). No significant difference was identified between mean age, sex, or rates of traditional cardiovascular risk factors across these two groups. There was a 1.41- (95% CI 1.03-1.94), 1.46- (95% CI 1.02-2.10) and 1.84-fold (95% CI 1.38-2.47) increased hazard of developing bilateral sequential RVO with baseline POAG, dry AMD and anemia, respectively.<br><br>CONCLUSION: The presence of primary open-angle glaucoma, dry age-related macular degeneration and anemia is significantly associated with fellow-eye RVO and may help prognosticate the development of progressive disease in patients with unilateral RVO.}, }
@article {pmid42540322, year = {2026}, author = {Mohapatra, D and Seo, SY and Corson, TW}, title = {Development and characterization of a topical ferrochelatase inhibitor nanoemulsion for choroidal neovascularization therapy.}, journal = {International journal of pharmaceutics: X}, volume = {12}, number = {}, pages = {100619}, pmid = {42540322}, issn = {2590-1567}, abstract = {Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD). We previously identified the heme synthesis enzyme ferrochelatase (FECH) as a promising therapeutic target. This study aimed to develop and characterize topical ophthalmic nanoemulsions (NEs) of a novel FECH inhibitor, SH-17023, for CNV therapy, to avoid the intravitreal injections needed for standard-of-care anti-vascular endothelial growth factor (anti-VEGF) biologics. SH-17023-loaded NEs were prepared by spontaneous emulsification and optimized using D-optimal mixture design-based Quality-by-Design to obtain nanometric globule size (Zavg), low polydispersity index (PDI), and highest drug loading capacity (% LC). Therapeutic efficacy was assessed in the laser-induced CNV (L-CNV) mouse model with fundus imaging, optical coherence tomography (OCT), fluorescein angiography, and ex vivo vasculature staining. The optimized formulation was transparent with a globule size of 32.832 ± 2.125 nm, PDI 0.201 ± 0.003, spherical morphology, and LC of 7.436 ± 0.035%. It showed zeta potential of -29.2 ± 0.45 mV, sustained drug release, and robust accelerated and kinetic stability. Attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray diffraction revealed excellent drug-excipient compatibility. Ex vivo goat cornea permeation of NEs showed significantly higher drug transport (permeability coefficient (Kp) = 0.050 ± 0.012 h[-1].cm[-2], steady-state flux (Jss) = 37.51 ± 9.29 μg.h[-1].cm[-2]) than the drug in solution (Kp = 0.002 ± 0.0004 h[-1].cm[-2] and Jss = 1.575 ± 0.488 μg.h[-1].cm[-2]) with an enhancement ratio of 23.815. Optimized NEs significantly reduced L-CNV assessed by OCT and ex vivo staining by >45% compared to blank NEs, without ocular irritation or toxicity, indicating their promise for nAMD therapy.}, }
@article {pmid42541268, year = {2026}, author = {Vingopoulos, F and Stevanovic, M and Razavi, P and Romano, F and Ding, X and Rodriquez, J and Baldwin, G and Choi, H and Katz, R and Husain, D and Kim, LA and Miller, JW and Vavvas, DG and Miller, JB}, title = {Geographic Atrophy Size Progression Correlates Better with Longitudinal Changes in Quantitative Contrast Sensitivity than Visual Acuity.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101206}, pmid = {42541268}, issn = {2666-9145}, abstract = {PURPOSE: Investigate the cross-sectional and longitudinal correlations between total geographic atrophy (GA) size and quantitative contrast sensitivity function (qCSF).<br><br>DESIGN: Prospective, cross-sectional, and longitudinal observational study between November 2018 and March 2023 at Massachusetts Eye and Ear.<br><br>SUBJECTS: A total of 83 foveal involving GA eyes cross-sectionally and 30 foveal involving GA eyes longitudinally.<br><br>METHODS: Contrast sensitivity (CS) was measured with the qCSF device along with same day spectral-domain OCT and fundus autofluorescence (FAF). Geographic atrophy was defined as hypoautofluorescent lesions on FAF corresponding to complete retinal pigment epithelium and outer retinal atrophy on spectral-domain OCT. Total GA size was measured on FAF using the semiautomatic Heidelberg Region Finder tool. Mixed-effects multivariate regression models were performed to evaluate correlations between GA size, qCSF metrics, and visual acuity (VA).<br><br>MAIN OUTCOME MEASURES: Total GA size, longitudinal changes in total GA size, qCSF outcomes (area under the logarithm of contrast sensitivity function [AULCSF], low contrast VA [LCVA], CS thresholds at 1-18 cycles per degree [cpd]), and longitudinal changes in qCSF outcomes.<br><br>RESULTS: Cross-sectionally (n = 83), total GA was associated with multiple qCSF outcomes including AULCSF and CS thresholds at 1, 1.5, 3, 6, and 12 cpd (&#x3b2; = -0.23 to -0.39, all P < 0.05), but was not associated with VA (&#x3b2; = 0.08, P = 0.47). At 17.2 months follow-up (range: 6-37) (n = 30), an average increase of 1 mm[2] in total GA size was associated with a nonstatistically significant decrease of 0.01 in VA (P = 0.88), but a statistically significant decrease in CS (-0.05 for AUCLSF, -0.05 for LCVA, -0.04 for 1 cpd, -0.05 for 1.5 cpd, and -0.06 for 3 cpd, all P < 0.05). Standardized regression coefficients suggest that the statistically significant decrease in CS metrics per mm[2] of GA size increase are 11-fold to 20-fold bigger compared to the nonstatistically significant decrease in VA (-0.33 to -0.62 for qCSF versus -0.03 for VA).<br><br>CONCLUSIONS: Total GA and longitudinal change in GA size were found to be associated with significant changes in qCSF CS, but not with VA or change in VA. Contrast sensitivity seems to be a better functional endpoint to measure treatment effects in GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42544414, year = {2026}, author = {Sevugamurthi, K and Sivashanmugam, P and Jaju, S and Janani, PS and Sakthivel, V and Kumar, N and Elamurugan, V and Pandian, J and Amarakoon, S and Berendschot, TTJM and Narendran, S}, title = {Evaluating the impact of blue-filtering intraocular lenses on macular oxidative stress: A comparative analysis of 8-hydroxy-2'-deoxyguanosine levels in the retinal tissue of donor eyes.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {Suppl 2}, pages = {S215-S220}, doi = {10.4103/IJO.IJO_3121_25}, pmid = {42544414}, issn = {1998-3689}, mesh = {Humans ; *Oxidative Stress ; Male ; Female ; *8-Hydroxy-2'-Deoxyguanosine/metabolism ; Cross-Sectional Studies ; *Tissue Donors ; Middle Aged ; *Lenses, Intraocular ; Aged ; *Retinal Pigment Epithelium/metabolism ; Enzyme-Linked Immunosorbent Assay ; Blue Light ; *Macula Lutea/metabolism/pathology ; *Deoxyguanosine/analogs &amp; derivatives/metabolism ; Adult ; Biomarkers/metabolism ; }, abstract = {PURPOSE: To evaluate the impact of blue-filtering intraocular lenses (BFIOLs) on retinal oxidative stress by comparing 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the macular retina and submacular retinal pigment epithelium (RPE) of donor eyes with BFIOLs and non-BFIOLs.<br><br>DESIGN: Cross-sectional laboratory study using postmortem human donor eyes.<br><br>METHODS: Fifty-eight eyes from 39 donors were categorized as BFIOL (n = 16), non-BFIOL (n = 24), or phakic (n = 18). Macular retina and submacular RPE were dissected, genomic DNA extracted, and 8-OHdG quantified using ELISA. 8-OHdG levels were compared across lens groups, and associations with age and sex were examined.<br><br>RESULTS: Submacular RPE had higher 8-OHdG levels than the macular retina (0.95 vs 0.44 ng/mL; P < 0.0001). No significant differences in 8-OHdG were observed between BFIOL and non-BFIOL eyes in either tissue (all P &#x2265; 0.09). Age was not associated with 8-OHdG, whereas male donors showed higher RPE 8-OHdG levels than female donors (P = 0.03).<br><br>CONCLUSIONS: Macular retinal and RPE 8-OHdG levels did not differ significantly by IOL type. These biochemical observations, considered alongside existing clinical data, suggest that any retinal protective effect of BFIOLs on oxidative DNA damage is likely to be modest.}, }
@article {pmid42544785, year = {2026}, author = {Sutinen, P and Hecht, I and Tuuminen, R}, title = {Early high-dose aflibercept 8 mg clinical outcomes in wet age-related macular degeneration patients resistant to aflibercept 2 mg or faricimab.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70213}, pmid = {42544785}, issn = {1755-3768}, }
@article {pmid42537924, year = {2026}, author = {Xu, S and Zhuo, Q and Li, J and Li, B and Zhu, W and Xue, Y and Zhang, S and Zhao, C}, title = {EV30 suppresses choroidal neovascularization associated with modulation of the mTOR/NF-κB/p38 MAPK signaling pathway.}, journal = {Microvascular research}, volume = {}, number = {}, pages = {104992}, doi = {10.1016/j.mvr.2026.104992}, pmid = {42537924}, issn = {1095-9319}, abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of irreversible vision loss characterized by pathological choroidal neovascularization (CNV). While anti-VEGF therapies are the standard of care, limitations such as treatment resistance and side effects necessitate novel therapeutic agents. This study evaluates the therapeutic efficacy and mechanism of EV30, a novel pterostilbene derivative, in suppressing CNV. EV30 was synthesized based on the pterostilbene template. In vitro, the effects of EV30 on human umbilical vein endothelial cells (HUVECs) proliferation, migration, and tube formation were assessed using Cell Counting Kit-8 (CCK-8), scratch wound, and tube formation assays, respectively. Mechanistic pathways were investigated via Western blotting and RT-qPCR. In vivo, a laser-induced CNV mouse model was treated with intravitreal EV30. Efficacy was evaluated utilizing fundus photography, fluorescein angiography (FFA), optical coherence tomography (OCT), and choroidal flat mounts (IB4 staining). Finally, biosafety was assessed through histology (H&amp;E), electroretinography (ERG), and blood analysis. EV30 demonstrated potent anti-angiogenic properties in vitro, significantly inhibiting HUVEC proliferation, migration, and tube formation in a dose- and time-dependent manner. EV30 reduced vascular endothelial growth factor A (VEGFA) expression and modulated the phosphorylation status of proteins associated with the mTOR/NF-κB/p38 MAPK signaling pathway. In the laser-induced CNV model, EV30 effectively reduced lesion area and vascular leakage comparable to bevacizumab. Furthermore, ERG analysis revealed that EV30 partially preserved retinal electrophysiological function, as indicated by improved scotopic a-wave amplitudes, suggesting functional protection of the retina in the CNV model. EV30 exerted anti-angiogenic effects and was associated with modulation of mTOR/NF-κB/p38 MAPK signaling activity. Together, these findings suggest that EV30 represents a potential therapeutic candidate for CNV by suppressing pathological angiogenesis and modulating inflammation-associated signaling pathways.}, }
@article {pmid42537985, year = {2026}, author = {Li, X and Gui, F and Zheng, Z and Shi, K}, title = {Cell-state-resolved transcriptomic analysis reveals macrophage-centered pyroptosis-related inflammatory programs in age-related macular degeneration.}, journal = {SLAS technology}, volume = {}, number = {}, pages = {100456}, doi = {10.1016/j.slast.2026.100456}, pmid = {42537985}, issn = {2472-6311}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is accompanied by inflammatory changes in the retinal pigment epithelium/choroid complex, but the cellular sources of pyroptosis-related transcriptional programs in human AMD tissue remain unclear. This study profiled these programs at single-cell resolution and explored candidate regulatory molecules.<br><br>METHODS: We analyzed the human retinal pigment epithelium (RPE)/choroid single-cell RNA-sequencing dataset GSE135922 to define cell clusters, pyroptosis-related genes, and regulons. AUCell was applied to estimate pyroptosis-related signature activity in individual cell types. The macrophage cluster with the highest score was examined by pathway enrichment, subclustering, and Monocle 2 pseudo-time analysis, and SCENIC-based regulon analysis was used to infer candidate transcriptional regulators. Pyroptosis-related genes and transcription factors were also evaluated in T-cell, endothelial-cell, and fibroblast subclusters. Bulk RNA sequencing and immunofluorescence in a laser-induced choroidal neovascularization (CNV) mouse model were used for supportive evidence.<br><br>RESULTS: Across human RPE/choroid cell clusters, 60 cluster-specific pyroptosis-related marker genes were detected. At the cell-type ranking level, macrophages, T cells, endothelial cells, and fibroblasts showed relatively higher pyroptosis-related signature activity across clusters, with the highest signal in Macrophages-2 and lower activity in RPE cells. Marker genes of Macrophages-2 were enriched in immune and inflammatory pathways, including complement and coagulation cascades, NOD-like receptor signaling, and NF-&#x3ba;B signaling. Pseudo-time analysis resolved Macrophages-2 into divergent trajectories, and NLRP3 was enriched in one post-branch state, consistent with macrophage state heterogeneity rather than uniform activation. IRF1, STAT3, and NEAT1 recurred in cell-type-specific analyses, and Irf1/Stat3 protein signals were higher in CNV lesions.<br><br>CONCLUSION: These findings indicate a macrophage-centered, cell-state-specific pattern of pyroptosis-related inflammatory remodeling in AMD. Branch-associated NLRP3 inflammasome signatures, together with IRF1, STAT3, and NEAT1, define candidate molecular features that warrant further mechanistic evaluation.}, }
@article {pmid42538141, year = {2026}, author = {Meng, J and Zhang, Y and Pei, Y and Kang, C and Cheng, K and Qi, J and He, W and Zhang, K and Lu, Y and Zhu, X}, title = {Transcranial magnetic stimulation as a novel therapeutic approach for severe retinal degenerative diseases: a pilot study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329114}, pmid = {42538141}, issn = {1468-2079}, abstract = {BACKGROUND: Retinal degenerative diseases, including myopic macular degeneration (MMD) and retinitis pigmentosa (RP), lead to irreversible vision impairment, with limited treatment options. Transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique for rehabilitation, may hold potential for vision restoration. The pilot study explored whether TMS is associated with short-term functional visual improvements in patients with severe retinal degenerative diseases.<br><br>METHODS: This prospective, non-randomised, parallel-arm pilot study enrolled 98 patients with bilateral severe MMD or RP. Participants received either five consecutive days of theta-burst TMS or conventional conservative care. Primary outcomes were changes in best-corrected visual acuity (BCVA) and visual field from baseline to 4-week follow-up. Contrast sensitivity, macular sensitivity, fixation stability, Visual Function Index-14 (VF-14) and Visual Functioning Questionnaire-25 (VFQ-25) questionnaires were also evaluated. A subset of participants underwent resting-state functional magnetic resonance imaging (fMRI) to explore cortical functional changes.<br><br>RESULTS: The study analysed 174 eyes from 88 patients (mean age: 60.3&#xb1;9.1 years; 52% female). Compared with controls, the TMS group showed greater improvements in BCVA (MMD: 0.22&#xb1;0.28 logarithm of the minimum angle of resolution (logMAR); RP: 0.24&#xb1;0.21 logMAR) and VF mean defect (MMD: 1.96&#xb1;2.09&#x2009;dB; RP: 1.08&#xb1;1.28&#x2009;dB). Contrast sensitivity, macular sensitivity and fixation stability also showed short-term gains. Patient-reported outcomes improved in several functional domains. fMRI demonstrated increased activity and functional connectivity in visual-related cortical regions following TMS.<br><br>CONCLUSIONS: In this exploratory pilot study, TMS treatment was associated with short-term functional visual improvements and cortical modulation in individuals with severe retinal degenerative diseases. These findings are hypothesis-generating and warrant validation through larger, randomised, masked clinical trials with longer follow-up.}, }
@article {pmid42538387, year = {2026}, author = {She, W and She, M and Sun, T}, title = {Comment on: 'Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study'.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42538387}, issn = {1476-5454}, }
@article {pmid42539849, year = {2026}, author = {Malmin, A and Olsen, MVT and Thomseth, VM and Kjellevold Haugen, IB and Utheim, TP and Forsaa, VA}, title = {Long-term Impact of Intravitreal Injections on the ocular surface; a 2-year follow-up study.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1829818}, pmid = {42539849}, issn = {2674-0826}, abstract = {BACKGROUND: Intravitreal injection (IVI) therapy is the most frequently performed intraocular procedure worldwide, with topical povidone-iodine (PVP-I) as the standard pre-injection antiseptic. However, PVP-I has been shown to exert cytotoxic effects on the ocular surface. The purpose of this study was to evaluate the impact of two years of serial anti-vascular endothelial growth factor (VEGF) IVI on ocular surface parameters.<br><br>METHODS: Patients with neovascular age-related macular degeneration (nAMD) receiving unilateral intravitreal anti-VEGF injections were examined at two time points, separated by a two-year interval. An aseptic protocol with PVP-I was applied prior to each injection. Tear meniscus height (TMH), bulbar redness (BR), and meibomian gland (MG) loss were assessed using the Oculus Keratograph 5M, with the fellow eye serving as control. For statistical analysis, the related-samples Wilcoxon signed-rank test was applied to non-normally distributed data, and the paired-sample Student's t-test to normally distributed data.<br><br>RESULTS: Sixty patients (mean age, 78.6&#xa0;&#xb1;&#xa0;8.5 years; range, 55-96) were included. Between examinations, patients received a mean of 15.5&#xa0;&#xb1;&#xa0;6.5 IVI (range, 5-30). A significant increase in mean BR was observed in untreated fellow eyes compared with baseline measurements (1.68&#xa0;&#xb1;&#xa0;0.47 vs. 1.41&#xa0;&#xb1;&#xa0;0.46; p&#xa0;<&#xa0;0.001). At follow-up, BR was significantly higher in fellow eyes than in treated eyes (p&#xa0;<&#xa0;0.001), and this difference had increased over the study period. Median TMH increased significantly in untreated eyes (0.42&#xa0;mm [IQR, 0.28-0.57] vs. 0.31&#xa0;mm [IQR, 0.23-0.47]; p&#xa0;=&#xa0;0.003), whereas the increase in treated eyes was not significant (p&#xa0;=&#xa0;0.74). At follow-up, mean TMH did not differ significantly between treated and fellow eyes (p&#xa0;=&#xa0;0.15). Both treated and untreated eyes showed significant MG loss after two years of serial IVI; however, no significant differences in mean MG loss were detected between eyes in either the upper or lower eyelid at follow-up.<br><br>CONCLUSIONS: Eyes receiving repeated intravitreal anti-VEGF injections with preoperative PVP-I antisepsis were significantly less hyperemic than fellow untreated eyes, and this difference increased over two years of continued treatment. Potential mechanisms include a beneficial alteration of the ocular surface microbiome by PVP-I or an antiangiogenic effect of anti-VEGF therapy.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04458012, identifier NCT04458012.}, }
@article {pmid42536333, year = {2026}, author = {Hashiya, N and Maruko, I and Tanaka, K and Honjo, J and Miyara, Y and Watanabe, Y and Maruko, R and Nakai, A and Wakatsuki, Y and Itagaki, K and Maehira, M and Terao, N and Kataoka, K and Okada, AA and Koizumi, H and Mukai, R and Sekiryu, T and Mori, R and , }, title = {Six-month outcomes with a reduced two-injection induction (2+TAE) regimen of aflibercept 8 mg in treatment-naive neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42536333}, issn = {1613-2246}, abstract = {PURPOSE: To evaluate 6-month outcomes of aflibercept 8 mg administered with two monthly injections followed by a treat-and-extend (TAE) regimen in treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Multicenter retrospective study.<br><br>METHODS: This study included 107 treatment-na&#xef;ve eyes with nAMD, of which 91 eyes of 90 patients (mean age, 74.7&#x2009;&#xb1;&#x2009;9.4 years) followed for 6 months were analyzed. All eyes received two consecutive monthly injections of aflibercept 8 mg (induction), followed by TAE. Best-corrected visual acuity (BCVA, logMAR), optical coherence tomography (OCT)-based anatomical outcomes, and adverse events were assessed.<br><br>RESULTS: Sixteen eyes were excluded, mainly due to being lost-to-follow-up or having had treatment changed to an alternative drug. No serious adverse events were observed. Mean BCVA improved from 0.43 &#xb1; 0.36 at baseline to 0.37 &#xb1; 0.42 at 6 months (P = 0.032). Retinal thickness, pigment epithelial detachment height, and subfoveal choroidal thickness significantly improved (all P < 0.05). The mean number of injections over 6 months was 3.4 &#xb1; 0.5, and the mean treatment interval at the end of 6 months was 11.6 &#xb1; 2.2 weeks. A dry macula was achieved in 70.3% of eyes, with a higher rate in eyes achieving a dry macula after a two-injection induction than in those requiring a three-injection induction (80.0% vs 51.6%, P < 0.01).<br><br>CONCLUSIONS: Eyes achieving a dry macula after two injections had higher 6-month dry rates than those requiring a third injection. Early treatment response may help predict treatment burden and guide individualized management strategies.}, }
@article {pmid42536362, year = {2026}, author = {Chujo, S and Baek, J and Uji, A and Quarta, A and Chung, YC and Kwak, H and Soylu, C and Abbasgholizadeh, R and Alhelaly, M and Rattu, R and Huang, J and Corradetti, G and Velaga, S and Nittala, MG and Sadda, SR}, title = {Quantitative Evaluation of Geographic Atrophy Progression Using Geographic Atrophy Lesion Front Displacement.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {64}, doi = {10.1167/iovs.67.8.64}, pmid = {42536362}, issn = {1552-5783}, mesh = {*Geographic Atrophy/diagnosis ; Humans ; Disease Progression ; Retrospective Studies ; Fluorescein Angiography/methods ; Female ; Male ; Aged ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; }, abstract = {PURPOSE: To evaluate the temporal behavior and relative variability of a margin-based metric, lesion front displacement, for quantifying geographic atrophy (GA) progression secondary to age-related macular degeneration and to compare its performance with conventional metrics.<br><br>METHODS: This retrospective longitudinal analysis included 103 untreated fellow eyes from the MAHALO clinical trial with GA and 18-month follow-up. Fundus autofluorescence images were obtained at baseline and 6, 12, and 18 months. Five progression metrics were calculated: total area change, square root area change, total perimeter change, perimeter-adjusted growth rate (&#x3bb;'PA), and lesion front displacement. Linearity was assessed using simple linear regression and the Harvey-Collier test. Variability was evaluated using standard deviation, variance ratios, and the Fligner-Killeen test.<br><br>RESULTS: Linearity was rejected for area and square root area change but not for lesion front displacement, perimeter change, or &#x3bb;'PA. Lesion front displacement showed a relatively higher coefficient of determination (R2 = 0.504), whereas area (0.116), square root area (0.104), perimeter (0.001), and &#x3bb;'PA (0.018) exhibited lower goodness of fit to a linear model. Lesion front displacement demonstrated lower dispersion across follow-up intervals. Variance ratio analysis indicated greater variability for all comparator metrics. Variability was significantly lower for lesion front displacement than for perimeter change and &#x3bb;'PA at 12 and 18 months (P < 0.05).<br><br>CONCLUSIONS: Lesion front displacement demonstrated more consistent linear approximation and lower variability compared with several conventional GA progression metrics. This margin-based approach may serve as a complementary metric for longitudinal assessment of GA progression.}, }
@article {pmid42536670, year = {2026}, author = {Cardaras, A and Kim, S and Yuan, Y and Livnat, I and Yanagihara, RT and Saul, R and De Oca, GM and Zheng, K and Browne, AW}, title = {A computer vision-based approach for automatically extracting data from bar chart raster images to facilitate meta-analysis of biomedical literature.}, journal = {PloS one}, volume = {21}, number = {7}, pages = {e0347081}, pmid = {42536670}, issn = {1932-6203}, mesh = {Convolutional Neural Networks ; *Image Processing, Computer-Assisted/methods ; Humans ; Macular Degeneration ; Algorithms ; Publications ; }, abstract = {Although bar charts are widely used in scientific publications, their rasterized format within Portable Document Format (PDF) files complicates automated data extraction, hindering large-scale evidence synthesis and meta-analysis. To address this, we developed and evaluated an automated pipeline for extracting quantitative data from bar charts embedded in the biomedical literature. The four-stage pipeline comprises (1) image extraction and panel segmentation, (2) optical character recognition (OCR)-based text detection, (3) image disassembly to identify chart components, and (4) data reconstruction using numeric parsing and axis-based interpolation. The system combines edge detection, morphological operations, and convolutional neural network (CNN)-based figure classification using a transfer-learned Inception v3 model. Performance was validated on randomized controlled trials in age-related macular degeneration, with manually annotated values from a semi-automated labeling tool as the reference standard, and agreement was assessed using Bland-Altman analysis. Across 28 bar charts from ten publications, the pipeline correctly recognized 92.9% (95% confidence interval [CI], 77.4-98.0) of figure types, 96.0% (95% CI, 94.2-97.3) of text blocks, and 79.1% (95% CI, 74.7-83.0) of bars. For numerical reconstruction, 81.2% (95% CI, 76.3-85.2) of bar values fell within ±5% of the reference standard, 63.0% (95% CI, 57.3-68.3) within ±2%, and 48.6% (95% CI, 43.0-54.3) within ±1%. Bland-Altman analysis showed a small negative bias of -0.18 (95% CI, -0.34 to -0.02), with 94.9% of differences within the limits of agreement. Most outliers arose from OCR digit misclassification or ambiguous bar boundaries. This proof-of-concept study demonstrates the feasibility of automated data extraction from bar charts using a hybrid approach that combines image-processing heuristics with CNN-based classification. Although currently limited to bar charts and a single clinical domain, the pipeline represents a step toward scalable, end-to-end systems for automated evidence extraction to support meta-analyses across the biomedical literature.}, }
@article {pmid42527415, year = {2026}, author = {Bhuiyan, A and Govindaiah, A and Otero-Marquez, O and Fabczak-Kubicka, A and Bhuiyan, T and Tai, K and Deobhakta, A and Smith, T}, title = {A prospective study for validating an automated AI-based system for detecting age-related macular degeneration in clinical settings.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {42527415}, issn = {2045-2322}, support = {R44EY031202/NH/NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; Female ; Aged ; Male ; Prospective Studies ; *Artificial Intelligence ; Sensitivity and Specificity ; Middle Aged ; Aged, 80 and over ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early detection is essential for implementing preventative measures that can slow or stop the progression of late AMD. This study evaluates the performance of an AI-based system designed to detect referable AMD, defined as more than early AMD (mteAMD), in adults over 50 who have not been previously diagnosed. Using color fundus photographs, we recruited 845 subjects from three primary care and three general ophthalmology clinics in New York City. Non-dilated images of both eyes were taken, and for validation, dilated images were reviewed by three ophthalmologists who classified the cases as no AMD, early, intermediate, or late AMD. The system's performance was assessed on both a per-patient and per-eye basis, comparing its results to expert gradings using metrics such as AUC, sensitivity, specificity, positive predictive value, and negative predictive value. For identifying mteAMD at the subject level, the AI system achieved an AUC of 0.92, with a sensitivity of 90.27% and specificity of 83.36%, demonstrating its strong potential for early diagnosis and screening of AMD in real-world clinical settings.}, }
@article {pmid42528138, year = {2026}, author = {Zeng, Y and Zhang, T and Cornish, E and Lee, SR and Yam, M and Eminhizer, M and Zeng, J and Zhang, J and Zeng, S and Arafah, ADB and Wei, X and Yang, J and Zhu, M and Chang, A and Zhang, M and Du, J and Zhu, L and Gillies, MC}, title = {Dysregulated Proline Metabolism Contributes to Retinal Fibrosis in Neovascular AMD: Therapeutic Potential of Prolyl-4-Hydroxylase Inhibition.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.07.044}, pmid = {42528138}, issn = {1525-0024}, abstract = {Subretinal fibrosis, a major cause of irreversible vision loss in neovascular age-related macular degeneration (nAMD), is driven by excessive deposition of extracellular matrix such as collagens. While proline metabolism is known to play a critical role in collagen biosynthesis and fibrosis, its involvement in subretinal fibrosis remains unclear. Here, we characterized the progression of fibrovascular lesions in JR5558 mice, observing significant molecular alterations as early as 4 weeks of age and phenotypic changes by 8 weeks. Transcriptomic and metabolomic analyses revealed elevated levels of 4-hydroxyproline, an essential component of collagen, alongside significant alterations of other fibrosis-related pathways. P4HA1, a catalytic subunit of prolyl-4-hydroxylase essential for 4-hydroxyproline biosynthesis, was prominently expressed in fibrotic lesions in retinas of JR5558, laser-induced murine models and human eyes with nAMD. Targeting P4HA1 with the small-molecule inhibitor diethyl pythiDC significantly attenuated fibrovascular lesion expansion in the JR5558 mouse model and reduced collagen turnover in human retinal pigment epithelium cells. Treatment responses in JR5558 mice were lesion-cluster dependent, with the combination of diethyl pythiDC with aflibercept showing selective antifibrotic benefit in moderate lesion cluster. These findings support a potential role of proline metabolism, particularly proline hydroxylation, in subretinal fibrosis. Inhibiting P4HA1 with diethyl pythiDC inhibited fibrosis in the models we studied, highlighting a potential therapeutic strategy.}, }
@article {pmid42528715, year = {2026}, author = {Matsuki, T and Akiyama, K and Watanabe, K and Noda, T and Sasaki, M}, title = {Early retinal volume changes after switching to brolucizumab in refractory neovascular age-related macular degeneration.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1872499}, pmid = {42528715}, issn = {2674-0826}, abstract = {BACKGROUND: This retrospective observational study primarily focused on the evaluation of early anatomical changes and intraocular inflammation (IOI) following the switch to intravitreal injection of brolucizumab (IVBr) in patients with neovascular age-related macular degeneration (nAMD) who were refractory to aflibercept or ranibizumab and unable to extend injection interval beyond 10 weeks while resolving retinal fluids.<br><br>RESULTS: Data from 23 patients were analyzed. Switch to brolucizumab resulted in rapid decreases in central foveal retinal thickness (CRT) (247 (130) to 227 (94)) &#x3bc;m, P < 0.001), pigment epithelial detachment volume (0.18 (0.47) to 0.11 (0.19) mm&#xb3;, P&#xa0;=&#xa0;0.04) and central choroidal thickness (159 (118) to 168 (78) &#x3bc;m, P&#xa0;=&#xa0;0.018), although decrease in central retinal volume (CRV) (9.80 (1.40) to 9.70 (1.30) mm&#xb3;, P&#xa0;=&#xa0;0.111) was not significant.Three eyes exhibited IOI, observed on post-injection day 2 after the second IVBr. Two eyes exhibited only mild anterior chamber inflammation, while one eye exhibited vasculitis obliterans. While CRT decreased, CRV increased in all three eyes.As a post-hoc analysis, CRV in eyes without IOI exhibited significant decrease (9.90 (1.45) to 9.70 (1.20) mm&#xb3;, P&#xa0;=&#xa0;0.002).<br><br>CONCLUSION: Switch to brolucizumab therapy resulted in early anatomical changes. An increase in CRV despite improvement in central foveal parameters may represent a potential warning sign of brolucizumab-associated IOI and warrants further prospective validation.}, }
@article {pmid42529820, year = {2026}, author = {Kheirkhah, A and Oszvar-Kozma, M and Lamina, C and Stark, KJ and Afonyushkin, T and Zimmermann, ME and Brandl, C and Heid, IM and Kronenberg, F and Binder, CJ}, title = {Circulating IgM Antibody Levels Against Oxidation-Specific Epitopes and Their Association With Age-Related Macular Degeneration.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {}, number = {}, pages = {}, doi = {10.1161/ATVBAHA.126.324949}, pmid = {42529820}, issn = {1524-4636}, abstract = {BACKGROUND: Cardiovascular disease (CVD) is associated with age-related macular degeneration (AMD), suggesting shared pathogenic pathways. Natural IgM antibodies targeting oxidation-specific epitopes (OSEs) are well characterized in CVD and may contribute to AMD. To date, no observational study has assessed the association between OSE-IgM and AMD, including among individuals with concomitant CVD. Here, we investigate this relationship in large population-based cross-sectional data of old-aged individuals.<br><br>METHODS: We measured IgM antibodies against phosphocholine-modified BSA (PC), MDA-LDL (malondialdehyde-modified low-density lipoprotein), and CuOx-LDL (copper-oxidized LDL) in up to 2264 participants with and without AMD of the AugUR study (Age-Related Diseases: Understanding Genetic and Nongenetic Influences-a Study at the University of Regensburg; 627 cases, 1637 controls; age, 70-95 years). Antibody levels were inverse-normalized, and multinomial mixed regression analyses were performed to evaluate their associations with different AMD stages.<br><br>RESULTS: Women exhibited significantly higher levels of all 3 OSE-IgM compared with men. Elevated levels of IgM against PC were associated with 12% decreased odds (odds ratio, 0.88 [95% CI, 0.80-0.97]; P=0.01) for any AMD. When we investigated OSE-IgM associations with different stages of AMD (early AMD, late AMD), we found that all 3 OSE-IgM were associated with &#x2248;20% lower odds for late AMD, but none with early AMD. Associations of OSE-IgM with late AMD were stronger in men than in women. Of the participants, 490 individuals had documented CVD. A significant interaction was observed between levels of PC IgM and CVD status in their associations with early AMD (P=0.049). In a subset of participants with CVD, PC IgM levels were associated with 34% decreased odds (odds ratio, 0.66 [95% CI, 0.51-0.86]; P=0.002) for early AMD.<br><br>CONCLUSIONS: This study identifies an inverse association between IgM antibodies targeting PC, MDA-LDL, and CuOx-LDL and late AMD, but not with early AMD. However, in the early stage of AMD, an association with PC IgM is only observed when the participants had documented CVD. These findings may suggest a possible protective role of OSE-IgM antibodies in AMD pathogenesis and progression.}, }
@article {pmid42530462, year = {2026}, author = {Baddar, D and Fouad, Y and Salem, NO and Feo, A and Nowara, M and Sarraf, D}, title = {Type 4 macular neovascularization in eyes with diabetic retinopathy.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004948}, pmid = {42530462}, issn = {1539-2864}, abstract = {PURPOSE: To report recently described type 4 macular neovascularization (T4MNV) in eyes with diabetic retinopathy (DR).<br><br>METHODS: A retrospective analysis including nine eyes with DR (and without any features of age related macular degeneration or AMD) that displayed T4MNV with optical coherence tomography (OCT) and OCT angiography (OCTA).<br><br>RESULTS: The mean age of the patients was 64 years, and the mean duration of diabetes mellitus was 20 years. All patients displayed unilateral T4MNV with an average visual acuity of 20/500 in the affected eye. Seven of the nine patients (77.8%) were diagnosed with proliferative DR, and the remaining exhibited severe non-proliferative DR. Central posterior hyaloid fibrosis was detected in 7/9 eyes (77.8%) and showed flow on OCTA in 4/9 eyes (44.4%). All 9 eyes showed subretinal hyperreflective material (SHRM) on OCT corresponding to Type 2 (and Type 1) MNV on OCT and OCTA. Drusen were not detected in any of the 9 affected or fellow eyes.<br><br>CONCLUSION: T4MNV can occur in eyes with long-standing DR without signs of AMD. It is possible that early identification of T2MNV and timely anti-VEGF intervention may potentially mitigate progression to T4MNV, but this requires validation with prospective analysis. Early recognition of T4MNV imaging features is important in counseling patients about the poor visual prognosis.}, }
@article {pmid42530765, year = {2026}, author = {Wang, L and Guo, ZY and Hu, FX and Zhang, CY and Yuan, Y and Zhou, BQ and Peng, YT and Pang, L and Wang, Y}, title = {Correction: Next-generation sequencing reveals aqueous MicroRNA and piRNA signatures in age-related macular degeneration and polypoidal choroidal vasculopathy.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11010-026-05681-0}, pmid = {42530765}, issn = {1573-4919}, }
@article {pmid42530827, year = {2026}, author = {Lee, J}, title = {Beyond Typical AMD: A Vodcast Exploring the Clinical and Therapeutic Landscape of PCV.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, pmid = {42530827}, issn = {1865-8652}, abstract = {Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid characterized by polypoidal lesions and a branching vascular network, leading to recurrent exudation and hemorrhage. It is a major cause of visual disability and is particularly prevalent in Asian populations. PCV is similar to neovascular age-related macular degeneration (nAMD) in morphological characteristics but is increasingly recognized as part of the pachychoroid disease spectrum, although consensus has yet to be reached. Despite overlapping features with nAMD, PCV demonstrates distinct pathophysiology and treatment response, necessitating accurate differentiation for management optimization. Diagnosis relies on multimodal imaging, with indocyanine green angiography (ICGA) as the gold standard, supported by optical coherence tomography (OCT) and OCT angiography. Anti-vascular endothelial growth factor (VEGF) therapy is the mainstay of treatment; however, responses are heterogeneous and are often suboptimal or incomplete. Long-term outcomes are frequently influenced by complications such as hemorrhage, fibrosis, and atrophy, highlighting the need for durable disease control. Advances in imaging and a better understanding of pachychoroid biology are enabling more personalized, activity-guided treatment strategies, with the potential to improve long-term outcomes and reduce treatment burden. In this vodcast, Professor Junyeop Lee discusses the key clinical and pathological features of PCV, how it differs from nAMD, and why it remains challenging to diagnose and manage. The discussion also explores evolving diagnostic approaches, current treatment strategies, and emerging directions in PCV care. Vodcast available for this article. Supplementary file1 (MP4 279147 KB).}, }
@article {pmid42533499, year = {2026}, author = {Liu, Z and Li, H and Wang, C and Wang, T and Jiao, X}, title = {Beyond Glycemic Control: Metformin's Multi-Target Role in Preventing and Treating Major Ocular Pathologies.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {}, number = {}, pages = {10807683261474426}, doi = {10.1177/10807683261474426}, pmid = {42533499}, issn = {1557-7732}, abstract = {Metformin, a first-line therapy for type 2 diabetes, is increasingly recognized as a pleiotropic agent with potential relevance to ocular disease beyond glycemic control. Accumulating epidemiological evidence suggests that metformin exposure may be associated with reduced risk or slower progression of diabetic retinopathy, primary open-angle glaucoma, and age-related macular degeneration, while emerging data also implicate possible benefits in dry eye disease, uveitis, retinal vascular disorders, inherited retinal degeneration, and cataract. Mechanistically, metformin may modulate multiple disease-relevant pathways, including AMPK-mTOR signaling, autophagy, mitochondrial homeostasis, NRF2-mediated antioxidant defense, NF-κB/PARP-related inflammation, VEGF-driven angiogenesis, TXNIP-associated neurodegeneration, and TGF-β-dependent fibrosis. However, current evidence remains insufficient to support metformin as an established ophthalmic therapy. Most clinical data are observational and susceptible to confounding by diabetes severity, comorbidities, treatment indication, and survival bias; randomized evidence is limited, and the METforMIN trial did not significantly slow geographic atrophy progression. In addition, many preclinical studies use concentrations exceeding clinically achievable systemic exposure, whereas ocular pharmacokinetics, tissue bioavailability, transporter dependence, and dose-toxicity relationships remain poorly defined. Signals of dose-dependent risk, including high-intensity exposure in diabetic retinopathy and stress responses in meibomian gland epithelial cells, further underscore the need for caution. Future studies should prioritize prospective ocular endpoints, measured intraocular drug concentrations, target-engagement biomarkers, transporter-informed delivery strategies, and rigorous dose-ranging safety assessments.}, }
@article {pmid42534250, year = {2026}, author = {Contreras-Salinas, H and Vázquez-Beltrán, JC and García-Sánchez, G and Quirarte-Justo, S and Gómez-Macías, SDC and Rodríguez-Herrera, LY}, title = {Disproportionality analysis of off-label intravitreal bevacizumab in the FDA Adverse Event Reporting System database.}, journal = {Therapeutic advances in drug safety}, volume = {17}, number = {}, pages = {20420986261462682}, pmid = {42534250}, issn = {2042-0986}, abstract = {BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor agent initially approved for cancer treatment, is widely used off-label in retinal vascular diseases; however, this use may carry safety risks, particularly when evidence from controlled clinical trials is limited. In this context, real-world evidence derived from large pharmacovigilance databases plays a critical role in evaluating its safety profile.<br><br>OBJECTIVES: Evaluate the safety profile of off-label intravitreal bevacizumab for the treatment of retinal vascular diseases using the FDA Adverse Event Reporting System (FAERS) database.<br><br>DESIGN: Disproportionality analysis using data mining of the FAERS database.<br><br>METHODS: Individual case safety reports (ICSRs) of intravitreal bevacizumab from Q1 2015 to Q2 2025 were extracted, and data mining methods (reporting odds ratio, proportional reporting ratio and Bayesian confidence propagation neural network) were applied to identify statistical disproportionality. In addition, a comparative risk analysis (odds ratio) was performed against ranibizumab.<br><br>RESULTS: Of the 1495 ICSRs (5232 adverse events (AEs)), 114 preferred terms were statistically significant in the disproportionality analyses; 52% were expected, 15% were related to lack of efficacy and 33% were unexpected. Furthermore, the comparative analysis suggests a higher risk of serious cardiovascular, ocular and systemic events with ranibizumab.<br><br>CONCLUSION: Most of the disproportionately reported AEs associated with bevacizumab were expected or related to product handling, underscoring the importance of using approved single-dose formulations. While this analysis suggests a lower risk of serious systemic AEs with bevacizumab than with ranibizumab, this finding should be interpreted with caution, as disproportionality analyses based on spontaneous reporting systems cannot confirm causal associations. Further evidence is needed to confirm the observed associations.}, }
@article {pmid42534283, year = {2026}, author = {Ghorayeb, G and Ali, MH and Hadziahmetovic, M and Emerson, GG and Jumper, JM and Blim, JF and Lai, MM}, title = {OCT as a Dynamic Biomarker in Retinal Disease Management: Evidence, Decision Strategies, and Clinical Guidance for OCT Decision-Point Use.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261467124}, pmid = {42534283}, issn = {2474-1272}, abstract = {PURPOSE: To describe how optical coherence tomography (OCT) is used in retinal disease management to aid in decision-making, including whether to treat or observe, extend or shorten dosing intervals, switch therapy, and plan or assess surgical care.<br><br>METHODS: Pivotal randomized clinical trials and designs in neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were reviewed to characterize how OCT is used within evidence-based retreatment and monitoring strategies, including newer faricimab and aflibercept 8 mg trial programs. These decision strategies were translated into scenario-based clinical guidance for real-world decision-point use.<br><br>RESULTS: Where randomized evidence is limited, particularly for selected surgical retina decision points, guidance reflects the authors' expert opinion as informed by available literature and common retina practice. OCT is used in trial protocols as an anatomic biomarker for nAMD, DME, and RVO to assess disease activity, treatment response and recurrence, and to determine individualized follow-up and retreatment intervals. OCT was often obtained at protocol visits during active therapy phases and at key reassessment points. When new symptoms, suspected recurrence, incomplete response, diagnostic uncertainty, or high-risk features are present, shorter assessment intervals may be appropriate.<br><br>CONCLUSIONS: OCT-guided, decision-linked monitoring is supported by contemporary randomized clinical trials as integral to the management of nAMD, DME, and RVO, while recognizing that OCT frequency is generally not randomized as an isolated variable. The risk of avoidable vision loss can be reduced with scenario-based retina clinical guidance that emphasizes OCT at clinical decision points, improving patient safety and enhancing individualized care.}, }
@article {pmid42534291, year = {2026}, author = {Bhavsar, AP and Boucher, N and Fernando, R and Ishii, F and Sambhara, D}, title = {Examining Real-World Attrition Among Patients Undergoing Complement Inhibitor Intravitreal Therapy for Geographic Atrophy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261467244}, pmid = {42534291}, issn = {2474-1272}, abstract = {PURPOSE: To identify characteristics of patients with geographic atrophy (GA) who received pegcetacoplan or avacincaptad pegol and discontinued treatment.<br><br>METHODS: Two complementary retrospective cohort studies of a large, geographically and demographically diverse, deidentified database were performed. One analysis assessed baseline characteristics. Eyes with 12 months of data were included in a subsequent analysis of follow-up changes/characteristics. Univariate and multivariate mixed-effects Cox proportional hazard and logistic regression models, respectively, were used to estimate the hazard ratio (HR) and odds ratio (OR) of attrition.<br><br>RESULTS: A total of 21&#x2009;914 eyes were identified for the baseline analysis, 14&#x2009;690 (67%) of which received pegcetacoplan and 7224 (33%) avacincaptad pegol. Mean (&#xb1;SD) patient age was 82.1 &#xb1; 7.85 years. Treatment retention declined between 0 and 12 months. Baseline predictors of attrition were age older than 90 years (HR, 1.26; 95% CI, 1.03-1.55; P = .028), pegcetacoplan treatment (HR, 3.32; 95% CI, 2.92-3.76; P < .001), treated (HR, 1.56; 95% CI, 1.40-1.75; P < .001) and untreated (HR, 1.41; 95% CI, 1.21-1.64; P < .001) neovascular age-related macular degeneration (nAMD), visual acuity of less than 35 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (HR, 1.45; 95% CI, 1.25-1.67; P < .001), and subfoveal GA (HR, 1.15; 95% CI, 1.04-1.27; P = .007). Poor baseline visual acuity remained significant in the adjusted 12-month analysis. Significant predictors included new nAMD (OR, 3.02; 95% CI, 2.35-3.89; P < .001) and a loss of more than 5 ETDRS letters (OR, 1.36; 95% CI, 1.17-1.58; P < .001). nAMD treatment intervals of more than 6 weeks (OR, 0.59; 95% CI, 0.39-0.90; P = .014) and GA treatment intervals of 6 to 8 weeks (OR, 0.56; 95% CI, 0.43-0.74; P < .001) contributed to decreased odds of attrition.<br><br>CONCLUSIONS: Poor baseline vision and development of new nAMD are associated with patient attrition, and the combination of nAMD and GA and treatment burden challenges patient retention.}, }
@article {pmid42534447, year = {2026}, author = {Zhang, X and Liu, H}, title = {SPI1 Promotes TNF-α-Induced Epithelial-Mesenchymal Transition-Like Changes in Retinal Pigment Epithelial Cells: Implications for the Pathogenesis of Age-Related Macular Degeneration.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {8106992}, pmid = {42534447}, issn = {2090-004X}, abstract = {BACKGROUND/AIMS: Age-related macular degeneration (AMD) is a progressive degenerative disease of the retinal macula associated with aging, which is one of the main causes of vision loss in the elderly. This research aims to investigate the mechanism of SPI1 in EMT of RPE cells in AMD, providing new targets for AMD treatment.<br><br>METHODS: SPI1, ALKBH5, and NURR1 expression was assayed by RT-qPCR and Western blot in AMD patients and cell models. The relationship between SPI1 expression and clinical features of AMD patients was analyzed, and the correlations among SPI1, ALKBH5, and NURR1 were analyzed. The diagnostic value of SPI1 in AMD was verified via ROC curve. ROS levels were detected. N-cadherin and E-cadherin were detected by Western blot. Cell migration was detected by transwell assay. The binding of SPI1 to ALKBH5 in cells was verified. m6A levels on NURR1 were detected.<br><br>RESULTS: SPI1 and ALKBH5 were highly expressed, while NURR1 was lowly expressed in TNF-&#x3b1;-induced human RPE cells. SPI1 expression was correlated with age and staging of AMD patients. SPI1 expression exhibited a positive association with ALKBH5 expression, while showing a negative association with NURR1 expression. After downregulation of SPI1, N-cadherin was downregulated, E-cadherin was upregulated, ROS levels were decreased, and cell migration was reduced. SPI1 promoted ALKBH5 expression, and ALKBH5 downregulated NURR1 expression via m6A modification. ALKBH5 overexpression or NURR1 downregulation partially reversed the attenuating effect of SPI1 downregulation on EMT-like changes in RPE cells.<br><br>CONCLUSION: SPI1 stimulates EMT-like changes of RPE cells via the ALKBH5/NURR1 axis. This pathway may participate in AMD-related pathological processes.}, }
@article {pmid42534834, year = {2026}, author = {Zhu, M and Yu, W}, title = {The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.}, journal = {Frontiers in aging neuroscience}, volume = {18}, number = {}, pages = {1817987}, pmid = {42534834}, issn = {1663-4365}, abstract = {Age-related macular degeneration (AMD) is a fundus oculi disease that progressively impairs the central vision of patients. To date, its pathogenesis has not been fully elucidated, and therapeutic options for dry AMD remain limited. Recently, chronic low-grade inflammation has been recognized as an important pathogenic factor in various neurodegenerative diseases, including AMD. The NLRP3 inflammasome, a key component of the innate immune system, has emerged as a critical integrator of retinal stress signals. This review first delineates the molecular architecture and activation modalities of the NLRP3 inflammasome, encompassing canonical, noncanonical, and alternative pathways, as well as its downstream cell death programs, with a particular focus on pyroptosis and PANoptosis. We describe how AMD-associated danger signals converge on NLRP3 inflammasome activation within distinct retinal cell populations and discuss how cell-type-specific NLRP3 responses differently shape retinal homeostasis, degeneration, and neovascularization. We further summarize current evidence indicating that the pathological consequences of NLRP3 activation vary across AMD progression, from amplification of chronic inflammation in early and intermediate AMD to promotion of retinal atrophy in geographic atrophy and angiogenic signaling in neovascular AMD. Finally, we evaluate emerging therapeutic strategies targeting the NLRP3 pathway and discuss the major translational challenges related to cell-type and disease-stage specificity, retinal delivery, and long-term safety. By integrating retinal triggers, cellular responses, senescence-associated inflammation, inflammatory cell death, disease phenotypes, and therapeutic opportunities into a unified framework, this review provides a comprehensive perspective on the role of NLRP3 inflammasome signaling in AMD pathogenesis and treatment.}, }
@article {pmid42521465, year = {2026}, author = {Guo, X and Chen, Y and Xiong, R and Zhuo, S and Li, H and Zhu, Z and Zhu, Z and Zhang, L and Huang, W and Congdon, N and Wang, W}, title = {Persistence of severe global sex-based inequalities in the burden of visual impairment.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328771}, pmid = {42521465}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: Sex-based disparities in vision impairment are a major global health concern. This study quantifies these disparities across major blinding diseases and assesses their association with national-level gender inequality.<br><br>METHODS: In this repeated ecological analysis of Global Burden of Disease (GBD) 2023 data, we analysed sex-disaggregated age-standardised years lived with disability (YLD) rates and prevalence for major blinding diseases. Temporal trends were assessed using average annual per cent change (AAPC). Linear regression examined associations between sex differences and the Gender Development Index (GDI) and Gender Inequality Index (GII). Projections were performed using a Bayesian age-period-cohort model.<br><br>RESULTS: From 1990 to 2023, sex disparities persisted, with a higher AAPC in females than males (0.08% vs -0.06%). In 2023, females had higher YLD rates than males for blindness and vision loss (BVI) (300.9 vs 262.8 per 100 000; +14.5%), cataract (95.1 vs 75.0; +26.7%) and age-related macular degeneration (6.9 vs 5.8; +18.0%), while glaucoma was higher in males. The largest female excess for BVI was in South Asia (difference 69.9 per 100 000). Higher GII and lower GDI were significantly associated with larger sex disparities (&#x3b2;=34.3 per unit GII increase; &#x3b2;=-197.0 per unit GDI increase, all p<0.001). Without targeted intervention, disparities are projected to persist or widen by 2040.<br><br>CONCLUSION: Global sex disparities in vision impairment remained substantial from 1990 to 2023&#x2009;and are projected to continue. The strong association with GDI and GII indicates these disparities are modifiable and linked to structural factors. Gender-sensitive policies are needed to achieve equity in eye health.}, }
@article {pmid42522009, year = {2026}, author = {Tarhan, M and Jungk, NL and Brockmann, T and Meller, D and Hammer, M}, title = {Fluorescence lifetimes and choriocapillaris flow deficits in intermediate age-related macular degeneration: a cross-sectional study.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42522009}, issn = {1471-2415}, mesh = {Humans ; *Choroid/blood supply ; Female ; Cross-Sectional Studies ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Male ; *Regional Blood Flow/physiology ; Aged, 80 and over ; *Macular Degeneration/physiopathology/diagnosis ; Ophthalmoscopy/methods ; Aged ; Capillaries/physiopathology ; *Retinal Vessels/physiopathology ; }, abstract = {PURPOSE: To assess the association between retinal fluorescence lifetimes (τm) and choriocapillaris (CC) flow deficits (FD) in intermediate age-related macular degeneration (AMD).<br><br>METHODS: Twenty-six pseudophakic eyes with intermediate, non-exudative AMD (mean age 83&#x2009;&#xb1;&#x2009;5 years) underwent fluorescence lifetime imaging ophthalmoscopy (FLIO) and optical coherence tomography angiography (OCTA). Fluorescence lifetimes were recorded in short- and long-wavelength channels and analyzed across ETDRS subfields. CC flow deficits were quantified using local thresholding. Associations between &#x3c4;m and FD were evaluated using Spearman's rank correlation.<br><br>RESULTS: Mean &#x3c4;m values were consistently higher in the long-wavelength channel compared to the short-wavelength channel across all subfields. Mean CC FD increased from the outer ring (0.50&#x2009;&#xb1;&#x2009;0.07) to the central subfield (0.65&#x2009;&#xb1;&#x2009;0.11). Correlation coefficients between &#x3c4;m and FD ranged from -&#x2009;0.07 to 0.37, with no statistically significant associations (all p&#x2009;>&#x2009;0.05).<br><br>CONCLUSIONS: No statistically significant association was observed between fluorescence lifetimes and choriocapillaris flow deficits in this exploratory cohort. Although both biomarkers are known to be altered in AMD, the absence of evidence for a statistically significant spatial association suggests that FLIO and OCTA may reflect complementary aspects of disease pathology. Larger studies incorporating structural retinal biomarkers and longitudinal follow-up are warranted.<br><br>CLINICAL TRIAL REGISTRATION: Not applicable.}, }
@article {pmid42524100, year = {2026}, author = {Liu, L and Cheng, L and Ren, Q and Chu, Z and Cheng, H}, title = {Selective reduction of the light peak-to-dark trough ratio in reticular macular disease: an electrooculography study.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1865041}, pmid = {42524100}, issn = {1662-4548}, abstract = {PURPOSE: To compare electrooculogram (EOG) parameters between eyes with reticular macular disease (RMD) and eyes with early-to-intermediate age-related macular degeneration (AMD) without reticular pseudodrusen (RPD), and to assess whether RMD is associated with generalized RPE-photoreceptor complex dysfunction.<br><br>METHODS: In this observational cross-sectional study, 42 eyes from 21 patients were analyzed (without-RPD group: 28 eyes; RMD group: 14 eyes). RMD was diagnosed using multimodal imaging (infrared reflectance and SD-OCT). EOGs were recorded with the RETI-port/scan 21 system according to ISCEV standards. Extracted parameters included dark trough (DT), light peak (LP), light rise time (Light Rise), and the LP:DT ratio. Group comparisons used the Wilcoxon rank-sum test. Linear regression evaluated the association between RMD and LP:DT ratio with and without adjustment for age.<br><br>RESULTS: Age did not differ between groups (median 69 vs. 72 years; P = 0.5). Absolute standing potentials were similar (DT: 598 vs. 681 &#x3bc;V, P = 0.2; LP: 1,092 vs. 1,150 &#x3bc;V, P = 0.8). Light rise time was also similar (8.00 [IQR 7.50-9.00] vs. 8.00 [IQR 7.00-9.00] min; P = 0.6). In contrast, the LP:DT ratio was significantly reduced in RMD (1.65 [1.50-1.80]) compared with without-RPD controls (1.90 [1.80-2.10]; P = 0.0043). RMD was independently associated with a lower LP:DT ratio (&#x3b2; = -0.25, 95% CI [-0.41 to -0.09]; P = 0.004).<br><br>CONCLUSION: Compared with AMD eyes without RPD, RMD eyes demonstrate a selectively reduced LP:DT ratio without a change in absolute standing potentials or light rise timing. This EOG pattern supports attenuated light response consistent with generalized dysfunction of the RPE-photoreceptor complex in RMD.}, }
@article {pmid42524714, year = {2026}, author = {Birner, K and Frank-Publig, S and Mai, J and Eidenberger, A and Schrittwieser, J and Leitner-Barrios, G and Barasits, M and Gumpinger, M and Reiter, GS and Sacu, S and Schmidt-Erfurth, U}, title = {Systematic quantification of outer retinal morphology in three different SD-OCT devices in geographic atrophy.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70210}, pmid = {42524714}, issn = {1755-3768}, abstract = {PURPOSE: To define interdevice differences in quantitative outer retinal biomarkers across three spectral-domain (SD) optical coherence tomography (OCT) devices in geographic atrophy (GA).<br><br>METHODS: Patients with GA prospectively underwent imaging using Spectralis (Heidelberg Engineering), Cirrus (Zeiss) and Maestro (Topcon) OCT devices. Ellipsoid zone (EZ) and outer nuclear layer (ONL) thickness, as well as EZ and retinal pigment epithelium (RPE) loss, were automatically pre-segmented and manually corrected. Quantitative measurements were compared between OCT devices using anova or Friedman tests. Bland-Altman analysis determined mean differences and 95% limits of agreement (LoA).<br><br>RESULTS: A total of 7080 B-scans from 120 OCT volumes of 40 eyes were analysed. Mean patient age was 80&#x2009;&#xb1;&#x2009;7&#x2009;years. Mean EZ thickness in the 6-mm macular cube was 34.8&#x2009;&#xb1;&#x2009;4.6, 33.4&#x2009;&#xb1;&#x2009;4.1 and 31.0&#x2009;&#xb1;&#x2009;4.8&#x2009;&#x3bc;m for Spectralis, Cirrus and Maestro, respectively, while mean ONL thickness was 77.8&#x2009;&#xb1;&#x2009;9.2, 78.5&#x2009;&#xb1;&#x2009;9.4 and 75.8&#x2009;&#xb1;&#x2009;9.6&#x2009;&#x3bc;m. Interdevice differences were significant for EZ and ONL-thickness (all p&#x2009;<&#x2009;0.05). Mean EZ thickness bias ranged from 1.5 to 3.8&#x2009;&#x3bc;m, with the widest LoA between Spectralis and Maestro. Mean ONL-thickness bias ranged from -0.7 to 2.7&#x2009;&#x3bc;m, with the widest LoA between Cirrus and Maestro. EZ-loss and EZ/RPE-loss-area also differed significantly (both p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: Visualization and quantification of atrophic features at the level of the photoreceptors, including EZ thickness, EZ loss and ONL thickness, are influenced by the implemented OCT machine. Consistency in the OCT device during patient monitoring allows for the highest precision and eliminates interdevice differences in quantitative outcome measures.}, }
@article {pmid42525587, year = {2026}, author = {Abdin, AD and Bedros, L and Kahlert, J and Munteanu, C and Mirsalehi, M and Langenbucher, A and Suffo, S and Seitz, B}, title = {Influence of Structural OCT Biomarkers on Functional Outcomes in Eyes With Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1}, doi = {10.1159/oph/aeeag005}, pmid = {42525587}, issn = {1423-0267}, abstract = {Purpose To investigate the effect of structural optical coherence tomography (OCT) biomarkers on the functional outcome in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (VEGF) therapy. Patients and Methods This retrospective study included 305 eyes of 254 patients with primary onset nAMD followed for 2 years. At baseline, several OCT structural biomarkers were assessed. We evaluated the interaction between the presence of all these biomarkers and the best corrected visual acuity (BCVA) in logMAR and the number of intravitreal injections, (IVI) administered over 2 years of treatment. Results The BCVA was 0.44±0.24 before treatment and 0.53±0.20 after 24 months (p=0.10). BCVA in logMAR after 2 years was significantly positively correlated with baseline presence of intraretinal fluid (IRF) (p <0.001), vitreomacular traction/adhesion (VMT/A) (p=0.04), photoreceptor layer damage (PRD) (p <0.001), and prechoroidal clefts (P=0.02). A significant positive correlation was found between the number of IVIs administered over 2 years and the presence of IRF (p=0.02) and subretinal hyperreflective material (SHRM) (p=0.03) at baseline. Conclusions The baseline presence of IRF, VMT/A, PRD, and prechoroidal clefts may be limit recovery of BCVA after 2 years of treatment. In addition, the presence of IRF and SHRM may be associated with a higher number of IVIs over 2 years of treatment.}, }
@article {pmid42526538, year = {2026}, author = {Bantounou, MA and Emfietzoglou, M and Keenan, TDL and Baroutis, KG and Miller, JW and Vavvas, DG}, title = {Sustained High-Intensity Lipophilic Statin Use and Risk of Age-Related Macular Degeneration: A Target Trial Emulation.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.07.014}, pmid = {42526538}, issn = {2468-6530}, abstract = {OBJECTIVE: To evaluate whether sustained high-intensity lipophilic statin exposure is associated with reduced risk of incident nonexudative age-related macular degeneration (AMD) and progression from nonexudative to exudative AMD.<br><br>DESIGN: Target trial emulation retrospective cohort study.<br><br>PARTICIPANTS: Data were obtained from the Mass General Brigham database (2005-2025). For incident nonexudative AMD, hypertensive adults &#x2265;55 years old were included if they were treated or untreated with high-intensity lipophilic statins (atorvastatin 40-80 mg or simvastatin 40-80 mg) within 2 years following the hypertension date. For progression to exudative AMD, adults &#x2265;55 years old with hypertension and nonexudative AMD were included if they were treated or untreated within 1 year before the nonexudative AMD date.<br><br>METHODS: Sustained exposure was defined as &#x2265;80% cumulative exposure during the exposure window. Exposed and unexposed individuals were propensity-score matched 1:1 on demographics, diabetes, obesity, healthcare utilization, calendar time. Subdistribution hazard ratios (sHR) accounting for the competing risk of death and inverse probability of censoring weighting (IPCW) hazard ratios (HR) were estimated for exposed vs. unexposed, adjusting for cardiovascular and chronic kidney disease. Sensitivity analyses included: positive-control (cataract), negative-control [posterior vitreous detachment (PVD)], any statin vs no exposure.<br><br>MAIN OUTCOME MEASURES: Incident clinically documented nonexudative AMD and progression to exudative AMD.<br><br>RESULTS: Over 2.8&#xb1;1.8 years, 68/8,633 participants (0.79%) in the high-intensity lipophilic statin-exposed cohort and 88/8,633 (1.02%) in the unexposed cohort developed nonexudative AMD (sHR=0.53, 95%-CI, 0.38-0.74; P=0.0002; IPCW HR=0.53, 95%-CI, 0.37-0.76; P=0.0005). In the progression cohort, over 2.1&#xb1;1.6 years, 66/1,082 high-intensity lipophilic statin-exposed participants (6.10%) and 85/1,082 unexposed participants (7.86%) progressed to exudative AMD (sHR=0.62, 95%-CI, 0.45-0.87; P=0.006; IPCW HR=0.61, 95%-CI, 0.43-0.87; P=0.006). Any statin use was not associated with AMD. For cataract, the sHR was 1.18 (95%-CI, 1.03-1.34; P=0.015), and the IPCW HR was 1.20 (95%-CI, 1.05-1.38; P=0.007). For PVD, the sHR was 1.00 (95%-CI, 0.81-1.22; P=0.96), and the IPCW HR was 1.00 (95%-CI, 0.81-1.24; P=0.99).<br><br>CONCLUSIONS: High-intensity lipophilic statin exposure was associated with lower clinically documented nonexudative AMD and progression to exudative AMD risk, whereas any statin exposure was not. These findings support regimen-specific statin effects on AMD risk. Confirmation in prospective studies and randomized trials with retinal outcomes is needed.}, }
@article {pmid42519412, year = {2026}, author = {Chen, J and Tu, S and Zhu, Y and Li, Z and Chen, X and Shen, X and Deng, S and Zhuo, Y}, title = {Association between regular hypnotic use and age-related macular degeneration.}, journal = {Advances in ophthalmology practice and research}, volume = {6}, number = {3}, pages = {219-227}, pmid = {42519412}, issn = {2667-3762}, abstract = {BACKGROUND: Previous studies have confirmed the presence of benzodiazepine receptors in the retina, and exploratory research has suggested that the use of hypnotics may be linked to changes in retinal function and an increased risk of maculopathy. This indicates that regular use of hypnotic medications is likely associated with age-related macular degeneration (AMD). However, the precise relationship remains largely unclear. In this study, we aimed to investigate this association in the UK Biobank.<br><br>METHODS: Regular use of hypnotics, including benzodiazepines or Z-meds (non-benzodiazepine hypnotics such as zolpidem and zaleplon) were assessed at baseline. Nearest-neighbor propensity score matchings (PSM) were implemented to control for potential confounding variables. Cox proportional hazards regression with robust variance estimation was utilized to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for demographic, socioeconomic, systemic, and lifestyle variables. Sensitivity analyses were performed using traditional Cox proportional hazards regression on the original cohort, with additional subgroup analyses stratified by age group and sex.<br><br>RESULTS: Following the PSM procedure, 1899 benzodiazepine users and 7557 non-users were selected from the benzodiazepines cohort, and 321 Z-meds users and 1284 non-users were selected from the Z-meds cohort. A total of 262 participants in the benzodiazepines cohort developed incident AMD during follow-up after PSM, compared with 49 participants in the Z-meds cohort. Upon adjusting for covariates, the prolonged use of Z-meds was associated with an elevated AMD risk (HR: 2.15, 95% CI: 1.23-3.74, P=0.007), whereas no significant association was observed for the regular use of benzodiazepines (HR: 0.97, 95% CI: 0.73-1.30, P=0.854). Sensitivity analyses demonstrated consistent associations. Subgroup analyses also indicated consistent associations across various categories.<br><br>CONCLUSIONS: Prolonged use of Z-meds may elevate the risk of developing AMD. Given the increasing prescription of Z-meds for the treatment of insomnia, these findings underscore the necessity of considering potential ocular risks and requiring more frequent monitoring.}, }
@article {pmid42519923, year = {2026}, author = {Gollamudi, S and Magdum, R and Bajpayee, P and Giri, N and Gupta, A and Lende, D}, title = {Clinical and Diagnostic Challenges of a Sporadic Adult-onset Vitelliform Macular Dystrophy.}, journal = {Annals of African medicine}, volume = {}, number = {}, pages = {}, doi = {10.4103/aam.aam_523_26}, pmid = {42519923}, issn = {0975-5764}, abstract = {Adult-onset vitelliform macular dystrophy (AVMD) is a relatively uncommon macular pattern dystrophy characterized by bilateral, symmetric, yellowish subretinal foveal lesions presenting in the fourth to sixth decades of life. It is frequently misdiagnosed as age-related macular degeneration or Best vitelliform macular dystrophy, making accurate diagnosis through multimodal imaging essential. We report a case of a 51-year-old male laundry worker who presented with bilateral gradual visual impairment and difficulty with near vision for 1 month. Best-corrected visual acuity was 6/6 in the right eye, whereas in the left eye, it was 6/36p-NI with appropriate correction. Anterior segment examination revealed bilateral posterior subcapsular cataracts and seborrheic blepharitis. Dilated fundus examination demonstrated multiple discrete yellowish subretinal deposits at the fovea in the right eye and a single, elevated, circular vitelliform lesion at the center of the macula in the left eye, with absent foveal reflex bilaterally. Fundus autofluorescence imaging confirmed focal hyperautofluorescence corresponding to the vitelliform deposits bilaterally. Structural optical coherence tomography (OCT) revealed dome-shaped subretinal hyperreflective material between the retinal pigment epithelium and photoreceptor layer in both eyes, consistent with Stage II vitelliform disease in the left eye and an earlier stage in the right eye. OCT angiography excluded choroidal neovascularization in both eyes. Karyotype report and Sanger sequencing show no chromosomal abnormality. A diagnosis of AVMD was established based on clinical and multimodal imaging findings. This case underscores the diagnostic value of multimodal imaging in establishing an accurate diagnosis of AVMD, a condition that carries a generally favorable prognosis when identified early and monitored appropriately. Clinician awareness of AVMD and its distinguishing imaging characteristics is critical to avoid misdiagnosis and ensure timely patient counseling and surveillance.}, }
@article {pmid42520050, year = {2026}, author = {Öncül, H and Dağ, U and Alakuş, MF and Dertsiz Kozan, B and Savar Çağlayan, M}, title = {Association between ABO and Rh blood groups and subtypes of age-related macular degeneration: A cross-sectional study.}, journal = {PloS one}, volume = {21}, number = {7}, pages = {e0354886}, pmid = {42520050}, issn = {1932-6203}, mesh = {Humans ; *ABO Blood-Group System ; Cross-Sectional Studies ; Female ; Male ; Aged ; *Macular Degeneration/blood ; *Rh-Hr Blood-Group System ; Risk Factors ; Middle Aged ; Odds Ratio ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment and is driven by complex genetic, inflammatory, and vascular mechanisms. ABO and Rh blood group antigens, which are expressed on vascular endothelium and involved in immune and hemostatic pathways, have been implicated in various systemic diseases; however, their potential association with AMD phenotypic variation remains unclear. In this cross-sectional study, 488 patients with clinically confirmed AMD from a tertiary referral center were included. AMD was classified as neovascular AMD (wet AMD) or nonneovascular AMD (dry AMD) based on multimodal imaging and standardized diagnostic criteria. ABO and Rh blood group data were obtained from medical records, and individuals with major known AMD risk factors, including smoking, alcohol consumption, and obesity, were excluded to reduce confounding. Associations between AMD subtypes and ABO blood groups and Rh factor were evaluated using the Pearson chi-square test, and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The mean age of participants was 66.9 ± 4.7 years, and 273 patients (55.9%) had neovascular AMD. A statistically significant association was observed between ABO blood group distribution and AMD subtypes (χ[2] = 8.31, p = 0.040). A higher proportion of patients with neovascular AMD had blood group A, whereas blood group B was relatively more common among patients with nonneovascular AMD. However, individual pairwise crude odds ratio analyses did not demonstrate statistically significant associations for specific ABO blood groups. No association was observed for Rh status. These findings suggest a possible modest association between overall ABO blood group distribution and AMD phenotype; however, the clinical significance of this relationship remains uncertain, particularly in the absence of multivariable adjustment. Larger multicenter studies with comprehensive multivariable analyses are warranted.}, }
@article {pmid42520059, year = {2026}, author = {Lu, Z and Cao, H and Ma, C and Zheng, J and Ma, X}, title = {Mapping the Reliability-Readability Gap in the Education of Patients With Age-Related Macular Degeneration Across 6 Large Language Models: Comparative Evaluation Study.}, journal = {JMIR medical informatics}, volume = {14}, number = {}, pages = {e91016}, pmid = {42520059}, issn = {2291-9694}, mesh = {Large Language Models ; Humans ; *Macular Degeneration/therapy ; Reproducibility of Results ; *Patient Education as Topic/standards/methods ; *Comprehension ; }, abstract = {BACKGROUND: Artificial intelligence-generated health information is increasingly used by patients, but its reliability, visible transparency indicators, and readability remain uncertain in specialized ophthalmic conditions such as age-related macular degeneration (AMD).<br><br>OBJECTIVE: This study aimed to evaluate and compare the informational reliability, visible transparency indicators, overall quality, and readability of responses generated by 6 publicly accessible large language models (LLMs) to AMD-related patient-facing prompts under a zero-shot, single-turn prompting scenario.<br><br>METHODS: Thirty English-language AMD-related prompts were curated from Google Trends, the 2023 Chinese AMD guideline, and the 2025 American Academy of Ophthalmology Preferred Practice Pattern. Chinese guideline-derived prompts were translated and reviewed before model querying. Each finalized prompt was entered verbatim into ChatGPT-5.1-auto, DeepSeek-v3.2, Gemini-2.5-Flash-Thinking, Grok 4, Claude-Sonnet 4.5, and Qwen3-Max between October 10 and November 25, 2025. Two senior ophthalmologists (ZL and XM) blinded to model identity independently scored all responses using DISCERN, Ensuring Quality Information for Patients (EQIP), Global Quality Scale, and Journal of the American Medical Association benchmark criteria, with adjudication for disagreements. Readability was assessed using 6 standard formulas against a sixth-grade benchmark. Between-model differences were analyzed using Friedman tests with Holm-adjusted pairwise comparisons.<br><br>RESULTS: A total of 180 responses were analyzed. Interrater agreement was substantial to near-perfect across reliability instruments (&#x3ba;=0.72-0.97). No model met the recommended sixth-grade readability target. Grok 4 achieved the highest scores on reliability-related instruments, including DISCERN (mean 46.40, SD 7.43) and EQIP (mean 74.33, SD 9.07), whereas DeepSeek-v3.2 generated the most readable responses, with the highest Flesch Reading Ease Score (mean 48.23, SD 9.16) and lowest Flesch-Kincaid Grade Level (mean 9.95, SD 1.87). Significant between-model differences were observed across all reliability and readability metrics (all P<.001).<br><br>CONCLUSIONS: Under zero-shot, single-turn prompting conditions, the evaluated public LLMs showed substantial model-dependent differences in AMD-related patient education quality and readability. No model met the sixth-grade readability benchmark, including those with comparatively stronger reliability performance. These findings support clinician oversight, readability optimization, and further evaluation before LLM-generated AMD information is used directly in patient-facing settings.}, }
@article {pmid42521210, year = {2026}, author = {Choi, S and Kim, J and Park, MS and Kwon, S and Cho, BJ}, title = {Real-World Treatment Outcome of Intravitreal Ranibizumab and Aflibercept in Pseudophakic Eyes with Neovascular Age-Related Macular Degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2026.0030}, pmid = {42521210}, issn = {2092-9382}, abstract = {PURPOSE: To evaluate the long-term real-world treatment outcome of intravitreal ranibizumab and aflibercept injections in pseudophakic eyes with neovascular age-related macular degeneration (nAMD), independently of the effect of cataract progression.<br><br>METHODS: Medical records of pseudophakic patients with nAMD who were treatment-na&#xef;ve, underwent intravitreal injection of ranibizumab or aflibercept between March 2010 and August 2023, and then were followed up for at least 1 year were retrospectively reviewed. Demographic and clinical variables, including visual acuity (VA), central subfield thickness (CST), and total number of injections, were analyzed to assess the risk of poor treatment outcome.<br><br>RESULTS: A total of 93 treatment-na&#xef;ve pseudophakic eyes from 93 patients were included, with 46 eyes receiving aflibercept injection. The mean VA improved from 51.0 letters at baseline to 57.4 letters at 3 months showing the greatest improvement, and then gradually declined to 53.0 letters, 52.9 letters, and 49.7 letters at 1, 2, and 5 years after the initiation of injections, respectively. In contrast, the mean CST significantly decreased from 351.2 &#xb1; 114.6 &#x3bc;m to 230.7 &#xb1; 93.5 &#x3bc;m at 3 months, followed by a mild increase to 271.8 &#xb1; 117.1 &#x3bc;m at 1 year, and remained stable at 271.4 &#xb1; 160.5 &#x3bc;m at 2 years. Thereafter, CST gradually decreased reaching 251.7 &#xb1; 125.2 &#x3bc;m by the fifth year. There were no statistically significant differences in VA or CST between the ranibizumab and aflibercept groups throughout the period. Factors associated with poor visual outcome defined as &#x2264; 35 letters at 3 years were solely limited to baseline VA.<br><br>CONCLUSIONS: For eyes with sustained long-term follow-up, the visual outcomes of pseudophakic patients with nAMD, unaffected by cataract progression, were maintained at a good level above baseline over 4 years after intravitreal injection in the real-world, while CST decreased consistently from 2 to 5 years after treatment.}, }
@article {pmid42427844, 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 = {Research square}, volume = {}, number = {}, pages = {}, pmid = {42427844}, issn = {2693-5015}, 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 {pmid42504723, year = {2026}, author = {XinYu, F and Yi, L and Liu, Z}, title = {Targeting of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signaling Pathway in Age-Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy.}, journal = {Journal of biochemical and molecular toxicology}, volume = {40}, number = {8}, pages = {e70968}, pmid = {42504723}, issn = {1099-0461}, mesh = {Humans ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/drug effects ; Animals ; *Eye Diseases/metabolism/therapy/drug therapy/pathology ; Oxidative Stress ; *Aging/metabolism/pathology ; Macular Degeneration/metabolism ; }, abstract = {Age-related eye diseases (AREDs), such as diabetic retinopathy (DR), cataract, glaucoma, age-related macular degeneration (AMD), presbyopia, and represent the primary sources of vision impairment globally. Numerous investigations have indicated that the onset and progression of these conditions are significantly linked to oxidative stress (OS) affecting the eye. The Keap1-Nrf2-ARE signaling pathway is a well-established mechanism that defends the body against OS and inflammation. This pathway is also implicated in the advancement of AREDs. However, the contribution of Nrf2 is likely to be disease-context dependent, and in multifactorial conditions such as glaucoma and dry eye disease, OS should be viewed as one interacting mechanism among several pathogenic processes rather than the sole or dominant driver. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) serves as a key modulator of numerous life processes, playing a critical role in antioxidant mechanisms, anti-inflammatory activities, antifibrotic responses, and cancer development. This review emphasizes the possible role of Nrf2 in the onset and progression of AREDs. Additionally, it explores various Nrf2 activators, encompassing noncoding RNAs and external substances, that regulate Nrf2 expression via distinct pathways within ocular disease models and eye cells, thereby safeguarding them from harmful alterations. However, most evidence supporting Nrf2-targeted interventions in age-related eye diseases remains preclinical, and important issues including disease-specific ocular delivery, target engagement in human tissues, long-term safety, and the potential risks of chronic Nrf2 activation must be addressed before clinical translation can be considered feasible. Consequently, Nrf2 may represent a significant target for the safeguarding of ocular cells against assorted stressors and the prevention of ocular ailments.}, }
@article {pmid42506901, year = {2026}, author = {Chen, J and Li, Y and Xiao, Y and Chen, D and Huang, W and Li, N and Liang, J and Zhan, J and Zhuo, Y and Leng, Y and Zhu, Y}, title = {Association between Pre-diagnostic Macular Thickness With Risk of Age-related Macular Degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004935}, pmid = {42506901}, issn = {1539-2864}, abstract = {PURPOSE: To determine whether specific pre-diagnostic macular thickness are associated with an increased risk of age-related macular degeneration (AMD).<br><br>METHODS: A total of 40,078 UK Biobank participants without baseline AMD who underwent optical coherence tomography (OCT) imaging were included. Macular thickness measurements were obtained via OCT across nine subfields of the Early Treatment Diabetic Retinopathy Study. Latent Profile Analysis (LPA) was employed to classify distinct pre-diagnostic macular thickness profiles, while cox proportional hazards models were utilized to estimate hazard ratios (HRs) between the identified profiles.<br><br>RESULTS: Two distinct pre-diagnostic macular thickness profiles were identified. Compared to profile 1 (n = 31,942), profile 2 (n = 8,136) was characterized by thinner inner and outer superior subfields, alongside thicker central and other outer subfields. Profile 2 was associated with significantly increased AMD risk compared to profile 1 (HR, 1.59; 95% confidence interval [CI], 1.32-1.90; P < 0.001). After adjustment for all covariates, the observed association persisted (HR, 1.39; 95% CI, 1.16-1.67; P < 0.001).<br><br>CONCLUSION: Distinct pre-diagnostic macular thickness patterns are associated with elevated AMD risk. These findings provide novel insights into potential early macular structural changes prior to AMD diagnosis, and may serve as novel biomarkers for early identification of AMD.}, }
@article {pmid42506910, year = {2026}, author = {Bacherini, D and Kawamoto, K and Virgili, G and Rizzo, C and Baumal, CR and Chakravarthy, U and Curcio, CA and Faes, L and Freund, KB and Huang, D and Munk, MR and Pircher, M and Querques, G and Souied, E and Waheed, NK and Schwartz, R}, title = {Do OCTA morphological patterns in neovascular AMD actually matter? A scoping review of clinical utility and terminological overlap.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004936}, pmid = {42506910}, issn = {1539-2864}, abstract = {PURPOSE: Optical coherence tomography angiography (OCTA) has enabled detailed in vivo imaging of macular neovascularization (MNV) in neovascular age-related macular degeneration (nAMD), leading to a proliferation of morphological descriptive terms. This scoping review aimed to systematically map the existing literature on OCTA-based MNV morphology and evaluate its correlation with disease activity.<br><br>METHODS: A systematic literature search covering publications through 2025 was performed. After screening 2,445 titles and obtaining 60 full texts, 43 studies were included. Data on morphological terminology, study design, and correlation with disease activity were extracted and synthesized.<br><br>RESULTS: The included studies, encompassing a total of 2,712 eyes, identified a vast and heterogeneous lexicon of qualitative descriptors, including terms such as "medusa," "sea-fan," and "glomerulus", characterized by significant terminological overlap and inconsistent definitions across studies. Inconsistent, low-certainty associations between specific OCTA morphologies and MNV activity were identified across studies, with findings limited by significant methodological heterogeneity. The evidence for these patterns as reliable biomarkers of disease activity is weak and often contradictory, and several studies were found to use OCTA features to define activity, creating circular arguments that undermine their conclusions.<br><br>CONCLUSION: The current terminology for OCTA morphology in nAMD is fragmented and inconsistently applied. The link between these patterns and disease activity is poorly established, severely limiting their clinical utility. These findings highlight a need for a standardized, consensus-based framework for describing and interpreting OCTA findings in nAMD.}, }
@article {pmid42506959, year = {2026}, author = {Satake, K and Koshiba, S and Haniuda, H and Amano, T and Hiura, M and Ishii, T and Horita, S}, title = {Preclinical Ocular Pharmacokinetics and Efficacy of Novel Tivozanib Eye Drops for Neovascular Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {55}, doi = {10.1167/iovs.67.8.55}, pmid = {42506959}, issn = {1552-5783}, mesh = {Animals ; Rabbits ; *Quinolines/pharmacokinetics/administration &amp; dosage ; Ophthalmic Solutions ; Disease Models, Animal ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage ; *Choroidal Neovascularization/drug therapy/metabolism ; *Phenylurea Compounds/pharmacokinetics/administration &amp; dosage ; *Macular Degeneration/drug therapy/metabolism ; Choroid/metabolism ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Retina/metabolism ; Tissue Distribution ; Macaca fascicularis ; }, abstract = {PURPOSE: In neovascular age-related macular degeneration (nAMD), invasive intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is the current standard of care, highlighting the need for noninvasive eye drop formulations. We aimed to assess the ocular pharmacokinetics and anti-angiogenic efficacy of nanocrystallized tivozanib (nTivo) eye drops in rabbits and monkeys.<br><br>METHODS: We investigated the ocular distribution of nTivo eye drops and conventional microcrystallized tivozanib eye drops in albino and pigmented rabbits. The anti-angiogenic efficacy of nTivo eye drops was evaluated in laser-induced choroidal neovascularization (CNV) model monkeys.<br><br>RESULTS: In pigmented rabbits, nTivo eye drops showed up to 9.5-fold higher drug delivery efficiency to the retina/choroid relative to microcrystal formulations, indicating that nanocrystallization enhances the drug delivery efficiency of tivozanib to posterior eye tissues. Additionally, accumulation of the ocular exposure was observed with the repeated instillation of nTivo eye drops, and the elimination half-life (t1/2) of tivozanib was longer in the retina/choroid (247.5 hours) than in serum (49.7 hours). In comparison to albino rabbits, pigmented rabbits showed higher exposure (3.2-fold) and longer t1/2 (5.7-fold) in the retina/choroid, suggesting that the melanin binding properties of tivozanib potentially contribute to its accumulation and prolonged retention in the retina and choroid. In the monkey CNV model, nTivo eye drops significantly reduced the neovascularization lesion area.<br><br>CONCLUSIONS: The nTivo eye drop formulation may be a potential new treatment option for nAMD due to its preferable ocular pharmacokinetic and anti-angiogenic profiles based on potential contributions of nanocrystallization and the melanin binding properties of tivozanib.}, }
@article {pmid42507292, year = {2026}, author = {Fu, DJ and Riotto, E and Nicholson, L and Fasolo, S and Trivizki, O and Spooner, K and Sivaprasad, S and Faes, L}, title = {Real-World Outcomes of Faricimab for Polypoidal Choroidal Vasculopathy in a Multi-ethnic Cohort: A 12-Month Retrospective Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42507292}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to evaluate 12-month real-world outcomes of faricimab for polypoidal choroidal vasculopathy (PCV) in a multi-ethnic cohort.<br><br>METHODS: This was a&#xa0;single-center retrospective cohort study of consecutive eyes with PCV diagnosed in routine care, treated with intravitreal faricimab, and with complete baseline and 12-month follow-up. One eye per patient was analyzed. Outcomes were reported for treatment-na&#xef;ve and treatment-experienced eyes switched for persistent activity or limited durability. Primary endpoints were change in visual acuity (VA) and central subfield thickness (CST) at 12&#xa0;months. Ethnicity-stratified outcomes were assessed secondarily.<br><br>RESULTS: The cohort comprised 159 eyes (40 treatment-na&#xef;ve, 119 treatment-experienced). In treatment-na&#xef;ve eyes, mean VA improved from 61 (standard deviation [SD] 14) letters at baseline by&#x2009;+&#x2009;6.8 letters (SD 16; P&#x2009;<&#x2009;0.01) at 12&#xa0;months, with CST reduction of -&#xa0;54&#xa0;&#xb5;m (SD 100; P&#x2009;<&#x2009;0.01) and mean 9.6 (SD 4.2) injections. In treatment-experienced eyes, paired VA change at 12&#xa0;months was minimal (+&#x2009;0.27 letters, SD 12; P&#x2009;>&#x2009;0.05), while CST decreased significantly by&#x2009;-&#x2009;40&#xa0;&#xb5;m (SD 110; P&#x2009;<&#x2009;0.01). Eyes received a mean of 8.2 (SD 4.2) faricimab injections over 12&#xa0;months. Exploratory ethnicity-stratified analyses demonstrated baseline heterogeneity across groups, with broadly favorable anatomical and functional outcomes observed across the multi-ethnic cohort, but subgroup sizes precluded comparative efficacy assessment.<br><br>CONCLUSIONS: In routine care, faricimab was associated with clinically meaningful visual improvement in treatment-na&#xef;ve PCV and anatomical improvement in both treatment-na&#xef;ve and -experienced eyes. Prospective studies with adequate ethnic representation are needed to validate these findings.}, }
@article {pmid42509296, year = {2026}, author = {Kananen, F and Bode, H and Ollikainen, M and Immonen, I}, title = {Blood DNA methylation at AMD candidate loci in discordant monozygotic twins.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {42509296}, issn = {2045-2322}, abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment in older adults, with both genetic and environmental factors contributing to disease risk. Epigenetic mechanisms, particularly DNA methylation, may mediate the effects of environmental exposures on disease-relevant genes, yet their role in AMD remains poorly understood. To investigate blood DNA methylation differences associated with AMD severity, we studied 29 monozygotic twin pairs discordant for AMD from the Finnish Twin Cohort. This design controls for genetic background, sex, age, and shared early-life environment. Genome-wide DNA methylation was measured in whole blood using the Illumina HumanMethylation EPIC BeadChip. Analyses were restricted to 263 AMD candidate genes identified through prior genetic, epigenetic, and transcriptomic studies. Of 9,694 analyzed CpG sites, one site within ESYT1 reached statistical significance after multiple testing correction, but the corresponding methylation difference was below our predefined threshold for biological relevance. No CpG sites met both statistical and biological significance criteria. These findings do not provide evidence for large, systemic DNA methylation differences in peripheral blood at established AMD loci, though subtle effects below the detection limit of the current sample size cannot be excluded.}, }
@article {pmid42509399, year = {2026}, author = {Lizzio, RAU and Mattioli, S and Nucci, P}, title = {Massive suprachoroidal haemorrhage in a patient with neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-026-04774-w}, pmid = {42509399}, issn = {1476-5454}, }
@article {pmid42510615, year = {2026}, author = {Szulim, D and Kucharska, E and Machalińska, A and Kuprjanowicz, L and Czupryński, P and Szczuko, M}, title = {Effect of a Nutraceutical-Oriented Dietary Intervention on Serum Carotenoids and Antioxidant Vitamin Concentrations in Patients with Neovascular Age-Related Macular Degeneration.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {7}, pages = {}, doi = {10.3390/antiox15070884}, pmid = {42510615}, issn = {2076-3921}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is one of the most common causes of irreversible impairment of central vision in the elderly population. Although anti-VEGF therapy remains the standard treatment for neovascular AMD, nutritional factors may influence disease progression and retinal health. The aim of this prospective controlled study was to evaluate the effects of an individualized dietary intervention with nutraceutical characteristics on serum concentrations of lutein, zeaxanthin, lycopene, vitamin A, and vitamin E in patients with neovascular AMD receiving anti-VEGF therapy.<br><br>METHODS: This prospective controlled study included 43 patients with neovascular AMD who completed a six-month follow-up period. Participants were allocated to either a control group receiving anti-VEGF therapy alone or an intervention group receiving anti-VEGF therapy combined with an individualized dietary plan. The dietary intervention emphasized foods naturally rich in carotenoids, antioxidant vitamins, trace elements, dietary fiber, and omega-3 fatty acids. Serum concentrations of lutein + zeaxanthin, lycopene, vitamin A, and vitamin E were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at baseline and after six months.<br><br>RESULTS: Serum lutein + zeaxanthin concentrations increased significantly within both groups (control 0.31 &#xb1; 0.61 to 0.49 &#xb1; 0.69 mg/L; intervention 0.51 &#xb1; 0.54 to 0.87 &#xb1; 0.89 mg/L). The increase was numerically larger in the intervention group, but the between-group difference was not statistically significant after adjustment for baseline concentrations (ANCOVA, p = 0.30). Lycopene increased significantly within the intervention group only (0.20 &#xb1; 0.15 to 0.43 &#xb1; 0.30 &#x3bc;mol/L); the between-group difference was not significant after baseline adjustment (p = 0.24). Vitamin A increased significantly within both groups and vitamin E within the intervention group only; however, no between-group difference remained significant after baseline adjustment (vitamin A p &#x2248; 1.00, vitamin E p = 0.96). The greatest increase in lutein + zeaxanthin concentrations was observed among participants with improved retinal status. These descriptive findings should be interpreted cautiously because subgroup analyses were not powered. Correlation analyses performed after six months demonstrated positive associations between serum lutein + zeaxanthin, lycopene, and vitamin A concentrations.<br><br>CONCLUSIONS: An individualized dietary intervention rich in naturally occurring bioactive compounds was associated with within-group improvements in serum carotenoid and antioxidant vitamin status. After adjustment for baseline values, between-group differences did not reach statistical significance, consistent with the exploratory, non-powered pilot design. These preliminary findings, including the observed effect sizes, are intended to inform the design of an adequately powered future study rather than to establish a between-group benefit of dietary management. Particularly pronounced changes were observed for lutein + zeaxanthin and lycopene concentrations. These findings support the potential role of dietary management as an adjunct to anti-VEGF therapy. However, given the nature of the study and the relatively small sample size, larger multicenter studies are needed to confirm these observations.}, }
@article {pmid42510910, year = {2026}, author = {Kim, YR and Seol, A and Lee, SJ and Kim, JE and Song, HJ and Lim, SJ and Wang, SH and Ryu, YE and Choi, YW and Choi, SI and Hwang, DY}, title = {α-Iso-Cubebene Alleviates AMD-like Retinal Injury Through Modulation of Oxidative Stress and Inflammatory Response.}, journal = {Current issues in molecular biology}, volume = {48}, number = {7}, pages = {}, doi = {10.3390/cimb48070669}, pmid = {42510910}, issn = {1467-3045}, support = {F25YY8109033//National Research Foundation of Korea/ ; F26YY8109033//National Research Foundation of Korea/ ; }, abstract = {Although oxidative stress plays a critical role in age-related macular degeneration (AMD) progression, natural product-derived single compounds against AMD remain largely unexplored. We investigated the protective effects and underlying mechanism of α-iso-cubebene against AMD-like retinal injury. Alterations in key phenotypes for AMD were analyzed in AMD-mimicking models using ARPE-19 cells co-treated with blue light (BL) and N-retinylidene-N-retinylethanolamine (A2E), as well as BL-exposed BALB/c mice. In BL+A2E-treated ARPE-19 cells, α-iso-cubebene reduced intracellular reactive oxygen species (ROS) and nitric oxide (NO) production and restored superoxide dismutase (SOD) activity and nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting enhancement of the antioxidant defense system. Furthermore, α-iso-cubebene improved cell viability, reduced apoptotic cell populations, and regulated apoptosis-related signaling pathways under oxidative stress conditions. It also attenuated cyclooxygenase-2 (COX-2)-mediated inducible nitric oxide synthase (iNOS) signaling and was associated with reduced inflammasome-related signaling. Importantly, these protective effects were consistently observed regarding the protection of histopathological structure and normalization of inflammatory cytokines in the retina of BL-exposed BALB/c mice. Collectively, our results demonstrate that α-iso-cubebene, as a potential therapeutic candidate, alleviates AMD-like retinal injury and was associated with enhanced antioxidant responses and reduced inflammatory and apoptotic signaling markers.}, }
@article {pmid42511632, year = {2026}, author = {Abdouh, M and Goyeneche, A and Yurchuk, M and Burnier, MN}, title = {Induction of Oxidative Stress on Retinal Pigment Epithelial Cells Triggered a Proangiogenic Environment.}, journal = {International journal of molecular sciences}, volume = {27}, number = {14}, pages = {}, pmid = {42511632}, issn = {1422-0067}, abstract = {Dry age-related macular degeneration (AMD) can progress to wet AMD when leaking capillaries grow under the macula. Although rare, this transition holds significant risk as it causes more rapid and severe vision loss. Oxidative stress is damaging to cellular components and plays a pivotal role in chronic diseases. We aim to determine whether oxidative stress in retinal pigment epithelial (RPE) cells elicits a proangiogenic microenvironment. We exposed human primary RPE cells to hydrogen peroxide (H2O2), and we analyzed their metabolic activity, and the production of reactive oxygen species (ROS) and angiogenic factors. In addition, we evaluated the potential of RPE cell-conditioned medium (CM) to induce HUVEC cell tube formation. RPE cells exposed to H2O2 displayed a dose-dependent decrease in their metabolic activity, and increased ROS levels. The analysis of the CM of exposed RPE cells revealed differential expression of a panel of proangiogenic factors. Notably, the expression of the major angiogenic factors (VEGF, FGF) was increased. Exposure of HUVEC cells to the CM of H2O2-exposed RPE cells promoted tube formation suggestive of microvessel formation. Our findings bring new insights into the role of oxidative stress in altering RPE cell behavior that might have consequences in the progression of AMD towards the exudative form.}, }
@article {pmid42512063, year = {2026}, author = {Ikeuchi, E and Miki, A and Oka, T and Kishimoto-Kishi, M and Nakamura, M}, title = {Baseline Biomarkers Associated with Early Anatomical Response After Faricimab Loading Therapy in Treatment-Naïve Neovascular Age-Related Macular Degeneration.}, journal = {Biomedicines}, volume = {14}, number = {7}, pages = {}, doi = {10.3390/biomedicines14071590}, pmid = {42512063}, issn = {2227-9059}, abstract = {Background/Objectives: We identified baseline factors associated with early anatomical response to faricimab. Methods: This single-center retrospective study included 78 treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) receiving three monthly faricimab injections. Eyes with complete resolution of intraretinal and subretinal fluid on optical coherence tomography (OCT) at 16 weeks constituted the fluid-free group, and the remaining eyes were assigned to the persistent-fluid group. Baseline OCT features (including subretinal hyperreflective material [SHRM], pigment epithelial detachment [PED] subtypes, and central retinal and choroidal thickness) and clinical characteristics were compared, and ARMS2 (rs10490924) and CFH (rs800292) were genotyped as an exploratory analysis. Multivariable logistic regression identified associated factors. Results: Fifty-five eyes (70.5%) achieved complete fluid resolution. In multivariable analysis, SHRM was independently associated with a favorable early anatomical response, and fibrovascular PED with incomplete early fluid resolution (p = 0.019 and p = 0.026); in an exploratory model, the ARMS2 risk allele was associated with incomplete fluid resolution (p = 0.008), whereas CFH was not. Conclusions: In treatment-naïve nAMD, baseline SHRM was associated with a favorable early anatomical response to faricimab, whereas fibrovascular PED and a higher ARMS2 T-allele count were associated with incomplete early fluid resolution. These characteristic OCT and genetic features may help identify eyes at risk of an incomplete early response.}, }
@article {pmid42512784, year = {2026}, author = {Sambhara, D and Abbey, AM and Eichenbaum, DA}, title = {Home OCT Monitoring as a Safety Net for Early Detection of Recurrent Disease Activity in Neovascular Age-Related Macular Degeneration Under Standard Care.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {7}, pages = {}, doi = {10.3390/medicina62071241}, pmid = {42512784}, issn = {1648-9144}, abstract = {Background and Objectives: Despite recent advancement, neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible vision loss. Undertreatment, fewer anti-VEGF injections and longer intervals than in clinical trials have been associated with sub-optimal visual outcomes. Visit-based regimens (Treat-and-Extend, PRN) may permit intervals of unrecognized retinal fluid between office visits. A home OCT system with near-daily self-imaging provides frequent structural retinal information between office visits that can support early detection of persistent or recurring fluid. The objective was to evaluate the duration and magnitude of fluid exposure between standard care visits and estimate the potential to shorten that exposure. Materials andMethods: Ad hoc analysis of three cohorts of treatment naïve and experienced nAMD eyes managed by standard care while participating in observational studies of the home OCT system, with treating physicians masked to home OCT data. AI-based analysis of fluid volume, rate of change and time of fluid onset was performed. Results: Data from 209 participants, mean age 76.4 years, 53% female, who performed 10,110 scans (6.0 scans/week) were analyzed. An amount of 119 eligible eyes provided data from 185 standard care intervals. Persistent or recurring fluid was identified in 121 (65%) intervals, on average 32 days prior to the next office visit. Of these, 84 (69%) had potential visit advancement within labeled minimal treatment intervals of 19 days. Mean fluid volume at the earliest possible notification was 26 nL and recurrence rate averaged 4.4 nL/day. Conclusions: A substantial proportion of patients experience unrecognized disease activity between visits. Home OCT monitoring provides adjunctive information to support early detection of fluid and may facilitate timely clinical evaluation. In this context, such monitoring may be considered reasonable and necessary to inform management of nAMD within established standards of care, while not replacing clinician-directed diagnosis or treatment decisions.}, }
@article {pmid42512849, year = {2026}, author = {Živković, MLJ and Zlatanović, M and Zlatanović, N and Brzaković, M and Jovanović, M}, title = {Real-World Faricimab for Treatment-Naïve Neovascular AMD and Diabetic Macular Edema: 24-Month Outcomes from a Single-Center Pilot Cohort in South-Eastern Europe.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {7}, pages = {}, doi = {10.3390/medicina62071307}, pmid = {42512849}, issn = {1648-9144}, abstract = {Background and Objectives: Faricimab, the first bispecific antibody targeting VEGF-A and angiopoietin-2, has demonstrated durable efficacy in pivotal phase 3 trials for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Real-world data on treatment-naïve patients managed with fixed-interval maintenance protocols, particularly from South-Eastern Europe, remain limited. This pilot study evaluated 24-month outcomes of intravitreal faricimab in treatment-naïve nAMD and DME, using a standardized four-injection loading phase followed by fixed every-16-week (Q16W) maintenance. Materials and Methods: This study conducted a retrospective, observational, single-center pilot cohort study of 20 consecutive treatment-naïve eyes (9 nAMD, 11 DME). All patients received four monthly loading injections followed by a fixed every-16-week (Q16W) maintenance schedule, supplemented by discretionary additional injections for residual or recurrent disease activity (215 injections total; mean 10.75 ± 0.79 per patient; range 9-12). Primary outcomes were changes in central foveal thickness (CFT) and best-corrected visual acuity (BCVA; Snellen lines with ETDRS letter equivalents) at months 4 and 24. Prespecified secondary analyses included bootstrap 95% confidence intervals, a linear mixed-effects model with a time × disease-group interaction, Bayesian credible intervals with weakly informative priors, false-discovery-rate (FDR) correction, and a minimum detectable effect-size analysis. Results: All 20 eyes completed 24-month follow-up. In nAMD, mean CFT decreased by 186.9 ± 71.9 µm (35.9%; bootstrap 95% CI 148.1-236.0; p < 0.001; d = 2.60), and BCVA improved by 3.89 ± 0.78 Snellen lines (~19 ETDRS letters; 95% CI 3.44-4.33; p < 0.001; d = 4.97). In DME, CFT decreased by 197.7 ± 65.7 µm (39.3%; 95% CI 162.5-237.3; p < 0.001; d = 3.01), and BCVA improved by 4.55 ± 1.04 lines (~23 ETDRS letters; 95% CI 4.00-5.09; p < 0.001; d = 4.39). All 20 eyes (100%) achieved ≥ 3 Snellen lines gain and ≥20% CFT reduction; 80% reached final BCVA ≥ 7 lines. A linear mixed-effects model showed a significant time effect (p < 0.001) but no time × group interaction (CFT p = 0.84; BCVA p = 0.51), indicating concordant trajectories across diseases. Bayesian analysis with weakly informative priors yielded posterior P(|d| > 0.8) ≥ 0.99 for all primary outcomes. After FDR correction, all pre-specified primary comparisons remained significant. The minimum detectable effect size with the realized sample sizes (Cohen's d ≈ 0.66 combined, 1.07 nAMD, 0.94 DME at 80% power) was substantially below all observed effect sizes. No ocular or systemic adverse events were recorded. Conclusions: In this small, single-center, treatment-naïve pilot cohort, a fixed Q16W faricimab maintenance schedule with discretionary additional injections was associated with durable anatomical and functional improvements over 24 months in both nAMD and DME, with no adverse events recorded across 215 injections. Given the limited sample, these findings should be regarded as hypothesis-generating. The high responder rates likely reflect the cohort's substantial baseline visual impairment (mean baseline BCVA ~20/120-20/200), which provides greater absolute capacity for measurable gain than in higher-acuity registration trial populations. These pilot data support fixed-interval faricimab as a logistically feasible candidate strategy in resource-constrained settings and should be confirmed in larger multicenter cohorts using standardized ETDRS acuity assessment.}, }
@article {pmid42513510, year = {2026}, author = {Piñero, DP and Bataille, L and Martín, JCM and Pérez-Cambrodí, RJ}, title = {Clinician and Patient Perspectives of Geographic Atrophy Age-Related Macular Degeneration in Spain: A Preliminary Exploratory Study.}, journal = {Journal of clinical medicine}, volume = {15}, number = {14}, pages = {}, pmid = {42513510}, issn = {2077-0383}, support = {Unrestricted grant//Samsara Vision/ ; }, abstract = {Background/Objectives: We aim to characterize, through a survey-based approach conducted in Spain, the perspectives of healthcare professionals (HCPs) and patients regarding geographic atrophy (GA). Methods: A survey-based study assessed ophthalmologists', optometrists', and AMD patients' perceptions and practices regarding geographic atrophy management in Spain, including disease journey challenges. Results: The study sample comprised 30 ophthalmologists, 35 optometrists, and 37 patients. A substantial majority of ophthalmologists followed a specific protocol for the management of GA, in which optical coherence tomography, visual acuity assessment, and fundus examination constituted the core diagnostic procedures. Although most HCPs reported recommending low vision aids, only 5.4% of patients reported having received such a recommendation or prescription (p < 0.001). Considerable variability among the optometrists surveyed was identified regarding visual rehabilitation programmes involving low vision aids. Furthermore, while most ophthalmologists and optometrists reported having provided various types of disease-related information, a significantly lower proportion of patients reported having received information on several aspects such as the disease itself (p < 0.001), disease progression (p < 0.001), impact on quality of life (p < 0.001), or low vision aids (p < 0.001). Multiple limitations in daily living activities were reported by patients, with those diagnosed with GA experiencing significantly greater difficulty reading television subtitles (p = 0.026) and performing manual tasks (p = 0.005). Conclusions: HCPs appear to follow specific protocols and guidelines in the management of GA; however, a potential deficit in effective HCP-patient communication has been identified that should be investigated further.}, }
@article {pmid42514118, year = {2026}, author = {Tsvetkov, PO and Tiulina, VV and Iomdina, EN and Petrov, SY and Kushnarevich, NY and Suleiman, EA and Filippova, OM and Markelova, OI and Papyan, VN and Chistyakov, TA and Bougaev, AA and Shebardina, NG and Shishkin, ML and Lipatov, DV and Chistyakov, DV and Senin, II and Mitkevich, VA and Zernii, EY}, title = {Fast nanoDSF Tear Fluid Profiling: Toward Diagnosis of Age-Related Macular Degeneration.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {42514118}, issn = {2075-1729}, support = {24-15-00171//Russian Science Foundation/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in older adults. An important challenge is the recognition of its early asymptomatic stages and the monitoring of its progression, which requires reliable biomarkers. Growing evidence indicates that AMD-related biochemical changes are reflected in the proteome of tear fluid (TF). Although TF is a non-invasive and easily collectable diagnostic material, its proteomic analysis is complex and costly and therefore has limited clinical value. Methods: In this pilot single-center retrospective cross-sectional study, we developed a new method for dry AMD screening based on analysis of nano-differential scanning fluorimetry (nanoDSF) tear protein denaturation profiles (TDPs) within 15 min. The TDPs were recorded in representative groups of dry AMD patients (37% early, 48% intermediate, 15% geographic atrophy), and in control groups, including patients with refractive abnormalities (basic control), other retinal degenerative diseases (diabetic retinopathy, peripheral retinal dystrophy), or TF-affecting conditions (dry eye syndrome). High-dimensional TDP data were processed using unsupervised machine learning followed by k-means cluster analysis. Results: The presented pipeline distinguished AMD from the basic control with 74% accuracy and a sensitivity of 0.81 without relying on prior labels. The specificity of AMD detection was confirmed by its effective differentiation from diabetic retinopathy (72%; 0.74), peripheral retinal dystrophy (79%; 0.76) and dry eye disease (76%; 0.81). Classifying the AMD group from the entire population of other patients yielded an accuracy of 71% and a sensitivity of 85%, with a false-negative rate of only 15%. Conclusions: This study is a proof of concept for the nanoDSF-based approach, which can be considered a fast, cost-effective, and convenient tool for population screening for dry AMD, suitable for use in preventive medicine and public health.}, }
@article {pmid42514168, year = {2026}, author = {Desmettre, T and Mordon, S}, title = {Photobiomodulation in Age-Related Macular Degeneration: A Mitochondrial Bioenergetic Framework and Translational Perspective.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {42514168}, issn = {2075-1729}, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in aging populations. While effective treatments exist for neovascular AMD and, more recently, geographic atrophy, no widely accepted therapy prevents disease progression in earlier stages. Photobiomodulation (PBM) has emerged as a potential approach to modulate retinal metabolism. This review examines the biological mechanisms proposed to explain PBM effects and explores how mitochondrial physiology may support a bioenergetic framework linking these mechanisms to retinal function in AMD. Methods: We conducted a targeted review of experimental and clinical literature addressing photobiomodulation, mitochondrial function, and retinal metabolism in AMD. Results: Experimental studies indicate that PBM may influence mitochondrial activity through multiple mechanisms, including modulation of cytochrome c oxidase, nitric oxide photodissociation, and redox signaling pathways. However, the diversity of mechanisms and variability of clinical outcomes suggest that the biological basis of PBM remains incompletely understood. Emerging insights from mitochondrial physiology, including the debated concept of local thermal microenvironments, support interpreting PBM effects as modulation of mitochondrial bioenergetics rather than isolated molecular pathways. Conclusions: We propose a conceptual framework in which PBM responses are governed by the interaction between a dose-dependent bioenergetic window and the mitochondrial functional reserve of retinal cells. Within this model, therapeutic effects are most likely when PBM is delivered within an optimal range of stimulation and in retinal tissues where mitochondrial dysfunction remains partially reversible. This framework may help explain variability across studies and support more rational use of PBM in early and intermediate AMD.}, }
@article {pmid42514939, year = {2026}, author = {Wang, S and Liu, L and Zeng, X and Tang, C and Chen, W and Li, X and Lu, W}, title = {Nanocarrier-Mediated Non-Invasive Drug Delivery for Wet Age-Related Macular Degeneration: Advances and Translational Challenges.}, journal = {Pharmaceutics}, volume = {18}, number = {7}, pages = {}, doi = {10.3390/pharmaceutics18070861}, pmid = {42514939}, issn = {1999-4923}, support = {2023YFC2506100//National Key Research and Development Program of China/ ; 82220108016//National Natural Science Foundation of China/ ; U25A6002//National Natural Science Foundation of China/ ; 82471087//National Natural Science Foundation of China/ ; 2024A1515030268//Natural Science Foundation of Guangdong Province grant/ ; 20250ZLH08//Research Funds of the State Key Laboratory of Ophthalmology/ ; GCCRC-2026006//Program for Supporting and Cultivating Outstanding Scientific and Technological Talents, Zhongshan Oph-thalmic Center, Sun Yat-sen University/ ; GJYXQN-001//Program for Supporting and Cultivating Outstanding Scientific and Technological Talents, Zhongshan Oph-thalmic Center, Sun Yat-sen University/ ; //GBRCE for Major Blinding Eye Diseases Prevention and Treatment/ ; }, abstract = {Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose-safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management.}, }
@article {pmid42515909, year = {2026}, author = {Ahirwar, H and Singhai, H and Rathee, S and Soni, S and Patil, UK}, title = {Harnessing Natural Bioactive Compounds for Ocular Health: A Comprehensive Review.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128473797260709112308}, pmid = {42515909}, issn = {1873-4286}, abstract = {Ocular disorders such as age-related macular degeneration, cataract, dry eye disease, and diabetic retinopathy represent a growing global public health burden. Natural bioactive compounds, particularly carotenoids, flavonoids, and traditional herbal extracts, have demonstrated significant antioxidant, antiinflammatory, and neuroprotective effects on ocular tissues. However, the clinical translation of these phytomolecules is often limited by poor solubility, low stability, and inadequate ocular bioavailability. Recent advances in nanotechnology have enabled the development of targeted delivery platforms, including nanoparticles, nanoemulsions, hydrogels, and liposomes, which enhance tissue-specific delivery, bioavailability, and therapeutic efficacy. This review critically evaluates current evidence from in vitro, in vivo, and clinical studies on the role of natural compounds in ocular health, highlighting their mechanisms of action, safety profiles, and pharmacological potential. Furthermore, the integration of traditional medicinal systems with modern ophthalmic strategies, supported by personalised nanoformulation approaches, offers promising avenues for holistic and patient-centred eye care. Key challenges related to standardisation, regulatory compliance, quality control, and large-scale manufacturing are discussed, along with future directions for bioprospecting novel ocular bioactives and advancing integrative strategies for sustainable eye health management.}, }
@article {pmid42517850, year = {2026}, author = {Smith, SR and Hyman, MJ and Moir, JT and Yehia, M and Flores, A and Skondra, D}, title = {Association of Antibiotic Use and New-Onset ICD Coding of Geographic Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {58}, doi = {10.1167/iovs.67.8.58}, pmid = {42517850}, issn = {1552-5783}, abstract = {PURPOSE: To determine whether exposure to antibiotics is associated with new-onset International Classification of Diseases (ICD) coding of geographic atrophy (GA).<br><br>METHODS: This case-control study of patients ages sixty and older used health insurance claims data from the Merative MarketScan Research Databases. A total of 3254 cases with new-onset ICD coding of GA between 2019 and 2021 were matched by year to 3249 controls without GA using propensity scores estimated by age, hypertension, U.S. Census Bureau region, and Charlson Comorbidity Index. For cases, we analyzed prescription drug claims of antibiotics in the two years before GA diagnosis. For controls, we analyzed claims in the two years before a randomly selected eye examination. We calculated the odds of new-onset ICD coding of GA controlling for age-related macular degeneration risk factors.<br><br>RESULTS: Exposure to any antibiotics (OR = 1.25; 95% confidence interval [CI], 1.11-1.41; P < 0.001), tetracyclines (OR = 1.18; 95% CI, 1.03-1.36; P = 0.021), quinolones (OR = 1.16; 95% CI, 1.03-1.31; P = 0.017), or broad-spectrum antibiotics (OR = 1.20; 95% CI, 1.07-1.34; P = 0.003) was associated with increased odds of new-onset ICD coding of GA. Greater cumulative day supply was associated with increasing odds, suggesting a dose-dependent relationship.<br><br>CONCLUSIONS: Exposure to antibiotics is associated with increased odds of new-onset ICD coding of GA. This association may be dose dependent. These findings suggest that antibiotic exposure could be a novel modifiable risk factor for GA, although this conclusion is tempered by potential confounding by health status or misclassification of GA and by multiple comparisons. Further investigation will be needed to validate these findings.}, }
@article {pmid42517922, year = {2026}, author = {Li, J and Ng, K and Sebag, J and Ling, S and Jin, G and Wang, T and Jia, X and Deng, J and Sun, Y}, title = {Clinical characteristics and treatment willingness of outpatients with vitreous floaters: a real-world study in China.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42517922}, issn = {1435-702X}, support = {A2024471//Medical Scientific Research Foundation of Guangdong/ ; }, abstract = {PURPOSE: Vision Degrading Myodesopsia from vitreous floaters is underappreciated as a disease. We characterized the demographic and clinical profiles of outpatients with vitreous floaters in a real-world Chinese outpatient clinic setting.<br><br>METHODS: A cross-sectional study was conducted on outpatients with the chief complaint of floaters between 2022 and 2025. Age, gender, systemic history, refractive status, and treatment willingness were assessed. Fundus imaging using scanning laser ophthalmoscopy diagnosed posterior vitreous detachment (PVD).<br><br>RESULTS: Enrolled were 589 phakic patients (205 males, 384 females). Females (65.2% of the study population) were older (48.9&#x2009;&#xb1;&#x2009;13.4 years) than males (43.8&#x2009;&#xb1;&#x2009;14.9 years) (P&#x2009;<&#x2009;0.001). Bilateral vitreous floaters were present in 29.5% of patients who were younger (43.4&#x2009;&#xb1;&#x2009;15.1 years) than those with unilateral symptoms (48.7&#x2009;&#xb1;&#x2009;13.4 years) (P&#x2009;<&#x2009;0.001). Myopia (median refraction&#x2009;-&#x2009;5.00D; range: -0.50D to -14.00D) was present in 231/589 (39.2%), and myopic patients were younger (38.9&#x2009;&#xb1;&#x2009;12.0 years) than non-myopic patients (52.4&#x2009;&#xb1;&#x2009;12.8 years; P&#x2009;<&#x2009;0.001). Myopia prevalence was lower in females (34.9%) than males (47.3%) (P&#x2009;=&#x2009;0.003), and lower in unilateral (35.2%) than bilateral cases (48.9%) (P&#x2009;=&#x2009;0.002). The fundus was normal in 420/589 (71.3%). The most common abnormalities were peripheral retinal degeneration (45/589, 7.6%), retinal breaks (25/589, 4.2%), PVD (19/589, 3.2%), retinal hemorrhage (18/589, 3.1%), and age-related macular degeneration (16/589, 2.7%), The overwhelming majority (385/420, 91.7%) expressed a willingness to receive treatment to alleviate floater symptoms.<br><br>CONCLUSIONS: In real-world China, outpatients with vitreous floaters are primarily young and myopic, with bilateral symptoms. The high willingness to undergo treatment underscores the unmet need for safe and effective therapies for vitreous floaters in China.}, }
@article {pmid42518077, year = {2026}, author = {Grant, P and Szlyk, JP and Royster, M and Jackson, CC and Seiple, W}, title = {Evaluation of a Self-Guided Eye Movement Training for Individuals with Central Vision Loss.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {}, number = {}, pages = {}, pmid = {42518077}, issn = {1475-1313}, abstract = {PURPOSE: To evaluate reading performance following an 8-week self-guided eye-movement training programme in people with central vision loss.<br><br>METHODS: Thirty-three adults with a retinal disease affecting the central retina, a documented central scotoma and best-corrected visual acuity between 6/21 and 6/120 in the better-seeing eye were enroled. Of these, 25 participants completed a self-guided eye-movement training programme in a clinical setting, for 2&#x2009;h per week over 8 weeks. To assess the feasibility of remote delivery, eight participants engaged with the same training platform at home. The primary outcome was maximum reading speed, measured binocularly using Minnesota Low Vision Reading (MNREAD) acuity charts. Visual acuity, depression, adaptation to vision loss and self-reported visual function measures were collected at baseline and following the training period.<br><br>RESULTS: Reading speed increased significantly from baseline following training, by an average of 23&#x2009;+&#x2009;24.6 words per minute (wpm), representing a 55% gain. Median reading speed increased by an average of 22.6 wpm for the in-clinic group (n&#x2009;=&#x2009;25) and 24.3 wpm for the home-based group (n&#x2009;=&#x2009;8). These findings suggest that self-guided training can enhance reading performance effectively and may be suitable for implementation in both clinical and remote settings.<br><br>CONCLUSIONS: The self-guided eye movement training programme offers an effective and accessible approach to improve reading performance in individuals with central vision loss. This approach has the potential to complement standard care while broadening access to vision rehabilitation services across both clinical and remote settings.<br><br>GOV ID: NCT01853930 (5-10-2013).}, }
@article {pmid42518473, year = {2026}, author = {Guidi, L and Cascone, MG and Riccio, G and Patri, S and Dabas, R and Lavista, L and Camposeo, A and Pisignano, D and Rosellini, E and Kamaly, N}, title = {Light-Triggered and Sustained Delivery of Dexamethasone Using Chitosan-Coated PLGA Nanoparticles for Posterior Eye Disease Treatment.}, journal = {ACS omega}, volume = {11}, number = {27}, pages = {40218-40231}, doi = {10.1021/acsomega.6c02332}, pmid = {42518473}, issn = {2470-1343}, abstract = {Degenerative eye disorders (DEDs) such as age-related macular degeneration and diabetic retinopathy pose significant therapeutic challenges due to anatomical barriers limiting drug access to posterior ocular tissues. Current treatments, including intravitreal injections, offer localized delivery but require repeated administration, increasing risks and reducing patient compliance. This study introduces a dual-functional nanoparticulate platform for sustained and light-triggered delivery of dexamethasone, a corticosteroid widely used in DED management. Poly-(lactic-co-glycolic acid) (PLGA) nanoparticles were fabricated via nanoprecipitation, coloaded with dexamethasone and the near-infrared (NIR)-responsive dye IR820, and coated with chitosan to enhance mucoadhesion. Physicochemical characterization confirmed nanoscale size, monodispersity, and positive surface charge upon chitosan coating. Drug release studies revealed biphasic kinetics, with chitosan-coated formulations exhibiting prolonged release compared to uncoated particles. Under irradiation (800 nm), photothermal activation mediated by a NIR-absorbing dye induced a 2.0-2.3-fold increase in dexamethasone release during early exposure phases, enabling on-demand dosing. Cyto- compatibility assays on NIH-3T3 fibroblasts confirmed high cell viability (>70%) across all formulations and exposure conditions. These findings demonstrate a robust, light-responsive, mucoadhesive nanoparticle system with the potential to improve therapeutic precision and reduce invasiveness in posterior eye disease treatment.}, }
@article {pmid42518711, year = {2026}, author = {Mansour, HA and Eandi, CM and Pichi, F and Foster, RE and Charbaji, SA and Chakraborty, D and Ellabban, AA and Belotto, S and Abu Serhan, H and Magnin, S and Lopez-Guajardo, L and Pérez-Salvador García, E and Schwartz, SG and Stewart, MW and Rey, A and Jürgens, I and Casella, AMB and Upadhyay, A and Sheth, JU and Lima, LH and Sinawat, S and Abengoechea, S and Capella, MJ and Viver Oller, S and Elizalde, J and Kheir, WJ and Mammo, D and Barbosa, GCS and Villegas, VM and Desai, A and Tripathy, K and Bala, S and Mohan, N and Elnahry, AG and Uwaydat, SH and Cherfan, DG and Parodi, MB and Mansour, AM}, title = {Visual Gains with Faricimab vs Aflibercept 8 mg in Naïve Retinovascular Disease: Global Real-World Cases and Literature Review.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {622037}, doi = {10.2147/OPTH.S622037}, pmid = {42518711}, issn = {1177-5467}, abstract = {BACKGROUND: To compare the visual gains of faricimab and aflibercept 8 mg as first-line in real-world management of retinovascular diseases.<br><br>METHODS: Retrospective multicenter interventional case series with retinovascular diseases initiated on faricimab or aflibercept 8 mg till August 30, 2025. Main outcome measure was visual gain in logMAR. Linear mixed-effects model was used to compare vision increase between the two drug groups. In addition, comparative Phase 3 trials were supplemented by a literature review of treatment-na&#xef;ve eyes using major databases till September 30, 2025.<br><br>RESULTS: We collected 500 treated eyes from 35 collaborating centers. The treatment groups included 395 eyes receiving faricimab vs 105 receiving aflibercept 8 mg distributed into neovascular macular degeneration (270 vs 58), diabetic macular edema (97 vs 39) and macular edema associated with retinal vein occlusion (28 vs 8). Adjusted visual gains were comparable between the two drugs in various retinal categories (p=0.672).<br><br>CONCLUSION: Visual acuity improved significantly and equally in both aflibercept 8 mg and faricimab in several treatment-na&#xef;ve retinovascular diseases.}, }
@article {pmid42518791, year = {2026}, author = {Cohen, Y and Usdin, M and McLeod, M and Kikuchi, Y and Zhang, M and Yang, Q and Mesquida, M}, title = {Deep Learning-Based Quantification of Vitreous Hyperreflective Foci as a Biomarker for Intraocular Inflammation.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101263}, doi = {10.1016/j.xops.2026.101263}, pmid = {42518791}, issn = {2666-9145}, abstract = {OBJECTIVE: To develop and validate an artificial intelligence (AI)-driven pipeline to quantify vitreous hyperreflective foci (vHRF) from OCT images and assess their association with intraocular inflammation (IOI).<br><br>DESIGN: A retrospective analysis of a multicenter double-masked placebo-controlled clinical trial cohort.<br><br>SUBJECTS: A clinical analysis cohort of 369 patients from the GALLEGO clinical trial (Galegenimab vs. placebo in patients with geographic atrophy, clinical trial ID: NCT03972709).<br><br>METHODS: We trained a deep learning segmentation model, U-Net Transformer (UNETR) with a Vision Transformer backbone on 491 OCT B-scans with expert vHRF annotations from the GALLEGO, BURGUNDY (neovascular age-related macular degeneration; NCT04567303), and DOVETAIL (uveitic macular edema; NCT06771271) clinical trials. We applied the optimized model to a clinical analysis cohort from the GALLEGO clinical trial, comprising 1049 OCT volumes (34 images of IOI-positive cases), and evaluated the association between the resulting quantitative vHRF metrics and clinically diagnosed IOI.<br><br>MAIN OUTCOME MEASURES: Segmentation performance and the association of quantitative vHRF metrics with clinically diagnosed concurrent IOI, including receiver operating characteristic, precision-recall, predictive value, and eye-clustered generalized estimating equation analyses.<br><br>RESULTS: The UNETR model demonstrated strong segmentation performance. In the clinical cohort, IOI-positive eyes showed significantly elevated vHRF metrics (P < 0.001), and vHRF volume density was the strongest biomarker for concurrent IOI detection with an area under the receiver operating characteristic curve of 0.84. In eye-clustered logistic generalized estimating equation models, 5 filtered biomarkers were significantly associated with inflammation, with the strongest association for filtered vHRF density [vHRF/&#x3bc;m[3]] (odds ratio per standard deviation 1.62, 95% confidence interval 1.26-2.07, P < 0.001). At the optimal threshold for vHRF density, sensitivity was 67.7%, specificity 89.0%, and positive predictive value was 16.9% despite an IOI prevalence of 3.2%.<br><br>CONCLUSIONS: Our AI-driven pipeline accurately quantified vHRF from OCT images, and the resulting metrics, particularly vHRF volume density, were significantly associated with concurrent IOI. These findings support automated vHRF quantification as a promising imaging biomarker for inflammation assessment, although further validation in larger and more diverse datasets is needed.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42518796, year = {2026}, author = {Razavi, S and Menna, M and Fragiotta, S and Van Herreweghe, S and Lazzerini, A and Battista, M and Beretta, F and Sacconi, R and Querques, G}, title = {Choroidal Changes after Intravitreal Aflibercept, Faricimab, Brolucizumab, and High-Dose Aflibercept in Treatment-Naïve Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101275}, doi = {10.1016/j.xops.2026.101275}, pmid = {42518796}, issn = {2666-9145}, abstract = {PURPOSE: To compare choroidal structural changes after a loading phase of different anti-VEGF agents in treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, monocentric, observational cohort study.<br><br>SUBJECTS: Fifty-six eyes of 56 treatment-na&#xef;ve patients with nAMD.<br><br>Patients received 3 consecutive monthly intravitreal injections of aflibercept 2 mg, aflibercept 8 mg, brolucizumab, or faricimab. Multimodal imaging was performed at baseline and at 3 months using swept-source OCT. Central choroidal thickness (CCT) and choroidal vascularity index (CVI) were quantified. Changes from baseline were analyzed within and between treatment groups, with adjustment for age.<br><br>MAIN OUTCOME MEASURES: Change in CCT and CVI after the loading phase.<br><br>RESULTS: All treatment groups demonstrated a significant reduction in CCT at 3 months (all P &#x2264; 0.006). The greatest mean CCT reduction was observed with brolucizumab, followed by aflibercept 8 mg, faricimab, and aflibercept 2 mg. Age-adjusted analysis showed a significant effect of treatment on CCT change, with a significant treatment-by-age interaction (F(3, 48) = 6.24; P = 0.001; &#x3b7;[2] = 0.197). Choroidal vascularity index decreased significantly only in the aflibercept 8 mg group (mean change: -4.9; P = 0.01), driven by a preferential reduction in the luminal component (P = 0.002). Brolucizumab predominantly affected the stromal component (P = 0.006) without significant change in CVI.<br><br>CONCLUSIONS: Anti-VEGF therapy induces significant choroidal thinning in treatment-na&#xef;ve nAMD during the loading phase. However, different agents demonstrate distinct choroidal compartmental effects. These findings suggest drug-specific patterns of choroidal remodeling, potentially influenced by molecular and pharmacologic properties, warranting further prospective evaluation to determine their clinical implications.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42518877, year = {2026}, author = {Shaer, A and Yokoi, T and Ragam, E and Weintraub, J and Lipchin, B and Ortiz, T and Masoud, O and Orprayoon, N and Hsu, J and Regillo, C}, title = {Real-World Safety of Intravitreal Complement Inhibitor Avacincaptad Pegol for Geographic Atrophy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261468998}, doi = {10.1177/24741264261468998}, pmid = {42518877}, issn = {2474-1272}, abstract = {Purpose: To evaluate the real-world ocular safety profile of intravitreal (IVT) avacincaptad pegol for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods: This retrospective study evaluated eyes with GA secondary to AMD, including those with concurrent neovascular AMD (nAMD) treated with avacincaptad pegol. Conversion (new-onset nAMD) and reactivation (>1 year treatment-free quiescence) were defined as exudation requiring antivascular endothelial growth factor (anti-VEGF) treatment. Demographics, treatment characteristics, visual acuity (VA), intraocular pressure, and adverse events were assessed. Results: Overall, 845 eyes of 590 patients (mean age, 81.8 ± 7.6 years; 71.9% female) received 5608 avacincaptad pegol injections. The mean injection interval was 53.7 ± 22.5 days, with a mean follow-up of 304 ± 173 days. Intraocular inflammation and endophthalmitis rates were low (1 eye each; 0.02% per injection). Conversion occurred in 21 of 590 at-risk eyes (3.6%; 4.3% annualized) after a median of 3 injections (interquartile range, 3-5; range, 1-22). At baseline, nAMD was present in 25.1% of fellow eyes but accounted for 38.1% of conversions, reflecting a higher subgroup conversion rate of 5.4% (6.7% annualized). Among 26 eyes with quiescent nAMD, reactivation occurred in 1 eye (3.8%) after a treatment-free interval of 7.5 years. For eyes requiring concurrent therapy, anti-VEGF treatment intervals remained unchanged. VA remained largely stable (+0.03 logMAR). Persistent ocular hypertension occurred in 8 eyes (1.0%), with no ischemic optic neuropathy or retinal vasculitis observed. Conclusions: In this real-world cohort, a favorable safety profile was found with avacincaptad pegol, with low rates of inflammatory events, endophthalmitis, persistent ocular hypertension, and nAMD conversion, providing clinically relevant data to inform patient counseling and monitoring.}, }
@article {pmid42518983, year = {2026}, author = {Spooner, KL and Gaston, A and Irodi, A and Lim, A and Trivizki, O and Faes, L and Sivaprasad, S and Fu, DJ}, title = {CLEAR report 1: a scoping review and meta-analysis for definitions, imaging metrics, and functional correlates of photoreceptor integrity in AMD.}, journal = {Frontiers in medicine}, volume = {16}, number = {}, pages = {1578813}, doi = {10.3389/fmed.2026.1887548}, pmid = {42518983}, issn = {2296-858X}, abstract = {PURPOSE: Advanced age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide, with photoreceptor degeneration representing the final common pathway of functional impairment. Optical coherence tomography (OCT) enables noninvasive, layer-resolved quantification of photoreceptor integrity using biomarkers of the ellipsoid zone (EZ), the outer nuclear layer (ONL), and the external limiting membrane (ELM). However, substantial heterogeneity in definitions, measurement protocols, and reporting practices limits cross-study comparability and the adoption of clinical trials. This scoping review with nested meta-analyses maps how axial photoreceptor biomarkers are operationalized, segmented, validated, and related to functional and multimodal endpoints in AMD.<br><br>METHODS: MEDLINE, Embase, and Scopus were searched from January 2015 to December 2025 following PRISMA-ScR guidelines. Eligible studies reported OCT-based photoreceptor biomarkers in AMD populations. Data extraction captured boundary definitions, imaging platforms, segmentation approaches, analytic domains, ROI strategies, phenotypic context, reliability statistics, structure-function correlations, and OCT-FAF agreement.<br><br>RESULTS: Ninety-four studies met inclusion criteria, spanning spectral-domain and swept-source OCT platforms and diverse AMD phenotypes. Marked variability was observed in boundary definitions (e.g., EZ-RPE vs. EZ-Bruch's membrane), measurement strategies (thickness, area, volume, reflectivity), and spatial sampling (central 1 mm, ETDRS subfields, lesion-centric masks). When segmentation boundaries and analytic conventions were explicitly defined and consistently applied, reliability for EZ and ONL metrics was high (ICC > 0.90), with automated and deep-learning methods performing comparably to expert manual grading. Structure-function analyses demonstrated moderate-to-strong correlations between photoreceptor loss and microperimetry sensitivity (r = 0.50-0.80) and best-corrected visual acuity (r = 0.40-0.70), particularly in advanced disease stages. OCT-FAF agreement for geographic atrophy detection was similarly high (&#x3ba; > 0.80), although early atrophic features showed greater definitional variability. Phenotypic stratification and topographic reporting were inconsistently documented.<br><br>CONCLUSION: OCT-derived photoreceptor biomarkers show high analytical reliability and clinically meaningful structure-function associations when segmentation boundaries, analytic domains, and reporting conventions are clearly specified. However, the review identifies substantial construct heterogeneity that complicates cross-study comparability and endpoint interpretation. Adoption of consensus boundary definitions, minimum reporting standards, and harmonized validation frameworks is necessary to ensure reproducibility, facilitate regulatory evaluation, and enable integration of photoreceptor metrics into AMD prevention and early-intervention trials. These findings provide the conceptual foundation for the CLEAR initiative (Consensus Layer Evaluation for AI Algorithm Reporting).}, }
@article {pmid42519008, year = {2026}, author = {Dave, A and Ng, ESY and Jiang, Z and Hu, J and Tatang, J and Paniagua, A and Doeve, J and Parikh, S and Williams, KJ and Stiles, L and Radu, RA}, title = {DGAT1-associated lipid-retinoid dysregulation correlates with metabolic impairment in the RPE of Stargardt disease.}, journal = {iScience}, volume = {29}, number = {8}, pages = {116727}, doi = {10.1016/j.isci.2026.116727}, pmid = {42519008}, issn = {2589-0042}, abstract = {Mutations in ABCA4 cause Stargardt disease (STGD1) by disrupting retinoid handling and retinal pigment epithelium (RPE) homeostasis, yet the metabolic drivers of RPE degeneration remain unclear. Given that photoreceptor health relies heavily on the support of the RPE, loss of the RPE cells is central to STGD1 pathology. In this study, we show that dysregulation of diacylglycerol O-acyltransferase-1 (DGAT1) is associated with disrupted retinoid-lipid metabolism in STGD1 RPE cells, accompanied by excess retinyl esters and neutral lipid accumulation, impaired lipid processing, and reduced mitochondrial activity. These findings implicate DGAT1-mediated lipid remodeling as a contributing factor to RPE dysfunction in ABCA4-associated retinopathies.}, }
@article {pmid42500198, year = {2026}, author = {Abbas, KF and Malvankar-Mehta, MS and Juncal, V and Hooper, P and Sheidow, T}, title = {Using Large Language Models to Generate Retina Patient Education Material: A Comparative Analysis With American Society of Retina Specialists Patient Brochures.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261460669}, pmid = {42500198}, issn = {2474-1272}, abstract = {PURPOSE: To evaluate the readability, quality, and misinformation of patient education materials generated by large language models, including ChatGPT-4o (OpenAI), Gemini 1.5 Pro (Google), and Copilot Pro (Microsoft), compared with American Society of Retina Specialists (ASRS) brochures for retinal diseases.<br><br>METHODS: A cross-sectional comparative analysis was performed by generating patient education materials on 3 retinal conditions: retinal detachment, diabetic retinopathy, and age-related macular degeneration. Materials were created using a general prompt (prompt A) and a prompt specifying a sixth-grade readability level (prompt B). Readability was evaluated using 6 validated metrics. Quality was assessed through DISCERN and the Patient Education Materials Assessment Tool. Misinformation was graded using a 5-point Likert scale. Assessments were performed independently by 2 masked retina specialists.<br><br>RESULTS: Average readability of Gemini (11.65; P = .005) and Copilot (11.23; P = .003) materials was significantly better than that of ASRS materials (14.17), whereas ChatGPT showed no significant difference (12.85; P = .06). ChatGPT's average readability was significantly lower compared with Gemini (12.85 vs 11.65; P = .01) and Copilot (12.85 vs 11.23; P < .001). Prompt B significantly improved readability across all large language models relative to ASRS but still exceeded the sixth-grade readability level. DISCERN scores were comparable across groups. ASRS materials had an understandability score of 74.37%, which was significantly lower than ChatGPT (94.44%; P = .02) and Gemini 1.5 (95.83%, P = .02) scores. No significant differences were observed for actionability or misinformation. Readability showed no significant correlation with quality or misinformation (P > .05).<br><br>CONCLUSIONS: Large language models, when appropriately prompted, can generate retina-related patient education material with superior readability compared with existing ASRS brochures, while maintaining comparable quality and accuracy. Large language models represent a promising approach for addressing literacy barriers, though expert oversight remains essential.}, }
@article {pmid42501021, year = {2026}, author = {Maguire, MG}, title = {Glucagon-Like Peptide-1 Receptor Agonist and Age-related Macular Degeneration: Adding to the Story.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.06.025}, pmid = {42501021}, issn = {1549-4713}, }
@article {pmid42501956, year = {2026}, author = {Surawatsatien, N and Solanky, RM and van de Werken, RP and Kong, M and Diaconita, V and Tsang, SH}, title = {Retinal Pigment Epithelium and Microglia Transplantation in Age-related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.036}, pmid = {42501956}, issn = {1879-1891}, abstract = {Age-related macular degeneration (AMD) remains a leading cause of irreversible blindness worldwide, characterized by the progressive breakdown of the outer blood-retinal barrier, accumulation of protein and lipid deposits in the subretinal space, and the consequential degeneration of macular photoreceptors. Geographic atrophy (GA) is one of the blinding end points of AMD. While current pharmaceutical interventions can slow lesion expansion or counter choroidal neovascularization, they fail to address the most significant clinical unmet need: regeneration of damaged retinal tissue to restore vision. Regenerative medicine via stem cell transplantation offers a definitive curative approach by replacing the structural and immune framework of the outer retina. This review synthesizes current advancements in human embryonic and pluripotent stem cells platforms engineered for outer retinal reconstruction. We evaluate the differentiation, culturing, and quality validation required to generate clinical-grade, polarized RPE monolayers and homeostatic microglia-like cells. Structurally, single-cell suspensions are contrasted against bioengineered patches, scaffold-free cell sheets, and advanced cell strips, analyzing how graft configuration dictates post-transplantation integration and visual recovery while balancing procedural adverse events like cell reflux and epiretinal membrane formation. Furthermore, this review addresses the microenvironmental challenges of transplanting allogeneic constructs into an inflamed, senescent host niche. We examine CRISPR-Cas9 genome editing paradigms, including cytosine base and prime editing, designed to rectify cell-intrinsic genetic vulnerabilities such as the complement factor H (CFH) risk variant. We highlight translational applications, such as knocking out the Class II transactivator to eliminate major histocompatibility complex class II (MHC-II) expression, which successfully circumvents host T-cell immune surveillance and prevents graft rejection in non-human primates. Additionally, we analyze how engineering an inhibitor-resistant colony-stimulating factor 1 receptor (CSF1R) point mutation enables exogenously administered microglia to robustly outcompete and replace maladaptive, pro-inflammatory host microglia under selective small-molecule pressure. Finally, we discuss future directions, emphasizing multi-lineage bilayered co-transplantation models that combine genome-edited RPE patches with homeostatic microglia or retinal organoids to achieve durable synaptic repair, alongside automated artificial intelligence manufacturing pipelines. Together, these combined structural, molecular, and immune-modulating strategies represent the next clinical frontier in restoring clear central vision and achieving permanent neurovascular rescue in advanced macular degeneration.}, }
@article {pmid42501958, year = {2026}, author = {Alamoudi, A and Alnabihi, A and Almufarriji, N and Sawad, MHB and Helmi, KW and Batais, W and Althagafi, LA and Aljiayyd, AAS and Batawi, H and Abdulkarem, M}, title = {Renal Impairment and Age-related Macular Degeneration: A Comprehensive Systematic Review and Meta-Analysis.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.046}, pmid = {42501958}, issn = {1879-1891}, abstract = {TOPIC: Chronic kidney disease (CKD) and age-related macular degeneration (AMD) share vascular and inflammatory pathways. Clarifying their association could inform risk stratification across nephrology and ophthalmology.<br><br>CLINICAL RELEVANCE: In adults with renal impairment, especially those with more advanced kidney dysfunction, closer AMD risk surveillance may be warranted, supporting integrated care between ophthalmology and nephrology even though causality cannot be fully confirmed from observational evidence alone.<br><br>METHODS: We systematically searched MEDLINE, Embase, Scopus, and Web of Science from inception to 11 August 2025. Eligible human observational studies and Mendelian randomization (MR) analyses assessed CKD/renal metrics (eGFR, albuminuria/proteinuria, dialysis) in relation to AMD. Random-effects meta-analyses used REML with Hartung-Knapp adjustments, and pooled evidence using odds ratios (ORs) and 95% confidence intervals (95%CI). Heterogeneity was quantified using I&#xb2;, subgroup analyses explored design, phenotype, and CKD severity, and small-study effects were assessed using funnel plots and Egger's test when appropriate. Certainty of evidence was rated using the GRADE prognostic-factor framework.<br><br>RESULTS: Nineteen studies contributed to the primary meta-analysis. CKD was associated with higher odds of AMD (OR&#x202f;=&#x202f;1.27, 95% CI 1.07-1.50; I&#xb2;&#x202f;=&#x202f;95.1%). Effects were similar by design (P for subgroup difference&#x202f;=&#x202f;0.84): cohorts OR&#x202f;=&#x202f;1.29 (0.98-1.69) and cross-sectional studies OR&#x202f;=&#x202f;1.25 (0.96-1.62). By phenotype, associations were significant for non-exudative AMD (OR&#x202f;=&#x202f;1.46, 1.06-1.99), while exudative AMD showed an imprecise increase (OR&#x202f;=&#x202f;1.71, 0.72-4.08), and early AMD was not statistically significant (OR&#x202f;=&#x202f;1.32, 0.90-1.93). CKD severity analyses suggested significantly higher odds with eGFR <60 mL/min/1.73 m&#xb2; (OR&#x202f;=&#x202f;1.40, 1.15-1.72), and a stronger association in dialysis &#x2265;90 days (OR&#x202f;=&#x202f;1.74, 1.52-2.00). Continuous renal markers aligned with a biological gradient (per SD decrease in eGFR OR&#x202f;=&#x202f;1.30, 1.11-1.52). Two Mendelian randomization studies supported a causal association between lower eGFR and AMD (pooled OR&#x202f;=&#x202f;1.65, 1.54-1.76). Overall certainty ranged from moderate (any AMD overall, non-exudative AMD, dialysis exposure, MR) to low/very low for most subgroups due to heterogeneity and imprecision.<br><br>CONCLUSIONS: Renal impairment, particularly reduced eGFR (<60 mL/min/1.73 m&#xb2;), elevated serum creatinine, and dialysis exposure, was associated with modestly higher odds of AMD, and the association was most consistent for non-exudative disease. A biological gradient across continuous renal markers and concordant Mendelian randomization evidence support a plausible eye-kidney link, but the very high heterogeneity (I&#xb2;&#x202f;=&#x202f;95.1%) means the pooled estimate should be read as a central tendency of a diverse evidence base rather than a precise, individually applicable risk. Causal inference therefore remains premature. In practice, these findings support integrated ocular surveillance in patients with CKD, shared vascular risk reduction across nephrology and ophthalmology, and standardized prospective studies with harmonized CKD and AMD definitions to confirm the association and clarify its direction.<br><br>PROSPERO: CRD420251123871.}, }
@article {pmid42501959, year = {2026}, author = {Watane, A and Witkin, A and Heier, J and Shah, C}, title = {Cost-Effectiveness of Photobiomodulation for Intermediate Dry Age-Related Macular Degeneration: A Model-Based Analysis Using the LIGHTSITE III 24-Month Trial.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.035}, pmid = {42501959}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate the cost-effectiveness of photobiomodulation (PBM) for intermediate dry age-related macular degeneration (AMD) from the US healthcare payer perspective, using 24-month LIGHTSITE III trial data.<br><br>DESIGN: Model-based cost-effectiveness analysis using a 5-state Markov model with 6-month cycles over a 10-year horizon, discounting costs and outcomes at 3% annually.<br><br>PARTICIPANTS: Modeled cohort of adults with bilateral intermediate dry AMD and best-corrected visual acuity (BCVA) 20/32-20/100, consistent with LIGHTSITE III eligibility.<br><br>METHODS: Transition probabilities were derived from LIGHTSITE III 24-month outcomes and AREDS natural history data. Costs were derived from 2025 Medicare Physician Fee Schedule and published claims-based sources. One-way and probabilistic sensitivity analyses, a societal perspective, a two-year limited treatment scenario, and a 5-year national budget impact analysis were conducted.<br><br>MAIN OUTCOME MEASURES: Quality-adjusted life-years (QALYs) derived from published visual acuity-to-utility mapping and VFQ-25-to-EQ-5D conversion of LIGHTSITE III quality-of-life data; incremental cost-effectiveness ratio (ICER) as cost per QALY; 5-year national budget impact.<br><br>RESULTS: PBM yielded 5.244 discounted QALYs at an incremental cost of $29,556 over 10 years, producing a base-case ICER of $73,910 per QALY, below both the $100,000 and $150,000 US willingness-to-pay thresholds. The ICER ranged from $36,700 ($1,000/course) to $117,694 per QALY (30% geographic atrophy [GA] reduction) across clinically realistic scenarios. Only the $5,000/course scenario exceeded both thresholds. The 5-year cumulative national budget impact was $25.0 billion at 20% uptake.<br><br>CONCLUSIONS: PBM is cost-effective at conventional US willingness-to-pay thresholds, driven primarily by a 71.7% relative reduction in incident GA at 24 months. These findings support coverage consideration of PBM for intermediate dry AMD, pending independent replication of the GA reduction and prospective EQ-5D data collection.}, }
@article {pmid42502129, year = {2026}, author = {Pearson, RA}, title = {Photoreceptor replacement: a disease-agnostic approach for the treatment of advanced retinal degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42502129}, issn = {1476-5454}, support = {MR/T002735/2//RCUK | Medical Research Council (MRC)/ ; MR/V038559/1//RCUK | Medical Research Council (MRC)/ ; UKRI3826//RCUK | Medical Research Council (MRC)/ ; }, abstract = {Retinal dystrophies such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) affect millions of individuals worldwide and remain leading causes of irreversible blindness. Photoreceptor transplantation has emerged as a promising and disease-agnostic therapeutic approach for restoring vision in advanced degenerative retinal diseases characterised by the loss of rods and/or cones. This brief review summarises some key areas of progress and future directions for photoreceptor replacement therapy, with consideration given to translating pre-clinical findings to the clinic.}, }
@article {pmid42502615, year = {2026}, author = {Tandon, D and Patel, R and Chhabra, Y and Subash, M and Sandhu, R}, title = {NICE-Informed Quality Improvement for Neovascular Age-Related Macular Degeneration: A Single-Centre Two-Cycle Audit of the Two-week Referral-to-Injection Standard.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {614936}, pmid = {42502615}, issn = {1177-5467}, abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is a time-critical cause of irreversible central vision loss. National audit standards operationalise timely treatment as intravitreal anti-VEGF therapy within two weeks of community referral. This retrospective, single-centre, two-cycle quality improvement audit evaluated compliance with the referral-to-first-injection (RTFI) standard and the impact of targeted service optimisation on pathway performance and early outcomes.<br><br>METHODS: Cycle 1 included 81 consecutive community referrals receiving first intravitreal injection for nAMD at Luton and Dunstable University Hospital (March-December 2024); Cycle 2 included 50 patients (May-November 2025). The primary outcome was the proportion meeting the two-week RTFI target. Referral-to-first-appointment (RTFA) and first-appointment-to-first-injection (FATFI) intervals were analysed as pathway components. Secondary outcomes were change in ETDRS visual acuity and OCT-derived central macular thickness (CMT) between baseline and first post-injection follow-up. Following Cycle 1, interventions included a one-week internal assessment deadline, increased injection capacity, and enhanced clinician awareness of referral timelines.<br><br>RESULTS: Demographics were similar across cycles (Cycle 1: 60% female, median age 84; Cycle 2: 54% female, median age 81). Two-week RTFI compliance increased from 41% (33/81) to 76% (38/50) after service optimisation (&#x3c7;[2]=14.10, p=0.00017). Median RTFA reduced from 2&#xa0;weeks (IQR 2) to 1&#xa0;week (IQR 1) (U=2645.5, p=0.0016). Median FATFI remained 1&#xa0;week in both cycles, with reduced variability (IQR 1 to 0) (U=2537.0, p=0.007). No statistically significant difference was detected in early secondary outcomes: median ETDRS change was +3 letters (IQR 13.8) versus +8 letters (IQR 16.0) (p=0.08), and median CMT change was -80&#xa0;&#x3bc;m (IQR 105) versus -82&#xa0;&#x3bc;m (IQR 105) (p=0.71).<br><br>CONCLUSION: Pragmatic service redesign was associated with significantly improved compliance with the two-week RTFI standard for nAMD, driven by faster first assessment and more reliable injection delivery. Residual delays were predominantly patient-related, supporting patient-facing interventions and further audit cycles to assess sustainability.}, }
@article {pmid42504692, year = {2026}, author = {Jiang, X and Yang, F and Gong, H and Mou, Y and An, J and Wang, L and Wang, X and Zhang, Z and Wei, X and Sun, L and Wang, W and Cao, F and Zhao, Y and Qu, D}, title = {Sustained Retinal Delivery of Baicalin and Ranibizumab Overcomes the Anti-VEGF Monotherapy Dilemma in wAMD.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {}, number = {}, pages = {e74813}, doi = {10.1002/smll.74813}, pmid = {42504692}, issn = {1613-6829}, support = {82474086//National Natural Science Foundation of China/ ; 82173980//National Natural Science Foundation of China/ ; BE2023788//Jiangsu Province Key Research and Development Program for Social Development Project/ ; ZD202322//Key Projects of Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; JSYB2024KF-20//Open Project of the Jiangsu Province TCM Epidemic Research Center/ ; CBCM2023108//Foundation of State Key Laboratory of Component-based Chinese Medicine/ ; //Tianjin University of Traditional Chinese Medicine/ ; //"333 project" of Jiangsu Province/ ; //Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), faces a clinical challenge of diminishing efficacy during long-term anti-VEGF monotherapy. An AI-assisted analytical framework pinpointed impaired retinal pigment epithelium (RPE) autophagy and a pro-inflammatory microenvironment driven by retinal microglia-recruited monocytes as co-conspirators in CNV progression. To tackle these dual culprits, we developed an intravitreal injectable hydrogel (Rab&amp;BCL-M@G) that co-encapsulates ranibizumab (Rab) and a small-sized baicalin-loaded microemulsion (BCL-M), enabling controlled and sustained co-delivery of both agents to the retina for over 14 days. Guided by the AI-identified targets, we demonstrated that baicalin promoted dysfunctional mitochondria clearance via the AKT2-PGC-1α-mediated autophagic flux and suppressed monocyte recruitment by disrupting microglial CCL4 signaling. This two-pronged action ameliorated inflammation and angiogenesis, synergizing with Rab. In a laser-induced wAMD mouse model, a single intravitreal injection of Rab&amp;BCL-M@G sustainably reduced CNV area, promoted repair, restored autophagy, and diminished microglial infiltration. Crucially, subsequent wet-lab validation confirmed a positive pathological correlation among defective autophagy, inflammation, and angiogenesis, thereby closing the loop from computational prediction to experimental verification and explaining suboptimal long-term performance after Rab monotherapy. This study proposes a promising synergistic strategy, advancing wAMD therapy through precision delivery and AI-informed mechanism discovery.}, }
@article {pmid42499120, year = {2026}, author = {Tang, M and Sun, S and Liu, Y and Dong, L}, title = {Association between vitamin B6 metabolism and the prevalence of age-related macular degeneration: A cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES).}, journal = {Medicine}, volume = {105}, number = {30}, pages = {e49963}, doi = {10.1097/MD.0000000000049963}, pmid = {42499120}, issn = {1536-5964}, mesh = {Humans ; *Macular Degeneration/epidemiology/metabolism/blood ; Cross-Sectional Studies ; *Vitamin B 6/metabolism/blood ; Nutrition Surveys ; Prevalence ; Female ; Male ; *Pyridoxal Phosphate/blood ; Middle Aged ; *Pyridoxic Acid/blood ; Aged ; United States/epidemiology ; Odds Ratio ; Logistic Models ; }, abstract = {B vitamins may be involved in the development of age-related macular degeneration (AMD). This investigation intended to examine the association between vitamin B6 catabolic status and the prevalence of AMD. Individuals ≥ 40 years old in the 2005 to 2008 National Health and Nutrition Examination Survey who had complete vitamin B6 measurement and AMD diagnostic data were included in this cross-sectional study. The catabolic status of vitamin B6 was evaluated using serum levels of pyridoxal 5'-phosphate (PLP) (the active form) and its metabolite 4-pyridoxic acid (4-PA). The analysis of 4-PA, PLP, and the 4-PA to PLP ratio (4-PA/PLP) used continuous variables and quartiles (Q1-Q4). The associations of 4-PA, PLP, and 4-PA/PLP with the prevalence of AMD were evaluated via weighted logistic regression, with odds ratio (OR) and 95% confidence interval (CI) estimates provided. Nonlinear relationships were explored utilizing restricted cubic splines. Of these 4202 included individuals, 549 were diagnosed with AMD and 3653 were non-AMD patients. High PLP levels (Q4 [≥ 55.475 nmol/L] vs Q1: OR [95% CI] = 0.69 [0.48-0.97]) were significantly associated with lower odds of AMD, whereas high 4-PA/PLP levels (Q3 [0.668-0.976]: OR [95% CI] = 1.57 [1.07-2.29]; Q4 [≥ 0.976]: OR [95% CI] = 2.00 [1.35-2.96]) were related to higher odds of AMD. The associations of PLP levels (Q4: OR [95% CI] = 0.49 [0.32-0.76]) and 4-PA/PLP levels (Q4: OR [95% CI] = 2.18 [1.27-3.75]) with the prevalence of AMD were observed only in individuals aged ≥ 65 years and not in those aged < 65 years. No significant association was found between 4-PA levels and the odds of AMD (P > .05). The restricted cubic splines curves demonstrated that the nonlinear relationships of 4-PA (Poverall = .002; Pnon-linear = .730) and PLP (Poverall < .001; Pnon-linear = .791) with the prevalence of AMD were not significant, whereas the levels of 4-PA/PLP (Poverall < .001; Pnon-linear < .001) had a significant nonlinear association with the prevalence of AMD. High 4-PA/PLP levels showed an association with high odds of AMD, suggesting that vitamin B6 catabolic status may influence the prevalence of AMD.}, }
@article {pmid42495980, year = {2026}, author = {Paliwal, S and Mota, N and Upadhyaya, P}, title = {Beyond clinical efficacy: Measuring the life impact of repeated Anti-VEGF Injections in Indian patients.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_2372_25}, pmid = {42495980}, issn = {1998-3689}, abstract = {PURPOSE: To evaluate the psychosocial and economic burden associated with repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in Indian patients.<br><br>METHODS: This cross-sectional study included adults with age-related macular degeneration (AMD) or diabetic macular edema who had received &#x2265;3 anti-VEGF injections at a tertiary eye care hospital between January 2022 and January 2025. A 25-item questionnaire, adapted from the QUALITII tool, assessed discomfort, anxiety, inconvenience, time loss, and satisfaction. A nine-item Intravitreal Injection Burden Score (range: 9-54) was developed. Internal consistency was assessed with Cronbach's alpha.<br><br>RESULTS: One hundred patients were included (mean age 58.05 &#xb1; 12.77 years; 53% male). Treatment burden was multidimensional, involving procedural discomfort, anxiety, time burden, and caregiver dependence. Injection-related discomfort and anxiety were commonly reported, with 65% experiencing predominantly mild discomfort. Treatment visits imposed a considerable time burden, with most patients spending 4-8 hours per visit and 85% requiring caregiver assistance. Activity restriction and postinjection analgesic use were noted in 24% and 26% of patients, respectively. The mean Intravitreal Injection Burden Score was 19.28 &#xb1; 6.3 (range 9-36), with moderate internal consistency (Cronbach's &#x3b1; = 0.67).<br><br>CONCLUSION: While anti-VEGF therapy remains the standard of care for exudative retinal diseases, repeated injections impose significant psychosocial and economic burdens in Indian patients. Patient-centered care and supportive frameworks play a crucial role in improving adherence and health outcomes.}, }
@article {pmid42496199, year = {2026}, author = {Wolfrum, P and Böhm, EW and Welzel, AM and König, S and Beck, A and Lorenz, K and Stoffelns, B and Korb, CA}, title = {Functional outcomes and cRORA incidence and progression over a 10-year course of anti-VEGF therapy for neovascular AMD.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261472219}, doi = {10.1177/11206721261472219}, pmid = {42496199}, issn = {1724-6016}, abstract = {BackgroundPatients affected by neovascular age-related macular degeneration (nAMD) require long-term anti-vascular endothelial growth factor (VEGF) therapy to maintain visual function. This study assessed 10-year functional outcomes as well as the cumulative incidence and progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in a real-world cohort.MethodsTreatment-naïve eyes of nAMD patients receiving intravitreal anti-VEGF therapy under a pro re nata regimen over 10 years were retrospectively analyzed. Demographics, visual acuity (VA) (LogMAR), number of injections, macular neovascularization (MNV) subtype, and treatment agents were collected. cRORA incidence was assessed according to the Classification of Atrophy Meeting (CAM) group, and the progression rate was quantified. Factors associated with final VA and cRORA progression rate were further investigated.Results35 eyes from 30 patients (63.3% female; mean age 74.9 ± 6.6 years) were analyzed. The median number of injections over 10 years was 69. VA declined by +0.016 logMAR/year, with a significant change compared to baseline only at the 10-year visit (p < 0.05). Baseline and 5-year VA correlated strongly with final VA (p < 0.001). cRORA developed in 48.6% of eyes, with a mean progression rate of 0.26 ± 0.11 mm/year.ConclusionOver 10 years, nAMD-affected eyes receiving anti-VEGF therapy demonstrated only a modest decline in visual function. While cRORA developed in nearly half of the eyes, no association with treatment intensity or MNV type was observed in this cohort. Early VA was significantly associated with long-term functional outcomes.}, }
@article {pmid42497058, year = {2026}, author = {Yang, F and Li, R and Lv, X and Chu, B and Luo, J and Ge, R and Luo, Y and Ren, L and Liu, B and Hu, J and Zhang, H and Qian, H}, title = {Protocol for purifying iPSC-derived retinal pigment epithelial cells by sequential digestion and intrinsic autofluorescence sorting.}, journal = {STAR protocols}, volume = {7}, number = {3}, pages = {104731}, doi = {10.1016/j.xpro.2026.104731}, pmid = {42497058}, issn = {2666-1667}, abstract = {Induced pluripotent stem cells (iPSC)-derived retinal pigment epithelium cells serve as a promising cell source for transplantation therapy in age-related macular degeneration. Here, we present a protocol for purifying the mature retinal pigment epithelium (RPE) cells post-differentiation. We describe steps for sequentially digesting cells with different enzymes and sorting them based on the autofluorescence of mature RPE cells, avoiding fixation and immunostaining. By maintaining high cell viability and purity, this cost-efficient protocol has broad implications for both in vitro research and transplantation applications.}, }
@article {pmid42497935, year = {2026}, author = {Lana, SD and Bertocchi, F and Ricci, C and Sissa, C and Bianchera, A and Favero, ED and Padula, C and Pescina, S and Santi, P and Nicoli, S}, title = {Repurposing glibenclamide for retinal protection: TUDCA-modified liposomes for ocular delivery.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {127203}, doi = {10.1016/j.ijpharm.2026.127203}, pmid = {42497935}, issn = {1873-3476}, abstract = {Glibenclamide, widely used as an oral treatment for type 2 diabetes, represents a promising example of drug repurposing. This second-generation sulfonylurea has demonstrated neuroprotective effects on ocular tissues following oral administration, showing potential benefits in the prevention and management of diabetic retinopathy and age-related macular degeneration (AMD). These findings suggest that local administration could be particularly advantageous for patients not receiving systemic glibenclamide therapy. However, to enhance ocular bioavailability and achieve sustained drug release, an appropriate delivery system is required. This study aimed to develop a topical liposomal formulation for the ocular delivery of glibenclamide. To improve penetration across biological barriers, liposome properties were optimized by incorporating tauroursodeoxycholic acid (TUDCA), a bile salt derivative that also demonstrated neuroprotective activity. The inclusion of this molecule within the lipid bilayer impacted phospholipid organization, increasing vesicle deformability, as confirmed by small-angle X-ray scattering (SAXS) analysis. Glibenclamide loading did not affect vesicle deformability and was higher in TUDCA-modified liposomes compared to conventional liposomes. Ex vivo permeation studies using isolated porcine ocular tissues (cornea, conjunctiva, and sclera) further supported TUDCA's role as an edge activator, enhancing drug penetration. Notably, glibenclamide liposomes were also able to accumulate in the sclera, forming a reservoir for sustained release over time. Finally, the liposomal formulation demonstrated good tolerability in ARPE-19 cell lines, highlighting its potential as a safe and effective system for ocular delivery of glibenclamide.}, }
@article {pmid42497940, year = {2026}, author = {Zhang, X and Huang, Z and Cheng, J and Yan, M and Ye, Y and Song, Y}, title = {Quantitative analysis of choroidal parameters of intermediate and neovascular age-related macular degeneration using ultra-widefield swept-source OCTA.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105589}, doi = {10.1016/j.pdpdt.2026.105589}, pmid = {42497940}, issn = {1873-1597}, abstract = {PURPOSE: To evaluate wide-field choroidal alterations in intermediate AMD (iAMD) and neovascular AMD (nAMD) using ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA).<br><br>METHODS: This cross-sectional study included 40 iAMD eyes, 81 nAMD eyes, and 68 age-matched normal eyes. Eight choroidal parameters-thickness (ChT), volume (CV), vascularity index (CVI), vascular volume/area (CVV/a), stromal volume/area (CSV/a), stromal index (CSI), choriocapillaris density (CCD), and large choroidal vessel density (LCVD)-were measured across nine subfields using 24&#x202f;&#xd7;&#x202f;20 mm scans. Generalized estimating equations (GEE) and receiver operating characteristic (ROC) analysis were used. Subgroup analyses evaluated the effects of treatment status and macular neovascularization (MNV) type within nAMD.<br><br>RESULTS: Baseline demographics were comparable across groups (all P > 0.05). Compared with normal eyes, nAMD eyes showed lower ChT in 8/9 subfields and lower CV in 7/9; compared with iAMD eyes, both were lower in 3/9 (all Bonferroni-corrected pairwise P < 0.05). CSI was higher than normal in 5/9 subfields for both iAMD and nAMD, with no significant iAMD-nAMD differences in any subfield. For distinguishing nAMD from controls, central ChT had the highest diagnostic accuracy (AUC&#x202f;=&#x202f;0.894), followed by CV (AUC&#x202f;=&#x202f;0.883) and CSV/a (AUC&#x202f;=&#x202f;0.840). Only CSV/a differed by treatment status; no Bonferroni-corrected pairwise differences were detected among MNV subtypes.<br><br>CONCLUSION: nAMD showed broader ChT and CV reductions, whereas higher CSI was confined to selected subfields in both AMD groups, without significant iAMD-nAMD differences. These findings indicate distinct stage-associated choroidal patterns. Central ChT showed the strongest discrimination between nAMD and normal eyes.}, }
@article {pmid42498181, year = {2026}, author = {McLellan, FC and Liang, G and Jin, Y and Madigan, MC and Ng, PQ and White, AG and Williams, PA and Shu, DY}, title = {Synergistic cytokine signaling drives angiofibrotic gene pathways in primary human retinal endothelial cells.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.06.007}, pmid = {42498181}, issn = {1525-2191}, abstract = {Neovascularization of the posterior eye is a progressive disease state, marked by an inflammatory initiation, angiogenic growth, and subsequent fibrotic degeneration of ECs (ECs). Although implicated in age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) as a leading cause of irreversible vision loss worldwide, the mechanisms underpinning retinal EC dysregulation in neovascularization and fibrosis are not well understood. This study presents a transcriptomic investigation of cultured primary human microvascular retinal EC dysregulation following exposure to 10 ng/mL of six retinal neovascularization-associated signaling molecules (IL-6, TNF-α, TGF-β1, TGF-β2, thrombin, and VEGF-A) both individually and as a combined treatment for 24 hours. TNF-α, thrombin and TGF-β2 alone induced significant enhancement of inflammatory and angiofibrotic pathways, including PI3K/Akt, NF-κB and SMAD. BGN, CD34, COL1A2, CXCL8, IGFBP5, INHBA, SERPINE1, SNAI1, TGFB2 and TNFSF11 were identified as having overlapping, nodal roles in the pathological dysfunction of retinal ECs. Co-treatment with all six ligands significantly enhanced differential gene expression, revealing 889 unique differentially expressed genes. Using a novel network-based gene correlation engine, GeneBunny, the cocktail group was found to mimic published retinal and choroidal EC transcriptomes from AMD patient tissue more accurately than individual treatment groups. These findings provide a biologically relevant characterization of the pathological mechanisms driven by key retinal neovascularization-associated signaling molecules in retinal, enabling the identification of novel anti-fibrotic therapeutic targets.}, }
@article {pmid42498777, year = {2026}, author = {Elfalah, M and Borelli, E and Marolo, P and Reibaldi, M and De Angelis, V and De Rosa, C and Iatì, F and Castellino, N and Zweifel, SA and Yousef, YA and Bacherini, D and Lucisano, A and Carnevali, A and Rejdak, R and Giannaccare, G and Scorcia, V and Toro, MD}, title = {Short-term efficacy and safety of transcleral lutein iontophoresis in patients with intermediate amd and reticular pseudodrusen: A retrospective study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42498777}, issn = {1476-5454}, abstract = {BACKGROUND: There is limited data available on the efficacy and safety of Transscleral Lutein Iontophoresis (TSLI) in patients with intermediate age-related macular degeneration (iAMD) and reticular pseudodrusen (RPD).<br><br>METHODS: This retrospective multicentre study evaluated the functional and morphological outcomes of TSLI in patients with stage 2 and stage 3 iAMD with RPD. Autofluorescence (AF), Optical Coherence Tomography (OCT), Best Corrected Visual Acuity (BCVA), Intraocular Pressure (IOP), Macular Sensitivity (MS) and adverse events, were recorded at baseline, 1 month and 3 months follow-up after treatment.<br><br>RESULTS: Thirty eyes from 30 patients, (15 &#x2642;: 15 &#x2640;), mean age (70.3&#x2009;&#xb1;&#x2009;7.8 years) were included. BCVA improved significantly, from mean baseline 65.6&#x2009;&#xb1;&#x2009;8.6 ETDRS letters to 66.9&#x2009;&#xb1;&#x2009;8.0 at 1 month and 69.1&#x2009;&#xb1;&#x2009;7.8 at 3 months (ANOVA, p&#x2009;<&#x2009;0.0001, respectively), along with MS, (ANOVA p&#x2009;<&#x2009;0.001). There was a significant increase of stage 1 RPD (p&#x2009;=&#x2009;0.002) and a decrease in stage 3 RPD (p&#x2009;=&#x2009;0.020). The Outer Nuclear Layer (ONL) thickness increased significantly (ANOVA, p&#x2009;<&#x2009;0.0001). No adverse events were recorded.<br><br>CONCLUSION: TSLI appears to be an effective, safe technique in patients with iAMD and RPD, leading to structural and functional improvements in short-term follow-up.}, }
@article {pmid42488349, year = {2026}, author = {Sannan, NS}, title = {Correction: Genetic determinants of age-related macular degeneration in Middle Eastern populations: a systematic review.}, journal = {Frontiers in genetics}, volume = {17}, number = {}, pages = {1893561}, doi = {10.3389/fgene.2026.1893561}, pmid = {42488349}, issn = {1664-8021}, abstract = {[This corrects the article DOI: 10.3389/fgene.2026.1776779.].}, }
@article {pmid42488638, year = {2026}, author = {Lin, H and Wolfrum, P and Kempf, LF and Wolters, D and Perumal, N and Korb, CA and Grus, FH}, title = {Stage-associated immunoproteomic profiling of serum autoantibody-captured retinal antigens in age-related macular degeneration.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1824524}, pmid = {42488638}, issn = {1664-3224}, mesh = {Humans ; *Autoantibodies/blood/immunology ; Female ; Male ; *Proteomics/methods ; *Retina/immunology ; *Macular Degeneration/immunology/blood ; *Autoantigens/immunology ; Aged ; Animals ; Aged, 80 and over ; Middle Aged ; }, abstract = {INTRODUCTION: Increasing evidence suggests that autoimmune responses are involved in the pathogenesis of age-related macular degeneration (AMD). This study aimed to characterize changes in serum autoantibody-captured retinal antigens in patients with different AMD subtypes, in order to gain further insight into the immunological mechanisms associated with AMD progression.<br><br>METHODS: Serum samples were collected from healthy controls (CTRL, n = 15) and patients with early AMD (n = 15), intermediate AMD (Int. AMD, n = 15), late AMD (n = 15), neovascular AMD with type 1 macular neovascularization (nAMD type 1, n = 10), and neovascular AMD with type 2 macular neovascularization (nAMD type 2, n = 10). Serum antibodies were isolated using Protein G magnetic beads and incubated with porcine retinal lysates to capture antigen-antibody complexes. After elution, the captured retinal antigens were subjected to proteomic analysis.<br><br>RESULTS: Mass spectrometry identified 91 differentially captured retinal antigen targets across AMD subtypes. Compared with controls, 11, 9, 11, 18, and 22 retinal antigen targets were significantly increased in serum samples from patients with early AMD, intermediate AMD, late AMD, nAMD type 1, and nAMD type 2, respectively. Conversely, 14, 11, 9, 10, and 20 retinal antigen targets were decreased in the corresponding AMD subtypes, respectively (FDR < 0.05; p < 0.05). Selected mass spectrometryderived retinal antigen targets were further evaluated in serum and tear samples using antigen microarray analysis. Consistent with the proteomics results, anti-ATP5A1, anti-HIST2H2AA3, and anti-PFKM autoantibody levels were significantly increased in tears from patients with nAMD type 2 (p = 0.03, p = 0.01, and p = 0.04, respectively). In addition, anti-FTH1 autoantibody levels were decreased in serum from patients with nAMD type 1.<br><br>DISCUSSION: Comprehensive screening of serum autoantibody-captured retinal antigens across AMD stages, together with pathway enrichment and STRING network analyses, revealed subtype-specific immune alterations. These findings provide new insights into the immunopathological features of AMD.}, }
@article {pmid42489419, year = {2026}, author = {Horozoglu Ceran, T and Jabbarova, G and Yokus, R and Akdogan, M and Dogan, M}, title = {Real-World outcomes of intravitreal treatment switching in retinal diseases: Analysis of 3,038 treated cases.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261471209}, doi = {10.1177/11206721261471209}, pmid = {42489419}, issn = {1724-6016}, abstract = {PurposeTo evaluate the frequency and patterns of intravitreal therapy (IVT) switching in retinal diseases and describe associated visual acuity outcomes in real-world clinical practice.Materials and MethodsThis retrospective, monocentric study evaluated consecutive IVT-treated cases at a tertiary retina unit. Demographic data, diagnoses, initial agent, injection number, and treatment switches were recorded. Best-corrected visual acuity (BCVA, LogMAR) was assessed at baseline and final follow-up. Switching was defined as a change to another anti-VEGF agent or intravitreal dexamethasone (DEX) implant for inadequate functional and/or anatomical response. BCVA changes were compared using appropriate tests, stratified by indication (diabetic macular edema [DME], neovascular age-related macular degeneration [nAMD], retinal vein occlusion [RVO]).ResultsA total of 3,038 IVT-treated cases (11,345 injections) were analyzed. The main indications were DME (55.5%), nAMD (36.4%), and RVO (6.0%). Overall, 22.9% of treated cases underwent treatment switching, most frequently in DME (24.8%) and nAMD (20.8%). Within-group analyses showed significant BCVA improvement after switching in DME (p = 0.001), RVO (p = 0.032), and nAMD (p = 0.009), while non-switched groups showed no significant change. Aflibercept was the most commonly selected second-line agent (81.7%), and the aflibercept subgroup showed significant within-group BCVA improvement (p < 0.001). Because treatment choice was not randomized, this finding should not be interpreted as evidence of superiority over other second-line agents.ConclusionsIn this retrospective real-world cohort, treatment switching was common in routine retinal practice, and switched cases showed within-group BCVA improvement in some diagnostic subgroups. These findings should be interpreted as descriptive associations rather than evidence of a causal treatment effect.}, }
@article {pmid42491086, year = {2026}, author = {Zhou, S and Yang, N and Xiong, C and Hu, Y and Hui, Q and Feng, S and Gao, M and Li, F and Shao, Y and Zhou, X and Jin, Q and Xu, X}, title = {Diosgenin mitigates laser-induced choroidal neovascularization by suppressing the endothelial-to-mesenchymal transition via the TGF-β/Smad and MAPKs signaling pathways.}, journal = {American journal of translational research}, volume = {18}, number = {6}, pages = {5000-5014}, pmid = {42491086}, issn = {1943-8141}, abstract = {OBJECTIVES: To explore whether diosgenin (Dio), a natural steroidal saponin, alleviates laser-induced choroidal neovascularization (CNV) and its underlying mechanism related to endothelial to mesenchymal transition (EndMT) and signaling pathways.<br><br>METHODS: A mouse model of laser-induced CNV was established; mice were treated with Dio (50 &#x3bc;M, 100 &#x3bc;M) or ranibizumab. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized low-density lipoprotein (Ox-LDL) and pretreated with Dio. CNV leakage, lesion size, EndMT markers, and TGF-&#x3b2;/Smad and MAPKs pathway activities were detected by fundus angiography, Western blot, Transwell, and tube formation assays.<br><br>RESULTS: Dio reduced CNV leakage and lesion area in mice, inhibited HUVEC migration and tube formation. It downregulated mesenchymal markers (&#x3b1;-SMA, vimentin), upregulated endothelial markers (VE-cadherin, ZO-1), and suppressed phosphorylation of Smad2/3, p38, ERK1/2, and JNK.<br><br>CONCLUSIONS: Dio mitigates laser-induced CNV by inhibiting EndMT via the TGF-&#x3b2;/Smad and MAPKs signaling pathways, serving as a potential candidate for neovascular age-related macular degeneration.}, }
@article {pmid42492228, year = {2026}, author = {Yang, Y and Zou, H}, title = {Associations between dietary nutrient intake and the risk of multiple age-related ocular diseases: evidence from longitudinal analysis.}, journal = {The journal of nutrition, health &amp; aging}, volume = {30}, number = {9}, pages = {100927}, doi = {10.1016/j.jnha.2026.100927}, pmid = {42492228}, issn = {1760-4788}, abstract = {BACKGROUND: This study aims to assess how dietary nutrient intake relates to the risk of developing four common age-related ocular diseases, including age-related macular degeneration, cataract, diabetic retinopathy, and glaucoma.<br><br>METHODS: This study utilized data from the UK Biobank, covering 36 nutrients. The analysis included 103192 participants after applying predefined inclusion and exclusion criteria. The outcomes were the incidences of four age-related ocular diseases, including age-related macular degeneration, cataract, diabetic retinopathy, and glaucoma, derived from UK Biobank hospital records. Associations between nutrient intake and the incidence risk of four diseases were evaluated using Cox proportional hazards models. Subgroup and sensitivity analyses were also performed.<br><br>RESULTS: During a median follow-up time of approximately 13 years, 1977 age-related macular degeneration cases, 11312 cataract cases, 618 diabetic retinopathy cases and 2213 glaucoma cases became incident. Pantothenic acid intake was positively associated with an elevated risk of AMD (HR: 1.05, 95%CI: 1.01-1.09, p = 0.013), which is more pronounced among older participants and men. Total iron (HR: 0.99, 95%CI: 0.98-1.00, p = 0.019), non-haem iron (HR: 0.99, 95% CI: 0.98-1.00, p = 0.014) and manganese (HR: 0.98, 95%CI: 0.96-1.00, p = 0.020) showed protective associations with cataract. The effects of total iron (HR: 1.05, 95%CI: 1.01-1.10, p = 0.022) and haem iron (HR: 1.34, 95%CI: 1.06-1.69, p = 0.014) on DR risk were also observed. Copper intake appeared to exert a protective effect against glaucoma (HR: 0.86, 95%CI: 0.75-0.99, p = 0.032).<br><br>CONCLUSIONS: Several dietary nutrients were associated with the incidence of age-related eye diseases.}, }
@article {pmid42492595, year = {2026}, author = {Huang, L and Yao, E and Yang, M and Chen, DF}, title = {Reprogramming Mammal Müller Glial Cells for Retinal Neuroregeneration.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.06.006}, pmid = {42492595}, issn = {1525-2191}, abstract = {Müller glia (MG) are the predominant non-neuronal cells of the vertebrate retina, playing an integral role in retinal homeostasis and photopic signal transmission. In lower vertebrates, MG retain robust regenerative potential, acting as a source of neuronal progenitors following injury. In contrast, mammalian MG primarily responds to damage with gliosis, a process that provides initial neuroprotection but ultimately restricts their neurogenic capacity. This limitation is especially consequential in humans, where genetic disorders and age-related diseases such as diabetic retinopathy, glaucoma, and macular degeneration lead to retinal neuron death and irreversible visual loss. One promising therapeutic strategy is to reprogram MG in vivo into stem-like progenitor cells capable of replacing lost neurons, with the expectation that these new cells can form functional synaptic circuits, replace lost neurons, and restore retinal function. Recent studies have reviewed integrated regulatory network, encompassing signaling pathways including Notch, Wnt/β-catenin, MAPK/ERK, PI3K/AKT, SMADs, and Hippo-YAP, alongside key transcription factors and epigenetic mechanisms, that collectively govern MG cell cycle reentry and neurogenesis in mammals. This review synthesizes current knowledge of this integrated regulatory network, mainly focusing on the role of signaling pathways in MG regeneration, highlighting strategies to harness the intrinsic neurogenic potential of MG for retinal repair, underscoring their promise as cellular targets for curing degenerative retinal diseases from intrinsic cellular sources.}, }
@article {pmid42493579, 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 = {Correction: 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 = {}, doi = {10.1038/s41433-026-04771-z}, pmid = {42493579}, issn = {1476-5454}, }
@article {pmid42494979, year = {2026}, author = {Cui, M and Liu, H and Cai, L and Zhang, Q and Yuan, L and Gao, C and Li, C and Xi, J and Li, Y and Wu, C and Zheng, Q and Liu, L and Chen, P and Zhou, S and Mou, X and Wekselblatt, J and Zhang, Y and Han, L and Ren, S}, title = {AI-engineered AAV capsid enables intravitreal delivery for the treatment of diverse retinal degenerations.}, journal = {Molecular therapy. Advances}, volume = {34}, number = {3}, pages = {201806}, pmid = {42494979}, issn = {3117-387X}, abstract = {Retinal degenerations, including Leber's congenital amaurosis type 1 (LCA1) and wet age-related macular degeneration (wAMD), represent leading causes of vision impairment and blindness, driven by a range of factors, including genetic mutations and pathological neovascularization. While adeno-associated viruses (AAVs) have emerged as a promising platform for sustained gene therapy, most AAVs typically require subretinal injections to reach target cells, which carry risks to retinal integrity. To overcome this limitation, we employed an AI-guided approach to AAV capsid engineering and developed AAV2.PN168, a novel AAV2-derived variant. AAV2.PN168 exhibits extensive retinal transduction via intravitreal injection in both non-human primates and mice. Furthermore, AAV2.PN168 demonstrates high therapeutic efficacy in mouse models both LCA1 and wAMD, respectively. These findings suggest that AAV2.PN168 has translational potential in treating various retinal degenerations, and other ocular diseases requiring efficient, wide-range retinal delivery of therapeutic agents.}, }
@article {pmid42495049, year = {2026}, author = {Wang, MH and Lee, SMY and Hou, G and Wang, Y and Alves, JC and Xie, R and He, Y and Liu, J and Fang, X and Yang, Y and Cai, X and Zheng, S and Yu, Z and Lin, EZ and Cheang, C and Ian, KK and Qin, S}, title = {Explainable multimodal AI and neuro-symbolic clinical decision support system for chronic eye disease management: a digital health implementation study.}, journal = {Frontiers in digital health}, volume = {8}, number = {}, pages = {1836890}, pmid = {42495049}, issn = {2673-253X}, abstract = {INTRODUCTION: Administrative burden and documentation workload are increasingly recognized as major contributors to healthcare costs and clinician burnout, particularly in chronic disease management such as age-related macular degeneration (AMD). These non-clinical tasks reduce time available for patient care and introduce inefficiencies in coding, billing, and compliance workflows. This study aimed to evaluate the technical feasibility and economic impact of an artificial intelligence-based system for automating administrative documentation in AMD care.<br><br>METHODS: A longitudinal proof-of-concept study was conducted in a tertiary ophthalmology network. A hybrid Neuro-Symbolic and Large Language Model (LLM) framework was developed to automate information extraction, clinical documentation structuring, and billing code validation. The system was applied to 24 de-identified unstructured clinical documents, including outpatient notes, operative reports, optical coherence tomography reports, and billing records. The processing pipeline included optical character recognition, knowledge-augmented LLM-based entity extraction, and neuro-symbolic rule-based validation to ensure clinical consistency, ICD-10/CPT coding accuracy, and reimbursement eligibility. Outputs were structured into standardized JSON clinical documentation formats.<br><br>RESULTS: The system achieved 98.3% accuracy in clinical entity extraction and 96.7% accuracy in administrative information extraction. Automated rule validation achieved 100% reimbursement compliance with no denied insurance claims. Mean documentation time per encounter decreased from 25.0&#x2009;&#xb1;&#x2009;5.0&#x2005;min to 3.2&#x2009;&#xb1;&#x2009;1.1&#x2005;min, representing an 88% reduction in documentation time. This resulted in an estimated labor cost saving of approximately 52 CNY (&#x2248;7 USD) per visit and projected annual savings of 42-56 USD per AMD patient under standard treatment schedules.<br><br>DISCUSSION: This study demonstrates the feasibility of integrating neuro-symbolic reasoning with large language models to automate administrative workflows in ophthalmology. The proposed system improves documentation efficiency, coding accuracy, and auditability while reducing hidden administrative costs. Although limited by a small sample size and single-center design, the framework provides a scalable and explainable architecture for AI-assisted administrative automation in digital health systems and chronic disease management.<br><br>CONCLUSION: AI-enabled administrative automation using a neuro-symbolic and LLM framework has the potential to significantly improve operational efficiency and reduce costs in AMD care, supporting the development of sustainable and value-based digital healthcare systems.}, }
@article {pmid42250602, year = {2026}, author = {Herwig-Carl, MC and Loeffler, KU and Liermann, YN and Bulirsch, LM and Liegl, R and Hornig, R and Palanker, D and Kilani, A and Ach, T and Sahel, JA and Wolf, A and Holz, FG}, title = {Histologic Findings after Subretinal Implantation of the PRIMA Photovoltaic Array in Patients with Geographic Atrophy due to Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.05.019}, pmid = {42250602}, issn = {2468-6530}, abstract = {OBJECTIVE: To describe the histologic findings 7 weeks and 18 months after subretinal implantation of the PRIMA photovoltaic array in eyes with geographic atrophy.<br><br>DESIGN: Comparative case series.<br><br>SUBJECTS AND CONTROLS: Four globes of 2 deceased study participants from the prospective PRIMAvera study were analyzed.<br><br>METHODS: The subretinal implant was removed after horizontal sectioning of the globe. Serial sections were performed and stained with hematoxylin-eosin, Masson trichrome, as well as periodic acid-Schiff for histopathologic analysis. Selected sections were immunohistochemically stained for CD68, CD163, GFAP, CD31, CK18, ARR3, RBPMS, and TRPM1. Both study and fellow eyes were analyzed.<br><br>MAIN OUTCOME MEASURES: The histopathologic analysis focused on the anatomical implant localization, wound healing processes, potential inflammatory reactions adjacent to the implant and at the retinotomy site, the development of retinal gliosis and retinal atrophy. as well as a potential encapsulation.<br><br>RESULTS: Both implants could be removed in toto without obvious retinal trauma. Histologically, the implants were located at the level of the outer plexiform layer, as intended, close to the inner nuclear layer. A tissue layer was identified beneath the implant, consisting of a basement membrane deposit and cellular components. A small rupture of Bruch's membrane was detected (in the globe with an 18-months follow-up) associated with localized subretinal fibrosis. At the implant-retina interface, there was only a minimal tissue response without pseudocapsule formation. Furthermore, no significant inflammatory response was detected. The retina overlying the implant was comparable with the fellow eyes in most areas, with limited focal atrophy of the inner retina 18 months after PRIMA implantation. At the retinotomy site, a full-thickness scar was noted with mild atrophic changes in the implant insertion area.<br><br>CONCLUSIONS: The wireless subretinal PRIMA implant demonstrated good biocompatibility with no significant encapsulation or surrounding inflammatory response. At 7 weeks and 18 months after implantation, retina overlying the implant was viable and layered as in control areas. Histopathologic analysis after innovative surgical techniques can provide important information in addition to in vivo findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42479956, year = {2026}, author = {Keleş Yeşiltaş, S and Uçak, T and Tiryaki Demir, S and Çakır, E and Dursun Yılmazşamlı, T and Güven, D}, title = {Longitudinal Optical Coherence Tomography Angiography Analysis of Nonexudative Macular Neovascularization in Age-Related Macular Degeneration: Prognostic Biomarkers for Exudative Conversion.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/02713683.2026.2704361}, pmid = {42479956}, issn = {1460-2202}, abstract = {PURPOSE: To investigate the development of macular neovascularization (MNV) and its conversion to the exudative form in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD) over two years, identify prognostic factors, and assess retinal and choroidal vascular changes using optical coherence tomography angiography (OCTA).<br><br>MATERIALS AND METHODS: This prospective cohort study initially enrolled 62 patients with exudative AMD in one eye and non-exudative AMD in the fellow eye. Thirty patients completed the two-year follow-up and were categorized into three groups: eyes with nonexudative MNV (neMNV) that developed exudative conversion (Group 1), eyes with stable neMNV without exudative conversion (Group 2), and eyes without detectable MNV (Group 3). Best-corrected visual acuity (BCVA), OCTA parameters, MNV area/flow area and choroidal vascularity index were evaluated at baseline, one-year, and two-years.<br><br>RESULTS: Group 1 showed significant declines in mean BCVA and choriocapillaris flow area (p&#x2009;=&#x2009;0.042 and p&#x2009;=&#x2009;0.022). Group 2 exhibited a reduction in outer retinal flow area with increased superficial capillary plexus vascular density in parafoveal and temporal regions (p&#x2009;=&#x2009;0.011, p&#x2009;=&#x2009;0.008, p&#x2009;=&#x2009;0.021). Group 3 demonstrated an increase in pigment epithelial detachment (PED) width (p&#x2009;<&#x2009;0.001). When between and within groups changes over 2&#x2009;years were analyzed, Group 1 demonstrated greater increases in PED width and central macular thickness, along with reduced choriocapillaris flow area compared with the other groups. Group 2 showed a more pronounced reduction in outer retinal flow area and a significant increase in temporal superficial capillary plexus density relative to the remaining groups.<br><br>CONCLUSION: In patients with unilateral eMNV, OCTA may provide prognostic biomarkers for early detection and monitoring of neMNV in fellow eyes with non-exudative AMD.}, }
@article {pmid42484200, year = {2026}, author = {Abreu, PAT and Camargo, JSL and Souza, LB and Vasconcelos, JPC and Souza, OF}, title = {Comparative impact of pro re nata and treat-and-extend regimens on quality of life in patients with neovascular age-related macular degeneration.}, journal = {Arquivos brasileiros de oftalmologia}, volume = {89}, number = {4}, pages = {e20250225}, doi = {10.5935/0004-2749.2025-0225}, pmid = {42484200}, issn = {1678-2925}, mesh = {Humans ; *Quality of Life ; Cross-Sectional Studies ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Male ; Surveys and Questionnaires ; Aged ; *Macular Degeneration/drug therapy ; Visual Acuity/drug effects ; Aged, 80 and over ; Treatment Outcome ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Ranibizumab ; Bevacizumab ; Middle Aged ; }, abstract = {PURPOSE: To compare the impact of pro re nata and treat-and-extend regimens on quality of life in patients with neovascular age-related macular degeneration.<br><br>METHODS: This cross-sectional study included 81 patients with neovascular age-related macular degeneration who completed the National Eye Institute Visual Function Questionnaire-25.<br><br>RESULTS: No statistically significant differences were observed between pro re nata and treat-and-extend regimens across quality-of-life domains measured by National Eye Institute Visual Function Questionnaire-25.<br><br>CONCLUSIONS: Pro re nata and treat-and-extend regimens demonstrated comparable effects on quality of life in patients with neovascular age-related macular degeneration. Further studies are warranted to determine optimal standardized treatment strategies.}, }
@article {pmid42484373, year = {2026}, author = {Inoue, Y and Ikeda, HO and Hata, M and Iida, Y and Okamoto-Furuta, K and Asaka, I and Arita, M and Tsujikawa, A}, title = {Restoration of impaired lysosomal function mitigates drusen-like deposit formation and cell death in Malattia Leventinese.}, journal = {JCI insight}, volume = {11}, number = {14}, pages = {}, doi = {10.1172/jci.insight.194102}, pmid = {42484373}, issn = {2379-3708}, mesh = {Humans ; *Lysosomes/metabolism/pathology/drug effects ; Retinal Pigment Epithelium/pathology/metabolism/cytology ; *Macular Degeneration/pathology/genetics/congenital/metabolism ; Extracellular Matrix Proteins/genetics/metabolism ; Induced Pluripotent Stem Cells/metabolism ; *Retinal Drusen/pathology/genetics/metabolism ; Apoptosis ; Apolipoproteins E/metabolism ; *Corneal Dystrophies, Hereditary/pathology/genetics/metabolism ; Endoplasmic Reticulum Stress ; Optic Disk Drusen/congenital ; }, abstract = {Malattia Leventinese (MAL) is an inherited macular degeneration disorder characterized by retinal drusen formation in adolescence, leading to vision loss. A mutation in the fibulin-3 gene (EFEMP1) causes MAL; however, the mechanisms underlying disease onset and drusen formation remain unclear. In this study, we generated induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells from a patient with MAL to investigate disease mechanisms and potential therapies. MAL iPSC-RPE exhibited fibulin-3 and apolipoprotein E (ApoE) aggregation, increased endoplasmic reticulum stress, and enhanced apoptosis. Long-term culture with photoreceptor outer segments led to drusen-like deposits containing ApoE, complement components, and collagen IV accumulation, and it showed activation of matrix metalloproteinase-2 (MMP2). Untargeted lipid analysis revealed increased hexosylceramide and bis-monoacylglycerophosphate levels in MAL iPSC-RPE cells. A key pathological feature was lysosomal dysfunction associated with altered regulation of lysosomal gene programs, including reduced transcription factor EB transcript levels. Treatment with trehalose, a lysosome-modulating compound, increased lysosomal content and function, reducing drusen-like deposit formation, inhibiting MMP2 activation, and suppressing apoptosis. This study highlighted lysosomal dysfunction as a contributor to RPE damage, drusen-like deposit accumulation, and extracellular matrix degradation. Pharmacological restoration of lysosomal function alleviated these defects, suggesting therapeutic potential for MAL and other drusen-related diseases, including age-related macular degeneration.}, }
@article {pmid42484495, year = {2026}, author = {Treichel, AM and Chen, JHK and Thomas, KM and McCormick, T and Cooper, K and Apte, R and Mehta, NN and González-Cantero, &#xc1;}, title = {Psoriasis is associated with increased risk of non-exudative age-related macular degeneration.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {}, number = {}, pages = {}, doi = {10.1111/jdv.70590}, pmid = {42484495}, issn = {1468-3083}, support = {//David P. Miller Scholars and Research Program/ ; //Dermatology Foundation/ ; //Elaine and Beno Michel Dermatology Research and Education Fund/ ; T32TR005420/TR/NCATS NIH HHS/United States ; //Clinical and Translational Science Collaborative of Northern Ohio/ ; }, }
@article {pmid42484679, year = {2026}, author = {Jeong, A and Baek, SC and Sagong, M}, title = {Comparative outcomes of aflibercept 8 mg and faricimab in neovascular AMD refractory to aflibercept 2 mg.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42484679}, issn = {1435-702X}, abstract = {PURPOSE: To evaluate the real-world outcomes of switching to aflibercept 8 mg or faricimab in patients with neovascular age-related macular degeneration (nAMD) who showed resistance to aflibercept 2 mg.<br><br>METHODS: This retrospective chart review included 159 patients with refractory nAMD who had received at least three consecutive injections of aflibercept 2&#xa0;mg at 4-6-week intervals before switching therapy. Patients who showed resistance to aflibercept 2&#xa0;mg were switched to faricimab or aflibercept 8&#xa0;mg between February 2024 and January 2025. After switching, assessments included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal thickness, maximum height and width of pigment epithelial detachment (PED), choroidal vascularity index (CVI), and the presence of intraretinal or subretinal fluid (IRF/SRF).<br><br>RESULTS: Over six months, mean BCVA and CRT did not show a significant difference between aflibercept 8&#xa0;mg group (n&#x2009;=&#x2009;78) and the faricimab group (n&#x2009;=&#x2009;81). At month 6, the faricimab group demonstrated significant reductions in CRT, subfoveal choroidal thickness (SFCT), Haller layer thickness, and maximum PED height, whereas the aflibercept 8&#xa0;mg group did not show significant changes in these parameters. CVI increased significantly after switching to faricimab, whereas no significant change was observed after switching to aflibercept 8&#xa0;mg. In addition, a lower proportion of eyes with IRF and/or SRF was observed in the faricimab group at month 6.<br><br>CONCLUSION: In nAMD patients resistant to aflibercept 2&#xa0;mg, aflibercept 8&#xa0;mg and faricimab achieved similar BCVA and CRT outcomes. However, faricimab induced greater anatomical changes, characterized by larger reductions in PED height and Haller layer thickness, improved fluid resolution, and a greater increase in CVI. These findings suggest that faricimab may provide additional anatomical benefits, particularly in choroidal structural parameters, in aflibercept 2&#xa0;mg-resistant nAMD.}, }
@article {pmid42484729, year = {2026}, author = {Sharma, K and Shah, K and Raman, R}, title = {Teleophthalmology for Retinal Disease Screening and Referral in Low- and Middle-Income Countries: A Case Overview of India.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42484729}, issn = {1573-2630}, mesh = {Humans ; India ; *Telemedicine ; *Referral and Consultation ; *Developing Countries ; *Ophthalmology/methods ; *Retinal Diseases/diagnosis/epidemiology ; *Mass Screening/methods ; }, abstract = {Innovations like teleophthalmology have made great strides in improving access to care for patients with retinal disease by enabling prompt screening and referral, especially in underprivileged areas. This review highlights the growing role of teleophthalmology in addressing the burden of few retinal diseases like diabetic retinopathy (DR), age-related macular degeneration (ARMD), and retinopathy of prematurity (ROP), artificial intelligence (AI), electronic medical records (EMR) and portable imaging technologies have greatly increased the precision of detection and care coordination. Its scalability is further supported by high patient satisfaction and cost-effectiveness. Barriers to implementation, however, include inadequate training, data security concerns, limited infrastructure and upfront investment costs. We offer focused solutions to address existing gaps, drawing primarily on evidence and national teleophthalmology initiatives from India, which is presented as a representative LMIC case study. The findings may guide the development and scale-up of teleophthalmology services in other LMICs settings. Teleophthalmology can become the backbone of equitable retinal disease care delivery with appropriate policy support and standardization of processes involved. These findings have broader implications for teleophthalmology implementation in LMICs that face similar healthcare delivery challenges.}, }
@article {pmid42484821, year = {2026}, author = {Moribe, JH and Masaoka, M and Yamashiro, K}, title = {Aflibercept 8mg for neovascular age related macular degeneration refractory to faricimab.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42484821}, issn = {1613-2246}, abstract = {PURPOSE: To evaluate the short-term efficacy of intravitreal aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) who exhibited persistent or recurrent exudation two months after faricimab treatment during the maintenance phase following anti-vascular endothelial growth factor (VEGF) loading therapy.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Twenty-seven eyes with nAMD were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) biomarkers-including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (sub-RPE) fluid at the subfoveal and macular areas-were evaluated before and two months after treatment with faricimab and aflibercept 8 mg. Subgroup analyses were performed according to AMD subtype (typical nAMD vs. polypoidal choroidal vasculopathy [PCV]) and pachychoroid characteristics (pachychoroid vs. non-pachychoroid).<br><br>RESULTS: BCVA did not show significant changes after either faricimab or aflibercept 8 mg treatment. However, aflibercept 8 mg resulted in a significant reduction in subfoveal SRF (from 44.4% to 11.1%, P = 0.014) and macular SRF (from 85.2% to 29.6%, P < 0.0001), whereas faricimab did not produce significant anatomical improvements. No significant changes were observed in IRF or sub-RPE fluid with either treatment, possibly due to the low prevalence of the fluid at baseline. Subgroup analyses demonstrated no substantial differences in treatment response between typical nAMD and PCV, or between pachychoroid and non-pachychoroid eyes.<br><br>CONCLUSION: Intravitreal aflibercept 8 mg may provide short-term anatomical benefits, particularly in reducing subretinal fluid, in eyes with nAMD showing persistent or recurrent exudation after faricimab treatment during the maintenance phase, regardless of nAMD subtype or pachychoroid status.}, }
@article {pmid42486229, year = {2026}, author = {Michelitsch, M and Riedl, R and Strini, S and Posch-Pertl, L and Wallisch, F and Djavid, D and Haas, A and Wedrich, A and Weger, M}, title = {Faricimab for High-Need Aflibercept 2 mg Treated Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.07.009}, pmid = {42486229}, issn = {2468-6530}, abstract = {PURPOSE: To assess whether "high-need" treated neovascular age-related macular degeneration (nAMD) eyes, requiring aflibercept 2 mg every 3-5 weeks, can be extended in their treatment interval when switched to faricimab.<br><br>DESIGN: monocenter, randomized, double-masked, two-part clinical trial (NCT05941715) with a comparator-controlled period of 32 weeks, followed by a single-arm open-label treatment period up to 56 weeks.<br><br>PARTICIPANTS: Aflibercept 2 mg treated nAMD patients, exhibiting retinal fluid at &#x2264; 6-week treatment intervals within a treat-and-extend (TandE) regimen, were recruited at the Medical University of Graz between July 2023 - January 2024.<br><br>METHODS: 70 participants were randomized 1:1 receiving either faricimab TandE (comparator group {n=35}) or aflibercept 2 mg (control group {n=35}) TandE until week 32. Beginning from week 4 intervals were extended/reduced by 2 weeks depending if retinal fluid was present/absent on optical coherence tomography (OCT). From week 32 until week 56 both groups received faricimab TandE. Treatment intervals, change in central subfield thickness (CST) and visual acuity were assessed.<br><br>MAIN OUTCOME MEASURE: The proportion of eyes with at least one successful extension, meaning no retinal fluid at a 6-week treatment interval, up to &#x2264; 32 weeks.<br><br>RESULTS: In the comparator-controlled period, 12 (34.3%) faricimab treated eyes versus 3 (8.6%) aflibercept 2 mg treated eyes were successfully extended by &#x2265; 2 weeks (p=0.018). At 56 weeks, after both groups were treated with faricimab 14 (40%) and 13 (37.1%) eyes, respectively, were successfully extended. Least square mean difference (LSMD) CST significantly reduced in the comparator group from baseline to 32 weeks by -36.4 &#x3bc;m (95% confidence interval (CI) -56.0 to -16.8; p<0.001) and to 56 weeks by -43.7 &#x3bc;m (95% CI -64.3 to -23.2, p<0.001). In the control group LSMD CST remained stable from baseline to 32 weeks with +2.7 &#x3bc;m (95% CI -17.5 to 22.8, p=0.793), when switched to faricimab significantly reduced at 56 weeks by -47.0 &#x3bc;m (95% CI -67.7 to -26.4, p<0.001). Visual acuity remained stable for both groups.<br><br>CONCLUSIONS: In this first randomized clinical trial comparing faricimab with aflibercept 2 mg in "high-need" aflibercept 2 mg treated nAMD eyes, switching to faricimab was effective in extending treatment intervals in more than a third of eyes.}, }
@article {pmid42486282, year = {2026}, author = {Vienne-Jumeau, A and Merle, D and Sacconi, R and Querques, G}, title = {Non-exudative fluid in age-related macular degeneration: Imaging, pathophysiology, and clinical implications.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.07.008}, pmid = {42486282}, issn = {1879-3304}, abstract = {Non-exudative retinal fluid in age-related macular degeneration (AMD) challenges the long-standing paradigm that any fluid on structural optical coherence tomography necessarily reflects neovascular exudation. Advances in multimodal imaging have revealed that both intraretinal fluid and subretinal fluid (SRF) may arise from non-neovascular mechanisms across intermediate AMD and geographic atrophy (GA). Non-exudative IRF encompasses 3 distinct processes: (1) degenerative mechanisms occurring in progressive atrophy, (2) "burnt-out" contraction with cavitation overlying chronic fibrotic scars, and (3) mechanical stress induced by underlying lesions (e.g., drusenoid pigment epithelium detachment [PED]), subretinal hyperreflective material) or traction at the vitreomacular interface. Non-exudative SRF reflects retinal pigment epithelium pump failure over drusen or drusenoid PEDs, but may also result from alterations within the photoreceptor outer segments (subretinal pseudocysts). Integrating these mechanisms into clinical interpretation shifts management from a fluid-based to a pathophysiology-based approach, recognizing that non-exudative fluid does not respond to anti-vascular endothelial growth factor therapy and instead signals advanced tissue stress and increased risk of GA progression.}, }
@article {pmid42487123, year = {2026}, author = {Hall, JC and Sudhakar, KK 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 = {Correction: 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 = {}, doi = {10.1186/s13073-026-01728-5}, pmid = {42487123}, issn = {1756-994X}, }
@article {pmid42487566, year = {2026}, author = {Patel, S and de Carlo Forest, T and Lisker-Cervantes, A and Gnanaraj, R and Lynch, A and Mandava, N and Mathias, M and Manoharan, N and Patnaik, J}, title = {Visual Functioning and Progression from Intermediate Age-Related Macular Degeneration (AMD) to Advanced AMD.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/09286586.2026.2702462}, pmid = {42487566}, issn = {1744-5086}, abstract = {PURPOSE: To investigate whether the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) can predict the progression of intermediate age-related macular degeneration (iAMD) to advanced non-neovascular (NNV) or neovascular (NV).<br><br>METHODS: 380 patients aged 55-99&#x2009;years with iAMD in one or both eyes and no evidence of geographic atrophy (GA) or NV AMD in either eye were enrolled (2014-2023 into the University of Colorado AMD registry) with follow-up through November 2024. AMD classification and progression were based on multimodal imaging review by two vitreoretinal surgeons. Baseline visual acuity (LogMAR) and VFQ-25 scores were collected at enrollment. Cox proportional hazards models assessed time to progression. Kaplan-Meier analysis evaluated significant VFQ-25 subscales.<br><br>RESULTS: Among 380 iAMD participants (mean age 76.1&#x2009;years, 95.8% white), 131 (34.5%) progressed to advanced AMD over a median 32-month follow up (SD- 27). Worse baseline LogMAR in both the better- (HR: 6.39, 95% CI: 1.57-26; p&#x2009;=&#x2009;0.001) and worse- (HR: 2.64, 95% CI: 1.26-5.55; p&#x2009;=&#x2009;0.010) seeing eyes predicted progression. Lower baseline VFQ-25 general vision (HR: 0.84 per 10-point increase, 95% CI: 0.74-0.95, p&#x2009;=&#x2009;0.006) and distance activities scores (HR: 0.89 per 10-point increase, 95% CI: 0.80-0.98, p&#x2009;=&#x2009;0.019) predicted progression during follow-up. In multivariable analysis adjusting for age and LogMAR for both eyes, this remained significant for general vision (HR: 0.85, 95% CI:0.75-0.98, p&#x2009;=&#x2009;0.022). Kaplan-Meier analysis showed faster progression for patients with baseline general vision and distance activity subscores below 85 (p&#x2009;=&#x2009;0.013 and p&#x2009;=&#x2009;0.011, respectively).<br><br>CONCLUSION: Lower NEI-VFQ-25 general vision subscale scores independently predicted progression to advanced AMD.}, }
@article {pmid42473438, year = {2026}, author = {Wei, B and Zhang, J and Duan, Y and Cheng, N and Wu, X}, title = {Integrative Network Pharmacology Analysis of Gut Microbial Metabolite-Mediated Gut-Eye Axis Regulation in Major Blinding Retinal Diseases.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101284}, pmid = {42473438}, issn = {2666-9145}, abstract = {OBJECTIVE: To systematically investigate the shared and disease-specific mechanisms by which gut microbial metabolites may regulate age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO) through a network pharmacology framework.<br><br>DESIGN: Bioinformatics-based network pharmacology study.<br><br>SUBJECTS: Publicly available gut microbial metabolite, metabolite-target, and disease-associated gene data sets related to AMD, DR, and RVO were analyzed.<br><br>METHODS: Gut microbial metabolites were retrieved from gutMGene, and potential human targets were predicted using the Similarity Ensemble Approach and SwissTargetPrediction. Disease-associated genes were collected from GeneCards, Online Mendelian Inheritance in Man, and the Comparative Toxicogenomics Database. Intersection genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Protein-protein interaction networks were constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and candidate hub targets were prioritized in Cytoscape. Drug-likeness and toxicity profiles of key metabolites were evaluated using SwissADME and ADMETlab 3.0. An integrated microbiota-substrate-metabolite-target (M-S-M-T) network was constructed to characterize gut-eye axis regulation.<br><br>MAIN OUTCOME MEASURES: Intersection genes, enriched biological functions and pathways, high-centrality candidate hub targets, predicted drug-likeness and toxicity profiles of metabolites, and M-S-M-T regulatory relationships.<br><br>RESULTS: A total of 226 gut microbial metabolites and 1518 predicted host targets were identified. Intersection analysis revealed 47, 44, and 40 metabolite-related genes associated with AMD, DR, and RVO, respectively, including 38 genes shared across all 3 diseases. Enrichment analyses showed convergent involvement of microbial signal sensing, inflammatory regulation, oxidative stress, apoptosis, and vascular homeostasis. Nuclear factor kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase-protein kinase B, tumor necrosis factor, VEGF, Toll-like receptor, and nucleotide-binding oligomerization domain-like receptor pathways formed a shared inflammatory-oxidative-vascular signaling module. Protein-protein interaction analysis identified interleukin 6, tumor necrosis factor, protein kinase B alpha, and tumor protein p53 as recurrent high-centrality candidate hub targets. Key metabolites, including indole-3-propionic acid, tryptamine, phenylalanine, and indole-3-lactic acid, showed favorable predicted drug-likeness and safety profiles.<br><br>CONCLUSIONS: Gut microbial metabolites may contribute to AMD, DR, and RVO through shared inflammatory, oxidative stress, and vascular signaling networks. These findings provide a systems-level framework for gut-eye axis regulation and support further experimental validation of microbiota-based systemic intervention strategies.<br><br>FINANCIAL DISCLOSURES: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42473439, year = {2026}, author = {Chakravarthy, U and Gemmy Cheung, CM and Staurenghi, G and Sadda, S and Guymer, R and Jaffe, GJ and Curcio, CA and Holekamp, NM and Bachmeier, I and Scherb, MP and Blotner, S and Rabena, M and Cordeiro, MC and Armendariz, BG and Kanku, MS and Heinrich, D}, title = {Low Rates of Fibrosis in Eyes Treated with the Port Delivery Platform with Ranibizumab or with Monthly Ranibizumab in the Archway Trial.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101276}, pmid = {42473439}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the proportion of eyes with fibrosis in the Archway neovascular age-related macular degeneration trial, which compared efficacy and safety between monthly injections of ranibizumab with treatment via the Port Delivery Platform with ranibizumab (PDS), an intraocular implant providing continuous release of ranibizumab into the vitreous, in eyes that had previously demonstrated a response to anti-VEGF treatment.<br><br>DESIGN: Archway (NCT03677934) post hoc analysis.<br><br>PARTICIPANTS: Patients received PDS 100 mg/mL with fixed 24-week refill-exchanges (Q24W; n = 248) or monthly intravitreal ranibizumab 0.5 mg injections (n = 167). Patients with subfoveal fibrosis/atrophy on color fundus photography (CFP) were excluded from the trial.<br><br>METHODS: Masked graders initially assessed CFP images at baseline, week 48, and week 96 for subretinal fibrosis. If grading was uncertain on CFP, spectral-domain OCT (SD-OCT) scans were used to confirm/rule out fibrosis. Two graders assessed images; a senior grader confirmed all cases and arbitrated disagreement. Subretinal hyperreflective material volumes were quantified using deep learning SD-OCT image segmentation.<br><br>MAIN OUTCOME MEASURES: Proportion of study eyes with fibrosis at baseline, week 48, and week 96. Mean (95% confidence interval) change from baseline in best-corrected visual acuity up to week 96 by presence/absence of fibrosis.<br><br>RESULTS: The proportion of eyes with fibrosis was low in both arms (PDS Q24W, monthly ranibizumab) throughout the trial (baseline: 5.4%, 4.7%; week 48: 7.2%, 4.7%; week 96: 7.7%, 5.4%). In eyes without baseline fibrosis on CFP, 2.4% (5/210) in the PDS Q24W arm and 0.7% (1/141) in the monthly ranibizumab arm developed fibrosis by week 96. Subretinal hyperreflective material volumes were low throughout the trial in both arms. At week 96, eyes with fibrosis gained 3.2 (-2.0, 8.4; n = 17) ETDRS letters in the PDS Q24W arm and lost -9.9 (-30.3, 10.6; n = 8) letters in the monthly ranibizumab arm.<br><br>CONCLUSIONS: Rates of fibrosis were low with both continuous delivery (PDS) and monthly ranibizumab in VEGF-experienced patients with no fibrosis at baseline based on CFP. The PDS, which removes the need for monthly injections, represents a useful strategy to reduce treatment burden while preventing development of fibrosis and maintaining visual acuity.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42476291, year = {2026}, author = {Wang, J and Wu, Z and Fang, L and Guo, Y and Li, H and Liang, F}, title = {Qi Huang granules attenuate sodium iodate-induced retinal injury and inflammation via regulation of mitochondrial dynamics homeostasis.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {200}, number = {}, pages = {107000}, doi = {10.1016/j.biocel.2026.107000}, pmid = {42476291}, issn = {1878-5875}, abstract = {Qi Huang Granules (QHG), a traditional Chinese medicine (TCM) formulation, have been applied clinically for over two decades to treat dry age-related macular degeneration (AMD) and associated fundus lesions. Although its retinoprotective effects have been documented, the associated underlying mechanisms are largely unexplored. The present work focused on investigating the therapeutic efficacy of QHG in sodium iodate (NaIO3)-induced retinal damage, with a particular focus on how the formula regulated the interaction between inflammatory responses and imbalances in mitochondrial dynamics. UPLC-HRMS, network pharmacology, and molecular docking analyses were integrated for identifying mitochondria-associated bioactive constituents and potential targets of QHG. In the experimental model, retinal injury was induced in rats through tail vein injection of NaIO3. Retinal morphological and ultrastructural changes were assessed by HE staining and transmission electron microscopy. To assess mitochondrial function, mitochondrial membrane potential, mtROS levels, and mtDNA integrity were measured. Additionally, ELISA was performed to quantify IL-1β and IL-18 levels. Key marker levels, including p-DRP1, DRP1, OPA1, MFN2, and NLRP3, were determined by Western blotting, IHC, and qRT-PCR. DNM1L (encoding DRP1) and MFN2 were identified as the primary targets of QHG through UPLC-HRMS and computational analyses. In vivo experimental results showed that treatment with QHG alleviated morphological alterations and ultrastructural damage to the retina and mitochondria in model rats. Furthermore, QHG treatment increased mitochondrial membrane potential, reduced mtROS levels, mitigated mtDNA damage, and reduced IL-1β and IL-18 contents. Mechanistically, QHG downregulated p-DRP1, DRP1, and NLRP3, while upregulating MFN2 and OPA1. Collectively, these findings demonstrate that QHG can ameliorate retinal morphology and ultrastructural damage in mitochondria, such as cellular mitochondria, improve mitochondrial function, and attenuate retinal inflammation, thereby exerting a protective effect against NaIO3-induced retinal injury. The underlying mechanism may involve the mitochondrial dynamics-NLRP3 pathway.}, }
@article {pmid42476724, year = {2026}, author = {Schwartz, R and Olvera-Barrios, A and N Warwick, A and Khalid, H and Phatak, S and Jhingan, M and de Vente, C and Valmaggia, P and Liakopoulos, S and Ouyang, Y and I Sanchez-Guiterrez, C and Egan, C and Tufail, A}, title = {Reticular pseudodrusen load is associated with an increased risk of stroke.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {3}, pages = {}, pmid = {42476724}, issn = {2397-3269}, mesh = {Humans ; *Retinal Drusen/diagnosis/complications/epidemiology ; Female ; Retrospective Studies ; Male ; *Stroke/epidemiology/diagnosis/etiology ; Aged ; Tomography, Optical Coherence/methods ; Risk Factors ; *Macular Degeneration/complications/diagnosis ; United Kingdom/epidemiology ; Middle Aged ; }, abstract = {BACKGROUND/AIMS: Reticular pseudodrusen (RPD) are increasingly recognised as a distinct phenotype in the age-related macular degeneration (AMD) disease spectrum. This study investigates the association between RPD and cardiovascular outcomes, specifically myocardial infarction (MI) and stroke in the UK Biobank (UKBB).<br><br>METHODS: Retrospective analysis of UKBB participants (n=2010). A validated deep learning framework identified and quantified subjects with RPD, drusen and controls on optical coherence tomography. Five retina specialists validated the artificial intelligence findings. Multivariable logistic regression models assessed the association between RPD/drusen and stroke, MI and combined MI/stroke, adjusting for age, sex, high-density lipoprotein cholesterol/low-density lipoprotein cholesterol ratio and smoking history.<br><br>RESULTS: The study cohort included 71 subjects with pure RPD, 401 with pure drusen, 368 with both and 1170 controls. Univariable analysis showed that for every 20 RPD lesions, the OR for stroke increased by 1.02 (95% CI 1.00 to 1.04, p=0.028). The mean number of RPD per patient in this cohort was 199, indicating an increased stroke risk of 20%. Multivariable analysis showed a significant association between RPD load and stroke risk (OR 1.02, 95% CI 1.00 to 1.04, p=0.042) after adjustment for confounders. No significant association was found between drusen and stroke or between RPD/drusen and MI.<br><br>CONCLUSION: Increased RPD load is associated with a higher risk of stroke, independent of traditional cardiovascular risk factors. Drusen did not have similar associations, suggesting that RPD may represent a distinct disease entity. Evaluating cardiovascular risk in patients with numerous RPD might be advisable. Further prospective studies are needed to validate these findings and explore the underlying mechanisms.}, }
@article {pmid42477295, year = {2026}, author = {Varghese, RT and John, AA}, title = {Ocular Manifestations of Metabolic Syndrome: A Systemic Vascular Phenotype.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.71133}, pmid = {42477295}, issn = {1463-1326}, abstract = {CONTEXT: Metabolic syndrome (MetS) is defined by central obesity, insulin resistance, hypertension and dyslipidemia. MetS affects over one-third of US adults. Beyond its cardiovascular burden, MetS has clinically relevant associations with ocular health and may contribute to a systemic vascular and neuro-metabolic phenotype involving the retina, optic nerve, lens, ocular surface and choroid.<br><br>EVIDENCE ACQUISITION: This narrative review searched PubMed through May 2026 using combinations of free-text and MeSH-based terms related to 'metabolic syndrome', 'insulin resistance', 'obesity', 'hypertension', 'dyslipidemia', 'diabetes', 'diabetic retinopathy', 'diabetic macular edema', 'glaucoma', 'cataract', 'dry eye', 'macular degeneration', 'retinal vascular occlusion' and 'optic neuropathy'. Reference lists of relevant reviews and primary studies were also screened. English-language human, translational, epidemiologic, clinical-trial, systematic-review and meta-analysis articles were prioritized. This was not designed as a systematic review, and formal PRISMA screening, risk-of-bias grading and meta-analysis were not performed.<br><br>EVIDENCE SYNTHESIS: MetS and its components are associated with diabetic retinopathy, diabetic macular edema (DME), non-diabetic retinopathy, primary open-angle glaucoma, cataract, dry eye disease, age-related macular degeneration (AMD), retinal vascular occlusions and non-arteritic anterior ischemic optic neuropathy (NAION). Shared mechanisms include chronic inflammation, oxidative stress, endothelial dysfunction, insulin resistance-driven retinal neurodegeneration, dyslipidemia-related lipotoxicity, hypertension-related microvascular injury and microvascular rarefaction. Management requires both systemic risk-factor optimization and disease-specific ophthalmic therapy, including anti-VEGF therapy, intraocular pressure reduction, laser or surgical procedures when indicated, ocular surface-directed therapy and cataract surgery when visually significant.<br><br>CONCLUSIONS: Ocular complications associated with MetS are common and may be vision-threatening. Risk-based ocular surveillance and metabolic optimization are justified, particularly in patients with diabetes, hypertension, dyslipidemia, visual symptoms or established vascular disease. However, the strength of disease-specific evidence varies: interventional evidence is strongest for diabetic retinopathy risk reduction and glaucoma treatment through intraocular pressure lowering, whereas evidence for AMD, NAION, RVO, cataract and dry eye disease is more frequently observational or indirect.}, }
@article {pmid42479493, year = {2026}, author = {Franco, JJ and Song, A and Pan, WW and Williams, GA and Johnson, MW and Wubben, TJ}, title = {Community-Level Variation in On-Label Versus Off-Label Anti-VEGF Use and Medicare Part B Spending.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004920}, pmid = {42479493}, issn = {1539-2864}, abstract = {PURPOSE: To examine whether community-level sociodemographic characteristics are associated with differences in on-label versus off-label anti-VEGF agent use under Medicare Part B and to estimate differential spending attributable to variation in community-level agent mix.<br><br>METHODS: Part B claims data (2013-2023) were analyzed to identify providers billing for on-label (aflibercept, ranibizumab, faricimab, brolucizumab, and biosimilars) or off-label (bevacizumab) anti-VEGF injections. For each provider year, 15-min drive-time service areas were generated and overlaid on U.S. Census tracts enriched with American Community Survey-derived sociodemographic data. Community-level profiles were generated through population-weighted aggregation of tracts within each service area. Multivariable logistic regression estimated adjusted marginal effects (AMEs) of sociodemographic variables on on-label anti-VEGF proportion. Counterfactual simulations estimated Part B spending under alternative community-level agent mix scenarios.<br><br>RESULTS: From 2013-2023, 5,178 providers billed Part B for 34.5 million anti-VEGF injections. Higher on-label use was associated with greater community-level proportions of Medicare-aged (AME per 10-percentage-point [pp] increase: +6.1 pp [95% CI: 3.1-9.0]), Black/African American (+2.4 [1.5-3.3]), and college-educated residents (+3.2 [1.9-4.5]). An inverse association was observed for proportion very low-income residents (-3.1 [-5.3 to -0.8]), while no association was observed for proportion Hispanic/Latino residents (+0.4 [-0.6-1.3]) or population density (AME per doubling: +0.8 [-0.2-1.8]). Equalizing anti-VEGF mix to that of the highest-poverty quartile would have resulted in approximately $4.2 billion lower spending.<br><br>CONCLUSIONS: Despite uniform reimbursement, significant community-level differences exist in on-label anti-VEGF use within Medicare Part B. These gradients produce billions of dollars in differential spending and raise questions of access, equity, and value-based care.}, }
@article {pmid42472016, year = {2026}, author = {Demircan, E and Rabinovitch, D and Ahmed, IIK and Varma, DK}, title = {Visual and Patient-Reported Outcomes of a Non-Diffractive Extended Depth-of-Focus Intraocular Lens with Micro-Monovision in Eyes with Early Macular Pathology.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {618031}, pmid = {42472016}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate visual and patient-reported outcomes after bilateral implantation of a non-diffractive extended depth of focus (EDOF) IOL (AcrySof IQ Vivity, Alcon) in patients with early macular pathology.<br><br>DESIGN: Single-site, prospective, non-comparative pilot cohort study.<br><br>PATIENTS AND METHODS: The study included 20 patients (40 eyes) undergoing bilateral cataract surgery with at least one eye with early-stage macular pathology, specifically age-related macular degeneration (AREDS category 2) or epiretinal membrane (stage 0). All patients received bilateral implantation of the non-diffractive EDOF IOL targeted for micro-monovision. Primary outcomes were monocular corrected distance visual acuity (CDVA) and distance-corrected intermediate visual acuity (DCIVA) at 3 months. Secondary outcomes included binocular CDVA, DCIVA, and distance-corrected near visual acuity (DCNVA); uncorrected distance, intermediate and near visual acuity (UDVA, UIVA, UNVA); refractive outcomes; contrast sensitivity and patient-reported outcomes, including satisfaction and visual disturbances.<br><br>RESULTS: At 3 months, median (IQR) monocular CDVA, DCIVA, and DCNVA were 0.00 (0.00-0.10), 0.18 (0.08-0.28), and 0.40 (0.30-0.50) logMAR, respectively. Binocular CDVA, DCIVA, and DCNVA were 0.00 (0.00-0.00), 0.13 (0.08-0.18), and 0.35 (0.22-0.40). Binocular UDVA, UIVA, and UNVA were 0.00 (0.00-0.00), 0.08 (-0.01-0.11), and 0.30 (0.20-0.33) logMAR, respectively. 90% of dominant and 95% of non-dominant eyes were within &#xb1;0.50 D of the intended outcome. Photopic contrast sensitivity was within normal range, while mesopic values were near the lower end of normal. Most patients (90%) were satisfied with their vision. Visual disturbances were low in frequency, severity, and bothersomeness, with median Rasch-calibrated scores of 32, 27, and 29, respectively.<br><br>CONCLUSION: In patients with early macular pathology, bilateral implantation of a non-diffractive EDOF IOL demonstrated promising distance and intermediate vision, favorable near visual outcomes, and high patient satisfaction with minimal visual disturbances. Larger, prospective, comparative studies are warranted to define candidacy for patients with macular pathology.}, }
@article {pmid42472489, year = {2026}, author = {Wu, W and Cao, Y and Li, Q and Hu, S and Wong, DSL and Barathi, VA and Lingam, G and Wang, L and Xue, J and Liu, Z}, title = {Incorporation of low-oxidation graphene oxide into electrospun poly(ε-caprolactone) /gelatin scaffolds for human embryonic stem cell-derived retinal pigment epithelium cell transplantation.}, journal = {Biomaterials}, volume = {336}, number = {}, pages = {124466}, doi = {10.1016/j.biomaterials.2026.124466}, pmid = {42472489}, issn = {1878-5905}, abstract = {Scaffold-based retinal pigment epithelium (RPE) transplantation is a candidate approach to preserve or recover vision for macular degeneration. Electrospun poly(ε-caprolactone) (PCL)/Gelatin (Gel) scaffolds have demonstrated support for cellular proliferation and function, yet their inadequate mechanical performance compromises surgical handling and deliverability. In this study, we incorporated low-oxidation graphene oxide (GO) into electrospun PCL/Gel scaffolds and evaluated their performance for human embryonic stem cell (hESC)-derived RPE cell transplantation. We found that the incorporation of low-oxidation GO improved scaffolds' WCA from 45.47 ± 8.44° to 27.48 ± 1.42° and tensile strength from 1.60 ± 0.06 MPa with an ultimate strain of 16% to 1.75 ± 0.07 MPa with an elongation at break of 44%, while maintaining fibrous formability and biocompatibility. The PCL/Gel/GO scaffolds supported RPE-specific protein expression (MITF, PAX6, CRALBP, ZO-1) and established favorable cell polarity, as indicated by apical Na[+]/K[+]-ATPase. Transmission electron microscopy assay also showed that the hESC-RPE cells on PCL/Gel/GO scaffolds formed apical microvilli. RNA-seq revealed the preservation of trophic factors and phagocytic function on PCL/Gel/GO scaffolds, which was further validated by augmented expression levels of CNTF, IGF1, and VEGFA, as well as improved fluorescent microsphere uptake capacity. Furthermore, the enhanced mechanical properties of the PCL/Gel/GO scaffold eliminated the need for additional treatment before implantation and facilitated surgical handling during implantation. In addition, the scaffold did not cause any observable short-term retinal dysfunction, indicating good short-term feasibility. Collectively, the scaffold structural features, RPE functional profiles, and surgical findings establish PCL/Gel/GO scaffolds as a versatile platform, warranting further investigation into their application in scaffold-based cell therapy for the treatment of macular degeneration.}, }
@article {pmid42468166, year = {2026}, author = {Bai, Y and Xie, M and Yao, Y and Zhou, B and Zhu, Y}, title = {Kinsenoside alleviates retinal pigment epithelium cell injury in age-related macular degeneration-like retinal injury through exosome-associated modulation of JNK/MAPK signaling.}, journal = {International immunopharmacology}, volume = {186}, number = {}, pages = {117139}, doi = {10.1016/j.intimp.2026.117139}, pmid = {42468166}, issn = {1878-1705}, abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is driven largely by retinal pigment epithelium (RPE) cell injury. Kinsenoside (KN) exhibits protective activity on RPE cells, but the direct effect on dry AMD and underlying molecular mechanisms remain unclear.<br><br>OBJECTIVE: This study aimed to investigate the protective effects of KN against RPE cell injury and dysfunction in dry AMD and to elucidate its regulatory mechanisms.<br><br>METHODS: An A2E- and blue light-induced ARPE-19 cell injury model and a blue light-induced AMD-like retinal injury mouse model were established. RPE cytotoxicity, apoptosis, senescence, inflammation, and melanogenesis-associated marker expression were evaluated. MAPK signaling was analyzed by Western blotting, and mechanistic analyses were performed using a JNK inhibitor, molecular docking analysis, an in vitro JNK enzymatic activity assay, exosome characterization, and exosome functional assays.<br><br>RESULTS: KN treatment significantly attenuated cytotoxicity, apoptosis, cellular senescence, inflammatory responses, and melanogenesis-associated marker alterations in AMD-like ARPE-19 cells. In vivo, KN reduced drusen-like deposition, improved retinal structural integrity, and partially restored outer nuclear layer thickness while suppressing senescence and inflammation. Mechanistically, KN preferentially attenuated pathological JNK activation under the examined conditions and reduced JNK enzymatic activity in vitro. Pharmacological JNK inhibition phenocopied the protective effects of KN with no additive benefit, indicating pathway convergence. Exosome inhibition, transfer, and depletion experiments supported the contribution of exosome-associated signaling to KN-mediated cytoprotection.<br><br>CONCLUSION: These findings suggest that KN alleviates RPE cell injury under AMD-like stress, at least partly through exosome-associated modulation of JNK/MAPK signaling.}, }
@article {pmid42468899, year = {2026}, author = {Chen, W and Zhu, L and Ren, C and Li, J and Liang, S and Yu, W and Liu, Z and Du, W and Yan, H and Wen, Y and Fong, HKW and Zhao, M}, title = {RGR-opsin maintains cellular homeostasis by ameliorating the proteotoxicity of its exon-skipping splice variant.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111125}, doi = {10.1016/j.exer.2026.111125}, pmid = {42468899}, issn = {1096-0007}, abstract = {PURPOSE: One of the alternative splicing variants of retinal G protein-coupled receptor (RGR), RGR-d, is recognized as a misfolded protein. With or without inhibition of the proteasome system, RGR-d has a cytotoxic effect on retinal pigment epithelium (RPE) cells. RGR-d mutant mice exhibit age-related macular degeneration-like pathologic changes. However, humans with RGR-d likely express both wild-type and splice variant forms. In this study, we investigate the protective influence of the co-expression of RGR and RGR-d protein in RPE cells.<br><br>METHODS: ARPE-19 cells overexpressing both RGR and RGR-d were treated with or without MG132. The protein-protein interaction, ubiquitination, endoplasmic reticulum (ER) stress, autophagy flux, and subcellular localization were explored. Aged RGR-d mice were subjected to ocular examination.<br><br>RESULTS: We confirm that RGR binds RGR-d in RPE cells and decreases the polyubiquitin of RGR-d. Formation of the RGR/RGR-d complex could assist RGR-d in correctly folding on the endoplasmic reticulum (ER), and ameliorate ER stress and autophagy inhibition that were induced by misfolded RGR-d protein. The complexes highly colocalize with Golgi apparatus and maintain its typical morphology, avoiding degradation by lysosomes. We observed that RGR-d mice exhibited AMD-like subretinal hyper-reflective deposits on fundus examination.<br><br>CONCLUSIONS: We have identified a fundamental mechanism in which RGR-opsin binds its splice variant, RGR-d, to form a protective complex that alleviates cytotoxicity to RPE. This discovery is significant as it reveals a previously unknown endogenous defense against proteotoxicity in the retina. Targeting the RGR-d may represent a novel and highly promising intervention for the protein-misfolding pathology of dry age-related macular degeneration.}, }
@article {pmid42469565, year = {2026}, author = {Nakanishi, Y and Akada, M and Tamiya, R and Ideyama, M and Kogo, T and Ichioka, A and Yamamoto, A and Ueda-Arakawa, N and Tamura, H and Miyata, M and Takahashi, A and Kido, A and Muraoka, Y and Miyake, M and Ooto, S and Tsujikawa, A and Hata, M}, title = {Effects of vascular endothelial growth factor and angiopoietin-2 inhibitions on intraretinal hyperreflective foci in neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42469565}, issn = {1613-2246}, support = {No. 21H03092//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: To investigate the association of hyperreflective foci (HRFs) with disease activity in treatment-naïve neovascular age-related macular degeneration (nAMD) and to compare the effects of anti-vascular endothelial growth factor (VEGF) therapy versus dual VEGF-A/angiopoietin-2 (Ang-2) inhibition on HRFs.<br><br>STUDY DESIGN: Retrospective, single-center, interventional study METHODS: This study included 72 eyes with treatment-na&#xef;ve nAMD. Thirty-two consecutive eyes received aflibercept 2mg and 40 consecutive eyes received faricimab, each undergoing three monthly loading injections. HRF presence and area, central retinal thickness (CRT), best-corrected visual acuity (BCVA), and associated parameters were evaluated at baseline and after loading. HRFs were quantified using binarized spectral-domain optical coherence tomography (SD-OCT) images with automated assistance.<br><br>RESULTS: At baseline, 45 eyes (62.5%) exhibited HRFs, all in the outer retina, with 10 eyes (13.9%) also showing inner retinal HRFs. Outer HRF area positively correlated with CRT and the maximum height of serous retinal detachment (SRD), while inner HRFs were associated with intraretinal fluid. Both treatments significantly improved BCVA and CRT. HRF presence and area decreased after treatment, primarily in the outer retina. After adjustment for baseline HRF area and clinical parameters, faricimab achieved a more substantial reduction in total, outer, and inner HRF areas than aflibercept.<br><br>CONCLUSIONS: HRFs correlated with layer-specific exudative change. Faricimab resulted in a more pronounced reduction in HRFs than aflibercept despite comparable anatomical improvements, suggesting superior control of inflammation-related retinal changes.}, }
@article {pmid42469820, year = {2026}, author = {Elbaz-Hayoun, S and Omari, L and Jaskoll, S and Kramer, A and Rinsky, B and Eiger-Moscovich, M and Song, Y and Dunaief, JL and De Zanet, S and Apostolopoulos, S and Ciller, C and Chowers, I}, title = {CCR1 signaling as a common injury pathway in retinal degeneration.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-026-03952-7}, pmid = {42469820}, issn = {1742-2094}, support = {0007972//the Israeli Ministry of Science/ ; 2080/23//Israel Science Foundation/ ; }, abstract = {Inflammation is a key driver of atrophic Age-Related Macular Degeneration (aAMD), and also plays a role in Inherited Retinal Degenerations (IRDs), two major causes of irreversible visual loss. We previously demonstrated that the C-C chemokine receptor type 1 (CCR1) is upregulated in monocytes from AMD patients, and that it mediates the recruitment of neurotoxic macrophages and activates Müller glial cells in rodent model of photic retinal injury. Here we report that CCR1 is expressed in Müller glia in eyes affected by AMD and that variants in CCR1 are potentially associated with the rate of macular atrophy progression in AMD. We also show that Ccr1 deletion is associated with reduced inflammation, and with rescue of photoreceptor integrity and function in Crb1[rd8/rd8] mice and in Pde6b[rd10] mice, two models of genetically-driven retinal degeneration. Finally, we demonstrate that treatment with small molecule CCR1 antagonists delayed photoreceptor loss in Pde6b[rd10] mice. These data suggest that CCR1 is a mediator of retinal inflammation and injury in different forms of retinal degeneration, and that CCR1 may serve as a novel therapeutic target for atrophic AMD and IRDs.}, }
@article {pmid42471600, year = {2026}, author = {Chakraborty, D and Sinha, TK and Das, A and Boral, SK and Sheth, J and Rungta, D and Mondal, S and Bhattacharya, R}, title = {Clinical evaluation of faricimab in real-world neovascular age-related macular degeneration in India: a multicenter observational study.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-05131-x}, pmid = {42471600}, issn = {1471-2415}, abstract = {PURPOSE: To evaluate the 12-month effectiveness and treatment burden of intravitreal faricimab in treatment-naive neovascular age-related macular degeneration (nAMD) in real-world clinical practice across multiple Indian centers.<br><br>METHODS: This retrospective multicenter observational study included 45 eyes with treatment-naive nAMD treated with intravitreal faricimab (6.0&#xa0;mg) using four monthly loading injections followed by pro re nata (PRN) retreatment. Best-corrected visual acuity (BCVA, logMAR) and central subfield thickness (CST) were recorded at baseline and at 1, 2, 3, 4, 6, 9, and 12 months. The presence of subretinal fluid (SRF), intraretinal fluid (IRF), and sub-retinal pigment epithelium (sub-RPE) fluid was documented. Fluorescein angiography (FA) was performed in 36 eyes and enabled angiographic lesion characterization in these eyes; indocyanine green angiography was performed selectively when clinically indicated. Injection burden and safety outcomes were also assessed.<br><br>RESULTS: Mean BCVA improved from 0.52&#x2009;&#xb1;&#x2009;0.18 logMAR at baseline to 0.08&#x2009;&#xb1;&#x2009;0.07 at month 12 (mean change, -0.44&#x2009;&#xb1;&#x2009;0.19; P&#x2009;<&#x2009;0.0001). Mean CST decreased from 418.38&#x2009;&#xb1;&#x2009;49.87&#xa0;&#x3bc;m to 201.53&#x2009;&#xb1;&#x2009;10.47&#xa0;&#x3bc;m (mean change, -216.85&#x2009;&#xb1;&#x2009;50.65&#xa0;&#x3bc;m; P&#x2009;<&#x2009;0.0001). The proportions of eyes with SRF, IRF, and sub-RPE fluid declined from 82.2%, 86.7%, and 60.0% at baseline to 13.3%, 4.4%, and 0%, respectively, at month 12 (all P&#x2009;<&#x2009;0.0001). Complete OCT drying was achieved in 39/45 eyes (86.7%). The mean total injection count was 5.09&#x2009;&#xb1;&#x2009;0.42, including 1.09&#x2009;&#xb1;&#x2009;0.42 maintenance injections after loading. No hemorrhagic recurrence or serious ocular or systemic adverse events were observed.<br><br>CONCLUSIONS: In this real-world Indian cohort, faricimab was associated with favorable visual and anatomical outcomes over 12 months, with a low maintenance injection burden. These findings should be interpreted cautiously because of the retrospective design and absence of a comparator arm.}, }
@article {pmid42467134, year = {2026}, author = {Peyla, A and Bonanata, M and Pache, M and Clerici, M and Menghini, M and Grimaldi, G and Volpe, G}, title = {Short-Term Intraocular Pressure Changes After Intravitreal Aflibercept 8 mg via Prefilled Syringe.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42467134}, issn = {2193-8245}, abstract = {INTRODUCTION: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is a standard treatment for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). A transient rise in intraocular pressure (IOP) following injection is a well-established short-term effect. Aflibercept 8 mg has recently been introduced in a prefilled syringe (PFS), although data on its short-term effect on IOP are still lacking. The aim of this study was to assess short-term IOP changes after intravitreal aflibercept 8 mg administered via PFS and to compare these results with historical cohorts receiving aflibercept 8 mg via standard syringe and aflibercept 2 mg via PFS.<br><br>METHODS: This single-centre comparative observational cohort study included a prospectively enrolled cohort of patients with nAMD or DMO receiving aflibercept 8&#xa0;mg via PFS (0.07&#xa0;mL), while two retrospective historical cohorts receiving aflibercept 8&#xa0;mg via standard syringe (0.07&#xa0;mL) or aflibercept 2&#xa0;mg via PFS (0.05&#xa0;mL) were used for comparison. IOP was measured with the iCare IC200 rebound tonometer at baseline (T0), 30&#xa0;s (T1), 5&#xa0;min (T2), and 15&#xa0;min (T3) post-injection. Patients with glaucoma or ocular hypertension were excluded. Statistical analysis was performed using Friedman and Kruskal-Wallis tests.<br><br>RESULTS: Forty-six eyes treated with aflibercept 8&#xa0;mg PFS were analysed. Baseline IOP was similar across the three groups (p&#x2009;=&#x2009;0.54). In the aflibercept 8&#xa0;mg PFS cohort, mean IOP increased from 13.92&#x2009;&#xb1;&#x2009;4.25&#xa0;mmHg at baseline to 51.29&#x2009;&#xb1;&#x2009;15.07&#xa0;mmHg at 30&#xa0;s, then fell to 31.32&#x2009;&#xb1;&#x2009;12.24&#xa0;mmHg at 5&#xa0;min and to 20.25&#x2009;&#xb1;&#x2009;7.08&#xa0;mmHg at 15&#xa0;min (p&#x2009;<&#x2009;0.001). No statistically significant between-group differences were detected at any timepoint (all p&#x2009;&#x2265;&#x2009;0.18).<br><br>CONCLUSION: Intravitreal aflibercept 8&#xa0;mg administered via PFS was associated with a transient rise in IOP immediately after injection, which resolved within 15&#xa0;min and was similar to that observed with aflibercept 2&#xa0;mg via PFS and aflibercept 8&#xa0;mg via standard syringe. These findings contribute to the characterization of the short-term IOP response associated with aflibercept 8&#xa0;mg PFS administration and may help inform routine clinical practice.}, }
@article {pmid42467820, year = {2026}, author = {Adrean, SD and Han, W and Hui, J and Pirouz, A}, title = {One-Year Results of Geographic Atrophy Patients with Pre-Existing nAMD treated with both anti-VEGF therapy and pegcetacoplan.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004915}, pmid = {42467820}, issn = {1539-2864}, abstract = {PURPOSE: To examine geographic atrophy (GA) progression in patients receiving pegcetacoplan injections with pre-existing neovascular age-related macular degeneration (nAMD) treated previously and concurrently with anti-VEGF (vascular endothelial growth factor) injections.<br><br>METHODS: Retrospective cohort study of 31 nAMD and co-existing GA patients from March 2023 to July 2025. Inclusion criteria were previous anti-VEGF treatment for &#x2265;1 year and concurrent anti-VEGF and pegcetacoplan treatments in the following year. Subfoveal GA patients were excluded. Spectral-domain optical coherence tomography (OCT), infrared reflectance (IR) data, fundus autofluorescence, and fundus photography were used to measure GA area at five time points: 1 year before pegcetacoplan initiation, then every 6 months until 1 year after pegcetacoplan initiation. Longitudinal change in GA area was analyzed using a linear mixed-effects model (LMM) with square-root transformed GA area to account for repeated measurements within eyes. Visual acuity (VA) was recorded and converted to ETDRS letters for analysis.<br><br>RESULTS: Twelve patients were male and 19 female, with an average age of 87.2 years. Mean anti-VEGF treatment interval was 11.8 weeks, and 8.1 weeks for pegcetacoplan. Average treatment duration of nAMD was 6.5 years. Square-root transformed GA area increased +0.39 mm from -1 year to pegcetacoplan initiation, then +0.22 mm from initiation to +1 year, a 44% decrease in GA growth rate (p < 0.0001). VA remained stable, starting at 67.5 letters, increasing to 67.9 letters after 2 years (p = 0.93).<br><br>CONCLUSION: Concurrent anti-VEGF and pegcetacoplan therapy was associated with an overall reduction in GA lesion growth rate and stabilized nAMD.}, }
@article {pmid42466416, year = {2026}, author = {Rivolta, C and Kaminska, K and Moye, A and Quinodoz, M and Zehr, E and Aiteur, A and Calzetti, G and Barberán-Martínez, P and Kühlewein, L and Bodenbender, JP and Ehrenberg, M and Khandhadia, S and Zur, D and Soudry, S and Barili, V and Ambrosini, E and Ottonelli, G and Feliciano-Sánchez, A and Müller, I and Wallerich, S and Galliker, P and Moulin, A and Zuleger, T and Haack, T and Wissinger, B and Stingl, K and García-García, G and Menghini, M and Vincent, A and Heon, E and Mahroo, O and Lotery, A and Webster, A and Arno, G and Millan, J and Ben-Yosef, T and Michaelides, M and Lin, S and Kohl, S and Roll-Mecak, A and Tran, V}, title = {Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-8880283/v1}, pmid = {42466416}, issn = {2693-5015}, abstract = {Inherited retinal diseases (IRDs) encompass a broad spectrum of genetic conditions leading to visual impairment. In this study, we identify KATNA1, encoding the catalytic p60 subunit of the microtubule-severing enzyme katanin, as a previously unrecognized cause of autosomal dominant macular dystrophy (adMD), a form of IRD. Specifically, we could ascertain the presence of 10 heterozygous missense changes affecting six conserved amino acids in 21 individuals from 16 unrelated families from various parts of the world, all presenting with non-syndromic MD of variable severity. Structure-guided analyses indicated that the identified variants potentially disrupt katanin's assembly into hexamers or its ability to bind or hydrolyze ATP, thus compromising its microtubule-severing function. Characterization of patient-derived fibroblasts revealed accumulation of acetylated microtubules both in the cytoplasm and within the primary cilium, together with an altered subcellular distribution of KATNA1. Immunostaining of human retinal tissue showed that KATNA1 specifically localizes to photoreceptors, with distinct distribution patterns between rod and cone photoreceptors. Immunogold transmission electron microscopy confirmed this finding, revealing KATNA1 distribution along the rod axoneme and predominantly within the cone connecting cilium. Together, these results establish KATNA1 as a novel gene associated with adMD, possibly accounting for ~4% of all unresolved MD cases, and associate defective microtubule severing and cytoskeletal dysregulation with macular degeneration.}, }
@article {pmid42457102, year = {2026}, author = {Zerti, D and Donato, L and Chust, IB and Carozza, G and Giangiulio, O and Stefanini, M and Faella, E and Feligioni, M and Di Gregorio, J and Flati, V and Carl, M and Poggi, L and D'Angelo, R and Passacantando, M and Maccarone, R}, title = {Mitochondrial preservation underlies the antioxidant activity of nanoceria particles in light-induced retinal degeneration.}, journal = {Nanomedicine : nanotechnology, biology, and medicine}, volume = {}, number = {}, pages = {102995}, doi = {10.1016/j.nano.2026.102995}, pmid = {42457102}, issn = {1549-9642}, abstract = {Age-related Macular Degeneration (AMD), the leading cause of blindness worldwide, is a multifactorial disease with mitochondrial dysfunction recognized as an early pathogenic event. In our preclinical studies, we demonstrated that a single Cerium-Oxide Nanoparticles (CeO2-NPs) intravitreal injection in a light-induced degeneration model, was able to counteract the retinal degeneration. Our aim was to investigate whether neuroprotection activity could be correlated with mitochondrial morpho-functional preservation. Bulk transcriptomic profiling of whole retinal tissue revealed that light-induced retinal injury was associated with suppression of mitochondrial-related gene networks, including components of the electron transport chain and regulators of mitochondrial dynamics, whereas CeO2-NPs treatment restored the expression of antioxidant and mitochondrial biogenesis-related genes. Ultrastructural analysis by electron microscopy showed preservation of Retinal Pigmented Epithelial mitochondria's morphology and by high-resolution crystallographic analysis confirmed the intracellular localization of CeO2-NPs in proximity to mitochondria. Furthermore, Western blot analysis demonstrated that CeO2-NPs maintained mitophagy markers at basal levels, preventing excessive activation of mitochondrial quality-control pathways. Together, these findings support mitochondrial preservation as a key mechanism underlying nanoceria-mediated retinal neuroprotection and highlight CeO2-NPs as promising candidates for maintaining retinal homeostasis in AMD.}, }
@article {pmid42457199, year = {2026}, author = {Barrett, P and Carey, C and O'Riordan, S and Wu, AD and Wallace, E and Biba, M and Kublickiene, K and McCarthy, F and Khashan, A}, title = {Hypertensive Disorders of Pregnancy and the Long-Term Risk of Maternal Retinal and Ophthalmic Disease: A Systematic Review and Meta-Analysis.}, journal = {BJOG : an international journal of obstetrics and gynaecology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1471-0528.70307}, pmid = {42457199}, issn = {1471-0528}, support = {CSF-2023-006/HRBI_/Health Research Board/Ireland ; }, abstract = {BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk of maternal cardio-metabolic disease, but links with future retinal diseases remain unclear.<br><br>OBJECTIVE: The objective of this study is to synthesise the published literature on HDP and subsequent retinal and other ophthalmic disease.<br><br>SEARCH STRATEGY: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched to March 2026 following a pre-registered PROSPERO protocol, CRD42024589508.<br><br>SELECTION CRITERIA: These included: a population of parous women, exposure to HDP at least once, at least one primary outcome (retinal disease) or secondary outcome (other ophthalmic disease). Women with pre-pregnancy retinal/ophthalmic diseases were excluded.<br><br>DATA COLLECTION AND ANALYSIS: Two reviewers independently screened studies, extracted data, and assessed bias using an adapted Newcastle-Ottawa tool. Random-effects meta-analyses were performed.<br><br>RESULTS: Of 5673 studies retrieved, 13 were eligible for inclusion (2&#x2009;450&#x2009;072 participants). HDP was associated with increased risk of diabetic retinopathy (aRR 3.54, 95% CI 2.19-5.74), particularly after preeclampsia (aRR 4.24, 95% CI 3.51-5.12). HDP-exposed women were also at higher risk of non-diabetic retinopathy (aRR 3.65, 95% CI 1.18-11.33), retinal detachment (aRR 1.54, 95% CI 1.28-1.86), and retinal vascular occlusion (aRR 2.09, 95% CI 1.55-2.81). HDP-exposed women may also be at risk of hypertensive retinopathy and central serous chorioretinopathy, but aRRs did not reach statistical significance. Across individual studies, HDP-exposed women were reported to be at increased risk of cataract extraction, non-infectious uveitis, and choroidal neovascular age-related macular degeneration.<br><br>CONCLUSION: Women who experience HDP may be at future risk of retinal and other ophthalmic diseases, particularly diabetic retinopathy. Further observational research is required to confirm these associations.}, }
@article {pmid42458644, year = {2026}, author = {Matsuyama, A and Miki, A and Oka, T and Ikeuchi, E and Kishimoto-Kishi, M and Miki, K and Imai, H and Nakamura, M}, title = {Real-world functional and anatomical outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration: a phenotype-based analysis by pachychoroid and polypoidal lesion status.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00901-7}, pmid = {42458644}, issn = {2056-9920}, abstract = {BACKGROUND: To evaluate the short-term functional and anatomical outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration (nAMD), and to explore whether the early treatment response varied according to pachychoroid and polypoidal lesion status.<br><br>METHODS: This retrospective, multicenter observational study evaluated 45 treatment-na&#xef;ve eyes of 45 patients with nAMD who received three monthly loading injections of aflibercept 8&#xa0;mg. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative findings (subretinal fluid [SRF], intraretinal fluid [IRF], and subretinal hyperreflective material [SHRM]) were assessed at baseline and at 1, 2, and 4 months. Pachychoroid and polypoidal lesion status was determined using multimodal imaging. Longitudinal changes were analyzed using linear mixed-effects models, with subgroup analyses by pachychoroid and polypoidal lesion status.<br><br>RESULTS: At 4 months, mean BCVA improved from 0.27&#x2009;&#xb1;&#x2009;0.33 to 0.20&#x2009;&#xb1;&#x2009;0.31 logMAR (P&#x2009;=&#x2009;0.005), CRT decreased from 382.1&#x2009;&#xb1;&#x2009;189.7 to 231.3&#x2009;&#xb1;&#x2009;109.1&#xa0;&#x3bc;m, and CCT from 263.0&#x2009;&#xb1;&#x2009;146.5 to 231.0&#x2009;&#xb1;&#x2009;127.2&#xa0;&#x3bc;m (both P&#x2009;<&#x2009;0.001). The dry macula rate (absence of both SRF and IRF) increased from 17.8% to 75.6% (P&#x2009;<&#x2009;0.001). Functional and retinal anatomical responses were broadly consistent across phenotypes, with no significant time-by-phenotype interactions for BCVA or CRT. Pachychoroid eyes showed a greater CCT reduction (interaction P&#x2009;<&#x2009;0.001), but this was no longer significant after adjusting for baseline CCT. As exploratory observations, the time-by-polypoidal-lesion interaction for BCVA was not significant (P&#x2009;=&#x2009;0.052), and residual SHRM at 4 months was present in 0% of polypoidal-lesion eyes versus 22.2% of those without (P&#x2009;=&#x2009;0.067).<br><br>CONCLUSIONS: Intravitreal aflibercept 8&#xa0;mg led to significant short-term improvements in BCVA, CRT, CCT, and exudative findings in treatment-na&#xef;ve nAMD, with benefit observed irrespective of pachychoroid or polypoidal lesion status.}, }
@article {pmid42459964, year = {2026}, author = {Rothaus, K and Grün, M and Faatz, H and Ziegler, M and Spital, G and Lommatzsch, A and Gutfleisch, M and Heimes-Bussmann, B and Lange, C}, title = {Real-world evaluation of an OCT-based AI decision-support system for neovascular AMD activity triage in teleophthalmology.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1870572}, pmid = {42459964}, issn = {2674-0826}, abstract = {PURPOSE: To evaluate real-world agreement between a CE-marked OCT-based AI decision-support system and routine retreatment decisions for neovascular AMD within a teleophthalmology workflow.<br><br>METHODS: Retrospective clinical study including 429 OCT examinations from 247 patients (306 treated eyes) with neovascular AMD. Retinal specialists made routine retreatment decisions ("inject" vs "watch-and-wait") using full clinical context. Independently, the AI system (deepeye[&#xae;] TPS, version 1.2) analyzed the current OCT volume only (no prior OCT, visual acuity, treatment interval, or clinical notes) and generated a Disease Activity Score (DAS; 0-100) used to derive an "inject" vs "watch-and-wait" recommendation. Discrepant cases were re-evaluated by senior graders to establish a double-senior-graded (DSG) reference standard. Implementation analyses assessed a deferral ("safety zone") strategy. Main outcome measures included agreement/accuracy, sensitivity, and specificity versus real-world decisions and the double-senior-graded (DSG) reference standard, as well as decision coverage under deferral.<br><br>RESULTS: Agreement between real-world decisions and AI recommendations was 83.2% (sensitivity 74.7%, specificity 88.0%). Against the double-senior-graded reference standard (DSG), accuracy in the full analysis set (FAS), analyzed at the examination level, was 85.5% (sensitivity 77.2%, specificity 90.4%). Using an empirically optimized DAS threshold, accuracy increased to 88.6% (sensitivity 78.5%, specificity 94.9%) in the eligible retreatment-decision set (ERDS). Application of a deferral policy ("safety zone", DAS 33-64) resulted in automated recommendations for 78.4% of eligible examinations, while 21.6% were deferred due to intermediate DAS values; among examinations with an automated recommendation, accuracy was 92.3% (sensitivity 83.2%, specificity 97.5%). Most misclassifications involved subtle IRF/SRF and SHRM as identified by the reading center and tended to be underestimated by the AI.<br><br>CONCLUSION: The evaluated OCT-only AI decision-support output showed substantial agreement with routine retinal-specialist retreatment decisions in a real-world teleophthalmology workflow, particularly when intermediate Disease Activity Scores were deferred to human review. However, false-negative cases and context-dependent discrepancies highlight that the system should support, not replace, clinician judgement. Prospective multicenter validation using longitudinal and multimodal input data is required before broader workflow integration can be recommended.}, }
@article {pmid42460002, year = {2026}, author = {Choo, DM and Durham, TA and Patel, KG}, title = {Assessing retina-specific ophthalmic counseling generated by an early public large language model across different levels of clinical urgency.}, journal = {Frontiers in digital health}, volume = {8}, number = {}, pages = {1849883}, pmid = {42460002}, issn = {2673-253X}, abstract = {PURPOSE: To evaluate how the quality of retina-specific ophthalmology counseling provided by an early publicly available large language model (LLM) differs when advising patients with varying clinical characteristics and risk factors.<br><br>DESIGN: Prospective, cross-sectional study.<br><br>SUBJECTS: 18 ophthalmologists.<br><br>METHODS: Six patient vignettes were constructed with high- and low-urgency clinical scenarios for diabetic retinopathy (DR), retinal detachment (RD), and age-related macular degeneration (AMD). Based on these vignettes, an LLM (ChatGPT-3.5) was asked to provide written medical counseling in February 2024. Each response was rated on several metrics via 5-point Likert scale by 18 independent reviewers. Notably, readability was assessed both qualitatively via survey and quantitatively via Readable (an online readability tool that incorporates 5 different metrics).<br><br>MAIN OUTCOME MEASURES: Counseling generated by the LLM was graded on accuracy, appropriate communication of urgency and empathy, readability, and potential for clinically significant harm.<br><br>RESULTS: Counseling accuracy differed across levels of clinical urgency (p&#x2009;=&#x2009;0.002) but remained consistent between high- and low-urgency vignettes of AMD (p&#x2009;=&#x2009;0.081) and DR (p&#x2009;=&#x2009;0.5), albeit not for RD (P&#x2009;<&#x2009;0.001). Counseling urgency did not differ significantly from clinical urgency of all vignettes, except for the high-urgency AMD (p&#x2009;=&#x2009;0.013) and high-urgency RD (p&#x2009;<&#x2009;0.001). While counseling urgency did not significantly differ between high- and low-urgency vignettes of AMD (p&#x2009;=&#x2009;0.055) and RD (p&#x2009;=&#x2009;0.3), it did differ for the DR vignettes (p&#x2009;<&#x2009;0.001). Counseling empathy did not differ across clinical urgency (p&#x2009;=&#x2009;0.2). Four readability indices (e.g., Flesch Kincaid Grade Level) consistently indicated that college graduation would be required to understand every counseling output. Across all vignettes, the most common reasons for potential difficulty in understanding the counseling were having too much medical (49%) and non-medical (45%) terminology.<br><br>CONCLUSIONS: The evaluated LLM-generated counseling outputs were largely similar across the sampled retinal vignettes with differing clinical urgency. Future studies should investigate the optimization of LLM prompting needed to garner counseling of consistent/appropriate accuracy, readability, empathy, and communication of urgency for specific conditions.}, }
@article {pmid42460402, year = {2026}, author = {Fossataro, C and Savastano, MC and Cusato, M and Cestrone, V and Mottola, F and Hu, L and Campaniello, G and Oreste, G and Giannuzzi, F and Maiola, E and Mastropietro, G and Savastano, A and Valentini, CG and Pellegrino, C and Teofili, L and Rizzo, S}, title = {Transitory vitreous opacities after CB-PRP intravitreal injections in dry AMD patients.}, journal = {Therapeutic advances in ophthalmology}, volume = {18}, number = {}, pages = {25158414261462410}, pmid = {42460402}, issn = {2515-8414}, abstract = {BACKGROUND: Dry age-related macular degeneration currently lacks effective treatments for geographic atrophy. Cord blood platelet-rich (CB-PRP) plasma intravitreal injections are a novel therapy under investigation with promising ad interim results.<br><br>OBJECTIVES: To describe the safety profile of cord blood platelet-rich plasma intravitreal injections (IVIs) in dry age-related macular degeneration (AMD) patients.<br><br>DESIGN: This prospective, randomized, sham-controlled, open-label experimental trial evaluated the safety of repeated intravitreal CB-PRP injections.<br><br>METHODS: The study, conducted from January 2023 to January 2025, investigated the safety and efficacy of CB-PRP IVIs to slow down the progression of geographic atrophy (GA). One eye of each patient was randomly assigned to the monthly, every other month, or every 3&#x2009;months arm and received 0.05&#x2009;mL CB-PRP, while the other eye underwent only a sham injection. Complete ophthalmological evaluations were performed at baseline, 3-, 6-, 12-, 18-, and 24-month follow-ups. In addition, slit-lamp and fundus examinations were performed the day after the injection to exclude any adverse effect.<br><br>RESULTS: In a total of 328 intravitreal injections, vitreous opacities were observed in the absence of other signs of infection or inflammation only in three cases. All of them showed progressive improvement without treatment, and complete recovery was observed within 2&#x2009;weeks.<br><br>CONCLUSION: Although the pathogenesis of the detected vitreous thickening was not completely clear, the most likely hypothesis was the coexistence of a slightly lower temperature of the CB-PRP sample and individual factors. This mild adverse event occurred only once in each patient involved, with no recurrence during subsequent intravitreal injections. The occurrence of this self-limiting finding after CB-PRP IVIs has not invalidated the safety profile of the procedure.}, }
@article {pmid42460478, year = {2026}, author = {Yuan, F and Tu, J and Liu, X and Wang, L and Zhou, W and Jin, Y}, title = {Serum NLR, PLR and MNV characteristics as predictors of anti-VEGF plus glucocorticoid efficacy in nAMD.}, journal = {Biomarkers in medicine}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17520363.2026.2704571}, pmid = {42460478}, issn = {1752-0371}, abstract = {AIM: To evaluate the combined predictive value of serum neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and macular neovascularization (MNV) characteristics for treatment efficacy in neovascular age-related macular degeneration (nAMD) patients receiving anti-VEGF plus glucocorticoid therapy.<br><br>PATIENTS AND METHODS: This retrospective study included 145 patients (153 eyes) with nAMD receiving conbercept combined with dexamethasone implant. Patients were categorized as Inactive (n&#x2009;=&#x2009;89) or Active (n&#x2009;=&#x2009;64) based on post-treatment MNV activity. Baseline NLR, PLR, and MNV morphology were assessed. Multivariate logistic regression identified independent predictors, and ROC analyses evaluated predictive value.<br><br>RESULTS: Patients with persistent MNV activity showed significantly higher baseline NLR, PLR, MNV area, and fractal dimension (all p&#x2009;<&#x2009;0.001). Multivariate analysis identified baseline visual acuity, MNV type, fluid volumes, MNV morphological parameters, and inflammatory markers as independent predictors. The combined model incorporating inflammatory markers and MNV characteristics demonstrated superior performance (AUC&#x2009;=&#x2009;0.92, 95% CI: 0.87-0.96) with 79.69% sensitivity and 91.01% specificity.<br><br>CONCLUSION: Combining serum inflammatory markers with MNV morphological characteristics enhanced predictive value for treatment response in nAMD patients receiving combination therapy. This integrated approach may facilitate personalized treatment strategies in nAMD management.}, }
@article {pmid42464986, year = {2026}, author = {Betancourt Sanchez, A and Huynh, A and Blanchard, L and De Groot, A and Klopp, C and Loubière, K and Andriantsiferana, C and Lajoie, B}, title = {Zeaxanthin-Producing Winogradskyella schleiferi Strains.}, journal = {Journal of basic microbiology}, volume = {66}, number = {7}, pages = {e70187}, doi = {10.1002/jobm.70187}, pmid = {42464986}, issn = {1521-4028}, mesh = {*Zeaxanthins/biosynthesis ; Phylogeny ; Mediterranean Sea ; Seawater/microbiology ; RNA, Ribosomal, 16S/genetics ; Temperature ; Carotenoids ; }, abstract = {Two pigmented bacteria strains were isolated from the Mediterranean Sea. Phylogenetic analysis revealed that both strains are affiliated with Winograsdskyella schleiferi Z215. However, in contrast to this reference strain, they can assimilate additional carbon sources such as d-mannose, l-arabinose, d-mannitol, and citrate. Zeaxanthin was identified as the major carotenoid produced by both strains, predominantly in the all-trans configuration. Carotenoid biosynthesis kinetics revealed that pigment production commenced at the early stages of growth, with maximal yields reached between 48 and 56 h (between 1 and 1.3 mg L[-1]). Specific production yields were 0.7 and 0.9 mg g[-1] for the two strains, respectively. Total carotenoid production was influenced by incubation temperature in both strains. Overall, these findings expand the scientific knowledge on carotenoid-producing marine bacteria and highlight the potential of these newly isolated strains as promising candidates for zeaxanthin biotechnological production for a wide range of novel applications ranging from feed additives to treatments for macular degeneration and melanoma.}, }
@article {pmid42465049, year = {2026}, author = {Bozal, S and Yue, JS and DiStasio, M and Rothrock, A and Zhang, X and Sutova, HE and Bhatta, S and Deschenes, E and Ju, G and Saltzman, WM and Hafler, BP}, title = {Erratum: 415 Designing nanoparticle therapies for age-related macular degeneration - ERRATUM.}, journal = {Journal of clinical and translational science}, volume = {10}, number = {1}, pages = {e105}, pmid = {42465049}, issn = {2059-8661}, abstract = {[This corrects the article DOI: 10.1017/cts.2026.10567.].}, }
@article {pmid42465550, year = {2026}, author = {Fila, M and Krekora, J and Drożdż, J and Kaarniranta, K and Blasiak, J}, title = {Retinal connections to migraine.}, journal = {Frontiers in neurology}, volume = {17}, number = {}, pages = {1835914}, pmid = {42465550}, issn = {1664-2295}, abstract = {OBJECTIVE: This narrative review aims to examine potential associations between migraine and retinal disorders, with particular attention to retinal migraine, age-related macular degeneration (AMD), retinal vascular occlusions, and photophobia.<br><br>BACKGROUND: The role of retinal pathways in migraine pathophysiology remains poorly understood. As a component of the central nervous system, the retina provides a unique and accessible window into neuronal structure and function. Emerging observations suggest that structural and functional retinal changes may occur in individuals with migraine; however, their relevance and consistency across studies remain uncertain.<br><br>RESULTS: Visual phenomena are characteristic of migraine aura, yet the extent to which migraine affects retinal structure and function is still unclear. Retinal migraine, while suggestive of a direct retinal involvement, is rare and insufficiently characterized to support mechanistic conclusions. Epidemiological data indicate that individuals with migraine may have an increased risk of neovascular AMD, raising the possibility of shared pathogenic pathways. In addition, photophobia, retinal artery occlusion, and alterations in retinal nerve fiber layer thickness have been reported more frequently in migraine patients than in controls, although causality has not been established. Mechanisms implicated in AMD, including microvascular dysfunction, impaired DNA damage response, disrupted autophagy, and mitochondrial dysregulation, have also been proposed in migraine, but evidence remains limited.<br><br>CONCLUSION: Migraine has been linked to several retinal conditions, with AMD showing the most consistent association. While overlapping biological processes are suggested, further studies are needed to clarify their significance and determine whether retinal alterations contribute to migraine pathophysiology or represent secondary phenomena.}, }
@article {pmid42450389, year = {2026}, author = {Predescu, NC and Papuc, C and Stefan, G and Rosu, PM and Chervenkov, M and Saracila, M and Panaite, TD and Ionascu, I}, title = {Anthocyanins as Adjunctive Dietary Modulators of the Gut-Eye Axis: Bioavailability, Biotransformation, and Implications for Ocular Health.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {13}, pages = {}, doi = {10.3390/foods15132270}, pmid = {42450389}, issn = {2304-8158}, abstract = {Retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are major causes of visual impairment and are closely associated with oxidative stress, inflammation, vascular dysfunction, and metabolic imbalance. Increasing evidence suggests that gut microbiota also contributes to retinal homeostasis, supporting the emerging concept of the gut-eye axis. In this context, dietary anthocyanins-with blueberry anthocyanins serving as a primary representative model-have attracted attention as potential adjunctive nutritional modulators of ocular health. However, their biological effects are strongly influenced by their limited bioavailability and extensive gastrointestinal metabolism. The objective of this review is to analyze the gastrointestinal fate of dietary anthocyanins and to discuss how their absorption, enzymatic transformation, and microbial biotransformation may influence ocular protection through the gut-eye axis. The review summarizes current knowledge regarding anthocyanin stability in the oral cavity, stomach, small intestine, and colon, as well as the formation of circulating phenolic metabolites generated by the host and through microbial metabolism. In addition, the molecular mechanisms through which anthocyanins and their metabolites may support retinal health are examined, including antioxidant, anti-inflammatory, vasoprotective, and neuroprotective actions. Overall, dietary anthocyanins, illustrated through the rich profile of blueberries, represent promising adjunctive compounds for supporting ocular health, although further clinical and mechanistic studies are still required.}, }
@article {pmid42452359, year = {2026}, author = {Sandali, O and Tahiri Joutei Hassani, R and Audo, I and Gualino, V and Tchikladze Merand, C and Borderie, V}, title = {Effect of Minimizing Light Exposure with Digital Visualization on Macular Function After Cataract Surgery in Patients with AMD: A Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {15}, number = {13}, pages = {}, doi = {10.3390/jcm15134897}, pmid = {42452359}, issn = {2077-0383}, support = {IIT#73473171//Alcon (United States)/ ; }, abstract = {Purpose: To assess whether reducing intraoperative light exposure preserves macular function after cataract surgery in patients with AMD. Methods: A total of 42 eyes of 42 patients with AMD were randomized in a prospective study. The primary outcome was the change in photopic (ERG) b-wave amplitude at one hour after surgery (V2). Secondary outcomes included ERG implicit time, multifocal ERG, visual acuity, and macular thickness, assessed at V2, V3 (day 1), and V4 (1 month). Results: Mean intraoperative light exposure was significantly lower in the 3D group than in the standard group (3938 vs 47,142 lux, p < 0.001). At 1 h after surgery, the decrease in photopic b-wave amplitude did not differ significantly between the two groups (-1.83 µV; 3D group, vs. -1.56 µV; standard group, p = 0.76). In exploratory analyses, ERG implicit time increased significantly in the standard group (p = 0.02) but remained stable in the 3D group (p = 0.24). At 1 month, an increase in macular thickness was observed only in the standard group (V1 265.9 ± 27.7 µm, V4 278.8 ± 34.9 µm; p = 0.003). Conclusions: Digital visualization significantly reduced intraoperative light exposure. However, no significant difference was observed for the primary endpoint of photopic ERG b-wave amplitude at 1 h postoperatively. Secondary findings regarding ERG implicit time and macular thickness should be considered exploratory and require confirmation in larger studies.}, }
@article {pmid42452475, year = {2026}, author = {Asanad, S and Thomspon, J}, title = {Clinical Value of Optical Coherence Tomography Angiography in Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {13}, pages = {}, doi = {10.3390/jcm15135013}, pmid = {42452475}, issn = {2077-0383}, abstract = {Background/Objectives: The utility of optical coherence tomography angiography (OCTA) for neovascular age-related macular degeneration (nAMD) remains unclear. The current study investigated the choroidal neovascularization (CNV) detection rate by OCTA in comparison with standard fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Methods: Subjects underwent multimodal imaging, including FA, SD-OCT, and OCTA imaging, which were compared. In patients with unilateral nAMD, the contralateral eye with dry AMD (n = 39) was included to determine imaging modality sensitivity and specificity. Eyes with inaccurate automated segmentation from retinal distortion were manually resegmented. Results: The diagnostic performance for nAMD was 86% sensitivity and 100% specificity by OCT (AUC: 0.93; 95% CI 0.87-0.99; p < 0.001); 82% sensitivity and 100% specificity by FA (AUC: 0.91; 95% CI 0.84-0.98; p < 0.001); and 68% sensitivity and 100% specificity by automatically segmented OCTA (AUC: 0.84; 95% CI 0.76-0.93; p < 0.001). OCTA diagnostic accuracy improved following manual resegmentation to 88% sensitivity and 100% specificity (AUC: 0.94; 95% CI 0.89-1.0; p < 0.001). Diagnostic accuracy of OCT combined with manually resegmented OCTA (AUC: 1.0; 95% CI 1.0-1.0; p < 0.001) was greater than that of OCT or FA combined (AUC: 0.96; 95% CI 0.92-1.0; p < 0.001) but both were very accurate. Conclusions: Manual segmentation of the OCTA images can help identify CNV in eyes otherwise undetected by automated segmentation algorithms due to errors in segmentation of retinal layers. Eyes with substantial elevation in one or more layers of the retina were most likely to benefit from resegmentation.}, }
@article {pmid42454894, year = {2026}, author = {Sortino, R and González-Díez, A and Milla-Navarro, S and Martínez-Tambella, J and Paleo-García, V and Calatayud, E and de Saralegui, P and Opar, E and Claparols, &#xc0; and Quintanilla, JA and Martínez-Soler, X and Riefolo, F and Matera, C and Hernando, J and Gomila, AMJ and Pérez-Batlle, G and Pereira, C and Camarero, N and Serra, C and Gómez-Santacana, X and Llebaria, A and Rovira, X and de la Villa, P and Gorostiza, P}, title = {Restoration of Saccadic Eye Movements and Visually Guided Behavior in Ambient White Light with Photoswitchable Small Molecules.}, journal = {Journal of the American Chemical Society}, volume = {}, number = {}, pages = {}, doi = {10.1021/jacs.5c18611}, pmid = {42454894}, issn = {1520-5126}, abstract = {Blinding diseases due to the degeneration of photoreceptors (PhRs), such as geographic atrophy (GA) secondary to dry age-related macular degeneration and retinitis pigmentosa (RP), leave the rest of the retinal circuitry largely intact, albeit unable to respond to light. Gene therapy has been able to revert PhR degeneration, but it can be applied only to a rare mutation affecting a small subset of RP patients. Alternatively, implanted electronic retinal prostheses aim at a larger population by electrically stimulating surviving neurons. However, the treatment is invasive and costly and provides limited resolution. Photopharmacology can develop photoswitchable small molecules to restore vision impairment by conferring light sensitivity to ion channels that are widely expressed in the remaining inner retinal neurons, and a first-in-human clinical trial is ongoing. Here, we have developed novel photoswitchable small-molecule ligands of metabotropic glutamate 6 (mGlu6) receptors, which are located exclusively at the dendrites of ON bipolar cells (postsynaptic to PhRs) and can leverage a privileged position to mimic physiological signals in the remnant retinal circuit. These photoswitchable ligands (prosthe6) thus act as "molecular prostheses" that can restore the light input to the retina via upstream-targeted control of the circuit after PhR degeneration. Prosthe6 compounds are allosteric, drug-like, water-soluble, and display outstanding in vitro properties including full efficacy, nanomolar potency, fast deactivation in ambient white light, and fast reactivation in the dark. In vivo experiments show that they readily recover the saccadic eye movements of blinded zebrafish larvae and restore the innate light-avoidance behavior in the mouse models of blindness (GA and RP). These effects are mediated by mGlu6 receptors in vivo. In addition, at least two compounds (prosthe6-12 and -15) can restore sight by topical administration and display promising safety properties to become potential drug candidates for sight restoration in patients with degenerative blinding diseases.}, }
@article {pmid42456794, year = {2026}, author = {Papafotiou, E and Arampatzis, K and Ferreira, A and Koumpoulis, I and Tsinopoulos, I}, title = {Prognostic value of subretinal hyperreflective material as an imaging biomarker in the treatment of neovascular age-related macular degeneration: A systematic review.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.07.007}, pmid = {42456794}, issn = {1879-3304}, abstract = {Subretinal hyperreflective material (SHRM) is now recognized as a biomarker in neovascular age-related macular degeneration (nAMD), with potential prognostic value for visual and structural outcomes. We synthesize and critically evaluate the evidence on the prognostic role of SHRM characteristics in patients with nAMD. We conducted a systematic search of PubMed, Scopus and Web of Science for studies published between March, 2015, and March, 2025. Eligible studies included human participants with nAMD, under anti-vascular endothelial growth factor (VEGF) treatment, in which SHRM was assessed using optical coherence tomography and outcomes included best-corrected visual acuity (BCVA), fibrosis and macular atrophy. Thirty-three studies met the inclusion criteria. Most of the studies demonstrated a significant association between the presence of SHRM and worse BCVA over time, particularly correlated to SHRM thickness, width or persistence after anti-VEGF therapy. Well-defined and hyperreflective SHRM was repeatedly linked to poorer functional outcomes. Twelve studies reported SHRM as a strong predictor of subretinal fibrosis, with larger size, defined borders and persistence conferring the greatest risk. The relationship with macular atrophy was less clear; while some studies suggested that thicker or persistent SHRM increased the likelihood of atrophy, others found no association. Overall, the evidence suggests that SHRM is a strong imaging biomarker of poor prognosis in nAMD. While this review highlights consistent patterns, differences in how SHRM is measured remain a limitation. It will be important for future research to standardize SHRM assessment and establish its use in personalized treatment decisions.}, }
@article {pmid42439430, year = {2026}, author = {Beqiri, S and Moxam, J and Pan, H and Kumar, BS and Berni, A and Shen, M and El-Mulki, OS and Herrera, G and Badla, O and Lam, W and Herrera, E and Ascioti, N and Le, VH and Trivizki, O and O'Brien, RC and Waheed, NK and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Impact of Swept-Source OCT Angiographic Scanning Speeds on the Detection of Choriocapillaris Flow Deficits in Eyes With AMD.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {7}, pages = {16}, doi = {10.1167/tvst.15.7.16}, pmid = {42439430}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Female ; Retrospective Studies ; *Macular Degeneration/physiopathology/diagnostic imaging ; Male ; Aged ; Regional Blood Flow/physiology ; *Fluorescein Angiography/methods ; Aged, 80 and over ; Prospective Studies ; Blood Flow Velocity ; Capillaries/physiopathology/diagnostic imaging ; }, abstract = {PURPOSE: The impact of swept-source optical coherence tomography angiography (SS-OCTA) scanning speeds (interscan times) on the quantification of choriocapillaris flow deficit percentages (CCFD%) was studied in eyes with nonexudative age-related macular degeneration.<br><br>METHODS: We conducted a retrospective review of 30 pairs of scans from 24 age-related macular degeneration subjects enrolled in an ongoing prospective SS-OCTA imaging study. Patients underwent imaging with same day scans at two scanning speeds: 100&#xa0;kHz and 200&#xa0;kHz (corresponding with 5.0-ms and 2.5-ms interscan times, respectively). Best practices for CC slab processing and CCFD quantification were implemented, and the compensation level was optimized for each scan. CCFD% measurements were obtained from the 3-mm and 5-mm fovea-centered circles.<br><br>RESULTS: The mean CCFD% measurements from the 3-mm fovea-centered circles for the 100-kHz and 200-kHz scans were 14.20% and 17.17% respectively, and 10.77% and 12.86% for the 5-mm circles. An agreement analysis showed a significant bias with mean values of 2.96% and 2.09% for the 3-mm and 5-mm circles. The limits of agreement extended predominantly in the positive direction with values of -1.96% to 7.89% and -0.60% to 4.78% in the 3-mm and 5-mm circles, respectively, that emphasize the systematically higher CCFD% recorded using the 200-kHz pattern. No confidence interval for the bias included zero, supporting the significant systematic bias across measurement strategies.<br><br>CONCLUSIONS: SS-OCTA scanning speeds have a significant impact on CCFD% quantification, with slower speeds yielding a lower CCFD%, likely due to the detection of slower CC flow, because of the higher associated interscan times.<br><br>TRANSLATIONAL RELEVANCE: When following and comparing choriocapillaris flow deficit percentage measurements over time, the same scanning speed should be used at each visit.}, }
@article {pmid42441062, year = {2026}, author = {Wang, Y and Zhang, W and Cheng, F and Wang, J and Xiao, K and Wang, D and Zhao, X and Zou, R and Yao, Q}, title = {Mannose-modified miR-223 nanoparticles remodel pathological microenvironment to suppress inflammation and angiogenesis for neovascular AMD therapy.}, journal = {International journal of pharmaceutics: X}, volume = {12}, number = {}, pages = {100589}, pmid = {42441062}, issn = {2590-1567}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with neovascular AMD (nAMD) driven by choroidal neovascularization (CNV), persistent inflammation, and oxidative stress. Although combinatorial strategies targeting these pathological factors hold therapeutic promise, their clinical translation is constrained by the lack of effective delivery systems. In this study, we designed a mannose-functionalized poly(aspartic acid)-based nanocarrier bearing quaternary ammonium and boronic acid groups (MDA/QPABA) for the targeted delivery of microRNA-223 (miR-223). The system exploits charge-driven self-assembly to form stable nanoparticles with high loading efficiency, favorable colloidal stability, and tunable surface properties. The mannose moieties enable specific recognition by mannose receptors on target cells, facilitating cellular uptake and subsequent lysosomal escape. The resulting MDA/QPABA/miR-223 nanoparticles demonstrated pronounced anti-inflammatory, antioxidant, and anti-angiogenic activities in vitro. In a laser-induced CNV mouse model, they effectively reduced inflammatory and angiogenic cytokines, suppressed pathological neovascularization, restored retinal and choroidal structure, and preserved photoreceptor function, with an excellent biosafety. These findings highlight the potential of rationally engineered poly(aspartic acid)-based nanoarchitectures with tailored surface chemistry and biointerfacial properties for multifunctional nucleic acid delivery in nAMD therapy.}, }
@article {pmid42445785, year = {2026}, author = {Wang, Y and Wan, X}, title = {Metabolic vulnerability, genetic susceptibility, and incident age-related eye diseases: a prospective cohort study.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1840459}, pmid = {42445785}, issn = {2296-861X}, abstract = {BACKGROUND: Metabolic dysregulation is increasingly recognized as a systemic process contributing to chronic disease development, yet prospective evidence linking integrated metabolic vulnerability to age-related eye diseases remains limited. We investigated whether a biomarker-based metabolic vulnerability index (MVX) was associated with incident age-related ocular diseases and whether joint consideration of MVX and genetic susceptibility may help characterize relative risk patterns.<br><br>METHODS: A prospective population-based cohort of 206,311 participants from the UK Biobank was analyzed. MVX was evaluated as the primary exposure. Incident age-related macular degeneration (AMD), cataract, diabetic retinopathy (DR), and glaucoma were ascertained as outcomes. Associations were examined using Cox proportional hazards models, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated per 1-standard deviation (SD) increase in MVX. As secondary exploratory analyses, polygenic risk score (PRS) analyses were performed to explore whether metabolic vulnerability and genetic susceptibility jointly characterized relative risk patterns.<br><br>RESULTS: During follow-up, 4,144 participants developed AMD, 13,574 cataract, 1,483 DR, and 5,525 glaucoma. After multivariable adjustment for demographic, socioeconomic, clinical, and lifestyle factors, each 1-SD increase in MVX was associated with higher risks of incident AMD (HR = 1.07; 95% CI: 1.03-1.11), cataract (HR = 1.04; 95% CI: 1.02-1.06), and DR (HR = 1.11; 95% CI: 1.05-1.18), whereas no significant association was observed for glaucoma (HR = 1.00; 95% CI: 0.97-1.03). In joint analyses, individuals with both high genetic risk and elevated MVX exhibited the greatest risks of AMD (HR = 2.32; 95% CI: 2.01-2.67), cataract (HR = 1.62; 95% CI: 1.49-1.76), and DR (HR = 3.84; 95% CI: 2.91-5.06), compared with those with low genetic risk and low MVX.<br><br>CONCLUSION: These findings suggest that MVX may be relevant to population-level patterns of risk for several age-related eye diseases. However, further studies are needed to determine whether MVX provides meaningful predictive value or clinical utility beyond conventional risk factors.}, }
@article {pmid42448079, year = {2026}, author = {Sakamoto, T and Kadomoto, S and Nakanishi, Y and Muraoka, Y and Hata, M and Ooto, S and Tsujikawa, A}, title = {In Vivo Quantification of Bruch's Membrane Changes in Angioid Streaks and Neovascular AMD Using Multimodal Imaging.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.011}, pmid = {42448079}, issn = {1879-1891}, abstract = {PURPOSE: To investigate Bruch's membrane (BrM) morphology in angioid streak (AS)-associated macular neovascularization (MNV) and neovascular age-related macular degeneration (nAMD) using multimodal imaging.<br><br>DESIGN: Retrospective clinical cohort study.<br><br>SUBJECTS: Treatment-na&#xef;ve eyes with MNV secondary to AS or nAMD that achieved a dry macula after three loading intravitreal anti-vascular endothelial growth factor (VEGF) injections.<br><br>METHODS: Baseline indocyanine green angiography (ICGA) images obtained before anti-VEGF treatment were used to measure axial length-corrected MNV area and identify late-phase speckled hypofluorescent areas (SHA). Optical coherence tomography (OCT) images after dry macula achievement were used to assess central foveal thickness (CFT), subfoveal choroidal thickness (SCT), fibrovascular pigment epithelial detachment (PED) thickness, BrM undulation, and a newly defined BrM reflectivity index (BRI) calculated from intensity-normalized images. Group comparisons assessed BrM-related biomarker differences, and receiver operating characteristic (ROC) analyses evaluated their diagnostic performance.<br><br>MAIN OUTCOME MEASURES: Differences in ICGA- and OCT-derived findings between AS-associated MNV and nAMD, including SHA, BrM undulation, and BRI, and the diagnostic performance of BRI and BrM undulation in differentiating AS-associated MNV from nAMD.<br><br>RESULTS: Twenty-five eyes with AS and 32 eyes with nAMD were analyzed. Among eyes with available ICGA, MNV area was larger in AS than in nAMD (5.34 &#xb1; 3.29 mm&#xb2; vs 3.45 &#xb1; 1.22 mm&#xb2;, P&#x202f;=&#x202f;0.005), and late-phase SHA was more frequent in AS (86.4% vs 18.8%, P<0.001). CFT and fibrovascular PED thickness did not differ significantly, whereas SCT was lower in AS-associated MNV than in nAMD (166.0 &#xb1; 67.1 &#x3bc;m vs. 217.2 &#xb1; 112.0 &#x3bc;m; P&#x202f;=&#x202f;0.049). BrM undulation was more common in the AS group (24.0% vs. 3.1%, P=0.036). BRI was higher in AS than in nAMD (0.905 &#xb1; 0.148 vs 0.663 &#xb1; 0.169, P<0.001). The ROC curve for BRI showed an area under the curve of 0.850 (95% confidence interval, 0.754-0.946) with an optimal cutoff of 0.749, yielding 0.880 sensitivity and 0.656 specificity.<br><br>CONCLUSIONS: Compared with nAMD, AS-associated MNV showed distinct ICGA and OCT features, including larger MNV area, more frequent late-phase SHA and BrM undulation, and higher BRI after anti-VEGF loading. These findings may reflect BrM alterations associated with calcification and mechanical instability. BrM-derived ICGA and OCT biomarkers may help characterize AS pathophysiology and differentiate AS-associated MNV from nAMD.}, }
@article {pmid42448244, year = {2026}, author = {Paracini, M and Radwan, A and Peron, G}, title = {Food-derived bioactive compounds in ocular diseases: molecular mechanisms, clinical evidence, and translational challenges.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110465}, doi = {10.1016/j.jnutbio.2026.110465}, pmid = {42448244}, issn = {1873-4847}, abstract = {Age-related and chronic ocular diseases share common underlying mechanisms including oxidative stress, low-grade inflammation, mitochondrial dysfunction, and neurodegeneration. In parallel with advances in conventional therapies, interest in bioactive compounds derived from dietary sources (nutraceuticals) has increased due to their multiple molecular effects and potential to modulate the pathways leading to ocular disease. In this work, the current evidence for major classes of nutraceuticals, including carotenoids, polyphenols, organosulfur compounds, and other plant-derived metabolites was examined, with emphasis on their pharmacodynamic properties, mechanisms of action, and clinical relevance in ocular health. Mechanistic insights from in vitro and animal models were integrated with findings from clinical studies, highlighting molecular targets such as Nrf2-mediated antioxidant responses, NF-κB-driven inflammation, angiogenic signalling, and mitochondrial function. Carotenoids including lutein and zeaxanthin show the most consistent clinical evidence, particularly in increasing macular pigment optical density and reducing progression to advanced macular degeneration. In contrast, other carotenoids and most polyphenols including flavonoids, curcumin, and resveratrol demonstrate promising anti-inflammatory and anti-angiogenic effects primarily supported by preclinical data, with limited and heterogeneous clinical validation. Overall, current evidence suggests that nutraceuticals may have different effects and applicability in managing ocular diseases, although the majority of compounds discussed remain supported only by mechanistic and preclinical data, instead of clinical evidence. Future progress will require rigorously designed clinical studies, improved pharmacokinetic characterization, and precise stratification of patient populations to establish their therapeutic efficacy and relevance.}, }
@article {pmid42448736, year = {2026}, author = {Ma, CC and Lu, CC and Chien, WC and Chung, CH and Weng, TH and Tsai, CT and Chen, JT and Chen, YH and Chen, CL}, title = {Association between silymarin and age-related macular degeneration in patients with liver dysfunction: a nationwide cohort study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-62141-x}, pmid = {42448736}, issn = {2045-2322}, support = {MND-MAB-D-112114, MND-MAB-D-114117, MND-MAB-D-115128//Ministry of National Defense/ ; TSGH-E-112242, TSGH_E_113268, TSGH_E_114266, TSGH_E_115268//Tri-Service General Hospital Research Foundation/ ; }, abstract = {We investigated the association between silymarin use and age-related macular degeneration (AMD) in patients with liver dysfunction using data from the Taiwan National Health Insurance Research Database from 2000 to 2021. Patients with liver dysfunction were classified into silymarin users and non-users, followed by 1:4 propensity score matching. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs), and Kaplan-Meier analysis was performed to compare cumulative AMD incidence. AMD subtype analyses and lag-time sensitivity analyses were also conducted. A total of 4,965 silymarin users and 19,860 matched non-users were included. The incidence of AMD was lower in the silymarin group than in the non-silymarin group (7.33% vs. 9.24%, P < 0.001). Kaplan-Meier analysis showed a lower cumulative incidence of AMD among silymarin users (log-rank P < 0.001). Silymarin use was associated with a lower risk of AMD (aHR = 0.846, P = 0.001), including both wet AMD (aHR = 0.772, P < 0.001) and dry AMD (aHR = 0.852, P = 0.004). A lower risk of transition from dry to wet AMD was also observed among silymarin users. Similar associations were identified in lag-time sensitivity analyses. Further prospective studies are warranted to clarify this association and its potential clinical implications.}, }
@article {pmid42448987, year = {2026}, author = {Mira, F and Donato, S and Vaz, F and Madeira, F and Picoto, M and Mendes, A and Beato, J and Torres-Costa, S and Pinto, C and Oliveira, N and Feliciano, S and Lume, M and Carreiro, R and Couto, M and Carneiro, &#xc2;}, title = {Real-World Outcomes of Faricimab in Patients with Highly Refractory Neovascular Age-Related Macular Degeneration in Portugal: The REVEAL Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42448987}, issn = {2193-8245}, support = {#SL45612//Roche Farmac&#xea;utica Qu&#xed;mica Lda./ ; }, abstract = {INTRODUCTION: Management of highly refractory exudative neovascular age-related macular degeneration (nAMD) remains challenging when multiple antivascular endothelial growth factor (VEGF) therapies fail to control the disease. Faricimab, through dual inhibition of VEGF-A and angiopoietin-2, may represent a potential therapeutic alternative for this difficult-to-treat population. However, real-world evidence in highly refractory nAMD remains limited and is lacking in the Portuguese population.<br><br>METHODS: This multicenter, retrospective, real-world study included patients with nAMD highly refractory to previous anti-VEGF therapies who were treated with faricimab and followed for at least 6 months. Functional and anatomical outcomes were assessed, including changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and evolution of intraretinal fluid (IRF) and subretinal fluid (SRF).<br><br>RESULTS: A total of 46 eyes from 40 patients were included, characterized by a long-standing disease (median [25th percentile (P25); 75th percentile (P75)] duration, 5.0 [3.0; 6.0] years) and a high prior treatment burden (32.0 [24.0; 45.8] anti-VEGF injections and median treatment interval of 4.0 [4.0; 6.0] weeks). After faricimab, functional stability was observed (median change in BCVA of 0.0 [-0.1; 0.1] logMAR). Anatomical outcomes showed improvement, with a median reduction in CST of&#x2009;-12 [-58; 7] &#xb5;m and complete SRF resolution in 47.8% of eyes. Median treatment intervals of 8.0 [6.0-10.0] weeks were achieved, representing a twofold increase in the median treatment interval.<br><br>CONCLUSIONS: In this real-world study of highly refractory nAMD, faricimab was associated with stabilization of functional outcomes and improvement in anatomical outcomes over short- to mid-term follow-up, alongside a twofold increase in treatment-interval length in routine clinical practice. These findings support the clinical relevance of inhibiting angiopoietin-2 (Ang-2) and represent the first evaluation conducted in routine clinical practice in Portugal, with potential implications for treatment burden and patient adherence.}, }
@article {pmid42449255, year = {2026}, author = {Okutucu, M and Arpa, M}, title = {Evaluation of serum semaphorin-3A and interleukin 6 levels in patients with neovascular age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-05128-6}, pmid = {42449255}, issn = {1471-2415}, abstract = {PURPOSE: To determine whether serum semaphorin 3 A (Sema3A) and interleukin 6 (IL-6) play a role in the common etiopathogenesis of nAMD and nAMD-associated systemic diseases by evaluating these mediators levels.<br><br>METHODS: This prospective case-control study included 74 patients divided into nAMD (n&#x2009;=&#x2009;33) and a control group (n&#x2009;=&#x2009;41). Serum Sema3A and IL-6 levels were analyzed using the enzyme-linked immunosorbent assay.<br><br>RESULTS: The nAMD group had a statistically higher IL-6 level [5,9 (1-16,9) pg/mL], compared to the control group [1,5 (0,38&#x2009;-&#x2009;2,96) pg/mL] (p&#x2009;<&#x2009;0.001). On the other hand, the Sema3A level of the nAMD group was lower at [26,3 (11,5-100) ng/mL] compared to the control group at [44,7 (16,8-100) ng/mL] (p&#x2009;<&#x2009;0.001). The IL-6 level in the hypertension (+) group [2,5 (0,5-16,9) pg/ml] was significantly higher than that in the hypertension (-) group [1,7 (0,4-15,3) pg/ml] (p&#x2009;<&#x2009;0.001). No significant difference was found between the hypertension (+) and hypertension (-) groups in terms of SEMA3A level. There was a negative correlation between serum SEMA3A and serum IL-6 levels of the whole participants (p&#x2009;<&#x2009;0.001, r=-0.471).<br><br>CONCLUSIONS: Decreased levels of the anti-inflammatory and anti-angiogenic mediator Sema3A and increased levels of inflammatory mediator IL-6 detected in nAMD suggest that these molecules may play a role in systemic manifestations of this syndrome, such as inflammation, cardiovascular diseases, atrial fibrillation, and Alzheimer's disease.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid42449377, year = {2026}, author = {Zhu, X and Wordsworth, S and Lee, CN and Wafa, HA and Wang, Y and Desai, R and Ramazzotto, L and Reeves, BC and Jackson, TL and Dakin, H and , }, title = {EQ-5D vision bolt-on in macular degeneration: associations with visual measures and effect on utility differences and cost-effectiveness of stereotactic radiotherapy.}, journal = {Health and quality of life outcomes}, volume = {24}, number = {1}, pages = {}, pmid = {42449377}, issn = {1477-7525}, mesh = {Humans ; Cost-Benefit Analysis ; Female ; *Visual Acuity ; Male ; *Macular Degeneration/drug therapy/radiotherapy ; Aged ; Cost-Effectiveness Analysis ; United Kingdom ; *Quality of Life ; Surveys and Questionnaires ; *Radiosurgery/economics/methods ; Double-Blind Method ; Ranibizumab/therapeutic use/economics ; Quality-Adjusted Life Years ; Angiogenesis Inhibitors/therapeutic use/economics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Patient Reported Outcome Measures ; Aged, 80 and over ; }, abstract = {BACKGROUND: The UK STAR trial [Stereotactic Radiotherapy (SRT) for neovascular age-related macular degeneration (nAMD)] compared 16-Gray SRT (n = 274) with double-masked sham SRT (n = 137) in participants with chronic active nAMD. SRT reduced intravitreal anti-vascular endothelial growth factor (VEGF) re-treatments over two years of pro re nata ranibizumab, followed by two years of routine care. However, this resulted in worse best-corrected visual acuity (BCVA) in Years 3 and 4. This paper describes: associations between the EQ-5D vision bolt-on and visual acuity and patient-reported outcome measures; the impact of SRT on utilities with and without vision bolt-on; how the vision bolt-on affects the cost-effectiveness of SRT plus anti-VEGF versus anti-VEGF alone.<br><br>METHODS: Using data from the entire STAR trial cohort, we compared mean BCVA, EQ-5D-5L, and Visual Function Questionnaire-25 (VFQ-25) scores across the three levels of the EQ-5D vision bolt-on. We examined the relationship between BCVA and EQ-5D (with/without the bolt-on) and VFQ-25. An economic evaluation estimated the cost-effectiveness of SRT from a UK national health service perspective over two years and over four years. This used prospective data on EQ-5D-5L and eye-related direct healthcare use.<br><br>RESULTS: Participants reporting vision problems on the bolt-on had significantly worse BCVA, EQ-5D-5L, and VFQ-25 scores than those who did not. EQ-5D utilities (with and without the bolt-on) increased with BCVA but showed weaker correlations than VFQ-25 composite scores. Quality-adjusted life years (QALYs) did not differ significantly between treatment groups, with or without the bolt-on. The economic evaluation suggested SRT would reduce healthcare costs by &#xa3;404 (95% CI: -&#xa3;1282 to &#xa3;2092) per patient at a four-year time horizon. The probability of SRT plus anti-VEGF being cost-effective at a &#xa3;20,000 per QALY threshold was 65% at a four-year time horizon. Sensitivity analyses confirmed the robustness of incorporating the vision bolt-on did not alter the cost-effectiveness conclusion.<br><br>CONCLUSIONS: Resource use data from the trial and routine follow-up could be used for future economic models. The vision bolt-on captured quality of life differences between participants but may not be sufficiently responsive to visual acuity decline in trials where only one eye is treated.<br><br>TRIAL REGISTRATION: ISRCTN12884465, registration date 01/12/2014.}, }
@article {pmid42449957, year = {2026}, author = {Siqueira, RC}, title = {Molecular Mechanisms of Photobiomodulation in Retinal Diseases: Cytochrome c Oxidase, Mitochondrial Bioenergetics and Cytoprotective Signalling.}, journal = {International journal of molecular sciences}, volume = {27}, number = {13}, pages = {}, doi = {10.3390/ijms27135683}, pmid = {42449957}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/metabolism/radiation effects ; Animals ; *Signal Transduction/radiation effects ; *Electron Transport Complex IV/metabolism ; *Energy Metabolism/radiation effects ; *Retinal Diseases/metabolism/therapy/radiotherapy ; *Low-Level Light Therapy/methods ; }, abstract = {Photobiomodulation (PBM) is a non-invasive therapeutic strategy that uses red and near-infrared (NIR) light in the 590-950 nm range to modulate the cellular and molecular pathways involved in retinal homeostasis. At the molecular level, PBM acts primarily through photon absorption by cytochrome c oxidase (CcO, complex IV of the mitochondrial electron transport chain), whose four metal centres-two copper (CuA and CuB) and two heme groups (heme a and heme a3)-absorb light across approximately 600-1000 nm. Photon capture promotes photodissociation of inhibitory nitric oxide (NO) from the binuclear CuB-heme a3 centre, accelerates electron transfer, restores the proton-motive force and increases ATP synthesis. These primary events trigger a coordinated molecular programme that includes (i) transient mitochondrial reactive oxygen species (ROS) bursts that activate the Nrf2/Keap1/ARE axis and upregulate phase II antioxidant enzymes (HO-1, NQO1, GCLC, SOD2, catalase, GPx); (ii) calcium- and cAMP-dependent secondary signalling that converges on PI3K/Akt, MAPK/ERK, AMPK and mTOR pathways; (iii) suppression of NF-κB-driven cytokine production (TNF-α, IL-1β, IL-6) and of NLRP3 inflammasome activation; (iv) downregulation of the HIF-1α/VEGF axis, particularly at 590 nm; (v) anti-apoptotic remodelling of the Bcl-2/Bax ratio with reduced cytochrome c release and caspase-3/9 activation; and (vi) PGC-1α/TFAM/NRF1-driven mitochondrial biogenesis, alongside restoration of fission/fusion homeostasis (Drp1, Mfn1/2, Opa1) and PINK1/Parkin-mediated mitophagy. Wavelength specificity has a defined molecular basis: 590 nm modulates VEGF signalling and RPE pump activity, 660 nm interacts with the CuB centre and enhances O2 binding at CcO, and 850 nm is absorbed by CuA and supports electron entry into complex IV. A second molecular axis is the bidirectional crosstalk between PBM and the circadian system: mitochondrial respiration, ATP turnover and CcO activity oscillate over the 24 h cycle under the control of the BMAL1/CLOCK and PER/CRY core machinery, the NAD[+]/SIRT1-SIRT3 axis and REV-ERBα. Preliminary preclinical and human observations suggest that NIR-induced bioenergetic and functional gains may be coupled to this rhythm, with greater benefit reported when light is delivered in the morning window (≈08:00-11:00); this time dependence should be regarded as an emerging hypothesis rather than an established clinical principle. The clinical evidence is unevenly developed across indications. It is most robust for non-exudative age-related macular degeneration, where multiwavelength PBM (590/660/850 nm; Valeda Light Delivery System) has shown disease-modifying potential in randomized controlled trials (LIGHTSITE I-III and the LIGHTSITE IIIB extension), with sustained BCVA gains and reduced incidence of geographic atrophy over 24 months and beyond. Evidence for retinitis pigmentosa, central serous chorioretinopathy and, with red-light monotherapy, childhood myopia is at present limited to small or short-term studies and remains preliminary. This narrative review synthesizes the molecular machinery engaged by PBM, integrates clinical findings across retinal diseases and discusses how chronotherapeutic delivery of light, aligned with the molecular clock, may further optimize therapeutic efficacy.}, }
@article {pmid42435833, year = {2026}, author = {Gagliardi, OM and Sahoo, NK and Hasan, N and Gregori, G and Peña, DF and Iannetta, D and Chhablani, J}, title = {Tomographic predictors of foveal versus extrafoveal atrophy onset in intermediate age-related macular degeneration.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.010}, pmid = {42435833}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate whether baseline foveal tomographic lesions are associated with foveal-first versus extrafoveal-first onset of complete retinal pigment epithelial and outer retinal atrophy (cRORA) in intermediate age-related macular degeneration (iAMD).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: A total of 129 eyes of 89 patients with iAMD developing cRORA.<br><br>METHODS: Consecutive eyes with iAMD progressing to cRORA were identified through back-tracking grading on spectral-domain optical coherence tomography. Eligible eyes had at least 3 years of follow-up before cRORA onset, with no pre-cRORA inter-visit gap exceeding 6 months. The foveal region was operationally defined as the 1-mm Early Treatment Diabetic Retinopathy Study central subfield. Baseline foveal lesions included soft drusen, subretinal drusenoid deposits (SDD), drusenoid pigment epithelial detachment (dPED), acquired vitelliform lesions (AVL), and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). Hyperreflective foci (HRF) were recorded as present/absent.<br><br>MAIN OUTCOME MEASURES: Foveal-first versus extrafoveal-first cRORA onset; interval-censored time from extrafoveal cRORA onset to foveal involvement.<br><br>RESULTS: Over a mean follow-up of 10.4 &#xb1; 3.4 years, 108 eyes (83.7%) developed foveal cRORA. cRORA onset was foveal-first in 60 eyes (46.5%) and extrafoveal-first in 69 eyes (53.5%). Onset pattern differed across baseline lesions (p < 0.001). SDD and soft drusen were more frequently associated with extrafoveal-first onset (20/22 [91%] and 25/40 [63%]), whereas AVL, iRORA, and dPED were more frequently associated with foveal-first onset (16/23 [70%], 7/10 [70%], and 20/34 [59%]). Among 48 extrafoveal-first eyes that reached the fovea, time to foveal involvement was similar across lesion types (median, 1.5-1.8 years; p&#x202f;=&#x202f;0.97). Compared with soft drusen, the time to foveal cRORA was shorter for iRORA, dPED, and AVL (time ratios: 0.12, 0.40, and 0.50; 95% CIs: 0.06-0.23, 0.30-0.55, and 0.35-0.71). Foveal HRF independently predicted faster progression (time ratio, 0.66; 95% CI, 0.51-0.85; p&#x202f;=&#x202f;0.001).<br><br>CONCLUSION: In iAMD eyes progressing to cRORA, distinct tomographic lesions at the fovea were associated with a different propensity to foveal-first versus extrafoveal-first atrophic onset. Once extrafoveal cRORA was established, time to foveal involvement did not differ across tomographic lesions. These findings may inform lesion-specific risk stratification for emerging dry AMD therapies.}, }
@article {pmid42437111, year = {2026}, author = {Tandon, NR and Vasquez, E and Csaky, KG}, title = {Test-Retest Repeatability of a Novel Photopic Microperimetry Approach in Patients with Geographic Atrophy.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101267}, pmid = {42437111}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate test-retest repeatability of novel focal photopic microperimetry approach targeting central 1 mm of the fovea and explore its relationships with geographic atrophy (GA) lesion area and other visual function metrics.<br><br>DESIGN: A prospective, single arm, observational study.<br><br>SUBJECTS: Participants with nonsubfoveal GA as determined by spectral-domain OCT and fundus autofluorescence.<br><br>METHODS: Twelve participants (17 eyes) performed focal photopic tests using a 45-loci focal grid (0.5&#xb0; spacing; Goldmann II stimuli) on Nidek MP-3, along with other visual function assessments. To assess test-retest repeatability of MP-3, 2 tests up to 4 weeks apart were performed. The interval was short relative to expected GA progression, and thus measurements are interpreted as reflecting test-retest repeatability.<br><br>MAIN OUTCOME MEASURES: Coefficient of repeatability (CoR), intraclass correlation coefficient (ICC), and Bland-Altman were analyzed for mean sensitivity (MS) and point-wise sensitivity (PWS). Correlations of adjusted MS (excluding floor effect) with GA lesion size, best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), and contrast sensitivity were also analyzed.<br><br>RESULTS: Focal photopic MP-3 showed good test-retest repeatability with CoR of MS at 2.42 dB (intraclass correlation coefficient [ICC] = 0.98) and CoR of PWS at 8.2 dB (ICC = 0.89). Excluding the floor effect improved the CoR of MS and PWS to 2.03 dB and 7.06 dB, respectively. Mean test duration was 4.33 minutes per eye with fixation stability >89%. Structure-function analysis showed weak correlation between GA lesion size and adjusted MS (P = 0.05; R [2] = 0.44). Adjusted MS showed a significant correlation with LLVA (P = 0.001) and low-luminance quick contrast sensitivity function (qCSF) (P = 0.01), a weak association with qCSF (P = 0.05), but no correlation with BCVA.<br><br>CONCLUSIONS: Focal photopic microperimetry using Goldmann II stimuli provides a highly repeatable measure of central cone-mediated function in patients with nonsubfoveal GA. Mean sensitivity demonstrated high repeatability and supports its use as a robust, clinically relevant endpoint for longitudinal and interventional studies, while PWS may provide spatial information for deeper structure-function analyses. Weak associations with GA lesion size and BCVA suggest that conventional measures may underestimate visual impairment, highlighting the value of focal photopic microperimetry within central 1 mm region as a sensitive, patient-centered outcome in age-related macular degeneration.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42437114, year = {2026}, author = {Gao, Y and Xu, J and Yu, J and Zhang, Y and Chen, H and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ}, title = {Shared Genetic Architecture and Multidimensional Modifiable Correlates between Myopia and Retinal-Optic Nerve Diseases.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101277}, pmid = {42437114}, issn = {2666-9145}, abstract = {PURPOSE: This study aimed to characterize the shared genetic architecture and modifiable correlates between myopia and retinal-optic nerve diseases (RONDs).<br><br>DESIGN: Genetic pleiotropy analysis and population-based cohort study.<br><br>PARTICIPANTS: A total of 81 491 UK Biobank participants and summary statistics from large-scale genome-wide association studies were included.<br><br>METHODS: We examined associations between myopia and 5 common RONDs using population-based analyses of prevalent and incident outcomes, followed by cross-trait genetic analyses, locus-level annotation, colocalization, and enrichment analyses. Among myopic individuals, modifiable correlates and gene-environment interactions were evaluated, and Mendelian randomization was used as complementary evidence for selected associations.<br><br>MAIN OUTCOME MEASURES: Myopia and RONDs.<br><br>RESULTS: The primary findings were that, in baseline prevalent analyses, myopia was associated with higher risks of retinal detachment (RD) and primary open-angle glaucoma (POAG), but a lower risk of primary angle-closure glaucoma (PACG), with evident risk gradients across myopia severity, especially for RD. Diabetic retinopathy (DR) risk estimates were <1.0 across myopia severity categories but were not statistically significant. A U-shaped association was observed between refractive status and age-related macular degeneration, with elevated risk in both high myopia and hyperopia. Incident analyses during follow-up showed broadly consistent patterns. As supportive genetic evidence, cross-trait analyses revealed significant genetic correlations and overlaps between myopia and RONDs, identifying 66 pleiotropic loci and 115 candidate genes, with enrichment in immune-inflammatory, receptor-mediated signaling, and retinal developmental pathways. Among myopic individuals, exploratory analyses further showed that prevalent myopia-ROND comorbidity was associated with various modifiable correlates spanning health status, lifestyle, diet, mental health, sleep patterns, and medication use, and that 7 environmental factors interacted with 5 pleiotropic variants. Mendelian randomization analyses provided complementary and hypothesis-supporting evidence consistent with a positive association of myopia with RD and an inverse association with PACG, whereas findings for DR and POAG required more cautious interpretation because of pleiotropy or heterogeneity.<br><br>CONCLUSIONS: This study reveals a shared genetic architecture and identifies modifiable correlates linking myopia to five common RONDs. These findings provide new insights into shared susceptibility patterns and offer a framework for future mechanistic, validation, and prevention-oriented research in myopic populations.<br><br>FINANCIAL DISCLOSURES: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42437118, year = {2026}, author = {Wu, A and Au, A and Hanson, J and Yamamoto, M and Cheng, J and Lee, S and Lior, TE and Avram, O and Sadda, SR and Coyne, AB and Acharya, NR and Madow, B and Chiang, JN and Tsui, E}, title = {Quantitative Analysis of Retinal Fluid by a Deep Learning Model in Uveitic Macular Edema.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101241}, pmid = {42437118}, issn = {2666-9145}, abstract = {OBJECTIVE: To assess whether artificial intelligence (AI)-derived fluid volume provides prognostic value for visual outcomes in uveitic macular edema (UME) and to compare model performance to central macular thickness (CMT) measurements alone.<br><br>DESIGN: Secondary subanalysis of patients with UME in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) clinical trial using a deep learning segmentation model trained on patients with age-related macular degeneration (AMD) and patients with retinal vein occlusion.<br><br>PARTICIPANTS: Patients with UME secondary to noninfectious uveitis from the FAST Uveitis Trial.<br><br>METHODS: A 2-dimensional U-Net model, trained on patients with AMD and retinal vein occlusion using the RETOUCH data set, was applied to segment intraretinal fluid (IRF) and subretinal fluid (SRF) in Heidelberg Spectralis OCT scans from the FAST Uveitis Trial. Model performance was validated against binary fluid gradings. Linear mixed-effects models evaluated fluid resolution during treatment. Likelihood ratio tests and leave-one-subject-out cross-validation assessed whether baseline IRF and SRF volumes provided improved model fit for visual acuity (VA) change over 6 months of treatment compared to CMT alone.<br><br>MAIN OUTCOME MEASURES: Segmentation accuracy, correlation of fluid volume with VA, and association of VA change with baseline fluid volumes and CMT versus CMT only.<br><br>RESULTS: The model achieved Dice scores of 0.61 for IRF and 0.74 for SRF on the RETOUCH data set. In the FAST data set, fluid segmentation correlated with binary gradings (biserial correlation: IRF 0.39, SRF 0.63; Mann-Whitney U test: IRF and SRF P < 0.01). Longitudinal fluid modeling showed no significant treatment differences in IRF or SRF resolution. However, baseline IRF volume had a significant interaction with treatment assignment (P = 0.02) when modeling VA change, suggesting that baseline IRF was more strongly associated with worse outcomes in the methotrexate group than the mycophenolate mofetil group. The likelihood ratio test confirmed that adding IRF and SRF improved fit over a model using CMT alone (P < 0.01) while leave-one-subject-out cross-validation showed a small, nonsignificant difference in prediction error.<br><br>CONCLUSIONS: Artificial intelligence-based segmentation of IRF and SRF enabled quantitative fluid measurements in UME and may provide additional prognostic signal for VA change in UME compared to CMT alone, although larger cohorts will be needed to determine the magnitude of generalizable performance gains, if any. These findings support integrating AI-driven fluid analysis in clinical workflows and suggest that future clinical trials should consider stratifying by baseline fluid characteristics using AI fluid analysis.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42437329, year = {2026}, author = {Fu, L and Huang, L and Guo, R and Wu, L and Zeng, X and Fu, Z}, title = {Study on retinal pharmacokinetic characteristics and precision drug administration strategy in patients with fundus diseases.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {39}, number = {9}, pages = {2825-2836}, doi = {10.36721/PJPS.2026.39.9.263.1}, pmid = {42437329}, issn = {3105-9686}, mesh = {Humans ; Female ; Blood-Retinal Barrier/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Retrospective Studies ; *Diabetic Retinopathy/drug therapy/metabolism/diagnostic imaging ; Male ; Aged ; Tomography, Optical Coherence ; Precision Medicine ; Middle Aged ; *Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; Aged, 80 and over ; }, abstract = {BACKGROUND: Fundus diseases are major causes of irreversible visual impairment. Retinal pharmacokinetic behavior may differ between diabetic retinopathy (DR) and age-related macular degeneration (AMD), but disease-specific dosing principles remain insufficiently defined.<br><br>OBJECTIVES: Disease-stratified retinal pharmacokinetic characteristics were evaluated, and a precision drug administration strategy for patients with fundus diseases was developed.<br><br>METHODS: Blood-retinal barrier (BRB) cell models, retinal organoids, retinal pigment epithelium (RPE) models, optical coherence tomography (OCT), serum biomarkers and clinical records were integrated. A retrospective, controlled clinical analysis was performed in patients with DR or AMD, in accordance with ethics approval No. 20240923.<br><br>RESULTS: DR was characterized by greater barrier permeability and transporter-related retention, whereas AMD was characterized by lipid-associated RPE dysfunction and restricted trans-retinal penetration. The DR model predicted retinal peak concentration with R2 = 0.89, and the AMD model predicted drug half-life with 86% accuracy. Precision administration was associated with reduced injection frequency in DR and AMD and improved anatomical and visual outcomes.<br><br>CONCLUSION: Disease-specific retinal pharmacokinetic differences support individualized dosing strategies for fundus diseases. The proposed platform provides a practical framework for precision anti-VEGF therapy and targeted retinal drug delivery.}, }
@article {pmid42435130, year = {2026}, author = {Panos, GD}, title = {Letter to the Editor Regarding "Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials".}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42435130}, issn = {2193-8245}, }
@article {pmid42435540, year = {2026}, author = {Jaber, B and Abd, MA and Younis, SMD and Rizaev, J and Salih, RM and Jaber, MA and Kholboyev, N and Farajipour, H}, title = {Retinal organoids and stem cell therapy for vision restoration: current progress, persistent challenges, and future directions.}, journal = {International immunopharmacology}, volume = {186}, number = {}, pages = {117120}, doi = {10.1016/j.intimp.2026.117120}, pmid = {42435540}, issn = {1878-1705}, abstract = {Vision restoration is a vital yet challenging objective in ophthalmology, as traditional therapies cannot reverse irreversible retinal damage. This issue is of significant concern, considering that millions globally are afflicted by untreatable degenerative conditions such as retinitis pigmentosa (RP) and age-related macular degeneration. Stem cell treatments and retinal organoid (RO) technology have emerged as revolutionary methodologies. ROs derived from pluripotent stem cells (PSCs) autonomously form three-dimensional (3D) laminar structures that mimic the natural human retina, providing exceptional platforms for disease modeling, pharmacological screening, and cellular replacement. Clinical studies indicate that retinal pigment epithelium (RPE) transplantation enhances visual function. In contrast, PSC-derived mesenchymal stem cells (MSCs), retinal progenitor cells (RPCs), and RPE grafts have neuroprotective and regenerative capabilities in preclinical and early-phase trials. Notwithstanding this advancement, several challenges remain, including suboptimal cell survival, insufficient functional synaptic integration, immunological rejection, tumorigenic potential, and the absence of standardized production processes. This article presents three unique contributions, diverging from previous reviews that focus solely on positive outcomes: (1) a comprehensive assessment of advancements and challenges in PSCs, MSCs, RPCs, and RPE; (2) a methodical examination of the disparity between structural engraftment and genuine functional integration; and (3) a cohesive discourse on innovative strategies such as optogenetics, 3D bioprinting, and extracellular vesicle-based therapies. We consolidate recent clinical discoveries, highlight persistent obstacles, and provide a roadmap for the future. Growing evidence suggests that, despite significant obstacles, effective retinal regeneration is gradually becoming a reality.}, }
@article {pmid42433372, year = {2026}, author = {Schlecht, A and Müllerbauer, L and Fitz, K and Brunne, B and Hofmann, N and Müller, C and Hillenkamp, J and Ergün, S and Neueder, A and Braunger, BM}, title = {Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1813788}, pmid = {42433372}, issn = {1664-3224}, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/etiology ; *Signal Transduction ; Mice ; *Transforming Growth Factor beta/metabolism ; *Endothelial Cells/metabolism ; Receptor, Transforming Growth Factor-beta Type II/genetics/metabolism ; Disease Models, Animal ; Mice, Knockout ; *Myeloid Cells/metabolism ; *Cell Communication ; Microglia/metabolism ; Blood-Retinal Barrier/metabolism ; Fibrinogen/metabolism/genetics ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: The blood-retinal barrier (BRB) is essential for maintaining retinal homeostasis, consequently its disruption contributes to pathological angiogenesis in diseases such as neovascular age-related macular degeneration (nAMD). Choroidal neovascularization (CNV) is considered as a hallmark of nAMD. These newly formed vessels break through the BRB leading to rapid and severe vision loss. Here, we investigated how endothelial TGFβ signaling interacts with mononuclear phagocytes (MP), such as microglia to regulate choroidal neovascularization (CNV).<br><br>METHODS: In this study, we used a laser-induced CNV model in mice with endothelial-specific Tgfbr2 deletion and concomitant MP depletion via PLX5622.<br><br>RESULTS: We demonstrate that loss of endothelial TGF&#x3b2; signaling significantly exacerbates CNV. Strikingly, this effect is fully rescued by MP depletion. Transcriptome and RNA localization of CNV lesions identified fibrinogen alpha chain (Fga) as a MP-derived factor that is exclusively upregulated in mice without endothelial TGF&#x3b2; signaling.<br><br>DISCUSSION: These findings suggest a novel TGF&#x3b2;-dependent interaction between endothelial cells and MP that promotes angiogenesis through microglia derived Fga expression.}, }
@article {pmid42434188, year = {2026}, author = {Ruiz-Medrano, J and Puertas, M and Hinojosa-Gonzalez, M and Moreno-Alboran, C and Ruiz-Moreno, JM}, title = {Pharmacoeconomic analysis of switch to faricimab for neovascular age-related macular degeneration in real clinical practice.}, journal = {Global &amp; regional health technology assessment}, volume = {13}, number = {}, pages = {185-191}, pmid = {42434188}, issn = {2283-5733}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is one of the leading causes of severe vision loss among older adults. This condition impairs patients' quality of life and imposes a significant economic burden on the healthcare system. This study aims to determine the difference in direct healthcare cost (DHC) after switching the current pharmacological treatment in patients with nAMD, under a treat-and-extend regimen, to faricimab.<br><br>METHODS: Treatment interval data obtained after switching to faricimab in 225 eyes with nAMD was used to calculate total DHC in comparison with the theoretical DHC had if patients remained on their previous treatment (drug and treatment interval). An "optimal responder" was defined as a patient whose interval between intravital injections was extended by more than 8 weeks relative to the baseline treatment interval.<br><br>RESULTS: The theoretical DHC of treatment for this series of nAMD eyes would have been &#x20ac;2,351,241.90, compared with an actual DHC after switching to faricimab of &#x20ac;1,718,015.83, representing a saving of &#x20ac;633,226.06 for 225 eyes. The mean theoretical DHC would have been &#x20ac;10,449.96 &#xb1; 4,340.18 (from 1,423.75 to 23,695.20), compared with a mean actual total cost of &#x20ac;7,635.62 &#xb1; 2,465.07 (from 2,571.88 to 15,431.28). The mean actual DHC was &#x20ac;8,499.74 &#xb1; 2,678.42 in the "non-optimal responder" group versus &#x20ac;6,593.59 &#xb1; 1,674.91 in the "optimal responder" group (p < 0.001).<br><br>CONCLUSION: Switching to faricimab in patients with nAMD on a treat-and-extend regimen with a treatment interval of less than 12 weeks resulted in a significant reduction in total DHC, particularly in the "optimal responder" group.}, }
@article {pmid42434330, year = {2026}, author = {Qin, Z and Liu, Y and Yin, YU and Ding, J and Zhang, H and Li, A and Campbell, D and Wu, X and Zou, KE and Keenan, TDL and Chew, EY and Lu, Z and Tham, YC and Liu, N and Zhang, X and Chen, Q}, title = {LMOD+: A Comprehensive Multimodal Dataset and Benchmark for Developing and Evaluating Multimodal Large Language Models in Ophthalmology.}, journal = {ACM transactions on computing for healthcare}, volume = {7}, number = {3}, pages = {}, pmid = {42434330}, issn = {2637-8051}, abstract = {The rising prevalence of vision-threatening eye diseases poses a major global health and economic burden, yet timely diagnosis remains limited by workforce shortages, diagnostic delays, and restricted access to specialized care. Artificial intelligence (AI) offers potential solutions. In particular, recent progress in foundation models and large language models-especially multimodal large language models (MLLMs)-has shown promise in medical image interpretation and automated clinical documentation. However, advancing MLLMs for ophthalmology is hindered by the lack of unified, comprehensive benchmark datasets for development and evaluation. Most existing benchmarks were designed for earlier models, which focused on narrow tasks or specific disease conditions. These benchmarks typically provide outputs in the form of disease labels rather than free-text responses. As a result, they are less suitable for assessing emerging generative models. In this work, we present LMOD+, a large-scale multimodal ophthalmology benchmark dataset comprising 32,633 instances with multi-granular annotations across 12 common ophthalmic conditions and 5 imaging modalities. The dataset integrates imaging, anatomical structures, demographics, and free-text annotations. It supports primary ophthalmic applications such as anatomical structure recognition, disease screening, disease staging, and demographic prediction for potential performance bias evaluation. Alongside the dataset, we introduce a systematic and unified data curation pipeline that repurposes existing or new datasets for MLLM development. LMOD+ extends our preliminary LMOD benchmark-the first multimodal ophthalmology benchmark for MLLMs-with three major enhancements. First, we expanded the dataset by nearly 50% (from 21,933 to 32,633 instances). The color fundus photography (CFP) modality, the most accessible imaging modality in ophthalmology, was significantly enlarged to cover a broader range of pathological conditions. Second, we broadened task coverage to include (a) 12 binary disease diagnosis tasks for prevalent conditions such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion; (b) multi-class ophthalmic disease diagnosis; (c) disease severity classification, including a diabetic retinopathy staging task, which uses two internationally adopted grading standards: the international clinical diabetic retinopathy classification and the Scottish diabetic retinopathy grading scheme classification; and (d) demographic prediction (age and sex) to assess potential model bias. Third, we systematically evaluated 24 state-of-the-art MLLMs, including recent models from the InternVL, Qwen, and DeepSeek families. Our evaluations highlight both the promise and limitations of current MLLMs in ophthalmology. For example, Qwen-7B and InternVL achieved accuracies of 58.26% and 57.83% in disease screening under a zero-shot setting with a single model-a considerably more challenging paradigm than traditional fine-tuning, where separate models are trained for each specific task. InternVL also demonstrated potential in anatomical recognition. Nonetheless, overall performance remained suboptimal and often close to random baselines for challenging tasks such as disease staging, underscoring the substantial gap between general-domain MLLMs and the specialized requirements of ophthalmology. We publicly release the dataset, curation pipeline, and leaderboard to encourage community-wide development and evaluation of MLLMs, with the goal of advancing ophthalmic applications and ultimately reducing the global burden of vision-threatening diseases through AI. The dataset website, benchmark leaderboard, and download link are available at https://kfzyqin.github.io/lmod_plus.}, }
@article {pmid42435129, year = {2026}, author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, N}, title = {A Response to: Letter to the Editor Regarding "Aflibercept 8 mg Versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials".}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42435129}, issn = {2193-8245}, support = {P30-EY026877//Prevent Blindness/ ; }, }
@article {pmid42410910, year = {2026}, author = {Ji, Y and Sun, Y and Huang, X and Liang, J and Fang, D and Yang, W and Feng, L and Zhang, S}, title = {Targeting the SNAI1-LAMP3 axis to restore lysosomal function and alleviate autophagic flux impairment to delay retinal degeneration.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-21}, doi = {10.1080/15548627.2026.2700025}, pmid = {42410910}, issn = {1554-8635}, abstract = {Retinal degenerative diseases are a leading cause of irreversible blindness. Their pathogenesis is intricately linked to oxidative stress-induced dysfunction of retinal pigment epithelial (RPE) cells and subsequent retinal degeneration. Macroautophagy/autophagy, a critical cellular degradation pathway, plays a vital role in maintaining RPE homeostasis, yet its dysregulation in retinal degenerative diseases remains poorly understood. In this study, we observed that sodium iodate (NaIO3), an oxidative stress inducer, triggered lysosomal dysfunction via lysosomal membrane permeabilization (LMP), thereby impairing autophagic flux in RPE cells and exacerbating retinal degeneration. RNA sequencing identified LAMP3 (lysosomal-associated membrane protein 3) as a downregulated gene following NaIO3 treatment. Functionally, LAMP3 overexpression alleviated NaIO3-induced LMP, improved lysosomal function, and alleviated autophagic impairment. Furthermore, upregulation of LAMP3 reduced oxidative stress and apoptosis in RPE cells, while alleviating retinal degeneration in a NaIO3-induced mouse model. Mechanistically, our data suggested that NaIO3 upregulated the transcription factor SNAI1, which acts as a transcriptional repressor of LAMP3. SNAI1 knockdown increased LAMP3 expression, thereby facilitating the recovery of lysosomal function and the alleviation of autophagic impairment. Collectively, our findings indicate that the SNAI1-LAMP3 axis contributes to the regulation of the autophagy-lysosomal pathway in retinal degeneration, highlighting a potential therapeutic target for delaying disease progression.Abbreviations: AMD: age-related macular degeneration; AO: acridine orange; Baf A1: bafilomycin A1; BAX: BCL2-associated X protein; BCL2: B cell leukemia/lymphoma 2; BSA: bovine serum albumin; CCK-8: cell counting kit-8; ChIP: chromatin immunoprecipitation; CM-H2DCFDA: chloromethyl-2',7'-dichlorodihydrofluorescein diacetate; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; DEGs: differentially expressed genes; DHE: dihydroethidium; EdU: 5-ethynyl-2'-deoxyuridine; ERG: electroretinography; GSEA: gene set enrichment analysis; H&amp;E: hematoxylin and eosin; HsRPE: human primary retinal pigment epithelial; JC-1: 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; LAMP3: lysosomal-associated membrane protein 3; LGALS3: lectin, galactose binding, soluble 3; LLOMe: leu-leu methyl ester; LMP: lysosomal membrane permeabilization; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MMP: mitochondrial membrane potential; NAC: N-acetyl-L-cysteine; NaIO3: sodium iodte; NC: negative control; OCT: optical coherence tomography; PCA: principal component analysis; PI: propidium iodide; qRT-PCR: quantitative real-time polymerase chain reaction; Rapa: rapamycin; ROS: reactive oxygen species; RP: retinitis pigmentosa; RPE: retinal pigment epithelium; RPE65: retinal pigment epithelium 65; siRNA: small interfering RNA; SNAI1: snail family zinc finger 1; SQSTM1/p62: sequestosome 1; TJP1/ZO-1: tight junction protein 1; ZNF135: zinc finger protein 135.}, }
@article {pmid42423410, year = {2026}, author = {Quarta, A and Huang, J and Abbasgholizadeh, R and Soylu, C and Chujo, S and Alhelaly, M and Velaga, SB and Nittala, MG and Corradetti, G and Ip, M and Mastropasqua, R and Sadda, SR}, title = {Clinical and Imaging Characteristics of Thin and Thick Idiopathic Epiretinal Membranes Assessed by High-Resolution OCT.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {28}, doi = {10.1167/iovs.67.8.28}, pmid = {42423410}, issn = {1552-5783}, mesh = {Humans ; *Epiretinal Membrane/diagnosis/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; Visual Acuity ; Aged, 80 and over ; Retrospective Studies ; Prevalence ; }, abstract = {PURPOSE: The purpose of this study was to determine the prevalence and imaging characteristics of thin and thick idiopathic epiretinal membranes (ERMs) using high-resolution (HR) optical coherence tomography (OCT) and to identify clinical factors associated with ERM thickness phenotype.<br><br>METHODS: All patients underwent comprehensive ophthalmologic examination and multimodal imaging, including HR-OCT. ERM morphology was evaluated on fovea-centered OCT scans and classified as thin or thick based on preretinal reflectivity patterns. Multivariable generalized estimating equations (GEEs) were used to identify factors independently associated with ERM type while accounting for inter-eye correlation.<br><br>RESULTS: Fifty-four eyes included in this analysis and 28 (51.9%) were classified as thin ERM, whereas 26 (48.1%) were thick ERM. Patients with thick ERM were significantly older than those with thin ERM (81.6 &#xb1; 6.2 vs. 75.7 &#xb1; 10.8 years, P = 0.039). Pseudophakia was more prevalent in the thick ERM group (84.6% vs. 60.7%, P < 0.001), as was the presence of AMD (69.2% vs. 28.6%, P = 0.003). Mean central macular thickness (CMT) and best-corrected visual acuity (BCVA) did not differ significantly between thin and thick ERM groups (P > 0.05). In multivariable analysis, pseudophakia (odds ratio [OR] = 10.33, 95% confidence interval [CI] = 1.29-83.10, P = 0.028) and age-related macular degeneration (AMD; OR = 4.12, 95% CI = 1.01-16.87, P = 0.049) were independently associated with thick ERM.<br><br>CONCLUSIONS: HR-OCT enables in vivo differentiation of thin and thick idiopathic ERMs. Thick ERM is independently associated with pseudophakia and AMD but not with greater CMT or worse BCVA, suggesting that ERM thickness phenotype may reflect differences in factors other than vitreoretinal interface biology alone.}, }
@article {pmid42424405, year = {2026}, author = {Osba, AA and Saleh, F and Verma, AV and Mihalache, A and El Aziz Hendy, A and Osba, RA and Mishra, AV and Kertes, PJ and Kohly, RP and Muni, RH and Popovic, M}, title = {Post-Marketing Ocular Adverse Events Associated with Tamoxifen and Raloxifene: A Population-Based Pharmacovigilance Study.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004916}, pmid = {42424405}, issn = {1539-2864}, abstract = {PURPOSE: Tamoxifen and raloxifene are selective estrogen receptor modulators used for breast cancer treatment, and osteoporosis prevention. While systemic adverse events (AEs) are well recognized, ocular AEs have been less comprehensively characterized. The purpose of this study was to evaluate postmarketing ocular AEs associated with tamoxifen and raloxifene using a pharmacovigilance database.<br><br>METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) data from Q4 2003 to Q2 2025 were analyzed using OpenVigil 2.1. Disproportionality analyses were conducted to calculate reporting odds ratios (RORs) for drug-AE pairs compared with all other drugs.<br><br>RESULTS: There were a total of 4,084 reports of AEs associated with tamoxifen (mean age 56.7 years), including 505 ocular AEs. The strongest signals were for corneal graft rejection (ROR 118.9), retrobulbar hemorrhage (104.6), ophthalmic vein thrombosis (82.7), retinal deposits (80.7), and macular hole (78.6). Additional events included maculopathy, retinopathy, and optic neuropathy. There were 5,600 reports of AEs associated with raloxifene (mean age 68.6 years), including 437 ocular AEs. The most prominent signals were vascular, including retinal vein thrombosis (ROR 340.0), retinal vascular thrombosis (133.8), retinal artery thrombosis (54.9), and retinal vein occlusion (42.9). Other events included reduced visual acuity, cataract, macular degeneration, and glaucoma.<br><br>CONCLUSIONS: Tamoxifen and raloxifene had unique ocular AE profiles. Tamoxifen was primarily linked to retinal, optic nerve, and corneal disorders, whereas raloxifene was strongly associated with retinal vascular and thromboembolic events. These findings underscore the importance of clinician awareness and future prospective studies to further elucidate the risks.}, }
@article {pmid42424532, year = {2026}, author = {Wu, HC and Gu, A and Chang, YL and Lu, CK and Lee, YC and Yu, PW and Lee, TH}, title = {Utilize Metabolomics Molecular Networking to Guide the Discovery of Chemical Entities from Cordyceps militaris Against Blue Light Hazards.}, journal = {Journal of natural products}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jnatprod.6c00427}, pmid = {42424532}, issn = {1520-6025}, abstract = {Increasing exposure to blue light has raised concern about retinal injury, particularly in retinal pigment epithelial (RPE) cells. N-retinylidene-N-retinylethanolamine (A2E), a photosensitive fluorophore associated with age-related macular degeneration, is an important mediator of this process. In this study, feature-based molecular networking guided the identification of cordylutenes A-J (1-10), a new molecular family of blue light-protective fungal pigments from Cordyceps militaris. These metabolites possess a previously unreported symmetric all-E C20 polyene dicarbonyl skeleton with carotenoid-like UV absorption. They were characterized at the molecular-family level by shared UV features and diagnostic, internally consistent MS[2] fragmentation patterns. Cordylutenes A (1) and B (2) were isolated as representative members for structural characterization. In an A2E-mediated blue-light injury model in ARPE-19 cells, the cordylutene complex (CCL, 1 μg/mL) and cordylutene A (1, 0.1 μg/mL) improved cell viability to 84.78 ± 4.02% and 92.14 ± 1.88%, respectively, and reduced intracellular oxidative stress to 63.67 ± 3.33% and 43.89 ± 9.59%, respectively. These findings identify cordylutenes as a new family of fungal pigments with protective effects in an A2E-mediated photo-oxidative retinal cell injury model.}, }
@article {pmid42425278, year = {2026}, author = {Badla, O and Shen, M and El-Mulki, OS and Berni, A and Kumar, BS and Herrera, G and Beqiri, S and Lam, W and Herrera, E and Moxam, J and Trivizki, O and O'Brien, R and Waheed, NK and Gregori, G and Wang, RK and Rosenfeld, PJ}, title = {Comparing Eye-Level and Site-Specific High-Risk OCT Biomarkers Preceding the Onset of Large Hypertransmission Defects.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.002}, pmid = {42425278}, issn = {1879-1891}, abstract = {PURPOSE: To compare the site-specific optical coherence tomography (OCT) biomarkers that appear prior to the formation of large hypertransmission defects (hyperTDs) with the eye-level OCT biomarkers that were shown to predict disease progression in eyes with intermediate AMD (iAMD).<br><br>DESIGN: Retrospective subgroup analysis of a prospective cohort study.<br><br>METHODS: A prospectively enrolled cohort of eyes with iAMD, imaged with swept-source OCT (SS-OCT), was retrospectively reviewed to identify eyes that developed large hyperTDs. Large hyperTDs were defined as bright lesions with a greatest linear dimension (GLD) of &#x2265;250 &#x3bc;m on an en face sub-retinal pigment epithelium (RPE) slab image created using segmentation boundaries positioned 64-400 &#x3bc;m below Bruch's membrane (BM). All visits prior to the formation of the large hyperTDs were retrospectively reviewed to identify the OCT biomarker at the retinal location where the initial large hyperTD formed.<br><br>RESULTS: 82 of 171 eyes (48%) with iAMD developed at least one large hyperTD. At the first visits when the large hyperTD developed, a total of 119 large hyperTDs were detected. Hyperreflective foci (HRF) were the most frequent OCT biomarker at the sites prior to the formation of hyperTDs (88/119, 74%). Soft drusenoid lesions were the second-most frequent biomarker (77/119, 65%); however, 67 of these lesions occurred in conjunction with HRF. Calcified drusen (CaD) were present at 19 of 119 sites (16%). Of these 19 CaD lesions, 7 contained hyporeflective cores (hypoRC-CaD), and 11 were associated with HRF. Non-calcified hyporeflective core drusen (hypoRCD) were present at 16/119 (13%) sites, with three of the hypoRCD associated with HRF. Basal laminar deposits (BLamD) were present at 2 of 119 sites (2%), both of which were associated with HRF. Single cases of a vitelliform lesion and a small hyperTD were also identified prior to the large hyperTDs.<br><br>CONCLUSIONS: Site-specific analysis showed that HRF were the most frequent OCT biomarker at the sites prior to the formation of large hyperTDs. Soft drusenoid lesions and HRF were frequently observed together, consistent with our previous eye-level multivariable analysis, which showed that drusen volume was not independently predictive of the future formation of large hyperTDs.}, }
@article {pmid42425279, year = {2026}, author = {El-Mulki, OS and Badla, O and Kumar, BS and Berni, A and Shen, M and Kastner, J and Beqiri, S and Herrera, G and Lam, W and Herrera, E and Trivizki, O and Le, VH and Nicola, MD and O'Brien, R and Waheed, NK and Gregori, G and Wang, RK and Rosenfeld, PJ}, title = {Detection of Hyporeflective Core Drusen and the Onset of Large Choroidal Hypertransmission Defects in Intermediate AMD.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.001}, pmid = {42425279}, issn = {1879-1891}, abstract = {PURPOSE: To investigate the association between hyporeflective core drusen (hypoRCD) and the formation of large choroidal hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration (iAMD), we used swept-source optical coherence tomography (SS-OCT) imaging and a novel algorithm to detect and quantify hypoRCD before the onset of hyperTDs.<br><br>DESIGN: Post hoc subgroup analysis of a prospective cohort study.<br><br>METHODS: Eyes with iAMD enrolled in a prospective SS-OCT imaging study were retrospectively reviewed. SS-OCT angiography (SS-OCTA) scans were obtained at baseline and follow-up. En face images derived from a retinal pigment epithelium (RPE) to Bruch's membrane (BM) slab identified hyporeflective cores within drusen as dark spots. A sub-RPE slab located 64-400 &#x3bc;m beneath BM was used to identify calcified drusen (CaD) based on their characteristic choroidal hypotransmission defects (hypoTDs). Hyporeflective cores associated with CaD (hypoRC-CaD) were identified. Hyporeflective cores not associated with calcified drusen were labeled as non-calcified hypoRCD and quantified separately. Large hyperTDs, defined as bright lesions with a greatest linear dimension (GLD) &#x2265;250 &#x3bc;m on the sub-RPE slab, were graded. A semi-automated algorithm measured the areas of hypoRC-CaD and non-calcified hypoRCD within a 5 mm circle centered on the fovea, and their association with hyperTD formation was analyzed. The risk attributed to CaD with and without hyporeflective cores was evaluated.<br><br>RESULTS: The study included 171 eyes from 121 patients with a median follow-up of 59.1 months (95% CI: 52.0-67.8). Eighty-two eyes developed at least one large hyperTD during follow-up. The total hypoRCD area at the time of hyperTD onset was 0.026 mm&#xb2; (range: 0-0.349 mm&#xb2;), compared to 0.015 mm&#xb2; (range: 0-0.532 mm&#xb2;) at the final visit in eyes that did not develop hyperTDs. When drusen volume, hyperreflective foci (HRF) area, CaD area, and total hypoRCD area were studied as risk factors, the hypoRCD area was not a significant predictor of hyperTD onset in the univariable (P&#x202f;=&#x202f;0.36) or multivariable (P&#x202f;=&#x202f;0.60) Cox regression models.<br><br>CONCLUSIONS: HypoRCD alone were not predictive of progression to atrophy, but the risk of progression was found to be associated with CaD with or without hyporeflective cores.}, }
@article {pmid42426273, year = {2026}, author = {Schmidt, R and Weissenbacher, LM and Vécsei-Marlovits, V and Weingessel, B}, title = {Comparison of intravitreal anti-VEGF treatment burden in different retinal diseases.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42426273}, issn = {1476-5454}, abstract = {BACKGROUND/OBJECTIVES: To compare the subjective treatment burden of intravitreal anti-VEGF therapy (IVT) among patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), and macular oedema secondary to retinal vein occlusion (CME).<br><br>SUBJECTS/METHODS: This single-centre, cross-sectional study surveyed 393 patients at the Department of Ophthalmology, Hietzing Hospital, Vienna. All participants had received at least five anti-VEGF intravitreal injections and had been in treatment for at least six months. Data were collected via a structured questionnaire, assessing perceived treatment burden, sociodemographics, and treatment-related experiences. Statistical analysis was performed using SPSS, with nonparametric tests applied due to ordinal data.<br><br>RESULTS: Of the 393 participants (nAMD: 305; CME: 55; DME: 33), 64% reported no or only slight burden from treatment frequency or injections. There was no statistically significant difference in overall treatment burden between disease groups (p&#x2009;>&#x2009;0.4). However, the nature of the burden differed: nAMD patients most often cited fear of progressive vision loss, while CME and DME patients more frequently named the injection itself as the greatest burden. Better patient education significantly correlated with a lower perceived burden (p&#x2009;<&#x2009;0.001). Nearly half of the patients required assistance with clinic visits.<br><br>CONCLUSIONS: Although the overall perceived burden of anti-VEGF treatment was similar across retinal diseases, patients' specific concerns varied. Addressing these differences through personalised education and communication may help alleviate treatment-related anxiety and improve adherence. These findings highlight the importance of tailoring support strategies to individual patient experiences within long-term intravitreal treatment regimens.}, }
@article {pmid42431462, year = {2026}, author = {Cozzi, M and Zweifel, SA and Spooner, K and Romano, F and Guymer, R and Sadda, SR and Staurenghi, G and Invernizzi, A}, title = {Non-advanced age-related macular degeneration: current concepts and future perspectives.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100346}, doi = {10.1016/j.apjo.2026.100346}, pmid = {42431462}, issn = {2162-0989}, abstract = {Non-advanced age-related macular degeneration (AMD), encompassing early and intermediate stages, represents a critical therapeutic window before irreversible central vision loss. Traditionally defined by drusen size and pigmentary abnormalities on color fundus photography, disease characterization has evolved substantially with the integration of multimodal imaging biomarkers. Contemporary imaging enables detailed structural phenotyping, including reticular pseudodrusen (also known as subretinal drusenoid deposits), hyperreflective foci, and incomplete retinal pigment epithelium and outer retinal atrophy, which refine risk stratification and provide insight into progression toward advanced disease. Functional assessment has expanded beyond best-corrected visual acuity to include low-luminance visual acuity, contrast sensitivity, dark adaptation, and microperimetry, many of which are more sensitive to early dysfunction. However, standardization and regulatory approval of these endpoints remain ongoing challenges. Non-advanced AMD arises from complex interactions among genetic susceptibility, aging, environmental exposures, and systemic metabolic factors. Smoking remains the strongest modifiable risk factor, while Mediterranean dietary patterns appear protective. Currently, no pharmacologic therapies are approved for non-advanced AMD. The Age-Related Eye Disease Study formulations remain the only interventions proven to reduce progression in high-risk individuals. Emerging approaches, including subthreshold laser therapy and photobiomodulation, show preliminary promise but require validation in robust and adequately powered randomized clinical trials. Recent consensus efforts emphasize biomarker-driven classification and highlight the heterogeneity of AMD phenotypes across populations. Future research priorities include validation of quantitative imaging and functional endpoints, integration of artificial intelligence-based predictive models, and development of targeted therapies to delay progression. These endevours will be essential to advance precision prevention strategies.}, }
@article {pmid42431855, year = {2026}, author = {Litvin, DG and Boizot, A and Corna, A and Navarro, A and Keller, J and Heuschkel, MO and Roux, A and Zeck, G and Tran, HV and Ghezzi, D}, title = {Resting-state electroretinography reveals pathological retinal oscillations in retinitis pigmentosa mice and patients.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-75520-9}, pmid = {42431855}, issn = {2041-1723}, abstract = {Retinal remodeling occurs in both retinitis pigmentosa and age-related macular degeneration. However, it is still unknown whether spared retinal circuits are also functionally altered. Functional changes have been observed in animal models of retinitis pigmentosa, including the emergence of bursting oscillatory activity in retinal ganglion cells. Yet, comparable oscillatory activity, or other functional alterations, has not been demonstrated in patients. To address this gap, here we report a non-invasive corneal neurotechnology measuring in-vivo resting-state electroretinography and analyzing its frequency content and temporal characteristics to identify biomarkers of functional remodeling. We document that retinal remodeling induces bursting oscillatory activity in-vivo in retinitis pigmentosa mouse models and translate these results to patients. Moreover, we showed in mice that bursting oscillatory activity can be pharmacologically modulated in-vivo. Furthermore, reducing this oscillatory activity increases retinal excitability to electrical stimulation. These results are crucial for a better understanding of retinal degeneration and contribute to sight restoration efforts.}, }
@article {pmid42433200, year = {2026}, author = {Karuntu, JS and Nguyen, XT and Talib, M and van Schooneveld, MJ and Wijnholds, J and van Genderen, MM and Twisk, J and Schalij-Delfos, NE and Klaver, CCW and Florijn, RJ and Ten Brink, JB and Smoor, MA and van den Born, LI and Hoyng, CB and Thiadens, AAHJ and Boon, CJF}, title = {CRB1-Associated Inherited Retinal Dystrophies: Prospective Natural History Study With 4 Years of Follow-Up.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.70142}, pmid = {42433200}, issn = {1442-9071}, support = {//Algemene Nederlandse Vereniging ter voorkoming van Blindheid/ ; //Landelijke Stichting voor Blinden en Slechtzienden/ ; //Oogfonds/ ; //Curing Retinal Blindness Foundation/ ; //Stichting Retina Fonds/ ; //Bontius Stichting/ ; //Stichting Blindenhulp/ ; }, abstract = {BACKGROUND: The lack of validated and sensitive clinical endpoints remains a major challenge in the design of gene therapy trials for inherited retinal dystrophies (IRDs). This prospective longitudinal cohort study describes the natural disease progression of IRDs caused by pathogenic mutations in the Crumbs homologue 1 (CRB1) gene, and identifies sensitive clinical endpoints.<br><br>METHODS: In this single-centre study, patients with genetically confirmed CRB1-associated IRD were assessed at baseline, 2-year and 4-year follow-up. The phenotyping protocol included best-corrected visual acuity (BCVA), Goldmann perimetry, mesopic microperimetry, full-field stimulus testing (FST), ophthalmoscopy and assessment of retinal structural integrity on spectral-domain optical coherence tomography and fundus autofluorescence.<br><br>RESULTS: Twenty of the 22 enrolled patients completed the 4-year follow-up, including patients with retinitis pigmentosa (n&#x2009;=&#x2009;17), cone-rod dystrophy (n&#x2009;=&#x2009;2) or macular dystrophy (n&#x2009;=&#x2009;1). Significant decreases were observed for BCVA (-6.2 ETDRS letters, 95% confidence interval [CI] -10.1 to -2.3; p&#x2009;=&#x2009;0.003), V4e isopter seeing retinal area (-43.9&#x2009;mm[2], 95% CI, -72.3 to -15.5; p&#x2009;=&#x2009;0.003) and mean sensitivity on microperimetry (-2.5&#x2009;dB, 95% CI, -3.3 to -1.6; p&#x2009;<&#x2009;0.001). FST thresholds for white, blue and red stimuli did not significantly change over 4&#x2009;years (p&#x2009;=&#x2009;0.24; p&#x2009;=&#x2009;0.78; p&#x2009;=&#x2009;0.60, respectively). The continuity of the ellipsoid zone (EZ) and the external limiting membrane (ELM) on SD-OCT were increasingly disrupted in six patients over the course of this study.<br><br>CONCLUSION: Except for FST responses, a significant decrease was observed over 4&#x2009;years in the visual function parameters of BCVA, Goldmann perimetry and microperimetry and these may thus be used as sensitive clinical endpoints.}, }
@article {pmid42411867, year = {2026}, author = {Curcio, CA and Gao, L and Pu, J and Gooden, L and Thomas, TN and Kim, SS and Goerdt, L and Berlin, A and McGwin, G and Sloan, KR and Johnson, EJ and Owsley, C}, title = {Xanthophyll Carotenoid Intake, Plasma Levels, and Retinal Visualization in Aging and Age-Related Macular Degeneration: ALSTAR2.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {22}, doi = {10.1167/iovs.67.8.22}, pmid = {42411867}, issn = {1552-5783}, mesh = {Humans ; Female ; *Macular Degeneration/blood/diagnosis ; Aged ; Cross-Sectional Studies ; Male ; *Aging/physiology ; *Lutein/administration &amp; dosage/blood ; *Zeaxanthins/administration &amp; dosage/blood ; *Xanthophylls/administration &amp; dosage/blood ; Dietary Supplements ; Middle Aged ; Aged, 80 and over ; *Retina/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; Macular Pigment ; Tomography, Optical Coherence/methods ; }, abstract = {PURPOSE: The purpose of this study was to determine cross-sectional associations among intake of xanthophyll carotenoids lutein and zeaxanthin (L&amp;Z), plasma L&amp;Z, and two wavelength autofluorescence (2WAF) retinal imaging in aging and age-related macular degeneration (AMD).<br><br>METHODS: Adults &#x2265;63 years old from a comprehensive ophthalmology clinic underwent assessments: macular health (Age-Related Eye Disease Study [AREDS] 9-step); self-reported L&amp;Z intake from diet (LZQ Food Frequency Questionnaire) and supplements; total intake; macular pigment optical volume (MPOV; in 2WAF); non-fasting plasma L&amp;Z; and HDL and LDL cholesterol. Associations were adjusted for age and HDL/LDL.<br><br>RESULTS: We studied 369 persons (74 &#xb1; 5.8 years, 60% women, 89% White, 62% never-smoker, and 23% supplement use) and 369 eyes (48.4% healthy, 26.0% early AMD [eAMD], and 25.2% intermediate AMD [iAMD]). Diagnostic groups differed in supplement users (10%, 17%, and 56%), total L&amp;Z intake (5.3 &#xb1; 6.4, 5.5 &#xb1; 5.4, and 11.0 &#xb1; 8.3&#xa0;mg/d, P < 0.01), and MPOV (1.04 &#xb1; 0.46, 1.02 &#xb1; 0.52, and 1.33 &#xb1; 0.61). Groups did not differ in dietary intake (3.8 &#xb1; 4.5, 3.4 &#xb1; 3.2, and 3.7 &#xb1; 3.8&#xa0;mg/d), plasma HDL, or HDL/LDL. Associations were strong between plasma L&amp;Z and MPOV (r = 0.41-0.67, P < 0.01); moderate between total intake and plasma L&amp;Z (Spearman r = 0.29-0.50, P < 0.01); weaker but significant for L&amp;Z intake, and MPOV (r = 0.22-0.30, P < 0.01) of 3-mm-diameter macula lutea only, for eAMD and iAMD.<br><br>CONCLUSIONS: In a large US sample, we assess for the first time L&amp;Z intake from diet and supplements and determined the relative strength of correlations among intake, plasma, and retinal xanthophylls. We replicate our earlier finding of elevated retinal and plasma L&amp;Z in iAMD. LZQ and 2WAF are suitable outcome measures for future interventions that directly test the impact of L&amp;Z on AMD onset and progression.}, }
@article {pmid42414674, year = {2026}, author = {Beazley-Long, N and Horder, JL and Green, KR and Bourne, JH and Lynch, AP and Ahmed, NS and Tabrizi, ZB and Diez-Pinel, G and Carroll, CP and Allen, CL and Cresswell, CT and Harris, PE and Ferreira, I and Mosqueira, D and Rayes, J and Mongan, NP and King, J and Denning, C and McIntyre, A and Stemmler, MP and Brabletz, S and Brabletz, T and Bates, DO and Benest, AV}, title = {Loss of endothelial ZEB1 enhances neovascularisation during choroidal neovascularisation.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-026-10630-0}, pmid = {42414674}, issn = {2399-3642}, support = {PG/18/31/33759//British Heart Foundation (BHF)/ ; 223122/Z/21/Z//Wellcome Trust (Wellcome)/ ; }, abstract = {Choroidal neovascularisation (CNV) is a hallmark of wet/neovascular age-related macular degeneration (wAMD), characterized by aberrant blood vessel growth from the choroid into the retina. Both pathological angiogenesis and inflammation contribute to disease progression. Here we show that analsysis of single-cell RNA sequencing of experimental CNV lesions revealed upregulation of Zeb1 in angiogenic endothelial cells (ECs). We generated an endothelial-specific Zeb1 knockout (Zeb1[iECKO]) mouse model to assess its functional role. CNV was induced via laser photocoagulation, and vascular leakage and inflammation were evaluated using fluorescein angiography, immunohistochemistry, and transcriptomic analyses. Zeb1[iECKO] mice exhibited increased fluorescein leakage and enhanced vascular invasion during CNV, indicating destabilized neovascular structures. However, leukocyte infiltration within CNV lesions was not elevated. In vitro, ZEB1 knockdown in human ECs led to downregulation of inflammatory signalling pathways and reduced expression of adhesion molecules in response to TNF-α stimulation yet retained angiogenic capacity. ZEB1 coordinates angiogenic and inflammatory responses in CNV. Its loss enhances neovascularisation without promoting inflammation, suggesting a potential therapeutic target for modulating pathological angiogenesis in wAMD while minimizing inflammatory damage.}, }
@article {pmid42415636, year = {2026}, author = {Chun, J and Choi, YJ and Kim, TY and Park, SI and Lee, SM and Choi, EY and Lee, J and Kim, M}, title = {Subretinal Tissue Plasminogen Activator Injection Using a Nanovitreoretinal Device for Massive Submacular Hemorrhage: A Retrospective Case Series.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2026.0084}, pmid = {42415636}, issn = {2092-9382}, abstract = {PURPOSE: To evaluate the efficacy of subretinal tissue plasminogen activator (tPA) injection in patients with massive submacular hemorrhage (SMH) with or without vitrectomy.<br><br>METHODS: This retrospective study included patients with massive SMH treated with subretinal tPA injection (12.5 &#x3bc;g/0.1 mL) using a nanovitreoretinal (NVR) device at a single tertiary referral center between 2020 and 2024. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT); secondary outcomes included SMH thickness reduction and between-group comparison of surgical approaches.<br><br>RESULTS: 18 eyes of 15 patients (11 females, 61.1%) were analyzed. Twelve eyes underwent vitrectomy (66.7%), while six were treated without vitrectomy (33.3%). Baseline demographic and clinical characteristics were summarized descriptively because of the small and imbalanced subgroup sizes. Neovascular age-related macular degeneration was the leading etiology (17/18 eyes; 94.4%), comprising typical neovascular age-related macular degeneration (n=9, 50.0%), polypoidal choroidal vasculopathy (n=7, 38.9%), and retinal angiomatous proliferation (n=1, 5.6%); the remaining eye (5.6%) had peripheral exudative hemorrhagic chorioretinopathy. BCVA improved significantly from 1.79&#xb1;0.77 to 1.28&#xb1;0.83 logMAR (P=0.01), with 10 eyes (55.6%) achieving &#x2265;3-line improvement. CMT decreased significantly at 6 months (673.8&#xb1;346.7 to 266.0&#xb1;327.1 &#x3bc;m; P=0.019), and 81.3% of eyes achieved &#x2265;20% CMT reduction. SMH thickness decreased significantly post-injection (536.9&#xb1;345.0 to 221.4&#xb1;443.4 &#x3bc;m; P=0.02). No significant differences in final BCVA (1.24&#xb1;0.77 vs. 1.37&#xb1;1.01 logMAR; P=0.850) or CMT reduction rate (81.8% vs. 80.0%; P=0.999) were observed between vitrectomy and non-vitrectomy groups.<br><br>CONCLUSIONS: Subretinal tPA injection via the NVR device was associated with improvements in visual and anatomical outcomes in massive SMH. The non-vitrectomy approach showed no significant difference in outcomes compared with vitrectomy-assisted injection, but this exploratory finding should be interpreted cautiously given the small sample size.}, }
@article {pmid42419032, year = {2026}, author = {Lee, SJ and Noh, SE and Kim, JH}, title = {Exogenous mitochondrial transplantation attenuates oxidative stress-driven retinal degeneration in a sodium iodate - induced mouse model.}, journal = {Neurobiology of aging}, volume = {168}, number = {}, pages = {1-13}, doi = {10.1016/j.neurobiolaging.2026.07.002}, pmid = {42419032}, issn = {1558-1497}, abstract = {Age-related macular degeneration (AMD) is a degenerative retinal disease initiated by dysfunction of the retinal pigment epithelium (RPE), in which age-related mitochondrial impairment, oxidative stress, chronic inflammation, and complement activation collectively drive outer retinal dysfunction and RPE atrophy, ultimately leading to progressive central vision loss. Accumulating evidence indicates that mitochondrial abnormalities, including excessive reactive oxygen species (ROS) production, mitochondrial fragmentation, and inflammatory signaling, play a central role in AMD pathogenesis. In this study, we investigated the therapeutic potential of exogenous mitochondrial transplantation using a sodium iodate (SI)-induced retinal degeneration model that recapitulates key pathological features of dry AMD. In ARPE-19 cells, SI-induced oxidative stress triggered mitochondrial fragmentation, inflammasome activation, and tight junction disruption, whereas delivery of mitochondria isolated from bone marrow-derived mesenchymal stem cells attenuated mitochondrial dysfunction and preserved RPE barrier integrity by suppressing oxidative and inflammatory signaling. Consistent with these in vitro findings, intravitreal mitochondrial transplantation in SI-treated mice attenuated RPE shedding/migration and outer nuclear layer disorganization while suppressing retinal oxidative stress, inflammatory cytokine expression, and complement activation. Importantly, mitochondrial transplantation mitigated the decline in retinal function, as assessed by electroretinography and optokinetic response testing, without fully restoring responses to control levels. Collectively, these results support exogenous mitochondrial transplantation as a promising cell-free therapeutic strategy to attenuate oxidative stress-driven retinal degeneration by modulating mitochondrial dysfunction and associated inflammatory pathways in AMD.}, }
@article {pmid42419444, year = {2026}, author = {Li, FR and Peng, MJ and Lin, KQ and Zhou, Y and Yuan, FL and Jin, CY and Luo, H and Yu, L and Chi, W}, title = {Clonal Hematopoiesis of Indeterminate Potential and Genetic Susceptibility in Incident Age-Related Macular Degeneration: A Cohort Study.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.07.008}, pmid = {42419444}, issn = {1879-1891}, abstract = {PURPOSE: While inherited genetics strongly influence AMD risk, clonal hematopoiesis of indeterminate potential (CHIP), an age-related condition driven by somatic mutations and inflammation, is a novel, biologically plausible risk factor. Prospective evidence exploring their interplay with AMD incidence is lacking.<br><br>DESIGN: Prospective cohort study.<br><br>PARTICIPANTS: We conducted a prospective cohort study among 395,505 participants from the UK Biobank.<br><br>METHODS: CHIP was defined by somatic mutations (variant allele fraction &#x2265;2%) in leukemia-associated driver genes from blood-derived exome sequencing. A polygenic risk score (PRS) for AMD was calculated using established genetic variants. We used Cox proportional hazards models to assess the independent and joint associations of CHIP and PRS with incident AMD.<br><br>MAIN OUTCOME MEASURES: Age-related macular degeneration.<br><br>RESULTS: During a median follow-up of 15.5 years, we documented 7,178 incident AMD cases. CHIP was associated with a 14% higher risk of incident AMD (HR: 1.14; 95% CI: 1.03, 1.26; P=0.009). Gene-specific analyses showed significant associations for mutations in DNMT3A (HR: 1.20; 95% CI: 1.06, 1.36; P=0.005), spliceosome genes (HR: 1.72; 95% CI: 1.02, 2.97; P=0.042), and DNA damage repair genes (HR: 1.68; 95% CI: 1.06, 2.67; P=0.028). A high AMD PRS was also associated with AMD risk. Participants with both any CHIP and a high PRS had a 3.26-fold higher risk (95% CI: 2.75, 3.86; P<0.001) compared to those with neither, with evidence of additive interaction (relative excess risk due to interaction [RERI]&#x202f;=&#x202f;0.60; 95% CI: 0.07, 1.20). The joint effect was also strongest for DNMT3A mutation carriers with high PRS (HR: 3.69; 95% CI: 2.58, 3.96; P<0.001; RERI&#x202f;=&#x202f;0.34; 95% CI: 0.04, 1.12). These synergistic effects were more pronounced in older adults.<br><br>CONCLUSION: CHIP was an independent risk factor for incident AMD. The risk is amplified in individuals with high genetic susceptibility, suggesting a synergistic interplay between inherited genetic risk and somatic clonal expansion in AMD pathogenesis, with the strongest effects observed in older adults. These findings provide a rationale for future efforts to integrate somatic mutation status into risk stratification paradigms for AMD, especially among the elderly.}, }
@article {pmid42419576, year = {2026}, author = {Renfang-Zhu,  and Xu, Y and Nie, M and Li, H and Yuan, Y and Cui, Z and Wang, H and Zhai, Q and He, X and Mao, Y and Wei, Y and Guan, J and Zhang, X and Mao, S}, title = {Virus-biomimetic melanin nanoparticles with spiky structures and neutral zwitterionic shell for non-invasive prevention of dry AMD.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {}, number = {}, pages = {115168}, doi = {10.1016/j.jconrel.2026.115168}, pmid = {42419576}, issn = {1873-4995}, abstract = {Clinically, no effective preventive strategies currently exist to inhibit the progression of early dry age-related macular degeneration (dAMD). Moreover, current retinal therapies rely on intravitreal injections, which carry inherent procedural risks. Inspired by natural melanin and viral structures, we developed virus-biomimetic melanin nanoparticles (VMNPs) surface-modified with ergothioneine (ET), featuring virus-like spike structures and a neutral zwitterionic shell. This study aimed to evaluate whether virus-inspired engineered nanoparticles could enhance retinal delivery and improve the therapeutic potential of melanin-based nanodrugs for dAMD. The VMNPs facilitated cellular uptake through both their virus-mimetic architecture and OCTN1-mediated active transport. They also exhibited potent antioxidant activity, significantly reducing intracellular and mitochondrial reactive oxygen species (ROS) in oxidative stress models of ARPE-19 cells. Transcriptomic analyses revealed that VMNPs activated intrinsic cytoprotective pathways by upregulating HMOX1and SLC7A11, while downregulating inflammation-associated genes. Importantly, VMNPs promoted transcytosis and, following topical administration, demonstrated improved retention and deep penetration within the rabbit eye, effectively reaching the retinal pigment epithelium (RPE) and deeper retinal layers. Notably, twice-daily topical administration of VMNPs markedly inhibited retinal degeneration in rabbits, achieving therapeutic efficacy comparable to a single intravitreal injection of pegcetacoplan. Collectively, these findings establish a promising paradigm for the non-invasive clinical treatment of dAMD.}, }
@article {pmid42421757, year = {2026}, author = {Olivieri, C and Perin, G and Zhuang, X and Neri, G and Parisi, G and Marolo, P and Viggiano, P and Boscia, F and Reibaldi, M and Borrelli, E}, title = {Baseline Optical Coherence Tomography Biomarkers Associated with the 2-Year Development of Macular Atrophy or Fibrosis in Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101268}, pmid = {42421757}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate baseline structural OCT biomarkers associated with the development of macular atrophy or fibrosis in treatment-naïve eyes with exudative neovascular age-related macular degeneration (AMD) managed with a treat-and-extend (T&amp;E) anti-VEGF regimen.<br><br>DESIGN: A retrospective, cohort study.<br><br>PARTICIPANTS: Eighty-nine eyes of 89 patients with newly diagnosed exudative neovascular AMD, treated with a T&amp;E regimen and followed for 24 months. Eyes with evidence of macular atrophy or fibrosis at baseline were excluded.<br><br>METHODS: Structural OCT scans were assessed at baseline for morphological features including, macular neovascularization (MNV) subtype and presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material, hyperreflective foci, and subretinal drusenoid deposits. Two masked graders independently evaluated each scan, with adjudication for discrepancies. Cox regression models were used to determine baseline predictors of macular atrophy and fibrosis over 24 months.<br><br>MAIN OUTCOME MEASURES: Development of macular atrophy or fibrosis during 24 months, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).<br><br>RESULTS: During follow-up, 28 eyes (31.5%) developed macular atrophy and 12 eyes (13.5%) developed macular fibrosis, with 10 eyes showing both complications. Multivariate Cox regression identified baseline IRF (HR, 6.07; 95% CI, 2.23-16.48) and type 3 MNV (HR, 4.38; 95% CI, 1.63-11.73) as independent predictors of macular atrophy, whereas type 1 MNV was protective (HR, 0.23; 95% CI, 0.09-0.61). Type 2 MNV emerged as the strongest predictor of macular fibrosis (HR, 7.28; 95% CI, 1.51-35.10).<br><br>CONCLUSIONS: Baseline OCT biomarkers, particularly IRF and type 3 MNV, strongly predict macular atrophy, while type 2 MNV predicts fibrosis in eyes with exudative neovascular AMD treated with a T&amp;E regimen. Type 1 MNV may confer protection against atrophy. These exploratory findings underscore the value of comprehensive baseline OCT assessment for anticipating long-term structural outcomes and guiding clinical management.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42421758, year = {2026}, author = {Wright, DM and Trifonov, I and Shahar-Gonen, M and Loewenstein, A and Zur, D and Peto, T}, title = {Machine Learning to Predict Outcomes of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101238}, pmid = {42421758}, issn = {2666-9145}, abstract = {OBJECTIVE: To develop machine learning models using OCT fluid metrics to predict long-term anti-VEGF treatment intensity and visual acuity (VA) outcomes in 2 large clinical data sets of patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, multicenter cohort study.<br><br>SUBJECTS: The study included a total of 2922 eyes from 2475 patients with nAMD treated at 2 tertiary centers in the United Kingdom (Belfast) and Israel (Tel Aviv Medical Center).<br><br>METHODS: Longitudinal clinical data and OCT scans obtained at baseline and 6 months after treatment initiation were analyzed using a validated deep learning algorithm to extract quantitative volumetric retinal fluid measurements. Machine learning ensemble models were trained using the Belfast data set to predict total anti-VEGF injections and absolute VA at 1, 2, and 3 years from treatment initiation. External validation was performed by applying the trained models to an independent cohort to assess generalizability across health care systems.<br><br>MAIN OUTCOME MEASURES: Prediction accuracy for the total number of anti-VEGF injections and absolute VA at years 1 to 3 since treatment initiation, assessed by agreement with observed outcomes.<br><br>RESULTS: In the main cohort, prediction of total anti-VEGF injections was accurate, with 99.6%, 95.5%, and 97.1% of eyes predicted within 2 injections of observed values at years 1, 2, and 3, respectively. Visual acuity predictions were within &#x2264;0.2 logarithm of the minimum angle of resolution units (&#x2264;2 ETDRS lines) for 92.5%, 73.5%, and 76.5% of eyes at the corresponding time points. In the external cohort, model performance was reduced, with 45.0% to 53.8% of injection predictions and 26.3% to 41.1% of VA predictions meeting accuracy thresholds. Subretinal fluid at 6 months was the primary driver of injection burden predictions, whereas intraretinal fluid was most influential for VA outcomes.<br><br>CONCLUSIONS: Machine learning models based on automated fluid metrics can accurately predict treatment burden and VA outcomes within the clinical environment in which they are developed. Although performance declined with external validation, reflecting differences in treatment policies and health care systems, locally trained models remain clinically valuable. Early identification of high- and low-burden treatment trajectories may support individualized decision-making, patient counseling, and more efficient allocation of ophthalmology resources in the growing nAMD population.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42406041, year = {2026}, author = {Veritti, D and Sarao, V and Lupidi, M and Viggiano, P and Lombardo, M and Parravano, M and Savastano, MC and Boscia, G and Borrelli, E and Toto, L and Martin, AA and Termite, AC and Ribezzi, G and Nacciarriti, E and Fossataro, C and Gisotti, EN and Neri, G and Persavalli, C and Boscia, F and Mariotti, C and Mastropasqua, R and Reibaldi, M and Ricci, F and Rizzo, S and Savastano, A and Varano, M and Lanzetta, P}, title = {Switching to aflibercept 8 mg in neovascular age-related macular degeneration: real-world outcomes according to switch indication.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42406041}, issn = {1435-702X}, abstract = {PURPOSE: To evaluate visual and anatomical outcomes after switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD), and to assess outcomes according to the clinical indication for switching.<br><br>METHODS: Multicentre retrospective observational study including 300 eyes with nAMD previously treated with anti-vascular endothelial growth factor therapy and switched to aflibercept 8&#xa0;mg for non-response (n:74, 24.7%), suboptimal response (n:159, 53.0%), or durability-driven reasons (n:67, 22.3%). Longitudinal data from the 6&#xa0;months preceding the switch and post-switch visits at 3 and 6&#xa0;months were analyzed. The primary outcome was change in best-corrected visual acuity (BCVA, ETDRS letters) from the switch visit to the 3-month post-switch visit. Secondary outcomes included changes in central subfield thickness (CST) and retinal fluid status.<br><br>RESULTS: During the pre-switch period, mean BCVA declined by&#x2009;-&#x2009;1.9&#x2009;&#xb1;&#x2009;8.2 letters and CST increased. At 3&#xa0;months after switching, BCVA improved by&#x2009;+&#x2009;2.0&#x2009;&#xb1;&#x2009;9.2 letters (95% CI,&#x2009;+&#x2009;0.8 to&#x2009;+&#x2009;3.2; p&#x2009;<&#x2009;0.01), with greater gains in eyes switched for non-response (+&#x2009;2.8&#x2009;&#xb1;&#x2009;12.6 letters). Mean CST decreased by&#x2009;-&#x2009;45.3&#x2009;&#xb1;&#x2009;79.8&#xa0;&#xb5;m (95% CI,&#x2009;-&#x2009;55.4 to&#x2009;-&#x2009;35.2; p&#x2009;<&#x2009;0.001), with corresponding reductions in retinal fluid. Anatomical improvements were more pronounced in eyes switched for non-response, whereas more modest but consistent changes were observed in suboptimal and durability-driven groups. Visual and anatomical outcomes were maintained at 6&#xa0;months.<br><br>CONCLUSIONS: In previously treated nAMD eyes, switching to aflibercept 8&#xa0;mg was associated with reversal of pre-switch anatomical worsening, reduction in retinal fluid, and modest visual gains. Greater responses were observed in eyes with inadequate pre-switch disease control, supporting its role as a treatment escalation strategy in clinical practice.}, }
@article {pmid42406042, year = {2026}, author = {Sakai, R and Ichioka, A and Ideyama, M and Akada, M and Ueda-Arakawa, N and Kido, A and Takahashi, A and Miyake, M and Muraoka, Y and Miyata, M and Tamura, H and Ooto, S and Tsujikawa, A and Hata, M}, title = {Association between angiogenic features and responsiveness to faricimab in treatment-naïve neovascular age-related macular degeneration with OCT angiography.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42406042}, issn = {1435-702X}, abstract = {PURPOSE: To investigate morphological changes in macular neovascularization (MNV) using optical coherence tomography angiography (OCTA) and identify imaging biomarkers associated with treatment responsiveness to faricimab in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study investigated consecutive eyes of patients with treatment-na&#xef;ve nAMD who were treated with faricimab. After 3-monthly loading doses, the patients received a fixed 8-, 12-, or 16-week treatment regimen (Q8W/Q12W/Q16W) and were grouped as poor responders (Q8W/Q12W) or good responders (Q16W). Dosing interval determination depended on disease activity post-loading phase. Baseline and 14-month quantitative OCTA parameters were analyzed.<br><br>RESULTS: Forty-four eyes (pure type 1 MNV: 35 eyes, mixed type 1 and type 2 MNV: 9 eyes) were analyzed. The visual acuity (P&#x2009;<&#x2009;0.001) and central retinal thickness (P&#x2009;<&#x2009;0.0001) significantly improved post-faricimab treatment from baseline to Month 14. In mixed type 1 and type 2 MNV, total vessel length decreased from baseline to Month 14 (P&#x2009;<&#x2009;0.05), whereas vessel area did not significantly change (P&#x2009;=&#x2009;0.11). No significant changes in total vessel length or vessel area were detected in pure type 1 MNV (P&#x2009;=&#x2009;0.23 and P&#x2009;=&#x2009;0.30, respectively). In the subgroup of type 1 MNV, a significant decrease in endpoint density was observed only in good responders (P&#x2009;=&#x2009;0.04), with no corresponding change in poor responders.<br><br>CONCLUSION: A fixed faricimab regimen through Month 14 was associated with improved visual and anatomical outcomes in treatment-na&#xef;ve nAMD. OCTA-based vascular changes differed according to MNV type and treatment responsiveness. In pure type 1 MNV, endpoint density may be a potential OCTA-based biomarker associated with treatment responsiveness, contributing to a more personalized therapeutic approach for nAMD.}, }
@article {pmid42406913, year = {2026}, author = {Kuo, BI and Wang, TA and Chu, TC and Chan, DC and Cheng, SY and Tsai, CT and Tsai, CL and Lee, YC and Chen, CJ and Chen, WL and Lee, JT and Tsai, CY and Liu, PY and Chang, CY and Chao, CT and Kao, JH and Hsieh, YT and , }, title = {Artificial Intelligence-Assisted Screening for Patients With Diabetic Retinopathy and Age-Related Macular Degeneration in Family Medicine and Geriatric and Gerontology Care: Protocol for a Pragmatic Randomized Clinical Trial.}, journal = {JMIR research protocols}, volume = {15}, number = {}, pages = {e91699}, pmid = {42406913}, issn = {1929-0748}, mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; *Macular Degeneration/diagnosis ; *Artificial Intelligence ; *Mass Screening/methods ; Pragmatic Clinical Trials as Topic ; Aged ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Family Practice/methods ; Female ; Cost-Benefit Analysis ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are 2 of the leading causes of vision loss worldwide. As population aging and diabetes prevalence increase, timely detection of these conditions has become essential. However, limited professionalism and insufficient training in ophthalmic screening among general medicine physicians may lead to delayed diagnosis and treatment. Artificial intelligence (AI)-assisted diagnostic tools may help to improve the screening of DR and AMD in routine clinical practice.<br><br>OBJECTIVE: This study aims to evaluate the clinical effectiveness and cost-effectiveness of AI-assisted fundus imaging for DR and AMD screening in adults with diabetes and older adults at risk of macular degeneration.<br><br>METHODS: This multicenter, 2-arm, parallel-group, open-label, individual-level randomized controlled trial and patient recruitment are performed at the settings of Family Medicine and Geriatric and Gerontology Care over 4 medical centers in Taiwan. Eligibility includes (1) diabetic individuals aged &#x2265;20 years for DR screening, and (2) individuals aged &#x2265;50 years for AMD screening. The study protocol has been approved by the ethics committees of all participating hospitals, and all participants will provide written informed consent.<br><br>RESULTS: The study was funded in September 2024, began on October 2, 2025, and is expected to be completed in December 2027. After the pilot implementation phase without randomization, participants will be randomized 1:1 into two groups: (1) AI-assisted screening, and (2) usual physician-only screening. The primary outcomes will include the detection rates (defined as participants with confirmed DR or AMD among all screened participants) and the positive predictive values (defined as participants with confirmed DR or AMD among those who tested positive). Cost-effectiveness analyses will be performed using data derived from the trial results.<br><br>CONCLUSIONS: This study will provide robust evidence on the effectiveness of AI-assisted ophthalmic screening in improving patient eye health outcomes through timely screening and accurate early detection. This strategy may be cost-effective.}, }
@article {pmid42410200, year = {2026}, author = {Beretta, F and Scalabrin, G and Balduzzi, E and Puligheddu, S and Bandello, F and Sacconi, R and Querques, G}, title = {Real-Life 1-Year Results and Predictors of Visual Outcome with Intravitreal Faricimab for Treatment of Exudative Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42410200}, issn = {2193-8245}, abstract = {INTRODUCTION: The purpose of this study was to report 1-year real-world outcomes of faricimab for the treatment of macular neovascularization secondary to age-related macular degeneration (nAMD). Early predictors of functional outcome were investigated.<br><br>METHODS: This was a retrospective, longitudinal study including 132 eyes with nAMD (27% treatment-na&#xef;ve, 73% switchers) treated with faricimab following a treat-and-extend protocol. Primary outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes at 1-year follow-up. Secondary outcomes included possible early predictors of 1-year functional outcomes. Early predictors were investigated at the baseline and after the loading phase.<br><br>RESULTS: After the loading phase, both BCVA (from 0.40&#x2009;&#xb1;&#x2009;0.33 to 0.35&#x2009;&#xb1;&#x2009;0.34 LogMAR) and CMT (from 403&#x2009;&#xb1;&#x2009;135 to 317&#x2009;&#xb1;&#x2009;108 um) improved significantly (p&#x2009;=&#x2009;0.014 and p&#x2009;>&#x2009;0.001 respectively). At 1 year, only CMT reduced significantly (from 403&#x2009;&#xb1;&#x2009;135 to 317&#x2009;&#xb1;&#x2009;114 um, p&#x2009;<&#x2009;0.001), and 36% of eyes were defined as good visual responders (&#x2265;&#x2009;5 ETDRS letters gain). Predictors of good response were lower BCVA and absence of type 3 macular neovascularization (MNV) at baseline and lower CMT after loading phase. Approximately 60% of patients achieved&#x2009;&#x2265;&#x2009;Q12-week dosing. Treatment-na&#xef;ve patients achieved higher extension rates (82%&#x2009;&#x2265;&#x2009;Q12). No cases of intraocular inflammation were observed.<br><br>CONCLUSIONS: In our real-world practice, faricimab effectively controls nAMD, offering significant anatomical benefits and visual stability with extended dosing intervals. Approximately 80% of treatment-na&#xef;ve patients maintained&#x2009;&#x2265;&#x2009;Q12-week schedules. Early anatomical response, defined by reduction in CMT and absence of exudative signs on structural optical coherence tomography (OCT), emerged as a clinically relevant prognostic factor for 1-year outcomes.}, }
@article {pmid42410853, year = {2026}, author = {Song, Y and Ji, H and Xie, D and Huang, F and Yang, L}, title = {Elevated Food Inflammation Scores of individuals is a significant risk factor for age-related macular degeneration in adults in the United States: Evidence from NHANES.}, journal = {Medicine}, volume = {105}, number = {27}, pages = {e49604}, pmid = {42410853}, issn = {1536-5964}, mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; United States/epidemiology ; Nutrition Surveys ; Female ; Risk Factors ; *Inflammation/complications/epidemiology ; Middle Aged ; Male ; Aged ; Cross-Sectional Studies ; Adult ; *Diet/adverse effects ; }, abstract = {Inflammation has been implicated in the pathogenesis of age-related macular degeneration (AMD). We evaluated whether the inflammatory potential of the diet (quantified using the newly developed Food Inflammation Scores of individuals [FISI]) influences the incidence of AMD. Participants aged > 40 years were included from the National Health and Nutrition Examination Survey database, totaling 5293 participants, of whom 421 had AMD. Logistic regression analysis and restricted cubic spline were used to explore the relationship between FISI and AMD. Linear regression analysis was used to analyze the relationship between FISI and age. Path analysis was used to explore the correlation among age, FISI, and AMD. Subgroup analysis explored the relationship between FISI and AMD in subgroups. Interaction analysis explored the interaction between FISI and other variables on AMD. FISI was significantly higher in the AMD group than in the Non-AMD group. There was a significant positive linear association between FISI and AMD, and a higher FISI was associated with higher odds of AMD (odds ratios [95% confidence interval]: 1.040 [1.015-1.065]). The cross-sectional pattern was consistent with age being associated with AMD partly through FISI. Higher FISI was significantly associated with higher odds of AMD in some subgroups. FISI had no interaction with subgroup variables on AMD. In this nationally representative cross-sectional sample of the United States adults aged ≥ 40 years, a higher FISI was associated with a higher prevalence of AMD. Because the design is cross-sectional and a substantial portion of this association was attributable to age, the results should be interpreted as hypothesis-generating; prospective studies are needed before recommending FISI-guided dietary intervention as a primary-prevention strategy for AMD.}, }
@article {pmid42405678, year = {2026}, author = {Sadeghi, E and Gregori, G and DeCicco, J and Sadeghi, Z and Gandhi, P and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Distinct interactions between macular neovascularization and geographic atrophy: Growth dynamics and fellow-eye risk.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261461910}, doi = {10.1177/11206721261461910}, pmid = {42405678}, issn = {1724-6016}, abstract = {PurposeTo compare geographic atrophy (GA) growth in eyes with and without macular neovascularization (MNV) and evaluate anti-VEGF therapy effects on GA progression.MethodsOne eye per patient with GA with one-year of follow-up was included. Patients who developed MNV in previously diagnosed GA were assigned to the MNV-GA group, while those who did not were assigned to the non-MNV group. OCT determined MNV location and type. GA was quantified from RPE en-face images using ImageJ over one year. Fellow eyes were followed to last visit. Analyses used SPSS with Mann-Whitney U; P < 0.05 denoted significance, and prespecified thresholds applied throughout analyses.ResultsA total of 60 eyes from 60 patients were included (mean age: 82.75 ± 7.31; 56.7% female). A significant difference in GA area growth over one year was observed between two groups, with slower GA enlargement in MNV-GA group (1.15 mm[2] vs. 2.36 mm[2]; P = 0.001; and square root: 0.38 ± 0.28 vs. 0.46 ± 0.36; P = 0.040). In MNV-GA eyes, GA growth showed no correlation with the number of anti-VEGF injections (P = 0.692). Most MNVs were type 1 (46.7%) and type 2 (43.3%) and were predominantly located at the GA border (70.0%), particularly in the central (30.0%) and superior (30.0%) sectors. Among the 60 fellow-eyes, 27 (45.0%) developed MNV during follow-up. Of these, 25 eyes (83.3%) were from patients from MNV-GA group, whereas only 2 eyes (6.7%) were from non-MNV group (P < 0.001).ConclusionEyes with MNV-GA showed slower GA enlargement over one-year, regardless of anti-VEGF frequency, and higher fellow-eye MNV risk, indicating shared risk factors but distinct mechanisms influencing disease progression.}, }
@article {pmid42405917, year = {2026}, author = {Ying, GS}, title = {Nonsteroidal Anti-inflammatory Drug Use Reduces the Risk of Age-Related Macular Degeneration in Electronic Health Record Analysis: Signal or Solution?.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.06.013}, pmid = {42405917}, issn = {1549-4713}, }
@article {pmid42399507, year = {2026}, author = {Yuan, H and Hu, Y}, title = {Phenotypic age acceleration and genetic risk synergistically increase age-related eye disease risk in the UK Biobank.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-60932-w}, pmid = {42399507}, issn = {2045-2322}, support = {2026Y0015//Jiangxi Provincial Health Commission Introduced and Cultivated Talents Special Scientific Research Project/ ; 202610039//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; YK012//2024 Nanchang University Education Development Foundation "Changyi Leading Research" Clinical Scientific Research Project/ ; }, abstract = {To evaluate the independent and synergistic effects of phenotypic age acceleration (PhenoAgeAccel) and genetic risk on age-related eye diseases (AREDs). We analyzed 395,322 participants from the UK Biobank to assess the association between PhenoAgeAccel and polygenic risk scores for age-related macular degeneration (AMD) and age-related cataract (ARC). Cox proportional hazards models evaluated independent effects and potential synergistic interactions, adjusting for demographic, socioeconomic, and lifestyle factors. PhenoAgeAccel was independently associated with increased risk of AMD (HR = 1.15, 95% CI 1.10-1.21) and ARC (HR = 1.14, 95% CI 1.12-1.17). High genetic risk conferred stronger effects for AMD (HR = 1.88, 95% CI 1.78-1.98) and ARC (HR = 1.31, 95% CI 1.27-1.35). Participants with both elevated PhenoAgeAccel and high genetic risk had markedly higher risk (AMD: HR = 2.19; ARC: HR = 1.47) compared with biologically younger, low-risk individuals. A significant multiplicative interaction was observed for AMD, indicating a synergistic effect between accelerated phenotypic aging and genetic susceptibility. PhenoAgeAccel and genetic risk each contribute to the development of AREDs, and their combination exerts a synergistic effect. Integrating aging biomarkers with genetic profiling could enhance risk stratification and inform targeted prevention strategies for ocular health.}, }
@article {pmid42401235, year = {2026}, author = {Wei, P and Gao, S and Zhang, K and Jia, L and He, M and Lu, J and Li, C and Han, G}, title = {Tanshinone IIA inhibits choroidal neovascularization and restores outer blood-retinal barrier function in Vldlr knockout mice.}, journal = {Experimental eye research}, volume = {271}, number = {}, pages = {111158}, doi = {10.1016/j.exer.2026.111158}, pmid = {42401235}, issn = {1096-0007}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, with its neovascular form (nAMD) primarily treated using anti-VEGF agents; however, therapeutic resistance and nonresponse remain major clinical challenges. Tanshinone IIA (TIIA), a multi-target bioactive compound derived from Salvia miltiorrhiza, has shown potential in retinal disease treatment. In this study, we investigated the therapeutic effects and underlying mechanisms of TIIA on choroidal neovascularization (CNV) using Vldlr knockout (Vldlr[-/-]) mice as an nAMD model. TIIA was administered intraperitoneally for 8 weeks, and CNV progression and vascular leakage were evaluated by OCT and FFA, while outer blood-retinal barrier (oBRB) integrity was assessed by immunofluorescence staining. Proteomics analysis combined with western blotting was used to explore the molecular mechanisms. Our results showed that TIIA significantly reduced CNV area and leakage, and restored oBRB integrity by upregulating tight junction proteins ZO-1 and Occludin in the RPE/choroid complex. Mechanistically, TIIA inhibited angiogenesis via suppression of the PLCγ/ERK1/2 signaling pathway. In addition, proteomics analysis revealed enhanced cholesterol efflux, intermediate filament reorganization, and decreased autophagy-related proteins across the retina, RPE/choroid complex, and serum. Collectively, these findings demonstrate that TIIA alleviates nAMD pathology through multi-target mechanisms, including inhibition of angiogenesis, restoration of barrier function, metabolic reprogramming, and modulation of autophagy, highlighting its potential as an alternative therapeutic strategy for nAMD.}, }
@article {pmid42401373, year = {2026}, author = {Ding, J and Su, L and Chen, W and Wu, R and Gao, L}, title = {Notch signaling in anti-VEGF resistant arteriolar choroidal neovascularization.}, journal = {Biochemical pharmacology}, volume = {}, number = {}, pages = {118214}, doi = {10.1016/j.bcp.2026.118214}, pmid = {42401373}, issn = {1873-2968}, abstract = {Choroidal neovascularization (CNV) is a major pathological hallmark of fundus diseases, such as age-related macular degeneration, and is commonly treated with anti-vascular endothelial growth factor (VEGF) agents. However, resistance to or a suboptimal response to anti-VEGF therapy, particularly in arteriolar CNV, remains a significant clinical challenge. Arteriolar CNV, characterized by arterialized vessels, feeding arterioles with high blood flow, and prominent fibrosis, remains persistently active and responds poorly to standard anti-VEGF therapy. Notch signaling confers anti VEGF resistance in various diseases including cancer and corneal neovascularization. However, its role in anti-VEGF resistant arteriolar CNV has not been systematically summarized. This review highlights Notch signaling as a key regulator of both physiological and pathological arterial remodeling, driving arteriolar differentiation and contributing to resistance to VEGF inhibitors. In tumors, Notch signaling plays a crucial role in driving arteriolar neovessel formation, promoting macrophage-mediated vascular remodeling, and enhancing fibrosis, all of which contribute to anti-VEGF resistance. We also discuss whether and how similar mechanisms may operate in arteriolar CNV and proposes that Notch signaling represents a potential therapeutic target. Furthermore,combining Notch inhibitors with anti-VEGF therapy may improve outcomes in patients with arteriolar CNV resistant to anti-VEGF therapy, thereby providing a potential therapeutic strategies. Future studies are warranted to elucidate the specific roles of Notch signaling in CNV and optimize therapeutic strategies for improved safety and efficacy.}, }
@article {pmid42401656, year = {2026}, author = {Kamiński, P and Brodzka, S and Baszyński, J and Paczała, R and Stanek, E and Rektor, K and Grochowalska, R and Hromada, M and Stuczyński, T and Tkaczenko, H and Woźniak, A and Kurhaluk, N}, title = {Macular degeneration dependent on defense mechanisms conditioned by chemical elements and genetic polymorphism.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-59733-y}, pmid = {42401656}, issn = {2045-2322}, abstract = {Macular degeneration MD is a chronic, lifestyle-related eye disease developing in increasingly younger people. The cause is not fully understood, but oxidative stress is among the most critical factors. The subject of our research is the wet form of MD. The tested materials were whole blood and plasma from 84 patients with exudative MD and from 127 healthy volunteers, from SW Poland. The concentration of toxic metals (Hg, Cd, Pb, As, Be), macroelements (Ca, Mg, Na, K, P) and microelements (Mn, Fe, Zn, Cu, Se, Mo, Cr, Li, V, Co, Ag, Ba, Ti, Tl, Sr, Al, Ni, Sn, B, Sb) was analyzed (ICP-MS) in the blood to determine environmental exposure. The activity of antioxidant enzymes (superoxide dismutase SOD, catalase CAT, glutathione peroxidase GPx, glutathione reductase GR) was determined to demonstrate the ability to eliminate the effects of reactive oxygen species ROS. The activity of nonenzymatic antioxidant mechanisms (reduced glutathione GSH, bilirubin, uric acid, vitamins A and E) was examined to assess the body's ability to activate defense mechanisms against ROS. The intensity of lipoperoxidation (malondialdehyde, MDA), and the importance of ceruloplasmin CP in patients with exudative MD and their exposure to oxidative stress were determined. The presence of glutathione-S-transferase GST polymorphisms (GSTT1, GSTM1) was examined to determine their role in generating MD. The genetic polymorphism of interleukin-4 IL-4 and vascular endothelial growth factor VEGF-A was analyzed, and it was determined whether there is a genetic burden that can potentially increase the chance of developing MD. The activity of SOD, CAT, GPx, and GR, and the activity of nonenzymatic antioxidants (GSH, bilirubin, uric acid, all-trans retinol, and alpha-tocopherol) were determined using Cayman kits and HPLC chromatography. MDA was determined using Cayman reagents, and CP was determined using Wuhan reagents. In our exudative MD patients, P, Ca, Mn, Fe, Cu, and Zn were most involved in interactions, whereas in the control group, Pb, Ca, Mn, Zn, and Ba were most important. In the analysis of antioxidant parameters, significant differences were found between the studied groups for SOD, CAT, GPx, bilirubin, all-trans retinol, alpha-tocopherol, and uric acid. Also, MDA and CP showed significant differences. In MD patients and healthy individuals, many correlations were found. Significant differences were noted for IL-4 in the frequency of the T allele in MD patients, and for Sr. The frequency distributions of GSTT1 and GSTM1 polymorphisms showed no significant differences between the groups, whereas differences were observed for all-trans retinol. Changes within VEGF-A genotypes showed no significant differences between the studied groups (p > 0.5). Due to the presence of mutagenic substances in the environment, the changed genome plays an important role in MD development. The pathogenic process can be observed by analyzing the effectiveness of enzymatic and nonenzymatic mechanisms. The low diagnostic value of MDA and CP for patients with MD was indicated. The results highlighted the significant role of environmental factors and indicated new directions for research into MD etiology. They identified new parameters to be considered when examining predisposition to this disease (Na, P, Cr, Mn, Ba, MDA, bilirubin, A and E vitamins, SOD, CAT, GPx, IL-4). We compare the aspects we examine holistically, making this the first study of this type. Despite many elements of MD development being known so far, there are still many unanswered questions in this field that will require further analysis, especially regarding K, Pb, As, Hg, Cd, Sr, Al, Ba, V, Fe, mutations in IL-4, GSTM1, and GSTT1.}, }
@article {pmid42401735, year = {2026}, author = {Yu, J and Zhang, Y and Gao, YL and Ho, M and Kam, KW and Gong, B and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ}, title = {Association of baseline brain care score with the incidence of age-related eye diseases.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42401735}, issn = {1476-5454}, support = {82425017//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {OBJECTIVES: To evaluate the associations of baseline brain care score (BCS) with the incidence of age-related eye diseases (AREDs), and to examine the modifying effects of age and genetic susceptibility.<br><br>METHODS: We included 382,221 UK Biobank participants without cataract, glaucoma, or age-related macular degeneration (AMD) at baseline. Baseline BCS (0-19 point) encompassed physical, lifestyle and social-emotional factors. Higher BCS scores indicated better brain care. Multivariable Cox regression was used to estimate associations between baseline BCS and incident cataract, glaucoma, and AMD. Polygenic risk scores (PRSs) were used to test gene-BCS interactions.<br><br>RESULTS: Over a median follow-up of 14.28 (interquartile range: 13.34-15.11) years, 44,033 cataract cases, 9280 glaucoma cases, and 6754 AMD cases were identified. Compared with the lowest baseline BCS quintile, the highest baseline BCS quintile was associated with lower risk of cataract (adjusted hazard ratios [HR]: 0.89, 95% confidence interval [CI]: 0.86-0.92), glaucoma (0.92, 0.86-0.98), and AMD (0.90, 0.83-0.97). Stronger associations of per 5-unit increase in baseline BCS with incident cataract (0.78, 0.71-0.85) and glaucoma (0.72, 0.64-0.83) were observed in participants aged 40-50 years than in older groups, with significant interactions with age (P-interaction < 0.001). A significant interaction between baseline BCS and PRS was observed for cataract (P-interaction < 0.001), but not for glaucoma or AMD.<br><br>CONCLUSIONS: Higher baseline BCS is associated with lower long-term risk of AREDs, especially in middle-aged individuals. These findings underscore BCS as a novel and potentially modifiable factor for AREDs.}, }
@article {pmid42402434, year = {2026}, author = {Arnaiz-Camacho, A and Castany-Aregall, M and Pairó-Salvador, A and García-Hidalgo, S and Pablos-Jiménez, T and Bertolani, Y and Alarcón-Portabella, S and Zapata, M&#xc1;}, title = {The Amapola Test: description of a novel screening tool for visual alterations in primary care.}, journal = {Family practice}, volume = {43}, number = {4}, pages = {}, doi = {10.1093/fampra/cmag034}, pmid = {42402434}, issn = {1460-2229}, support = {//Fundaci&#xf3; Catalana d'Oftalmologia (Societat Catalana d'Oftalmologia-SCOFT)/ ; }, mesh = {Humans ; Prospective Studies ; Primary Health Care ; Female ; Male ; *Vision Disorders/diagnosis ; Aged ; Middle Aged ; Aged, 80 and over ; Adult ; *Vision Screening/methods ; *Vision Tests/methods ; Feasibility Studies ; }, abstract = {PURPOSE: To describe a novel screening tool for the detection of visual alterations in primary care.<br><br>METHODS: A prospective study was conducted in order to assess concordance and feasibility of the Amapola Test. In patients with a visual complaint, a primary care resident physician identified the visual symptom using the Amapola Test and the results were then compared with an expert history-taking conducted by an ophthalmologist.<br><br>RESULTS: The Amapola Test was administered to 350 patients with visual disturbances. Of these, 321 patients identified the symptom on the visual charts. The test showed a high concordance rate, with a usability of 89.4% (95% CI: 86.2%-92.6%). The most frequently identified visual symptoms were blurred vision (109), isolated floaters (75), floaters combined with photopsia (23), and isolated photopsia (20). The most common diagnoses were posterior vitreous detachment (100), migraine visual aura (28), and exudative age-related macular degeneration (19).<br><br>CONCLUSION: The Amapola Test allows for correct identification of visual symptoms. This study demonstrates a high level of concordance between patient-reported symptoms using the test and expert clinical history, and indicates potential application as a supportive tool in primary care. However, further studies in real-life settings are needed to demonstrate its usefulness and to evaluate its diagnostic performance.<br><br>CLINICAL TRIAL NUMBER: not applicable.}, }
@article {pmid42403183, year = {2026}, author = {Yoon, E and Shin, JY and Ahn, J}, title = {Impact of Early Residual Fluid after Aflibercept Loading on 12-Month Outcomes in Neovascular Age-Related Macular Degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2026.0060}, pmid = {42403183}, issn = {2092-9382}, abstract = {PURPOSE: To evaluate the impact of early residual fluid (ERF) following aflibercept loading on 12-month anatomical and functional outcomes in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective study included 111 eyes of 107 treatment-na&#xef;ve nAMD patients. ERF was defined as the presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) observed after three loading doses of aflibercept. Patients were divided into ERF (n = 28) and ERF-free (n = 83) groups. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at baseline, post-loading, and at 12 months. Subgroup analyses were conducted based on fluid location within the ERF group.<br><br>RESULTS: ERF was observed in 25.2% of eyes after loading. The ERF group exhibited significantly greater CMT at all time points (P < 0.050). Although BCVA did not differ significantly between groups, the ERF group required a significantly higher injection burden (7.36 &#xb1; 1.95 vs. 5.29 &#xb1; 1.44; P = 0.001). Subgroup analysis within the ERF group revealed that eyes with IRF had worse baseline BCVA (P = 0.038) and a higher rate of persistent IRF at 12 months (87.5%). Multivariate analysis identified post-loading ERF (OR: 3.41, P = 0.046), thicker post-loading CMT (OR: 1.01, P = 0.030), and higher injection frequency (OR: 1.31, P = 0.022) as independent predictors of residual fluid at 12 months.<br><br>CONCLUSIONS: ERF after aflibercept loading is a significant independent predictor of long-term fluid persistence. While ERF signifies a more recalcitrant disease course, comparable visual outcomes can be achieved through proactive, individualized treatment.}, }
@article {pmid42404552, year = {2026}, author = {Macha, NN and Yu, M and Naqvi, S and Birch, D and Tolentino, M and Callanan, D and Maturi, RK}, title = {Multifocal Electroretinography Outcomes Following AVD-104 Treatment for Geographic Atrophy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261438431}, pmid = {42404552}, issn = {2474-1272}, abstract = {Purpose: To assess the treatment effect of AVD-104 in eyes with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in dry AMD studies. Methods: This prospective case series included 6 patients enrolled in part 1 of the phase 2/3 SIGLEC clinical trial, all of whom were diagnosed with advanced bilateral GA. Subjects received a single intravitreal injection of AVD-104 in the study eye. At a screening visit, baseline, and months 1, 2, and 3, mfERG testing and best-corrected visual acuity (BCVA) were collected in the study eyes. mfERG testing was also collected at a screening visit, baseline, and month 3 in fellow eyes. We analyzed the overall N1-P1 response density, overall P1 implicit time, junctional N1-P1 response density, and junctional P1 implicit time at each visit. Results: After AVD-104 treatment, the largest improvements in mean overall N1-P1 response density and junctional N1-P1 response density occurred at month 2, with gains of 17.1% (P = .47) and 40.1% (P = .01), respectively. Five of 6 study eyes achieved a greater than 20% gain in mean junctional N1-P1 response density at month 2, and 3 study eyes maintained more than a 20% gain at month 3. Mean BCVA also improved incrementally at each follow-up visit, reaching +6.0 letters over baseline at month 3 (P = .04). Conclusions: mfERG and BCVA data supported the benefit of AVD-104 treatment in eyes with GA and revealed the potential to recover retinal function in the junctional zone 2 months after treatment.}, }
@article {pmid42404560, year = {2026}, author = {Zhou, F and Bai, W and Zhao, Y and Jiang, Q and Wang, C and Xu, X and Yao, J}, title = {Short-term outcomes of intravitreal faricimab on refractory neovascular age-related macular degeneration patients in China.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1855248}, pmid = {42404560}, issn = {2296-858X}, abstract = {PURPOSE: To assess the real-world clinical outcomes of faricimab in patients receiving treatment for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This real-world prospective observational study included patients with refractory nAMD. In total, 37 patients were analyzed. All patients had previously undergone at least three consecutive intravitreal injections of other anti-vascular endothelial growth factor (anti-VEGF) agents. The primary outcomes were best-corrected visual acuity (BCVA) and anatomical outcomes on optical coherence tomography angiography (OCTA) at a four-month follow-up period.<br><br>RESULTS: The faricimab regimen resulted in significant improvements in both visual and anatomical parameters among patients with refractory nAMD. LogMAR BCVA decreased substantially from 0.82&#x202f;&#xb1;&#x202f;0.42 to 0.57&#x202f;&#xb1;&#x202f;0.32 (p&#x202f;<&#x202f;0.001). Central subfield thickness (CST) was reduced significantly from 336.89&#x202f;&#xb1;&#x202f;141.52&#x202f;&#x3bc;m to 244.19&#x202f;&#xb1;&#x202f;69.91&#x202f;&#x3bc;m (p&#x202f;<&#x202f;0.001). The pigment epithelial detachment (PED) area decreased from 1.30&#x202f;&#xb1;&#x202f;0.71 to 0.94&#x202f;&#xb1;&#x202f;0.55&#x202f;mm[2] (p&#x202f;<&#x202f;0.001), and the choroidal neovascularization (CNV) area shrank from 1.11&#x202f;&#xb1;&#x202f;0.64 to 0.97&#x202f;&#xb1;&#x202f;0.56&#x202f;mm[2] (p&#x202f;<&#x202f;0.001). Both the subretinal fluid (SRF) and SRF &amp; Intraretinal fluid (IRF) subgroups exhibited notable improvements in both vision and anatomical structure. Eyes with isolated SRF achieved longer dosing interval extensions (66.7% reached &#x2265;3&#x202f;months) compared to the SRF &amp; IRF group (47% reached &#x2265;3&#x202f;months).<br><br>CONCLUSION: Faricimab given as three monthly loading doses demonstrates significant short-term improvement in vision and anatomical outcomes, including rapid gains in BCVA and reductions in CST and retinal fluid. It appears effective and well-tolerated for refractory nAMD, particularly in reducing SRF and improving visual acuity, though its effect on IRF resolution was limited and not statistically significant. However, because the study design confounded drug switch with increased injection frequency, the independent contribution of faricimab itself cannot be determined. No adverse safety signals were observed.}, }
@article {pmid42405673, year = {2026}, author = {Zong, Y and Fan, Q and Qiu, S and Zhang, H and Cen, Z}, title = {The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {13}, doi = {10.1167/iovs.67.8.13}, pmid = {42405673}, issn = {1552-5783}, mesh = {Humans ; *Aging/physiology ; Animals ; Cellular Senescence/physiology ; Mitochondria ; *Macular Degeneration/metabolism ; *Diabetic Retinopathy ; *Eye Diseases/therapy ; *Glaucoma ; Epigenesis, Genetic ; }, abstract = {Age-related eye diseases (AREDs)-including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy-are leading causes of permanent blindness. Current treatments manage clinical manifestations but do not halt the molecular processes that drive disease progression. This limitation has shifted attention toward "geroscience," a strategy that targets the fundamental biology of aging rather than treating each disease in isolation. Four key hallmarks of aging-mitochondrial dysfunction, loss of proteostasis, cellular senescence, and epigenetic drift-are widely implicated in AREDs. We review evidence that these hallmarks do not act independently; instead, they form an interactive, self-reinforcing network. The way this network engages differs from tissue to tissue. In the high-energy environment of the retinal pigment epithelium, mitochondrial dysfunction dominates and drives AMD. In the mechanically stressed trabecular meshwork (TM), senescence and epigenetic drift take precedence, leading to glaucoma. In the neurovascular unit, chronic hyperglycemia routes the same network into a metabolic-epigenetic amplification loop that sustains diabetic retinopathy. The same aging mechanisms, routed through distinct tissue contexts, thus produce divergent clinical phenotypes. We also evaluate emerging therapies, including senolytics, mitochondria-targeted agents, and partial epigenetic reprogramming, and identify key intervention nodes such as NLRP3, p62, and NAD[+] metabolism. Dismantling these pathological feedback loops offers a path beyond symptom management toward combination strategies that restore tissue resilience.}, }
@article {pmid42398914, year = {2026}, author = {Garweg, JG and Chaudhary, V and Zhang, X and Leal, S and Machewitz, T and Munk, MR and Zarranz-Ventura, J and Stahl, A and Lanzetta, P and , }, title = {Effect of key baseline disease characteristics on aflibercept 8 mg dosing interval extension: A post hoc 96-week analysis of PULSAR.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.06.032}, pmid = {42398914}, issn = {2468-6530}, abstract = {OBJECTIVE: Post hoc analysis of the PULSAR Phase 3 trial (NCT04423718) to describe whether dosing interval outcomes were associated with key baseline disease characteristics.<br><br>DESIGN: Exploratory post hoc analysis of PULSAR, a 96-week, double-masked, active-controlled, randomized clinical trial in patients with treatment-na&#xef;ve neovascular age-related macular degeneration (nAMD) treated with aflibercept 8 mg or aflibercept 2 mg. For the main analysis, patients receiving aflibercept 8 mg were grouped according to their last assigned dosing interval at Weeks 48 and 96.<br><br>PARTICIPANTS: Patients with treatment-na&#xef;ve nAMD who were randomly assigned to receive aflibercept 8 mg in PULSAR.<br><br>INTERVENTION: Aflibercept 8 mg was administered every 12 weeks (8q12) or 16 weeks (8q16) following 3 initial monthly injections. Dosing intervals could be shortened in Year 1 based on prespecified disease activity criteria, whereas in Year 2, both interval shortening and extension were allowed. Patients were monitored every 4 weeks but assessed for interval modification at dosing visits only.<br><br>MAIN OUTCOME MEASURES: Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT), and macular neovascularization (MNV) area were assessed in patients grouped by their last assigned dosing interval (Q8, Q12, Q16, Q20, or Q24) at Weeks 48 and 96.<br><br>RESULTS: In 86.6% and 78.4% of patients assigned to the 8q12 and 8q16 arms in PULSAR, respectively, randomized dosing intervals were maintained or extended through Week 96. In the 8q12 arm, no trends were observed in baseline BCVA, CRT, and MNV area across groups based on patients' last assigned dosing intervals. In the 8q16 arm, no trends were observed in baseline BCVA across treatment arms; however, patients with shorter last assigned dosing intervals (Q8 and Q12) at Weeks 48 and 96 tended to have a greater baseline CRT or MNV area compared with patients with longer dosing intervals (Q16 to Q24).<br><br>CONCLUSIONS: Overall, findings from this PULSAR post hoc analysis of key baseline characteristics in patients grouped by dosing interval suggest that the aflibercept 8q12 and 8q16 regimens were suitable for most patients across a broad range of baseline BCVA, CRT, and MNV area values, with a large proportion of patients able to achieve and maintain extended dosing intervals through Week 96.}, }
@article {pmid42396341, year = {2026}, author = {Siraz, S and Kamanda, H and Nabil, AS and Gholami, S and Rao, NT and Ong, SS and Alam, MN}, title = {Sequential Deep Learning to Predict Non-Central to Central Geographic Atrophy Progression from OCT Imaging.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.06.17.26355882}, pmid = {42396341}, abstract = {PURPOSE: To develop and validate a temporal deep learning framework for predicting geographic atrophy (GA) progression across multi-year horizons using longitudinal optical coherence tomography (OCT) sequences.<br><br>DESIGN: Retrospective longitudinal cohort study.<br><br>A total of 91 patients with dry age-related macular degeneration (AMD) were identified from Wake Forest University School of Medicine (2013-2023), yielding 455 OCT volumes. Two prediction cohorts were defined: 32 patients with no GA (NGA) at baseline who subsequently developed GA, and 35 patients whose earliest GA manifestation was non-central GA (NCGA). Non-progressing patients served as negative controls.<br><br>METHODS: OCT B-scan volumes were encoded into visit-level feature representations using three pretrained architectures (ResNet-18, ResNet-50, ViT-B/16). Chronologically ordered visit embeddings, optionally augmented with inter-visit time intervals (&#x394;t), were processed through recurrent neural networks (RNN), long short-term memory networks (LSTM), and Transformer encoders to model longitudinal disease trajectories. Models were trained and evaluated independently for prediction horizons of 2, 3, 4, 5, and 6 years using patient-level stratified splits (80/20). Performance was assessed across five random seeds.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (ROC-AUC), F1-score, and accuracy for predicting two clinically critical transitions: NGA to GA onset and NCGA to central GA (CGA) involvement.<br><br>RESULTS: For NGA to GA prediction, models achieved ROC-AUC of 0.84-0.94 at 2-4 years and 1.00 at 5-6 years. For NCGA to CGA prediction, Transformer-based models achieved peak AUC of 0.95 (&#xb1;0.11) at 4 years and 0.96 (&#xb1;0.06) at 5 years. Longer input sequences (8 visits vs. 4 visits) consistently improved NCGA to CGA performance at extended horizons. Temporal interval encoding improved stability in several LSTM configurations.<br><br>CONCLUSIONS: Temporal deep learning applied to longitudinal OCT sequences can predict GA progression across clinically meaningful 2-6 year horizons without pixel-level annotations. These findings support the feasibility of automated, individualized risk stratification to guide complement inhibitor therapy decisions in patients with GA.}, }
@article {pmid42397104, year = {2026}, author = {Olevson, C and Kramer, B and Terveen, DC and Berdahl, JP and Thompson, V and Ferguson, TJ}, title = {Light adjustable lens implantation with cataract surgery in eyes with macular pathology.}, journal = {Journal of cataract and refractive surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/j.jcrs.0000000000002017}, pmid = {42397104}, issn = {1873-4502}, abstract = {PURPOSE: To evaluate the visual, refractive and safety outcomes of the light adjustable lens (LAL) in eyes with pre-existing macular pathology undergoing cataract surgery.<br><br>SETTING: Private practice, multiple locations.<br><br>DESIGN: Retrospective, consecutive case series.<br><br>METHODS: Patients with macular pathology undergoing cataract surgery with LAL implantation were included. Diagnoses comprised epiretinal membrane (ERM), dry age-related macular degeneration (AMD)/drusen, and other macular conditions. Primary outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and the percentage of eyes within &#xb1;0.25 D (diopter), &#xb1;0.50 D and &#xb1;1.00 D of the refractive target. Safety endpoints included intraoperative and postoperative complications and changes in CDVA pre- and post-adjustments.<br><br>RESULTS: 171 eyes from 106 patients were included. The most common diagnoses were ERM and dry AMD. Among eyes targeted for distance (n=95), 96% achieved UDVA of 20/25 or better and 85% achieved 20/20 or better. For refractive accuracy, 87% of eyes were within &#xb1;0.50 D and 68% were within &#xb1;0.25 D of the target. The percentage of eyes within &#xb1;0.50 D of target rose from 66% to 87% following the adjustment process and the percentage of eyes achieving 20/20 or better climbed from 26% to 85%.<br><br>CONCLUSIONS: In eyes with macular pathology, the LAL provides excellent uncorrected visual acuity and highly accurate refractive outcomes with a favorable safety profile. These findings position the LAL as a viable advanced IOL option in patients traditionally considered suboptimal candidates due to underlying macular disease.}, }
@article {pmid42397425, year = {2026}, author = {Grün, M and Rothaus, K and Beger, A and Winter, C and Lommatzsch, A and Faatz, H}, title = {[Real-world experience with aflibercept 8 mg for treatment of neovascular age-related macular degeneration after 12 months].}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42397425}, issn = {2731-7218}, abstract = {BACKGROUND: The phase 3 clinical trial PULSAR demonstrated extended treatment intervals with aflibercept 8 mg in treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) in a large proportion of the cohort, with good drug safety. Early clinical experience in real-world settings confirmed the efficacy in both treatment-naïve and pretreated patients but no data on longer observation periods are available yet.<br><br>OBJECTIVE: The aim of the study was to investigate the efficacy, treatment frequency and tolerability of aflibercept 8&#x202f;mg over a&#xa0;period of 12&#xa0;months in a&#xa0;group of pretreated nAMD patients.<br><br>MATERIAL AND METHODS: A&#xa0;retrospective study of 73&#xa0;eyes with nAMD and pretreatment with anti-VEGF switched to aflibercept 8&#x202f;mg. Eyes were initially uploaded with 3&#xa0;monthly intravitreal injections (IVI), followed by a&#xa0;pro re nata (PRN) regimen. Outcome parameters included visual acuity development and central retinal thickness (CSRT) after upload and 12&#xa0;months, treatment frequency in the year before and after switching to aflibercept 8&#x202f;mg, and the overall tolerability of the drug.<br><br>RESULTS: Of the initial 73&#xa0;eyes, 27&#xa0;eyes (37.0%) were still receiving aflibercept 8&#x202f;mg after 12&#xa0;months. In these eyes CSRT was reduced from 387.9&#x202f;&#xb1;&#x2009;138.4&#x202f;&#xb5;m initially to 305.5&#x202f;&#xb1;&#x2009;93.2&#x202f;&#xb5;m after upload and 328.9&#x202f;&#xb1;&#x2009;105.6&#x202f;&#xb5;m after 12&#xa0;months (p&#x202f;<&#x2009;0.001). Visual acuity remained stable (p&#x202f;>&#x2009;0.05). Compared to the year prior to switching, the injection frequency was reduced from 8.2&#x202f;&#xb1;&#x2009;2.1 to 6.9&#x202f;&#xb1;&#x2009;1.0 IVIs (p&#x202f;<&#x2009;0.005). During the observation period, a&#xa0;total of 5&#xa0;eyes (6.8%) developed noninfectious intraocular inflammation (IOI), with all cases completely regressing with topical treatment.<br><br>CONCLUSION: These results confirm a&#xa0;good efficacy of aflibercept 8&#x202f;mg for the treatment of nAMD with reduced injection frequency after 12&#xa0;months of treatment in a&#xa0;portion of pretreated eyes that were often previously refractory to treatment. Longer observation intervals and experience with other treatment regimens are necessary to confirm this observation.}, }
@article {pmid42397502, year = {2026}, author = {Dugiełło, B and Bujała, K and Bolek, B and Wylęgała, A and Wylęgała, E}, title = {Identification of OCTA Biomarkers and Cutoff Values Associated with Disease Severity in Dry Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42397502}, issn = {2193-8245}, abstract = {INTRODUCTION: Optical coherence tomography angiography (OCTA) enables noninvasive assessment of retinal and choroidal microvasculature and may provide quantitative biomarkers of disease severity in dry age-related macular degeneration (AMD). This study aimed to identify OCTA-derived vascular parameters associated with consecutive stages of dry AMD and determine cutoff values for stage differentiation.<br><br>METHODS: This cross-sectional study included 182 eyes of 123 participants. Eyes were classified according to the Beckman classification into control, early, intermediate, and late dry AMD groups. OCTA imaging was performed using the ZEISS PLEX Elite&#xa0;9000 swept-source OCTA system. Quantitative analysis of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) was conducted using AngioTool software. Vessel density, vessel length, junction-related parameters, endpoints, and lacunarity were analyzed. Group comparisons were performed using analysis of variance (ANOVA) or the Kruskal-Wallis test with post hoc analysis. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance and determine optimal cutoff values.<br><br>RESULTS: In the SCP, vessel density decreased from 43.83&#x2009;&#xb1;&#x2009;2.08% in controls to 41.27&#x2009;&#xb1;&#x2009;3.96% in intermediate AMD (p&#x2009;<&#x2009;0.001), and mean lacunarity increased from 0.05&#x2009;&#xb1;&#x2009;0.01 to 0.07&#x2009;&#xb1;&#x2009;0.03 (p&#x2009;<&#x2009;0.001), while other parameters showed no significant differences. In the DCP, vessel density declined from 51.71&#x2009;&#xb1;&#x2009;2.38% in controls to 48.73&#x2009;&#xb1;&#x2009;4.66% and 43.80&#x2009;&#xb1;&#x2009;4.98% across disease stages (p&#x2009;<&#x2009;0.001), with total vessel length decreasing from 73.32&#x2009;&#xb1;&#x2009;2.72 to 61.58&#x2009;&#xb1;&#x2009;6.69 (p&#x2009;<&#x2009;0.001), indicating progressive vascular simplification. The most pronounced changes were observed in the choriocapillaris, where vessel density decreased from 63.28&#x2009;&#xb1;&#x2009;0.94 to 60.31&#x2009;&#xb1;&#x2009;1.83% and 26.62&#x2009;&#xb1;&#x2009;22.30% (p&#x2009;<&#x2009;0.001), and total vessel length from 102.80&#x2009;&#xb1;&#x2009;2.24 to 35.68&#x2009;&#xb1;&#x2009;38.42 (p&#x2009;<&#x2009;0.001). ROC analysis identified SCP mean lacunarity (cutoff 0.0575, AUC 0.76) as a marker of early disease. In the DCP, total number of junctions below 254 and total vessel length below 66.10 were associated with advanced disease. The highest diagnostic performance was observed for choriocapillaris parameters, including vessel density below 57.38 and total vessel length below 91.10, with sensitivity exceeding 94% and specificity above 80%.<br><br>CONCLUSION: OCTA-derived microvascular parameters demonstrate layer-specific alterations in dry AMD. Mean lacunarity in the SCP appeared to be the most sensitive marker of early changes, whereas reductions in junction density and total vessel length in the DCP reflected progressive vascular simplification. The strongest association with disease severity was observed in the choriocapillaris, particularly for vessel density and total vessel length. The identified cutoff values for DCP and CC parameters were associated with different stages of dry AMD and may support stage differentiation and quantitative assessment of disease severity in clinical settings.}, }
@article {pmid42008392, year = {2026}, author = {Bedersdorfer, M and von Ehrlich-Treuenstätt, G and Früh, T and Boden, KT and Szurman, P and Stanzel, BV}, title = {Visual and Microperimetry Outcomes of an Extended Macular Vision Intraocular Lens in Macular Atrophy.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000552124}, pmid = {42008392}, issn = {1423-0267}, abstract = {INTRODUCTION: This study aimed to evaluate visual acuity and microperimetry correlated with anatomical changes in eyes with macular diseases implanted with the EyeMax Mono intraocular lens (IOL) (SharpView Ophthalmology).<br><br>METHODS: A single-center retrospective, real-world case series was set in Knappschaft Eye Hospital, Sulzbach, Germany. Patients with macular disease who underwent EyeMax Mono IOL implantation were included. The outcome measures were corrected distance visual acuity (CDVA) and microperimetry indices: fixation stability and bivariate contour ellipse areas (BCEAs) at 63% and 95%. The geographic atrophy (GA) monitor (RetInSight) was used to analyze changes in retinal integrity.<br><br>RESULTS: Twenty-one eyes (11 patients; mean age 72.8 &#xb1; 8.3 years, mean follow-up 7.4 &#xb1; 4.0 months) were included. Preoperative GA measured 4.7 &#xb1; 4.0 mm2 (n = 14), and EZ loss on SD-OCT was 2,433.1 &#xb1; 1,009.5 &#xb5;m (n = 17). The CDVA improved by 0.2 logMAR (p = 0.007, n = 21), with 12 eyes gaining &#x2265;1 line and seven eyes gaining &#x2265;3 lines. Fixation stability improved in two eyes, stabilized in nine eyes, and worsened in four eyes. The changes in BCEA were not statistically significant. Higher preoperative BCEA correlated with greater postoperative improvement (p < 0.001). In the foveal fixation group (n = 4), 75% and 50% of patients showed improved BCEA and CDVA, respectively. In extrafoveal fixation (n = 11), BCEA improved in 50% of patients, while 64% showed CDVA improvement. The GA monitor showed worsening in 9/15 eyes, and 4 eyes showed worsening on microperimetry without a CDVA decline. Anatomical changes stabilized in six eyes; of these, two exhibited a decline in microperimetry without a CDVA decline.<br><br>CONCLUSIONS: EyeMax Mono IOL improved CDVA, although no significant changes were observed in the microperimetry indices. Better microperimetry outcomes were observed in extrafoveal fixation cases. While the optical design of the IOL likely contributes to visual improvement, the small sample size limited the statistical power to detect significant microperimetry changes.}, }
@article {pmid42390573, year = {2026}, author = {Nagar, NB and Ostrovsky, M and Shoham-Hazon, N and Tuli, R and Lee, TKM and Buchnick, N and Beluga, S and Bramnik, L and Shcolnik, E and Goldfeather Ben Zaken, S and Levy, N and Bareket, M and Berco, E}, title = {Real-world comparison of faricimab and aflibercept as second-line therapies for neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42390573}, issn = {1435-702X}, abstract = {PURPOSE: To compare real-world effectiveness of faricimab versus aflibercept as second-line therapies for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This multicenter retrospective cohort study included patients with nAMD who switched to faricimab or aflibercept as second-line anti-VEGF therapy and were followed&#x2009;&#x2265;&#x2009;12 months. Outcomes included best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, &#xb5;m), injection intervals, and switching rates. Multivariable linear regression identified predictors of visual and anatomical change.<br><br>RESULTS: A total of 170 eyes (84 faricimab, 86 aflibercept) were analyzed. Faricimab-treated eyes had worse baseline BCVA (0.60&#x2009;&#xb1;&#x2009;0.49 vs. 0.47&#x2009;&#xb1;&#x2009;0.37 logMAR; p&#x2009;=&#x2009;0.048) and numerically lower baseline CMT (332.7&#x2009;&#xb1;&#x2009;107.9 vs. 367.5&#x2009;&#xb1;&#x2009;103.5&#xa0;&#x3bc;m; p&#x2009;=&#x2009;0.057). At final follow-up, faricimab achieved a significant BCVA gain (-&#x2009;0.16&#x2009;&#xb1;&#x2009;0.42 logMAR; p&#x2009;<&#x2009;0.001), while aflibercept maintained stable vision (p&#x2009;=&#x2009;0.923). Both agents significantly reduced CMT (p&#x2009;<&#x2009;0.001), with a greater mean reduction observed in the aflibercept group (-&#x2009;96.7&#x2009;&#xb1;&#x2009;127.5 vs.&#x2009;-&#x2009;56.8&#x2009;&#xb1;&#x2009;132.0&#xa0;&#x3bc;m; p&#x2009;=&#x2009;0.046). Final BCVA and CMT did not differ significantly between groups. Final injection intervals were similar between groups (7.5&#x2009;&#xb1;&#x2009;2.9 vs. 7.6&#x2009;&#xb1;&#x2009;3.1 weeks; p&#x2009;=&#x2009;0.906), and switching to third-line therapy occurred less frequently in the faricimab group (4.8% vs. 12.8%; p&#x2009;=&#x2009;0.065). Baseline BCVA predicted visual gain (B&#x2009;=&#x2009;-&#x2009;0.199; p&#x2009;=&#x2009;0.010) and baseline CMT predicted anatomical improvement (B&#x2009;=&#x2009;-&#x2009;0.517; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: In this real-world multicenter cohort, both faricimab and aflibercept were associated with visual and anatomical improvement after switching to second-line therapy for nAMD. No statistically significant difference in final BCVA, final CMT or injection interval was observed between treatment groups. Baseline disease severity predicted treatment response. Given the retrospective design and residual confounding, these findings should be interpreted as associative rather than causal.}, }
@article {pmid42391281, year = {2026}, author = {Yoshida, N and Kobayakawa, Y and Funakoshi, K and Kimura, S and Hosoya, K and Shinkawa, Y and Furukawa, T and Mitsutake, T and Hoshiko, T and Takamori, A and Kawahara, N and Terasaki, H and Oishi, A and Koizumi, H and Inoue, T and Takeda, A and Ikeda, Y and Yoshida, S and Morizane, Y and Kadonosono, K and Inoue, M and Kamei, M and Todaka, K and Sonoda, KH and Enaida, H}, title = {Protocol for the SACLA trial: Efficacy and safety of subretinal monteplase for submacular hemorrhage in a phase II single-arm multicenter decentralized clinical trial.}, journal = {PloS one}, volume = {21}, number = {7}, pages = {e0353127}, pmid = {42391281}, issn = {1932-6203}, mesh = {Humans ; *Retinal Hemorrhage/drug therapy ; *Tissue Plasminogen Activator/administration &amp; dosage/therapeutic use/adverse effects ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; Treatment Outcome ; *Fibrinolytic Agents/administration &amp; dosage/therapeutic use ; Vitrectomy ; Visual Acuity ; Female ; }, abstract = {Submacular hemorrhage (SMH), which may arise from age-related macular degeneration, retinal arterial macroaneurysm, and other causes, can result in severe vision loss and central visual field impairment. Although tissue plasminogen activator (tPA) is used off-label to treat SMH in many countries, no formulation has been approved for this indication. Because early intervention is critical when tPA is used for SMH, limited access to centers that can provide this treatment may delay care and reduce treatment opportunities. Decentralized clinical trials (DCTs) reduce or eliminate the need for participants to travel to trial sites. We therefore designed the investigator-initiated SACLA trial to evaluate subretinal tPA for SMH. The DCT framework is intended to reduce logistical barriers related to the disease severity and rarity. The SACLA trial is a phase II multicenter, open-label, single-arm surgical study with a pre-post comparison design (jRCT2071250003). Twenty eligible participants will undergo pars plana vitrectomy followed by subretinal injection of 0.1 mL (8,000 IU) of tPA. Participants will remain hospitalized at the trial site until the primary outcome, change in central foveal thickness (CFT) from baseline at Week 1, is assessed. Thereafter, follow-up visits will be conducted at either the trial site or partner sites within the DCT framework. Secondary efficacy outcomes include change in CFT from baseline, presence of a foveal hemorrhage measuring at least 1 disc diameter, best-corrected visual acuity (BCVA), and change in BCVA from baseline at Weeks 4 and 12. Adverse events will be collected throughout the 12-week observation period to assess safety. The protocol and related study documents were reviewed and approved by the Saga University Hospital Institutional Review Board. This study is designed to generate prospective evidence on the feasibility, short-term anatomical response, and safety of subretinal tPA for SMH.}, }
@article {pmid42392211, year = {2026}, author = {Eiselen, C and Long, M and Chong, EW}, title = {Age-related macular degeneration: Updates for general practitioners.}, journal = {Australian journal of general practice}, volume = {55}, number = {7}, pages = {455-460}, doi = {10.31128/AJGP-10-25-7882}, pmid = {42392211}, issn = {2208-7958}, mesh = {Humans ; *Macular Degeneration/diagnosis/physiopathology/therapy ; Australia/epidemiology ; Risk Factors ; *General Practitioners/trends ; Aged ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness in Australians over 50 years, accounting for 60% of all blindness. AMD progresses from asymptomatic early and intermediate stages to late neovascular ('wet') or atrophic ('dry') forms that cause irreversible central vision loss. Age and family history are the strongest risk factors, while smoking, poor diet and cardiovascular disease are key modifiable contributors.<br><br>OBJECTIVE: To raise awareness of AMD in general practice and provide some advice on what general practitioners (GPs) can do to assist in early detection and prevention with an ageing population. GPs can examine the macula in at-risk&#xa0;adults, as well as encourage smoking cessation, a&#xa0;Mediterranean-style diet, regular exercise, and Age-&#x200a;Related Eye Disease Study 2 (AREDS2) supplementation for intermediate disease. Sudden distortion or vision loss requires urgent ophthalmology referral for possible neovascular AMD.<br><br>DISCUSSION: Intravitreal anti-VEGF (vascular endothelial growth factor) therapy remains the mainstay for wet AMD, while complement inhibitors show promise for geographic atrophy. Emerging gene, sustained-delivery and laser therapies might soon reduce treatment burden and improve adherence.}, }
@article {pmid42392259, year = {2026}, author = {Priya, S and McLellan, FC and Wich, PR and Kumeria, T and Willcox, M and Shu, DY}, title = {Fumaric Acid Esters as Modulators of Ocular Inflammation and Angiogenesis.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.05.014}, pmid = {42392259}, issn = {1525-2191}, abstract = {Ocular diseases leading to irreversible vision loss are driven by convergent pathological processes, including chronic inflammation, oxidative stress, and angiogenesis. Despite therapeutic advances, corneal neovascularization, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma remain major causes of vision impairment. Conventional therapies for these diseases pose challenges related to non-responsiveness and long-term inefficacy, highlighting the need for treatments that target upstream mechanisms shared across ocular pathologies. Fumaric acid esters (FAEs), particularly dimethyl fumarate (DMFu) and its active metabolite, monomethyl fumarate (MMF), have emerged as promising drug candidates due to their potent immunomodulatory and antioxidant properties. Mechanistically, DMFu activates nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to enhance antioxidant defense while suppressing nuclear factor-κB (NF-κB)-mediated pro-inflammatory responses. Beyond inflammation, DMFu inhibits VEGF-driven angiogenesis through metabolic rewiring in endothelial cells. This review discusses the efficacy of FAEs across various ocular pathologies and addresses the pharmacokinetics of the drugs and hurdles such as rapid systemic hydrolysis and ocular barriers. Despite translational challenges, the multimodal mechanisms of FAEs offer a unique advantage over single-target therapies, positioning them as promising candidates for targeting convergent pathways in complex ocular diseases.}, }
@article {pmid42392261, year = {2026}, author = {Yao, PL and Malek, G}, title = {Lxrα Deficiency Primes Retinal Degeneration, but Aging Drives Disease Severity.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.05.012}, pmid = {42392261}, issn = {1525-2191}, abstract = {The liver X receptor alpha (LXRα) regulates serum cholesterol and lipoprotein levels under homeostatic conditions and in response to dietary fat. Previously aged Lxrα[-]/[-] mice fed a standard diet were shown to develop phenotypes resembling early age-related macular degeneration (AMD). Herein, the hypothesis tested was that introducing a high-fat, high-cholesterol (HFC) diet in young Lxrα[-]/[-] mice could bypass aging and accelerate onset of AMD-like pathology. Young Lxrα[+]/[+] and Lxrα[-]/[-] mice (2-3 months old) were fed either a standard diet or an HFC diet for up to two months. Retinal function and morphology were assessed by electroretinography and fundus/OCT imaging, histopathology was evaluated by transmission electron microscopy, and retinal markers were examined by immunostaining. Young Lxrα[-]/[-] mice fed an HFC diet exhibited impaired retinal function with reduced scotopic a- and b-waves, photopic b-waves, and c-waves. While the retinal ultrastructure of control and HFC-fed Lxrα[+]/[+] mice appeared normal, HFC-fed Lxrα[-]/[-] mice showed RPE thinning, disorganized basal infoldings, intracellular lipid droplets, thin basal laminar deposits, and Bruch's membrane thickening enriched in apolipoprotein E. Increased microglia/macrophage infiltration in the retina and choroid suggested elevated local inflammation. Although an HFC diet accelerated AMD-like changes in young Lxrα[-]/[-] mice, these lesions were less severe than those observed in aged Lxrα[-]/[-] mice on a standard diet, indicating that aging remains the dominant driver of disease severity.}, }
@article {pmid42393152, year = {2026}, author = {Samra, N and Moustafa, H and Aouf, M and Samra, WA and Abdelslam, MM}, title = {Dual branch fundus deep learning network as an enhanced multi classification system for ocular disease detection via hybrid feature fusion.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-58277-5}, pmid = {42393152}, issn = {2045-2322}, abstract = {Ophthalmic diagnosis relies heavily on the interpretation of fundus images to identify a range of debilitating diseases. However, the presence of multiple, co-existing pathologies and the subtle visual cues associated with early-stage disease pose a significant challenge, necessitating the development of advanced diagnostic tools. We present DFD-Net (Dual-Branch Fundus Deep Learning Network), a deep learning solution that performs multi-label classification of various ocular diseases. The system achieves this by integrating the attribute maps from bilateral retinal photographs, like those from the right and left eyes. This study starts with a thorough pre-processing operation on the fundus images, represented in image rescaling, black border image cropping, contrast enhancement, and data augmentation of retinal photographs. Following this, the processing pipeline begins with a dual-branch feature extraction framework. A part of the system employs a ConvNeXt architecture to obtain complex semantic characteristics, while the parallel branch employs a U-Net encoder to capture fine-grained, structural characteristics across several scales. These complementary feature representations are then combined via a fusion mechanism. The fused feature representations are subsequently enhanced by a SENet Block for greater robustness through channel-wise recalibration. The resulting feature maps are reduced via Global Average Pooling, and then passed through a Dense layer for feature refinement. Finally, the features are classified by a Softmax output layer, consistent with the single-label multi-class formulation adopted in this work, to identify one of eight possible categories. The testing was implemented on the Ocular Disease Intelligent Recognition-Ophthalmic Image analysis (OIA-ODIR) dataset, which has retinal photographs that represent six distinct ophthalmic categories, macular degeneration, cataracts, glaucoma, hypertension, diabetic retinopathy, and myopia, images that present normal cases, and images that represent multiple other diseases, depicting eight different categories. The proposed DFD-Net system established precision, recall, F1- scores, and overall accuracy of 92.75%, 93.17%, 94.45%, and 93.77% on the On-Site testing collection and 91.50%, 93.19%, 92.11%, and 92.97% on the Off-Site testing collection, respectively. Ultimately, the suggested DFD-Net system proved high efficiency in precisely classifying multiple ocular diseases, offering a novel and outstanding approach for early detection of fundus diseases.}, }
@article {pmid42394911, year = {2026}, author = {Cui, H and Wu, H and Zhao, B and Zhao, Y and Zhang, C and Wang, M and Zhang, J and Wang, K and Wang, Y and Song, Z and Tao, Y}, title = {Harnessing nanotechnology: Transforming ocular drug delivery with advanced hydrogel systems.}, journal = {Bioengineering &amp; translational medicine}, volume = {11}, number = {4}, pages = {e70099}, pmid = {42394911}, issn = {2380-6761}, abstract = {Ocular drug delivery faces tremendous challenges in clinical practice. The eyeball possesses sophisticated anatomical and physiological characteristics that uniquely influence the pharmacokinetics of delivered drugs. This complexity necessitates innovative solutions to ensure effective drug delivery. Conventional ocular drug administration routes (topical, intravitreal, and systemic) each pose unique limitations. With the advancements of biomaterials science and medical engineering technology, nanofiber hydrogels have garnered significant attention, primarily represented by self-assembled peptide-based hydrogels and cellulose nanofiber-based hydrogels. They can be tailored to have precise physical and chemical properties, enabling controlled release of drugs and enhanced biocompatibility. Furthermore, their nanofibrous structure mimics the extracellular matrix, promoting cell adhesion and tissue regeneration. This review introduces advanced manufacturing techniques which are capable of precisely modifying the properties of nanofiber hydrogels to meet specific therapeutic needs. The distinctive advantages of nanofiber hydrogels are elaborated in detail, including their ability to enhance drug penetration, provide sustained release, and reduce systemic toxicity. We also delve into the therapeutic applications, potential limitations, and developmental perspectives of nanofiber hydrogels. Preclinical studies have validated their efficacy in treating ophthalmologic conditions such as age-related macular degeneration, bacterial keratitis, ocular alkali burns, and non-infectious uveitis. However, translating these laboratory findings into clinical applications remains limited, primarily due to significant challenges in human trials, including species-specific responses, the complexity of human biology, and the safety of nanofiber hydrogels. Future refinements in fabrication techniques and rigorous safety assessments are necessary to revolutionize the clinical application of nanofiber hydrogels.}, }
@article {pmid42395092, year = {2026}, author = {Nelson, AJ and Kastelein, JJ and Ditmarsch, M and Hall, C and Kling, D and Ortiz, N and Wicks, DL and Hsieh, A and Szarek, M and Ray, KK and Davidson, MH and Nicholls, SJ}, title = {Obicetrapib safety analysis: Pooled phase 3 clinical trial experience.}, journal = {American journal of preventive cardiology}, volume = {28}, number = {}, pages = {101547}, pmid = {42395092}, issn = {2666-6677}, abstract = {BACKGROUND: Obicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that lowers LDL-C and raises HDL-C. Although prior studies have demonstrated efficacy and general tolerability, a comprehensive evaluation of its safety profile across later-stage clinical trials is needed.<br><br>METHODS: Safety outcomes were assessed in a pooled analysis of two phase III trials comparing obicetrapib 10 mg daily with placebo in adults with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD). Participants received treatment for 365 days. Safety endpoints included treatment-emergent adverse events (TEAEs) and prespecified events of special interest including hepatic, muscular, glycemic, renal and ocular parameters as well as overall rates of discontinuation.<br><br>RESULTS: A total of 2,880 participants were included (mean age 64 years; 36 % female; 82 % with ASCVD; 35.8 % with diabetes). Overall TEAE rates were similar between obicetrapib and placebo (60.2 % vs 62.0 %). AEs leading to treatment discontinuation occurred in 4.1 % of obicetrapib-treated participants and 5.3 % on placebo, Risk Ratio (RR) 0.77 [0.54-1.08]. No clinically significant change in blood pressure was observed between groups and hypertension events were comparable. There was no difference between the groups in liver or muscle-related endpoints. Reduction in eGFR occurred less often with obicetrapib (compared to placebo (6.7 % vs. 8.7 % RR 0.77 [0.59, 1.00])). Macular degeneration was reported once in the obicetrapib group (n= 1 [0.1 %]). Deaths were similar between treatment groups. No new safety signals were identified.<br><br>CONCLUSIONS: Obicetrapib demonstrated a favorable safety profile over 12 months, with AE rates comparable to placebo. These findings extend our understanding of the safety and tolerability of obicetrapib.}, }
@article {pmid42395855, year = {2026}, author = {Kim, D and Stunkel, L}, title = {Retrograde Maculopathy or Microcystic Macular Degeneration in Patients With Optic Neuritis due to Neuromyelitis Optica.}, journal = {Case reports in ophthalmological medicine}, volume = {2026}, number = {}, pages = {2502132}, pmid = {42395855}, issn = {2090-6722}, abstract = {PURPOSE: The aim of this study is to highlight findings of retrograde maculopathy (RM) on optical coherence tomography (OCT) as a sequela of neuromyelitis optica associated optic neuropathy.<br><br>OBSERVATIONS: We report two patients with demyelinating lesions involving the visual pathways due to neuromyelitis optica in whom RM was seen, and in whom the location of the RM corresponded to their visual deficits. In one case, we describe a patient who had a demyelinating chiasmal lesion with bitemporal hemianopia and who had corresponding binasal RM. In another case, we describe a patient who had generalized vision loss in the right eye and who had corresponding diffuse RM in the right macula.<br><br>CONCLUSIONS AND IMPORTANCE: RM is a potential sequela of severe optic neuropathy in neuromyelitis optica and topographically corresponds to severe visual field defects, as well as severe ganglion cell complex loss. Providers should recognize this finding and be aware that they do not need to pursue diagnostic evaluation due to concern for primary macular disease.}, }
@article {pmid42384341, year = {2026}, author = {Wang, L and Guo, ZY and Hu, FX and Zhang, CY and Yuan, Y and Zhou, BQ and Peng, YT and Pang, L and Wang, Y}, title = {Next-generation sequencing reveals aqueous MicroRNA and piRNA signatures in age-related macular degeneration and polypoidal choroidal vasculopathy.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, pmid = {42384341}, issn = {1573-4919}, support = {82405485//National Natural Science Foundation of China/ ; 2023A03J0751//Guangzhou Science and Technology Program/ ; YN2023WSSQ06//Special Research Project in Guangdong Provincial Hospital of Chinese Medicine/ ; }, abstract = {MicroRNAs (miRNAs) play important roles in the pathogenesis of age-related macular degeneration (AMD), while whether polypoidal choroidal vasculopathy (PCV) represents a subtype of AMD remains controversial. However, the differential small non-coding RNA profiles in aqueous humor (AH) between neovascular AMD (nAMD) and PCV remain insufficiently characterized. Therefore, this study aimed to characterize miRNA and piRNA expression profiles in AH samples from nAMD and PCV patients and to explore the potential involvement of these small non-coding RNAs in angiogenesis-related pathways. AH samples were collected from nine cataract controls, eight treatment-naïve nAMD patients, and eight treatment-naïve PCV patients. Small RNA profiles in AH were analyzed using next-generation sequencing (NGS). Differential expression analysis was performed using DESeq2 with adjustment for age, sex, best-corrected visual acuity (BCVA), intraocular pressure (IOP), batch effects, and quality-control covariates. Target gene prediction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. Selected miRNAs were partially validated by quantitative PCR (qPCR). To further evaluate their potential relevance to angiogenesis, expression levels of selected miRNAs were additionally examined in a laser-induced choroidal neovascularization (CNV) mouse model. A total of 35 differentially expressed miRNAs were identified between nAMD and PCV, including 28 upregulated and 7 downregulated miRNAs. Moreover, 27 and 47 uniquely expressed miRNAs were detected in nAMD and PCV, respectively. Four miRNAs exhibited opposite expression patterns between the two diseases. Functional enrichment analysis revealed significant involvement of Hippo, MAPK, and neurodegeneration-related signaling pathways. qPCR validation confirmed the differential expression of miR-150-5p and VEGF. In the laser-induced CNV mouse model, miR-150-5p showed expression changes consistent with the human AH sequencing results. Distinct miRNA and piRNA expression profiles were identified between nAMD and PCV, suggesting differential molecular mechanisms underlying the two diseases. These findings improve our understanding of AMD and PCV pathogenesis and may provide potential biomarkers for disease differentiation and angiogenesis-related research.}, }
@article {pmid42385173, year = {2026}, author = {Colijn, JM and Holz, FG and Pas, J and Hoyng, C}, title = {Retinal dystrophies simulating geographic atrophy: A diagnostic challenge.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70184}, pmid = {42385173}, issn = {1755-3768}, abstract = {Geographic atrophy (GA) is the chronic loss of retinal pigment epithelium, photoreceptors and choriocapillaris, marking the dry late stage of age-related macular degeneration (AMD). GA prevalence is expected to rise in the upcoming decades. Advanced GA leads to central scotomas, reducing visual acuity and quality of life, potentially resulting in profound central vision loss. GA shares features with various retinal diseases and can therefore be complicated to distinguish from mimicking diseases. While no cure exists for GA, therapies like pegcetacoplan and avacincaptad aim to slow atrophy growth, making an accurate diagnosis essential for effective treatment. Misdiagnosis can lead to inappropriate treatment recommendations, impacting patient health and financial burden. This paper outlines the similarities and differences among prevalent diseases such as late-onset Stargardt disease, PRPH2-associated disease and maternally inherited diabetes and deafness (MIDD), resembling GA to aid in accurate diagnosis.}, }
@article {pmid42385795, year = {2026}, author = {Zhou, Q and Zhang, Z and Wu, Y and Dong, C and Wu, CC and Handa, JT and Ma, J and Wang, S}, title = {A Critical Role for Mitochondrial Dynamics in Cigarette Smoke Condensate-induced RPE Senescence.}, journal = {Free radical biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2026.06.060}, pmid = {42385795}, issn = {1873-4596}, abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Its pathogenesis remains incompletely understood, partly due to the complex interplay of genetic risk, aging, and environmental stressors. Cigarette smoking (CS) is a major modifiable risk factor for AMD, yet the mechanism linking CS to disease progression remains unclear. We hypothesize that CS accelerates AMD pathogenesis by exacerbating cellular senescence in the retinal pigment epithelium (RPE), thereby driving age-related RPE dysfunction and degeneration. In this study, differentiated ARPE-19 cells or mice were exposed to low-dose cigarette smoke condensate (CSC), and stress-induced senescence-like RPE phenotypes were induced, characterized by increased senescence markers, mitochondrial dysfunction, and retinal functional impairment. RPE senescence phenotypes were also confirmed in mice exposed to 6 months of CS in the smoking chamber. CSC-induced RPE senescence was associated with a biphasic alteration in mitochondrial morphology, progressing from early mitochondrial fragmentation to late mitochondrial hyperfusion, as well as impaired mitophagy flux, reduced mitochondrial turnover, and decreased mitochondrial biogenesis. Mechanistically, CSC increased dynamin-related protein 1 (DRP1) phosphorylation and promoted cleavage of the mitochondrial phosphatase PGAM5, mitochondrial remodeling associated with decreased DRP1 activities, elevated mitochondrial oxidative stress, and activation of mTOR signaling. Notably, overexpression of a DRP1 activity mutant (K38A) mimics the CSC-induced RPE senescence, while overexpression of the phosphodeficient DRP1-S637A mutant significantly attenuates both mTOR signaling and CSC-induced RPE senescence by restoring mitochondrial fission balance, improving mitochondrial quality-control responses, reducing mitochondrial oxidative stress. Collectively, these findings identify impaired DRP1-dependent mitochondrial remodeling as a key mechanism linking CSC exposure to RPE senescence. While we confirmed the RPE senescence phenotype in mice after 6 months of CS exposure, the specific mechanisms observed in this study require further validation in a chronic CS model. These findings encourage future research into mitochondrial dynamics and RPE senescence in AMD, suggesting that modulating RPE mitochondrial dynamics holds therapeutic potential for delaying AMD progression.}, }
@article {pmid42386027, year = {2026}, author = {Sheibani, N and Wang, S and Darjatmoko, SR and Sorenson, CM}, title = {Caffeine suppresses inflammation and subretinal fibrosis through modulation of the thrombospondin-1-Bim axis.}, journal = {Experimental eye research}, volume = {271}, number = {}, pages = {111152}, doi = {10.1016/j.exer.2026.111152}, pmid = {42386027}, issn = {1096-0007}, abstract = {Age-related macular degeneration (AMD) in the aging population frequently leads to vision impairment. Treatment for neovascular AMD (nAMD) focuses on the tortuous leaky vessels that typify choroidal neovascularization (CNV). Subretinal fibrosis in nAMD patients is more challenging to treat, as few effective options exist. This fibrosis notably impairs vision and typically develops in patients who do not fully respond to current treatments. To gain a better understanding of pathways that could be utilized to subvert subretinal fibrosis, we examined the role Bim, a pro-apoptotic mediator in the intrinsic cell death pathway, and thrombospondin-1 (TSP1), a key regulator of ocular angioinflammatory processes, have in moderating fibrosis. Here we show caffeine treatment significantly reduced subretinal fibrosis in the mouse laser photocoagulation model consistent with its known ability to enhance mononuclear phagocyte (MP) clearance and reduce CNV. Since the TSP1-Bim axis facilitates MP clearance, suppresses inflammation, prevents subretinal fibrosis and CNV, we assessed its necessity for the mitigation of fibrosis by caffeine. We show that caffeine did not prevent subretinal fibrosis or CNV in mice lacking Bim or TSP1. Thus, caffeine utilizes the intrinsic death pathway though TSP1-Bim axis to subvert subretinal fibrosis, likely by suppressing inflammation during CNV.}, }
@article {pmid42386395, year = {2026}, author = {Vingopoulos, F and Katz, R and Patel, NS and Garg, I and Lu, ES and Laíns, I and Kasetty, M and Silverman, RF and Nigalye, A and Kim, L and Husain, D and Miller, JW and Vavvas, DG and Miller, JB}, title = {Reference map of multimodal vision deficits in intermediate age-related macular degeneration: contrast sensitivity and low-contrast visual acuity.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329091}, pmid = {42386395}, issn = {1468-2079}, abstract = {PURPOSE: To provide a reference map of deficits in contrast sensitivity (CS) and low-contrast visual acuity (LCVA) across stages of non-exudative age-related macular degeneration (AMD) and evaluate functional consequences of optical coherence tomography structural biomarkers.<br><br>METHOD: Prospective cross-sectional study of 509 eyes of 358&#x2009;subjects: 317 dry AMD eyes (99 early, 177 intermediate, 41 advanced), 192 healthy control eyes. Reference limits defined from control eye measures of best-corrected visual acuity (BCVA), quantitative contrast sensitivity function (CSF) measures of LCVA, area under the logarithm CSF (AULCSF), CS at multiple frequencies. Risk scores defined by the sum of structural biomarkers in each eye were associated with visual outcomes across and within AMD stages using multiple linear regression analyses.<br><br>RESULTS: Compared with controls, AULCSF declined by 2.2 decibels (dB) in early AMD (eAMD), 3.7 dB in intermediate AMD (iAMD) and 8 dB in advanced AMD. Proportions iAMD eyes breaching reference limits: 50% for AULCSF, 36% for BCVA, 39% for LCVA. For eAMD and iAMD, risk scores were significantly correlated with AULCSF (p<0.02) and CS at low frequencies (1-3&#x2009;cpd, p<0.005) but not BCVA and LCVA (p>0.05). High-risk eyes breached 1-3&#x2009;cpd reference limits at higher rates (60-68%)&#x2009;than low-risk eyes (24-30%). AULCSF and LCVA deficits were presented on a novel map of multimodal vision loss.<br><br>CONCLUSION: The functional consequences of AMD structural biomarkers were validated by structure-function analyses. We provide a reference map of multimodal vision deficits in AMD for CS and LCVA that could be useful to follow the progression of vision loss in AMD in routine clinical practice and as a clinical trial endpoint.}, }
@article {pmid42386641, year = {2026}, author = {Otsu, W}, title = {[Light stress-induced damage to intracellular membrane organelles and its preventive strategies].}, journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica}, volume = {161}, number = {4}, pages = {257-262}, doi = {10.1254/fpj.26030}, pmid = {42386641}, issn = {0015-5691}, mesh = {Humans ; *Light/adverse effects ; Animals ; *Oxidative Stress ; Mitochondria/radiation effects ; *Intracellular Membranes/radiation effects ; Blue Light ; Endoplasmic Reticulum/radiation effects ; }, abstract = {Photoreceptor cells in the retina are highly specialized sensory cells that function as light receptors. During the conversion of light into neural signals, photoreceptors are constantly exposed to oxidative stress. Although environmental stressors, such as excessive light exposure, have been implicated in the progression of various retinal diseases, including dry age-related macular degeneration (AMD), the molecular mechanisms underlying the light-induced stress response remain incompletely elucidated. Excessive light exposure triggers the endoplasmic reticulum (ER) stress response in cells and also induces mitochondrial dysfunction characterized by depolarization and fragmentation, ultimately leading to cell death. We have shown that compounds derived from natural products, such as delphinidins and pentadecyl, exert protective effects against blue light-induced cellular damage. Furthermore, crocetin, a natural carotenoid pigment, has been shown to suppress ultraviolet-A (UV-A)-induced mitochondrial fragmentation in corneal epithelial cells. In this review, we provide an overview of light stress-induced injuries to intracellular membrane organelles, particularly mitochondria and the ER, and the cellular response mechanisms that are mediated through these organelles. These findings suggest that maintaining the homeostasis of intracellular membrane organelles represents an important therapeutic target for the prevention and treatment of retinal degenerative diseases.}, }
@article {pmid42387875, year = {2026}, author = {Zhao, Q and Xie, Z and Zhao, X and Wei, L and Cheng, S and Gu, X and Chen, Y}, title = {Distinguish polypoidal choroidal vasculopathy through choroidal alterations: A systematic review, meta-analysis and narrative synthesis.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70190}, pmid = {42387875}, issn = {1755-3768}, support = {82271112//National Natural Science Foundation of China/ ; kyfyjj202506//Peking Union Medical College Hospital Research Funding for Postdoc/ ; }, abstract = {PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a vision-threatening choroidal vascular abnormality historically categorized as a subtype of neovascular age-related macular degeneration (nAMD). Accumulating evidence suggests that PCV may instead belong to the pachychoroid spectrum diseases, although its choroidal characteristics remain incompletely characterized and inconsistently reported.<br><br>METHODS: PubMed, Embase and Ovid were searched for studies comparing choroidal structural and vascular parameters of PCV with healthy controls (HC), fellow eyes, nAMD or pachychoroid spectrum diseases. Outcomes supported by three or more studies were synthesized using quantitative meta-analysis, whereas outcomes supported by fewer than three studies were summarized using narrative synthesis and exploratory meta-analysis.<br><br>RESULTS: Forty studies were included in the final analysis. Meta-analysis revealed that subfoveal choroidal thickness (SFCT) was significantly greater in PCV eyes than in HC, nAMD, and fellow eyes, but lower than central serous chorioretinopathy and pachychoroid neovasculopathy (PNV) eyes (all p&#x2009;<&#x2009;0.05). PCV eyes also had lower choroidal vascularity index within the standard subfoveal width of 1.5&#x2009;mm and higher choroidal vascular density (CVD) within the r&#x2009;=&#x2009;10&#x2009;mm FOV than HC eyes (p&#x2009;<&#x2009;0.05). Narrative synthesis and exploratory meta-analysis suggested that PCV eyes may have greater total choroidal thickness than HC and nAMD eyes, as well as a higher ratio of Haller layer thickness to SFCT and larger choroidal luminal area than nAMD eyes at specific locations or areas. Besides, thick-choroid PCV demonstrated higher CVD in 200&#xb0; ultra-wide ICGA images than nAMD, while the thin-choroid subtype exhibited lower CVD than PNV.<br><br>CONCLUSIONS: PCV is characterized by a thicker and more vascular choroid than nAMD and HC, but a thinner and less vascular choroid than CSC and PNV. These findings, supported by both primary and exploratory meta-analyses, provide insights into PCV pathogenesis and its distinction from nAMD and other pachychoroid spectrum disorders.}, }
@article {pmid42388147, year = {2026}, author = {Agrawal, BK and Charan, GS and Bharti, R and Phougat, J and Kaur, M}, title = {Effectiveness of an Educational Intervention to Assess Knowledge and Attitudes Regarding Age-related Macular Degeneration among Nursing Students.}, journal = {Annals of African medicine}, volume = {}, number = {}, pages = {}, doi = {10.4103/aam.aam_400_26}, pmid = {42388147}, issn = {0975-5764}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. This study aimed to assess the effectiveness of an educational intervention in improving nursing students' knowledge and attitudes toward AMD.<br><br>MATERIALS AND METHODS: A quasi-experimental pretest-posttest design was conducted with 144 nursing students from M. M. Institute of Nursing, Haryana. A structured knowledge questionnaire and attitude scale were used to assess the students before and after the intervention. The educational intervention, delivered via PowerPoint presentation, covered AMD's definition, prevalence, risk factors, clinical features, management, and the nursing role in AMD care.<br><br>RESULTS: The results indicated that in the pretest, 44.4% of the students demonstrated good knowledge, which increased to 79.2% in the posttest. Positive attitude improved from 77.8% to 85.4%, while neutral attitude decreased from 22.2% to 14.6%. In terms of knowledge, the mean score improved from 21.78 &#xb1; 6.29 in the pretest to 26.34 &#xb1; 5.07 in the posttest, showing a statistically significant improvement (P = 0.001). For attitude, the mean score increased from 54.09 &#xb1; 6.00 in the pretest to 55.73 &#xb1; 5.98 in the posttest, with a statistically significant improvement (P = 0.021). Therefore, the educational intervention significantly enhanced nursing students' knowledge and attitudes toward AMD.<br><br>CONCLUSION: The educational intervention significantly improved nursing students' knowledge and attitudes toward AMD. These findings emphasize the need to integrate eye health education into nursing curricula to enhance the effective management of AMD so that nursing students can manage patients with AMD in the community as well as in hospitals.}, }
@article {pmid42388256, year = {2026}, author = {Zhou, L and White, E and Matteson, A and Andrews, A and Bailey, ST and Lujan, BJ and Jia, Y and Huang, D and Chen, S}, title = {Split-Spectrum Amplitude-Decorrelation Optoretinography Detects Impaired Photoreceptor Function in Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {8}, pages = {101250}, pmid = {42388256}, issn = {2666-9145}, abstract = {PURPOSE: To assess photoreceptor functional impairment in eyes with early-to-intermediate age-related macular degeneration (AMD) using OCT-based split-spectrum amplitude-decorrelation optoretinography (SSADOR).<br><br>DESIGN: Prospective observational comparative study.<br><br>PARTICIPANTS: Adults &#x2265;50 years of age with early or intermediate AMD and age-matched control subjects.<br><br>METHODS: Split-spectrum amplitude-decorrelation optoretinography measures flash-evoked OCT amplitude fluctuations within the photoreceptor outer segment band to objectively quantify photoreceptor light responses. We compared SSADOR mean decorrelation between AMD and control eyes within the central 3-mm macula and across ETDRS subfields and evaluated associations with best-corrected visual acuity (BCVA) and drusen volume.<br><br>MAIN OUTCOME MEASURES: Split-spectrum amplitude-decorrelation optoretinography mean decorrelation within ETDRS subfields, as a surrogate marker of the light sensing function of photoreceptors.<br><br>RESULTS: Twenty-two eyes with early-to-intermediate AMD and 12 control eyes were enrolled in the study. Split-spectrum amplitude-decorrelation optoretinography decorrelation was significantly reduced in AMD eyes compared with controls across all ETDRS subfields (all P < 0.05), with the greatest reduction in the fovea (P < 0.001). Although visual inspection showed localized reductions over large drusen, regression analysis revealed no meaningful correlation between SSADOR and drusen volume. In AMD eyes, foveal SSADOR decorrelation was moderately associated with BCVA (R[2] = 0.349, P = 0.0002). Split-spectrum amplitude-decorrelation optoretinography distinguished AMD eyes from controls with higher accuracy than BCVA (area under the receiver operating characteristic curve 0.989 vs. 0.795; DeLong test P = 0.002).<br><br>CONCLUSIONS: Split-spectrum amplitude-decorrelation optoretinography detected impaired photoreceptor light responses in eyes with early-to-intermediate AMD compared with age-matched controls and outperformed BCVA in differentiating AMD from normal eyes. Split-spectrum amplitude-decorrelation optoretinography decorrelation may serve as a sensitive, objective biomarker for detecting and monitoring early or subtle photoreceptor dysfunction in AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42388486, year = {2026}, author = {Zang, H and Han, L and Shi, D}, title = {Risk factors for age-related macular degeneration: an umbrella analysis of systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1878292}, pmid = {42388486}, issn = {2296-858X}, abstract = {BACKGROUND: The objective of the current study was to conduct an umbrella review of meta-analyses to systematically assess the methodological quality, potential biases, and validity of all epidemiological evidence addressing risk factors associated with age-related macular degeneration (AMD), and to synthesize the available evidence regarding AMD risk factors.<br><br>METHODS: We searched PubMed, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to April 2025 (last update) for systematic reviews and meta-analyses that focused on the risk factors for AMD. The methodological quality of each study was assessed independently by two reviewers using AMSTAR and the GRADE framework.<br><br>RESULTS: Following a comprehensive systematic search, a total of 53 distinct risk factors were identified, comprising 30 factors with statistically significant associations and 23 without significant associations. Based on the GRADE framework, most of the evidence was classified as low or very low quality, with three factors achieving a moderate level of evidence. Consistent associations were observed for age and smoking, as well as for certain lifestyle and systemic factors, including diet, diabetes, and hypertension. Circulating biomarkers, including carotenoids, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL-C), were also found to be associated with AMD, although the strength of evidence varied across studies.<br><br>CONCLUSION: This umbrella review indicates that AMD risk is associated with multiple modifiable lifestyle and systemic factors. Healthy diet and physical activity may have protective roles, while several circulating biomarkers, including carotenoids and C-reactive protein, have been identified as related to AMD risk. However, given that most of the available evidence is of low or very low certainty, these findings should be considered with caution.<br><br>PROSPERO, CRD420251045558, URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251045558.}, }
@article {pmid42389069, year = {2026}, author = {Şatırtav, G and Lövestam-Adrian, MK and Chang, W and Charles, M and Chen, LJ and Cheung, CMG and Kodjikian, L and Ohji, M and Zinkernagel, M and Wolf, S}, title = {Discontinuing Anti-VEGF Therapy in Patients with Neovascular Age-Related Macular Degeneration That Remains Inactive with Treatment at the Maximum Injection Interval.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {587803}, pmid = {42389069}, issn = {1177-5467}, abstract = {This review aims to provide guidance on the management of patients with neovascular age-related macular degeneration (nAMD) whose disease becomes inactive on anti-vascular endothelial growth factor (VEGF) treatment. The Vision Academy's membership of international retinal disease experts reviewed the literature and developed consensus recommendations and an algorithm to determine the appropriate timing of treatment suspension and a post-treatment follow-up strategy for appropriate patients with nAMD who achieve a good response to anti-VEGF therapy. Patients with inactive disease (defined as absence of both intraretinal and subretinal fluid, absence of deterioration in vision, and absence of new retinal hemorrhage) for at least three consecutive maximum treatment intervals as outlined in the clinic's protocol may be considered for treatment exit. However, in patients with stable disease that remains active and those with only one good seeing eye and a history of disease recurrence, treatment continuation may be preferred. An appropriate interval for continued monitoring with optical coherence tomography and visual acuity testing should be decided following discussion with the patient and consideration of patient-specific factors. This article presents consensus guidelines for nAMD management in patients who respond well to anti-VEGF therapy, and for the discontinuation of treatment in cases of success.}, }
@article {pmid42389194, year = {2026}, author = {Shao, N and Tan, K and Chen, P and Luo, Q}, title = {Multi-omics triangulation identifies complement factor H as a genetically supported protective factor in IgA nephropathy.}, journal = {Clinical kidney journal}, volume = {19}, number = {7}, pages = {sfag176}, pmid = {42389194}, issn = {2048-8505}, abstract = {BACKGROUND: IgA nephropathy is the most prevalent primary glomerulonephritis globally. Dysregulation of the complement system, specifically the alternative pathway, is a critical driver of its pathogenesis. While genome-wide association studies consistently map a primary susceptibility locus to the complement factor H gene cluster, extensive linkage disequilibrium and complex structural variations have historically obscured precise causal targets.<br><br>METHODS: We employed a multi-omics triangulation framework to evaluate the genetic association and potential protective effects of circulating complement proteins in IgA nephropathy. The analytical pipeline integrated large-scale plasma proteomics, blood-derived expression quantitative trait loci, Bayesian colocalization, computational clinical transcriptomics, and phenome-wide association studies. Two-sample, bidirectional, and multivariable Mendelian randomization analyses were performed using summary-level data from global genome-wide association studies.<br><br>RESULTS: Genetically predicted higher circulating levels of complement factor H were significantly associated with a lower risk of IgA nephropathy. Bayesian colocalization decoupled the complex locus, isolating this protective signal to a single missense variant within the complement factor H gene and demonstrating independence from the adjacent complement factor H-related 1 gene. Spatial profiling and clinical transcriptomics suggested a dual-compartment model: the liver supplies the systemic pool, while intrinsic renal cells mount a hypothesized severity-driven compensatory upregulation of complement factor H during active disease. Furthermore, phenome-wide association studies indicated that enhancing complement factor H offers dual protective benefits against IgA nephropathy and age-related macular degeneration without broad chronic systemic pleiotropy.<br><br>CONCLUSIONS: This study provides convergent genomic and transcriptomic evidence supporting complement factor H as a genetically supported protective factor in IgA nephropathy. Genetic variation consistent with enhanced complement factor H-mediated regulation is associated with reduced disease susceptibility. These findings provide a theoretical framework for exploring direct recombinant supplementation therapies and offer genetic support for the ongoing clinical development of upstream alternative pathway inhibitors.}, }
@article {pmid42389246, year = {2026}, author = {Gu, R and Hou, B and Hébert, M and Indurkar, A and Yang, Y and Chew, EY and Keenan, TDL and Lu, Z}, title = {Toward Multimodal Conversational AI for Age-Related Macular Degeneration.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {42389246}, issn = {2331-8422}, abstract = {Despite strong performance of deep learning models in retinal disease detection, most systems produce static predictions without clinical reasoning or interactive explanation. Recent advances in multimodal large language models (MLLMs) integrate diagnostic predictions with clinically meaningful dialogue to support clinical decision-making and patient counseling. In this study, OcularChat, an MLLM, was fine-tuned from Qwen2.5-VL using simulated patient-physician dialogues to diagnose age-related macular degeneration (AMD) through visual question answering on color fundus photographs (CFPs). A total of 705,850 simulated dialogues paired with 46,167 CFPs were generated to train OcularChat to identify key AMD features and produce reasoned predictions. OcularChat demonstrated strong classification performance in AREDS, achieving accuracies of 0.954, 0.849, and 0.678 for the three diagnostic tasks: advanced AMD, pigmentary abnormalities, and drusen size, significantly outperforming existing MLLMs. On AREDS2, OcularChat remained the top-performing method on all tasks. Across three independent ophthalmologist graders, OcularChat achieved higher mean scores than a strong baseline model for advanced AMD (3.503 vs. 2.833), pigmentary abnormalities (3.272 vs. 2.828), drusen size (3.064 vs. 2.433), and overall impression (2.978 vs. 2.464) on a 5-point clinical grading rubric. Beyond strong objective performance in AMD severity classification, OcularChat demonstrated the ability to provide diagnostic reasoning, clinically relevant explanations, and interactive dialogue, with high performance in subjective ophthalmologist evaluation. These findings suggest that MLLMs may enable accurate, interpretable, and clinically useful image-based diagnosis and classification of AMD.}, }
@article {pmid42390175, year = {2026}, author = {Alhelaly, M and Lee, M and Quarta, A and Nittala, MG and Soylu, C and Bellisario, G and Abbasgholizadeh, R and Chujo, S and Elfert, A and Velaga, SB and Racioppo, P and Wang, ZC and Hu, J and Xu, E and Xu, S and Hu, ZJ and Sadda, SR}, title = {Impact of Subretinal Drusenoid Deposits on Ellipsoid Zone-Related Thickness Metrics.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {8}, pages = {10}, doi = {10.1167/iovs.67.8.10}, pmid = {42390175}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/pathology ; *Retinal Pigment Epithelium/pathology ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis/pathology ; Aged, 80 and over ; Retinal Photoreceptor Cell Outer Segment/pathology ; Visual Acuity ; }, abstract = {PURPOSE: Ellipsoid zone (EZ) attenuation is a widely used endpoint in retinal disease trials and is quantified as the distance between the EZ and retinal pigment epithelium (RPE). This study assessed the impact of subretinal drusenoid deposits (SDDs) on EZ-based quantitative metrics in nonneovascular age-related macular degeneration (AMD).<br><br>METHODS: Spectral-domain optical coherence tomography volumes from 83 eyes (44 patients) with SDDs from the Amish Eye Study were analyzed. A semi-automated deep learning-based segmentation with manual correction delineated the inner EZ, inner RPE, and inner SDD surfaces. Photoreceptor outer segment (POS; EZ-SDD) thickness, SDD thickness, and EZ-RPE thickness were measured within Early Treatment Diabetic Retinopathy Study subfields. The proportional SDD contribution to EZ thickness (SDD/EZ ratio) and longitudinal changes over 2 years were evaluated.<br><br>RESULTS: Mean POS and EZ-RPE thickness were 24.4 &#xb1; 4.3 &#xb5;m and 26.3 &#xb1; 5.1 &#xb5;m, respectively. Mean SDD thickness was 1.95 &#xb1; 2.5 &#xb5;m, increasing to 6.75 &#xb1; 3.9 &#xb5;m in SDD-dominant regions. The SDD/EZ ratio averaged 6.9% &#xb1; 6.7% and exceeded 10% in 24% of eyes, mainly in the outer macular ring. Over 2 years, POS thickness and EZ-RPE thickness decreased significantly (&#x394;POS = -2.59 &#xb5;m; &#x394;EZ-RPE = -2.86 &#xb5;m; P = 0.002, P = 0.006, respectively) with a strong correlation (R2 = 0.79), which weakened in eyes with high SDD burden (R2 = 0.16).<br><br>CONCLUSIONS: SDDs cause variable inflation of EZ-RPE thickness, particularly perifoveally. While EZ-RPE thinning reflects POS loss, its reliability may decrease with substantial SDDs. POS-specific metrics and SDD/EZ ratios may improve EZ-based endpoints in AMD trials.}, }
@article {pmid42373614, year = {2026}, author = {Song, J and Wei, X and He, K and Ge, R and Li, M and Bai, T and Han, H and You, C and Liao, M and Pan, W and Chen, M and Belfort, R and Fernandes, RAB and Xie, S and Yan, H}, title = {Tetrahedral DNA nano-PROTACs enable enhanced ocular penetration and efficient nucleolin degradation for choroidal neovascularization therapy.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {}, pmid = {42373614}, issn = {2059-3635}, support = {32270892//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82574321//National Natural Science Foundation of China (National Science Foundation of China)/ ; 23JCQNJC01180//Natural Science Foundation of Tianjin City (Natural Science Foundation of Tianjin)/ ; 22PTZWHZ00030, 25JCZDJC00390//Tianjin Science and Technology Committee (Tianjin Municipal Science and Technology Commission)/ ; }, mesh = {Nucleolin ; *Choroidal Neovascularization/drug therapy/genetics/pathology/metabolism ; Humans ; *Phosphoproteins/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Animals ; Proteolysis Targeting Chimera ; DNA Nanostructures/chemistry ; Vascular Endothelial Growth Factor A/genetics/antagonists &amp; inhibitors ; Mice ; Aptamers, Nucleotide/chemistry/pharmacology ; *Macular Degeneration/genetics/drug therapy/pathology ; }, abstract = {Despite the paradigm shift brought about by anti-VEGF therapy against neovascular age-related macular degeneration, significant challenges persist, including the risk of intraocular infection and retinal structural damage caused by frequent intravitreal injections, suboptimal long-term outcomes in some patients, as well as economic and psychological burdens. Attempts to identify novel therapeutic targets with more compliant drug delivery strategies are warranted. In this study, we identify that nucleolin (NCL) is upregulated in choroidal neovascularization lesions and mobilized to the endothelial cell surface upon VEGF stimulation. Inspired by this localization change and the critical role of NCL in angiogenesis, we developed an integrated delivery and degradation platform, named dNCL@tFNAs, which leverages tetrahedral framework nucleic acids (tFNAs) to decorate an aptamer-based proteolysis-targeting chimera for NCL through a simple Watson-Crick pairing. dNCL@tFNAs exhibits notable stability, improved ocular penetration and degradation efficiency. Mechanistic study reveals that membrane-associated NCL promotes the uptake of dNCL@tFNAs into the endothelial cells, followed by engaging the cytosolic PROTAC machinery to degrade intracellular NCL via the ubiquitin-proteasome pathway. In vivo study demonstrates that dNCL@tFNAs enables administration via a minimally invasive subconjunctival injection to suppress choroidal neovascularization with a favorable safety profile. Collectively, our work establishes a programmable delivery and degradation modality for the treatment of choroidal neovascularization and other ocular neovascular diseases.}, }
@article {pmid42376188, year = {2026}, author = {Brown, D and Zeitz, O and Bailey, C and Garg, S and Csaky, K and Talks, J and Sivaprasad, S and Benz, PM and Herrmann, R and Bakker, RA and Bandholtz, S and Mittal, A and Huang, Q and Kosobokovs, S and Simons, G and Giani, A and Huber, J and Gliem, M and , }, title = {Tropomyosin-Related Kinase Receptor Type B Agonism in Geographic Atrophy-The Translational Challenges from Preclinical Data to a First-in-Human Trial.}, journal = {Ophthalmology science}, volume = {6}, number = {7}, pages = {101216}, pmid = {42376188}, issn = {2666-9145}, abstract = {OBJECTIVE: To report results of the first-in-human trial of intravitreal tropomyosin-related kinase receptor type B (TrkB) agonist BI 754132 in participants with geographic atrophy (GA). To discuss BI 754132 clinical data in the context of the preclinical findings and their translation into human data.<br><br>DESIGN: An open-label, uncontrolled, nonrandomized phase I trial (NCT04002310) assessing the safety, tolerability, and pharmacokinetics of BI 754132 in participants with GA supported by preclinical data.<br><br>PARTICIPANTS: Participants with GA recruited between July 2019 and August 2022 in the United States and UK.<br><br>METHODS: Clinical trial comprising a single rising dose (SRD) part (n = 15) and multiple dose (MD) part (n = 3). Of 18 participants treated, 16 received a single dose of BI 754132 0.3 to 6 mg (SRD, n = 15; MD, n = 1) and 2 received 3 doses each of BI 754132 6 mg (MD part).<br><br>MAIN OUTCOME MEASURES: The primary SRD endpoint was the incidence of ocular and systemic dose-limiting events until day 100; the primary MD endpoint was treatment-related adverse events (AEs) until day 155. Exploratory endpoints included change from baseline in best-corrected visual acuity (BCVA), GA lesion area, central retinal thickness, and selected electroretinogram parameters.<br><br>RESULTS: Preclinical data supported a potential treatment effect and a favorable safety profile of BI 754132, supporting clinical development. In the phase I study (SRD and MD parts), 12 of 18 (67%) participants had an AE; of which, 4 had ischemic optic neuropathy in the study eye. Considering the frequency of ischemic optic neuropathy in the absence of efficacy data, the benefit-risk assessment of BI 754132 could not be considered as positive, and the clinical study was terminated. There was a mild increase in central retinal thickness (&#x2264;25 &#x3bc;m) of all study eyes. No relevant changes in BCVA, GA lesion area, or electroretinogram parameters were noted.<br><br>CONCLUSIONS: Clinical data suggested a potential association between BI 754132 and development of ischemic optic neuropathy. Although the underlying mechanisms remain unclear, these data warrant caution during further exploration of TrkB agonism in GA and highlight the role of monitoring safety data during early clinical development, especially when studying new modes of action.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42377418, year = {2026}, author = {Fan, R and Liu, D}, title = {A real-world study of Faricimab: efficacy and biomarkers in treatment-experienced neovascular age-related macular degeneration(nAMD) and diabetic macular edema (DME) patients.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42377418}, issn = {1435-702X}, abstract = {BACKGROUND: Faricimab, a monoclonal bispecific antibody, has recently been incorporated into clinical practice in China. This study main to evaluate the efficacy and safety of intravitreal faricimab in patients with previously treated nAMD and DME under real-world clinical conditions, and to investigate potential associations.<br><br>METHODS: In this study, patients with nAMD or DME previously treated with other anti-VEGF (Anti-vascular endothelial growth factor) agents or Ozurdex received faricimab. Changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and central subfield maximum thickness (CSMT) were assessed. For nAMD, choroidal neovascularization cross-sectional area (CSA) was measured. Optical coherence tomography (OCT) biomarkers were analyzed, and their correlation with BCVA was examined using Spearman analysis.<br><br>RESULTS: At week 16, BCVA improved from 0.92 to 0.76 logMAR in nAMD and from 0.86 to 0.68 logMAR in DME. CST and CSMT significantly decreased from week 4 to 16 (CST: 539.38 to 408.50&#xa0;&#x3bc;m in nAMD, 502.81 to 292.64&#xa0;&#x3bc;m in DME; CSMT: 710.18 to 526.79&#xa0;&#x3bc;m in nAMD, 586.96 to 356.82&#xa0;&#x3bc;m in DME). CSA reduced from 9.06 to 7.26&#xa0;mm&#xb2;. BCVA positively correlated with subretinal fluid in nAMD and with external limiting membrane/ellipsoid zone integrity in DME, but negatively with subretinal hyperreflective material. No serious adverse events occurred. No serious adverse events were observed.<br><br>CONCLUSIONS: In a real-world setting, intravitreal faricimab demonstrated a favorable safety profile and robust anatomical response in treating treatment-experienced nAMD and DME. However, the anatomical response was stronger than the visual gain in these treatment-experienced eyes, which often have limited visual potential.<br><br>TRIAL REGISTRATION: This study was a Retrospective observational study that approved by the Second Affiliated Hospital of Chongqing Medical University(2025IIT904).}, }
@article {pmid42377419, year = {2026}, author = {Gagliardi, OM and Sahoo, NK and Gregori, G and Hasan, N and Lall, SR and Lupidi, M and Iannetta, D and Chhablani, J}, title = {Tomographic phenotypes and conditional time to atrophic conversion in dry age-related macular degeneration among progressors: an interval-censored study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42377419}, issn = {1435-702X}, abstract = {PURPOSE: Identifying progression trajectories of intermediate age-related macular degeneration (iAMD) is crucial to determine candidates for future therapies. This study assessed whether the OCT phenotype could predict the progression to complete retinal pigment epithelium and outer retinal atrophy (cRORA).<br><br>METHODS: This retrospective study included eyes with dry AMD progressing to cRORA. Baseline OCT phenotypes were assigned with a stepwise clinical rationale: incomplete RORA (iRORA) > acquired vitelliform lesions (AVL) > drusenoid pigment epithelial detachment (dPED) > subretinal drusenoid deposits (SDD) > soft drusen, with soft drusen as the reference group. Time to cRORA was estimated with accelerated failure time models.<br><br>RESULTS: Among the 129 eyes of 89 patients progressing to cRORA, the median time to cRORA for the overall cohort was 4.83 years. Eyes with iRORA showed the shortest median time to cRORA (0.75 years), followed by dPED (2.53 years) and AVL (4.07 years). SDD and soft drusen demonstrated the slowest progression (6.76 and 6.48 years, respectively). In adjusted AFT models baseline hyperreflective foci (HRF), iRORA (TR, 0.21; 95% CI, 0.13-0.33; p&#x2009;<&#x2009;0.001) and dPED (TR, 0.59; 95% CI, 0.40-0.86; p&#x2009;=&#x2009;0.007) independently predicted shorter time to cRORA. Presence of HRF was independently associated with faster progression (TR, 0.57; 95% CI, 0.44-0.74; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: In eyes with dry AMD progressing to cRORA, baseline OCT phenotypes were associated with different temporal trajectories to cRORA. These findings will help prognostic stratification and the selection of candidates for emerging therapeutic interventions.}, }
@article {pmid42379510, year = {2026}, author = {Pan, SY and Weng, CH and Sheen, YJ and Tsai, SF and Lin, JF and Chen, JP and Lin, CH and Huang, SP and Chang, CJ and Lin, HJ and Wang, IJ and Chou, CC}, title = {GLP-1 Receptor Agonists and Age-related Macular Degeneration Risk in Diabetes or Non-diabetic Obesity: A Retrospective Cohort Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2026.06.023}, pmid = {42379510}, issn = {1555-7162}, abstract = {OBJECTIVE: To examine the association between GLP-1RAs and age-related macular degeneration.<br><br>METHODS: This is a retrospective cohort study including two cohorts of adults aged &#x2265;50 years free of macular degeneration at baseline, including (i) the diabetes cohort comparing age-related macular degeneration risk between GLP-1RAs and metformin users, and (ii) the obesity cohort, consisting of individuals with a body mass index &#x2265;30 kg/m[2] without type 2 diabetes, comparing the risk of age-related macular degeneration between GLP-1RAs and other weight-loss medications. A 1:1 propensity score matching was performed to balance covariates. Cox proportional hazards models and Kaplan-Meier analysis were used to assess the risk of age-related macular degeneration across 5 years of follow-up.<br><br>RESULTS: A total of 147,800 participants with diabetes and 49,518 participants with obesity were included. In the diabetes cohort, GLP-1RAs were associated with lower total age-related macular degeneration (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.75-0.91) and dry age-related macular degeneration (HR, 0.84; 95% CI, 0.73-0.98) risks compared to metformin. In the obesity cohort, GLP-1RAs were associated with a lower risk of total age-related macular degeneration (HR, 0.77; 95% CI, 0.61-0.98) and dry age-related macular degeneration (HR, 0.65; 95% CI, 0.46-0.94) compared to other weight-loss medications.<br><br>CONCLUSIONS: GLP-1RAs were associated with a lower risk of age-related macular degeneration, particularly dry form, compared with metformin or other weight-loss medications.}, }
@article {pmid42379522, year = {2026}, author = {Ehlers, JP and Cetin, H and Amine, R and Matar, K and Indurkar, A and Mamone, J and Della Vecchia, L and Tang, A and Reese, J and Luo, D and Abulon, DJK and Talcott, KE}, title = {Avacincaptad Pegol Slows Progressive Ellipsoid Zone Degradation/Loss in Eyes With Geographic Atrophy.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.06.023}, pmid = {42379522}, issn = {1549-4713}, abstract = {PURPOSE: Ellipsoid zone (EZ) integrity as measured by spectral-domain optical coherence tomography (SD-OCT) is a key biomarker and surrogate for photoreceptor health, including in age-related macular degeneration (AMD). The objectives of this study were to determine (1) the association of baseline EZ measures with geographic atrophy (GA) progression and photoreceptor loss, and (2) the impact of avacincaptad pegol (ACP), a complement inhibitor, on EZ integrity over the first year of treatment.<br><br>DESIGN: Post hoc analysis of pooled data from the phase 2/3 GATHER1 and phase 3 GATHER2 trials.<br><br>PARTICIPANTS: Patients &#x2265;50 years of age with non&#x2012;center point involving GA in the study eye.<br><br>METHODS: SD-OCT images were evaluated using advanced multilayer segmentation with certified reader validation for EZ integrity, measuring total EZ attenuation or loss (EZ to retinal pigment epithelium [RPE] thickness of 0 &#x3bc;m; i.e., total loss of EZ) and partial EZ attenuation or degradation (EZ-RPE thickness of &#x2264;20 &#x3bc;m). GA lesion growth was assessed through fundus autofluorescence.<br><br>MAIN OUTCOME MEASURES: (1) Natural history assessment of progression of GA and total EZ attenuation in sham-treated eyes based on quartiles of baseline EZ measures, and (2) the impact of ACP treatment vs sham on progression of total and partial EZ attenuation over 12 months were evaluated.<br><br>RESULTS: This study included 292 ACP 2 mg and 332 sham eyes. In sham-treated eyes, mean GA growth and progression of total EZ attenuation were substantially greater in higher quartiles of baseline total EZ attenuation and partial EZ attenuation measures over 12 months. ACP 2 mg significantly reduced mean growth in total EZ attenuation by 19.5% (P=0.0009) and mean growth in percentage of partial EZ attenuation by 55.3% (P<0.0001) vs sham over 12 months.<br><br>CONCLUSIONS: Greater baseline total and partial EZ attenuation were associated with higher rates of GA lesion growth and progressive EZ loss over time, establishing these EZ measures as important predictors of future GA growth and photoreceptor loss. Treatment with ACP reduced EZ loss and degradation over 12 months vs sham. EZ measures may enhance identification of patients at high risk of disease progression who would benefit from early therapeutic intervention.}, }
@article {pmid42381356, year = {2026}, author = {Bihorel, S and Chiu, J and Chittenden, J and Eissing, T and Turner, KC and Höchel, J and Zimmermann, T and He, ZW and Davis, JD and DiCioccio, AT and Harnisch, LO}, title = {Integrated Population Pharmacokinetic Analysis of Intravitreal Aflibercept Drug Products.}, journal = {CPT: pharmacometrics &amp; systems pharmacology}, volume = {15}, number = {7}, pages = {e70287}, doi = {10.1002/psp4.70287}, pmid = {42381356}, issn = {2163-8306}, mesh = {Humans ; *Recombinant Fusion Proteins/pharmacokinetics/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Intravitreal Injections ; Female ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage ; Male ; Macular Edema/drug therapy ; *Macular Degeneration/drug therapy ; Models, Biological ; Diabetic Retinopathy/drug therapy ; Aged ; }, abstract = {Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) can cause substantial vision loss. The 2-mg drug product of aflibercept (AFL-2)-an anti-vascular endothelial growth factor agent-has established efficacy and safety in both diseases. In pivotal trials, a high-dose drug product (AFL-HD) using a formulation distinct from AFL-2 and delivering 8-mg aflibercept every 12 or 16 weeks (following initial monthly dosing) provided visual gains non-inferior to AFL-2 administered every 8 weeks (following initial monthly dosing) and comparable safety with fewer injections over 96 weeks. Free and bound aflibercept concentrations in plasma from 2744 participants in 16 clinical trials where aflibercept was administered intravitreally, subcutaneously, or intravenously were analyzed by population pharmacokinetic modeling. A semi-mechanistic model described the release of free aflibercept from the eye and its target-mediated elimination from plasma. The evaluated covariates (weight, age, sex, albumin, disease, racial classification, Japanese origin, renal and hepatic functions) resulted in only small numerical differences in systemic exposure. Ocular clearance (QE; characterizing the bidirectional transfer of free aflibercept between the eye and central compartment) was comparable across both diseases after adjusting for an age-dependent decrease. The change in drug product, and not just the dose increase, was responsible for a 39.4% slower QE and extended exposure in the ocular space for AFL-HD versus AFL-2. The median ocular concentrations of free aflibercept predicted at the end of the 8-week dosing interval for AFL-2 were typically reached 14 weeks after AFL-HD injections, versus 9-9.5 weeks if QE was identical for both drug products.}, }
@article {pmid42382025, year = {2026}, author = {Cho, M and Lee, J and Lee, J and Doguer, C and Hwang, JH and Ha, JH}, title = {Freeze-Dried Extracts of Eruca sativa Selectively Inhibit Nuclear Factor-κB and Vascular Endothelial Growth Factor Levels in Retinal Pigment Epithelial Cells.}, journal = {Preventive nutrition and food science}, volume = {31}, number = {3}, pages = {}, pmid = {42382025}, issn = {2287-1098}, abstract = {Diabetic retinopathy and age-related macular degeneration are driven by retinal pigment epithelium (RPE) dysfunction accompanied by chronic inflammation and an upregulation of vascular endothelial growth factor (VEGF). This study investigated the protective effects of Eruca sativa freeze-dried extract against metabolic and inflammatory stress in the ARPE-19 retinal epithelial cell line. Gene expression levels and protein contents were assessed via quantitative real-time polymerase chain reaction and Western blots. VEGF secretion and cell calcium levels were quantified using enzyme-linked immunosorbent assay and Fluo-4 NW calcium assay, respectively. Freeze-dried E. sativa extract (ESF) exposure did not induce any cytotoxicity across the concentration range tested. Under thapsigargin (Tg) stimulation, ESF at 1 mg/mL significantly reduced VEGF expression and protein secretion by 32% and 34%, respectively. Tg-induced calcium mobilization within cells and the expression of unfolded protein response markers, including CCAAT/enhancer-binding protein homologous protein, binding immunoglobulin protein, and X-box binding protein-1, remained unchanged following ESF exposure. Under lipopolysaccharide stimulation, in a dose-dependent manner, ESF suppressed nuclear factor-κB (NF-κB) phosphorylation, tumor necrosis factor-α, and interleukin-1β expression; however, c-Jun N-terminal kinase signaling was not affected. Hot-air-dried E. sativa extract demonstrated contrasting regulatory profiles, which exhibited a broader modulation of endoplasmic reticulum stress and mitogen-activated protein kinase signaling. Collectively, the findings demonstrate that ESF selectively attenuates inflammatory and angiogenic responses by specifically inhibiting the NF-κB-VEGF axis. Dehydration, therefore, is a critical method determining ESF bioactivity, preserving native phytochemicals that confer focused anti-inflammatory and anti-angiogenic efficacy in RPE cells.}, }
@article {pmid42382171, year = {2026}, author = {Eandi, CM and Borgo, A and de Oliveira Figueiredo, E and de Haro, D and Kaufmann, DE and Roduit, R}, title = {Proteomic profiling reveals treatment-dependent inflammatory signatures and identifies biomarkers of refractory age-related macular degeneration.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1793714}, pmid = {42382171}, issn = {1663-9812}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a severe eye disease that affects the macula, the central area of the retina. Current treatment consists of intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. However, some patients remain refractory to treatment even after maximal anti-VEGF dosage. We longitudinally analyzed angiogenic and inflammatory biomarkers in the aqueous humor (AH) of these patients.<br><br>OBJECTIVES: 1) To confirm the presence of angiogenic and inflammatory biomarkers before (in the naive state) and after two anti-VEGF injections; and 2) to characterize the inflammatory response according to the type of anti-VEGF used (ranibizumab, aflibercept, brolucizumab, or faricimab).<br><br>METHODS: AH samples were collected from two groups of patients: 35 patients with AMD and 17 control patients with no retinopathy. Eleven of the 35 patients with AMD were characterized as refractory (rAMD) after long-term anti-VEGF treatment. Multiplex and proximity extension assays (PEA) were performed on these samples to define their inflammatory profiles. Free VEGFA was detected using an additional AlphaLISA VEGFA assay.<br><br>RESULTS: Several inflammatory molecules are upregulated in AMD, while a smaller subset is downregulated in rAMD, indicating that these could serve as markers of a refractory state. In contrast, no differences were observed in the biomarkers previously reported as increased in rAMD after long term treatment. These findings suggest that anti-VEGF treatment induces the expression of angiogenic and inflammatory biomarkers. Analysis of the inflammatory response following the injection of different anti-VEGF agents revealed exacerbated inflammation in patients treated with brolucizumab, whereas ranibizumab caused the lowest inflammatory response. In addition, we compared three different assays to assess AH VEGFA, but only the AlphaLISA assay could detect free VEGFA.<br><br>CONCLUSION: Our results indicate that anti-VEGFA therapy shapes AMD-associated inflammation; therefore, the choice of anti-VEGFA therapy remains important in reducing secondary inflammatory effects. Furthermore, the detection of free VEGF is dependent on the assay used.}, }
@article {pmid42382961, year = {2026}, author = {Knott, RM and Grove, N and Patnaik, JL and Manoharan, N and Lynch, AM and Christopher, KL}, title = {Visual functioning in patients with macular degeneration compared to patients with cataracts.}, journal = {International journal of ophthalmology}, volume = {19}, number = {7}, pages = {1278-1283}, pmid = {42382961}, issn = {2222-3959}, abstract = {AIM: To compare Visual Functioning Questionnaire-25 (VFQ) response data in patients with age-related macular degeneration (AMD) to patients with cataracts.<br><br>METHODS: In total 415 individuals with early or intermediate AMD and 236 patients with visually significant cataracts who completed the VFQ-25 from a single academic eye center registry between July 2014 and May 2022 were identified. The effect of disease (AMD versus cataract) on VFQ composite score was analyzed using univariate and multivariable linear regression, controlling for age, race/ethnicity, history of transient ischemic attack (TIA)/stroke, and visual acuity.<br><br>RESULTS: AMD patients were older than the cataract group (76.0&#xb1;7.4y vs 73.2&#xb1;5.9y, P<0.001). There was no difference in sex between groups with both being predominantly female (63% for AMD vs 61% for cataracts, P=0.801). The VFQ composite score was higher in the AMD group (88.8&#xb1;10.7 vs 82.8&#xb1;14.5, P<0.001). All vision-related and socio-emotional subscales had significantly higher scores among AMD compared to cataract patients. When adjusted for age, race/ethnicity, history of TIA/stroke, better-eye visual acuity, and worse-eye visual acuity, patients with cataracts had a 3.3-point lower VFQ composite score (95%CI: -5.3 to -1.4, P<0.001) compared to patients with AMD.<br><br>CONCLUSION: Patients with early or intermediate AMD report higher visual functioning compared to patients with cataracts in composite score and all VFQ subscale categories in both unadjusted and adjusted analyses.}, }
@article {pmid42382963, year = {2026}, author = {Zhang, RY and Su, HM and Ding, Y and Zou, YY}, title = {Molecular mechanisms and intervention strategies for age-related macular degeneration.}, journal = {International journal of ophthalmology}, volume = {19}, number = {7}, pages = {1383-1394}, pmid = {42382963}, issn = {2222-3959}, abstract = {Age-related macular degeneration (AMD) is a leading ocular disorder that causes irreversible visual impairment and blindness in the elderly population. Accumulating evidence demonstrates that AMD is the end-stage outcome of various retinal degenerative lesions and vascular anomalies. Its core pathogenic mechanisms mainly involve dysfunction and atrophy of retinal pigment epithelium (RPE) cells, choroidal capillary degeneration, pathological choroidal neovascularization (CNV), chronic inflammation, oxidative stress injury, deposition of extracellular substances such as drusen, and genetic predisposition. Given its multifactorial origin and complicated pathophysiological processes, the full molecular regulatory network of AMD has not been fully clarified, which restricts the development of more efficient intervention regimens. This review systematically summarizes the latest research progress concerning the molecular mechanisms of AMD, and comprehensively discusses mainstream and emerging therapeutic strategies, including anti-vascular endothelial growth factor (VEGF) drugs, antioxidant and mineral supplements, photodynamic therapy, and laser therapy, as well as innovative modalities such as gene therapy, stem cell therapy, and targeted regulation of complement and inflammatory pathways. It is intended to provide theoretical basis and research references for in-depth mechanistic exploration, early prevention and precise clinical management of AMD.}, }
@article {pmid42383220, year = {2026}, author = {Quarta, A and Abbasgholizadeh, R and Huang, J and Chujo, S and Soylu, C and Velaga, SB and Mahmoudi, A and Lindeberg, S and Alhelaly, M and Nittala, MG and Corradetti, G and Mastropasqua, R and Wykoff, C and Sadda, SR}, title = {Epiretinal Membrane Is Associated with Acquired Vitelliform Lesion Morphometrics in Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {7}, pages = {101228}, pmid = {42383220}, issn = {2666-9145}, abstract = {PURPOSE: To investigate the impact of epiretinal membrane (ERM) on the structural characteristics of acquired vitelliform lesions (AVLs) in eyes with intermediate age-related macular degeneration (iAMD).<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: Eyes of patients with iAMD-associated AVLs were identified from a tertiary referral center database.<br><br>METHODS: Multimodal imaging, including spectral-domain OCT, was reviewed. Eyes were stratified according to the presence (ERM + AVL) or absence (AVL-only) of ERM. Quantitative OCT parameters, including apical AVL height and width, and qualitative structural features such as intraretinal hyperreflective foci (IHRF), ellipsoid zone (EZ), and external limiting membrane (ELM) disruption, and AVL location relative to drusen, were assessed by masked graders. Effect sizes were calculated using Hedges' g. Group comparisons were performed using appropriate parametric or nonparametric tests.<br><br>MAIN OUTCOME MEASURES: Differences in AVL structural characteristics between eyes with and without ERM.<br><br>RESULTS: A total of 234 eyes with age-related macular degeneration (AMD)-associated AVLs were included, of which 17 eyes had concomitant ERM. Eyes with ERM demonstrated significantly greater apical AVL height compared with AVL-only eyes (169.9 &#xb1; 52.5 &#x3bc;m vs. 134.8 &#xb1; 55.0 &#x3bc;m; P = 0.016). Acquired vitelliform lesion width was greater in the ERM + AVL group, although this difference did not reach statistical significance (811.1 &#xb1; 251.0 &#x3bc;m vs. 676.8 &#xb1; 416.0 &#x3bc;m; P = 0.057). The prevalence of IHRF, EZ disruption, ELM disruption, and AVL location over drusen did not differ significantly between groups. Effect size analysis demonstrated a moderate positive effect for apical AVL height (Hedges' g &#x2248; 0.65; 95% confidence interval [CI] &#x223c;0.15 to 1.10), whereas AVL width showed a small-to-moderate effect size with CIs crossing 0.<br><br>CONCLUSIONS: In eyes with AMD-associated AVLs, the presence of ERM is associated with increased AVL height without corresponding differences in other outer retinal structural features. These findings suggest that vitreomacular traction may selectively influence AVL configuration. Longitudinal studies are needed to determine whether traction-related modulation of AVL morphology impacts AMD disease progression and AVL collapse.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42383222, year = {2026}, author = {Teo, KYC and Margaron, P and Lai, TYY and Lee, WK and Sadda, SR and Staurenghi, G and Patel, S and Cheung, CMG}, title = {Assessing Polypoidal Choroidal Vasculopathy-Related OCT Features in the TENAYA and LUCERNE Trials.}, journal = {Ophthalmology science}, volume = {6}, number = {7}, pages = {101217}, pmid = {42383222}, issn = {2666-9145}, abstract = {OBJECTIVE: To describe OCT features associated with polypoidal choroidal vasculopathy (PCV) in the TENAYA and LUCERNE clinical trial cohorts.<br><br>DESIGN: Imaging analysis within 2 multinational, double-masked, randomized controlled phase III trials.<br><br>SUBJECTS: Participants with treatment-na&#xef;ve neovascular age-related macular degeneration enrolled in TENAYA and LUCERNE with baseline OCT and in a subset, baseline indocyanine green angiography (ICGA).<br><br>METHODS: Previously described OCT features associated with PCV were evaluated among 1329 participants. Two major OCT features were evaluated (sharp-peaked pigment epithelial detachment [SPED] and sub-retinal pigment epithelium ring-like lesion) to determine the occurrence of OCT-defined PCV. Subretinal fluid, intraretinal fluid (IRF), and hyperreflective material (HRM), were compared between OCT-defined PCV and non-PCV eyes. A sensitivity analysis was performed in the subset of eyes with available ICGA to assess concordance between OCT and ICGA-confirmed PCV.<br><br>MAIN OUTCOME MEASURES: Occurrence of OCT-defined PCV and distribution of OCT-based disease activity biomarkers by PCV status.<br><br>RESULTS: Using the 2 major OCT criteria, 88 (6.7%) of eyes were classified as OCT-defined PCV. Fewer OCT-defined PCV eyes had IRF and HRM compared with non-PCV eyes (27.3% vs. 45.5%, P = 0.002, 19.3% vs. 47.0%, P < 0.001). In the ICGA subset (n = 274), the combination of SPED and ring demonstrated good sensitivity (85.2%) and high specificity (98.8%) relative to ICGA.<br><br>CONCLUSIONS: Using 2 Asia-Pacific Ocular Imaging Society major OCT features, OCT-based diagnostic strategy may help triage or screen for PCV when ICGA is unavailable.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42383239, year = {2026}, author = {Durán-Cristiano, SC and Ospina-Villa, JD and Gijs, M}, title = {Aptamers in Ocular Disease Therapy and Drug Delivery: Current Progress and Future Opportunities.}, journal = {Current therapeutic research, clinical and experimental}, volume = {105}, number = {}, pages = {100834}, pmid = {42383239}, issn = {0011-393X}, abstract = {PURPOSE: Aptamers are single-stranded oligonucleotides with the ability to bind specific target molecules with high affinity and selectivity, positioning them as valuable tools for precision therapeutics and targeted drug delivery. In ophthalmology, aptamer-based platforms have emerged as effective solutions for managing retinal diseases, glaucoma, and ocular surface disorders. This review provides a comprehensive overview of aptamers that have received approval or are in experimental, preclinical, or clinical development stages for ocular diseases.<br><br>METHODS: A narrative literature search was conducted using PubMed, Scopus, Cochrane Library, Embase, and Web of Science databases, concentrating on aptamers that have reached experimental, preclinical, clinical, or FDA-approved stages. Studies published up to March 2026 were screened according to predefined inclusion and exclusion criteria, based on their reported efficacy, molecular targets, and relevance to ocular diseases.<br><br>RESULTS: Twenty-four records were included, comprising 24 aptamer-based platforms. Across ocular diseases, aptamers were identified in three principal application domains: therapeutic intervention, diagnostic, and targeted drug delivery. In age-related macular degeneration, aptamers development was predominantly therapeutic, with agents targeting vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor 2, complement components, nucleolin, CBF1, and CD44. In glaucoma, aptamers were mainly directed toward neuroprotection, antifibrotic modulation, aqueous humor outflow regulation, biomarker detection, and topical drug delivery. In ocular surface diseases, aptamers were primarily developed for antimicrobial and antiviral therapy, antiangiogenic treatment, anti-allergic modulation, corneal surface targeting, and controlled topical drug delivery. Overall, aptamers demonstrated broad translational versatility across both posterior and anterior segment diseases.<br><br>CONCLUSIONS: The available evidence demonstrates a diverse and rapidly expanding repertoire of aptamers developed for ocular diseases, underscoring their versatile potential as next-generation platforms for therapeutic, biomarker-guided diagnosis, and targeted drug delivery in ophthalmology.}, }
@article {pmid42383569, year = {2026}, author = {Recalde, S and Moreno Orduña, M and Bezunartea, J and Belza, I and Chas, A and Fernández-Sánchez, L and Cuenca Navarro, N and García-Layana, A and Fernández-Robredo, P and Hernández, M}, title = {ApoE- and Cfh-deficient mice exhibit structural and molecular features of human early-intermediate retinal degeneration.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.70243}, pmid = {42383569}, issn = {2576-2095}, support = {RD21/0002/0010//Inflammatory Disease Network/ ; SAF2016-81876-REDT//Red Nacional de Investigaci&#xf3;n en Complemento/ ; //Fundaci&#xf3;n Gangoiti (Spain)/ ; //Fundaci&#xf3;n Multi&#xf3;pticas (Spain)/ ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which alterations in lipid metabolism and dysregulation of the complement system play a central role. The aim of this study was to characterize a novel double-knockout (DK) mouse model deficient in apolipoprotein E and complement factor H (ApoE[-/-]Cfh[-/-]) as an experimental model of early and intermediate AMD.<br><br>METHODS: ApoE[-/-]Cfh[-/-] mice and wild-type controls underwent comprehensive morphological, ultrastructural, biochemical, and molecular analyses. Retinal and retinal pigment epithelium (RPE) integrity, Bruch's membrane (BM) morphology, lipid accumulation, complement activation, angiogenic signaling, and synaptic organization were evaluated using histology, electron microscopy, immunohistochemistry, biochemical assays, and gene expression analyses.<br><br>RESULTS: DK mice exhibited significant RPE thinning, disruption of tight junctions, vacuolization, and BM thickening (p&#x2009;<&#x2009;0.05). Lipid accumulation and plasma lipid levels significantly increased compared with controls (p&#x2009;<&#x2009;0.01). Complement activation was significantly enhanced, as evidenced by increased C5b-9 deposition (p&#x2009;<&#x2009;0.01). In addition, DK mice exhibited increased vascular endothelial growth factor expression (p&#x2009;<&#x2009;0.05), altered matrix metalloproteinase activity (p&#x2009;<&#x2009;0.05), and significant synaptic disorganization between photoreceptors and second-order neurons (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: The ApoE[-/-]Cfh[-/-] mouse reproduces key molecular and structural features of early and intermediate retinal degeneration with statistically significant alterations. Although it does not progress to advanced disease stages, it represents a valuable model to investigate several factors of AMD pathogenesis and evaluate therapeutic strategies targeting early disease mechanisms.}, }
@article {pmid42384180, year = {2026}, author = {Iskin, AE and Simsek, A and Kizmaz, MA and Kaçmaz, E and Bozkurt, T and Ucan Gunduz, G and Baykara, M and Budak, F}, title = {Impact of intravitreal bevacizumab on immune cells in neovascular age related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42384180}, issn = {1435-702X}, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease that leads to progressive central vision loss. Bevacizumab (Avastin), a therapeutic agent used in the treatment of AMD, exerts its effect by binding to all isoforms of vascular endothelial growth factor (VEGF), thereby inhibiting angiogenesis. This study aimed to investigate the effects of Bevacizumab on immune system cells in the context of neovascular AMD (nAMD) treatment.<br><br>METHODS: Patients with nAMD receiving Bevacizumab treatment (n&#x2009;=&#x2009;18) and a control group of individuals undergoing cataract surgery (n&#x2009;=&#x2009;19) were included in the study. Peripheral blood samples were collected from nAMD patients before Bevacizumab treatment (baseline, 0 month) and after three monthly intravitreal injections. Following staining with monoclonal antibodies, innate immune cell, T cell, and B cell subsets were analyzed using flow cytometry panels.<br><br>RESULTS: In the innate immune cell subsets of patients with neovascular AMD (nAMD), immature and suppressive neutrophils were significantly increased, whereas intermediate and non-classical monocytes were significantly decreased. Following intravitreal bevacizumab (IVB) treatment, these cell populations tended to return toward baseline levels. In the adaptive immune compartment, effector memory (EM) T cell subsets, particularly EM1 (effector memory 1) and EM3 (effector memory 3), exhibited opposing dynamics, showing significant changes both before and after IVB treatment.<br><br>CONCLUSION: In conclusion, the findings from this study provide preliminary evidence that various immune cell subsets in both innate and adaptive compartments show associations with AMD pathogenesis and with IVB treatment.}, }
@article {pmid42384329, year = {2026}, author = {Sherif, MZ and Teo, KYC and Lai, TYY and Chan, HH and Fenner, BJ and Lee, WK and Cheung, CMG}, title = {Advances in Polypoidal Choroidal Vasculopathy (PCV) Management: Emerging Evidence for Faricimab and Aflibercept 8 mg.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42384329}, issn = {2193-8245}, abstract = {INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a major subtype of neovascular age-related macular degeneration (nAMD), particularly prevalent in Asian and pigmented populations. While anti-vascular endothelial growth factor (anti-VEGF) therapy has improved outcomes, limitations in durability and incomplete polypoidal lesion regression remain. This review provides an updated synthesis of emerging evidence on newer anti-VEGF agents in PCV management.<br><br>METHODS: This narrative review synthesizes recent evidence in PCV management, integrating data from clinical trials and emerging real-world studies, with a focus on newer anti-VEGF agents including faricimab (Vabysmo, Roche/Genentech)and aflibercept 8&#xa0;mg (Eylea HD, Regeneron).<br><br>RESULTS: Faricimab, a bispecific antibody targeting VEGFA and angiopoietin-2 (Ang-2), demonstrated non-inferior efficacy compared with aflibercept 2&#xa0;mg administered every 8&#xa0;weeks in the TENAYA/LUCERNE trials, with over 70% of patients achieving dosing intervals of &#x2265;&#x2009;12&#xa0;weeks. The SALWEEN study further evaluated faricimab in 135 patients with PCV, reporting robust visual gains (+&#x2009;8.9 letters), 61% polypoidal lesion regression, and over 80% of patients achieving&#x2009;&#x2265;&#x2009;12-week dosing intervals at 48&#xa0;weeks. Aflibercept 8&#xa0;mg, evaluated in the PULSAR trial, demonstrated comparable safety and efficacy with improved anatomical drying and extended dosing intervals (12-16&#xa0;weeks) compared with aflibercept 2&#xa0;mg. In a subgroup analysis of 139 eyes with indocyanine green angiography (ICGA)-confirmed PCV, outcomes were consistent with the overall study population, with similar visual and anatomical improvements but reduced injection burden. More than 80% of eyes achieved dosing intervals of &#x2265;&#x2009;12&#xa0;weeks at 2&#xa0;years.<br><br>CONCLUSIONS: Faricimab and aflibercept 8&#xa0;mg represent important advances in PCV management, offering more durable treatment options and reducing treatment burden. However, important gaps remain, including limited real-world data for aflibercept 8&#xa0;mg, absence of head-to-head PCV-specific trials, and uncertainty regarding long-term recurrence and lesion inactivation. These findings support a shift toward increasingly individualized and durable treatment strategies in PCV.}, }
@article {pmid42366659, year = {2026}, author = {Ismailova, HS and Sheludchenko, VM and Levkina, AS and Yusef, S and Karpilova, MA}, title = {[Diagnostic significance of perimetry and microperimetry in common retinal diseases].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {3}, pages = {50-55}, doi = {10.17116/oftalma202614203150}, pmid = {42366659}, issn = {0042-465X}, mesh = {Humans ; *Visual Field Tests/methods ; *Retinal Diseases/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; *Retina/physiopathology/diagnostic imaging ; Visual Fields ; *Diabetic Retinopathy/diagnosis/physiopathology ; }, abstract = {Perimetry with assessment of the light sensitivity threshold and indices of its loss has wide use in ophthalmology. This review considers three diseases in which static perimetry and microperimetry are used and for which outcome data are available - age-related macular degeneration, diabetic retinopathy, and hypertensive retinopathy. Despite differing opinions on the feasibility of using perimetry in the early stages of these diseases, the obtained data differ from normal values. Microperimetry is more often performed in combination with optical coherence tomography of the retina. Since perimetry is a subjective assessment method, its findings should be verified with the data of local bioelectrical potential, or "objective perimetry".}, }
@article {pmid42370003, year = {2026}, author = {Abraham, CH and Abu, EK and Owusu, P and Mensah, TO and Botchway, E and Mensah, PA and Dadzie, AK and Kyei, S}, title = {Disease-specific data augmentation enhances deep learning classification of age-related macular degeneration, diabetic retinopathy, and glaucoma.}, journal = {Digital health}, volume = {12}, number = {}, pages = {20552076261461391}, pmid = {42370003}, issn = {2055-2076}, abstract = {OBJECTIVE: To determine which data augmentation technique yields the best performance for deep learning models in classifying age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and normal fundus images.<br><br>METHODS: This study employed an in silico experimental study design. Six data augmentation techniques: Colour Jitter, Contrast-Limited Adaptive Histogram Equalisation (CLAHE), Rotation, Translation, Gaussian Noise, and Poisson Noise were evaluated using controlled experiments with an EfficientNet-B0 model on a balanced dataset of 1,200 fundus photographs, 250 cases each for AMD, DR and glaucoma, and 450 normal fundus images curated from four main publicly available databases. The experiments were conducted in four phases: baseline, single augmentations, combined augmentations, and the impact of augmented dataset volume. Evaluation metrics and visualisations were computed with Python-based statistical and visualisation libraries.<br><br>RESULTS: The results from this study show that data augmentation consistently increased the area under the curve (AUC) from 96.55% to 97.23% and accuracy from 85.83% (baseline) to 89.58%. The results indicate that augmentation effectiveness is disease-specific: Rotation and Colour Jitter yielded the highest sensitivity for AMD (99%), CLAHE maximised sensitivity for Diabetic Retinopathy (96%), and Translation was most effective for Glaucoma (83%). While single augmentations provided descriptive clinical improvements, the comprehensive combination of photometric, geometric, and noise augmentations yielded the best overall performance and achieved a statistically significant improvement over the baseline (Mean bootstrapped AUC = 0.9800, 95% CI: 0.9678, 0.9895; p= 0.0050).<br><br>CONCLUSION: Data augmentation effectiveness is disease-dependent; specific pathologies respond better to distinct augmentation techniques due to different retinal biomarkers.}, }
@article {pmid42371388, year = {2026}, author = {Jungmichel, S and Kreideweiß, S and Scheifele, F and Sobieraj, A and Richle, P and Gupta, P and Lenherr-Frey, D and Bakker, RA and Borras, L}, title = {Pharmacological Characterization of a Novel Complement C3 Inhibitor Antibody Fragment.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42371388}, issn = {2193-8245}, abstract = {INTRODUCTION: The complement system is a key driver of geographic atrophy (GA), a disease that leads to progressive, irreversible vision loss. Pharmacological preclinical studies characterizing an antibody fragment, which is a novel complement C3 inhibitor under investigation for GA treatment, are presented.<br><br>METHODS: Kinetic parameters were determined for the antibody fragment binding to C3, C3b, and C3 variants associated with GA. Inhibition of membrane attack complex (MAC) formation after classical (CP), alternative (AP), and lectin (LP) pathway activation was determined. Comparisons with the second-generation compstatin derivative (APL-1) were made because of the expected similarity of binding behavior and in vitro potency with pegcetacoplan (which could not be sourced at the time of the study). Diffusion through Bruch's membrane (BrM) was investigated for the antibody fragment and a pegcetacoplan-similar (PEG-s) molecule using enriched porcine BrM in Ussing chamber devices.<br><br>RESULTS: The antibody fragment showed high (picomolar) affinity for all tested C3 ligands. APL-1 showed lower (single-digit nanomolar) affinity than the antibody fragment, comparable with published values. The antibody fragment exhibited dose-dependent inhibition of MAC formation via CP (half-maximal inhibitory concentration [IC50] 79&#xa0;nM), AP (344&#xa0;nM), and LP (67&#xa0;nM), with enhanced potency for inhibiting CP- and LP-mediated complement activation vs. APL-1. More efficient permeation of the BrM was observed with the antibody fragment than with the PEG-s molecule.<br><br>CONCLUSION: The antibody fragment is a potent and specific C3 inhibitor that displays dose-dependent inhibition of MAC formation across all three complement pathways and effectively crosses the BrM. In line with these results, the antibody fragment is being investigated in patients with GA. Graphical abstract available for this article.}, }
@article {pmid42372461, year = {2026}, author = {Canbulat, Z and Yalcin, E and Eroglu, Z and Khadra, R and Hasanreisoglu, M and Metin, O and Kizilel, S}, title = {Suppressing angiogenic phenotypes in retinal cell models through light-triggered anti-VEGF release from upconversion nanoparticle-loaded chitosan microgels.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {267}, number = {}, pages = {115936}, doi = {10.1016/j.colsurfb.2026.115936}, pmid = {42372461}, issn = {1873-4367}, abstract = {Anti-VEGF injections are effective for neovascular age-related macular degeneration (nAMD) but require frequent intravitreal dosing and provide limited spatiotemporal control. We engineered injectable chitosan-methacrylate (ChiMA) microgels that co-localize upconversion nanoparticles (UCNPs) with a photocaged anti-VEGF peptide to enable on-demand, near-infrared (980 nm)-triggered release. Colloidal UCNPs (β-NaYF4: Yb,Tm core/shell) were synthesized via a thermal decomposition method and subsequently embedded into visible-light-crosslinked ChiMA microgels together with a nitrobenzyl-linked anti-VEGF peptide. We quantified microgel morphology, swelling and injectability, peptide loading/release under near infra-red (NIR) irradiation (20 mW/cm[2]) and durations (30 min), and cytocompatibility in MIO-M1, RPE-1, and HUVEC cells. Anti-angiogenic activity was assessed by VEGF-driven scratch migration, tube formation, and signaling (HIF-1α, p-Akt, p-p38, occludin, ZO-1). Microgels with 10 wt% UCNPs showed the most efficient NIR-triggered release around 85%. Cytocompatibility assays indicated approximately 90% viability for UCNPs-loaded microgels, consistent with minimal cytotoxicity. In vitro, NIR irradiation of anti-VEGF-peptide-functionalized ChiMA microgels reduced endothelial migration and tube formation by 20% and 15%, respectively, relative to VEGF-stimulated controls. VEGF-responsive signaling was concomitantly decreased by 50%, and Akt phosphorylation was likewise halved compared to VEGF alone. These findings indicate that UCNPs-loaded ChiMA microgels enable non-invasive, repeatable, on-demand peptide delivery and attenuate pro-angiogenic pathways, supporting subsequent in vivo evaluation.}, }
@article {pmid42373197, year = {2026}, author = {Chauhan, R and Gupta, V and Natesh, S and Vohra, R and Agarwal, V and Ganapathi, PC and Bose, D and Loganathan, S}, title = {Safety and efficacy of biosimilar aflibercept MYL-1701P in diabetic macular oedema: 20-week extension results following the INSIGHT pivotal trial.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {2}, pages = {}, doi = {10.1136/bmjophth-2025-002637}, pmid = {42373197}, issn = {2397-3269}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/adverse effects ; *Diabetic Retinopathy/drug therapy/diagnosis/complications/physiopathology ; *Macular Edema/drug therapy/diagnosis/etiology/physiopathology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Female ; Male ; *Visual Acuity ; Intravitreal Injections ; Middle Aged ; Tomography, Optical Coherence ; Treatment Outcome ; *Biosimilar Pharmaceuticals/administration &amp; dosage/therapeutic use ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; }, abstract = {AIM: To evaluate the safety, efficacy and immunogenicity of biosimilar aflibercept (MYL-1701P) in participants with diabetic macular oedema who completed the 52-week global phase III trial and were enrolled in an extension study.<br><br>METHODS: In a 20-week, multicentre, open-label extension study at 15 sites in India, safety and efficacy were assessed in 52 participants who received three doses (2&#x2009;mg intravitreal) of MYL-1701P either continuing on MYL-1701P (continuation arm) or switching to it from reference aflibercept (switch arm). The primary outcome was safety, assessed by the incidence of treatment-emergent adverse events (TEAEs). The secondary outcome was efficacy and included change in visual acuity (best corrected visual acuity (BCVA) based on Early Treatment Diabetic Retinopathy Study (ETDRS) letters) and central subfield thickness ((CST); by spectral-domain optical coherence tomography).<br><br>RESULTS: Of the 52 participants enrolled, 46 completed week 76. Participants in both arms had comparable baseline characteristics. Incident TEAEs were noted in 9/29 participants in the continuation arm and 7/23 in the switch arm. No participant reported treatment-induced or boosted antidrug antibodies. The adjusted mean difference in BCVA change between baseline of parent study and week 76 (end of extension study) was -1.20 (2.95) ETDRS letters (90%&#x2009;CI -6.15 to 3.75) and from baseline of extension study to week 20 (week 76-parent study) was 1.59 (1.1) (90%&#x2009;CI -0.26 to 3.43). The adjusted mean difference in CST from baseline of parent study to week 76 was -15.9 (38.07) &#xb5;m (90%&#x2009;CI -80.47 to 48.62) and from baseline of extension study to its end was 13.53 (16.13) &#xb5;m (90%&#x2009;CI -13.86 to 40.92).<br><br>CONCLUSION: The study had certain limitations, including participation from one geographical area, an open-label design and small number of participants. Despite the limited number of exposures in the switch arm, it still constituted a reasonable exposure, and similar safety, efficacy and immunogenicity profiles were observed between those who continued receiving MYL-1701P and those who switched from reference aflibercept to MYL-1701P in the 20-week extension study of the pivotal trial.<br><br>TRIAL REGISTRATION NUMBER: NCT04674800, NCT03610646.}, }
@article {pmid42363829, year = {2026}, author = {Cui, X and Wen, D and Yu-Wai-Man, P and Li, X}, title = {ORBIT-AMD: Ordinal Risk, Bilateral Imaging, and Trajectory Learning for Age-Related Macular Degeneration in Multi-Cohorts.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e76361}, doi = {10.1002/advs.76361}, pmid = {42363829}, issn = {2198-3844}, support = {2024tjswmg-004//2024 Independent and Open Research Project of Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Medical University Eye Hospital/ ; }, abstract = {Age-related macular degeneration (AMD) is an ordered, bilateral, and longitudinal disease, yet many artificial intelligence systems treat it as static binary image classification. We developed ORBIT-AMD, a multimodal trajectory-learning framework integrating color fundus photography and optical coherence tomography, bilateral eye-graph attention, concept bottlenecks, ordinal staging, cause-specific discrete-time survival prediction, and protocol alignment. In a UK Biobank development/internal-testing cohort of 58 214 participants and 109 691 eyes, and an external Tianjin Medical University Eye Hospital cohort of 1996 participants and 3780 eyes, ORBIT-AMD achieved AUROC values of 0.984 internally and 0.975 externally for prevalent late-AMD detection. Five-year late-AMD progression prediction achieved AUROC values of 0.825 and 0.767, respectively. Calibration and threshold analyses showed cohort-dependent workload and absolute-risk behavior, supporting site-specific calibration assessment and clinical-workflow evaluation before deployment. The concept bottleneck provided auditable lesion-level explanations, but these outputs should be interpreted as structured predictive explanations rather than causal evidence. ORBIT-AMD provides a trajectory-aware framework for AMD risk stratification and review prioritization, with prospective validation required before clinical implementation.}, }
@article {pmid42364841, year = {2026}, author = {Alemán-González-Duhart, D and Mandujano-Ferrer, L}, title = {"Chrononutrition as a modulator of retinal metabolic resilience: A translational framework linking circadian biology to ocular disease".}, journal = {Biochimie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biochi.2026.06.017}, pmid = {42364841}, issn = {1638-6183}, abstract = {Chrononutrition-the alignment of feeding-fasting cycles with endogenous circadian rhythms-has emerged as a key determinant of systemic metabolic homeostasis. However, its relevance in ocular biology and retinal disease remains insufficiently defined within a translational framework. The retina, characterized by high energetic demand, intrinsic circadian oscillators, and tight coupling between mitochondrial function and redox balance, represents a uniquely vulnerable target to chrono-metabolic disruption. Here, we propose a mechanistically integrated model in which feeding timing acts as a systemic regulator of retinal metabolic resilience. We synthesize evidence demonstrating that circadian misalignment and irregular nutrient intake disrupt retinal bioenergetics, impair insulin signaling, and promote mitochondrial dysfunction and oxidative stress-hallmarks of major retinal diseases including diabetic retinopathy, age-related macular degeneration, and glaucomatous neurodegeneration. Particular emphasis is placed on nutrient-sensitive pathways, including peroxisome proliferator-activated receptors (PPARs), the AMPK/SIRT1 axis, and melatonin-mediated chronoregulation, as key interfaces linking metabolic cues with retinal circadian control. Importantly, we advance the concept that chrononutrition extends beyond dietary composition to function as a temporal modulator of disease-relevant pathways. Based on convergent experimental evidence, we outline a translational framework in which rhythm-aligned feeding patterns and time-dependent nutritional interventions may enhance mitochondrial efficiency, stabilize redox homeostasis, and improve retinal stress adaptation. Although direct clinical evidence remains limited, this paradigm provides a biologically grounded basis for the development of chrono-nutritional strategies as adjunctive approaches in retinal disease prevention and management.}, }
@article {pmid42365191, year = {2026}, author = {Pardhan, S and Wijewicrama, R and Tayo, B and Scolding, P and Pereira, A and Mason, J and Ahluwalia, S and Piyasena, MP}, title = {Exploring variations in Certificate of Vision Impairment (CVI) with geographical locations, deprivation indices, density of optometry practices and number of older people living in Mid and South Essex: an analysis of publicly available data.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42365191}, issn = {1476-5454}, abstract = {BACKGROUND: Examining factors that contribute to Certification of Vision Impairment (CVI) is important to enable an overview of progression, plan policies and distribution eye care services.<br><br>OBJECTIVES: To investigate associations between CVI, rate of change of CVI over a two-year period (2021-2023), percentage of people living in the 20% most deprived areas of Mid and South Essex (MSE), density of optometry practices and population of older people (>60 years) living in five sub-Integrated Care Board locations [Sub-ICB 1-5]) within MSE.<br><br>METHODS: Data were obtained from ICB databases and publicly available sources. Descriptive statistics were summarised to present data, and associations were explored using Spearman's rank correlation.<br><br>RESULTS: CVI increased over the 2021-2023 period with age-related macular degeneration being the most common cause. In 2023, different Sub-ICB areas showed varying burden with Sub-ICB-2 having the lowest number of CVI (29.2 per 100,000) while Sub-ICB-4 and Sub-ICB-5 showing the highest (75.3-76.3 per 100,000). Sub-ICB-4 also had the highest percentage of older people (>60 years). Strong positive association (&#x3c1;&#x2009;=&#x2009;0.90, p&#x2009;=&#x2009;0.0374) was found between rate of change of CVI and deprivation. Moderate positive associations between CVI with density of optometry practices (&#x3c1;&#x2009;=&#x2009;0.60, p&#x2009;=&#x2009;0.285); and the percentage of people over the age of 60 years (&#x3c1;&#x2009;=&#x2009;0.50, p&#x2009;=&#x2009;0.391).<br><br>CONCLUSIONS: CVI increases in areas with older population, and also in those living in 20% most deprived areas, highlighting the potential link between socio-economic factors and vision impairment. These factors are important for targeting interventions in specific areas to reduce the risk of blindness in MSE.}, }
@article {pmid42365435, year = {2026}, author = {Ozaki, A and Kawai, A and Akiba, R and Okayama, S and Ohno, N and Kajita, K and Masuda, T and Yokota, S and Ito, SI and Peiyan, D and Onoue, K and Yonemura, S and Kondo, M and Kurimoto, Y and Fu, Y and Mandai, M}, title = {Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.06.037}, pmid = {42365435}, issn = {1525-0024}, abstract = {Retinal organoids represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but the capacity of host cone bipolar cells in the primate macula to rewire with transplanted photoreceptors has not been established. In this study, we transplanted genome-edited ISL1[-/-] human retinal organoids lacking ON-bipolar cells into an acute laser-induced macular photoreceptor ablation nonhuman primate model. Using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography (FMERG), we demonstrate that host rod and cone bipolar cells actively extend dendrites toward grafted photoreceptors and form synaptic contacts, with evidence of functional signal transmission in a subset of transplanted eyes. Longitudinal, per-eye analyses revealed that host ON-bipolar responses improved in two of four eyes with ISL1[-/-] graft by up to 21.6% and remained stable for up to 2 years post-transplantation. Moreover, OFF-pathway connectivity showed potential progressive maturation, with delayed increase in d-wave after 13 months in one of those eyes. These findings provide the first demonstration of long-term anatomical host-graft synaptic integration in the primate macula, establishing that central cone bipolar circuits retain the capacity for durable rewiring with human stem cell-derived grafts. Our results highlight ISL1[-/-] retinal organoids as a promising approach for central vision restoration in macular degeneration.}, }
@article {pmid42366194, year = {2026}, author = {Tang, R and Liu, Y and Li, L and Wang, Z and Wang, J and Cui, W and Li, X and Fu, S and Wang, H}, title = {A multi-scale feature fusion network for CNV segmentation in SD-OCT images toward quantitative assessment of neovascular AMD.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-59215-1}, pmid = {42366194}, issn = {2045-2322}, support = {12426310, 12571534, 62571299, 12371492//National Natural Science Foundation of China/ ; ZR2025MS70//Natural Science Foundation of Shandong Province/ ; }, abstract = {Choroidal neovascularization (CNV) is a characteristic feature of neovascular age-related macular degeneration (AMD), a leading cause of irreversible visual impairment in the elderly. Accurate segmentation of CNV in spectral-domain optical coherence tomography (SD-OCT) images is crucial for quantitative assessment and treatment monitoring. However, the complex morphology and subtle boundaries of CNV lesions pose significant challenges for fully automated segmentation. In this study, we propose a deep learning-based multi-scale feature fusion network (MFF-Net) for precise and quantitative delineation of CNV in SD-OCT images. The MFF-Net integrates a multi-scale feature fusion module within an encoder-decoder architecture, effectively combining high-level semantic information with low-level details to strengthen skip connections and ensure efficient information flow. To improve boundary delineation, a gradient constraint is incorporated into the loss function, enhancing the network's ability to capture the upper edges of CNV. Furthermore, an optional interactive attention mechanism is introduced to address cases where fully automatic segmentation is insufficient. Ophthalmologists can provide minimal guidance by marking the four extreme points (top, bottom, left, and right) of the CNV region, from which a Gaussian attention heatmap is generated. This heatmap is then concatenated with the original OCT image to guide network retraining, refining the segmentation using interactive prior knowledge. Experimental results demonstrate that MFF-Net achieves reliable CNV segmentation performance. The automatic version of MFF-Net achieves the highest mean Intersection over Union (IoU) score of 0.686 among all compared methods and also outperforms them on other quantitative metrics. Remarkably, when equipped with the interactive attention module, the interactive version of MFF-Net achieves a substantial IoU improvement from 0.686 obtained by the automatic version to 0.802, demonstrating the effectiveness of the proposed interactive mechanism in enhancing segmentation accuracy. These results indicate that the proposed method provides an effective solution for accurate and efficient clinical quantitative assessment.}, }
@article {pmid42366374, year = {2026}, author = {Zhao, X and Yang, Y}, title = {Comparative efficacy and safety of Ranibizumab and Aflibercept for neovascular age-related macular degeneration: a systematic review and meta-analysis.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04988-2}, pmid = {42366374}, issn = {1471-2415}, abstract = {BACKGROUND: Ranibizumab and Aflibercept are widely used anti-VEGF agents for treating neovascular age-related macular degeneration (nAMD). This meta-analysis compares their efficacy, anatomical outcomes, treatment burden, and safety profiles.<br><br>METHODS: A systematic search of PubMed, Cochrane, and Google Scholar yielded 1,734 unique records. After screening and applying eligibility criteria, 11 studies were included. Primary outcomes were changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), proportion of dry retina, and injection frequency. Subgroup analyses and funnel plots assessed heterogeneity and publication bias.<br><br>RESULTS: Aflibercept showed a trend toward greater BCVA improvement compared with Ranibizumab, although the difference did not reach statistical significance (MD: 3.87 letters; 95% CI: -0.47 to 8.21; p&#x2009;=&#x2009;0.07; I[2]&#x2009;=&#x2009;97%). Similarly, CRT reduction tended to favor Aflibercept (MD: -85.35&#x2009;&#xb5;m; 95% CI: -178.45 to 7.75; p&#x2009;=&#x2009;0.09), but with substantial heterogeneity. The proportion of dry retina was significantly higher with Aflibercept (MD: 18.74%; 95% CI: 15.20 to 22.28; p&#x2009;<&#x2009;0.001), with no heterogeneity (I[2]&#x2009;=&#x2009;0%). Although Aflibercept was associated with fewer injections (MD: -0.91; 95% CI: -1.67 to -0.15; p&#x2009;=&#x2009;0.02), this finding was accompanied by substantial heterogeneity (I[2]&#x2009;=&#x2009;93%) and should be interpreted cautiously given the variability in study design, patient populations, and treatment regimens across included studies. Moreover, although the reduction in injection frequency was statistically significant, its magnitude was modest and its clinical importance remains uncertain given the high heterogeneity and very low certainty of evidence.<br><br>CONCLUSIONS: Both agents demonstrated comparable visual efficacy for nAMD. No statistically significant differences were observed for BCVA improvement or CRT reduction, and the available evidence does not establish clear superiority of either treatment. Although differences in dry retina outcomes and injection frequency were observed, these findings should be interpreted cautiously because of substantial heterogeneity, mixed study designs, and predominantly low-certainty evidence. Further standardized head-to-head studies are required to clarify the clinical relevance of these observations.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid42363196, year = {2026}, author = {Pan, M and Sunkara, N and Digbeu, BDE and Gupta, PK}, title = {Baseline visual acuity gaps in age-related macular degeneration: AREDS smokers and non-smokers.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-05035-w}, pmid = {42363196}, issn = {1471-2415}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Smoking is the only modifiable risk factor and is associated with faster AMD progression. While Age-Related Eye Disease Study (AREDS) supplements are recommended for intermediate AMD, their impact on visual acuity over time remains unclear.<br><br>OBJECTIVE: To describe baseline disparities and visual acuity trajectories in patients with intermediate dry AMD stratified by AREDS use and smoking status.<br><br>DESIGN: Retrospective observational study of patients with intermediate dry AMD conducted under IRB protocol 22-0267. Data collected from January 1, 2014 to January 1, 2024.<br><br>SETTING: Single academic medical center.<br><br>PARTICIPANTS: A total of 450 patients (759 eligible eyes) with intermediate dry AMD (ICD code H35.3192) were included. Patients were stratified by smoking status and AREDS use. Participants with fewer than three ophthalmology visits during the 10-year study period were excluded.<br><br>EXPOSURE: AREDS supplementation (AREDS1 or AREDS2) and smoking status (current/former vs. never).<br><br>MAIN OUTCOMES AND MEASURES: Visual acuity measured in Logarithm of the Minimum Angle of Resolution (LogMAR) at first and final clinic visits. ANOVA, Chi-square tests, and mixed effect regression models were used for analysis. Changes in LogMAR over time were calculated descriptively.<br><br>RESULTS: Among 450 patients (mean age, 82.32 years), 255 were smokers (423 eyes) and 195 were non-smokers (336 eyes). Baseline vision was better in non-smokers (mean LogMAR 0.28; SD 0.28) and smokers (mean LogMAR 0.30; SD 0.33) taking AREDS compared to non-smokers (mean LogMAR 0.48; SD 0.44) and smokers (mean LogMAR 0.45; SD 0.47) not taking AREDS (P&#x2009;<&#x2009;0.0001). All groups experienced visual acuity decline from baseline with no significant differences in final visual acuity among the groups in a mean follow up period of 3.62 years. In a sub-analysis of greater than 5 years follow up mean years of 6.93&#x2009;&#xb1;&#x2009;1.55 years), a statistically significant difference in final LogMAR values across groups was observed (p&#x2009;=&#x2009;0.033). The Smokers &amp; AREDS group demonstrated the best final visual acuity (mean 0.39, SD 0.40), followed by Smokers &amp; No-AREDS (mean 0.44, SD 0.43), Non-smokers &amp; AREDS (mean 0.46, SD 0.47), and Non-smokers &amp; No-AREDS (mean 0.72, SD 0.60).<br><br>CONCLUSIONS AND RELEVANCE: These results suggest that less than 5 years AREDS users had larger decline in vision from baseline, protective associations of AREDS supplementation may become more discernible over longer follow-up horizons. Real-world observational findings should be interpreted cautiously and do not contradict AREDS efficacy shown in randomized trials.}, }
@article {pmid42363252, year = {2026}, author = {Sun, X and Dai, H and Chen, Y and Sun, X and Tao, L and Xiao, J and Han, M and Zhao, M and Wang, L and Schulze, A and Schmidt-Ott, UM and Zhao, M and Zhang, X and Wang, Z and Leal, S and Wei, W and , }, title = {Intravitreal aflibercept 8 mg in patients with neovascular age-related macular degeneration from China: 48-week results from the PULSAR trial.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00876-5}, pmid = {42363252}, issn = {2056-9920}, abstract = {BACKGROUND: PULSAR (NCT04423718) was a global, phase 3, randomized, double-masked, non-inferiority study of adults with neovascular age-related macular degeneration (nAMD). Patients were randomized 1:1:1 to receive aflibercept 8 mg every 12 (8q12), or 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following 3 initial monthly doses. This subgroup analysis investigated the efficacy and safety of aflibercept 8 mg vs. aflibercept 2 mg in patients from China with nAMD from the PULSAR trial.<br><br>METHODS: This exploratory analysis evaluated the change from baseline in best-corrected visual acuity (BCVA), central retinal thickness (CRT), durability, and safety outcomes through week 48 in patients from China. All results were descriptive in nature.<br><br>RESULTS: Least squares (LS) mean (95% confidence interval [CI]) change from baseline in BCVA at week 48 was +&#x2009;13.2 (+9.0, +17.4), +9.7 (+5.8, +13.7), and +&#x2009;10.0 (+6.9, +13.1) letters for patients from China in the 8q12 (n&#x2009;=&#x2009;31), 8q16 (n&#x2009;=&#x2009;31), and 2q8 (n =&#x2009;39) groups, respectively. LS mean (95% CI) change from baseline in CRT (&#xb5;m) at week 48 was -167 (-183, -151), -166 (-195, -137), and -180 (-195, -165) for patients in the 8q12, 8q16, and 2q8 groups, respectively. Randomized dosing intervals were maintained by 88.5% and 73.1% of patients in the 8q12 and 8q16 groups, respectively. The incidence of ocular treatment-emergent adverse events was similar across treatment groups.<br><br>CONCLUSIONS: In patients with nAMD from China, aflibercept 8&#xa0;mg administered over extended dosing intervals demonstrated efficacy and a safety profile consistent with that observed with aflibercept 2&#xa0;mg, in line with the overall PULSAR cohort.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, TRN NCT04423718. Registration date 8 June 2020.}, }
@article {pmid42363601, year = {2026}, author = {Kim, J and Min, S and Yum, M and Park, S and Park, S and Shin, D and Park, SW and Park, SY and Do, YJ and Park, JH and Lee, DK}, title = {Cell-penetrating asymmetric siRNA targeting MyD88 suppresses inflammasome-driven ocular degeneration and angiogenesis.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.06.036}, pmid = {42363601}, issn = {1525-0024}, abstract = {Chronic inflammation mediated by innate immune signaling contributes to retinal degeneration, pathological angiogenesis, and ocular surface damage in age-related macular degeneration (AMD) and dry eye disease (DED). Myeloid differentiation primary response 88 (MyD88), a central adaptor downstream of Toll-like and IL-1 receptors, integrates NF-κB-dependent cytokine induction and inflammasome priming. In this study, we developed OLX10212, a chemically optimized palmitoyl-conjugated, cell-penetrating asymmetric siRNA (cp-asiRNA) that silences MyD88 without an external delivery vehicle. Following intravitreal administration, OLX10212 achieved broad retinal distribution and sustained MyD88 knockdown in mice and rabbits. In sodium iodate- and Alu RNA-induced geographic atrophy models, OLX10212 preserved retinal architecture and electroretinographic function while suppressing NLRP3-associated transcripts, consistent with the inhibition of inflammasome signaling. A single intravitreal dose reduced lesion volume in laser-induced choroidal neovascularization models in mice and cynomolgus monkeys. Vascular endothelial growth factor (VEGF) expression was also decreased in mice, suggesting that OLX10212 modulates pro-angiogenic inflammatory pathways. Topical administration further ameliorated corneal epithelial injury and inflammatory cytokine expression in a benzalkonium chloride-induced DED model. A phase 1 clinical trial of intravitreal OLX10212 in patients with neovascular AMD is ongoing, and phase 2 studies are planned.}, }
@article {pmid42360467, year = {2026}, author = {Honjo, J and Mukai, R and Itagaki, K and Kato, Y and Tsuchiya, Y and Shioya, T and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sekiryu, T}, title = {Long-term analysis of fibrosis in neovascular age-related macular degeneration: A 7-year follow-up.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42360467}, issn = {1435-702X}, abstract = {PURPOSE: We investigated the 7-year incidence rate of macular fibrosis and its related factors in Japanese patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor therapy.<br><br>METHODS: This retrospective study involved 301 eyes of 301 treatment-na&#xef;ve Japanese patients. Macular fibrosis was diagnosed using color fundus photography and spectral-domain optical coherence tomography. We compared clinical parameters between eyes with and without fibrosis. Fibrosis incidence, lesion morphology, and visual outcomes were assessed across nAMD subtypes. A multivariable logistic regression analysis was performed to identify independent factors associated with fibrosis development.<br><br>RESULTS: Fibrosis development was observed in 73 eyes (24.3%). Fibrosis incidence was significantly higher in type 2 macular neovascularization (MNV; 42.1%) than in type 1 MNV (18.1%) and polypoidal choroidal vasculopathy (20.6%). The fibrosis group had significantly worse baseline logarithm of the minimum angle of resolution visual acuity, greater central macular thickness (CMT), and higher incidences of intraretinal fluid (IRF), subretinal hyperreflective material, and retinal hemorrhage than the non-fibrosis group. The most common fibrosis subtype was mixed-type fibrosis, with subretinal fibrosis being more prevalent in type 2 MNV than in type 1 MNV. Visual acuity significantly improved in the non-fibrosis group but not in the fibrosis group. Final visual acuity did not significantly differ across nAMD subtypes in the fibrosis group. In multivariable analysis, worse baseline visual acuity, greater CMT, retinal hemorrhage, IRF, and nAMD subtype were independently associated with fibrosis development.<br><br>CONCLUSION: Macular fibrosis occurred across all nAMD subtypes and was associated with poor visual outcomes. Worse baseline visual acuity, greater CMT, retinal hemorrhage, IRF, and nAMD subtype were independently associated with fibrosis development. Thus, baseline disease severity and active exudative lesion characteristics may contribute to fibrotic progression in nAMD.}, }
@article {pmid42361041, year = {2026}, author = {Ozaki, E and Aktas, S and Mulfaul, K and Brennan, K and Roubeix, C and Palko, S and Robb, K and Ou Yang, TH and Schanne-Klein, MC and Toidze, A and Watson, A and Cahill, M and Westenskow, PD and Feenstra, D and Doyle, SL}, title = {Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {26}, pages = {e2519056123}, doi = {10.1073/pnas.2519056123}, pmid = {42361041}, issn = {1091-6490}, support = {Immunolgy incubator programme//F. Hoffmann-La Roche/ ; SFI 21/SPP/3732//Science Foundation Ireland (SFI)/ ; M2023011//BrightFocus Foundation (BFF)/ ; }, mesh = {Animals ; *Fibroblasts/metabolism/pathology ; Fibrosis/metabolism ; Mice ; *Collagen/metabolism ; *Retina/metabolism/pathology ; Extracellular Matrix/metabolism ; *Macular Degeneration/pathology/metabolism ; Periostin ; Disease Models, Animal ; Collagen Type I/metabolism/genetics ; Humans ; Cell Adhesion Molecules ; }, abstract = {Fibrosis is the end-stage of a maladaptive process that occurs when the body's normal wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage of neovascular age-related macular degeneration (nAMD), the most common cause of central vision loss in people over the age of 50. The cellular sources of excess extracellular matrix (ECM) contributing to subretinal fibrosis are unknown, as is the heterogeneity of cells involved in the fibrotic process. Here we identify cells contributing to subretinal fibrosis by using Col1a1-YFP reporter mice to noninvasively image collagen production in real-time in vivo in two disease models, 1) a resolving retinal injury model and 2) a fibrotic model of subretinal disease. We create a collagen-producing eye cell atlas for subretinal injury and demonstrate subretinal fibroblast heterogeneity in healthy, resolving, and fibrotic tissue. We identify distinct molecular characteristics of general repair/resolving fibroblast populations versus pathogenic pro-fibrotic collagen-producing fibroblasts. Integration of this collagen-producing eye cell atlas with a published collagen-producing lung cell atlas shows conserved pro-fibrotic fibroblasts in both organs, yet also uncovers tissue-specific fibroblast populations unique to subretinal fibrosis. A Fap[+]Fgl2[+] fibroblast population significantly expands in subretinal fibrosis that expresses the highest levels of collagens and distinctively expresses ECM components Periostin, Col15a1 and Col6a5. Immunolabeling of mouse and human-donor eye tissue support the fibroblastic expression and perivascular location of periostin as clearly distinguishing between bona fide fibrosis and early disease in nAMD. Our collagen-producing eye cell atlas is a valuable resource for studying distinct fibroblast subsets in homeostasis, early injury, and fibrosis.}, }
@article {pmid42362585, year = {2026}, author = {Chan, KS and Cheng, BT and Banker, MM and Zee, PC and Mirza, RG}, title = {Daylight saving time transition and new-onset retinal vascular disease: a nationwide cohort study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-55281-7}, pmid = {42362585}, issn = {2045-2322}, abstract = {Daylight saving time (DST) transitions lead to disruptions in circadian rhythm, and studies have identified an association between DST transitions and cardiovascular events. Changes in retinal microvasculature can reflect systemic cardiovascular health. This study investigated the relationship between DST transitions and retinal vascular disease. Patients aged 18-64 years old enrolled in the Merative MarketScan Commercial Database between 2012 and 2014 were identified. Incidence of new diagnosis of retinal artery occlusion (RAO), retinal vein occlusion (RVO), proliferative diabetic retinopathy (PDR), and neovascular age-related macular degeneration (nvAMD) were determined after autumn DST transition, spring DST transition, and a summer or winter control period. Survival analysis via Kaplan Meier curves and Cox proportional hazards models were used to determine the effect of variables of interest on new-onset retinal vascular disease during one-week and one-month periods following DST transition. We identified 12,640,343 patients who met inclusion criteria. With a summer control period, there was lower risk of RVO (adjusted hazard ratio [98.75% confidence interval]: 0.84 [0.72-0.99], P = 0.033), and PDR (0.83 [0.73-0.94], P = 0.001) in the month following autumn DST transition. There was higher risk of PDR (1.34 [1.19-1.50], P<0.0001) and nvAMD (1.24 [1.03-1.50], P = 0.015) in the month following spring DST transition. With a winter control period, there was lower risk of RAO (0.75 [0.60-0.94], P = 0.005), RVO (0.66 [0.53-0.82], P<0.0001), PDR (0.61 [0.51-0.72], P<0.0001), and nvAMD (0.64 [0.49-0.83], P < 0.0001) in the month following autumn DST transition. Further investigation into the effects of circadian disruption on ocular health is warranted.}, }
@article {pmid42362987, year = {2026}, author = {Sun, G and Zeraatkar, D and Man, REK and Sivaprasad, S and Borrelli, E and Steel, DH and Guymer, RH and Wong, TY and Wykoff, CC and Ma, J and Chaudhary, V}, title = {Vision-related quality of life in non-neovascular age-related macular degeneration: a protocol for systematic review and meta-analysis.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42362987}, issn = {1476-5454}, abstract = {Age-related macular degeneration (AMD) is a progressive retinal disease and a major cause of visual impairment in older adults. Non-neovascular AMD (non-nAMD), the more common phenotype, can substantially impair vision-related quality of life (QoL) even when visual acuity remains relatively preserved. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) is the most widely used instrument for assessing vision-related QoL in AMD. However, QoL in non-nAMD has not been systematically synthesised across disease stages and settings. This review aims to summarise vision-related QoL in treatment-naive patients with non-nAMD, examine how QoL varies by disease stage and measurement instrument and identify study-level factors associated with QoL differences. We will search MEDLINE, Embase, EBM Reviews and APA PsycINFO from inception for original studies reporting mean values or mean differences, with corresponding variability, for overall or subscale scores from the NEI-VFQ-25 or other validated vision-related QoL instruments. Two reviewers will independently screen studies, extract data and assess risk of bias using the appropriate Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Random-effects meta-analyses will be conducted to pool NEI-VFQ-25 composite and subscale scores by non-nAMD stage and, where available, to estimate differences between stages or versus controls. Instrument-specific meta-analyses will be performed for other QoL measures when feasible and standardised metrics will be used to combine instruments assessing similar constructs but using different scales. Meta-regression will explore whether QoL varies with study-level characteristics. The findings will clarify the functional burden of non-nAMD and support future clinical research and trial design.}, }
@article {pmid42346801, year = {2026}, author = {Shad, HH and Dörschmann, P and Hautmann, SL and Roider, J and Klettner, A}, title = {Marine-Derived Fucoidan Modulates Pathways Associated with Age-Related Macular Degeneration in Cellular and Zebrafish Models.}, journal = {Marine drugs}, volume = {24}, number = {6}, pages = {}, pmid = {42346801}, issn = {1660-3397}, mesh = {Animals ; *Polysaccharides/pharmacology ; Zebrafish ; Retinal Pigment Epithelium/drug effects/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; Oxidative Stress/drug effects ; Swine ; Anti-Inflammatory Agents/pharmacology ; Cytokines/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Antioxidants/pharmacology ; }, abstract = {Fucoidan, a sulfated polysaccharide, is known for its beneficial bioactive effects, for example antioxidant, anti-inflammatory, and vascular modulatory effects. Such a bioactive compound may also be useful for treating neurodegenerative diseases like age-related macular degeneration (AMD). Our research focuses on AMD-related pathomechanisms using primary porcine retinal pigment epithelium (RPE) cells in vitro and zebrafish (Danio rerio) models in vivo. We tested the bioactivity of a commercially available fucoidan (FVs) from bladderwrack with regard to pathomechanisms of AMD. We performed multiplex assays, RT-qPCR and fluorescence-based assays for the formation of nitric oxide (DAF-FM assay) and reactive oxygen species (DCF-DA assay) to analyze angiogenesis-related chemokines and pro-inflammatory cytokines as well as protection against oxidative stress and inflammatory insult. Our results showed that FVs significantly reduced the secretion of pro-angiogenic vascular endothelial growth factor A (VEGF-A) and follistatin as well as the pro-inflammatory cytokines interleukin 8 (IL-8) after lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC) induction. Interleukin 6 (IL-6) was also reduced in the supernatant of the RPE cells. Additionally, in zebrafish, fucoidan decreased the production of NO and ROS. Gene expression of zebrafish embryos revealed anti-inflammatory effects by suppressing pro-inflammatory genes and significantly downregulating, e.g., interleukin 1 beta (IL-1β). These findings indicate modulation of oxidative stress, inflammatory responses, and VEGF secretion of the used FVs. This study demonstrates that fucoidan possesses AMD-relevant bioactivities in vitro and in vivo, suggesting fucoidan warrants further investigation in AMD-related research and related pathological mechanisms.}, }
@article {pmid42347571, year = {2026}, author = {Tlaiss, Y and Warrak, J and Warrak, E}, title = {Ultra-Early OCT Changes After Intravitreal Injection: Evidence Consistent with Transient Mechanical Compression.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/vision10020035}, pmid = {42347571}, issn = {2411-5150}, abstract = {(1) Background: Ultra-early optical coherence tomography (OCT) changes following intravitreal injection may reflect transient mechanical compression rather than pharmacologic effects; however, this temporal profile has not been rigorously characterised with appropriate statistical methodology. (2) Methods: In this prospective observational study, 40 eyes of 40 consecutive patients (one per patient) with macular edema secondary to neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or chronic central serous retinopathy (CSR) underwent intravitreal bevacizumab (n = 35) or triamcinolone acetonide (n = 5). Goldmann applanation tonometry and spectral-domain OCT were performed at baseline, 2-5 min, 15 ± 5 min, 24 h, and 48 h post-injection. Repeated-measures ANOVA with Greenhouse-Geisser correction, linear regression, and Spearman rank correlation were applied. (3) Results: Central subfield thickness (CST) decreased markedly at 15 ± 5 min (mean -24.8 ± 11.5%; 95% CI: -28.5% to -21.1%; p < 0.001; partial η[2] = 0.70), with near-complete rebound by 48 h (-1.0%; p = 0.400). Peak intraocular pressure (IOP) elevation correlated with CST reduction (Spearman rs = 0.61; 95% CI: 0.39-0.77; p < 0.001), and baseline CST predicted thinning magnitude (R[2] = 0.52; p < 0.001). (4) Conclusions: Ultra-early OCT thinning after intravitreal injection is consistent with transient mechanical compression. Retinal thickness measurements within 48 h post-injection should be interpreted with caution when assessing treatment response, as early anatomic reduction may not reflect pharmacologic efficacy.}, }
@article {pmid42347990, year = {2026}, author = {Borrelli, E and Neri, G and Berni, A and Olivieri, C and Chhablani, J and Corradetti, G and Dolz-Marco, R and Reiter, GS and Zur, D and Bandello, F and Reibaldi, M}, title = {Review of emerging imaging findings to reveal a broader spectrum of lesions in AMD.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42347990}, issn = {1435-702X}, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in developed countries, with prevalence expected to reach nearly 288 million by 2040. Accurate classification of AMD is critical for patient care and clinical research, guiding prognosis, therapeutic strategies, and the design of clinical trials. A widely adopted framework, the Beckman classification, stratifies AMD based primarily on color fundus photography (CFP) findings, defining stages from early to late disease. While simple and clinically applicable, such systems do not account for several key phenotypes revealed by advances in multimodal imaging. Such novel phenotypes include reticular pseudodrusen (RPD), acquired vitelliform lesions (AVL), non-exudative macular neovascularization (MNV), incomplete retinal pigment epithelium and outer retina atrophy (iRORA), and non-neovascular exudative fluid. Recent imaging modalities-including optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA)-have uncovered features with important prognostic implications that are currently misclassified with respect to AMD. For example, eyes with RPD or AVL in the absence of drusen are currently misclassified as "early AMD" or excluded altogether, despite their high risk of progression. Similarly, the ambiguous status of non-exudative MNV, which carries both protective and harmful potential, highlights the need for greater granularity. The Classification of Atrophy Meetings (CAM) group has also introduced refined OCT-based definitions such as iRORA and cRORA, underscoring early degenerative changes that precede geographic atrophy. Moreover, novel entities like non-neovascular intraretinal or subretinal fluid challenge the assumption that exudation is synonymous with neovascular AMD. This review synthesizes recent evidence highlighting the limitations of current classification systems in light of these advances. Furthermore, we emphasize that intermediate AMD, currently treated as a uniform category, actually encompasses highly heterogeneous phenotypes with distinct risks and trajectories. A more nuanced, imaging-integrated classification system is urgently needed to improve disease staging, identify high-risk eyes, and ensure appropriate patient selection for emerging therapies. Such a framework would not only better reflect the complex natural history of AMD but also facilitate the regulatory shift toward continuous, quantitative endpoints in clinical trials.}, }
@article {pmid42348183, year = {2026}, author = {Wakefield, ZR and Reddy, AK and Wang, SY}, title = {Loneliness, Blindness, and Major Eye Disease.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.2168}, pmid = {42348183}, issn = {2168-6173}, }
@article {pmid42350446, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX}, title = {Localized interdigitation zone thinning in age-related macular degeneration.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-57489-z}, pmid = {42350446}, issn = {2045-2322}, abstract = {To assess prevalence and associations of localized thinnings of the interdigitation zone ("IZT") without adjacent drusen or reticular pseudodrusen in a general population, affected by age-related macular degeneration (AMD), or free of any other retinal disease. On optical coherence tomographic images, taken from the macula of participants of the population-based Beijing Eye Study, we searched for IZTs. The study population included 1271 eyes (mean age:64.7 ± 9.8 years; range:50-91 years). IZT prevalence increased from 2/442 (0.5%;95%CI:0.0,1.0) in the normal group to 49/543 (9.0%;95%CI:7.0,11.0), 90/275 (32.7%;95%CI:27.2,38.2), and 9/11 (81.8%;95%CI:55.0,100) in eyes with early, intermediate or late AMD (geographic atrophy), respectively. IZTs were spatially associated with ellipsoid zone (EZ) defects (114/150 (76.0%) eyes), external limiting membrane (ELM) defects (92/150 (61.3%) eyes), any intraretinal hyperreflective foci (iHRF) (143/150 (95.2%) eyes), iHRFs in the outer nuclear layer or beyond (111/150 (74.0%) eyes), macular hypopigmentation (76/150 (50.7%) eyes), and RPE hypertransmission (46/150 (30.7%) eyes), in addition to a non-spatial association with a higher prevalence of outer nuclear layer thinning (48/150 (32.0%) eyes). Higher IZT prevalence correlated (multivariable analysis) with higher AMD stage (OR:1.28;95%CI:1.08,1.51;P = 0.004), and higher prevalences of EZ defects (OR:7.97;95%CI:4.20,15.1;P < 0.001), iHRFs with a smoke-like appearance in the outer nuclear layer (OR:2.52;95%CI:1.32,4.82;P = 0.005), RPE hypertransmissions (OR:12.6;95%CI:2.92,54.7;P < 0.001), and outer nuclear layer thinning (OR:27.5;95%CI:6.12,123;P < 0.001). IZTs are a common feature of AMD including the early AMD stage. Their spatial association with defects in the overlying EZ, IHRFs and macular hypopigmentations may warrant further research of a potential involvement of an intraretinal RPE cell migration in the IZT etiology.}, }
@article {pmid42350598, year = {2026}, author = {Çelenk, E and Torun, IM}, title = {Evaluating the educational quality and reliability of YouTube videos on red light therapy for eye diseases.}, journal = {Lasers in medical science}, volume = {41}, number = {1}, pages = {}, pmid = {42350598}, issn = {1435-604X}, mesh = {Humans ; *Eye Diseases/therapy ; *Social Media ; *Video Recording/standards ; Red Light ; Reproducibility of Results ; *Ophthalmology/education ; *Patient Education as Topic ; }, abstract = {To investigate the use of YouTube videos as an educational and informational resource regarding the use of red light therapy in eye diseases. On May 1, 2025, a comprehensive search was conducted on the YouTube platform (https://www.youtube.com) using the keywords "Red light therapy in eye disease" and "Use of red light therapy in eye diseases for patient information". Videos under 60 s in duration, those lacking audio, duplicate entries, irrelevant content, and videos with disabled comment sections were excluded from the analysis. These exclusion criteria were predefined prior to data collection. Following video selection (E.Ç., M.T.), all videos were independently evaluated by two ophthalmologists, and statistical analyses were performed using the finalized dataset. Parameters assessed included total views, number of comments, likes, time elapsed since upload, video duration, view rate, interaction index, video source, and content characteristics. In addition, videos were categorized according to quality level based on Global Quality Score (GQS) scores as low-to-moderate quality (GQS < 4) and high quality (GQS ≥ 4). Comparisons were then performed according to quality category with respect to uploader source, video purpose, and engagement-related parameters. Out of 110 YouTube videos reviewed, 53 were excluded based on predefined criteria. The remaining 57 videos covered myopia (22.8%), dry eye (33.3%), diabetic retinopathy (12.3%), and age-related macular degeneration (31.6%). Inter-rater agreement was high (mDISCERN ICC: 0.952; JAMA ICC: 0.923; GQS ICC: 0.890). Videos uploaded by physicians had significantly higher mDISCERN, JAMA, and GQS scores. Educational videos had higher mDISCERN and JAMA scores than patient-information videos. A moderate positive correlation was found between the number of likes and the interaction index (r = 0.458, p < 0.01). The interaction index was not significantly associated with mDISCERN, JAMA, or GQS scores, indicating that engagement metrics were not reliable indicators of informational quality. Among disease categories, age-related macular degeneration videos had the highest mean quality scores, although the differences were not statistically significant. Most videos were classified as low-to-moderate quality (82.5%), while 17.5% were classified as high quality. High-quality videos had significantly higher view counts and like counts than low-to-moderate quality videos. The overall quality and formal reliability of YouTube videos on red light therapy in ophthalmology were low to moderate. Physician-uploaded and educational videos provided higher-quality information. Although high-quality videos showed greater engagement, popularity metrics were not reliable indicators of informational quality. More evidence-based and accessible video content is needed to support patient education.}, }
@article {pmid42351411, year = {2026}, author = {Sharifzadeh, M}, title = {Melanin Correction Is Essential for Quantitative Autofluorescence-Based Measurement of Macular Pigment.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {12}, pages = {}, doi = {10.3390/diagnostics16121751}, pmid = {42351411}, issn = {2075-4418}, abstract = {Macular pigment optical density (MPOD) is widely measured by dual-wavelength autofluorescence imaging (AFI) because the method is noninvasive, image-based, and clinically practical. AFI-derived MPOD and macular pigment optical volume (MPOV) are increasingly used as retinal biomarkers in clinical research, supplementation studies, disease-risk interpretation, and population-based comparisons. However, conventional dual-wavelength AFI assumes that posterior absorbers other than macular pigment (MP), particularly melanin, are negligible or sufficiently stable not to bias the measurement. This assumption may limit the diagnostic and biomarker reliability of AFI-derived MP metrics. This manuscript presents a focused biological, optical, and mathematical analysis of AFI-based MP quantification. The foundational AFI literature, the melanin imaging literature, retinal pigment epithelium (RPE) pigment biology, and related optical modeling concepts were examined to evaluate where melanin enters the AFI signal pathway, how it may confound MPOD and MPOV, and how a melanin-sensitive baseline could improve quantitative specificity within the AFI domain. Conventional dual-wavelength AFI estimates MP indirectly from attenuation of RPE lipofuscin autofluorescence under excitation wavelengths that differ in MP absorption. Because melanin is located in the RPE and choroid, varies with retinal location, age, and pigmentation, and can influence the same excitation and detection pathway, unmeasured melanin can become embedded in the apparent MPOD signal. Under these conditions, reported MPOD and derived MPOV are better understood as model-dependent estimates whose quantitative specificity may vary across subjects, retinal locations, devices, and studies. This has direct implications for diagnostic interpretation, normative databases, cross-subject comparison, supplementation-response studies, and biomarker-based retinal assessment. Melanin correction is not a minor refinement of AFI-based MP quantification. It is likely necessary when AFI-derived MP metrics are intended to be interpreted as quantitatively specific retinal biomarkers rather than conditionally approximate optical estimates. A melanin-corrected AFI framework, based on introducing a melanin-sensitive baseline wavelength outside the principal MP absorption range, offers a path toward more reliable MPOD and MPOV interpretation in clinical, diagnostic, and supplementation-related studies.}, }
@article {pmid42351718, year = {2026}, author = {Tîrziu, AT and Romanescu, M and Ciordas, PD and Mercea, N and Munteanu, M and Horhat, FG and Chis, AR and Preda, MA}, title = {Metagenomic Profiling of the Gut Microbiome in Age-Related Macular Degeneration-A Pilot Study.}, journal = {Biomedicines}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/biomedicines14061290}, pmid = {42351718}, issn = {2227-9059}, support = {CNFIS-FDI-2024-F-0451//Consiliul National pentru Finantarea Invatamantului Superior/ ; }, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease involving inflammatory, metabolic, and genetic factors. Increasing evidence suggests that the gut microbiome may contribute to systemic pathways involved in retinal homeostasis. This exploratory pilot study investigated gut microbiome alterations in AMD patients and controls using long-read whole-genome sequencing. Methods: Bacterial DNA was extracted from fecal samples and analyzed using Oxford Nanopore sequencing, followed by taxonomic profiling, alpha and beta diversity analyses, and differential abundance testing. Results: AMD patients showed significantly reduced microbial diversity, reflected by lower richness, Shannon and Simpson indices. Species-level beta diversity analyses revealed significant differences in microbial community composition, particularly with Bray-Curtis metrics, alongside increased inter-individual microbial heterogeneity in AMD samples. Differential abundance analyses identified the depletion of several potentially beneficial commensal taxa, including Faecalibacterium prausnitzii and Parabacteriodes distasonis, whereas Staphylococcus aureus was enriched in AMD patients. Comparisons between wet and dry subtypes showed no significant differences in alpha or beta diversity. Conclusions: Overall, the findings support the presence of gut microbial dysbiosis in AMD characterized by reduced diversity, abundance-driven community shifts, and increased microbiome heterogeneity. Given the small cohort size, cross-sectional design and lack of functional analysis, these results should be considered preliminary and hypothesis-generating.}, }
@article {pmid42351905, year = {2026}, author = {Mohanty, S and Batabyal, S and Kim, S and Carlson, M and Dibas, A}, title = {Therapeutic Efficacy of Multi-Characteristic Opsin Gene Therapy in a Mouse Model of Stargardt Disease.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {13}, number = {6}, pages = {}, doi = {10.3390/bioengineering13060660}, pmid = {42351905}, issn = {2306-5354}, support = {R44EY025905/EY/NEI NIH HHS/United States ; }, abstract = {Optogenetic gene therapy-based treatment offers a unique approach to bypass dysfunctional or degenerated photoreceptors in retinal degenerative disorders. Ambient light-activatable multi-characteristic opsin (MCO) targeted to bipolar cells of the retina has demonstrated partial vision restoration in animal models of retinitis pigmentosa (RP). Here, we describe the potential therapeutic efficacy of intravitreally delivered AAV-carried MCO-010 in a mouse model of Stargardt disease. MCO-010 treatment led to significantly improved behavioral outcomes in the visually guided radial arm water maze. Furthermore, longitudinal optical coherence tomographic imaging showed that the MCO-010 treatment led to no notable change in the retina thickness. Furthermore, the MCO-010-treated mice exhibited higher electrophysiological responses compared to the control group. Together, these findings demonstrate potential vision-restoring and disease-modifying aspects of ambient light-activatable intravitreal MCO-010 therapy.}, }
@article {pmid42352019, year = {2026}, author = {Yang, Y and Deng, Y and Li, X and Zhou, P and Peng, Q and Ratnayaka, JA}, title = {Epigenetic-Mitochondrial-Metabolic Crosstalk in Retinal Pigment Epithelium (RPE) Dysfunction in Age-Related Macular Degeneration (AMD).}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, doi = {10.3390/antiox15060713}, pmid = {42352019}, issn = {2076-3921}, support = {82274341//National Natural Science Foundation of China/ ; 2024JJ5304, 2025JJ60633//Natural Science Foundation of Hunan Province/ ; 2024JK2122//Key Research and Development Program of Hunan Province/ ; 23A0278, 23B0346//Scientific research project of Hunan Provincial Department of Education/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults and is characterized by progressive dysfunction of the retinal pigment epithelium (RPE). Although genetic susceptibility and environmental exposure both contribute to disease risk, the mechanisms through which chronic metabolic and oxidative stress are integrated into sustained RPE dysfunction remain incompletely understood. Increasing evidence from human AMD donor tissue and experimental RPE models indicates that epigenetic regulation operates at the interface between mitochondrial dysfunction, redox imbalance, and transcriptional remodeling. This review synthesizes current findings on DNA methylation, chromatin accessibility, histone modification, and RNA-based regulation in AMD, with emphasis on their metabolic and mitochondrial context. Studies in human AMD-RPE demonstrate that epigenetic alterations are generally selective rather than global and frequently involve pathways related to mitochondrial maintenance, lipid metabolism, oxidative stress responses, and cellular homeostasis. Mechanistically, mitochondrial dysfunction and reactive oxygen species (ROS) may influence epigenetic regulation through altered Nicotinamide adenine dinucleotide (NAD[+]) availability, acetyl-CoA metabolism, redox-sensitive chromatin regulation, and modulation of DNA methyltransferase and histone deacetylase activity. Redox-sensitive pathways, including antioxidant signaling, further connect mitochondrial stress to adaptive or maladaptive transcriptional responses in the RPE. Importantly, while several interactions discussed are supported by findings in human AMD tissue, other components of the proposed epigenetic-mitochondrial-redox framework remain inferential or model-based and require further validation. Rather than acting as isolated disease triggers, epigenetic changes are more likely to function as stress-responsive regulatory layers that stabilize transcriptional states over time in a long-lived post-mitotic tissue. We further discuss unresolved questions regarding causality, reversibility, therapeutic feasibility, and stage-specific intervention strategies. Collectively, this framework positions the epigenetic-mitochondrial-redox axis as a unifying model for understanding RPE vulnerability and AMD progression.}, }
@article {pmid42352071, year = {2026}, author = {Chen, TC and Vo, TL and Tsou, SC and Wang, HD and Wang, I and Chuang, CJ and Lin, HW and Chang, YY}, title = {Tetrahydrocurcumin Attenuates NaIO3-Induced Retinal Oxidative Injury via Suppression of NOX2-Derived ROS-Mediated Apoptosis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, doi = {10.3390/antiox15060765}, pmid = {42352071}, issn = {2076-3921}, support = {MOST 111-2320-B-040 -006 -MY3//National Science and Technology Council/ ; }, abstract = {Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of reactive oxygen species (ROS); however, its mechanistic role in sodium iodate (NaIO3)-induced oxidative injury remains unclear. Tetrahydrocurcumin (THC), the major metabolite of curcumin, exhibits potent antioxidant and cytoprotective activities, but its protective effects against AMD-associated retinal degeneration have not been fully elucidated. In the present study, we investigated whether THC protects against NaIO3-induced ROS-mediated apoptosis in RPE cells through regulation of NOX2 signaling. In vitro, THC significantly attenuated NaIO3-induced cytotoxicity and prevented apoptosis by suppressing hydrogen peroxide (H2O2) production and intracellular ROS accumulation in ARPE-19 cells. THC also preserved mitochondrial membrane potential by inhibiting the Src/p47[phox]/NOX2 signaling pathway and subsequently attenuated mitochondria-mediated apoptotic signaling. Furthermore, THC markedly reduced the expression of apoptotic proteins, including Bax, cleaved caspase-3, and cleaved PARP, concomitantly with suppression of Ras/Raf/MEK/ERK signaling. Mechanistically, treatment with the selective NOX2 inhibitor GSK2795039 significantly attenuated NaIO3-induced ROS accumulation and mitochondrial depolarization, while co-treatment with THC further enhanced these protective effects. In vivo, THC ameliorated NaIO3-induced retinal structural abnormalities by preserving the outer nuclear layer (ONL), reducing caspase-3 expression, and improving pupillary light responses in mice. Collectively, these findings demonstrate that THC protects against NaIO3-induced retinal degeneration through suppressing NOX2-dependent oxidative stress and downstream Ras/Raf/MEK/ERK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for AMD and other oxidative stress-related retinal disorders.}, }
@article {pmid42352232, year = {2026}, author = {Ding, S and Li, J and Chen, Z and Bai, W and Li, K}, title = {Calcium at the Helm: Mechanisms and Therapeutic Targets in the Retinal Neurovascular Unit.}, journal = {Biomolecules}, volume = {16}, number = {6}, pages = {}, doi = {10.3390/biom16060763}, pmid = {42352232}, issn = {2218-273X}, support = {82571232//National Natural Science Foundation of China/ ; BK20240122//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Humans ; Animals ; *Calcium/metabolism ; Diabetic Retinopathy/metabolism/drug therapy/pathology ; *Retina/metabolism/drug effects/pathology ; Glaucoma/metabolism/drug therapy/pathology ; Blood-Retinal Barrier/metabolism ; *Retinal Diseases/metabolism/drug therapy ; Calcium Channel Blockers/pharmacology/therapeutic use ; Retinal Ganglion Cells/metabolism/pathology ; }, abstract = {Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia-reperfusion (RIR) injury, and Alzheimer's disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood-retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β-driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders.}, }
@article {pmid42352349, year = {2026}, author = {Konukcu, O and Argun, M and Acer, S and Çelik, &#xd6; and Tök, &#xd6; and Tök, L and Nazıroğlu, M}, title = {An In Vitro Evaluation of a New Approach in AMD: Effects of the Combination of Resveratrol and Anti-VEGFs on ARPE-19 Cells.}, journal = {Biomolecules}, volume = {16}, number = {6}, pages = {}, doi = {10.3390/biom16060883}, pmid = {42352349}, issn = {2218-273X}, support = {SDU-BAP, Project No: TTU-2020-8124//S&#xfc;leyman Demirel University/ ; }, mesh = {Humans ; *Resveratrol/pharmacology ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Apoptosis/drug effects ; Cell Line ; Cell Survival/drug effects ; *Ranibizumab/pharmacology ; Oxidative Stress/drug effects ; *Recombinant Fusion Proteins/pharmacology ; Receptors, Vascular Endothelial Growth Factor ; Reactive Oxygen Species/metabolism ; Retinal Pigment Epithelium/drug effects/metabolism ; Antioxidants/pharmacology ; Mitochondria/drug effects/metabolism ; Angiogenesis Inhibitors/pharmacology ; }, abstract = {Anti-vascular endothelial growth factor agents (anti-VEGFs) are the cornerstone of treatment for neovascular age-related macular degeneration (AMD). Resveratrol is a natural polyphenol with well-established antioxidant and anti-apoptotic properties. This study investigated whether resveratrol exerts cytoprotective effects when combined with anti-VEGFs on ARPE-19 cells in vitro. Cells were treated with ranibizumab (RNZ), aflibercept (AFL), or ziv-aflibercept (ZFL), either alone or in combination with resveratrol. Mitochondrial and cytosolic reactive oxygen species (MitROS and CytROS), mitochondrial membrane depolarization (MitDep), caspase-3, -8 and -9 activities, cell viability, apoptosis, and VEGF-A levels were evaluated using confocal microscopy, plate reader-based assays, and ELISA techniques. Anti-VEGFs induced tolerable oxidative or apoptotic stress in ARPE-19 cells but did not exhibit intrinsic antioxidant and cytoprotective effects. The addition of resveratrol significantly enhanced beneficial effects by reducing oxidative stress, preserving mitochondrial integrity, and suppressing intrinsic apoptotic signalling, while increasing cell viability. VEGF-A levels were effectively reduced by anti-VEGF treatment, and this suppression was further augmented by resveratrol without compromising cellular survival. These findings indicate that resveratrol acts as an additive modulator that strengthens the cellular effects of anti-VEGFs on ARPE-19 cells. The combination strategy may represent a supportive approach to optimize long-term anti-VEGF therapy in AMD.}, }
@article {pmid42353616, year = {2026}, author = {Menna, F and Lupo, S and De Luca, L and Baldascino, A and Vingolo, EM and Meduri, A}, title = {Mitochondrial Dysfunction and Oxidative Stress in Retinal Degeneration: Mechanisms, Biomarkers, and Therapeutic Perspectives.}, journal = {Current issues in molecular biology}, volume = {48}, number = {6}, pages = {}, doi = {10.3390/cimb48060612}, pmid = {42353616}, issn = {1467-3045}, abstract = {Mitochondrial dysfunction and oxidative stress are increasingly recognized as key contributors to the development and progression of retinal degenerative diseases, including age-related macular degeneration and inherited retinal dystrophies. Growing evidence suggests that alterations in mitochondrial function, excessive production of reactive oxygen species, defective mitophagy, and chronic inflammatory responses are closely interconnected processes that contribute to retinal cell damage and degeneration. This review provides an overview of the current understanding of the molecular mechanisms linking mitochondrial dysfunction to retinal degeneration, with particular emphasis on the impact of oxidative stress, mitochondrial quality-control pathways, and inflammatory signaling. Available evidence indicates that mitochondrial DNA damage, impaired bioenergetics, and dysregulated mitochondrial dynamics play a crucial role in the degeneration of photoreceptors and retinal pigment epithelium cells. In turn, oxidative stress further exacerbates mitochondrial impairment, creating a self-sustaining cycle that promotes disease progression. Recent advances have also highlighted the therapeutic potential of targeting mitochondrial pathways. Although several mitochondria-directed strategies have shown encouraging results in experimental models, their translation into clinical practice remains at an early stage. Overall, the available data identify mitochondria as a promising therapeutic target and support the development of precision medicine approaches aimed at preserving retinal function and slowing disease progression in patients with retinal degenerative disorders.}, }
@article {pmid42355765, year = {2026}, author = {Bousamri, A and Kana'an, M and Alharbi, F and Alqudah, N}, title = {Real-World Outcomes of Switching to Aflibercept 8 mg in Previously Treated Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/jcm15124599}, pmid = {42355765}, issn = {2077-0383}, abstract = {Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung-Knapp-Sidik-Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: -0.017 logMAR; 95% CI: -0.027 to -0.007; +0.83 ETDRS letters; I[2] = 0%). CST decreased significantly (WMD: -21.5 µm; 95% CI: -29.3 to -13.7; I[2] = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I[2] = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes.}, }
@article {pmid42356258, year = {2026}, author = {Szulim, D and Kucharska, E and Machalińska, A and Kuprjanowicz, L and Czupryński, P and Szczuko, M}, title = {Impact of an Individualized Dietary Intervention on Body Composition and Clinical Outcomes in Patients with Neovascular Age-Related Macular Degeneration: A Pilot Study.}, journal = {Nutrients}, volume = {18}, number = {12}, pages = {}, doi = {10.3390/nu18121870}, pmid = {42356258}, issn = {2072-6643}, mesh = {Humans ; Pilot Projects ; Female ; *Body Composition ; Male ; Prospective Studies ; Aged ; *Macular Degeneration/diet therapy/physiopathology ; Treatment Outcome ; Aged, 80 and over ; }, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of permanent deterioration of central vision in elderly people. While anti-VEGF therapy remains the standard of care for neovascular AMD, disease progression and functional deterioration remain common. Methods: This pilot prospective controlled study evaluated the effects of an individualized dietary intervention in patients with neovascular AMD receiving anti-VEGF therapy. A total of 43 patients completed a six-month follow-up and were divided into a control group (standard treatment) and an intervention group receiving a personalized dietary plan. Anthropometric and body composition parameters were assessed using bioelectrical impedance analysis (BIA). Clinical retinal outcomes were classified as improvement, no change, or deterioration. Statistical analyses included parametric and non-parametric tests. Results: Retinal outcomes did not differ significantly between groups, although patients with retinal improvement or stabilization in the intervention group tended to exhibit more favorable changes in body composition. After adjustment for baseline values using analysis of covariance (ANCOVA), the dietary intervention remained significantly associated with reductions in body weight and BMI (p < 0.01). After 6 months, the intervention group demonstrated a numerically higher frequency of retinal improvement and a lower frequency of retinal deterioration compared with the control group; however, these differences were not statistically significant (p = 0.386). Conclusions: An individualized dietary intervention effectively improved body composition in patients with neovascular AMD but did not produce a statistically significant effect on retinal status over six months. Nevertheless, the dietary intervention group showed numerically more favorable retinal outcomes than the control group. Dietary modification may support general health and weight management.}, }
@article {pmid42356301, year = {2026}, author = {Kalu, KA and McMonnies, C and Lin, S and Arcot, J}, title = {The Relative Bioavailability of Lutein and Zeaxanthin in the Presence of Omega-3 Supplements and Their Effect on Oxidative Stress Levels in Humans: A Pilot Study.}, journal = {Nutrients}, volume = {18}, number = {12}, pages = {}, doi = {10.3390/nu18121914}, pmid = {42356301}, issn = {2072-6643}, mesh = {Humans ; *Lutein/pharmacokinetics/blood/administration &amp; dosage ; *Zeaxanthins/pharmacokinetics/blood/administration &amp; dosage ; Pilot Projects ; Male ; *Dietary Supplements ; Female ; *Fatty Acids, Omega-3/administration &amp; dosage/pharmacology ; Biological Availability ; *Oxidative Stress/drug effects ; Adult ; }, abstract = {Introduction: Lutein+Zeaxanthin (L+Z) are the major constituents of macular pigments of the retina. There is a lack of information on the bioavailability of the two compounds in the presence and absence of omega-3 fatty acids in L+Z supplements which are commonly prescribed to treat macular degeneration. Despite growing interest in L+Z supplementation, there remains a limited understanding of their short-term bioavailability dynamics and the potential added value of omega-3 co-supplementation. This pilot study reports on the bioavailability of serum responses to L+Z supplements in the presence of omega-3 fatty acids and evaluates time-resolved analytical approaches using Area Under the Curve. Subjects/Methods: A total of 10 men and six women with an average age of 31.38 ± 1.27 years participated in this randomised, non-blinded, controlled study for a total of 19 days (7-day wash-out period plus 12-day intervention period). The control group (n = 9) consumed the L+Z supplement (12 mg/d) only, while the intervention group (n = 7) consumed the L+Z supplement along with 900 mg/d of an omega-3 supplement (540 mg EPA + DHA 360 mg). Each group adhered to a comprehensive low-carotenoid and omega-3 diet list (LCOD) for the 7-day wash-out period and the 12-day intervention period. The participants reported the foods they consumed daily in their diet logbooks, online logs, and the ASA 24 diet assessment log over the study period. The body composition of each subject in the two groups was assessed before and after the study using a SECA body composition analyser, and the relative serum L+Z response in both groups was determined using Area Under the Curve (AUC and incremental AUC) by trapezoidal approximation. Results: The mean ± SEM baseline serum lutein+zeaxanthin (L+Z) concentrations measured at the end of the wash-out period (Day 7) were 2.23 ± 0.65 µg/mL in the control group and 1.20 ± 0.53 µg/mL in the intervention group. Following wash-out, serum L+Z concentrations increased in both groups, reaching 2.81 ± 0.90 µg/mL (control) and 2.63 ± 1.21 µg/mL (intervention) at Day 13, and 2.98 ± 0.69 µg/mL (control) and 3.02 µg/mL (intervention) at Day 19. Total exposure assessed by AUC7-13 and AUC13-19 did not differ significantly between the groups (p > 0.05). Incremental exposure analyses identified the post-wash-out period as the primary biologically responsive window, with higher mean incremental L+Z bioavailability in the intervention group (4.36 µg/day/mL) compared with the control group (3.00 µg/day/mL), although this difference was not statistically significant (p > 0.05). No significant effect of omega-3 co-supplementation on oxidative stress biomarkers was observed (p > 0.05). Conclusion: Omega-3 co-supplementation did not demonstrate a consistent additional benefit on L+Z bioavailability or oxidative stress markers. Day-resolved analyses using iAUC revealed temporal patterns not captured by conventional AUC measures. These exploratory findings should be interpreted with caution and confirmed in larger, longer-term studies.}, }
@article {pmid42356572, year = {2026}, author = {García-Quintanilla, L and Almuiña-Varela, P and Rodríguez-Cid, MJ and Gil-Martinez, M and Abraldes, MJ and Gomez-Ulla, F and González-Barcia, M and Castro-Fernández, DC and Cañizo-Outeiriño, A and Cuartero-Martínez, A and Estany-Gestal, A and Otero-Espinar, FJ and Fernández-Rodríguez, M and Fernández-Ferreiro, A}, title = {Systemic Immune and miRNA Signatures Associated with Long-Term Ranibizumab Response in Neovascular Age-Related Macular Degeneration.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {6}, pages = {}, doi = {10.3390/ph19060955}, pmid = {42356572}, issn = {1424-8247}, support = {PI17/00940//Instituto de Salud Carlos III/ ; PI23/00069//Instituto de Salud Carlos III/ ; IN607D 2021/001//Xunta de Galicia/ ; IN607A2023/04//Xunta de Galicia/ ; }, abstract = {Objectives: To characterize the one-year functional, anatomical, and molecular responses to intravitreal Ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), and to identify systemic immune and miRNA signatures associated with treatment response. Methods: This prospective longitudinal observational study included 44 treatment-naïve patients with nAMD. Patients received up to four monthly intravitreal Ranibizumab injections, followed by a treat-and-extend regimen. Best-corrected visual acuity using ETDRS letters, central retinal thickness by optical coherence tomography, fluorescein angiography, and OCT angiography were assessed at baseline and 12 months. Peripheral blood samples were collected at both time points to quantify seven circulating cytokines using an IMMULITE chemiluminescent immunoassay and to profile 37 candidate miRNAs by TaqMan OpenArray RT-qPCR from leukocyte-derived RNA. Treatment response was classified using composite anatomical and functional criteria, including intraretinal/subretinal fluid resolution, ≥25% central retinal thickness reduction, and a ≥5 ETDRS letter gain. Results: At one year, patients showed significant central retinal thickness reduction and overall visual stabilization, although good and poor responders differed according to composite response criteria. Statin use was numerically more frequent among poor responders, although this difference was not statistically significant. Soluble IL-2R increased significantly over time in the overall cohort, mainly driven by good responders who showed higher median levels at both visits. IL-8 also increased globally, without significant between-group differences. Among differentially expressed miRNAs, miR-3121 was the only candidate reaching statistical significance and was downregulated in good responders. ROC analysis showed moderate discriminative performance for miR-3121, with an AUC of 0.76. Conclusions: One-year response to Ranibizumab in nAMD may involve systemic immune activation and miRNA regulation. miR-3121 emerges as a candidate biomarker of treatment response, supporting further validation in larger independent cohorts.}, }
@article {pmid42357377, year = {2026}, author = {Liu, J and Wang, Z and Yang, Y and Yi, L and Li, S and Gao, J and Zhou, J and Cheng, N and Yin, X and Dong, X and Ni, J and Qu, C}, title = {Metformin and cRGDfc-Modified Nanoparticles Loaded with Curcumin for Age-Related Macular Degeneration: In Vitro Pharmacodynamics and Molecular Mechanisms.}, journal = {Pharmaceutics}, volume = {18}, number = {6}, pages = {}, doi = {10.3390/pharmaceutics18060761}, pmid = {42357377}, issn = {1999-4923}, abstract = {Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of -23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway.}, }
@article {pmid42358460, year = {2026}, author = {Morozov, P and Andreev, V and Yakovleva, M and Kostyukov, A and Feldman, T and Ryabova, A and Romanishkin, I and Shirmanova, M and Goltsman, G and Kuzmin, V and Ostrovsky, M and Arkhipchenko, A and Maksimov, E and Becker, W and Shcheslavskiy, V}, title = {Spectral dependence of lipofuscin fluorescence lifetimes revealed by FLIM with a superconducting nanowire single-photon detector.}, journal = {Journal of biomedical optics}, volume = {31}, number = {6}, pages = {066501}, pmid = {42358460}, issn = {1560-2281}, mesh = {*Lipofuscin/chemistry/analysis ; Humans ; Retinal Pigment Epithelium/diagnostic imaging ; Microscopy, Fluorescence/methods/instrumentation ; *Nanowires/chemistry ; Macular Degeneration/diagnostic imaging ; *Optical Imaging/methods/instrumentation ; }, abstract = {SIGNIFICANCE: The noninvasive assessment of oxidative stress in the retinal pigment epithelium (RPE), a key factor in the pathogenesis of age-related macular degeneration (AMD), is an important aspect in ophthalmic diagnostics. Although fundus autofluorescence (FAF) is clinically used, its diagnostic power is limited. Fluorescence lifetime imaging ophthalmoscopy shows promise, but the photophysical underpinnings of lifetime changes in lipofuscin-the dominant RPE fluorophore-remain poorly understood. Lipofuscin granules (LGs) in the RPE are a primary source of fundus autofluorescence and are critically involved in the pathogenesis of AMD. This study characterizes the spectral and lifetime properties of LGs using a fluorescence lifetime imaging microscopy (FLIM) system integrated with a wide-range sensitivity, large-active-area superconducting nanowire single-photon detector (SNSPD) coupled with a standard 50 μ m multimode fiber.<br><br>AIM: We present experiments on multispectral fluorescence lifetime imaging with a detailed analysis of the fluorescence decays and spectral profiles of LGs in the RPE cells to probe the molecular oxidative state of RPE lipofuscin, aiming to improve AMD understanding and propose a method for early diagnosis of retinal pathologies.<br><br>APPROACH: We use a cutting-edge FLIM system integrated via a multimode fiber with a large-active-area SNSPD. Unlike previous studies, our approach provides component-resolved and spatially resolved fluorescence decay kinetics across a broad spectral range (500 to 1000&#xa0;nm), which is typically inaccessible to conventional detectors. LGs were isolated from 100 human (aged 50 to 75 years) donor RPE cells and subjected to in vitro photo-oxidation to simulate AMD-like conditions. Steady-state spectroscopy revealed a blue shift in emission following photo-oxidation.<br><br>RESULTS: FLIM analysis, employing a tri-exponential decay model, showed a significant increase in the mean fluorescence lifetime &#x3c4; m from &#x223c; 247 to &#x223c; 587 &#x2009;&#x2009; ps after photo-oxidation. Crucially, we identified a pronounced direct spectral dependence of fluorescence lifetimes &#x3c4; m versus wavelength: for native LGs, &#x3c4; m increased from 136 to 319&#xa0;ps at registration range 500 to 650&#xa0;nm; for photo-oxidized LGs, it increased from 174 to 623&#xa0;ps over the same region. High-performance liquid chromatography confirmed the degradation of the bisretinoid A2E and accumulation of oxidized derivatives, correlating with the observed photophysical changes.<br><br>CONCLUSIONS: These findings demonstrate that component-resolved visible-near infrared spectral FLIM provides a sensitive, noninvasive approach to probe the molecular oxidative state of RPE lipofuscin, offering potential for early diagnosis of retinal pathologies.}, }
@article {pmid42359432, year = {2026}, author = {Liu, D and Bi, H and Sun, Y and Gao, Z and Lu, P}, title = {Patient Experiences of Intravitreal Anti-Vascular Endothelial Growth Factor Injections for Age-Related Macular Degeneration: A Meta-Synthesis of Qualitative Studies.}, journal = {Patient preference and adherence}, volume = {20}, number = {}, pages = {610930}, pmid = {42359432}, issn = {1177-889X}, abstract = {AIM: To synthesize evidence from qualitative studies on patients receiving intravitreal anti-vascular endothelial growth factor injections for age-related macular degeneration to explore their treatment burdens and life experiences.<br><br>METHODS: Five databases (PubMed, Web of Science, Embase, Cochrane Library, and CINAHL) were searched on 20 May 2025, with supplementation through hand-searching. The search was restricted to qualitative or mixed-methods studies published in English. The included studies were evaluated and synthesized by two independent reviewers using the Joanna Briggs Institute (JBI) critical appraisal tools and the JBI aggregative integration method.<br><br>RESULTS: Thirteen studies (2010-2023) from 11 countries were summarized into four themes: barriers to treatment and sources of anxiety, coping strategies and adaptation mechanisms, drivers of treatment adherence, and the impact of doctor-patient engagement.<br><br>CONCLUSION: Patients with age-related macular degeneration face significant physical, emotional, and logistical challenges during anti-vascular endothelial growth factor therapy. A series of measures can be integrated into the treatment process to improve patient adherence, including psychological support, structured patient education, and optimized treatment pathways.<br><br>REGISTRATION: PROSPERO CRD420251059151.}, }
@article {pmid42359981, year = {2026}, author = {Chen, J and Yuan, XL and Zhang, X and Huang, Q and Zhou, X and Ji, D and Zhu, W and Duan, X}, title = {Genome Wide Pleiotropic Analysis Reveals Shared Genetic Architecture and Pathological Basis Between Retinitis Pigmentosa and Relevant Ocular Comorbidities.}, journal = {Seminars in ophthalmology}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/08820538.2026.2694713}, pmid = {42359981}, issn = {1744-5205}, abstract = {PURPOSE: Retinitis pigmentosa (RP) is a leading cause of irreversible blindness in working-age populations and frequently cooccurs with multiple ocular disorders. As their shared genetic basis remains poorly understood, this study aimed to elucidate the shared genetic architecture underlying RP and relevant ocular comorbidities.<br><br>METHODS: Using large-scale genome-wide association data, we systematically investigated pleiotropy, genetic correlation, cell-type specificity, and genetically predicted causality between RP and major ophthalmic comorbidities.<br><br>RESULTS: We observed significant genetic correlations and pleiotropic enrichment between RP and retinal detachments and breaks (RDAB), retinal vascular occlusion (RVO), and age-related macular degeneration (AMD), with notable SNP-level overlap between RP and primary open-angle glaucoma (POAG). RP and RDAB, as well as AMD, shared genetic associations at chr1:196176201-197311241 and chr10:123900764-125869042. Totally, 41, 25, 114, and 397 pleiotropic loci were identified between RP and RDAB, RVO, POAG, and AMD, implicating pathways related to cell division, metabolic regulation, immune activation, and complement activation. A novel causal variant (rs36212731) and four pleiotropic genes (ARMS2, HTRA1, CFH, PLEKHA1) were discovered between RP and RDAB. Ten causal variants and 24 pleiotropic genes were identified between RP and AMD. MR analyses demonstrated a genetically causal effect of RP on an increased risk of RDAB and RVO (P&#x2c2;0.05), and AMD was associated with an increased risk of RP. Cell-type enrichment analyses highlighted vascular smooth muscle cells and retinal pigment epithelium as key mediators of shared susceptibility between RP and RDAB, and POAG.<br><br>CONCLUSIONS: This study reveals robust genetic and potential causal links between RP and RDAB, RVO, as well as AMD, along with complex pleiotropic associations with glaucoma. These findings provide novel genetic insights into the shared pathogenic mechanisms and generate hypotheses for future biological, translational, and clinical research.}, }
@article {pmid42360009, year = {2026}, author = {Dogru, E and Chavez, MP and Toth, O and Serafini, M and Kabaalioglu Guner, M}, title = {Port Delivery System Vs Monthly Ranibizumab in VEGF-Driven Macular Disease: A Systematic Review and Meta-Analysis.}, journal = {Seminars in ophthalmology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/08820538.2026.2693751}, pmid = {42360009}, issn = {1744-5205}, abstract = {PURPOSE: The comparative efficacy and safety of ranibizumab Port Delivery System (PDS) vs monthly intravitreal ranibizumab in Vascular Endothelial Growth Factor (VEGF)-driven macular diseases remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PDS vs monthly ranibizumab in neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).<br><br>METHODS: PubMed, Embase, and Cochrane were searched for randomized controlled trials enrolling adults with neovascular age-related macular degeneration or diabetic macular edema treated with the ranibizumab Port Delivery System (100&#x2009;mg/mL) versus monthly intravitreal ranibizumab 0.5&#x2009;mg. This systematic review and meta-analysis was conducted according to a predefined PICOTT framework. Continuous and binary outcomes were pooled with mean differences (MDs) and risk ratios (RRs) with a 95% confidence interval (CI), respectively, with a random-effects model. Statistical analyses were performed using RevMan.<br><br>RESULTS: Three trials were included, with a total of 1,149 eyes of which 688 (60%) received PDS and 461 (40%) received monthly ranibizumab. No significant differences were observed in BCVA (nAMD: MD&#x2009;-&#x2009;0.69 letters; 95% CI&#x2009;-&#x2009;2.52 to 1.14; p&#x2009;=&#x2009;.46; DME: MD 0.20; 95% CI&#x2009;-&#x2009;1.20 to 1.60; p&#x2009;=&#x2009;.78) or CRT (nAMD: MD 26.67&#x2009;&#xb5;m; 95% CI&#x2009;-&#x2009;16.55 to 69.88; p&#x2009;=&#x2009;.23; DME: MD&#x2009;-&#x2009;3.80; 95% CI&#x2009;-&#x2009;17.20 to 9.60; p&#x2009;=&#x2009;.58). Incidence of ocular AEs was significantly higher with PDS (RR 1.80; 95% CI 1.49-2.17; p&#x2009;<&#x2009;.00001; I[2]=74%). Among specific complications, conjunctival bleb or filtering bleb leak (RR 15.29; 95% CI 2.31-101.35; p&#x2009;=&#x2009;.005), conjunctival erosion (RR 8.87; 95% CI 1.66-47.35; p&#x2009;=&#x2009;.01), vitreous hemorrhage (RR 3.61; 95% CI 1.24-10.49; p&#x2009;=&#x2009;.02), hyphema (RR 5.77; 95% CI 1.03-32.20; p&#x2009;=&#x2009;.05), and conjunctival retraction (RR 5.78; 95% CI 1.04-32.29; p&#x2009;=&#x2009;.05) occurred significantly more often with PDS. Systemic AEs were comparable between treatment arms (RR 1.00; 95% CI 0.89-1.13; p&#x2009;=&#x2009;.98).<br><br>CONCLUSION: In this systematic review and meta-analysis of three randomized controlled trials, PDS was associated with visual and anatomical results comparable to monthly ranibizumab in patients with nAMD. Evidence in DME was limited to a single trial, and conclusions in this population should be considered exploratory. PDS was associated with a higher incidence of procedure- and device-related ocular complications.}, }
@article {pmid42360388, year = {2026}, author = {Hannig, L and Braunger, BM and Kleefeldt, N and Cagol, L and Zimmermann, J and Brunne, B and Ahmad, H and Vallon, M and Ergün, S and Hillenkamp, J and Neueder, A and Schlecht, A}, title = {Deletion of CEACAM1 does not affect retinal and choroidal morphology or transcriptome.}, journal = {Cell and tissue research}, volume = {405}, number = {1}, pages = {}, pmid = {42360388}, issn = {1432-0878}, support = {01/23//Helmut Ecker Stiftung/ ; }, mesh = {Animals ; *Choroid/metabolism/anatomy &amp; histology ; *Retina/metabolism/anatomy &amp; histology ; *CEACAM1 Protein/metabolism/genetics/deficiency ; *Transcriptome/genetics ; *Gene Deletion ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Carcinoembryonic Antigen ; }, abstract = {CEACAM1 (CC1) is an important mediator of cell proliferation and adhesion and serves as an angiogenic factor through interaction with VEGF. Although the role of CC1 has been extensively studied in organs such as the heart, liver and lung in which CC1 is considered an important regulator of various pathological conditions, little is known about the function of CEACAM1 in the eye. In this study, we investigated the expression and function of CC1 in the retina and choroid of healthy adult mice using immunohistochemistry, fluorescence activated cell sorting (FACS) and RNA sequencing. We found CC1 to be expressed in endothelial and myeloid cells of the retina and the choroid. However, deletion of CC1 did not result in vascular abnormalities of the retina and choroid or changes in retinal myeloid cell morphology and number. Furthermore, the retinal architecture was not affected and morphometric measurements of the thickness of the inner and outer retinal layers were not altered by deletion of CC1. Accordingly, we did not observe structural or transcriptomic changes in the choroid. Our data suggest that the role of CC1 in the adult eye during steady state is attenuated or can be compensated by other molecular mediators. However, one could speculate that CC1 may become functionally relevant during pathological conditions, such as in neovascular eye diseases like proliferative diabetic retinopathy or neovascular age-related macular degeneration.}, }
@article {pmid41068524, year = {2026}, author = {Chourasiya, S and Patel, P and Kumar, GS and Soni, A}, title = {A New Vision for Ocular Disease: Stem Cell Strategies in Regenerative Ophthalmology.}, journal = {Stem cell reviews and reports}, volume = {22}, number = {1}, pages = {144-169}, pmid = {41068524}, issn = {2629-3277}, abstract = {Degenerative ocular diseases such as age-related macular degeneration (AMD), glaucoma, cataracts, retinitis pigmentosa (RP), dry eye disease (DED), and limbal stem cell deficiency (LSCD) are major contributors to global visual impairment and blindness. These conditions not only affect vision but also significantly reduce patients’ quality of life. Conventional therapies largely aim to manage symptoms or slow disease progression, with limited ability to regenerate or restore damaged ocular tissues. In contrast, stem cell-based therapies have emerged as a promising strategy, offering the potential to repair, replace, or regenerate dysfunctional cells within the eye. Stem cells exhibit remarkable regenerative, anti-inflammatory, and neuroprotective properties, mediated both by direct differentiation and through paracrine mechanisms such as the secretion of growth factors and exosomes. A wide range of stem cell types—mesenchymal stem cells (MSCs), retinal progenitor cells (RPCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs)—are currently under investigation for the treatment of diverse ophthalmic conditions. These therapies target various ocular structures, from the cornea to the retina, aiming to restore tissue integrity and function. This review highlights the current progress, mechanisms, and therapeutic potential of stem cell applications in ocular regeneration, and underscores their growing relevance as a regenerative solution for previously untreatable or refractory eye diseases and the clinical trials that are currently ongoing.}, }
@article {pmid41903038, year = {2026}, author = {Palakkan, AA and Kumar, GS and Jayaraman, S and Ross, JA}, title = {Differential Effects of Retinal Fatty Acids Under Oxidative Stress Reveal DHA's Susceptibility to Ferroptosis and Polarity Disruption in iPSC Derived RPE Cells.}, journal = {Stem cell reviews and reports}, volume = {22}, number = {4}, pages = {1958-1973}, pmid = {41903038}, issn = {2629-3277}, support = {Ramalingaswami Re-entry Fellowship//Department of Biotechnology, Ministry of Science and Technology, India/ ; CRG/2022/004337//Anusandhan National Research Foundation (ANRF)/ ; }, abstract = {Age-related macular degeneration (AMD) is driven by chronic oxidative stress and lipid dysregulation in the retinal pigment epithelium (RPE), yet the specific contributions of individual retinal fatty acids remain unclear. Among these, docosahexaenoic acid (DHA)—the most abundant polyunsaturated fatty acid in the retina—may play a dual role, supporting visual function under physiological conditions but predisposing RPE cells to injury under oxidative stress. Here, we investigated how DHA and other retinal fatty acids modulate oxidative stress responses in induced pluripotent stem cell–derived RPE (iRPE) cells. Cells were exposed to DHA, arachidonic acid (ARA), or α-linolenic acid (ALA) with or without hydrogen peroxide (H2O2) to assess their effects on viability, lipid peroxidation, ferroptosis, necroptosis, barrier integrity, and VEGF secretion. Combined DHA and H2O2 exposure markedly reduced iRPE viability and trans-epithelial resistance, whereas ARA caused moderate and ALA minimal cytotoxicity. DHA uniquely induced hallmark features of ferroptosis, including lipid peroxidation, GPX4 downregulation, glutathione depletion, and iron accumulation. Treatment with ferroptosis inhibitors (ferrostatin-1, liproxstatin-1) restored viability, preserved polarity, and normalized VEGF secretion, while necroptosis inhibitors offered only partial protection. Notably, DHA-induced polarity loss occurred without activation of EMT transcription factors, revealing a ferroptosis-driven mechanism of barrier disruption. These findings identify DHA as a distinct sensitizer of ferroptosis in iRPE cells under oxidative stress, linking retinal lipid metabolism to ferroptotic vulnerability and suggesting that targeting ferroptosis may help preserve RPE integrity and slow AMD progression.Clinical Trial Number: Not applicable.}, }
@article {pmid42053728, year = {2026}, author = {Pirillo, A and Catapano, AL}, title = {CETP Renaissance with Obicetrapib.}, journal = {Current atherosclerosis reports}, volume = {28}, number = {1}, pages = {}, pmid = {42053728}, issn = {1534-6242}, abstract = {PURPOSE OF REVIEW: This review examines the emerging role of cholesteryl ester transfer protein (CETP) inhibition, with a focus on obicetrapib, in lipid management and its potential implications beyond atherosclerotic cardiovascular disease (ASCVD), including neurodegeneration, glycaemic control, age-related macular degeneration (AMD), sepsis, and kidney function. RECENT FINDINGS: Obicetrapib is a potent, selective CETP inhibitor that overcomes the limitations of earlier agents, demonstrating substantial reductions in LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a), alongside marked increases in HDL-C. Phase 2 and 3 trials confirm robust lipid-modifying efficacy and favourable safety. Emerging data suggest broader biological effects. Genetic and mechanistic studies link reduced CETP activity to improved brain structure and lower dementia risk, with biomarker analyses showing attenuation of Alzheimer’s disease-related markers, particularly in APOE ε4 carriers. Evidence further indicates potential metabolic benefits, including reduced risk of type 2 diabetes and improved glycaemic control. While genetic studies raise concerns about increased AMD risk, clinical trial data have not confirmed this association. Preclinical and human data suggest a protective role in sepsis via HDL-mediated endotoxin clearance, and early analyses indicate possible renal benefits through slower decline in kidney function. Obicetrapib represents a promising advancement in CETP inhibition, combining potent lipid-lowering effects with a good safety profile. Beyond cardiovascular risk reduction, emerging evidence supports potential roles in neurodegenerative disease, metabolic regulation, infection outcomes, and renal function. Ongoing outcome trials will determine its clinical impact and broader therapeutic relevance.}, }
@article {pmid42340610, year = {2026}, author = {Volpe, G and Bonanata, M and Peyla, A and Ruscitti, L and Eggarter, V and Pache, M and Paris, A and Menghini, M and Grimaldi, G}, title = {Peripapillary Retinal Nerve Fibre and Ganglion Cell Layer Changes Following Intravitreal Aflibercept 8 mg Therapy in Neovascular Age-Related Macular Degeneration: A Longitudinal OCT Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42340610}, issn = {2193-8245}, abstract = {INTRODUCTION: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard of care for neovascular age-related macular degeneration (nAMD) and other retinal vascular diseases. However, transient post-injection intraocular pressure elevations have raised concerns regarding potential cumulative effects on inner retinal structures, including the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIP). As longitudinal evidence on the neuro-retinal structural safety of higher-dose formulations such as aflibercept 8 mg remains limited, this study evaluated 12-month changes in pRNFL and mGCIP thickness following intravitreal aflibercept 8 mg.<br><br>METHODS: This single-centre, observational longitudinal cohort study included patients with nAMD treated with intravitreal aflibercept 8&#xa0;mg or aflibercept 2&#xa0;mg. Patients receiving aflibercept 8&#xa0;mg were prospectively enrolled, while patients treated with 2&#xa0;mg aflibercept were retrospectively identified. Spectral-domain optical coherence tomography was used to assess pRNFL and mGCIP thickness at baseline and at 3, 6 and 12&#xa0;months. Longitudinal within-eye changes relative to baseline were analysed, alongside inter-eye comparisons with fellow untreated eyes and between-treatment group comparisons at 12&#xa0;months.<br><br>RESULTS: Thirty-eight eyes from 35 patients were included. In eyes treated with aflibercept 8&#xa0;mg, mGCIP thickness remained stable throughout follow-up, with no significant changes at 3, 6 or 12&#xa0;months compared with baseline. At 12&#xa0;months, mGCIP thickness was comparable between aflibercept 8&#xa0;mg-treated eyes and fellow untreated eyes, as well as between aflibercept 8&#xa0;mg and aflibercept 2&#xa0;mg-treated eyes. Similarly, pRNFL thickness showed no significant global or sectoral changes over 12&#xa0;months and did not differ between treatment groups.<br><br>CONCLUSION: Over 12&#xa0;months of follow-up, intravitreal aflibercept 8&#xa0;mg was not associated with significant thinning of pRNFL or mGCIP thickness, supporting its neuro-retinal structural safety in routine clinical practice.}, }
@article {pmid42340770, year = {2026}, author = {Malvasi, M and Fragiotta, S and Pacella, E and Scuderi, G and Abdolrahimzadeh, S}, title = {Multimodal ophthalmic imaging in the search for the association between subretinal drusenoid deposits and systemic vascular comorbidity with metabolic dysregulation in age-related macular degeneration progression.}, journal = {La Clinica terapeutica}, volume = {177}, number = {4}, pages = {720-728}, doi = {10.7417/CT.2026.2063}, pmid = {42340770}, issn = {1972-6007}, mesh = {Humans ; Disease Progression ; Female ; Male ; Aged ; Retrospective Studies ; *Retinal Drusen/diagnostic imaging/etiology/complications ; *Macular Degeneration/complications/diagnostic imaging/metabolism ; *Multimodal Imaging ; Tomography, Optical Coherence ; Aged, 80 and over ; Longitudinal Studies ; Dyslipidemias/complications ; Eye Diseases, Hereditary ; Bruch Membrane/pathology ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is increasingly linked to systemic cardiovascular and metabolic dysfunction as well as cerebral small vessel disease. Subretinal drusenoid deposits (SDD) and basal laminar deposits (BLamD) have emerged as structural biomarkers associated with AMD progression and systemic vascular compromise. This study aimed to investigate associations between hypertension, dyslipidemia, and cerebrovascular disease - transient ischemic attack, stroke, and myocardial infarction - and retinal structural alterations in AMD patients presenting SDD in order to assess the relationship with progression of disease.<br><br>METHODS: Thirty-eight eyes of 31 patients with AMD and SDD were examined in this retrospective longitudinal study. Retinal imaging, including near-infrared reflectance and spectral-domain optical coherence tomography (SDOCT), was used to characterize retinal alterations. Systemic cardiovascular and small vessel disease profiles were obtained from the clinical history. Morphometric changes in retinal layers were quantified through SDOCT and correlated with systemic metabolic and vascular parameters.<br><br>RESULTS: During a mean follow-up of 2.1 &#xb1; 0.86 years, 44.7% of eyes progressed to advanced AMD: 23.6% to complete RPE and outer retinal atrophy (cRORA)/geographic atrophy, and 21% to macular neovascularization. High-risk vascular diseases were present in 32.3% of patients. BLamD significantly increased progression risk (P = 0.03), whereas conventional drusen did not (P = 0.79). Higher serum triglycerides correlated negatively with outer retinal layer changes (r = -0.66, P = 0.004) and perifoveal thinning (r = -0.75, P < 0.001), while HDL showed positive correlations. Hypertension was frequent (87.1%) but not independently predictive of progression.<br><br>CONCLUSION: AMD patients with SDD exhibit significant associations between systemic cardio/cerebro-vascular disease and metabolic dysregulation and retinal structural degeneration. BLamD further increase progression risk, underscoring their relevance as imaging biomarkers of vascular and metabolic compromise.}, }
@article {pmid42341259, year = {2026}, author = {Moir, JT and Kim, SB and Allan, KC and Kaelber, DC and Singh, RP and Talcott, KE}, title = {Demographic and Prevalence Dynamics of Macular Telangiectasia Type 2 From 2015 to 2024.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-6}, doi = {10.3928/23258160-20260513-01}, pmid = {42341259}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: This study sought to provide a recent estimate for the prevalence of macular telangiectasia type 2 (MacTel) with respect to age, race/ethnicity, and sex.<br><br>PATIENTS AND METHODS: A cross-sectional study from 2015 to 2024 was performed for adults in the United States aged &#x2265; 35 years within an electronic health record data platform. Patients with MacTel were identified as those with a corresponding International Classification of Diseases 10th revision (ICD-10) diagnosis code. The prevalence of MacTel was calculated at each year of the study period and stratification was performed by age, race, ethnicity, and sex.<br><br>RESULTS: In 2024, the prevalence of MacTel was 9.06 patients per 100,000, representing a 1.91-fold increase from 2015 (95% CI 1.79-2.03). Over that same timespan, the ratio of increase in MacTel was greater than the ratio of increase of age-related macular degeneration (AMD) (odds ratio 1.25, 95% 1.17-1.33).<br><br>CONCLUSION: The prevalence of MacTel is lower than previously estimated but has been increasing at a striking rate from 2015 to 2024 that outpaces AMD.}, }
@article {pmid42342678, year = {2026}, author = {Bangar, P and Garkal, A and Mehta, T}, title = {Next-Generation Drug Delivery for Age-related Macular Degeneration: Promise of Controlled Release Formulations.}, journal = {Drug development and industrial pharmacy}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/03639045.2026.2691481}, pmid = {42342678}, issn = {1520-5762}, abstract = {OBJECTIVE: To review emerging long-acting drug delivery and implantable systems developed to overcome the limitations of conventional intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD).<br><br>SIGNIFICANCE OF REVIEW: nAMD is a leading cause of irreversible vision loss worldwide. Although intravitreal anti-VEGF injections are clinically effective, their short intraocular half-life necessitates frequent administration, resulting in high treatment burden, poor patient compliance, and increased risk of procedure-related complications. Long-acting injectable and implantable drug delivery systems offer a promising approach to maintain therapeutic drug levels while reducing injection frequency and healthcare burden.<br><br>KEY FINDINGS: Recent advances in controlled-release technologies, including electrospun nanofibers, injectable microcapsules, core-shell nanofibers, 3D-printed implants, dip-cast tubular devices, nanostructured thin-film systems, suprachoroidal implants, encapsulated cell technologies, and gene therapy-based approaches, demonstrate sustained drug release ranging from several weeks to over 1 year. These platforms provide improved drug stability, higher payload capacity, tunable release kinetics, and favorable biocompatibility. Clinically validated refillable implants, such as Susvimo&#x2122;, confirm the feasibility of long-term intraocular anti-VEGF delivery.<br><br>CONCLUSIONS: Next-generation long-acting ocular drug delivery systems have the potential to transform nAMD management by reducing invasive procedures, improving patient adherence, and maintaining durable therapeutic efficacy. Continued optimization and clinical translation of these technologies are essential for their successful integration into routine ophthalmic care.}, }
@article {pmid42343082, year = {2026}, author = {Okuda, D and Mii, S and Miyai, Y and Kato, K and Ando, R and Shiraki, Y and Esaki, N and Yamada, K and Shimizu, H and Ushida, H and Kaneko, H and Nishiguchi, KM and Enomoto, A}, title = {Possible involvement of the mesenchymal cell marker Meflin in regeneration after retinal injury.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-58893-1}, pmid = {42343082}, issn = {2045-2322}, support = {JPMJSP2125//Japan Science and Technology Agency/ ; 22K07000//Japan Society for the Promotion of Science/ ; 22H02848//Japan Society for the Promotion of Science/ ; JP24gm1210009//Japan Agency for Medical Research and Development/ ; }, abstract = {Pathological tissue remodeling, including choroidal neovascularization (CNV) and fibrosis, is central to the development of retinal diseases such as age-related macular degeneration; however, its molecular mechanisms remain incompletely defined. We examined the intraocular expression patterns of Meflin encoded by the ISLR gene, a mesenchymal stromal cell marker with anti-fibrotic properties, in human surgical specimens and mouse retinal tissues, and evaluated its involvement in a retinal injury mouse model. Meflin expression was detected in fibroblast-like stromal cells within human proliferative vitreoretinopathy / proliferative diabetic retinopathy fibrovascular membranes and the ciliary body, lens epithelium, retinal pigment epithelium, optic nerve meningeal cells, and choroidal perivascular fibroblast-like cells of the mouse eye. Lineage-tracing using a Meflin reporter mouse line revealed accumulation of Meflin-lineage cells within laser-induced CNV lesions. Notably, adeno-associated virus-mediated Meflin overexpression increased CNV volume in the acute phase of retinal injury but suppressed subretinal fibrosis after the CNV growth phase. These findings suggest that Meflin overexpression modulates angiogenic and fibrotic remodeling after retinal injury in a phase-dependent manner, consistent with reported roles in cancer and fibrotic diseases. These results improve understanding of retinal disease pathology and identify Meflin as a potential target for future therapeutic studies on proliferative and fibrotic retinal diseases.}, }
@article {pmid42343583, year = {2026}, author = {Demirayak, B and Bozkurt, E and Tarakçıoğlu, HN and Aydoğan Gezginaslan, T and Karapapak, M and Özal, SA and Ayrancı Osmanbaşoğlu, &#xd6; and Özdoğan Erku, S and Erdoğan, M and Sayın, N and Öztürk, M and Ağın, A and Uzundede, T and Çakır, A and Özkaya, A}, title = {Assessment of Dietary Nutritional Profile in Turkish Patients with Age-Related Macular Degeneration.}, journal = {Turkish journal of ophthalmology}, volume = {56}, number = {3}, pages = {180-186}, doi = {10.4274/tjo.galenos.2026.26641}, pmid = {42343583}, issn = {2149-8709}, mesh = {Humans ; Female ; Male ; Turkey/epidemiology ; *Macular Degeneration/epidemiology/physiopathology ; Aged ; *Nutritional Status ; Surveys and Questionnaires ; *Diet ; Aged, 80 and over ; Middle Aged ; Follow-Up Studies ; *Nutrition Assessment ; }, abstract = {OBJECTIVES: To evaluate the dietary nutritional profile according to the suggestions of the Age-Related Eye Disease Study 2 (AREDS2) in Turkish patients with age-related macular degeneration (AMD).<br><br>MATERIALS AND METHODS: The study included patients diagnosed with non-neovascular AMD in one or both eyes and who underwent routine follow-up in retina clinics at tertiary centers in &#x130;stanbul between May 12 and May 27, 2025. An ocular nutrition questionnaire prepared according to AREDS2 suggestions was translated into Turkish. The survey was conducted among our cohort after its reproducibility and validity were confirmed. Consumption of fish-shellfish, hazelnut-walnut-peanut, eggs, leafy greens, red pepper, carrot-pumpkin, and peppers-green tea-strawberry-citrus (eicosapentaenoic acid, docosahexaenoic acid, omega 3, lutein, zeaxanthin, beta-carotene, and antioxidant-rich foods, respectively), micronutrient supplementation, smoking, physical activity, anxiety about vision loss, education level, and monthly income were recorded.<br><br>RESULTS: A total of 530 patients from 7 clinics who answered all questions were evaluated. Adequate consumption of omega-3-rich foods consumption was reported by 19.3% of participants, whereas 57.2% reported no fish intake in the last week. Adequate consumption of foods rich in lutein/zeaxanthin, beta-carotene, and antioxidants was reported by 63.6%, 41.7%, and 4.7% of patients, respectively, and regular micronutrient supplementation was reported by 35.5%. Of the patients, 23.6% reported high anxiety about vision loss, 69.8% reported elementary or lower education, and 64.9% had a 20,000 TRY or lower monthly income. Micronutrient intake was positively associated with anxiety (p=0.0001) and education (p=0.02) but not with monthly income (p=0.1).<br><br>CONCLUSION: According to this first report in Turkish patients with AMD which was evaluated nutrition profile based on AREDS2 suggestions, patients showed low adherence to AREDS recommendations for micronutrient intake and lifestyle modifications. Awareness among patients and ophthalmologists needs improvement.}, }
@article {pmid42345449, year = {2026}, author = {Salabati, M and Mabudian, L and Deshmukh, S and Afshar, E and Mahmoudzadeh, R and Brar, V}, title = {Association of interleukin-6 pathway inhibition with risk of age-related macular degeneration: A propensity-matched cohort study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261461923}, doi = {10.1177/11206721261461923}, pmid = {42345449}, issn = {1724-6016}, abstract = {PurposeTo evaluate the association between systemic tocilizumab exposure and the development of age-related macular degeneration (AMD) in a large real-world cohort.MethodsThis was a retrospective, propensity-matched cohort study including patients aged ≥40 years in the TriNetX Research Network with or without exposure to tocilizumab between May 2008 and May 2025. Patients with documented tocilizumab use were matched 1:1 to controls based on demographic and clinical characteristics within the TriNetX platform. Individuals with prior AMD were excluded from incident analyses. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for incident non-exudative and exudative AMD.ResultsAfter propensity score matching, 23,456 patients were included per group. Tocilizumab use was associated with a significantly lower risk of incident non-exudative AMD (RR, 0.282; 95% CI, 0.230-0.346; p < 0.001) and incident exudative AMD (RR, 0.234; 95% CI, 0.159-0.344; p < 0.001) compared with matched controls.ConclusionsSystemic tocilizumab exposure was associated with a lower incidence of both non-exudative and exudative AMD in this real-world cohort. These findings should be considered hypothesis-generating and support further study of the relationship between IL-6 signaling and AMD.}, }
@article {pmid42336230, year = {2026}, author = {Fazal, O and Loya, A and Muayad, J and Alsoudi, AF and Bordbar, DD and Chaaya, C and Weng, CY and Rahimy, E and Patel, NA}, title = {Dopamine-Enhancing Therapies and Risk of Neovascular AMD Conversion: A Target Trial Emulation.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.06.037}, pmid = {42336230}, issn = {1879-1891}, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of central vision loss worldwide. Emerging evidence suggests that targeting dopaminergic pathways may influence AMD progression. This study evaluates whether levodopa ± carbidopa or dopamine receptor D2 (DRD2) agonists are associated with reduced risk of conversion to neovascular AMD (nAMD).<br><br>DESIGN: Population-based clinical cohort study.<br><br>PARTICIPANTS: Adults aged &#x2265;18 years diagnosed with non-neovascular AMD between May 2005 and May 2025, within the TriNetX U.S. Collaborative Network, a federated electronic health record database spanning 69 healthcare organizations.<br><br>METHODS: This retrospective cohort study emulated four distinct target trials comparing new users of (1) levodopa (&#xb1; carbidopa) or (2) DRD2 agonists (pramipexole, ropinirole, bromocriptine, rotigotine, or cabergoline) to new users of two comparators (pantoprazole or gabapentin). Patients with prior nAMD or prescriptions of other dopamine-enhancing agents (e.g., selegiline, rasagiline, tolcapone) were excluded. Each exposure group was independently matched to comparators using 1:1 propensity score matching for selected demographics, social factors, comorbidities, and AMD stage.<br><br>MAIN OUTCOME MEASURES: The primary outcome was 3-year risk of conversion from non-neovascular AMD to nAMD. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. An &#x3b1; level of 0.05 was used to determine statistical significance.<br><br>RESULTS: Patients prescribed levodopa &#xb1; carbidopa had a reduced 3-year risk of conversion to nAMD relative to their matched counterparts prescribed pantoprazole (levodopa n=1312, control n=1312; HR 0.67; 95% CI, 0.45-0.98) and gabapentin (levodopa n=1675, control n=1675; HR 0.69; 95% CI, 0.50-0.95). No significant difference was observed in 3-year risk of conversion to nAMD between DRD2 agonists use relative to pantoprazole (DRD2 n=1603, control n=1603; HR 0.81; 95% CI, 0.58-1.13) or gabapentin (DRD2 n=2779, control n=2779; HR 0.92; 95% CI, 0.72-1.19).<br><br>CONCLUSIONS: In this cohort study, levodopa &#xb1; carbidopa use was associated with lower 3-year risk of conversion to nAMD in two independent matched comparisons, whereas DRD2 agonists were not associated with significant differences in risk. These findings suggest dopaminergic signaling may influence AMD progression and warrant further prospective investigation.}, }
@article {pmid42336282, year = {2026}, author = {Enyong, EN and Bankole, OO and Gurley, JM and McClellan, ME and Liu, L and Ding, SY and Agbaga, MP and Chucair-Elliott, AJ and Ash, JD and Elliott, MH}, title = {Non-caveolar caveolin-1 in retinal Müller glia promotes innate immune responses.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {113290}, doi = {10.1016/j.jbc.2026.113290}, pmid = {42336282}, issn = {1083-351X}, abstract = {Caveolae are specialized plasma membrane invaginations implicated in ocular diseases including primary open angle glaucoma, diabetic retinopathy and age-related macular degeneration. Caveolin-1 (CAV1) typically functions within caveolae where it associates with a co-regulatory protein, CAVIN1 (also known as polymerase I and transcript release factor; PTRF), which is necessary for caveolae formation. However, CAV1 can also reside outside of caveolae in planar "scaffolds," though the function of this non-caveolar CAV1 remains unclear. Here we show that Müller glia, the major macroglial cells of the retina, abundantly express CAV1 with minimal CAVIN1/PTRF expression both in situ and in the MIO-M1 Müller glial cell line. Transmission electron microscopy confirmed that morphologically identifiable caveolae are virtually absent in Müller glia, indicating that CAV1 is predominantly non-caveolar. Transgenic CAVIN1/PTRF expression induced caveolae formation, demonstrating functional competence. Non-caveolar CAV1 in MIO-M1 Müller glia promoted Toll-like receptor-4 (TLR4) signaling, as either CAV1 silencing or its sequestration into caveolae by CAVIN1/PTRF overexpression significantly suppressed lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) upregulation through reduced NF-κB activation. Conversely, in human retinal endothelial cells (HRECs) where CAV1 predominantly localizes to caveolae, CAV1 silencing enhanced inflammatory responses. These results demonstrate that non-caveolar CAV1 in Müller glia promotes a pro-inflammatory phenotype that can be attenuated by CAV1 silencing or sequestration into caveolae, suggesting cell context-specific roles for CAV1 in inflammatory regulation with potential therapeutic implications for ocular inflammatory diseases.}, }
@article {pmid42336619, year = {2026}, author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Wang, YX and Nangia, V and Panda-Jonas, S}, title = {Estimation of high myopia-associated optic neuropathies: the Two-Continent Eye Study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2026-329849}, pmid = {42336619}, issn = {1468-2079}, abstract = {PURPOSE: To estimate probabilities of high myopia-associated glaucomatous/glaucoma-like optic neuropathy (GLON) and non-glaucomatous optic neuropathy (NGON).<br><br>METHODS: Participants of four population-based investigations (Beijing Eye Study (n=3316 participants; age: 40+ years), Ural Eye and Medical Study (n=5372; age: 40+ years), Ural Very Old Study (n=586; age: 85+ years), Ural Children Eye Study (n=4328; age: 6+ years), Central India Eye and Medical Study (n=4374; age: 30+ years) underwent medical and ophthalmological examinations.<br><br>RESULTS: The study population (n=35&#x2009;167 eyes; 17&#x2009;996 individuals) was randomly divided (ratio: 1:1) into a development and validation subgroup. In the development subgroup, the GLON prevalence equation was: -20.221+0.359&#xd7;Axial Length+0.083&#xd7;Age+0.706&#xd7;Indian Ethnicity+0.198&#xd7;Intraocular Pressure (IOP)+0.780&#xd7;NGON-Presence. The NGON prevalence equation was: -38.136+1.202&#xd7;Axial Length+0.038&#xd7;Age-2.745&#xd7;Indian Ethnicity+0.566&#xd7;Myopic Macular Degeneration Stage+1.300&#xd7;GLON Presence. In the validation subgroup, these equations had an area under the receiver operating characteristic curve for GLON prevalence and NGON prevalence of 0.881 and 0.964, respectively. Applying the equations, a non-Indian individual (axial length: 28&#x2009;mm; IOP: 22&#x2009;mm Hg) had a GLON probability of 3.5% and 60.2% at the ages of 30 years and 75 years, respectively, and an NGON probability of 3.42% and 16.4%, respectively. With an axial length of 30&#x2009;mm, GLON probability and NGON probability increased from 6.9% to 75.6% and from 28.2% to 68.4% from age 30 years to 75 years.<br><br>CONCLUSIONS: The equations offer a rough estimate of optic nerve damage probability at present and at older age, based on axial length, IOP, ethnicity and ocular comorbidity. The calculated probability of GLON and NGON (IOP: 22&#x2009;mm Hg, age: 75 years) at an axial length of 28&#x2009;mm was 60.2% and 16.4%, respectively, and 75.6% and 68.4%, respectively, for an axial length of 30&#x2009;mm.}, }
@article {pmid42336620, year = {2026}, author = {Wu, AL and Guo, Y and Hormel, TT and Flaxel, CJ and Hwang, TS and Huang, D and Jia, Y and Bailey, ST}, title = {Drusen volume and reticular pseudodrusen volume from optical coherence tomography with deep learning as risk factors for progression to late age-related macular degeneration in eyes with reticular pseudodrusen and contralateral macular neovascularisation.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329021}, pmid = {42336620}, issn = {1468-2079}, abstract = {AIM: To implement a deep learning-based segmentation algorithm to quantify reticular pseudodrusen (RPD) and drusen volumes on optical coherence tomography (OCT) and investigate their association with progression to late age-related macular degeneration (AMD).<br><br>METHODS: A retrospective analysis included study eyes with RPD and contralateral neovascular AMD using 6&#xd7;6&#x2009;mm macular OCT (Solix; Visionix/Optovue, Inc). Automated segmentation quantified RPD and drusen volumes, including large drusen and drusenoid pigment epithelial detachment (PED), and late AMD development was evaluated over 2 years. Associations between baseline volumetric biomarkers and progression were evaluated using Cox proportional hazards models.<br><br>RESULTS: Fifty-one eyes (mean age 74.9&#xb1;7.65 years) were included. The median (IQR) baseline RPD volume was 0.018&#x2009;mm&#xb3; (0.004-0.52) and total drusen volume was 0.009&#x2009;mm&#xb3; (0.001-0.064). Over 24.2&#xb1;1.20 months, late AMD developed in 20 eyes (39.2%). In multivariable Cox regression models adjusted for age, each 0.01&#x2009;mm&#xb3; increase in baseline RPD volume (HR: 1.082; p=0.002) and total drusen volume (HR: 1.080; p<0.001) were associated with progression to late AMD. In an exploratory drusen subtype analysis, progression to late AMD was independently associated with baseline RPD volume, large drusen volume and drusenoid PED volume.<br><br>CONCLUSION: The deep learning-based volumetric segmentation tool allows OCT-derived automated volume quantification of different types of drusen based on OCT. In eyes with RPD and contralateral neovascular AMD, greater RPD volume and large drusen and/or drusenoid PED volume carried greater risk of developing late AMD in 2 years.}, }
@article {pmid42337105, year = {2026}, author = {Kazantzis, D and Keskin, AM and Thottarath, S and Kubravi, HS and Sheemar, A and Sivaprasad, S and , }, title = {Prevalence of bacillary layer detachment (BALAD) in treatment naive neovascular age-related macular degeneration (nAMD) and response to treatment after loading phase of aflibercept 2 mg: PRECISE study report 9.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42337105}, issn = {1476-5454}, abstract = {PURPOSE: To estimate the prevalence of BALAD in Treatment Naïve nAMD patients in the PRECISE study and report the response after loading phase of 2 mg aflibercept treatment.<br><br>METHODS: The PRECISE study included patients aged above 50 years with treatment na&#xef;ve nAMD and a baseline visual acuity (VA) between 24 and 78 letters ETDRS. All participants received three monthly aflibercept 2&#x2009;mg injections followed by 8-week post-treatment follow up. BALAD prevalence, baseline clinical characteristics and the visual and anatomical response to aflibercept loading were evaluated.<br><br>RESULTS: Among the 1981 eligible eyes, BALAD was observed in 69 eyes (3.6%). BALAD was found in 2.7% of eyes with type 1 MNV, 6.8% of eyes with type 2 MNV, 0.5% of eyes with retinal angiomatous proliferation (RAP) and in 1.6% of eyes with polypoidal choroidal vasculopathy (PCV) (p&#x2009;<&#x2009;0.0001). Eyes with BALAD at baseline had significantly lower VA and higher CST compared to eyes without BALAD. BALAD resolved in 63 out of 69 eyes (91.3%). VA improved and CST reduced post-treatment. Fibrosis was observed in 28 (40.6%) and ellipsoid zone disruption in 55 (79.7%) out of 69 eyes in the final visit.<br><br>CONCLUSIONS: This study estimated that BALAD was present in 3.6% of eyes with treatment na&#xef;ve nAMD and occurred more frequently in type 2 MNV. Although BALAD resolved in 91.3% of eyes and visual and anatomical recovery was achieved, eyes with BALAD showed a frequent early association with fibrosis and ellipsoid zone disruption at the post-loading phase visit.}, }
@article {pmid42337629, year = {2026}, author = {Egger, D and Amesbauer, F and Mohamed, H and Thiel, KE and Angermann, R and Waldstein, SM}, title = {Real-world outcomes after switching to faricimab in previously treated neovascular age-related macular degeneration: longitudinal outcomes up to 24 months.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00889-0}, pmid = {42337629}, issn = {2056-9920}, abstract = {BACKGROUND: In neovascular age-related macular degeneration (nAMD), persistent disease activity despite anti-VEGF therapy is common. Switching to faricimab may improve outcomes and extend treatment intervals in treatment-resistant patients, but long-term real-world data remain limited.<br><br>METHODS: In this retrospective, single-centre study, 43 eyes of 38 patients with treatment-resistant nAMD were switched to faricimab and followed for up to 24 months. Insufficient disease control was defined as inability to extend treatment intervals beyond 8 weeks under a treat-and-extend regimen. Outcomes included best-corrected visual acuity (BCVA), central subfield thickness (CST), pigment epithelial detachment (PED) height, fluid status, and treatment intervals. Longitudinal changes were analysed using mixed-effects models. Exploratory analyses of baseline and early response predictors were performed.<br><br>RESULTS: Mean BCVA remained stable throughout follow-up, with no significant change from baseline at any time point (p&#x2009;>&#x2009;0.05). CST decreased significantly at all visits, ranging from -&#x2009;45.8&#xa0;&#x3bc;m (95% CI&#x2009;-&#x2009;65.3&#xa0;&#x3bc;m to -&#x2009;26.3&#xa0;&#x3bc;m) at 1 month to -&#x2009;52.3&#xa0;&#x3bc;m (95% CI&#x2009;-&#x2009;73.7&#xa0;&#x3bc;m to -&#x2009;30.8&#xa0;&#x3bc;m) at 24 months (p&#x2009;<&#x2009;0.001). PED height decreased at 1 month (-&#x2009;19.0&#xa0;&#x3bc;m; 95% CI&#x2009;-&#x2009;33.6&#xa0;&#x3bc;m to -&#x2009;4.4&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.011) and remained reduced from 12 to 24 months, ranging from -&#x2009;25.9&#xa0;&#x3bc;m (95% CI&#x2009;-&#x2009;39.7&#xa0;&#x3bc;m to -&#x2009;12.1&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.001) to -&#x2009;49.1&#xa0;&#x3bc;m (95% CI&#x2009;-&#x2009;65.1&#xa0;&#x3bc;m to -&#x2009;33.0&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.001). Presence of subretinal fluid decreased significantly at all time points, with odds ratios (OR) ranging from 0.064 (95% CI 0.01 to 0.41, p&#x2009;=&#x2009;0.004) at 1 month to 0.012 (95% CI 0.01 to 0.10, p&#x2009;<&#x2009;0.001) at 24 months, whereas intraretinal fluid showed a variable response, with a significant reduction observed at 3 months only (OR 0.204, 95% CI 0.05 to 0.79, p&#x2009;=&#x2009;0.021). The proportion of eyes with a dry macula increased from 0% at baseline to 23.1% at 12 months and 24.0% at 24 months. Treatment intervals extended from 5.9&#x2009;&#xb1;&#x2009;1.2 weeks before switch to 8.7&#x2009;&#xb1;&#x2009;2.6 weeks at 12 months (p&#x2009;<&#x2009;0.001) and 10.6&#x2009;&#xb1;&#x2009;3.0 weeks at 24 months (p&#x2009;<&#x2009;0.001). No adverse events were observed.<br><br>CONCLUSION: Switching to faricimab was associated with improved anatomical outcomes and extended treatment intervals while maintaining stable visual acuity, suggesting benefits primarily related to anatomical control and reduced treatment burden.}, }
@article {pmid42339613, year = {2026}, author = {Panos, GD and Vagiakis, I and Empeslidis, T and Amoaku, W and Konstas, AG}, title = {Retinal anti-VEGF treatment now, and what next? From loading doses to long-game thinking.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14656566.2026.2695091}, pmid = {42339613}, issn = {1744-7666}, }
@article {pmid42339716, year = {2026}, author = {Kelkar, A and Kelkar, J and Garg, Y and Jain, HH and Sengupta, S}, title = {Smartphone-based offline AI for multi-disease retinal screening: Real-world accuracy.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261462321}, doi = {10.1177/11206721261462321}, pmid = {42339716}, issn = {1724-6016}, abstract = {ObjectiveTo evaluate the diagnostic accuracy of a multi-disease offline artificial intelligence system (Medios-AI, MAI), integrated into a smartphone-based fundus camera, for simultaneous screening of diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD) in a real-world setting.MethodsIn this prospective cross-sectional study, 193 adults (371 eyes) aged ≥18 years with DR, glaucoma, AMD, or normal fundus were enrolled between May and December 2024. Dilated fundus imaging was performed using the Remidio Fundus on Phone (FoP) and Zeiss Clarus 500 cameras. Ungradable images were excluded. The offline MAI algorithm generated disease-specific reports, which were compared to masked grading of Clarus images by two fellowship-trained ophthalmologists. In ambiguous cases, the AI report defaulted to "either DR or AMD."ResultsMAI achieved sensitivity of 99.3% (95% CI: 96-100), specificity of 95.7% (95% CI: 92-98), and AUROC of 0.99 for detecting any retinal disease. For glaucoma (n = 109), sensitivity was 98.2% (95% CI: 94-100), specificity 99.0% (95% CI: 97-100), AUROC 0.99. For AMD (n = 56), sensitivity was 88.9% (95% CI: 77-96), specificity 97.5% (95% CI: 95-99), AUROC 0.93. For DR (n = 78), sensitivity was 84.6% (95% CI: 75-92), specificity 99.0% (95% CI: 97-100), AUROC 0.92. Agreement on vertical cup-to-disc ratio between AI and graders ranged from -0.1 to +0.1, with intergrader ICC of 0.97 (P < 0.001 for all comparisons).ConclusionsMAI demonstrated significant diagnostic accuracy for DR, glaucoma, and AMD using an offline, smartphone-based platform, supporting scalable, point-of-care retinal screening in resource-limited settings.}, }
@article {pmid42340411, year = {2026}, author = {Romano, E and Capuano, V and Fragiotta, S and Parravano, M and Beretta, F and Sacconi, R and Lambiase, A and Souied, EH and Querques, G}, title = {Pachy-reticular pseudodrusen associated with pachyvitelliform maculopathy.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42340411}, issn = {1435-702X}, abstract = {PURPOSE: To characterize the phenotype of pachy-reticular pseudodrusen (pachy-RPD) associated with pachyvitelliform maculopathy (PVM).<br><br>METHODS: A retrospective, case-control study of patients over 50 with pachy-RPD (choroidal thickness&#x2009;>&#x2009;250&#xa0;&#x3bc;m) associated with PVM. Acquired vitelliform lesions (AVL) without other comorbidities were included as controls. Medical records and multimodal imaging from two tertiary centers were analyzed, including structural optical coherence tomography (OCT), fundus autofluorescence, OCT angiography (OCTA), and dye-based angiography.<br><br>RESULTS: Twenty-five eyes of 17 patients (mean age 74&#x2009;&#xb1;&#x2009;11 years) fulfilled the inclusion criteria. Best-corrected visual acuity was 20/64 (range 20/32 to 20/250). Most of the lesions were unilateral (59%) with foveal involvement. Pachy-RPD/PVM eyes had smaller lesions, lower central macular thickness (p&#x2009;=&#x2009;0.04), lesion height (p&#x2009;=&#x2009;0.008), and lesion width (p&#x2009;<&#x2009;0.001) compared to AVL eyes. Despite this, pachy-RPD/PVM eyes presented more frequent external limiting membrane discontinuities (56% vs. 27%, p&#x2009;=&#x2009;0.03) and hypertransmission (68%) compared to AVL eyes (8%, p&#x2009;<&#x2009;0.001). Six out of 25 eyes (24%) of PVM cases showed late-stage complications in the fellow eye, including type 1 macular neovascularization (4 eyes) and macular atrophy (2 eyes). These eyes exhibited thinning of the outer retina (306 &#xb1; 32&#xa0;&#x3bc;m vs. 277 &#xb1; 13&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.007) and macular cube (9.1 &#xb1; 1.0&#xa0;mm&#xb3; vs. 8.1 &#xb1; 0.4&#xa0;mm&#xb3;, p&#x2009;=&#x2009;0.01).<br><br>CONCLUSION: Pachy-RPD and PVM represent a phenotypic variant within the heterogenous spectrum of vitelliform lesions. The present study highlights distinct imaging and morphological features of pachy-RPD/PVM compared to AVL, revealing a stronger association between choroidal status, outer retina involvement, and hypertransmission.}, }
@article {pmid42331015, year = {2026}, author = {Prinz, J and Prokosch, V}, title = {Malnutrition as a Risk Factor for Cerebral and Glaucomatous Neurodegeneration - Mechanisms and Therapeutic Strategies.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2841-0517}, pmid = {42331015}, issn = {1439-3999}, abstract = {ABSTRACT: BACKGROUND: Neurodegenerative diseases are an increasing challenge for healthcare systems in the context of demographic change. They affect the central nervous system, including the brain-manifesting, for example, as dementia-as well as the retina, as seen in glaucoma or age-related macular degeneration. Malnutrition-defined as quantitative or qualitative under- or overnutrition-affects key mechanisms that contribute to neuronal and retinal neurodegeneration.<br><br>ABSTRACT: OBJECTIVE: The aim of this study is to systematically present the pathophysiological mechanisms of malnutrition-related neurodegeneration, to evaluate the current evidence on dietary patterns and cognitive health, and to derive practical clinical strategies for nutritional optimization.<br><br>ABSTRACT: METHODS: Narrative literature review based on peer-reviewed publications from the fields of nutritional medicine, geriatrics, neurology, ophthalmology, and public health.<br><br>ABSTRACT: RESULTS: Malnutrition promotes oxidative stress, mitochondrial dysfunction, chronic neuroinflammation, and vascular dysregulation, and it influences neurotransmitter synthesis. These mechanisms are relevant to both cerebral and ocular neurodegenerative processes. The Mediterranean diet and the MIND diet are associated with a significantly reduced risk of cognitive impairment; for ocular diseases, interventional studies in age-related macular degeneration in particular demonstrate protective effects of antioxidant supplementation, whereas evidence for glaucoma is currently based predominantly on observational data. Screening approaches and micronutrient diagnostics enable early identification of at-risk individuals. Building on this, individualised dietary interventions and targeted supplementation of selected nutrients could be potentially preventive and stabilising therapeutic strategies.<br><br>ABSTRACT: CONCLUSION: Malnutrition is a key modifiable risk factor for neurodegenerative diseases of the brain and retina. More intense integration of nutritional diagnostics and therapy into neurological, geriatric, and ophthalmological care structures appears warranted.}, }
@article {pmid42331067, year = {2026}, author = {Ashourizadeh, H and Gilbert, JB and Ross, C and Kearney, WC and Grinspan, N and Elze, T and Vavvas, DG and Miller, JW and Lorch, AC and Armstrong, GW and , }, title = {Cataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.06.016}, pmid = {42331067}, issn = {1549-4713}, abstract = {OBJECTIVE: To evaluate the association between cataract surgery (CS) and the risk of conversion from dry age-related macular degeneration (dAMD) to neovascular AMD (nvAMD), and to identify factors associated with conversion.<br><br>DESIGN: Population-based retrospective time-to-event study SUBJECTS: Eyes of patients aged &#x2265;55 years with early or intermediate dAMD and phakic status at baseline were identified in the American Academy of Ophthalmology IRIS&#xae; Registry (Intelligent Research in Sight) on or after January 1st, 2016, to December 31st, 2022. Eyes that underwent CS were classified as exposed; those without CS during the study period were nonexposed.<br><br>METHODS: Propensity score matching was used to match eyes 1:1 on age, sex, race, and ethnicity, laterality, AMD stage, and smoking status. CS was modeled as a time-varying exposure. We used Cox proportional hazards regression to estimate the hazard of conversion to nvAMD.<br><br>MAIN OUTCOME MEASURES: Conversion from dAMD to nvAMD, defined by registry-derived diagnosis codes, between exposed and nonexposed cohorts.<br><br>RESULTS: After matching, 40,053 eyes were included in each exposed and nonexposed cohort (total N = 80,106 eyes). CS was associated with a higher risk of nvAMD conversion (hazard ratio [HR] = 1.22; 95% CI, 1.16-1.30; P < 0.001). Time-varying analysis demonstrated that this association was strongest early in follow-up (HR &#x2248; 2.5 in year 1) and declined steadily, reaching non-significance (HR &#x2248; 1.0) by year 4. At year 6, the cumulative incidence of nvAMD was 17.7% in the exposed cohort versus 15.2% in the nonexposed cohort. Baseline AMD stage moderated the effect of CS, with weaker effects of CS for intermediate AMD (Interaction HR = 0.82, 95% CI, 0.78-0.92).<br><br>CONCLUSIONS: CS was associated with a modestly increased overall rate of conversion from dAMD to nvAMD; however, the time-dependent pattern suggests that the observed association likely reflects increased surveillance or unrecognized pre-existing nvAMD rather than a sustained biological effect of surgery. The absolute risk difference was small (&#x223c;3.3% over six years). These findings support careful perioperative evaluation in dAMD patients but do not implicate CS as a long-term driver of neovascular conversion.}, }
@article {pmid42331911, year = {2026}, author = {Vijay Singh, SH and Yeap, W and Too, LK and Allende, A and Hall, G and Hunyor, A and Madigan, MC and Merani, R and Ortiz, J and Rodriguez, M and Wong, J and Invernizzi, A and Killingsworth, M and Pye, V and Mehta, H and Petsoglou, C and Cherepanoff, S}, title = {A combined ex vivo fundus imaging-histology protocol for clinicopathological validation of human donor eyes with limited medical history.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-58078-w}, pmid = {42331911}, issn = {2045-2322}, abstract = {This study evaluated a combined ex vivo fundus imaging-histology protocol to improve accuracy of diagnosis in human donor eyes with limited medical history. Fifty-one formalin-fixed eyes from 32 donors underwent a standardised workflow comprising ex vivo fundus photography, selective spectral-domain optical coherence tomography (SD-OCT), and comprehensive histological examination. Medical/surgical retinal ophthalmologists independently reviewed imaging, while ophthalmic pathologists performed masked histological assessment. Diagnostic metrics were calculated using histology as the reference standard. Ex vivo imaging identified definitive pathology in 10 of 51 eyes (19.6%) and possible abnormalities in 4 eyes (7.8%). Histological analysis, however, revealed definitive pathology in 20 eyes (39.2%), detecting a broader range of diseases, including early age-related macular degeneration, hypertensive vasculopathy, and a rare choroidal tumour. Concordance was observed in 27 eyes (52.9%), mainly where no pathology was present. Significant discordance occurred in 24 eyes (47.1%), comprising 13 false negatives and 11 false positives (including misclassified pathology). Consequently, the sensitivity and specificity of ex vivo imaging for detecting pathology were 18.8% and 68.6%, respectively. While ex vivo imaging is a practical screening tool, imaging alone may miss or misclassify pathology due to postmortem artefacts and a lack of validated interpretive criteria. A combined imaging-histology approach validates the limited tissue available from eye-bank programs and maximises research value.}, }
@article {pmid42332210, year = {2026}, author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, NA}, title = {Summary of Research: Aflibercept 8 mg versus Faricimab Treat‑and‑Extend for Diabetic Macular Edema or Neovascular Age‑Related Macular Degeneration: A Bayesian Fixed‑Effect Network Meta‑analysis of Clinical Trials.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42332210}, issn = {2193-8245}, abstract = {This is a summary of the original research article "Aflibercept 8 mg versus Faricimab Treat‑and‑Extend for Diabetic Macular Edema or Neovascular Age‑Related Macular Degeneration: A Bayesian Fixed‑Effect Network Meta‑analysis of Clinical Trials." Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are eye diseases that can be treated with anti-vascular endothelial growth factor (anti-VEGF) therapies. As these therapies are given by injections into the eye, reducing the number of injections could reduce the treatment burden on patients and healthcare providers. Aflibercept 8 mg and faricimab treat-and-extend (T&amp;E) may enable longer dosing intervals compared with other available anti-VEGF therapies for patients with DME and nAMD; however, they have not been compared against each other directly in clinical trials. This study used a statistical method called a network meta-analysis (NMA) to compare aflibercept 8 mg and faricimab T&amp;E by synthesizing data from clinical trials, enabling an indirect comparison in the absence of head-to-head studies. Outcomes included the mean number of injections, changes in vision [best-corrected visual acuity (BCVA)] and changes in macula thickness [central subfield thickness (CST)]. CST should reduce if the treatment is working. On the basis of indirect comparison of available clinical trial data, this exploratory study found that there were significantly fewer injections with aflibercept 8 mg treatment compared with faricimab T&amp;E over 2 years, for both patients with DME and nAMD, and there were no significant differences between the two medications for BCVA or CST changes. NMAs are based on indirect comparisons and therefore have limitations, and clinical trials or real-world studies would be required to confirm these conclusions. Please refer to the original article for further details on the methods and limitations of this analysis.}, }
@article {pmid42332292, year = {2026}, author = {Owsley, C and Curcio, CA}, title = {Impaired Rod-Mediated Vision is the Functional Hallmark of Ageing and Early and Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {}, number = {}, pages = {}, pmid = {42332292}, issn = {1475-1313}, support = {R01AG04212/AG/NIA NIH HHS/United States ; R01EY029595/EY/NEI NIH HHS/United States ; R01EY029595/EY/NEI NIH HHS/United States ; }, abstract = {Laboratory and patient-oriented research on photoreceptors and vision in ageing and early and intermediate age-related macular degeneration (AMD) were conducted in parallel starting in the 1990s by Christine Curcio and Cynthia Owsley, respectively. They joined forces in two longitudinal observation studies, the Alabama Study on Age-related Macular Degeneration (ALSTAR) in 2009 and in ALSTAR2 in 2019, together involving >1100 participants. These studies established rod-mediated dark adaptation (RMDA) measured close to the fovea as the first functional biomarker for incident early AMD and the progression of AMD. These studies used standardised grading of colour fundus photography and prioritised large samples for statistical power. RMDA is a global measure of dysregulated transport between the circulation and photoreceptors, involving at least seven different steps in a retinoid re-supply route especially needed by rods, and a surrogate for the delivery of other essentials across this route. The choice of functional and imaging outcome measures was informed by a model of AMD pathophysiology based on drusen biology, as discovered in the laboratory using high-quality human donor eyes. Specifically, high-risk drusen in the central retina were thought to result from large lipoproteins constitutively made by the retinal pigment epithelium and impaired in transit to circulation by ageing changes in Bruch's membrane and choriocapillaris. Imaging studies in ALSTAR/2 thus included optical coherence tomography (OCT) angiography assessments of choriocapillaris flow signal and OCT assessments of outer bands involved in intercellular transfer (interdigitation zone). Of seven vision tests utilised in ALSTAR2, only RMDA achieved a Minimum Clinically Important Difference at 3 years follow-up. This research highlights the importance of developing functionally valid structural endpoints for use in early and intermediate AMD intervention trials. Research to date supports the idea that functional changes emerge earlier than structural changes in early and intermediate AMD. Clinicaltrials.gov # NCT04112667 (registration date October 7, 2019).}, }
@article {pmid42333298, year = {2026}, author = {Dasan, R and Chen, MY and Du, J and Do, BK and Osman, DH and Williams, BK and Ali, MH}, title = {Association Between the Social Deprivation Index and Neovascular Age-Related Macular Degeneration Outcomes.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261442916}, pmid = {42333298}, issn = {2474-1272}, abstract = {Purpose: To evaluate whether disease severity at diagnosis and treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) may be stratified by the Social Deprivation Index (SDI; a measure of socioeconomic status [SES] where higher scores indicate greater socioeconomic deprivation). Methods: We conducted a retrospective cohort study of 643 adults with newly diagnosed unilateral nAMD who were treated with antivascular endothelial growth factor (anti-VEGF) therapy at the Retina Group of Washington. Data collected included best-corrected visual acuity (BCVA) at baseline and 12 months, presence of submacular hemorrhage, and injection frequency in the first year of treatment. Logistic regression was used to assess associations between SDI and BCVA outcomes. Results: A higher SDI score was associated with lower odds of achieving a BCVA of ≥20/40 at 12 months (odds ratio, 0.69, 95% CI, 0.48-0.98; P = .039). Submacular hemorrhage and non-White race were predictive of poorer outcomes, whereas sex at birth was not predictive. The number of anti-VEGF injections received over 12 months was similar between the high SDI quantile group and low SDI quantile group (mean 9.1 vs 8.8; P = .053). Age, baseline BCVA ≥20/40, and race were significant predictors of achieving a BCVA ≥20/40 at 12 months. BCVA at baseline was not significantly different between the SDI quantile groups, suggesting that disparities emerge during treatment rather than at diagnosis. Conclusions: The SDI is a useful metric of social determinants of health in patients with nAMD. Higher SDI was associated with poorer visual outcomes despite similar baseline vision and treatment exposure, suggesting that disparities extend beyond diagnosis to treatment effectiveness. These findings underscore the multifactorial nature of socioeconomic influences, including race, treatment adherence, and access, and the need for targeted strategies to improve equitable care.}, }
@article {pmid42333299, year = {2026}, author = {Berkowitz, ST and Gilbert, JB and Ross, CJ and Kearney, WC and Lorch, A and Miller, JW and Rossin, EJ and Sternberg, P and Finn, AP}, title = {Intravitreal Anti-VEGF Injection Transitions Across Bevacizumab, Biosimilar, and Branded Medications: The IRIS Registry Study.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261455206}, pmid = {42333299}, issn = {2474-1272}, abstract = {Purpose: To characterize antivascular endothelial growth factor medication transitions among patients with neovascular age-related macular degeneration (nAMD), including delays in care and economic impacts. Methods: A retrospective observational cohort study analyzed participants with nAMD in the IRIS (Intelligent Research in Sight) Registry who were treated with antivascular endothelial growth factor agents from 2015 to 2024. Four cohorts were analyzed: (1) bevacizumab only, (2) bevacizumab transitioned to a biosimilar, (3) bevacizumab transitioned to a branded agent, and (4) bevacizumab transitioned to a biosimilar and then to a branded agent. The main outcome measures were number of intravitreal injection events, transitions in medications, and injection intervals. Results: A total of 182 757 eyes with nAMD met inclusion criteria: 136 451 received bevacizumab only; 2184, bevacizumab followed by a biosimilar; 335, bevacizumab followed by a biosimilar, followed by branded medication; and 43 787, bevacizumab followed by a branded agent. Newer agents (faricimab and aflibercept 8 mg) experienced additional delays of 8.6 days compared with aflibercept 2 mg (P < .001). Economic modeling based on IRIS transition rates and medication cost showed that bevacizumab transitioned to a biosimilar and then to a branded agent was 36.3% and 11.62% more costly than bevacizumab transitioned to a biosimilar (P < .001) and bevacizumab transitioned to a branded agent (P < .001), respectively, within 2 years. Similar cost differences persisted in 5- and 10-year projections. Bevacizumab transitioned to a biosimilar and then to a branded agent was the costliest pathway compared with transitions to biosimilars and branded agents, regardless of which branded agent was used. Conclusions: IRIS Registry cohort data suggest possible demographic differences in patients undergoing medication transitions, including biosimilar agents, as well as delays in care with medication transitions. Economic simulations suggest that multiple transitions may be more costly than direct transitions from bevacizumab to either biosimilar or branded agents.}, }
@article {pmid42333946, year = {2026}, author = {Jang, HY and Choi, S and Kim, SJ and Kim, S and Jo, DH and Lee, TG and Park, KS and Kim, JH}, title = {Humanin Mitigates Aβ-Induced Retinal Pigment Epithelium Injury via AMPK-Beclin1-Dependent Mitophagy.}, journal = {Aging cell}, volume = {25}, number = {7}, pages = {e70601}, doi = {10.1111/acel.70601}, pmid = {42333946}, issn = {1474-9726}, support = {2022M3A9E4017127//National Research Foundation of Korea/ ; RS-2023-00260351//National Research Foundation of Korea/ ; 202200004004//Kun-hee Lee Child Cancer and Rare Disease Project/ ; 18-2023-0010//Seoul National University Hospital/ ; GTL25021-000//National Research Council of Science and Technology/ ; }, mesh = {*Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; *Mitophagy/drug effects ; *Amyloid beta-Peptides/metabolism/toxicity ; *Beclin-1/metabolism ; *AMP-Activated Protein Kinases/metabolism ; *Intracellular Signaling Peptides and Proteins/metabolism/pharmacology ; Mitochondria/metabolism/drug effects ; Animals ; Cell Line ; Phosphorylation/drug effects ; Macular Degeneration/metabolism/pathology ; }, abstract = {Amyloid beta (Aβ), a key component of drusen in age-related macular degeneration (AMD), induces oxidative stress, mitochondrial dysfunction, and degeneration in the retinal pigment epithelium (RPE), contributing to progressive vision loss in the elderly. We investigated the protective role of Humanin (HN), a mitochondria-derived peptide with known neuroprotective effects in Aβ-related neurodegenerative diseases, in retinal pathology induced by subretinal injection of FITC-labeled Aβ. HN enhanced the clearance of Aβ-accumulated mitochondria in the RPE while preserving retinal function and RPE barrier integrity. In ARPE-19 cells, HN activated AMP-activated protein kinase (AMPK), leading to phosphorylation of ULK1 and Beclin1, which promoted the interaction between Beclin1 and Parkin and their translocation to mitochondria. This process facilitated the removal of Aβ-accumulated mitochondria in the RPE. Our results demonstrate that targeting mitophagy in the RPE with HN may offer a promising therapeutic strategy for AMD.}, }
@article {pmid42334128, year = {2026}, author = {Li, X and Wang, C and Duan, J and Shang, Q}, title = {Personalized Dosing System Guided by Cross-Scale Metabolic Imaging Biomarkers in Neovascular Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {6}, pages = {27}, doi = {10.1167/tvst.15.6.27}, pmid = {42334128}, issn = {2164-2591}, mesh = {Humans ; *Biomarkers/metabolism ; Female ; *Aqueous Humor/metabolism ; Retrospective Studies ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; *Precision Medicine/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Metabolomics/methods ; Bevacizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/metabolism/diagnostic imaging ; Aged, 80 and over ; }, abstract = {PURPOSE: Long-term anti-vascular endothelial growth factor (VEGF) response in neovascular age-related macular degeneration (nvAMD) varies widely, with no validated predictive biomarkers. We aimed to establish a metabolic imaging biomarker-based framework for personalized efficacy prediction and dosing.<br><br>METHODS: In this single-center retrospective study, patients with clinically confirmed nvAMD and age-matched controls (cataract surgery with normal fundus or non-neovascular AMD) were enrolled. Aqueous humor was analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Patients with nvAMD received anti-VEGF therapy (three doses then as needed, followed for &#x2265;12 months) and were classified by structural/functional outcomes as responders or nonresponder. Comparative metabolomics identified phenotype-associated metabolites. An integrated prediction model was built using orthogonal partial least squares discriminant analysis, receiver operating characteristic analysis, and multivariate logistic regression.<br><br>RESULTS: The aqueous humor of patients with nvAMD showed lipid remodeling and suppressed purine metabolism. Eight key metabolites were identified as phenotype-associated biomarkers (indole-3-acetic acid, N-acetyl-L-alanine, xanthine, arachidonoyl lysophosphatidic acid, taurine, indole-3-lactic acid, 4-acetoxyphenol, and Lys-Ile). Among them, indole-3-acetic acid and N-acetyl-L-alanine showed the highest predictive performance for long-term treatment response (area under the curve = 0.802 each). Integrating metabolic markers with baseline imaging and clinical parameters improved predictive accuracy (area under the curve = 0.86). Longitudinal analysis showed partial normalization of metabolite levels in responders after anti-VEGF therapy.<br><br>CONCLUSIONS: nvAMD involves responder-specific metabolic reprogramming. Integrating aqueous metabolites with imaging biomarkers enables accurate pretreatment prediction of anti-VEGF efficacy, supporting personalized therapy.<br><br>TRANSLATIONAL RELEVANCE: This work links aqueous metabolic profiling to clinical decision-making by identifying biomarkers predictive of long-term anti-vascular endothelial growth factor response. Their integration with routine imaging yields a pretreatment stratification model (area under the curve = 0.86), which may inform individualized monitoring and earlier regimen adjustment in predicted nonresponders.}, }
@article {pmid42323663, year = {2026}, author = {Shettigar, MP and Chhablani, J and Tyagi, M and Narula, R and Narayanan, R}, title = {Accuracy of Retinal Pigment Epithelium (RPE) undulations (Oscillatory sign) as an optical coherence tomography biomarker of acute RPE tears.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00874-7}, pmid = {42323663}, issn = {2056-9920}, abstract = {PURPOSE: To evaluate the sensitivity and specificity of Retinal Pigment Epithelium (RPE) undulations (Oscillatory sign) on Optical Coherence Tomography (OCT) and assess its potential role as a predictive OCT biomarker for RPE tears in eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Retrospective analysis of the patients who had RPE tears following nAMD, which were documented by multimodal imaging. All cases were evaluated for RPE undulations on OCT, and the sensitivity and specificity of the Oscillatory sign in eyes with documented RPE tears were assessed.<br><br>RESULTS: Seventy-nine eyes out of 936 eyes with nAMD, which were analyzed, were found to have RPE tears, as documented by colour fundus photographs (CFP) and fundus autofluorescence (FAF). OCT images were analyzed for RPE undulations, a sign of oscillatory activity. Thirty-eight eyes of 79 (48.1%) eyes were found to have the oscillatory sign. Oscillatory sign showed a high specificity of 98.95% and sensitivity of 48.10% for an underlying RPE tear. The negative predictive value of the Oscillatory sign was 95.39%, and the positive predictive value of 80.85%.<br><br>CONCLUSION: The Oscillatory sign of RPE undulations is not sensitive, but it is a highly specific biomarker and can help facilitate the diagnosis of occult RPE tears.}, }
@article {pmid42323782, year = {2026}, author = {Waisberg, E and Ong, J and Yaldo, L and Kumar, R and Wang, W and Calabresi, V and Coco, G and Gonzalez-Lima, F and Lee, AG and Giannaccare, G}, title = {Near-Infrared and Red-Light Photobiomodulation for Ocular Aging and Diseases: A Narrative Review.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42323782}, issn = {2193-8245}, abstract = {Near-infrared (NIR) and red light photobiomodulation (PBM) has gained increasing interest as a non-invasive therapeutic approach for a variety of medical conditions including ocular diseases. The eye represents a particularly suitable target for light-based therapies owing to its optical accessibility and the high mitochondrial demand of various tissues such as the retina and optic nerve. Ocular aging and several ophthalmic disorders are associated with mitochondrial dysfunction, oxidative stress, and chronic inflammation, providing a biological rationale for the use of PBM as a potential adjunctive approach. This narrative review provides an evidence-weighted, indication-specific synthesis of NIR and red-light PBM in ophthalmology, emphasizing device- and protocol-dependence, differences between multiwavelength PBM and repeated low-level red-light therapy, study-design limitations, safety considerations, and clinical translation gaps. A structured literature search was conducted using major scientific databases to identify relevant experimental studies, clinical trials, and observational reports. The review focuses on proposed mitochondria-centered mechanisms of action, including cytochrome c oxidase-mediated signaling, nitric oxide release, reactive oxygen species-driven hormetic responses, and downstream anti-inflammatory effects. Particular emphasis is reserved to dry age-related macular degeneration, for which literature is more relevant, and to dry eye disease owing to meibomian gland dysfunction and myopia, for which a body of evidence is progressively growing. For other ocular indications, data remain preliminary or exploratory. Overall, available data support biological plausibility and suggest possible functional or anatomical signals in selected ocular diseases, but the clinical evidence remains heterogeneous, with substantial variability in devices, wavelengths, dosimetry, treatment protocols, and study design, and remains insufficient to define PBM as established therapy for most indications. However, the clinical evidence remains heterogeneous, with substantial variability in devices, wavelengths, dosimetry, and treatment protocols. Although available studies generally report favorable short-term tolerability, long-term safety and the role of PBM in routine ophthalmic practice remain insufficiently defined. Well-designed, adequately randomized controlled trials with standardized treatment parameters are required to determine efficacy, optimal protocols, and long-term clinical relevance.}, }
@article {pmid42324318, year = {2026}, author = {Pu, J and Ji, Y and Li, M and Zhang, X and Zuo, C and Zhuang, X and Hao, X and He, G and Gan, Y and Su, Y and Zhang, Y and Yang, R and Chen, X and Mi, L and Wen, F}, title = {Indocyanine green angiography and machine learning analysis determine topographic distribution of peripheral hard drusen in a Chinese cohort.}, journal = {Communications medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s43856-026-01737-w}, pmid = {42324318}, issn = {2730-664X}, abstract = {BACKGROUND: Hard drusen appear as hyperfluorescent dots on indocyanine green angiography (ICGA) due to their high phospholipid content. This study aims to explore the distribution of peripheral hard drusen across age groups and retinal regions, and their correlation with macular pathology including hard drusen, soft drusen, and progression to neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A hospital-based retrospective study was conducted at Zhongshan Ophthalmic Center. Patients who underwent ICGA over a five-year period were included and categorised into seven age groups. Hard drusen were quantified across nine retinal quadrants using the Trainable Weka Segmentation machine learning plugin. A subgroup of patients underwent imaging follow-up to assess progression to nAMD.<br><br>RESULTS: Here we show, across 1562 normal eyes (14,058 ICGA images) quantified using a validated machine learning model (Dice coefficient: 0.697; sensitivity: 82.93%; ICC: 0.944), that age 50 represents a critical threshold for drusen accumulation, with significant increases observed across all nine quadrants. The nasal quadrants demonstrate earlier and more prominent drusen accumulation compared to the temporal quadrants (P&#x2009;<&#x2009;0.001 across ages 20-69 years). Notably, the central superior quadrant shows consistent associations with macular hard drusen counts (Std&#x3b2;&#x2009;=&#x2009;0.104, P&#x2009;=&#x2009;0.010), soft drusen volume (&#x3c1;&#x2009;=&#x2009;0.657, P&#x2009;=&#x2009;0.020), and progression to nAMD (OR&#x2009;=&#x2009;1.324, P&#x2009;=&#x2009;0.040).<br><br>CONCLUSIONS: Peripheral hard drusen accumulate preferentially in the nasal quadrants and increase markedly after age 50. Comprehensive peripheral retinal evaluation during ICGA examination may hold potential clinical value for AMD monitoring, pending further prospective validation.}, }
@article {pmid42324406, year = {2026}, author = {Serra, R and Français, C and Boulet, JF and Pinna, A and Philippakis, E and Zambrowski, O and Mathis, T and Kodjikian, L and Coscas, F}, title = {Vascular remodeling of macular neovascularization following switch to intravitreal faricimab in neovascular AMD.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42324406}, issn = {1435-702X}, abstract = {PURPOSE: To describe qualitative optical coherence tomography angiography (OCTA) changes in age-related macular degeneration (AMD) macular neovascularization (MNV) treated with faricimab.<br><br>METHODS: This was a retrospective study including 30 eyes with active AMD-related Type 1 MNV, resistant to traditional anti-vascular endothelial growth factor (VEGF) agents, receiving intravitreal faricimab. Complete ophthalmological evaluation, consisting of best corrected visual acuity (BCVA), traditional multimodal imaging, and OCTA scans, was performed at baseline and at the last examination. OCTA high-flow networks corresponding to MNV were qualitatively and quantitatively analyzed to assess morphological changes. Furthermore, the correlation between MNV OCTA pattern and presence/absence of exudation signs on spectral domain OCT (SD-OCT) was evaluated.<br><br>RESULTS: On baseline OCTA, 11/30 eyes showed a sea fan pattern, 13/30 a medusa pattern, and the remaining 6/30 an indistinct pattern. At the last follow-up, in 12/30 eyes, the MNV pattern remained unchanged. In these 12 cases, SD-OCT revealed the exudative signs in 11/12 eyes (one with intra-retinal fluid, ten with sub-retinal fluid) at the final evaluation. In the remaining 18/30, MNV pattern changed to a dead tree type with no exudation signs at the last follow-up in 17/18 eyes. The mean interval of intravitreal injection was significantly extended from 4 to 7.2&#xb1;2.3 weeks (p&#x2009;<&#x2009;0.0001) with BCVA stabilization. At the last follow-up the dead tree OCTA pattern resulted to be significantly related to the absence of exudation sings (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: Our study reveals that the initial MNV pattern frequently moves toward a dead tree pattern after switching from traditional anti-VEGF agents to faricimab therapy.}, }
@article {pmid42324407, year = {2026}, author = {Sarao, V and Veritti, D and Lanzetta, P}, title = {Comment to: Hashiya N, Maruko I, Maruko R et al. Increased intraocular pressure immediately after aflibercept 8 mg intravitreal injection for neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol (2026) 264:1611-1617. doi:10.1007/s00417-026-07117-3.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42324407}, issn = {1435-702X}, }
@article {pmid42326286, year = {2026}, author = {Orozco Loaiza, G and Alfaro Guerra, MJ and Murillo Sotela, A and Villalobos Villalobos, P}, title = {Complement Inhibition in Geographic Atrophy: Clinical Evidence for Pegcetacoplan and Avacincaptad Pegol.}, journal = {Cureus}, volume = {18}, number = {5}, pages = {e109282}, pmid = {42326286}, issn = {2168-8184}, abstract = {Geographic atrophy (GA) represents the advanced form of non-neovascular age-related macular degeneration (AMD) and is associated with progressive and irreversible vision loss. Evidence has implicated the dysregulation of the complement cascade as a pivotal factor in GA pathophysiology, leading to the development of complement inhibition therapies. Pegcetacoplan, a C3 inhibitor, and avacincaptad pegol, a C5 inhibitor, are currently the only therapies approved by the Food and Drug Administration (FDA) for GA secondary to AMD. Major clinical trials, including OAKS, DERBY, GALE, GATHER1, and GATHER2, have demonstrated a statistically significant reduction in GA lesion area, with reductions of approximately 16-22% for pegcetacoplan and 14-28% for avacincaptad pegol compared with sham. Despite favorable structural outcomes, functional endpoints like best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA) have shown limited improvement, and concerns remain regarding their side effect profile. This narrative review provides an overview of GA, emphasizing its pathophysiology and the role of the complement cascade, and discusses the clinical relevance of complement inhibitors in the current management of the disease.}, }
@article {pmid42326551, year = {2026}, author = {Ariza-Torrado, IP and Groman-Lupa, S and Martínez-Córdoba, CJ and Monje-Tobar, P}, title = {Evaluation of Structural and Functional Outcomes After the Application of an Initial Single Dose of Faricimab.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261451498}, pmid = {42326551}, issn = {2474-1272}, abstract = {Purpose: To evaluate functional and structural outcomes after application of a single intravitreal dose of faricimab in patients with chronic retinal diseases. Methods: In this observational, longitudinal, prospective study, best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated before and 4, 8, 12, and 16 weeks after a single dose of intravitreal faricimab. Results: A total of 49 eyes of 41 patients were included, of which 28 were treatment-naive eyes (had not previously received intravitreal therapy) and 21 were eyes in which a switch from a previous antiangiogenic agent was indicated. The main diagnoses were diabetic macular edema in 63.3% (31 eyes) and age-related macular degeneration in 24.5% (12 eyes). Ten eyes (20.4%) required additional antiangiogenic injections due to worsening or only partial improvement in CMT, whereas ~58% of eyes completing follow-up did not require further treatment and maintained anatomic improvement on optical coherence tomography throughout the study period. At 4 weeks after initial injection, CMT was reduced a mean 117.5 µm. Statistically significant decreases were maintained over 8, 12, and 16 weeks. In treatment-naive eyes, initial mean reduction in CMT was 119.7 µm, with sustained decreases at all time points, while in the treatment-switch group, initial mean reduction in CMT was 114.6 µm, with sustained decreases at weeks 4 and 8, but not at weeks 12 and 16. In the general sample, 53.1% to 61.0% of eyes demonstrated clinically modest improvements in BCVA, equivalent to 1 to 2 Early Treatment Diabetic Retinopathy Study lines of vision, but visual changes were not statistically significant. Conclusions: Clinically meaningful reductions in CMT were observed and sustained over the 16-week follow-up after a single intravitreal faricimab injection. Notably, a substantial proportion of eyes did not require additional antiangiogenic treatment during follow-up, suggesting that mandatory loading doses may not be universally required to achieve short-term anatomic benefit in selected patients. However, functional gains were modest and did not reach statistical significance, underscoring that anatomic improvement does not necessarily translate into meaningful visual recovery. These findings highlight the importance of individualized dosing strategies in real-world clinical practice and suggest potential implications for reducing treatment burden, costs, and barriers to access in eligible patients.}, }
@article {pmid42328256, year = {2026}, author = {Sukumaran, D and Benjamin, D and Abdul Karim, MN and Amankwah, R and Maharajan, P and Mubashar, M and Sarmad, A and Sharma, P and Dhar-Munshi, S}, title = {Real-World Functional and Anatomical Outcomes of Intravitreal Faricimab in Suboptimal Responders With Neovascular Age-Related Macular Degeneration: A 24-Month Clinical Audit.}, journal = {Cureus}, volume = {18}, number = {6}, pages = {e111161}, pmid = {42328256}, issn = {2168-8184}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a chronic sight-threatening disease requiring repeated intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Although established anti-VEGF agents have transformed the prognosis of nAMD, a proportion of patients demonstrate persistent exudation, limited durability, or inability to extend beyond short treatment intervals. Faricimab is a bispecific intravitreal antibody targeting both vascular endothelial growth factor A and angiopoietin-2, designed to improve vascular stability, reduce exudation, and increase treatment durability. This clinical audit evaluates 24-month real-world outcomes following switching to faricimab in suboptimal responders with nAMD in an NHS medical retina service.<br><br>METHODS: A retrospective clinical audit was conducted of 274 eyes with nAMD switched to faricimab at Sherwood Forest Hospitals NHS Foundation Trust between January 2023 and January 2025. All eyes had previously received at least one anti-VEGF agent and were switched because of persistent disease activity, inadequate anatomical response, or high treatment burden. Data were extracted from the Medisight electronic patient record and cross-checked against pharmacy records. Primary outcomes were best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters and central macular thickness (CMT) on optical coherence tomography. Secondary outcomes included injection interval extension, number of injections, and safety events.<br><br>RESULTS: Baseline mean BCVA was 58.1 letters. Mean BCVA improved to 59.7 letters at less than six months, representing a gain of +1.6 letters. At 12 months, mean BCVA was 56.9 letters, a change of -1.2 letters from baseline. At 24 months, mean BCVA was 54.4 letters, a change of -3.7 letters from baseline. Anatomical response was more consistent, with mean CMT reductions of -29.1 &#xb5;m at less than six months, -34.7 &#xb5;m at 12 months, and -45.7 &#xb5;m at 24 months. The mean injection interval increased from 7.88 weeks before switching to 10.67 weeks after switching, representing an extension of +2.79 weeks. No cases of intraocular inflammation, retinal vasculitis, or endophthalmitis were recorded.<br><br>CONCLUSION: In this real-world NHS audit, faricimab achieved meaningful anatomical improvement and reduced treatment burden in treatment-experienced nAMD eyes switched because of suboptimal response or limited durability on previous anti-VEGF therapy. Visual acuity improved modestly during early follow-up but declined slightly over 24 months, despite progressive anatomical drying. This functional-anatomical dissociation likely reflects the chronicity of disease and irreversible macular damage in a switch population. Faricimab appears to be a safe and effective second-line option for reducing exudation and extending treatment intervals, although expectations regarding long-term visual gain should be realistic.}, }
@article {pmid42328840, year = {2026}, author = {Xavier, C and Toutée, A and Sales de Gauzy, T and March de Ribot, F and Forte, PA and Bodaghi, B and Bousquet, E and Touhami, S}, title = {Bilateral Giant Pigment Epithelial Detachments and Unilateral RPE Tear and Exudative Retinal Detachment After Tadalafil Exposure: Case Report and Review of the Literature.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001947}, pmid = {42328840}, issn = {1937-1578}, abstract = {PURPOSE: To describe a case of bilateral giant pigment epithelial detachments (PEDs) complicated by unilateral giant retinal pigment epithelium (RPE) tear and macula-off exudative retinal detachment (RD) in the context of tadalafil exposure, and to place it in the spectrum of reported non-AMD giant RPE tears.<br><br>METHODS: Case report with multimodal imaging and comprehensive systemic work-up, combined with a focused literature review of exudative RD associated with giant RPE tears unrelated to age-related macular degeneration.<br><br>RESULTS: A 62-year-old man presented with blurred vision in the left eye. Examination revealed bilateral giant temporal PEDs and, in the left eye, a crescent-shaped giant RPE tear contiguous with an inferior macula-off exudative RD and bilateral pachychoroid on OCT. Extensive systemic and ocular investigations were unremarkable except for regular tadalafil use. Discontinuation of tadalafil led to rapid resolution of subretinal fluid and improvement of BCVA to 20/25 OS at one year, whereas re-exposure triggered recurrence of serous macular detachment. Using the Naranjo scale, the causal relationship between tadalafil and the ocular event was rated as "certain". Literature review identified 33 published patients (43 eyes) with exudative RD and giant RPE tears without AMD, most commonly associated with bullous CSC and other pachychoroid entities.<br><br>CONCLUSION: Bilateral giant PEDs with unilateral giant RPE tear and macula-off exudative RD can occur in the setting of tadalafil-associated bullous CSC. This case underscores the importance of systematically reviewing systemic medications, including phosphodiesterase-5 inhibitors, in patients with atypical serous retinal detachments and RPE tears.}, }
@article {pmid42329076, year = {2026}, author = {Zhang, R and Jin, A and Fan, X and Li, F and Feng, Y and Zeng, L and Wang, J and Fan, N and Niu, L and Liu, D}, title = {Accelerometer-Derived Moderate-to-Vigorous Physical Activity and the Risk of Four Common Vision-Threatening Ocular Diseases.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {6}, pages = {24}, doi = {10.1167/tvst.15.6.24}, pmid = {42329076}, issn = {2164-2591}, mesh = {Humans ; Female ; Aged ; *Accelerometry ; Male ; *Exercise/physiology ; Risk Factors ; *Cataract/epidemiology ; Middle Aged ; *Glaucoma/epidemiology ; Proportional Hazards Models ; *Eye Diseases/epidemiology ; United Kingdom/epidemiology ; *Diabetic Retinopathy/epidemiology ; Follow-Up Studies ; Incidence ; *Macular Degeneration/epidemiology ; }, abstract = {PURPOSE: The purpose of this study was to investigate the association between accelerometer-derived moderate-to-vigorous physical activity (MVPA) and four common vision-threatening ocular diseases: cataract, diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma.<br><br>METHODS: A total of 77,644 UK Biobank participants with accelerometer-derived MVPA data were included. MVPA was categorized into three groups following World Health Organization (WHO) guidelines (<150, 150-299, and &#x2265;300 min/week). Incident cataract, DR, AMD, and glaucoma were identified from linked hospital and primary care records. Restricted cubic splines and Cox proportional hazards models were used to estimate hazard ratios (HRs). Mediation analysis was performed to explore potential mechanisms.<br><br>RESULTS: During a median follow-up of 6.2 years, 4283 cataract, 248 DR, 891 AMD, and 762 glaucoma events occurred. We identified an L-shaped association for cataract and a nonlinear association for DR (both P < 0.001; P < 0.05 for nonlinearity), a modest negative association for AMD (P = 0.028; P = 0.026 for nonlinearity), and no significant association for glaucoma. Compared with the reference group (<150 min/week), the groups achieving 150-299 min/week and &#x2265;300 min/week of MVPA exhibited significantly lower risks of cataract (HR = 0.91, 95% confidence interval [CI] = 0.84-0.98 for 150-299 min/week; and HR = 0.88, 95% CI = 0.82-0.95 for &#x2265;300 min/week), and DR (HR = 0.62, 95% CI = 0.45-0.86 for 150-299 min/week; and HR = 0.51, 95% CI = 0.37-0.71 for &#x2265;300 min/week). Mediation analysis indicated that inflammatory and metabolic indicators partially mediated the protective effect of MVPA on DR.<br><br>CONCLUSIONS: Higher levels of MVPA were associated with significantly lower risks of cataract and DR, with partial mediation through inflammatory and metabolic pathways for DR.<br><br>TRANSLATIONAL RELEVANCE: Our findings highlight MVPA as a potentially modifiable behavioral factor for ocular disease prevention.}, }
@article {pmid42330208, year = {2026}, author = {Ramachandran, ON and Talwar, D and Khare, G and Verma, L and Jena, S and Singh, S and Singh, K}, title = {Real-world efficacy of higher-dose aflibercept in pro-re-nata dosing without loading phases: A cost-effective approach for resource-limited settings.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_2483_25}, pmid = {42330208}, issn = {1998-3689}, abstract = {BACKGROUND: Aflibercept therapy for chronic macular diseases mandates loading dose phases followed by fixed intervals, placing a heavy and often prohibitive treatment burden on elderly patients in resource-limited settings. We evaluated the real-world efficacy of higher-dose aflibercept (4 mg/0.1 mL) versus standard dose (2 mg/0.05 mL) using immediate modified pro-re-nata (PRN) dosing without loading phases, with specific focus on burden reduction while maintaining therapeutic outcomes.<br><br>METHODS: This retrospective comparative study included 194 eyes (101 receiving 4 mg/0.1 mL, 93 receiving 2 mg/0.05 mL) with diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion treated with immediate modified PRN aflibercept between October 2023 and September 2024. The primary outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcomes assessed injection intervals, visit frequency, caregiver accompaniment, time commitments, and safety.<br><br>RESULTS: The mean baseline BCVA was 0.55 &#xb1; 0.18 logMAR (4 mg group) and 0.54 &#xb1; 0.17 logMAR (2 mg group). At final follow-up, both groups achieved comparable improvement: 0.45 &#xb1; 0.15 logMAR (4 mg) versus 0.47 &#xb1; 0.16 logMAR (2 mg), with no significant difference between groups (P = 0.23). The mean CMT reduction was 85.2 &#xb1; 45.8 &#x3bc;m (4 mg) versus 86.6 &#xb1; 48.2 &#x3bc;m (2 mg), P = 0.82. The 4 mg group recorded 22.6% fewer annual visits (4.8 versus 6.2, P < 0.001), translating to 8.52 fewer hours per patient per year. No safety concerns emerged with higher-dose extraction.<br><br>CONCLUSION: Higher-dose aflibercept with immediate modified PRN dosing achieves visual and anatomical outcomes comparable to standard dosing, with a 22.6% reduction in annual visit frequency. This approach addresses practical barriers to care in elderly populations requiring long-term anti-VEGF therapy in resource-limited settings.}, }
@article {pmid42317230, year = {2026}, author = {Örnek, K and Erşekerci, TK}, title = {Streptococcus salivarius endophthalmitis and corneal ring infiltrate after intravitreal bevacizumab injection.}, journal = {GMS ophthalmology cases}, volume = {16}, number = {}, pages = {Doc06}, pmid = {42317230}, issn = {2193-1496}, abstract = {A 65-year-old male patient received intravitreal bevacizumab for age-related macular degeneration. On the first day, he presented with ocular pain, corneal stromal infiltration and dense vitritis. Prompt intravitreal vancomycin and ceftazidime were injected after sampling. Widespread gram-positive cocci were seen on microscopy after staining the vitreous sample. No significant improvement took place the following day and the cornea was completely opacified. The patient underwent an early vitrectomy combined with penetrating keratoplasty. Culture grew Streptococcus salivarius. Postoperative visual acuity was hand motions and the retina was attached.}, }
@article {pmid42318308, year = {2026}, author = {Yu, C and Dong, L and Zhang, R and Li, H and Shi, X and Wu, H and Zhou, W and Li, Y and Wei, WB}, title = {Causal Effects of Gut Microbiota and Associated Metabolites on Retinal Diseases and Visual Impairment: A Mendelian Randomization Study.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {4233490}, pmid = {42318308}, issn = {2090-004X}, abstract = {BACKGROUND: Previous observational study findings have indicated a vital association between gut microbiota features and retinal diseases based on the "gut-retina" axis. However, whether their relationships underlie causal effects remains to be established.<br><br>METHODS: Instrumental variables of 211 gut microbiota taxa were obtained from a genome-wide association study (GWAS), and 28 gut-associated metabolites and pathways were included as exposures. A two-sample Mendelian randomization (MR) study was carried out to estimate gut microbiota effects on diabetic retinopathy (DR), early age-related macular degeneration (eAMD), retinal detachments and breaks (RDs/RBs), retinal vascular occlusion (RVO), disorders of the choroid and retina (D-C/R), and visual impairment. MR methods, including inverse variance weighted (IVW), MR&#x2012;Egger, weighted median, simple mode, and weighted mode methods, were used to investigate the causal relationship between gut microbiota features and various outcomes. Heterogeneity, pleiotropy, and stability tests of MR results were performed, and Bonferroni's correction was used to test the strength of the causal relationships between exposures and outcomes, as well as reverse and multivariable MR analyses.<br><br>RESULTS: Through MR analysis of 211 microbes and six clinical phenotypes, a total of 35 gut microbiome and 3 associated metabolites were found to be associated with various outcomes. Cochrane's Q test revealed that there was no significant heterogeneity between various single-nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to the MR&#x2012;Egger and MR-PRESSO global tests. After the Bonferroni-corrected test, Genus id.2041 (OR&#x2009;=&#x2009;0.874, 95% CI: 0.816-0.936, p = 1.10e - 04, IVW) showed robust causality with D-C/R, which had a nominal association with multiple other retinal diseases as well. Seven exposure-outcome effects markedly remained valid when BMI or alcohol intake frequency was separately included in multivariable MR analyses. According to the results of reverse MR analysis, no significant causal effect of outcomes was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found.<br><br>CONCLUSION: We confirmed a potential causal relationship between some gut microbiota features and retinal diseases, thus providing new insights into the gut microbiota-mediated mechanism of retinopathy and indicating vital biomarkers for potential diagnostic, therapeutic, and prevention strategies.}, }
@article {pmid42320872, year = {2026}, author = {Wang, L and Zhang, C and Li, N and Zhang, J and Liu, Y and Xu, G}, title = {Research Advances in Claudin-1 in the Eye.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111132}, doi = {10.1016/j.exer.2026.111132}, pmid = {42320872}, issn = {1096-0007}, abstract = {Claudin-1, a transmembrane protein integral to tight junctions, is indispensable for paracellular barrier formation and the establishment and maintenance of cellular polarity. In the eye, claudin-1 exhibits tissue-specific expression in critical structures such as the cornea and retina, where it contributes fundamentally to corneal transparency, blood-retinal barrier integrity, and retinal homeostasis. This review comprehensively synthesizes current knowledge on the spatial distribution and physiological roles of claudin-1 across ocular tissues. We critically evaluate recent mechanistic and translational advances implicating claudin-1 dysregulation in a spectrum of ocular pathologies: anterior segment disorders (dry eye disease, pterygium, infectious keratitis, and gelatinous drop-like corneal dystrophy), retinal diseases (diabetic retinopathy, age-related macular degeneration, central serous chorioretinopathy, and retinoblastoma), and other conditions (uveitis, glaucoma, post-cataract macular edema, and cataract). Finally, we assess the emerging therapeutic potential of claudin-1-both as a molecular target for barrier modulation and as a facilitator of paracellular drug delivery in ophthalmology.}, }
@article {pmid42321202, year = {2026}, author = {Rajala, A and Rajala, R and Trevino, LJ and Black, TM and Moiseyev, G and Kinter, M and Rajala, RVS}, title = {Interdependent roles of PKM2 in photoreceptors and RPE: implications for retinal degeneration.}, journal = {Cell death &amp; disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08997-3}, pmid = {42321202}, issn = {2041-4889}, support = {EY035282//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; EY021725//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, abstract = {Pyruvate kinase M2 (PKM2) functions as both a glycolytic enzyme and a transcriptional co-activator that coordinates metabolism and cell survival. Here, we define the developmental timing, cellular distribution, and physiological role of PKM isoforms in the mouse retina. PKM2 expression begins at postnatal day 2, preceding PKM1, and is highly enriched in photoreceptors, whereas PKM1 predominates in retinal ganglion cells. Conditional deletion of PKM2 in the retina, rods, or retinal pigment epithelium (RPE) demonstrated that PKM2 is essential for maintaining retinal structure and function. Loss of PKM2 impaired glycolytic activity, decreased ATP generation, and disrupted metabolic balance, leading to cellular disorganization and degeneration in both photoreceptors and the RPE. In the RPE, PKM2 deficiency decreased RPE65 protein levels and impaired the regeneration of 11-cis-retinal, disrupting the visual cycle. PKM2 deletion disrupted the normal cone opsin gradient, indicating that PKM2-dependent metabolic and transcriptional functions are essential for maintaining proper cone organization in the retina. Moreover, rod-specific deletion of PKM2 in Abca4 mutant mice showed early signs of retinal degeneration. The studies described in this manuscript highlight the interdependence of photoreceptor and RPE metabolism and show that PKM2 plays an important role in retinal energy homeostasis and neuronal survival, providing insight into the mechanisms underlying photoreceptor and RPE degeneration in age-related macular degeneration.}, }
@article {pmid42321514, year = {2026}, author = {Huang, J and Nittala, MG and Corradetti, G and Chung, YC and Quarta, A and Abbasgholizadeh, R and Soylu, C and Chujo, S and Velaga, SB and Sadda, SR}, title = {Spatial distribution of cuticular drusen and its association with category-specific progression risk in intermediate AMD.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42321514}, issn = {1476-5454}, support = {RO1EY023164//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; 1R01EY030614//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; RO1EY023164//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; 1R01EY030614//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, abstract = {OBJECTIVES: To investigate the spatial distribution pattern of cuticular drusen using en face OCT and determine its relationship with 2-year progression of age-related macular degeneration (AMD).<br><br>METHODS: This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enroled in the Amish Eye Study who completed two years of follow-up. Multimodal imaging, including volume spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three Early Treatment Diabetic Retinopathy Study (ETDRS) grid zones using ImageJ. K-means clustering analysis was used to categorize distribution patterns. Firth's penalized logistic regression evaluated association between cuticular drusen distribution categories and progression to late AMD at 2 years.<br><br>RESULTS: Three spatial phenotypes of cuticular drusen were identified: central-dominant (57.5%), outer-macular-dominant (32.2%), and diffuse (10.3%). Over two years, five eyes progressed to late AMD, four of which belonged to the outer-macular-dominant group. In unadjusted Firth regression, the outer-macular-dominant phenotype was associated with higher odds of progression than the other phenotypes (OR 7.16; 95% CI 1.24-74.20, p&#x2009;=&#x2009;0.027). After adjustment for subretinal drusenoid deposits (SDDs) and large drusen, the association between spatial phenotype and progression remained (OR 11.53; 95% CI 1.62-169.00; p&#x2009;=&#x2009;0.013), while SDDs were also associated with progression (OR 9.26; 95% CI 1.36-78.65; p&#x2009;=&#x2009;0.023).<br><br>CONCLUSIONS: Clustering of en face OCT-derived spatial features identified distinct cuticular drusen phenotypes within the macula. The outer-macular-dominant phenotype may be associated with an increased likelihood of AMD progression in this exploratory analysis.}, }
@article {pmid42322415, year = {2026}, author = {Chujo, S and Quarta, A and Abbasgholizadeh, R and Chung, YC and Kwak, H and Soylu, C and Alhelaly, M and Rattu, R and Huang, J and Corradetti, G and Velaga, S and Nittala, MG and Uji, A and Sadda, SR}, title = {Development of a conceptual, HOV-inspired spatial weighting model for quantifying geographic atrophy severity.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42322415}, issn = {1435-702X}, abstract = {PURPOSE: To develop a Hill of Vision (HOV)-inspired severity score for geographic atrophy (GA) and evaluate its ability to capture spatial characteristics of disease progression, including lesion location and proximity to the foveal center, compared with the conventional lesion area (ΔArea) metric.<br><br>METHODS: This retrospective analysis included 103 untreated fellow eyes from the MAHALO study with fundus autofluorescence images available at all visits. GA lesions were delineated and binarized to generate mask images. A Gaussian weighting function based on the distance from the foveal center was applied to each lesion pixel to model the spatial distribution of retinal functional resolution, yielding a volumetric "severity score," that was kept unitless for the purpose of this exercise. For eyes with multifocal GA, total severity was defined as the sum of all lesion values. The correlation between &#x394;Area and &#x394;Severity (0-18 months) was assessed using Pearson's coefficient. Lesion expansion direction was visualized using Euclidean distance maps.<br><br>RESULTS: Mean changes in &#x394;Area and &#x394;Severity over 18 months were 1.02&#x2009;&#xb1;&#x2009;1.11&#xa0;mm&#xb2; and 5811&#x2009;&#xb1;&#x2009;4584, respectively. A weak but significant correlation was observed (r&#x2009;=&#x2009;0.36, p&#x2009;<&#x2009;0.01). Cases with peripheral enlargement showed modest severity increases, whereas parafoveal expansion caused steep severity rises despite relatively minimal area growth. Expansion maps revealed that the direction and expansion to the fovea strongly influenced severity progression.<br><br>CONCLUSIONS: The HOV-inspired severity score provides a spatially weighted framework for assessing GA progression and may complement conventional structural metrics by incorporating lesion location relative to the fovea.}, }
@article {pmid42323420, year = {2026}, author = {Zhang, Y and Gao, J and Zhou, A and Wang, J}, title = {Optical coherence tomography angiography imaging characteristics and clinical significance of the foveal vertical hyperreflective line in patients with macular neovascularisation.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42323420}, issn = {1476-5454}, support = {82501291//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {BACKGROUND: To investigate the incidence, characteristic manifestations, outcomes of changes, and potential clinical significance of the foveal vertical hyperreflective line (FVHL) on optical coherence tomography angiography (OCTA) in patients with macular neovascularisation (MNV).<br><br>METHODS: This retrospective observational case series was conducted using OCTA images, fundus photographs, best-corrected visual acuity measurements, and other clinical information of the eyes of patients with MNV who were followed up for at least 3 months between January 2024 and October 2025. The incidence of FVHLs, OCTA characteristics, FVHL changes, and prognoses were analysed.<br><br>RESULTS: Among the 322 eyes of 161 patients with MNV, 14 patients (8.7%) showed FVHLs in 15 eyes. The mean age of the patients was 69.29&#x2009;&#xb1;&#x2009;12.68 years. Among the eyes with an FVHL, 13 were of patients with age-related macular degeneration-MNV and two were of patients with pathological myopia-MNV. All cases showing FVHLs occurred in the early stages of the disease course (within 1-3 months) and did not disappear during follow-up. Among the cases with FVHLs, 80% showed no obvious changes in the FVHLs and 20% showed weakened reflexes. The eyes that showed FVHL maintenance had a higher interdigitation zone/ellipsoid zone (IZ/EZ) repair rate (91.7%) than those with reflex-weakened FVHLs (p&#x2009;=&#x2009;0.009).<br><br>CONCLUSIONS: FVHLs were present in 8.7% of patients with MNV. The eyes that maintained FVHLs exhibited a higher degree of IZ/EZ restoration than the eyes with reflex-weakened FVHLs. This OCTA finding may provide a foundation for assessing the recovery responses of retinal photoreceptors and M&#xfc;ller cells.}, }
@article {pmid42323551, year = {2026}, author = {Lan, L and Lan, J and Ren, X and Ye, B}, title = {Impact of a structured patient engagement program on treatment adherence, injection persistence, and visual outcomes in real-world anti-VEGF therapy for neovascular age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-05045-8}, pmid = {42323551}, issn = {1471-2415}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual impairment among older adults. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has improved visual outcomes, real-world effectiveness is often limited by poor adherence and treatment discontinuation. This study evaluated the impact of a structured patient engagement program on treatment adherence, injection persistence, visual outcomes, and patient-reported outcomes in patients receiving anti-VEGF therapy for nAMD.<br><br>METHODS: This single-center retrospective observational comparative cohort study included 350 patients with nAMD treated between January 2022 and December 2024. Patients received either standard care alone (n&#x2009;=&#x2009;175) or standard care plus a structured patient engagement program (n&#x2009;=&#x2009;175) incorporating individualized education, adherence counseling, appointment reminders, and proactive follow-up communication. Primary outcomes were treatment adherence and injection persistence. Secondary outcomes included best-corrected visual acuity (BCVA), patient satisfaction, and disease understanding.<br><br>RESULTS: Patients enrolled in the engagement program demonstrated significantly better adherence than those receiving standard care. The mean number of missed injection visits was lower (0.51&#x2009;&#xb1;&#x2009;0.68 vs. 1.48&#x2009;&#xb1;&#x2009;1.27; P&#x2009;<&#x2009;0.001), and delayed injections exceeding two weeks were less frequent (22.3% vs. 50.9%; P&#x2009;<&#x2009;0.001). Good adherence was achieved in 89.1% of patients in the engagement group compared with 50.3% in the standard care group (P&#x2009;<&#x2009;0.001), while treatment persistence was higher (90.9% vs. 77.7%; P&#x2009;=&#x2009;0.001). Final BCVA was significantly better in the engagement group (0.61&#x2009;&#xb1;&#x2009;0.30 vs. 0.70&#x2009;&#xb1;&#x2009;0.34 LogMAR; P&#x2009;=&#x2009;0.015), and a greater proportion of patients experienced visual improvement (65.1% vs. 52.6%; P&#x2009;=&#x2009;0.023). Patient satisfaction and disease understanding were also significantly higher among patients receiving the engagement intervention (P&#x2009;<&#x2009;0.001 for both). Safety outcomes were comparable between groups.<br><br>CONCLUSIONS: A structured patient engagement program was associated with improved treatment adherence, enhanced injection persistence, and better short- to mid-term visual outcomes in patients receiving anti-VEGF therapy for nAMD. These findings support the integration of patient-centered engagement strategies into routine retinal care to optimize real-world treatment outcomes.}, }
@article {pmid42314011, year = {2026}, author = {Saravia, MJ and Rojas, J and de Los Santos, C and Bazterrechea, P and Forgues, F and Monteros, N and Cortalezzi, JM and Zeolite, I and Sgattoni, E and Zeman, L and Vidosevich, M and Magnano, G and Zas, M and Rosendi, E and Franco, J and Calhoun, MW and Wilbur, LR and Rosenfeld, PJ and Lylyk, P}, title = {Feasibility Study of Balloon Angioplasty for the Treatment of Ophthalmic Artery Stenoses in Patients With Geographic Atrophy.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-9}, doi = {10.3928/23258160-20260527-01}, pmid = {42314011}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: A safety and feasibility study was conducted using balloon angioplasty to treat ophthalmic artery (OA) stenoses in patients with age-related macular degeneration (AMD) with geographic atrophy (GA).<br><br>PATIENTS AND METHODS: Patients &#x2265; 60 years of age received OA angioplasty using an investigational catheter system and were followed for 6 months. Changes in stenosis, best-corrected visual acuity (BCVA), MNRead acuity charts, ophthalmic imaging, and a validated questionnaire were evaluated.<br><br>RESULTS: Eleven patients were treated. All adverse events were treated as needed and resolved without sequelae. Treated patients demonstrated a mean improvement over baseline in BCVA (P = .01) and reading speed (P = .03) at study exit. Mean subfoveal choroidal thickness increased over baseline (P = .004) and fellow eyes (P = .03) through week 4, remaining above baseline at study exit. Participants reported mean improvements in both mobility and reading.<br><br>CONCLUSION: Treating OA stenoses using angioplasty in patients with GA was safe with apparent visual function benefit.}, }
@article {pmid42314743, year = {2026}, author = {Volle, DC}, title = {New-Onset Visual Snow Syndrome Following Prescription of Bupropion in a Patient With Macular Degeneration and Geographic Atrophy.}, journal = {The primary care companion for CNS disorders}, volume = {28}, number = {3}, pages = {}, doi = {10.4088/PCC.25cr04169}, pmid = {42314743}, issn = {2155-7780}, }
@article {pmid42314988, year = {2026}, author = {Lu, H and Rakoski, AI and Ri, K and Zhou, L and Shi, L and Cho, H and Wu, S and Chen, SS and Neill, AN and Catazaro, J and Wong, VW and Yoo, A and Wilson, DS and Doloff, JC and Duh, EJ}, title = {Intraocular delivery of crystalline sorafenib provides sustained, potent inhibition of wet age-related macular degeneration.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {}, number = {}, pages = {115120}, doi = {10.1016/j.jconrel.2026.115120}, pmid = {42314988}, issn = {1873-4995}, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness worldwide. Anti-VEGF agents are very beneficial for nAMD, with intravitreal (IVT) delivery becoming the gold standard for treatment of nAMD and other retinal conditions. Incomplete response remains a major challenge, as does the requirement for high-frequency, repeat IVT injections, which pose a significant burden on patients. Many potential drug candidates have attractive pharmacodynamic profiles but are limited by their insolubility, precluding IVT administration. These include tyrosine kinase inhibitors (TKIs), which target multiple receptors regulating angiogenesis, including the VEGF receptors. Thus, there is a great need for alternative treatment approaches. To this end, we developed a crystallization formulation approach for sorafenib (SFB), a very hydrophobic anti-angiogenic, multi-receptor TKI, for sustained intraocular release. We evaluated the efficacy of this formulation in two mouse models of nAMD: laser-induced choroidal neovascularization (LI-CNV) and Vldlr knockout (Vldlr-/-). Crystalline sorafenib ("Crystal SFB") exhibited controlled, prolonged drug release across both an accelerated release assay in vitro and in C57BL/6 mice, with ~13% remaining in the eye after 28 days in vivo. Further, a single IVT injection effectively suppressed both neovascularization and vascular leakage, two critical clinical parameters in nAMD, for at least 28 days. IVT administration of Crystal SFB did not have discernible adverse effects on intraocular pressure, retinal morphology assessed by OCT, or neuroretinal function as measured by ERG. These results suggest that Crystal SFB offers a promising alternative for long-term nAMD management and a proof-of-concept for ocular utilization of other crystallized drugs.}, }
@article {pmid42315290, year = {2026}, author = {Jackson, TL and Desai, R and Wafa, HA and Lee, CN and Wang, Y and Peacock, JL and Peto, T and Chakravarthy, U and Zhu, X and Dakin, H and Wordsworth, S and Clinch, P and Ramazzotto, L and Neffendorf, JE and O'Sullivan, JM and Reeves, BC and , }, title = {Stereotactic radiotherapy for neovascular age related macular degeneration: year 3 and 4 extended follow up results of a randomised, double masked, sham controlled, device trial (STAR).}, journal = {BMJ (Clinical research ed.)}, volume = {393}, number = {}, pages = {e729694}, doi = {10.1136/bmj-2026-729694}, pmid = {42315290}, issn = {1756-1833}, mesh = {Humans ; Female ; Double-Blind Method ; Visual Acuity ; Male ; Follow-Up Studies ; Treatment Outcome ; Aged ; *Radiosurgery/methods/adverse effects ; *Wet Macular Degeneration/drug therapy/radiotherapy ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; *Macular Degeneration ; }, abstract = {OBJECTIVE: To assess the effects of stereotactic radiotherapy (SRT) for neovascular age related macular degeneration (AMD) beyond the two year primary outcome of the StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR) trial.<br><br>DESIGN: Randomised, double masked, sham controlled, device trial involving preplanned recall from standard care.<br><br>SETTING: 30 NHS hospitals in the UK.<br><br>PARTICIPANTS: 411 participants aged at least 50 years with chronic, pretreated, active AMD.<br><br>INTERVENTION: Participants received one-off 16 Gray SRT or sham SRT delivered using a robotically controlled device. After two years of monthly study visits, participants reverted to routine care, with anti-VEGF drug selection and dosing intervals based on local practice, but with masking maintained, and repeat data collection at years 3 and 4 study visits.<br><br>MAIN OUTCOME MEASURES: The main efficacy outcome at year 4 was the number of anti-VEGF injections, tested for superiority (fewer injections). The other main outcome was visual acuity, tested for non-inferiority (five letter margin). Safety outcomes included adverse events, serious adverse events, and microvascular abnormalities. The same analyses were undertaken at years 2, 3, and 4. A within trial costing analysis was undertaken for participants with four years' follow-up.<br><br>RESULTS: Of 411 participants (204 (58%) women), 274 were allocated to SRT and 137 to sham SRT. The year 4 intention-to-treat efficacy analysis included 222 (81%) participants in the SRT group and 106 (77%) in the sham SRT group. The SRT group received a mean of 19.1 (standard deviation 10.9) injections over four years versus 21.6 (11.3) with sham SRT, an adjusted decrease of 3.2 injections (95% confidence interval (CI) of difference -5.7 to -0.7). During years 3 and 4, the SRT group received a mean cumulative 8.4 injections versus 8.3 injections in the sham SRT group. The final change in visual acuity in the SRT group was 8.3 letters worse than in the sham group (95% CI of difference -12.7 to -4.0). Adverse event rates were similar between groups, but reading centre-detected microvascular abnormalities occurred in 126/218 SRT treated eyes (58%) and 16/102 (16%) sham SRT treated eyes.<br><br>CONCLUSION: Although the overall reduction in intravitreal therapy was maintained to year 4, the inferior vision in SRT treated eyes effectively reversed the conclusions of the year 2 primary outcome analysis and no longer supports the use of SRT to treat neovascular AMD. Including standard care, masked, extended follow-up within a clinical trial may provide useful clinical insight.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02243878.}, }
@article {pmid42315822, year = {2026}, author = {Venkatesh, P}, title = {Tyrosine Kinase Receptors, Inhibition, and Potential Role in the Pharmacotherapy of Retinal Disorders.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42315822}, issn = {2193-8245}, abstract = {Over the past two decades, impressive gains in the restoration and maintenance of visual acuity have been made in patients with, otherwise blinding, chronic retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) using intravitreal pharmacotherapy against vascular endothelial growth factor (VEGF). However, there is serious economic burden, continued potential for risks, and potential drug resistance owing to the necessity of repeated injections so as to sustain the initial gains of therapy. Although efforts such as intravitreal treatment with dual pathway inhibitors and sustained drug release implants have been introduced to address such concerns, they do not seem to be the ideal approaches. Consequently researchers continue to explore more plausible solutions, among which tyrosine kinase inhibition seems to have a strong potential to reduce the treatment burden. In this review, the nature of protein kinases and tyrosine kinases, their receptors, and their downstream signaling effects are discussed, followed by the role of receptor tyrosine kinases (RTK) and their inhibitors in the treatment of retinal diseases such as nAMD and DME.}, }
@article {pmid42316110, year = {2026}, author = {Thakali, S and Shrestha, M and Gauchan, A and Gurung, HB}, title = {Indications and outcome of intravitreal bevacizumab injection in a Community Eye Hospital, Nepal.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {42316110}, issn = {1471-2415}, mesh = {Humans ; *Bevacizumab/administration &amp; dosage ; Retrospective Studies ; Male ; Intravitreal Injections ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Visual Acuity ; Middle Aged ; Treatment Outcome ; Aged ; Nepal ; Tomography, Optical Coherence ; Hospitals, Community ; Adult ; Follow-Up Studies ; *Retinal Diseases/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {BACKGROUND: This study aimed to evaluate the indications and real-world treatment outcomes of intravitreal bevacizumab in a resource-limited community eye hospital setting.<br><br>METHODS: This retrospective study included patients who received IVB injection at Hetauda Community Eye Hospital between January 2019 and December 2022.<br><br>INCLUSION CRITERIA: [Formula: see text]1 IVB injection; retinal diagnosis confirmed clinically and by Optical Coherence Tomography (OCT) where available.<br><br>EXCLUSION CRITERIA: missing baseline Visual Acuity (VA) or OCT,[Formula: see text] month follow-up. Median visual acuity (VA) and central macular thickness (CMT) changes were compared using Wilcoxon signed&#x2011;rank test.<br><br>RESULTS: A total of 418 injections were administered to 247 patients (260 eyes). After excluding those lost to follow&#x2011;up, 221 patients (234 eyes) were included in the analysis. Median baseline CMT was 366&#xa0;&#x3bc;m and improved to 236&#xa0;&#x3bc;m (p&#x2009;<&#x2009;0.001). Most patients received one injection (57%) followed by two injections (30%). The median baseline VA was 0.78 log MAR and remained 0.78 log MAR overall (p&#x2009;=&#x2009;0.108), but subgroup improvements were significant in DME, nAMD, BRVO, and central retinal vein occlusion (CRVO).<br><br>CONCLUSION: IVB resulted in significant anatomical and functional improvements in patients with retinal diseases. The findings reflect real&#x2011;world outcomes in a community&#x2011;level eye hospital, where cost barriers limit repeated injections. The limitations of this study include its retrospective design, variable follow&#x2011;up, absence of control group, and limited numbers of injections.}, }
@article {pmid42317156, year = {2026}, author = {Endo, H and Tanaka, T and Saito, M and Kase, S and Sawada, I and Katsuta, S and Sakaguchi, T and Ishida, S}, title = {Detection of Latent Macular Lesions by Preoperative Optical Coherence Tomography and Associated Factors in Japanese Cataract Patients.}, journal = {Journal of cataract and refractive surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/j.jcrs.0000000000002006}, pmid = {42317156}, issn = {1873-4502}, abstract = {PURPOSE: The purpose of this study was to determine the detection rate and associated factors of latent macular lesions using preoperative Spectral-domain optical coherence tomography (SD-OCT) in Japanese patients scheduled for cataract surgery with no clinically confirmed macular abnormalities.<br><br>SETTING: Teine Keijinkai Hospital, Sapporo, Japan.<br><br>DESIGN: Retrospective observational study.<br><br>METHODS: We included 316 eyes of 316 Japanese cataract patients scheduled for surgery between January 2023 and December 2024 who had no suspected macular pathology on slit-lamp biomicroscopy. All patients underwent comprehensive ophthalmic examinations and SD-OCT, and the detection rate of latent macular lesions and their associated factors were investigated.<br><br>RESULTS: Latent macular lesions were detected in 30 eyes (9.5%) of 316 patients with a mean age of 76.8 &#xb1; 8.8 years. The most frequent lesions were epiretinal membrane (15 eyes, 4.7%), followed by irregular elevation of the retinal pigment epithelium (10 eyes, 3.2%). Clinically significant lesions requiring immediate surgical modification or additional treatment were identified in 3 eyes (1.0%), including a full-thickness macular hole (1 eye) and neovascular age-related macular degeneration (2 eyes). Age was independently associated with latent macular lesions (odds ratio 1.10, 95% Confidence Interval 1.04-1.16, P<0.01).<br><br>CONCLUSION: Preoperative OCT screening may contribute to the evaluation of latent macular lesions, particulary in elderly cohort, and lead to optimized surgical planning.}, }
@article {pmid42307174, year = {2026}, author = {Su, Y and He, Y and Pu, J and Zhuang, X and Zhang, X and Gan, Y and Wen, F}, title = {Correlation Between RPE Aperture and Photoreceptor Integrity in Non-Neovascular AMD: A Longitudinal Study Using OCT and 3D Morphological Analysis.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {6}, pages = {21}, doi = {10.1167/tvst.15.6.21}, pmid = {42307174}, issn = {2164-2591}, mesh = {Humans ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; *Macular Degeneration/pathology/diagnostic imaging ; Aged ; *Imaging, Three-Dimensional/methods ; Longitudinal Studies ; *Photoreceptor Cells, Vertebrate/pathology ; Retinal Detachment/pathology/diagnostic imaging ; Aged, 80 and over ; Visual Acuity/physiology ; }, abstract = {PURPOSE: The purpose of this study was to investigate longitudinal morphological changes of retinal pigment epithelium (RPE) apertures within pigment epithelial detachment (PED) and their association with photoreceptor integrity in non-neovascular age-related macular degeneration (AMD).<br><br>METHODS: This retrospective analysis included 22 eyes from 21 patients with RPE apertures within PED. During a mean follow-up of 11.4 &#xb1; 5.8 months, optical coherence tomography (OCT) with 3D volumetric analysis was used to measure RPE aperture diameter/area, PED dimensions, and areas of ellipsoid zone (EZ) loss and outer nuclear layer (ONL) thinning. Correlation and multivariate regression analyses were performed.<br><br>RESULTS: RPE apertures significantly enlarged in diameter and area, accompanied by progressive EZ loss and ONL thinning (all P &#x2264; 0.001). PED height (P = 0.018) and volume (P = 0.031) decreased, whereas PED width increased (P = 0.019). RPE aperture size showed strong cross-sectional and longitudinal correlations with photoreceptor damage (r up to 0.942 and 0.928, respectively, all P < 0.001, remaining significant after false discovery rate [FDR] correction). Multivariate regression demonstrated that change in RPE aperture diameter was independently associated with concurrent changes in EZ loss (&#x3b2; = 1.009, P < 0.001) and ONL thinning (&#x3b2; = 0.679, P = 0.001). Additionally, a larger baseline aperture diameter was an independent factor associated with greater visual acuity decline (P = 0.015).<br><br>CONCLUSIONS: RPE apertures enlarge over time and are closely associated with worsening photoreceptor damage, supporting RPE aperture progression as a dynamic biomarker of ongoing photoreceptor degeneration in non-neovascular AMD.<br><br>TRANSLATIONAL RELEVANCE: Quantitative OCT-based assessment of RPE aperture expansion enables clinically applicable monitoring of photoreceptor degeneration and visual risk in non-neovascular AMD.}, }
@article {pmid42308567, year = {2026}, author = {Park, M and Kim, SH}, title = {Age-related macular degeneration and secondary fracture risk in patients with hip fractures.}, journal = {Injury}, volume = {57}, number = {8}, pages = {113450}, doi = {10.1016/j.injury.2026.113450}, pmid = {42308567}, issn = {1879-0267}, abstract = {Research on the relationship between age-related macular degeneration (AMD) and secondary fracture risk following hip fractures is scant. We aimed to examine whether AMD increases the risk of secondary fractures following hip fracture surgery. This retrospective cohort study was conducted using data from the Korean National Health Insurance Service Senior Cohort (2002-2019). Secondary fractures were defined as hip, wrist, humerus, spine, ankle, or pelvic fractures occurring within 6 months after hip fracture surgery. Patients diagnosed with AMD within 6 months postoperatively were identified. Covariates included age, sex, income, insurance type, Charlson Comorbidity Index, residential area, disability status, and hospital size and type. Associations between AMD and secondary fractures were analyzed using Cox proportional hazards models. Among 18 611 patients with hip fractures, 93 were diagnosed with AMD and 26 experienced secondary fractures. Patients with AMD had a significantly higher risk of secondary fractures than those without AMD (adjusted hazard ratio, 1.70; 95% confidence interval, 1.16-2.51). Overall, AMD was associated with an increased risk across all fracture types. Effective management of AMD may help reduce the risk of secondary fractures.}, }
@article {pmid42309064, year = {2026}, author = {Ma, J and Zhu, L and Duan, P and Ding, T and Cheng, Z and Li, B and Wang, Q and Ma, X and Deng, Y and Lamba, DA and Gao, Y}, title = {Paired pre- and post-transplant human immunoprofiling identifies an IFN-γ-JAK1 axis limiting stem-cell-derived RPE engraftment.}, journal = {Cell stem cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.stem.2026.05.006}, pmid = {42309064}, issn = {1875-9777}, abstract = {Neovascular age-related macular degeneration is a major cause of irreversible blindness, and current therapies do not restore photoreceptors or retinal pigment epithelium (RPE). Human embryonic stem-cell-derived RPE (hESC-RPE) transplantation represents a potential regenerative strategy, but immune rejection limits durable engraftment. Here, we combine immune profiling of blood, aqueous humor, and retinal tissue with allogeneic co-cultures and humanized models to define determinants of graft vulnerability and assess a graft-directed intervention. We identify a Th1-skewed, IFN-γ-rich immune milieu across the circulation and eye and show that IFN-γ-JAK1 signaling promotes an immunogenic state in hESC-RPE, marked by increased HLA expression and antigen presentation features. Brief ex vivo conditioning with ruxolitinib attenuates this response while preserving epithelial properties. In humanized retinal degeneration models, conditioned grafts show reduced T/natural killer (NK)-cell infiltration, prolonged survival, and improved visual function without chronic systemic immunosuppression, supporting ex vivo JAK inhibition as a feasible adjunct to RPE cell therapy.}, }
@article {pmid42309346, year = {2026}, author = {Vogels, DHJ and Ma, Q and Boote, C and Klaver, CCW and LaPointe, VLS and Dickman, MM}, title = {Scleral remodeling in myopia: mechanisms and therapeutic approaches.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101486}, doi = {10.1016/j.preteyeres.2026.101486}, pmid = {42309346}, issn = {1873-1635}, abstract = {High myopia is the leading cause of visual impairment worldwide, driven by excessive axial elongation resulting in biomechanical weakening of the sclera, and increasing the risk of complications such as posterior staphyloma, myopic macular degeneration, retinal detachment, cataract, and glaucoma. Conventional myopia management strategies aim to slow axial elongation in childhood, leaving patients with high myopia at risk of vision-threatening complications as they age. For these individuals, targeted therapies that strengthen the weakened sclera represent a promising, yet still experimental, approach. This review provides an overview of the role of the sclera in myopia progression, emphasizing changes in extracellular matrix composition, collagen organization, biomechanical integrity, and signaling pathways. Investigational scleral therapies are discussed, including posterior scleral reinforcement techniques, crosslinking modalities, pharmacological strategies, and tissue engineering approaches, with discussion of their mechanisms, preclinical and clinical evidence, and translational challenges. Particular attention is given to translational barriers, such as safe delivery to the posterior pole, retinal safety, and the absence of standardized outcome measures that link biomechanical reinforcement to functional benefit. Advances in imaging and in vivo biomechanical assessment, such as polarization-sensitive optical coherence tomography, Brillouin microscopy, and ultrasound-based elastography, hold promise for earlier risk stratification and treatment monitoring. By integrating insights from biomechanics, molecular biology, and therapeutic innovation, this review highlights the sclera as both a key driver of myopia pathology and a promising therapeutic target. Continued interdisciplinary collaboration will be essential to translate these experimental approaches into clinically viable treatments capable of reducing the growing burden of high myopia worldwide.}, }
@article {pmid42310032, year = {2026}, author = {Budnik, A and Tuchliński, J and Lisowski, &#x141; and Michnowska-Kobylińska, M and Dmuchowska, DA and Chlabicz, M and Szpakowicz, A and Dubatówka, M and Kondraciuk, M and Kamiński, K and Konopińska, J}, title = {Cardiovascular peptide markers are associated with age-related macular degeneration in the Bialystok PLUS general population cohort.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-55028-4}, pmid = {42310032}, issn = {2045-2322}, support = {2023/ABM/03/000024//Agencja Bada&#x144; Medycznych/ ; }, abstract = {Age-related macular degeneration (AMD) and cardiovascular disease (CVD) share numerous risk factors; however, protein biomarkers for AMD are lacking. We investigated whether circulating cardiovascular peptide biomarkers are associated with AMD in the population-based Białystok PLUS cohort. This cross-sectional analysis included 699 participants aged ≥ 50 years (AMD + = 93; AMD[-] = 606) examined between 2018 and 2023. AMD was graded from fundus photos with the use of the Wisconsin and modified International Classification systems. Ninety-two cardiovascular proteins were quantified in serum with the Olink Target Cardiovascular III panel. Age-adjusted linear or logistic regressions assessed biomarker-AMD associations, and receiver-operating-characteristic (ROC) curves evaluated discriminative performance. After adjustment, AMD+ participants exhibited lower galectin-4 (β = - 0.15, p = 0.043) and TNF-receptor-superfamily-member-10 C (TNFRSF10C) (β = - 0.17, p = 0.037) concentrations and higher von Willebrand factor (vWF) levels (β = 0.22, p = 0.036) versus AMD[-] individuals. Galectin-4, TNFRSF10C, and vWF predicted AMD with areas under the ROC curve of 0.613 (95% confidence interval [CI] 0.516-0.709), 0.606 (0.520-0.692), and 0.594 (0.500-0.687), respectively. Optimal cut-offs were 4.05 NPX for galectin-4, 5.09 NPX for TNFRSF10C, and 8.03 NPX for vWF, yielding sensitivities/specificities of 57%/63%, 58%/62% and 55%/63%, respectively. Elevated vWF and reduced galectin-4 and TNFRSF10C are independently associated with AMD, suggesting overlapping vascular, inflammatory and apoptotic pathways with CVD. Incorporation of these peptides into risk-stratification algorithms could enhance early AMD detection and motivate mechanistic studies targeting the TRAIL-TNFRSF10C axis and galectin-mediated signaling.}, }
@article {pmid42313414, year = {2026}, author = {Carrera, WM and Zeng, A and Cheong, KX and Hoang, QV and Jung, JJ and Rofagha, S}, title = {Outcomes in Neovascular Age-Related Macular Degeneration After Copayment Assistance Defunding.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.2093}, pmid = {42313414}, issn = {2168-6173}, }
@article {pmid42300673, year = {2026}, author = {Sagurski, N and Jaggi, D and Lincke, JB and Wolf, S and Zinkernagel, MS and Dysli, C}, title = {Monitoring of Geographic Atrophy Progression in Age-Related Macular Degeneration Using Fluorescence Lifetime Imaging Ophthalmoscopy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {6}, pages = {31}, doi = {10.1167/iovs.67.6.31}, pmid = {42300673}, issn = {1552-5783}, mesh = {Humans ; Female ; *Ophthalmoscopy/methods ; *Geographic Atrophy/diagnosis/etiology ; Disease Progression ; Aged ; Male ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; *Macular Degeneration/complications/diagnosis ; Aged, 80 and over ; Follow-Up Studies ; Fundus Oculi ; Optical Imaging/methods ; Visual Acuity ; }, abstract = {PURPOSE: The purpose of this study was to examine fluorescence lifetime (FLT) changes within the border zone of geographic atrophy (GA) due to age-related macular degeneration (AMD) using fluorescence lifetime imaging ophthalmoscopy (FLIO).<br><br>METHODS: Patients with GA due to AMD were included. Fundus autofluorescence (FAF) intensity, spectral-domain optical coherence tomography (OCT), color fundus photography, and FLIO imaging were carried out at baseline and approximately 5 years of follow-up. GA progression was measured based on FAF images. FLT were measured at five different regions of interest: fovea, retina unaffected by GA, GA, and two areas directly next to the border zone of atrophy.<br><br>RESULTS: Thirty-two eyes of 17 patients (9 female patients, mean age = 77.4 years) were included. The GA area increased by an average of 1.21 mm2/year. At the GA border, FLT gradually decreased toward the unaffected retina at each visit and gradually increased in all zones over time. The FLT gradient at the border zone correlated significantly with the GA growth rate (P = 0.02, r2 = 0.17).<br><br>CONCLUSIONS: Areas of GA showed significantly prolonged FLT compared to unaffected surrounding retinal tissue, confirming previous reports. The border zone FLT gradient was predictive of GA progression rate.}, }
@article {pmid42300675, year = {2026}, author = {Martinez, TL and Zacharias, ZR and Lee, K and Han, IC and Jiao, C and Bach, BB and Roos, B and Chava, S and McCormick, MM and Sinkey, C and Wu, AP and Mukhopadhyay, C and Coussa, RG and Russell, J and Binkley, EM and Boldt, HC and Folk, JC and Russell, SR and Mullins, RF and Fingert, JH and Wang, K and Abramoff, MD and Stone, EM and Scheetz, TE and Houtman, JCD and Sonka, M and Sohn, EH}, title = {MMP9 Genotype and Systemic T-Cell Subsets Correlate With Structural and Functional Outcomes in Neovascular Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {6}, pages = {29}, doi = {10.1167/iovs.67.6.29}, pmid = {42300675}, issn = {1552-5783}, mesh = {Humans ; *Matrix Metalloproteinase 9/genetics/metabolism ; Genotype ; Female ; *Polymorphism, Single Nucleotide ; Male ; Flow Cytometry ; Enzyme-Linked Immunosorbent Assay ; *T-Lymphocyte Subsets/immunology ; Tomography, Optical Coherence ; Aged ; Immunophenotyping ; Aged, 80 and over ; *Wet Macular Degeneration/genetics/immunology ; Subretinal Fluid ; *Choroidal Neovascularization/genetics ; }, abstract = {PURPOSE: Genetic studies implicate the matrix metalloproteinase-9 (MMP9) locus in neovascular age-related macular degeneration (nvAMD) risk but genotype-phenotype associations of MMP9 with nvAMD are lacking. This study aimed to investigate the influence of MMP9 genotype and T-cell subset frequency on structural and functional treatment outcomes in nvAMD.<br><br>METHODS: We reanalyzed single-cell RNA sequencing data and used ELISA and flow cytometry in THP-1-derived monocytes to measure immune cell expression of MMP9 within human choroids. In a clinical nvAMD cohort of 38 patients, we genotyped the nvAMD risk single nucleotide polymorphism (SNP; rs4810482) and quantified retinal fluid using deep-learning-based optical coherence tomography (OCT) image analysis. On a subset of nine patients, we performed high-dimensional immunophenotyping.<br><br>RESULTS: MMP9 is predominantly expressed in mature THP-1-derived dendritic-like cells (ELISA, P = 0.009; flow cytometry, P = 0.001). Patients with the TC genotype of MMP9 exhibited greater disease severity compared to CC or TT genotypes with a significantly higher total retinal fluid volume (P = 0.009). Immunophenotyping revealed that higher proportions of circulating CD8+ effector memory T cells re-expressing CD45RA (TEMRA) were associated with increased residual subretinal fluid (P = 0.03), indicating persistent disease activity.<br><br>CONCLUSIONS: MMP9 genotype affects structural and functional outcomes in patients with nvAMD. Along with the observed systemic immune dysregulation, these findings support the role of a MMP9-dendritic-T-cell axis in nvAMD immunopathogenesis and highlight this as a potential therapeutic target.}, }
@article {pmid42303288, year = {2026}, author = {Zhang, Y and Pu, J and Zhuang, X and Hao, X and Chen, X and He, Y and Zhang, G and Li, M and Ji, Y and Wen, F}, title = {Choroidal vascular hyperpermeability and submacular haemorrhage in polypoidal choroidal vasculopathy: a multi-field ICGA analysis.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2026-329600}, pmid = {42303288}, issn = {1468-2079}, abstract = {PURPOSE: To investigate the association between choroidal vascular hyperpermeability (CVH) and the occurrence of submacular haemorrhage (SMH) in polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This retrospective, cross-sectional study included 189 eyes of 159 patients with treatment-na&#xef;ve PCV. Eyes were categorised into haemorrhage (n=84) and non-haemorrhage (n=105) groups based on the extent of subretinal or subretinal pigment epithelium haemorrhage. Nine-field indocyanine green angiography (ICGA) was performed to evaluate the presence, number, topographic distribution and area of CVH. Logistic regression and correlation analysis were performed to identify factors associated with SMH.<br><br>RESULTS: The cohort comprised predominantly male patients (67.3%), with a mean age of 65.4&#xb1;7.6 years. The haemorrhage group showed significantly lower CVH prevalence (32.1% vs 68.6%; p<0.001) and median CVH count (0 vs 1; p<0.001) compared with the non-haemorrhage group. Multivariate model demonstrated that both the presence (p<0.001) and higher count (p=0.004) of CVH were independently associated with a reduced likelihood of SMH. Topographically, this negative association was most pronounced for CVH located in the posterior pole, central nasal and central superior quadrants (all p<0.05). A weak but significant inverse correlation was also observed between the total area of CVH and the area of haemorrhage (Spearman's r=-0.248).<br><br>CONCLUSIONS: The presence and counts of CVH are inversely associated with the occurrence of SMH in PCV, suggesting CVH may serve as a 'pressure-relief window' to dissipate suddenly elevated choroidal vascular pressure which predisposes to vessel rupture.}, }
@article {pmid42303289, year = {2026}, author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Milea, D and Bron, AM and Lamirel, C and Nangia, V and Wang, YX and Panda-Jonas, S}, title = {Intereye differences in myopic macular degeneration, intraocular pressure and axial length: the Two-Continent Eye Study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329068}, pmid = {42303289}, issn = {1468-2079}, abstract = {PURPOSE: To assess associations of myopic macular degeneration (MMD) with intraocular pressure (IOP).<br><br>METHODS: The project included the population-based Beijing Eye Study (n=3335 participants; age: 40+ years), Ural Eye and Medical Study (n=5589; age: 40+ years), Ural Very Old Study (n=566; age: 85+ years) and Ural Children Eye Study (n=4325; age: 6+ years) and Central India Eye and Medical Study (n=4514; age: 30+ years). MMD was defined according to the Meta-analysis for Pathologic Myopia Study Group.<br><br>RESULTS: The study population included 35&#x2009;778 eyes (18&#x2009;328 individuals) (age: 46.9&#xb1;23.1 years; range: 6-100 years) (axial length: 23.2&#xb1;1.0&#x2009;mm; range: 18.08-34.20 mm). Longer axial length was associated with higher IOP (&#xdf;:0.03; p<0.001) with adjusting for age (&#xdf;:0.01; p<0.001), sex (&#xdf;:-0.19; p=0.006) and MMD-stage (&#xdf;:0.47; p<0.001). Intereye axial length difference correlated (r[2]=0.11) with higher intereye difference in IOP (&#xdf;: 0.03; p<0.001) after adjusting for age (&#xdf;: 0.06; p<0.001), sex (&#xdf;: -0.07; p<0.001) and higher intereye difference in MMD-stage (&#xdf;: 0.32; p<0.001). Higher intereye IOP difference correlated (r[2]=0.03) with higher intereye axial length difference (&#xdf;: 0.03; p<0.001) after adjusting for age (&#xdf;: -0.15; p<0.001), but not with intereye difference in MMD-stage (p=0.90). Higher intereye difference in MMD-stage was associated (r[2]=0.10) only with higher intereye axial length difference (&#xdf;: 0.32; p<0.001) and sex (&#xdf;: 0.01; p=0.04). Higher intereye difference in MMD prevalence (defined as MMD-stage 3+) correlated with intereye axial length difference (&#xdf;: 0.24; p<0.001) and female sex (&#xdf;: 0.02; p=0.006) but not with intereye IOP difference (p=0.14).<br><br>CONCLUSIONS: Although IOP was associated with longer axial length, MMD stage and MMD prevalence were not significantly related to IOP, neither in an interindividual comparison nor in an intraindividual intereye comparison. The data point against a therapeutic IOP reduction as a measure to reduce development or progression of MMD.}, }
@article {pmid42304501, year = {2026}, author = {Chen, Y and Liu, C and Chen, J and Huang, Y and Pan, G and Wang, P and Hu, Y and Chen, L and Zhang, Y and Wang, Y}, title = {Single-cell and spatial analyses reveal endothelial-macrophage inflammatory crosstalk in dry age-related macular degeneration.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-08393-7}, pmid = {42304501}, issn = {1479-5876}, abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is characterized by progressive degeneration of the retinal pigment epithelium-choroid interface, accompanied by immune dysregulation. However, the cellular interactions and regulatory mechanisms driving macrophage activation in this process remain incompletely understood.<br><br>METHODS: We integrated spatial transcriptomics and single-cell RNA sequencing data from a photo-oxidative damage mouse model and human dry AMD samples. A series of bioinformatic analyses, including cell-cell communication analysis, enrichment analysis, and pseudotime trajectory analysis, were performed to characterize cellular features and regulatory pathways.<br><br>RESULTS: In the photo-oxidative damage mouse model, the RPE-choroid region showed marked infiltration of myeloid cells. In human dry AMD samples, SLC16A10-positive macrophages were enriched and exhibited pro-inflammatory features. Further analysis revealed that endothelial cells regulate SLC16A10-positive macrophages through the TNFSF10-TNFRSF10B pathway, with NFKB1 acting as a key regulator to activate NF-&#x3ba;B signaling, thereby promoting the formation of a vascular-immune inflammatory niche.<br><br>CONCLUSIONS: This study systematically characterizes immune remodeling in the RPE-choroid region in dry AMD and identifies an endothelial-macrophage TNFSF10-TNFRSF10B-NF-&#x3ba;B signaling pathway that drives disease progression. These findings provide new insights into disease mechanisms and suggest potential therapeutic targets for dry AMD.}, }
@article {pmid42304926, year = {2026}, author = {Mukherjee, S and Ray, SK and Mukherjee, S}, title = {Linking Neurodegeneration and Age-related Macular Degeneration: Unified Pathways and Intervention Strategies.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273450093260523224914}, pmid = {42304926}, issn = {1996-3181}, abstract = {Age-related macular degeneration (AMD) is caused by the degeneration of photoreceptors and retinal pigment epithelium (RPE) along with drusen deposition and is the leading cause of vision loss in older adults. Both these structures within the central nervous system (CNS) utilize common neuro-inflammatory mechanisms because the retina is an outgrowth of the brain. Like the brain, the eye has its own physical characteristics and surface molecules as well as a tendency towards specific immune reactions. Numerous distinct neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Frontotemporal dementia (FTD) that impact the brain present as eye symptoms, and the conventional diagnosis of these neurodegenerative disorders (NDs) is often preceded by ocular symptoms. Furthermore, several eye-specific disorders have characteristics in common with other CNS disorders. NDs and AMD share common key features, such as tau and amyloid-β deposits, oxidative stress response, chronic inflammation, and dysregulation of microglia and müller glia. Common pathological mechanisms include complement activation, amyloid aggregation, neuroinflammation, vascular impairment, and cell death, providing a basis for a convergent neuroimmune axis between retinal and cerebral degeneration. Comparing these age-related diseases will facilitate the identification of shared risk factors, convergent molecular pathways, and potential cross-applicable therapeutic strategies, such as anti-inflammatory, anti-complementary, anti-apoptotic, and anti-VEGF-based approaches. This knowledge may enhance understanding of neurodegenerative diseases, help identify early biomarker development for diagnosis, and enable the design of targeted therapeutic strategies.}, }
@article {pmid42305344, year = {2026}, author = {Sadikan, MZ and Ahmad Hairi, H and Lambuk, L}, title = {Understanding the link between lipid and ocular disorders for effective therapy.}, journal = {Archives of medical science : AMS}, volume = {22}, number = {2}, pages = {583-601}, pmid = {42305344}, issn = {1734-1922}, abstract = {Cholesterol is an essential lipid for cellular integrity and metabolic homeostasis; however, dysregulated cholesterol metabolism is increasingly recognized as a key contributor to multiple ocular diseases. Beyond its established role in cardiovascular pathology, emerging evidence implicates altered lipoprotein balance, impaired cholesterol transport, and lipid-driven inflammation in the pathogenesis of age-related macular degeneration, retinal vascular diseases, cataracts, and glaucoma. This review integrates current knowledge on cholesterol synthesis, transport, and regulation with ocular-specific mechanisms, emphasizing the differential roles of low-density lipoprotein, high-density lipoprotein, and triglyceride-rich lipoproteins. Key molecular pathways, including the mevalonate-SREBP axis, ABCA1/ABCG1-mediated reverse cholesterol transport, VEGF-driven angiogenesis, oxidative stress signaling, and inflammatory cascades, are critically discussed. Clinical and translational implications are highlighted, particularly the potential ocular benefits of lipid-modulating therapies such as statins, fenofibrate, and antioxidant supplementation. Understanding cholesterol as a modifiable determinant of ocular health may enable integrated preventive strategies and guide future therapeutic innovation in vision-threatening diseases.}, }
@article {pmid42305797, year = {2026}, author = {Conte, S and Nassisi, M and Mainetti, C and Seregni, L and Viola, F}, title = {Posterior segment inflammation with venous involvement following a switch to a ranibizumab biosimilar (Ximluci®): a case report.}, journal = {American journal of ophthalmology case reports}, volume = {43}, number = {}, pages = {102609}, pmid = {42305797}, issn = {2451-9936}, abstract = {PURPOSE: To describe an unusual case of posterior segment inflammation occurring in temporal association with a switch from reference ranibizumab to its biosimilar, Ximluci®.<br><br>OBSERVATIONS: A 77-year-old woman with neovascular age-related macular degeneration presented for an unscheduled visit reporting mild subjective visual loss one day after the second monthly intravitreal injection of ranibizumab biosimilar Ximluci following ten consecutive monthly injections of reference ranibizumab without adverse events. Clinical examination revealed mild optic disc edema, and peripapillary venous leakage on fluorescein angiography, without arteriovenous filling delay or ischemic signs. Multimodal imaging findings were consistent with posterior segment inflammation with venous involvement. Infectious and systemic inflammatory work-up was negative. The patient was treated with systemic and topical corticosteroids, resulting in progressive resolution of inflammatory signs. Due to suboptimal anatomical response of the underlying neovascular lesion and the recent inflammatory episode, therapy was subsequently switched to 2 mg Aflibercept, which was well tolerated without recurrence of intraocular inflammation.<br><br>CONCLUSION AND IMPORTANCE: This case highlights a rare episode of posterior segment inflammation occurring in temporal association with a switch to a ranibizumab biosimilar. Although ranibizumab biosimilars have demonstrated a favorable safety profile in clinical trials and regulatory assessments, uncommon inflammatory reactions may emerge in real-world settings. Careful clinical monitoring following treatment switching and continued post-marketing surveillance are essential to further characterize the ocular safety of these agents.}, }
@article {pmid42306086, year = {2026}, author = {Rezek, FO and Sanchez-Pintado, B and Eden, ER and Corral-Serrano, JC and Aychoua, N and Webster, AR and de Guimarães, TAC and Carr, AF and Michaelides, M and Cheetham, ME and van der Spuy, J}, title = {Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {2}, pages = {102955}, pmid = {42306086}, issn = {2162-2531}, abstract = {Doyne honeycomb retinal dystrophy is an incurable juvenile macular dystrophy that leads to visual impairment by early to mid-adulthood. It is an autosomal dominant disorder caused by a c.1033C>T, p.(Arg345Trp) variant in EFEMP1, and is characterized by the early onset of extracellular deposition of drusen between the retinal pigment epithelium and underlying Bruch's membrane. In this study, we developed an antisense oligonucleotide approach to target EFEMP1. We reprogrammed patient-derived renal epithelial cells to induced pluripotent stem cells, followed by directed differentiation to retinal pigment epithelium and compared the phenotype to gene-corrected and EFEMP1 knockout patient-derived retinal pigment epithelium. In the patient-derived disease model, remodeling of the extracellular matrix (ECM) occurred with progressive accumulation of the drusen-associated proteins apolipoprotein E and collagen IV, in addition to the intracellular accumulation and extracellular deposition of lipids. We developed an allele-specific antisense oligonucleotide which specifically and effectively promoted the clearance of the EFEMP1 c.1033C>T transcript in the patient-derived disease model following assisted or gymnotic delivery. Gymnotic delivery rescued remodeling of the ECM, reduced intracellular accumulation of lipids, and cleared extracellular deposits, even after the onset of the disease phenotype, suggesting that this could be a practical and effective therapeutic approach.}, }
@article {pmid42307030, year = {2026}, author = {Tang, J and Zgoda, N and Clark, SJ}, title = {Decoding the Factor H-Related Proteins: Gatekeepers of Complement Dysregulation in AMD.}, journal = {European journal of immunology}, volume = {56}, number = {6}, pages = {e70228}, doi = {10.1002/eji.70228}, pmid = {42307030}, issn = {1521-4141}, support = {//China Scholarship Council/ ; //Helmut Ecker Foundation/ ; 538134976//DFG/ ; }, mesh = {Humans ; *Macular Degeneration/immunology/genetics ; Animals ; *Complement System Proteins/immunology ; *Complement Factor H/immunology/genetics ; Complement Activation/immunology ; *Blood Proteins/genetics/immunology/metabolism ; Inflammation/immunology ; Complement C3b Inactivator Proteins/genetics ; }, abstract = {Age-related macular degeneration (AMD) is the third most common form of blindness in the Western world, with a predicted 288 million individuals affected worldwide by the year 2040. Both genetic and biochemical evidence point toward complement overactivation, through a diminished regulatory capacity, at the back of the eye, causing inflammation and tissue damage that helps drive this devastating disease. While much historic effort has gone into understanding the loss of regulatory control by complement factor H and factor H-like protein 1, recent studies have uncovered an emerging role of the factor H-related proteins and their capacity for driving forward complement amplification. FHR gene deletions have been shown to be protective against AMD, and increased circulating levels of FHR proteins have been found to associate with their deposition in the back of the eye at the site of disease pathogenesis. Here, we will explore the current understanding of FHR and their association with AMD risk, possible mechanisms by which they promote inflammation and extracellular matrix remodeling, and the potential effectiveness of their targeting as a novel therapeutic strategy for reducing the risk of AMD.}, }
@article {pmid42295759, year = {2026}, author = {Sharma, A and Jaber, A and Pal, B and Lawrenson, JG and Harper, RA and Tufail, A and Learoyd, AE and Robinson, E and Douiri, A and Burman, R and Kernohan, A and Vougioukalou, S and Read, S and Csontos, J and Jones, A and Mahmood, S and McKibbin, M and Peacock, JL and Gale, R and Patel, PJ and Keane, PA and Hamilton, R and Vale, L and Bunce, C and Balaskas, K}, title = {Community Optometrist-Led Monitoring of Quiescent Neovascular Age-Related Macular Degeneration: The FENETRE Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {9}, number = {6}, pages = {e2617984}, pmid = {42295759}, issn = {2574-3805}, mesh = {Humans ; Female ; Aged ; Male ; Middle Aged ; *Macular Degeneration/diagnosis/therapy ; *Optometrists ; Tomography, Optical Coherence ; Aged, 80 and over ; Visual Acuity ; }, abstract = {IMPORTANCE: Hospital-based ophthalmology faces increasing demand for long-term monitoring of neovascular age-related macular degeneration (nAMD). Safe redistribution of routine monitoring to community clinicians is relevant to integrated community (primary)-secondary care models.<br><br>OBJECTIVE: To examine whether community optometrist-led monitoring of nAMD is noninferior to hospital-based monitoring for detecting disease activity requiring treatment.<br><br>This multicenter, noninferiority randomized clinical trial was conducted from October 8, 2019, to January 31, 2024, at secondary centers (17 hospitals) and primary centers (60 community optometry practices) with 12-month follow-up. Statisticians were masked to patient grouping. Adults 55 years or older with quiescent AMD in at least 1 eye (and quiescent or nonneovascular disease in the other) were recruited at participating hospitals. Data analysis was performed from October 2024 to March 2025.<br><br>INTERVENTIONS: Participants were randomized 1:1 to monitoring sessions once every 2 months in hospitals (control) or community practices (intervention). Trained and accredited optometrists performed optical coherence tomography imaging, clinical examination, patient management, and online reporting at each visit.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome (participant level) was a binary indicator of whether a false-negative clinical management decision occurred at any visit within 12 months (missed quiescent nAMD reactivation or new fellow-eye nAMD, adjudicated by a central reading-center reference standard). The noninferiority margin was a 10-percentage point absolute risk difference. Secondary outcomes were false-positive clinical management decisions, attendance adherence, visual acuity change, harms, loss to follow-up, suspicious classifications, and confirmation visit outcomes.<br><br>RESULTS: Of 704 randomized participants, 635 (90.2%) completed at least 1 follow-up visit, including 287 at community practices (mean [SD] age, 80.6 [8.1] years; 236 [67.4%] female) and 348 at hospitals (mean [SD] age, 80.1 [8.5] years; 203 [57.3%] female). False-negative clinical management decisions occurred in 11 of 287 community participants (3.8%) vs 27 of 348 hospital participants (7.8%) (risk difference, -3.9 percentage points; 95% CI, -7.4 to -0.3 percentage points; P&#x2009;=&#x2009;.04; adjusted odds ratio, 0.51; 95% CI, 0.24-1.07; P&#x2009;=&#x2009;.08), meeting noninferiority. False-positive clinical management decisions occurred in 24 of 287 community participants (8.4%) vs 12 of 348 hospital participants (3.5%) (risk difference, 4.9 percentage points; 95% CI, 0.9-9.0 percentage points). Findings were consistent across per-protocol, cluster-adjusted, and relative risk sensitivity analyses. No adverse event-related withdrawals occurred.<br><br>CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, community optometrist-led monitoring of quiescent nAMD was noninferior to hospital monitoring for detecting disease activity requiring treatment. These results provide evidence for its use in integrated clinical care models.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03893474.}, }
@article {pmid42295862, year = {2026}, author = {Héjja, R and Thury, G and Hári Kovács, A and Kovács, A}, title = {[The clinical significance and management of submacular hemorrhage].}, journal = {Orvosi hetilap}, volume = {167}, number = {24}, pages = {943-951}, doi = {10.1556/650.2026.33570}, pmid = {42295862}, issn = {1788-6120}, mesh = {Humans ; *Retinal Hemorrhage/therapy/etiology ; Tissue Plasminogen Activator/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fibrinolytic Agents/therapeutic use ; Choroidal Neovascularization/complications ; Angiogenesis Inhibitors/therapeutic use ; }, abstract = {In submacular hemorrhage, blood accumulates in the macular area between the neuroretina and the retinal pigment epithelium. This ophthalmic condition can lead to potentially serious vision impairment and decline in the quality of life. Alarming symptom is a sudden, fixed, grayish-black scotoma appearing in the patient's central visual field, indicating macular involvement. It can be caused by various eye diseases, most commonly by choroidal neovascularization, especially in wet age-related macular degeneration. However, the course of the disease can be significantly influenced by systemic diseases (e.g., hypertension) and medications (e.g., antithrombotic drugs). The timing of adequate treatment plays an important role in its management, which is substantially supported by the advanced multimodal imaging. Although there is still no uniform treatment protocol, the Manchester Protocol can serve as a guideline for the treatment in the arsenal of available conservative and surgical solutions. If the criteria of the study (submacular hemorrhage exceeding the extent of 2 optic discs and occurring within 2 weeks without vitreous hemorrhage) are met, triple therapy: intravitreal injection of recombinant tissue plasminogen activator, vascular endothelial growth factor inhibitor and gas tamponade can be used effectively and safely in the treatment of submacular hemorrhage caused by choroidal neovascularization. Surgical procedure may be necessary in the case of contraindication or failure of the triple therapy. The aim of our summary statement is to emphasize the importance of holistic approach, early and step-by-step intervention in the management of submacular hemorrhage. Orv Hetil. 2026; 167(24): 943-951.}, }
@article {pmid42296206, year = {2026}, author = {Xu, Z and Li, M}, title = {Causal Effects of Dietary Macronutrients and Micronutrients on Myopia and Other Major Ocular Disorders: A Mendelian Randomization Study.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {231}, pages = {}, doi = {10.3791/70258}, pmid = {42296206}, issn = {1940-087X}, mesh = {*Mendelian Randomization Analysis/methods ; Humans ; *Micronutrients/administration &amp; dosage ; *Nutrients/administration &amp; dosage/adverse effects ; *Myopia/genetics/etiology ; *Diet ; Genome-Wide Association Study ; Macular Degeneration/genetics/etiology ; *Eye Diseases/genetics/etiology ; }, abstract = {Myopia and other major ocular disorders, such as cataracts, glaucoma, and age-related macular degeneration (AMD), pose growing public health concerns worldwide. While nutrition is believed to influence ocular development and degeneration, causal evidence remains limited. A two-sample Mendelian randomization (MR) analysis was performed using large-scale genome-wide association study (GWAS) summary data to evaluate the causal effects of dietary macronutrient and micronutrient intake on the risk of myopia and other ocular diseases. The inverse variance-weighted (IVW) method was used as the primary analysis, supported by weighted median, MR-Egger, and MR-PRESSO for sensitivity testing. To account for multiple comparisons, false discovery rate (FDR) correction was applied. After FDR adjustment, higher genetically predicted vitamin C levels remained significantly associated with an increased risk of AMD (odds ratio [OR] = 1.324, 95% confidence interval [CI]: 1.133-1.546). Several additional associations were observed at nominal significance levels (P < 0.05), including higher relative dietary fat intake with increased myopia risk (OR = 1.033, 95% CI: 1.003-1.063), sugar intake with reduced cataract risk (OR = 0.746, 95% CI: 0.561-0.993), iron with lower myopia risk (OR = 0.995, 95% CI: 0.991-0.999), vitamin D with increased cataract risk (OR = 1.256, 95% CI: 1.062-1.487), folic acid with reduced cataract risk (OR = 0.843, 95% CI: 0.724-0.981), and phosphorus with reduced glaucoma risk (OR = 0.727, 95% CI: 0.554-0.953). No evidence of horizontal pleiotropy or heterogeneity was observed. These findings suggest a potential causal role of certain nutrients in ocular disease risk, although most associations did not remain significant after multiple testing correction and should therefore be interpreted with caution. Further studies are needed to confirm these findings and explore underlying biological mechanisms.}, }
@article {pmid42296531, year = {2026}, author = {Zhu, Y and Niu, Y and Sun, S and Liu, W and Dou, Y and Guo, Y}, title = {Performance of Deep Learning in Classifying Age-Related Macular Degeneration From Images: Systematic Review and Meta-Analysis.}, journal = {Journal of medical Internet research}, volume = {28}, number = {}, pages = {e97174}, pmid = {42296531}, issn = {1438-8871}, mesh = {*Deep Learning ; Humans ; *Macular Degeneration/diagnostic imaging/classification/diagnosis ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide. Retinal imaging and deep learning (DL) may support scalable screening, but deployment requires evidence on pooled performance. This is important because missed neovascular disease may delay treatment, whereas excessive false positives may overload referral pathways.<br><br>OBJECTIVE: This study aimed to compare the diagnostic performance of DL algorithms with ophthalmologists for detecting AMD and differentiating wet AMD (wAMD) from dry AMD (dAMD) and to identify factors that influence DL performance.<br><br>METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched through October 5, 2025, and updated on April 19, 2026. Eligible studies applied DL to classify AMD from normal retinas or wAMD from dAMD using retinal images. Two reviewers (MHT and XL) independently extracted data and assessed risk of bias using the Prediction model Risk Of Bias Assessment Tool for Artificial Intelligence (PROBAST+AI) tool. Pooled sensitivity, specificity, accuracy, and area under the curve were estimated using bivariate random-effects models. Clinician comparisons were stratified by experience (junior vs senior). Small-study effects were assessed via Deeks' funnel plot asymmetry test. Evidence certainty was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation framework. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251243276).<br><br>RESULTS: Overall, 28 studies were included, comprising 77,485 samples for AMD detection and 28,705 samples for wAMD versus dAMD classification. For AMD detection, DL achieved a pooled sensitivity of 0.98 (95% CI 0.96-0.99; prediction interval [PI] 0.95-0.99), specificity of 0.98 (95% CI 0.95-0.99; PI 0.95-0.99), accuracy of 0.97 (95% CI 0.96-0.99), and area under the curve of 1.00 (95% CI 0.99-1.00). For wAMD versus dAMD, DL showed sensitivity of 0.95 (95% CI 0.91-0.97; PI 0.89-0.97), specificity of 0.95 (95% CI 0.93-0.97; PI 0.92-0.97), accuracy of 0.95 (95% CI 0.92-0.97), and area under the curve of 0.99 (95% CI 0.97-0.99). DL showed higher sensitivity than senior ophthalmologists for AMD (0.98 vs 0.75; P<.001) and higher specificity and accuracy than junior ophthalmologists for wAMD classification. Optical coherence tomography-based models performed more consistently than color fundus photography or multimodal models. Evidence certainty was moderate.<br><br>CONCLUSIONS: Compared with ophthalmologists, DL algorithms demonstrated superior and more balanced diagnostic performance in the available head-to-head evidence, potentially providing a consistent decision-support baseline that mitigates human threshold-dependent trade-offs. However, high heterogeneity, wide PIs, predominantly retrospective designs, and possible performance inflation from internal validation mean that these relative performance findings remain preliminary rather than deployment ready. DL should be viewed as a triage adjunct requiring local calibration, not an autonomous diagnostic replacement. Prospective, multicenter, patient-level external validation with prespecified human comparison arms is required.}, }
@article {pmid42300220, year = {2026}, author = {Xia, D and Li, W and Xie, J and Zhou, D and Su, H}, title = {Supramolecular peptide hydrogels for the treatment of ocular diseases: from tissue replacements to drug delivery systems.}, journal = {Journal of materials chemistry. B}, volume = {}, number = {}, pages = {}, doi = {10.1039/d6tb00761a}, pmid = {42300220}, issn = {2050-7518}, abstract = {Supramolecular peptide hydrogels (SPHs), a unique class of dynamic three-dimensional networks formed by self-assembly of peptides, have demonstrated strong potential for ocular tissue replacement and drug delivery in ophthalmic applications. On the one hand, their mechanical and physiochemical properties can be precisely tailored via rational design of peptides to emulate native ocular tissues. On the other hand, the intrinsic dynamic features of SPHs enable efficient encapsulation of commercial drugs and incorporation of stimuli-responsive or targeting moieties, which in turn facilitate ocular barrier penetration and enhance therapeutic efficacy. In this review, we systematically summarize recent advances of the use of SPHs in ocular disease treatment, focusing on their design principles and two key application aspects: ocular tissue substitutes (for vitreous and corneal repair) and drug delivery systems targeting prevalent ocular pathologies, including dry eye disease, corneal neovascularization, bacterial keratitis, anterior uveitis, diabetic retinopathy, and age-related macular degeneration. These findings highlight the promising potential of SPHs as next-generation biomaterials for precision ophthalmic therapy.}, }
@article {pmid41117921, year = {2026}, author = {Rahmanipour, E and Afazel, S and Ashrafi, S and Sadeghi, E and Ghorbani, M and Zarranz-Ventura, J and Chhablani, J}, title = {Artificial intelligence in ophthalmology clinical trials: a narrative review.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {1}, pages = {1-17}, pmid = {41117921}, issn = {1435-702X}, abstract = {Artificial intelligence (AI) is progressively advancing across various medical specialties, particularly ophthalmology, to evaluate medical data, prevent diseases, and facilitate individualized treatment strategies. This narrative review investigates the current state of AI applications in ophthalmology clinical trials, focusing on patient monitoring, treatment optimization, and the diagnosis of prevalent ocular disorders. The implementation of AI techniques, such as deep learning and machine learning, improves the precision and efficacy of the process by evaluating ocular imaging data, such as OCTs, to diagnose various conditions, including diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts. Furthermore, AI has transformed patient recruiting, data management, and outcome assessment in clinical trials. In resource-limited settings, the combination of AI and teleophthalmology resulted in greater access to care. Despite its many positive aspects, we must address challenges like data bias, transparency, and ethical concerns to ensure the safe and equitable implementation of AI. As AI progresses, it has the capability to transform ophthalmic care and research, significantly improving patient outcomes and worldwide healthcare accessibility.}, }
@article {pmid41518430, year = {2026}, author = {Gao, ML and Ju, YY and Zhang, J}, title = {Exploring retinal microglia: development, degeneration, and iPSC-derived model systems.}, journal = {Brain structure &amp; function}, volume = {231}, number = {1}, pages = {11}, pmid = {41518430}, issn = {1863-2661}, support = {82070981//Natural Science Foundation of China/ ; 2022YFA1105503//the National Key Research and Development Program of China/ ; }, abstract = {Microglia are key regulators of retinal development, immune surveillance, and neuroprotection. Derived from yolk sac progenitors, they exhibit precise laminar distribution within the retina and fulfill diverse physiological roles, including synaptic pruning, phagocytosis, and modulation of inflammation and angiogenesis. In retinal diseases such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy, microglial activation contributes to neurodegeneration and pathological remodeling. This review summarizes recent advances in our understanding of retinal microglial ontogeny, distribution, and function, with particular emphasis on human pluripotent stem cell (hPSC)-derived microglia (iMG) .We highlight in vitro and chimeric iMG-based models that facilitate human-specific studies and discuss their emerging applications in retinal disease modeling, therapeutic screening, and personalized medicine.}, }
@article {pmid41543775, year = {2026}, author = {Oku, K and Mizobuchi, K and Mochizuki, K and Tsunoda, K and Matsushita, I and Nagata, T and Fujinami, K and Suga, A and Yoshitake, K and Sakaguchi, H and Hayashi, T and Iwata, T and Kondo, H}, title = {Autosomal dominant pigmented paravenous retinochoroidal atrophy associated with pathogenic variant in HK1 gene.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {5}, pages = {1373-1382}, pmid = {41543775}, issn = {1435-702X}, support = {23K09053//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: To determine the clinical characteristics and the causative genetic variant of a familial case of pigmented paravenous retinochoroidal atrophy (PPRCA). METHODS: Whole exome sequencing (WES) was performed on ten individuals from four families. Their clinical characteristics were determined and compared to other patients with other inherited retinal dystrophies (IRDs) who had HK1 gene variants. RESULTS: A known heterozygous pathogenic variant in the hexokinase 1 (HK1) gene, c.2539G > A; p.Glu847Lys, segregated with the six family members. Four affected family members had signs of PPRCA associated with mild macular degeneration detected by fundus autofluorescence and optical coherence tomography. In addition, four patients from three families with the same variant were diagnosed with cone-rod dystrophy, retinitis pigmentosa, and enhanced S-cone syndrome. They had different degrees of macular and mid-peripheral degeneration but lacked the pathogenic features of PPRCA. CONCLUSION: This is the first study of familial PPRCA associated with the pathogenic HK1 variant. Patients with the HK1 variant had different clinical diagnoses based on the variations in the phenotypic severities. Their visual acuity and electroretinograms were less severely altered than expected given the structural abnormalities observed around the macula in imaging analyses.}, }
@article {pmid42284159, year = {2026}, author = {Krogh, M and Ørskov, M and Nørgaard, TL and Germund Nielsen, M and Jensen, MB and Jensen, MSA and Vorum, H and Kristensen, JK}, title = {The diagnostic accuracy of AI-assisted diabetic retinopathy screening in primary care: a prospective validation study.}, journal = {Scandinavian journal of primary health care}, volume = {44}, number = {1}, pages = {2683982}, doi = {10.1080/02813432.2026.2683982}, pmid = {42284159}, issn = {1502-7724}, mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; Primary Health Care ; Prospective Studies ; Female ; Sensitivity and Specificity ; Middle Aged ; *Diabetes Mellitus, Type 2/complications ; Male ; *Mass Screening/methods ; Aged ; *Artificial Intelligence ; Intelligent Systems ; }, abstract = {OBJECTIVES: This study investigated the diagnostic accuracy of AI-assisted diabetic retinopathy screening in primary care, using ophthalmologist-led screening as the reference standard.<br><br>METHODS: Patients with type 2 diabetes attending routine appointments at 10 primary care clinics underwent AI-assisted screening, followed by re-screening at an ophthalmology clinic. The quality of fundus images captured in primary care was independently assessed, and diagnostic accuracy was evaluated by comparing AI-assisted results with ophthalmologist results, including sensitivity, specificity, PPV, NPV, and AUC. Two analyses were conducted: one including all images and one excluding those of poor quality.<br><br>RESULTS: Among 183 patients (336 images), 18.6% of images were classified as poor quality. When all images were included, the AI-assisted screening achieved a sensitivity of 73.7%, specificity of 90.2%, PPV of 31.1%, NPV of 98.3%, and AUC of 0.82. Excluding poor-quality images improved sensitivity to 80.0%, NPV to 98.7%, and AUC to 0.84. Additional ocular findings unrelated to diabetic retinopathy were observed in 96 patients, including confirmed or non-specific signs of glaucoma, cataract, age-macular degeneration, benign nevus and reduced visual acuity.<br><br>CONCLUSION: AI-assisted screening in primary care shows potential for clinical application, but further validation in larger populations and improvements in image quality are needed before clinical implementation.}, }
@article {pmid42285094, year = {2026}, author = {Li, T and Feng, J and Yang, X and Yang, S and Chen, J and Wu, Y and Li, X and Ni, Z and Liu, Y and Song, M and Huang, P and Zheng, K and Wang, H and Xu, X and Sun, J and Wang, F and Jia, H and Sun, X}, title = {Subretinal rAAV2-based VEGF-Trap gene therapy for neovascular age-related macular degeneration: Preclinical assessment and phase 1 trial results.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102869}, doi = {10.1016/j.xcrm.2026.102869}, pmid = {42285094}, issn = {2666-3791}, abstract = {Intraocular vascular endothelial growth factor (VEGF) antagonists for neovascular age-related macular degeneration (nAMD) require frequent injections, leading to treatment burden and suboptimal outcomes. LX102 is an rAAV2-based gene therapy encoding VEGF-Trap via subretinal delivery. In laser-induced choroidal neovascularization (CNV) mouse models, LX102 prevents lesion formation and progression in a dose-dependent manner. In non-human primates, a single LX102 injection reduces grade IV CNV lesions by over 85% and maintains transgene expression for 26 weeks without drug-related ocular abnormalities. In a phase 1 dose-escalation study, 12 participants with nAMD receive a single LX102 administration (2 × 10[10] to 1.25 × 10[11] vector genomes/eye). LX102 is well tolerated with no clinically significant inflammation. Eleven participants (91.7%) require no supplemental anti-VEGF injections through 1 year, with stable visual acuity and reduced central subfield thickness in most cases. These findings support LX102 as a potential sustained therapeutic approach for nAMD. This study was registered at chinadrugtrials.org.cn (CTR20230194) and ClinicalTrials.gov (NCT06198413).}, }
@article {pmid42285217, year = {2026}, author = {Leon Agudelo, JA and Martínez Vallejo, H}, title = {Therapeutic applications of gene editing using CRISPR-Cas9 in the posterior segment: Review of the literature.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502582}, doi = {10.1016/j.oftale.2026.502582}, pmid = {42285217}, issn = {2173-5794}, abstract = {CRISPR-Cas gene editing has become increasingly relevant in the treatment of several ophthalmic diseases. Its ability to make precise modifications at the DNA or RNA level has enabled targeted approaches for specific mutations involved in conditions such as Leber congenital amaurosis type 10 (LCA10), certain forms of retinitis pigmentosa, and age-related macular degeneration. This article provides an organized overview of the biological basis of CRISPR-Cas technology and highlights key advances from preclinical studies and early clinical trials. Technical limitations and ongoing safety challenges are also discussed. Programs such as EDIT-101, EDIT-103, and HG202 stand out as important milestones in the evolution of ocular gene editing.}, }
@article {pmid42286041, year = {2026}, author = {Song, JR and Jeon, J and Baek, SC and Sharma, A and Sagong, M and Lee, CS and Woo, SJ and , }, title = {Aflibercept biosimilar use and real-world outcomes in various retinal diseases: the AURA Korea study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-52212-4}, pmid = {42286041}, issn = {2045-2322}, support = {RS-2025-25454860//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {This multicenter, retrospective real-world study evaluated the efficacy and safety of aflibercept 2 mg biosimilar SB15 (Afilivu®) across multiple retinal diseases. A total of 1083 eyes from 984 patients received 2762 injections between March 2023 and February 2025 at three South Korean tertiary centers, comprising 188 treatment-naïve (17.4%) and 895 switching eyes (82.6%). Diagnoses included neovascular age-related macular degeneration (nAMD, n = 611), retinal vein occlusion (RVO, n = 182), diabetic macular edema (DME, n = 173), and other conditions (n = 117). Over a mean follow-up of 5.17 ± 2.76 months with 2.55 ± 1.09 injections, central foveal thickness decreased significantly by - 47.5 µm (95% CI - 55.2 to - 39.8; P < 0.001), while best-corrected visual acuity remained stable (mean change - 0.003 LogMAR; P = 0.572). Treatment-naïve eyes demonstrated greater anatomical improvement than switching eyes (- 93.9 vs. - 37.9 µm; P < 0.001). Retinal fluid resolved significantly across diagnostic groups: in nAMD, subretinal fluid decreased from 51.2 to 29.6% (P < 0.001); in RVO, intraretinal fluid reduced from 92.9 to 76.4% (P < 0.001); and in DME, intraretinal fluid decreased from 90.8 to 84.4% (P = 0.002). One case (0.09%) of rhegmatogenous retinal detachment occurred; no intraocular inflammation or other serious adverse events were observed. These findings support the real-world effectiveness and safety of SB15 (Afilivu®) in both treatment-naïve and switching populations across diverse retinal diseases.}, }
@article {pmid42287526, year = {2026}, author = {Loewenstein, A and Schmidt-Ott, U and Do, DV and Lanzetta, P and Leal, S and Berliner, AJ and Chu, KW and Barakat, MR and Ghorayeb, G and Stewart, MW and Spitzer, MS and Zhang, X and McCullough, A and Tueckmantel, C and Avila, D and Morgan-Warren, P and Brunck, L and Dupljak, A and Hymowitz, M and Portnoy, A and Gale, R}, title = {Intraocular Pressure Outcomes with Intravitreal Aflibercept 8 mg: A 96-Week Pooled Analysis from PULSAR and PHOTON.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42287526}, issn = {2193-8245}, abstract = {INTRODUCTION: This abstract aimed to explore the potential effect of a higher injection volume with aflibercept 8 mg (70 μl) versus 2 mg (50 μl) on intraocular pressure (IOP).<br><br>METHODS: In PULSAR (NCT04423718), patients with neovascular age-related macular degeneration (nAMD) were randomised 1:1:1 to receive aflibercept 2&#xa0;mg every 8&#xa0;weeks (2q8) or aflibercept 8&#xa0;mg every 12 (8q12) or 16&#xa0;weeks (8q16), after three initial monthly doses. In PHOTON (NCT04429503), patients with diabetic macular oedema (DME) were randomised 1:2:1 to receive 2q8 after five monthly doses or 8q12 or 8q16 after three initial monthly doses. Increased IOP or glaucoma-related treatment-emergent adverse events (TEAEs) and pre- and post-injection IOP measurements were pooled through week 96 and summarised descriptively.<br><br>RESULTS: The safety analysis set included 1667 patients (8&#xa0;mg: n&#x2009;=&#x2009;1164; 2&#xa0;mg: n&#x2009;=&#x2009;503). Baseline mean (SD) IOP was 15.0 (3.2) mmHg and 15.1 (3.0) mmHg in patients receiving aflibercept 8&#xa0;mg and 2&#xa0;mg, respectively. Rates of TEAEs related to glaucoma (including TEAE of IOP increases) were low and similar across treatment groups (8&#xa0;mg: 9/1000 injections; 2&#xa0;mg: 6/1000 injections). Rates of paracentesis were low (8&#xa0;mg: 1/1000 injections; 2&#xa0;mg: 0). Mean pre-injection IOP values measured at each visit were similar, with no sustained increase over time across treatment groups.<br><br>CONCLUSIONS: Comparable IOP outcomes and no long-term IOP or glaucoma-related effects were observed with aflibercept 8&#xa0;mg versus aflibercept 2&#xa0;mg through week 96.<br><br>TRIAL REGISTRATION: PULSAR (NCT04423718) and PHOTON (NCT04429503) trials.}, }
@article {pmid42288324, year = {2026}, author = {Cheon, S and Kim, Y and Kang, ES and Lee, H and Jeong, S}, title = {Noncombustible Nicotine or Tobacco Product Use after Smoking Cessation and Major Vision-Impairing Diseases: A Nationwide Cohort Study.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.06.018}, pmid = {42288324}, issn = {1879-1891}, abstract = {OBJECTIVE: We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to non-combustible nicotine or tobacco products (NNTPs) compared with those who completely quit using tobacco.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: 179,273 adults from the Korean National Health Insurance Service who smoked CC in 2011-2012 and reported cessation in 2018-2019, classified into complete quitters and NNTP switchers.<br><br>METHODS: This nationwide longitudinal cohort study followed participants for up to 6 years and identified incident major vision-impairing eye diseases (cataract, glaucoma, age-related macular degeneration, diabetic retinopathy, and refractive and accommodation disorders) using standardized diagnostic codes. Propensity score matching was applied to emulate a pseudo-randomized comparison, balanced on key demographic, clinical, comorbidity, and lifestyle characteristics. Subdistribution hazard ratios (SHRs) were evaluated using the Fine-Gray subdistribution hazards model accounting for all-cause mortality as a competing risk.<br><br>MAIN OUTCOME MEASURES: Adjusted SHRs for incident major vision-impairing eye diseases.<br><br>RESULTS: Among 32,316 matched participants followed for a mean of 4.6 years, 6,328 incident major vision-impairing eye disease events occurred. The incidence was 41.1 and 44.0 per 1,000 person-years for complete quitters and NNTP switchers, respectively. Switching to NNTPs was associated with an increased risk of major vision-impairing eye disease (SHR, 1.07; 95% CI, 1.02-1.13). The risk elevation was most pronounced for diabetic retinopathy (SHR, 1.24; 95% CI, 1.00-1.53) and refractive and accommodation disorders (SHR, 1.07; 95% CI, 1.01-1.12). These findings were robust across inverse probability-weighted and Cox proportional hazards models. The association remained consistent in sensitivity analyses and across clinical subgroups.<br><br>CONCLUSIONS: Transitioning from CC to NNTPs is associated with a modest but consistent increase in the risk of major vision-impairing eye diseases compared with complete nicotine abstinence. These findings challenge the assumption that substituting NNTPs for CCs is visually harmless and indicate that, from an ophthalmic perspective, complete cessation of all nicotine products should remain the preferred cessation goal.}, }
@article {pmid42291838, year = {2026}, author = {Shadmani, A and Kovach, JL}, title = {Obstructive Sleep Apnea and the Risk of Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261450201}, pmid = {42291838}, issn = {2474-1272}, abstract = {Purpose: To evaluate the association between obstructive sleep apnea and age-related macular degeneration (AMD) and to characterize disease subtype distribution, age trends, and treatment patterns. Methods: A retrospective cross-sectional study was performed between January 1, 2020, and July 30, 2025, of patients aged 50 or older registered in the Epic electronic health record (EHR) system at the University of Miami. AMD prevalence was compared between patients with and without obstructive sleep apnea. Subanalyses included age distribution, AMD subtypes (exudative vs nonexudative), end-stage AMD, and intravitreal injections. Fisher exact test, χ[2] test, and Mann-Whitney U test were performed as appropriate. Results: The prevalence of AMD was higher in patients with obstructive sleep apnea compared with controls (1.996% of patients with obstructive sleep apnea vs 1.023% of controls; P < 4.4×10[-70]). Patients with AMD who had obstructive sleep apnea were younger (mean ≈ 80.8 vs 84.9 years; P < 1.3×10[-35]). Both exudative (odds ratio [OR], 1.71, P < .001) and nonexudative (OR, 1.47, P < .001) AMD were more common in patients with obstructive sleep apnea. Advanced nonexudative AMD, which was defined as nonexudative AMD with subfoveal involvement, was less frequent in patients with obstructive sleep apnea (7.7% vs 13.8%; OR, 0.52; P < 1×10[-6]). Number of intravitreal injections was higher among patients with exudative AMD who had obstructive sleep apnea (60.6% vs 48.0%; OR, 1.83; P < 1×10[-8]). Conclusions: Obstructive sleep apnea is associated with nearly double the prevalence of AMD, earlier age of onset, greater risk of both exudative and nonexudative subtypes, and higher intravitreal injection rates. These findings suggest obstructive sleep apnea may contribute to AMD pathogenesis and progression.}, }
@article {pmid42292229, year = {2026}, author = {Nowak, M and Cybulska, AM and Derezińska, A and Grochans, E and Panczyk, M and Kęcka, K and Rachubińska, K}, title = {Quality of life in patients with neovascular age-related macular degeneration before and after intravitreal therapy: a longitudinal observational study.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1731481}, pmid = {42292229}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related macular degeneration is a chronic and progressive disease that typically develops after the age of 50. Characterized by visual distortions, image blurring, and gradual central vision loss, age-related macular degeneration significantly impairs patients' ability to perform everyday activities and contributes to a marked reduction in quality of life. The gold standard treatment for the neovascular form of this condition consists of intravitreal injections. This therapy offers patients the possibility of improved vision-related quality of life by slowing disease progression and partially restoring visual function to levels approximating those prior to the onset of the condition. The aim of this study was to examine vision-related quality of life in individuals with neovascular age-related macular degeneration prior to treatment and following a course of seven intravitreal injections. The study also aimed to analyze its association with visual acuity, contrast sensitivity, and the occurrence and severity of metamorphopsia and central scotoma.<br><br>METHODS: This survey-based study was carried out using the author's questionnaire and a standardized research tool-the Polish version of National Eye Institute Visual Functioning Questionnaire. It also involved the analysis of the patients' medical records.<br><br>RESULTS: The study group consisted of 121 patients (121 eyes), comprising 60 women and 61 men, aged between 51 and 90 years. Following a course of intravitreal injections, a statistically significant improvement in vision-related quality of life, as measured by the Visual Functioning Questionnaire, was observed. The analysis also demonstrated an association between quality of life and visual function parameters.<br><br>CONCLUSION: Vision-related quality of life in patients with neovascular age-related macular degeneration was low at baseline and showed a modest improvement following initiation of intravitreal anti-VEGF therapy over the follow-up period. Across time points, better visual acuity, higher contrast sensitivity, and fewer visual disturbances on the Amsler grid were associated with higher vision-related quality of life scores. This study highlights the potential psychosocial benefits of intravitreal therapy in nAMD and may help support patients in initiating treatment or in maintaining adherence to continuing therapy.}, }
@article {pmid42292913, year = {2026}, author = {Xu, X and Luo, G}, title = {Preclinical evaluation of AAV2 anti-VEGF gene therapy using scFv for choroidal neovascularization.}, journal = {Molecular therapy. Advances}, volume = {34}, number = {3}, pages = {201767}, pmid = {42292913}, issn = {3117-387X}, abstract = {Single-chain variable fragments (scFvs) have been proposed as efficient therapeutic cargoes for gene therapy. However, their safety and efficacy in clinical settings remain to be fully established. In this study, we constructed a recombinant adeno-associated virus 2 (AAV2) vector encoding an anti-VEGF scFv to inhibit choroidal neovascularization (CNV), and evaluated its efficacy, biodistribution, and safety in non-human primates (NHPs) and chinchilla rabbits. Pharmacological studies demonstrated sustained inhibition of neovascularization and vascular leakage both in vivo and in vitro. Pharmacokinetic and biodistribution analyses further showed that a single subretinal injection of AAV2-antiVEGFscFv resulted in prolonged retention of the transgene product in the retina and choroid, with minimal distribution to non-target tissues. These results indicate that AAV2-antiVEGFscFv may provide a safe and durable therapeutic approach for wet age-related macular degeneration (AMD). Collectively, our results support the potential of scFvs as efficient and well-tolerated therapeutic payloads for in vivo gene therapy, with the capacity to overcome key limitations of conventional antibody-based therapies.}, }
@article {pmid42293250, year = {2026}, author = {Perrone, CD and Raucci, L and Papini, S and Tosi, GM and Galvagni, F and Olivucci, M and Incarnato, D and Orlandini, M}, title = {Rational design of hammerhead ribozymes as CD93 silencing tools for vascular diseases.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {2}, pages = {102968}, pmid = {42293250}, issn = {2162-2531}, abstract = {While targeting angiogenesis represents a key therapeutic strategy in several pathological contexts, it comes with significant challenges associated with therapeutic efficacy and drug resistance. Therefore, developing novel, more effective and durable therapeutic modalities is paramount. We have previously reported that antibody-mediated inhibition of CD93, a vascular endothelial cell surface glycoprotein, can inhibit angiogenesis. Here, we describe a novel strategy to efficiently inhibit CD93 expression in cells, based on the targeted degradation of CD93 mRNA using trans-acting hammerhead ribozymes. To pinpoint single-stranded regions in CD93 mRNA that are amenable to ribozyme targeting in living cells, we performed RNA secondary structure mapping via targeted DMS-MaPseq analysis. Next, since exogenous hammerhead ribozymes are easily degraded and lose catalytic activity when expressed in living cells, we developed a novel scaffold RNA based on short stems from the 3' UTR of histone mRNAs to stabilize the active ribozyme structure and promote the CD93 cleavage under physiological conditions. Ectopic expression of these engineered ribozymes in primary endothelial cells resulted in efficient inhibition of CD93 expression, cell migration, and formation of tube-like structures in functional assays. Collectively, our data provides the proof-of-concept for the use of ribozyme-based therapeutics for the treatment of neovascular pathologies.}, }
@article {pmid42293345, year = {2026}, author = {Bogost, J and Saunders, T and Heathcote, J and Pak, JW and Lopez, D and Froines, C and Blodi, B and Channa, R and Schildroth, K and Kurt, K and Mititelu, M and Stepien, K and Chang, JS and Altaweel, M and Gottlieb, J and Conlin, K and Sabb, P and Patel, N and Domalpally, A}, title = {Comparison of Clarus, Optos, and Heidelberg Systems for Geographic Atrophy Area Measurements.}, journal = {Ophthalmology science}, volume = {6}, number = {7}, pages = {101207}, pmid = {42293345}, issn = {2666-9145}, abstract = {PURPOSE: To compare geographic atrophy (GA) area measurements across 3 modern fundus autofluorescence (FAF) imaging platforms: Heidelberg Spectralis, Optos California, and Zeiss Clarus 700.<br><br>DESIGN: A prospective, single-center, cross-sectional comparative imaging study.<br><br>PARTICIPANTS: Sixty-one eyes from 39 participants aged &#x2265;50 years with GA secondary to age-related macular degeneration.<br><br>METHODS: Participants were imaged sequentially on the same day with all 3 devices: Optos California FAF (532 nm green excitation, 200&#xb0; ultra-widefield), Zeiss Clarus 700 FAF (blue 435-500 nm and green 500-585 nm channels, 133&#xb0; widefield), and Heidelberg Spectralis FAF (488 nm blue excitation, 30&#xb0; field). Geographic atrophy was segmented with manual planimetry for all modalities; Heidelberg images were also segmented semiautomatically with RegionFinder. RegionFinder area values served as the reference standard for comparisons.<br><br>MAIN OUTCOME MEASURES: Mean GA area by imaging system and agreement with RegionFinder.<br><br>RESULTS: Agreement with RegionFinder was high across imaging systems (intraclass correlation coefficients: 0.96-0.99), but systematic differences were noted in GA area measurements. Geographic atrophy measured larger on average with Clarus Green and Heidelberg manual planimetry (0.49 mm[2] [95% confidence interval [CI], 0.23 to 0.75] and 0.34 mm[2] [95% CI, 0.22 to 0.45], respectively), while Optos California measured smaller areas (-0.47 mm[2] [95% CI, -0.81 to -0.13]).<br><br>CONCLUSIONS: Geographic atrophy area measurements are reproducible within each FAF imaging system but systematically differ between platforms and wavelengths. Repeated use with the same device recommended for clinical trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42294393, year = {2026}, author = {Sheibani, N}, title = {Emerging Roles of Regulated Cell Death-mediated Inflammation in Pathophysiology of Ocular Diseases.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {21}, number = {}, pages = {}, pmid = {42294393}, issn = {2008-2010}, abstract = {Regulated cell death pathways are vital for proper developmental and homeostatic processes. Dysregulation of these pathways contributes to the pathogenesis of many diseases, including ocular inflammatory and neurodegenerative diseases such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and ocular surface diseases. Our knowledge of the regulated cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, has been extensively expanded in the recent years. The targeting of these pathways as a potential therapy for various ocular diseases is now widely recognized. In recent years, it has also become clear that in many circumstances, the engagement of multiple regulated cell death pathways could be coordinated through specific cross talks to drive a stress-specific cell death and disease pathogenesis. This knowledge is extended to the recognition that targeting multiple regulated cell death pathways could be more effective for the treatment of various pathologies. However, the identity of upstream regulatory pathways and the engagement hierarchy of individual pathways and their coordinated interactions require further investigation. Here, I will briefly introduce these regulated cell death processes, discuss the key regulatory pathways involved in determining cell death or survival, as well as upstream modulators. I will also highlight studies targeting these pathways as potential treatment strategies for various eye diseases.}, }
@article {pmid42294394, year = {2026}, author = {Khorrami-Nejad, M and Narooie-Noori, F and Al-Khafaji, Q and Hashemian, H and Balal, S and Dohlman, T and Daya, S}, title = {Quality of Life in Patients with Posterior Segment Eye Diseases.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {21}, number = {}, pages = {}, pmid = {42294394}, issn = {2008-2010}, abstract = {Posterior segment eye diseases pose a significant threat to vision-related quality of life, affecting functional independence, psychological health, and social well-being. Conditions such as diabetic retinopathy and age-related macular degeneration are leading causes of blindness, often resulting in severe emotional distress and reduced mobility. Optic neuritis and optic neuropathy can lead to vision loss and increase the risk of depression, particularly in patients with multiple sclerosis. Retinal disorders like central serous chorioretinopathy and retinitis pigmentosa disrupt daily tasks such as reading and driving, thus leading to social isolation and economic burden. Hypertensive retinopathy and retinal detachment further contribute to vision impairment, with long-term implications for functional ability and mental health. Inherited retinal diseases such as Stargardt disease and Leber congenital amaurosis significantly reduce quality of life from an early age and negatively affect education, employment opportunities, and psychological well-being. Additionally, the economic impact of these diseases is substantial, with high treatment costs and productivity loss. On the other hand, vision rehabilitation, psychological support, and advancements in gene and pharmacological therapy can largely mitigate the adverse effects on quality of life associated with posterior segment diseases. Therefore, a comprehensive approach that integrates medical, psychological, and social interventions is essential for improving patient outcomes. Future research should focus on developing innovative treatments and patient-centered care strategies to improve the quality of life for individuals affected by this condition.}, }
@article {pmid42294415, year = {2026}, author = {Ahmed, E and Goodchild, C and Bisoukis, A and Salvatore, S}, title = {Two-Year Real-World Outcomes of Faricimab in Treatment-Resistant Neovascular Age-Related Macular Degeneration.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {596406}, pmid = {42294415}, issn = {1177-5467}, abstract = {OBJECTIVE: To evaluate long-term visual and anatomical outcomes of faricimab (Vabysmo[®]) in patients with neovascular age-related macular degeneration (nAMD) showing suboptimal response to aflibercept 2mg (Eylea[®]) in a real-world setting.<br><br>METHODS: This retrospective cohort study evaluated 152 eyes from 126 patients switched to faricimab. All received four loading doses, then a treat-and-extend regimen with &#x2265; 20-month follow-up. Primary outcomes were changes in non-refracted best-recorded visual acuity (BRVA) and central subfield thickness (CST). Secondary outcomes: fluid status, treatment interval, and safety.<br><br>RESULTS: Baseline mean BRVA was 69.91 &#xb1; 13 letters, maintained at year 2 (65.9 &#xb1; 17.1, p = 0.622). CST decreased from 301.5 &#xb1; 86.9&#xa0;&#xb5;m at baseline to 222.2 &#xb1; 49.2&#xa0;&#xb5;m at year 2 (p <0.001). Complete fluid resolution rose from 12.5% at baseline to 50.7% and 49.3% in years 1 and 2 respectively. Subretinal fluid decreased from 79% to 34% (p <0.001), while intraretinal fluid improved post-loading (30% to 18%, p=0.005) but remained detectable in 25.7% by year 2 (p=0.36). Treatment intervals were extended from 5.8 &#xb1; 1.4&#xa0;weeks to 9.7 &#xb1; 3.1&#xa0;weeks at year 2 (p < 0.001). By year 2, 18% of eyes achieved &#x2265;12-week intervals; 7% achieved &#x2265;16-week intervals. No cases of endophthalmitis, vasculitis, or retinal artery occlusion were observed, and ocular adverse events occurred in 3% of eyes.<br><br>CONCLUSION: In treatment-resistant nAMD, switching from aflibercept 2mg to faricimab maintained vision, improved anatomical outcomes, enabled extended treatment intervals, and showed a favorable safety profile over 2 years.}, }
@article {pmid42294419, year = {2026}, author = {Csaky, K and Pepio, AM and Thomas, C and Levitan, B and Garg, S and Tran, N and Irony, I and Krucien, N and Doldos, A and Whitty, JA}, title = {US Retina Specialists' Preferences for Geographic Atrophy Treatment.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {594882}, pmid = {42294419}, issn = {1177-5467}, abstract = {PURPOSE: Two complement inhibitors are US-approved for geographic atrophy (GA) and other treatments are in development. We present the first quantitative assessment of retina specialists' (RS) preferences for GA treatment. We explored how GA treatment characteristics affect RS' preferences, the trade-offs RS are willing to make between them, and whether this varies across patient profiles.<br><br>METHODS: US-based RS with &#x2265;7 years of clinical experience and &#x2265;50 patients with GA in the previous year selected their best and second-best treatment recommendations for specific patient profiles in 12 tasks showing two hypothetical treatment options and no treatment (best-best discrete choice experiment, BB-DCE). Treatment characteristics comprised lesion growth rate reduction, three treatment risks (mild-to-moderate uveitis, progression to wet age-related macular degeneration [AMD], and retinal vasculitis), and intravitreal injection frequency (every month, every other month, and one-time [gene therapy]). Patient profiles were defined by GA lesion location and visual acuity. Preferences were evaluated using a mixed-logit model. Relative importance of each characteristic and trade-offs were analyzed.<br><br>RESULTS: Of 166 RS, 83.1% had experience treating GA with complement inhibitors. Improving lesion growth rate reduction from 10% to 50% had the greatest impact (almost half of decision-making). Among risks, reducing the chance of progressing to wet AMD from 15% to 1% had the greatest impact (~20% of decision-making). All else equal, RS preferred a one-time over monthly injection(s). Risk tolerance increased with higher lesion growth rate reduction and, to a lesser extent, with less frequent injections; risk tolerance was highest when considering patients with foveal-threatening GA lesions.<br><br>CONCLUSION: Across patient profiles, RS prioritized lesion growth rate reduction over risks; intravitreal injection frequency was the least important. However, RS were more risk-tolerant with patients with foveal-threatening lesions. RS would tolerate slightly higher risks for a one-time over monthly injection(s) if lesion growth rate reduction was comparable.}, }
@article {pmid42294805, year = {2026}, author = {Heatley, AC and Enbiyaoglu, M and Engelmann, J and Zhou, Y and Cortina-Borja, M and Khawaja, AP and Denniston, AK and Zhu, LZ and Keane, PA and Wagner, SK}, title = {Macula- Versus Disc-Centered Fundus Photography: Performance in Age-Prediction and Disease Associations.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {6}, pages = {24}, doi = {10.1167/iovs.67.6.24}, pmid = {42294805}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Female ; *Macula Lutea/diagnostic imaging ; Middle Aged ; Male ; Aged ; *Photography/methods ; *Aging/physiology ; *Optic Disk/diagnostic imaging ; Fundus Oculi ; *Macular Degeneration/diagnosis/diagnostic imaging ; Deep Learning ; Adult ; Reproducibility of Results ; }, abstract = {PURPOSE: The purpose of this study was to compare deep learning (DL)-based age prediction performance and inter-method agreement using macula- versus disc-centered color fundus photographs (CFPs), and to determine whether image fixation modifies the association between retinal age gap (RAG) and disease.<br><br>METHODS: This retrospective cohort study analyzed 12,230 same-day macula- and disc-centered CFP pairs from 5895 patients (&#x2265;40 years) attending Moorfields Eye Hospital (2008-2018). We used a previously validated model that predicts chronological age using either macula- or disc-centered CFPs. DL-predicted age was compared via mean absolute error (MAE), intraclass correlation coefficients (ICCs), and Bland-Altman analysis. Associations between RAG and clinical conditions were assessed using generalized linear mixed-effects models with a patient-level random intercept.<br><br>RESULTS: Macula-centered CFPs yielded a smaller MAE than disc-centered images (7.09 vs. 7.77 years), and age predictions differed significantly between fixation types (P < 0.01). Overall agreement between macula- and disc-centered predictions was high, with an ICC of 0.83 (95% confidence interval [CI] = 0.82-0.84). RAG was significantly associated with age-related macular degeneration (AMD; odds ratio [OR] = 3.57, 95% CI = 1.76-7.24, P < 0.001). No statistically significant interaction between RAG and fixation type was observed.<br><br>CONCLUSIONS: Although fixation type influenced absolute age predictions, it did not significantly modify RAG-disease associations. These findings support the use of either fixation type in oculomics research where imaging flexibility is required, although formal interchangeability cannot be claimed given the systematic bias, heteroscedasticity, and subgroup variation in agreement identified. Prospective validation in population-based cohorts is required before clinical application can be achieved.}, }
@article {pmid42295093, year = {2026}, author = {Zheng, G and Hu, S and Zhao, Y and Lin, Y and Jiao, H and He, W and Huang, T and Wang, S and Ye, C and Shen, M and Li, M and Chen, J and Liu, X and Lu, F}, title = {Community-Based Ocular Screening Integrated into Primary Healthcare for Older Adults: Design and 2-Year Follow-Up Results.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2026.10331}, pmid = {42295093}, issn = {2152-5250}, abstract = {This research aims to describe the design, objective and feasibility of a pioneering community-based eye screening program intended to facilitate the provision of ocular services to the elderly. As a prospective investigation, this project innovatively integrates comprehensive eye examinations into routine annual physical assessments by leveraging cutting-edge automation, digital documentation, and real-time data transmission technologies. Eligible participants included community-dwelling adults aged ≥ 60 years undergoing health check-ups. Four foundational ophthalmic assessments, namely presenting distance visual acuity, autorefraction, intraocular pressure and non-mydriatic fundus photography, were measured to detect prevalent age-related eye diseases. Further, a dual-validation system combining artificial intelligence-driven analysis with on-site expert confirmation was implemented for high-risk case identification. Additionally, a tiered management strategy featuring rapid referral pathways was established to ensure timely tertiary care access. Among 3785 eligible residents, 3459 (91.4% response rate) completed initial screening, with an average examination duration of 4-8 minutes. Following expert validation, 1679 participants (48.5%) required advanced evaluation. Substantial unmet ophthalmic needs were uncovered, with prevalence rates of cataract (43.5%), age-related macular degeneration (37.5%), uncorrected refractive errors (14.6%), glaucoma suspicion (12.4%) and diabetic retinopathy (4.8%). A two-year follow-up analysis demonstrated observed visual improvements, particularly in younger cohorts (60-69 years). In contrast, the relatively older subgroup (70-74 years) exhibited progressive decline. This investigation establishes a model for geriatric vision care that demonstrated feasibility through its synergistic integration of technological innovation and existing primary community health infrastructure, although scalability to other populations and low referral completion require further evaluation.}, }
@article {pmid42295499, year = {2026}, author = {Ren, X and Yu, X and Huang, S and Qi, X and Wang, S and Sun, Y}, title = {Serous Maculopathy due to Aspecific Choroidopathy (SMACH): a case report with differential diagnosis based on multimodal imaging analysis.}, journal = {Documenta ophthalmologica. Advances in ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {42295499}, issn = {1573-2622}, abstract = {BACKGROUND: Serous Maculopathy Due to Aspecific Choroidopathy (SMACH) is a rare chorioretinal disease characterized by polymorphic, non-pigmented choroidal lesions, with or without subretinal fluid (SRF). Its clinical manifestations overlap with common conditions such as central serous chorioretinopathy (CSC) and age-related macular degeneration (AMD), leading to a high risk of misdiagnosis, particularly in elderly patients. Multimodal imaging, including optical coherence tomography (OCT), OCT angiography (OCTA), fluorescein fundus angiography (FFA), and indocyanine green angiography (ICGA), is critical for accurate diagnosis.<br><br>CASE PRESENTATION: A 76-year-old Asian female presented with a 6-month history of blurred vision in her left eye. Ophthalmic examination revealed multiple yellowish-white subretinal lesions with mild elevation in the posterior pole of the left eye. OCT and OCTA demonstrated hyperreflective fibrinous exudates between the retinal pigment epithelium (RPE) and Bruch's membrane, choroidal thickening, and outer retinal damage. Fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) provided complementary findings consistent with choroidal dysfunction and blood-retinal barrier disruption. Systemic evaluations, including laboratory tests for rheumatological immune indicators, tuberculin test, syphilis serology, and imaging examinations, excluded other systemic diseases. Based on these multimodal imaging findings and exclusion of alternative diagnoses, the patient was diagnosed with SMACH.<br><br>CONCLUSIONS: This case report describes a typical presentation of SMACH in an elderly patient, emphasizing that multimodal imaging, as demonstrated in this case, can help identify characteristic features of SMACH (choroidal thickening, hyperreflective exudates), though its diagnostic reliability in larger populations requires further validation.The exclusion of systemic diseases and differentiation from similar chorioretinal disorders (e.g., CSC, AMD) are crucial for accurate diagnosis.This case adds to the existing limited data on SMACH in elderly populations and further supports the role of multimodal imaging in improving diagnostic accuracy to reduce misdiagnosis.}, }
@article {pmid42034834, year = {2026}, author = {Platania, CBM and Conti, F and Trotta, MC and Marchesi, N and Panico, S and Lazzara, F and Lepre, CC and Russo, M and Gesualdo, C and Simonelli, F and D'Amico, M and Drago, F and Pascale, A and Rossi, S and Tarallo, V and Bucolo, C}, title = {Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions.}, journal = {Inflammation}, volume = {49}, number = {1}, pages = {}, pmid = {42034834}, issn = {1573-2576}, abstract = {UNLABELLED: Purinergic receptor (P2X7R), an adenosine triphosphate (ATP) gated nonselective cation channel, is an emerging target for several neurodegenerative conditions, including retinal degeneration. In particular, P2X7R has an established role in multiple inflammatory and immune responses, being implicated in the formation and activation of NLRP3 inflammasome leading to inflammatory priming and release of immune cytokines. Despite several efforts in P2X7R antagonist design, no drugs have reached the market yet. In this perspective, through an integrated in silico and in vitro approach, we aimed to repurpose FDA approved drugs in search of novel safe treatments for retinal degenerative diseases, where P2X7R has been found to play a detrimental role. Virtual screening of about 10,000 FDA approved drugs identified 6 putative P2X7 antagonists. Three out of these six compounds inhibited hP2X7, but not rat receptors, while only one compound, tipranavir, inhibited also mouse P2X7R. Then, for these three P2X7R antagonists, namely bazedoxifene, teniposide and tipranavir, we have evaluated the in vitro tolerability by treating immortalized human Müller cells (MIO-M1), primary retinal endothelial cells (HRECs), human umbilical vein endothelial cells (HUVECs) and human retinal pigmented epithelial cells (hRPEs). Tipranavir and teniposide were well tolerated by the mentioned retinal cells, thereby they have been further evaluated in in vitro models of glaucoma, diabetic retinopathy, and age-related macular degeneration. Tipranavir and teniposide showed retinal cell protection, modulating the expression of HIF-1α, VEGF-A, and inflammatory cytokines. Therefore, these compounds are worthy of further investigation to manage retinal degenerative conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10753-026-02513-7.}, }
@article {pmid42276620, year = {2026}, author = {Shenoy, A and Eva, TA and Palanivel, V and Salkar, A and Gupta, VB and Chitranshi, N and Graham, SL and Gupta, V and Basavarajappa, D}, title = {Invisible threats of microplastics induced toxicity: Oxidative and inflammatory pathways in the CNS and retina.}, journal = {International review of neurobiology}, volume = {186}, number = {}, pages = {25-47}, doi = {10.1016/bs.irn.2026.01.003}, pmid = {42276620}, issn = {2162-5514}, mesh = {Humans ; Animals ; *Oxidative Stress/drug effects ; *Microplastics/toxicity ; *Neuroinflammatory Diseases/chemically induced/metabolism ; *Retina/drug effects/metabolism ; *Inflammation/chemically induced/metabolism ; *Central Nervous System/drug effects/metabolism ; Blood-Retinal Barrier/drug effects/metabolism ; }, abstract = {The global spread of microplastics has become a serious public health concern. Once thought to be inert, microplastics are now recognized as biologically active agents capable of accumulating in the body and causing toxic effects across organ systems. This review summarizes current evidence on their oxidative and inflammatory effects in the central nervous system (CNS) and the eye. Studies show that microplastics can cross biological barriers such as the blood-brain barrier (BBB) and blood-retinal barrier (BRB), where they are taken up by cells, impair mitochondria, and trigger inflammation. Microplastics have been found in cerebrospinal fluid, brain tissue, and ocular structures, raising concern about their link to neurodegenerative and retinal diseases, including Alzheimer's, Parkinson's, macular degeneration, and other disorders. Mechanistic data indicate activation of NF-κB and TGF-β1 pathways, promotion of protein aggregation, and disruption of neural signaling. In the eye, microplastics have been linked to oxidative stress, corneal thinning, and photoreceptor damage. However, human studies are limited due to challenges in detecting tiny particles and lack of microplastic-free controls. Research is further hindered by inconsistent definitions, particle diversity, and non-physiological exposure models. We highlight the need for standardized methods, multi-omics tools, and long-term studies to better understand exposure impacts. Given the rise in neurological and ocular diseases, clarifying the role of microplastics is essential for effective public health strategies.}, }
@article {pmid42276734, year = {2026}, author = {Mulyukov, Z and Olgac, U and Kearns, JD and Liu, C and Pigeolet, E and Weissgerber, G}, title = {Alternative posology for brolucizumab: a 6-week loading regimen is as effective as a 4-week regimen for the treatment of nAMD.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {2}, pages = {}, doi = {10.1136/bmjophth-2025-002660}, pmid = {42276734}, issn = {2397-3269}, mesh = {Humans ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage/pharmacokinetics ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/pharmacokinetics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Drug Administration Schedule ; Dose-Response Relationship, Drug ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Male ; Tomography, Optical Coherence ; Female ; Aged ; Time Factors ; }, abstract = {BACKGROUND: Extending the dosing interval with the anti-vascular endothelial growth factor (VEGF) brolucizumab in the loading phase may reduce treatment burden while maintaining functional and anatomical outcomes for patients with neovascular age-related macular degeneration.<br><br>METHODS: We integrated population pharmacokinetic/pharmacodynamic (PK/PD) and quantitative system pharmacology (QSP) modelling approaches to evaluate the effect of brolucizumab 6&#x2009;mg on central subfield thickness (CSFT) and best-corrected visual acuity (BCVA) using an alternative reduced loading regimen (two or three administrations every 6 weeks (q6w)) followed by individualised every 12 weeks/every 8 weeks (q12w/q8w) maintenance. The simulation results were compared with the CSFT and BCVA outcomes in the phase 3 HAWK and HARRIER studies, in which patients received the approved loading regimen of 3 monthly doses.<br><br>RESULTS: For both loading regimens, simulations of the QSP model showed almost complete VEGF inhibition during the loading phase and free VEGF recovery commenced 6&#x2012;7 weeks following the last loading dose, returning to baseline levels after 12&#x2012;13 weeks.The population PK/PD simulations showed that week 48 and week 36-48 mean BCVA and CSFT changes from baseline using the alternative loading regimen and individualised maintenance treatment were similar to&#x2009;HAWK and HARRIER study measures. Simulated disease activity assessments indicate that only 20% of patients needed third q6w loading dose before switching to q12w/q8w maintenance treatment.<br><br>CONCLUSIONS: This integrated modelling approach predicted that reducing the loading regimen of brolucizumab 6&#x2009;mg treatment to two or three doses every 6&#x2009;weeks is expected to result in similar efficacy outcomes, resulting in regulatory approval of this alternative dosing regimen in several countries.}, }
@article {pmid42276988, year = {2026}, author = {Bielmeier, CB and Schmitt, SI and Lehr, V and Grundl, A and Dillinger, AE and Jägle, H and von Toerne, C and Hauck, SM and Ergün, S and Tamm, ER and Schlecht, A and Neueder, A and Braunger, BM}, title = {VEGFR2 deletion increases susceptibility to photoreceptor degeneration through glial-neuronal interaction.}, journal = {Cell death &amp; disease}, volume = {17}, number = {1}, pages = {}, pmid = {42276988}, issn = {2041-4889}, support = {BR 4957/3-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Intraocular anti-VEGFA injections are frequently used to counteract neovascularization in diseases such as the neovascular form of age-related macular degeneration (AMD). However, in the clinical context, patients with atrophic (dry) and neovascular (wet) AMD in the same eye will receive anti-VEGFA injections, but there are reports that this severely promotes the development of atrophic areas in dry AMD. To study this, we used mice with a tamoxifen-dependent deletion of Vegfr2 in the eye (Vegfr2[Δeye]) and the light damage model to mimic certain aspects of dry AMD. We examined retinal morphology and function, the degree of photoreceptor degeneration, and alterations of the retinal proteome. While steady-state retinal morphology and function were not altered due to VEGF signaling deficiency, light-induced photoreceptor degeneration was drastically exacerbated in Vegfr2[Δeye] retinae, concomitant with attenuated activation of the AKT kinase pathway. Furthermore, using single nuclei RNA sequencing data, we showed that in humans, Vegfr2 is predominantly expressed in macroglial cells of healthy, dry- and wet AMD retinae. This suggests a VEGF-dependent neuroprotective crosstalk from macroglial cells to photoreceptors and poses promising therapeutic options to attenuate photoreceptor degeneration in humans. Yet, our data also indicate that anti-VEGF therapy should be carefully considered in the presence of neurodegenerative comorbidities.}, }
@article {pmid42277220, year = {2026}, author = {Al-Janabi, A and Gallagher, K and Stewart, C and Williams, G}, title = {Clinical characteristics and outcomes of intraocular inflammation following intravitreal faricimab for neovascular age-related macular degeneration: a single-centre retrospective study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42277220}, issn = {1476-5454}, abstract = {PURPOSE: To describe the clinical characteristics and outcomes of intraocular inflammation (IOI) following intravitreal faricimab injection in a real-world setting.<br><br>METHODS: This retrospective single-centre cohort study evaluated eyes developing IOI following intravitreal faricimab injection. Clinical characteristics, SUN-graded inflammatory features, intraocular pressure (IOP) changes, and time to resolution were analysed.<br><br>RESULTS: A total of 14 eyes from 13 patients developed IOI following intravitreal faricimab injection, corresponding to an incidence of 0.13% per injection. All eyes developed anterior chamber inflammation, with two-thirds also demonstrating associated vitritis. Fifty percent (7/14 eyes) presented with an IOP&#x2009;>&#x2009;21&#x2009;mmHg. Overall, IOP increased from baseline in 11/14 eyes (79%), with 5 eyes (36%) demonstrating a clinically significant rise of &#x2265;10&#x2009;mmHg. The severity of acute anterior uveitis and vitritis correlated positively with time to resolution, whereas the presence of hypertensive uveitis did not significantly affect resolution time. The mean time to resolution was approximately two months.<br><br>DISCUSSION: This study provides a comprehensive characterisation of post-faricimab IOI, including detailed SUN-graded phenotyping, IOP outcomes, and recurrent inflammatory episodes. Greater inflammatory severity was associated with prolonged resolution time, while hypertensive features did not appear to influence inflammatory recovery.}, }
@article {pmid42277682, year = {2026}, author = {Chang, W and Kim, J and Jeon, J and Park, S}, title = {Real-world outcomes of faricimab in treatment-naïve patients with neovascular age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-05019-w}, pmid = {42277682}, issn = {1471-2415}, abstract = {BACKGROUND: To evaluate real-world efficacy, durability, and safety of faricimab in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Retrospective study of treatment-na&#xef;ve nAMD eyes treated with faricimab at a single centre in South Korea. After four monthly loading doses, treatment intervals (Q8W, Q12W, Q16W) were assigned based on disease activity at weeks 20 and 24. Comprehensive assessments included best-corrected visual acuity (BCVA), central subfield thickness (CST), pigment epithelial detachment (PED) height, subfoveal choroidal thickness (SFCT), and intraretinal/subretinal fluid (IRF/SRF) presence.<br><br>RESULTS: Eighty-eight treatment-na&#xef;ve eyes were included. Mean age was 72.8 (9.0) years. At week 20, BCVA improved from 62.1 (15.4) to 69.3 (14.6) ETDRS letters (+&#x2009;7.1 letters, P&#x2009;<&#x2009;0.001). CST decreased from 414 (150) to 280 (94) &#xb5;m (-&#x2009;134&#xa0;&#x3bc;m, P&#x2009;<&#x2009;0.001). PED height decreased from 297 (167) to 171 (116) &#xb5;m (-&#x2009;43%, P&#x2009;<&#x2009;0.001). SFCT decreased from 208 (91) to 184 (83) &#xb5;m (-&#x2009;12%, P&#x2009;<&#x2009;0.001), with PCV eyes showing the greatest reduction (-&#x2009;32&#xa0;&#x3bc;m, P&#x2009;<&#x2009;0.001). IRF presence (1&#xa0;mm/6&#xa0;mm) decreased from 33%/34% to 7%/9%, and SRF from 78%/84% to 12%/20% at week 20. At week 60, 52.3% achieved Q16W and 67.0% achieved &#x2265;Q12W intervals. Among 168 eyes in the safety analysis, there was 1 case of mild vitritis and 2 cases of RPE tear, with no cases of endophthalmitis or retinal vasculitis reported.<br><br>CONCLUSIONS: Initiation of faricimab in treatment-na&#xef;ve nAMD patients resulted in favourable visual and anatomical outcomes with durable treatment intervals and a low incidence of adverse events in a real-world setting.}, }
@article {pmid42278605, year = {2026}, author = {Jakobsen, TS and Kaptain, K and Pedersen, K and Adsersen, RL and Aagaard, L and Askou, AL and Corydon, TJ}, title = {The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {11}, pages = {}, doi = {10.3390/ijms27115080}, pmid = {42278605}, issn = {1422-0067}, support = {NA//Fight for Sight, Denmark/ ; NA//Synoptik Foundation/ ; NA//AP Moller Foundation/ ; NA//Dagmar Marshalls Foundation/ ; 2034-00036B//Independent Research Fund Denmark/ ; 24OC0088426//Novo Nordisk Foundation/ ; R480-2024-1094//Lundbeck Foundation/ ; }, abstract = {Single-domain antibodies (sdAbs) are the smallest antigen-binding antibody (Ab) fragments (12-15 kDa) and have emerged as a versatile therapeutic platform. Their compact size, high solubility, stability, and ability to access cryptic epitopes distinguish them from conventional monoclonal Abs (mAbs) and larger Ab fragments. These properties are particularly attractive in ophthalmology, where molecular size, tissue penetration, and formulation constraints critically influence therapeutic performance. This narrative review summarizes the structural features, engineering strategies, immunogenicity considerations, and production platforms of sdAbs, with a focus on ocular applications. Preclinical studies demonstrate promising efficacy in retinal vascular diseases through targeting of VEGFA, ANG2, TNFα, and complement components, as well as in inflammatory and anterior segment disorders. SdAbs can be formatted as multimeric or Fc-fused constructs to extend intraocular half-life or delivered via gene therapy vectors as a sustained intraocular "biofactory" approach. Notably, recent work demonstrates the feasibility of vector-encoded sdAbs targeting complement C3 in vivo. While challenges remain regarding immunogenicity, pharmacokinetics, and regulatory pathways, the approval of several sdAb-based drugs in other fields underscores their clinical potential. SdAbs represent a promising next-generation modality for ocular therapeutics, enabling innovative strategies beyond conventional antibody formats.}, }
@article {pmid42278869, year = {2026}, author = {Ipek, SC and Durmaz Engin, C and Karatas, E and Yildirim, C and Grzybowski, A}, title = {Functional and Structural Outcomes of Photobiomodulation Therapy in Dry Age-Related Macular Degeneration: A Single-Center Experience.}, journal = {Journal of clinical medicine}, volume = {15}, number = {11}, pages = {}, doi = {10.3390/jcm15114007}, pmid = {42278869}, issn = {2077-0383}, abstract = {Purpose: To evaluate the anatomical and functional efficacy of photobiomodulation (PBM) therapy in patients with dry age-related macular degeneration (AMD) and to investigate structural predictors of visual response. Methods: This retrospective study included 47 eyes of 30 patients with dry AMD treated with PBM. Best-corrected visual acuity (BCVA) was recorded as Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, and visual change (ΔBCVA) was calculated. Spectral-domain optical coherence tomography parameters-central retinal thickness (CRT), central macular volume (ETDRS 9-subfield central zone), and photoreceptor layer integrity (external limiting membrane [ELM], ellipsoid zone [EZ], and interdigitation zone [IZ])-were assessed pre- and post-treatment. Age-Related Eye Disease Study (AREDS) stage was graded per eye. Because both eyes from some patients were included, generalized estimating equation (GEE) models with patient-level clustering were used to account for inter-eye correlation. Effect estimates were reported as unstandardized coefficients with 95% confidence intervals. Results: Visual acuity improved following PBM therapy, with mean ETDRS letter scores increasing from 75.0 ± 14.1 to 78.0 ± 12.1 letters. In the GEE model accounting for patient-level clustering, the estimated mean gain was 2.97 ETDRS letters (95% CI: 1.15 to 4.79; p = 0.001). Mean CRT showed no significant change following PBM therapy (210.32 ± 48.61 µm vs. 211.23 ± 50.27 µm; GEE estimate: +0.91 µm; 95% CI: -5.52 to 7.35; p = 0.780). Central macular volume likewise remained stable (0.1913 ± 0.030 vs. 0.1919 ± 0.033 mm[3]; GEE estimate: +0.0006 mm[3]; 95% CI: -0.0054 to 0.0067; p = 0.836). Photoreceptor layer integrity demonstrated limited structural change, with no significant time effect for EZ or IZ integrity in binary GEE models and no observed pre-post change in ELM integrity. In multivariable GEE analysis, baseline BCVA (p < 0.001), ELM integrity (p < 0.001) and central macular volume (p = 0.041) were associated with change in ETDRS letter score, whereas AREDS category, EZ integrity, and IZ integrity were not. Conclusions: PBM therapy demonstrated limited short-term anatomical change but variable functional outcomes in dry AMD. Baseline BCVA emerged as the primary determinant of visual response, suggesting that treatment benefit may be influenced predominantly by pre-treatment functional reserve.}, }
@article {pmid42278913, year = {2026}, author = {Tseng, CH and Lin, MY and Chiou, DI and Hsu, CH and Wu, CM}, title = {Preliminary Observations of Bilateral Neovascular Age-Related Macular Degeneration Progression: A Real-World Retrospective Case Series.}, journal = {Journal of clinical medicine}, volume = {15}, number = {11}, pages = {}, doi = {10.3390/jcm15114051}, pmid = {42278913}, issn = {2077-0383}, abstract = {Background: This study investigated the clinical timeline, patient monitoring behaviors, and cumulative bilateral treatment burden in patients with bilateral neovascular age-related macular degeneration. Methods: We retrospectively analyzed follow-up patterns and treatment intensity from first-eye (FE) diagnosis to second-eye (SE) conversion. Results: SE conversion occurred within a mean of 2.0 years in the FE-active group (62.5%) while the FE remained exudative, contrasting with 6.2 years in the FE-inactive group (37.5%). Upon SE conversion, the total annual intravitreal injection burden escalated 3.4-fold (p = 0.002). Notably, the FE-inactive group exhibited numerically lower annual outpatient visit counts (4.40 ± 2.71 vs. 10.29 ± 5.02; p = 0.116), which potentially widened the monitoring window. Additionally, baseline SE retinal pigment epithelium (RPE) abnormalities independently predicted progression (aOR: 19.04; p = 0.032). Conclusions: While previous literature focuses on individual eyes, our findings highlight a vigilance gap in SE detection based on FE status. Clinicians must maintain proactive surveillance for patients with baseline SE RPE abnormalities, particularly when FE stability or next-generation long-acting therapies extend clinic intervals. Due to the limited sample size, these preliminary findings warrant validation in larger prospective cohorts.}, }
@article {pmid42279565, year = {2026}, author = {Sobahi, N and Özçelik, STA and Atila, O and Sengur, A and Akpınar, MH}, title = {Query-Driven Retinal Layer Segmentation in OCT Using Cross-Attentive Feature Learning.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {11}, pages = {}, doi = {10.3390/diagnostics16111697}, pmid = {42279565}, issn = {2075-4418}, support = {TEKF.24.47//F&#x131;rat University/ ; }, abstract = {Background/Objectives: Retinal layer segmentation in optical coherence tomography (OCT) is essential for the diagnosis and monitoring of retinal diseases such as age-related macular degeneration (AMD) and diabetic macular edema (DME). Although deep learning methods have achieved strong performance, most rely on dense pixel-wise predictions and often struggle to preserve anatomical consistency, particularly in regions with low contrast or structural deformation. This study aims to address these limitations by introducing a query-based segmentation framework that explicitly models retinal layer structure. Methods: In this paper, we propose the RetiQueryNet architecture that employs encoding of retinal layers in the form of query embeddings with the use of cross attention to interact with pixel level features encoded by a transformer based encoder. The architecture integrates multi-scale features through a compact query-driven decoder with modest additional computational overhead. Normalization and resizing of OCT images preceded their usage as inputs, while the layer labels were converted to multi-class segmentation maps. In the training process, we used loss function with combination of cross entropy loss and Dice loss. Our model performance was compared with multiple state-of-the-art models such as U-Net, DeepLabV3, FPN, MANet and SegFormer, while performance metrics were Dice, IoU and mean surface distance (MSD). Results: RetiQueryNet was able to attain a mean Dice score of 0.934 ± 0.0046 and outperformed all baseline models on the main performance measures. Improvements were particularly evident in challenging retinal layers such as IBRPE and OBRPE, where boundary ambiguity is high. It should be noted that RetiQueryNet had a relatively lower MSD value, meaning that the predicted boundaries were more accurate. Furthermore, visual observations suggest that the approach generated smooth and coherent segmentations. Conclusions: The findings demonstrate that query-based modeling offers a viable approach to pixel-wise segmentation. In particular, by making use of structural priors in the form of learnable queries, RetiQueryNet improves not only segmentation accuracy but also anatomical consistency. Query-based modeling appears to be an exciting area for retinal image segmentation that could potentially be applied to other applications in medical image segmentation.}, }
@article {pmid42281177, year = {2026}, author = {Nguyen, A and Zhu, AY and Khouri, AS}, title = {Geroprotective Agents, Including Glucagon-Like Peptide-1 Receptor Agonists, for Ocular Health.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {}, number = {}, pages = {10807683261456222}, doi = {10.1177/10807683261456222}, pmid = {42281177}, issn = {1557-7732}, abstract = {Aging has long been implicated in the onset and progression of major retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Glaucoma is likewise increasingly recognized as an age-related disorder. Across these conditions, converging patterns of neurodegeneration and microvascular injury contribute to age-associated ocular decline. Structural and neuronal degeneration of the retina, including loss of retinal ganglion cell axons, along with impaired microvascular circulation and chronic inflammation, contribute to the pathogenesis of glaucoma, AMD, DR, and RVO. Geroprotectors, a class of longevity-promoting pharmacologic agents investigated for systemic benefits in cardiovascular and neurological aging, have therefore drawn growing ophthalmic interest for their potential relevance to ocular health and the management of age-associated eye diseases. These agents are now frequently encountered as concomitant medications in ophthalmic practice, yet their ocular effects remain incompletely characterized, variably reported, and in some cases controversial. Glucagon-like peptide-1 (GLP-1) receptor agonists, widely used for glycemic control and increasingly for weight management, have been associated with reduced risk of age-related glaucoma but also with unconfirmed reports of severe nonarteritic anterior ischemic optic neuropathy. Similar uncertainties surround other geroprotective, metabolic, and weight-modifying therapies, creating challenges for clinicians attempting to incorporate evolving pharmacologic evidence without compromising patient safety. This review synthesizes reported therapeutic and adverse ocular outcomes across geroprotective agents to support clinical awareness, identify knowledge gaps, and guide future investigation. The agents reviewed include GLP-1 receptor agonists, metformin, sodium-glucose cotransporter-2 inhibitors, statins, cannabinoids, calcium channel blockers, spermidine, taurine, nicotinamide adenine dinucleotide precursors, rapamycin, and mifepristone.}, }
@article {pmid42282075, year = {2026}, author = {Gong, X and Roccati, E and Shang, X}, title = {Editorial: Nutrition in neurodegeneration: bridging diet, brain, and eye health.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1869273}, pmid = {42282075}, issn = {2296-861X}, }
@article {pmid42283535, year = {2026}, author = {Johnson, BA and Soni, AK and Murlidaran, S and Beyeler, M and Eckstein, MP}, title = {Distinct roles of central and peripheral vision in rapid scene understanding.}, journal = {Journal of vision}, volume = {26}, number = {6}, pages = {6}, doi = {10.1167/jov.26.6.6}, pmid = {42283535}, issn = {1534-7362}, abstract = {Central and peripheral vision loss, caused by conditions such as age-related macular degeneration and retinitis pigmentosa, disrupt visual processing in distinct ways, yet their impact on real-world scene perception remains poorly understood. Here, we used a real-time, gaze-contingent simulation to examine how central vision loss and peripheral vision loss alter eye movements and scene understanding. Sighted participants (n = 32, five males) viewed 120 real-world scenes (50% social interaction, 50% neutral) under one- or three-saccade constraints and described each scene; description quality was quantified via semantic similarity to ground-truth responses. Peripheral vision loss observers produced significantly less informative descriptions than both central vision loss and control participants, particularly for social interaction scenes, suggesting that peripheral vision is critical for rapid extraction of scene semantics. In contrast, central vision loss primarily disrupted oculomotor behavior, including increased saccade amplitudes, delayed saccade initiation, and reduced intersubject fixation consistency. Description quality was not predicted by fixation similarity to controls but by fixations to labeled humans and critical objects, underscoring the role of semantically informative sampling for real-world scenes that include people. These results reveal a dissociation between perceptual and oculomotor consequences of vision loss and highlight the importance of peripheral input for real-world scene understanding.}, }
@article {pmid42262543, year = {2026}, author = {Kataoka, K and Watanabe, Y and Kumagai, M and Ko, R and Yamamoto, A and Okada, AA}, title = {Sub-retinal pigment epithelium features as predictors for limited interval extension of faricimab in treatment-naïve neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42262543}, issn = {1435-702X}, abstract = {PURPOSE: To explore subtypes of macular neovascularization (MNV) and anatomical features predictive for limited interval extension of faricimab injections in treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective study evaluated 82 eyes of 78 patients initiating treatment with faricimab using a treat-and-extend regimen. Age and best-corrected visual acuity (BCVA) were extracted from medical records. Optical coherence tomography parameters including central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximum pigment epithelial detachment (PED) height were measured.<br><br>RESULTS: At one year, 63 eyes (76.8%) continued faricimab treatment, while 19 eyes (23.2%) discontinued due to inability to maintain&#x2009;&#x2265;&#x2009;8-week intervals. Discontinued eyes exhibited significantly greater baseline maximum PED height (P&#x2009;=&#x2009;0.012). Eyes achieving intervals&#x2009;&#x2265;&#x2009;12 weeks (extended group, n&#x2009;=&#x2009;40) were compared with those not achieving this criterion (non-extended group, n&#x2009;=&#x2009;42). Post hoc residual analysis revealed that type 1 MNV without polypoidal lesions was significantly overrepresented in the non-extended group (P&#x2009;=&#x2009;0.033). Multivariable logistic regression analysis confirmed that greater baseline maximum PED height was the only independent predictor of limited interval extension (odds ratio, 0.965 per 10-&#xb5;m increase; 95% confidence interval, 0.935-0.995; P&#x2009;=&#x2009;0.021). Other baseline factors, including age, BCVA, CRT, and SFCT, showed no significant association.<br><br>CONCLUSION: Sub-RPE features at baseline, specifically type 1 MNV without polypoidal lesions and greater PED height, are significant predictors of limited treatment interval extension in treatment-na&#xef;ve nAMD eyes receiving faricimab. Recognizing these features prior to treatment initiation may guide clinical decision-making regarding injection frequency.}, }
@article {pmid42263559, year = {2026}, author = {Waescher, F and Spitzenberg, C and Pauly, D and Baeumner, AJ}, title = {Advances in analytical methods for regulatory complement proteins in research and clinical applications.}, journal = {Talanta}, volume = {310}, number = {}, pages = {130079}, doi = {10.1016/j.talanta.2026.130079}, pmid = {42263559}, issn = {1873-3573}, abstract = {The canonical complement system and its dysregulation are increasingly realized to be associated with pathologies like age-related macular degeneration, atypical hemolytic uremic syndrome, or dense deposit disease. Resulting drug development, clinical studies, and expanding fundamental research into the complement system and its regulatory proteins all require appropriate analytical methods with which the function of the complement system can be quantified. In clinical settings, two types of routine diagnostics are mostly used. Functional assays such as the hemolytic CH50 and AH50 tests are based on erythrocytes and typically monitor complete activation pathways. Assays that quantify certain complement proteins and activation products are typically based on turbidimetry, nephelometry, and ELISAs. However, there is the need and demand for more specific examination to also identify variants with defective functions that show no deviation from normal concentrations. New diagnostic test developments are therefore moving towards faster, simpler, and more standardized tests for application in both clinical laboratories and high-throughput facilities, with the ultimate goal of precision and personalized medicine. In recent years, significant progress has been made, particularly in functional assays for fluid-phase and in flow cytometry for membrane-bound regulatory complement proteins. Functional ELISAs and liposome assays may soon replace traditional hemolytic assays, while genetic analysis has yielded important new insights into complement-related diseases; overall, there is a strong trend toward multiplexing. This review discusses current advances in analytical methods of regulatory complement proteins, covering commercial assays from industry and newly developed assay strategies from research, and assesses their impact on the field.}, }
@article {pmid42266371, year = {2026}, author = {Wu, J and Luo, L and Huang, Y and Li, J and Li, X}, title = {Salvianolic acid a attenuates sodium iodate-induced ferroptosis in age-related macular degeneration models via the SLC7A11/GPX4 axis.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1803187}, pmid = {42266371}, issn = {1663-9812}, abstract = {INTRODUCTION: Oxidative stress-mediated retinal pigment epithelial (RPE) cell injury is a key pathological feature of age-related macular degeneration (AMD). Ferroptosis-an iron-dependent form of regulated cell death driven by lipid peroxidation-has been increasingly identified as a critical executor of RPE degeneration and a key pathogenic mechanism in AMD. This study aimed to investigate the mechanism by which Salvianolic acid A (SalA) alleviates ferroptosis in RPE cells under sodium iodate (NaIO3)-induced damage.<br><br>METHODS: Using in vitro (ARPE-19 cells) and in vivo (mice) NaIO3-induced injury models. We assessed cell viability, ferroptosis markers (iron, lipid peroxidation, glutathione), mitochondrial ultrastructure, and key protein expression via biochemical assays, flow cytometry, transmission electron microscopy, and Western blotting.<br><br>RESULTS: SalA pretreatment effectively mitigated NaIO3-induced ferroptosis, reducing lipid peroxidation, iron overload, and mitochondrial damage. Mechanistically, SalA upregulated the key ferroptosis regulators SLC7A11 and GPX4. Critically, this protection was significantly attenuated by the SLC7A11 inhibitor erastin, confirming the essential role of this axis. In mice, SalA attenuated NaIO3-induced retinal structural damage and enhanced SLC7A11/GPX4 expression in retina tissues.<br><br>CONCLUSION: This study identifies SalA as a potent inhibitor of ferroptosis in RPE cells, primarily through activation of the SLC7A11/GPX4 axis. These findings suggest that SalA may hold therapeutic potential for AMD and provide a preliminary pharmacological basis for further exploration in retinal degenerative diseases.}, }
@article {pmid42266935, year = {2026}, author = {Vasilev, R and Savchenko, A and Blinov, P and Svetina, T and Kudin, S and Romanenko, N and Sarana, Y and Khizhnyak, G and Demchinsky, A and Shcheglova, T}, title = {Artificial intelligence framework for multi-pathology risk assessment from retinal fundus images: deep learning approach to 15-disease screening.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1778404}, pmid = {42266935}, issn = {2296-858X}, abstract = {BACKGROUND: Automated disease screening systems face challenges when applied to multi-class medical image analysis, particularly under severe class imbalance inherent in clinical datasets. Retinal fundus imaging enables non-invasive screening for multiple ocular and systemic diseases simultaneously, yet current automated systems typically assess risk for only a single pathology or a limited disease range. We developed a comprehensive AI framework for simultaneous risk stratification of 15 distinct pathological conditions from retinal fundus images and report its preliminary evaluation in a real-world clinical setting.<br><br>METHODS: Our system combines fundus images from publicly available sources and proprietary clinical archives, addressing the significant class imbalance challenge inherent in rare condition risk assessment. We employed a hybrid deep learning architecture (CAFormer B36) with focal loss and targeted oversampling to ensure robust performance across common and rare conditions. The framework identifies retinal biomarkers associated with both primary ocular diseases (diabetic retinopathy, glaucoma, macular degeneration, cataracts, retinitis pigmentosa) and systemic conditions with retinal manifestations (hypertensive retinopathy, atherosclerotic changes, autoimmune manifestations). Dataset splitting was performed at the image level; all internal metrics should therefore be interpreted as exploratory upper-bound estimates pending patient-level replication.<br><br>RESULTS: On the internal image-level test set, the system achieved ROC AUC of 0.9524-0.9971 across all 15 pathological classes, with F1 scores of 0.8968-0.9649. Notably, rare conditions with fewer than 100 training examples demonstrated robust risk stratification performance. In an exploratory single-site evaluation on 68 real-world cases, overall accuracy was 64.7% (95% CI: 52.9-76.5%). Due to the very limited number of sight-threatening cases in this small cohort (glaucoma n = 2, diabetic retinopathy n = 4), sensitivity estimates for these categories carry extremely wide confidence intervals and cannot be considered statistically reliable. These findings underscore the need for larger, prospective, multicenter studies.<br><br>CONCLUSIONS: This pilot proof-of-concept demonstrates the feasibility of multi-pathology risk stratification under severe class imbalance using a hybrid deep learning architecture. Internal image-level metrics show strong discriminative capability, while the preliminary single-site evaluation (n = 68, 64.7% accuracy) reveals the challenges of real-world translation and the substantial gap that remains before clinical deployment. This work provides a methodological foundation for future prospectively validated screening systems.}, }
@article {pmid42268761, year = {2026}, author = {Zhang, D and Lu, C and Chen, T and Zheng, J and Li, Y and Tan, T and Yi, Q and Li, Z and Zhang, J}, title = {Multimodal Distillation and Fusion for Enhanced Age-Related Macular Degeneration Classification.}, journal = {IEEE journal of biomedical and health informatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/JBHI.2026.3701961}, pmid = {42268761}, issn = {2168-2208}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment and blindness in the elderly, making accurate diagnosis and fine-grained sub type classification essential for clinical decision-making. However, existing methods often fail to fully leverage complementary information from multiple imaging modalities due to complex lesion characteristics and heterogeneous data distributions. To address these challenges, we pro pose a novel Multimodality Distillation and Fusion Network (ModiF) for robust AMD classification. First, modality specific feature extractors are designed to capture hierarchical semantic representations from different imaging modalities such as OCT, OCTA, and CFP. To further enhance feature discriminability, an auxiliary cross-modal soft supervision strategy is introduced during training, in which modality-specific predictions are adaptively voted and used as soft targets for knowledge distillation. Building on these modality-specific features, a principal-modality guided distillation mechanism is designed to facilitate effective cross-modality knowledge transfer while preserving critical diagnostic information. Furthermore, a confidence aware fusion module is introduced to adaptively balance the contributions of different modalities by dynamically adjusting fusion weights based on the entropy of modality specific predictions. Experimental validations on one internal dataset (OCT and OCTA) and two public datasets (CFP andOCT)demonstrate that ModiF consistently outperforms existing state-of-the-art methods across different settings, highlighting its effectiveness and generalization capability in AMD classification.}, }
@article {pmid42269152, year = {2026}, author = {Liang, L and She, K and Ren, C and Li, R and Liao, M and Tao, Z and Liu, F and Su, J and Hu, M and Yang, Y and Wang, X and Zhang, CL and Bao, L and Chen, Q and Zhang, K and Wei, Y and Yang, Y and Lu, F}, title = {Subretinal Gene Therapy for X-Linked Retinoschisis.}, journal = {The New England journal of medicine}, volume = {394}, number = {22}, pages = {2223-2234}, doi = {10.1056/NEJMoa2515953}, pmid = {42269152}, issn = {1533-4406}, support = {82201210//National Natural Science Foundation of China/ ; 82201212//National Natural Science Foundation of China/ ; 82222030//National Natural Science Foundation of China/ ; W2431057//National Natural Science Foundation of China/ ; 2023YFC3403300//National Key Research and Development Program of China/ ; 2024YFC3406704//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: X-linked retinoschisis is a recessive disease characterized by progressive macular degeneration and vision loss due to pathogenic variation in RS1.<br><br>METHODS: We administered a single subretinal injection of an AAV8 vector containing human RS1 complementary DNA (scAAV8-hRS1) into one eye of patients 5 to 18 years of age who had X-linked retinoschisis. The primary end point was safety during the 52-week period after injection. Secondary end points included the change from baseline to week 52 in the best corrected visual acuity (BCVA), retinal structure (assessed with swept-source optical coherence tomography; SS-OCT), the function of photoreceptor and bipolar cells (assessed with full-field electroretinography), and macular sensitivity to light (assessed with microperimetry).<br><br>RESULTS: A total of 12 patients were enrolled. The dose-escalation phase included two cohorts of 3 patients each who received scAAV8-hRS1 at a dose of 7.5&#xd7;10[10] or 1&#xd7;10[11] vector genomes. In the dose-expansion phase, 3 additional patients were enrolled in each cohort. Overall, 56 adverse events were reported during the 52 weeks after surgery. No patient was reported to have an adverse event of grade 3 or higher or ocular inflammation. A macular hole in the treated eye was observed at week 1 in 1 patient. The mean increase at week 52 in the BCVA was 10.8 letters among the treated eyes and 2.4 letters among the untreated eyes. SS-OCT imaging showed closure of the macular schisis cavity by week 13 in the treated eye in all 12 patients. The mean change at week 52 in central retinal thickness was -437.7 &#x3bc;m among the treated eyes and -17.2 &#x3bc;m among the untreated eyes; the outer retinal layers in the treated eyes of 9 patients were continuous at week 52. No clinically meaningful changes in the function of photoreceptor and bipolar cells or macular retinal sensitivity were observed in the treated eyes.<br><br>CONCLUSIONS: In this study of subretinal gene therapy with scAAV8-hRS1 in 12 patients with X-linked retinoschisis, there were no reports of adverse events of grade 3 or higher or ocular inflammation. Further clinical testing of scAAV8-hRS1 is warranted. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, ChiCTR2300076682.).}, }
@article {pmid42270292, year = {2026}, author = {Duan, N and Zhao, X and Wu, Z and Yuan, D and Peng, S and Cui, K and Yu, Z and Yang, W and Wei, W and Chi, W and Zhang, G}, title = {Exploring the capabilities of three artificial intelligence chatbots in diagnosis and decision-making of age-related macular degeneration.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328860}, pmid = {42270292}, issn = {1468-2079}, abstract = {BACKGROUND: Compare the performance of three artificial intelligence (AI) chatbots, including ChatGPT o4-mini, Gemini 2.5 flash and DeepSeek-R1, in diagnosis, treatment suggestion and visual prognosis of age-related macular degeneration (AMD).<br><br>METHODS: A retrospective study was conducted on 54 participants with AMD from Shenzhen Eye Hospital and Huizhou Third People's Hospital (from January 2024 to June 2025). Each participant was analysed by three AI chatbots and an ophthalmology resident using standardised prompts. The main outcome measures included diagnosis agreement, treatment suggestion and visual prognosis. Global Quality Score (GQS, 1-5) was assessed to evaluate response quality. Statistical analysis was conducted using R (version 4.4.1), with significance set at p<0.05.<br><br>RESULTS: Diagnosis agreement was 96.3% for ChatGPT o4-mini, 94.4% for Gemini 2.5 flash, 90.7% for DeepSeek-R1 and resident (all p>0.05). Treatment suggestion agreement was 90.7% for Gemini 2.5 flash, 88.9% for ChatGPT o4-mini, DeepSeek-R1 and resident (all p>0.05). Visual prognosis agreement was 66.7% for ChatGPT o4-mini, 48.1% for Gemini 2.5 flash, 40.7% for DeepSeek-R1 and 37.0% for resident. ChatGPT o4-mini significantly outperformed DeepSeek-R1 (p=0.011) and the resident (p=0.006). GQS ratings favoured ChatGPT o4-mini, significantly higher than Gemini 2.5 flash and DeepSeek-R1, but comparable to the resident (all p>0.05).<br><br>CONCLUSIONS: Three AI chatbots showed strong capabilities in neovascular AMD diagnosis and treatment suggestions, with ChatGPT o4-mini superior in visual prognosis prediction. However, real-world clinical settings require large-scale studies, and integrative use of multiple large language models may improve robustness and clinical reliability.}, }
@article {pmid42270914, year = {2026}, author = {Abbasgholizadeh, R and Quarta, A and Alhelaly, M and Soylu, C and Habibi, A and Rattu, R and Au, A and Corradetti, G and Chung, YC and Chujo, S and Huang, J and Ip, MS and Sadda, SR}, title = {Factors impacting the assessment of geographic atrophy on ultra‑widefield fundus autofluorescence imaging.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42270914}, issn = {1435-702X}, abstract = {PURPOSE: To determine how often geographic atrophy (GA) lesions cannot be reliably delineated on ultrawidefield (UWF) green-light fundus autofluorescence (GAF) and to identify factors associated with poor lesion demarcation.<br><br>METHODS: Retrospective cross-sectional study. 88 patients (138 eyes) with GA due to non-exudative age-related macular degeneration (AMD). Consecutive retina clinic subjects with GA secondary to AMD and UWF-GAF, UWF pseudocolor, and OCT imaging at the same visit were included in this study. Eyes with AMD due to other causes, evidence of exudative AMD, or images with overall poor quality were excluded. Two independent masked graders classified the UWF-GAF images as gradable (clearly delineated GA borders amenable to measurement) or ungradable (indistinct borders), and discrepancies were adjudicated by the senior investigator. Choroidal thickness (CT) was measured on central horizontal B-scan at the foveal center and at points 1.5&#xa0;mm nasal and temporal to the center.<br><br>MAIN OUTCOME MEASURES: Frequency of ungradable UWF-GAF images and choroidal thickness measurements at the foveal, nasal, and temporal locations.<br><br>RESULTS: UWF-GAF images were deemed ungradable for GA size in 7/138 eyes (5.1%; 95% CI, 2.5-10.1). Inter-reader agreement for gradability was excellent (&#x3ba;&#x2009;=&#x2009;0.867; p&#x2009;<&#x2009;0.001). Ungradable eyes demonstrated a markedly thinner choroid at all measurement locations including the foveal center (74.71&#x2009;&#xb1;&#x2009;37.04&#xa0;&#x3bc;m vs. 177.41&#x2009;&#xb1;&#x2009;91.16&#xa0;&#x3bc;m; p&#x2009;=&#x2009;0.0002), nasal (58.14&#x2009;&#xb1;&#x2009;14.73&#xa0;&#x3bc;m vs. 132.70&#x2009;&#xb1;&#x2009;88.28&#xa0;&#x3bc;m ; p&#x2009;=&#x2009;0.0013), and temporal (85.29&#x2009;&#xb1;&#x2009;34.54&#xa0;&#x3bc;m vs. 177.40&#x2009;&#xb1;&#x2009;87.07&#xa0;&#x3bc;m; p&#x2009;=&#x2009;0.018) points.<br><br>CONCLUSION: In retina practices that routinely obtain Optos UWF-GAF imaging, approximately 5% of GA lesions may not be measurable on UWF GAF imaging, with a very thin choroid being a common feature among such cases. Green fluorescence from the unmasked sclera is the likely explanation for this phenomenon, though such GA lesions lend themselves to reliable quantification using the companion UWF pseudocolor image. These findings have implications for the monitoring of GA lesions in clinical practice in the era of GA therapeutics.}, }
@article {pmid42271146, year = {2026}, author = {Sacconi, R and Menna, M and Beretta, F and Polito, MS and Capuano, V and Costanzo, E and Marra, S and Parravano, M and Souied, E and Bandello, F and Querques, G}, title = {OCT predictors discerning progression to neovascular vs atrophic age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42271146}, issn = {1476-5454}, abstract = {PURPOSE: To characterise structural optical coherence tomography (OCT) biomarkers at intermediate age-related macular degeneration(iAMD) stage able to differentiate the progression to neovascular AMD(nAMD) or to geographic atrophy (GA) in a high-risk iAMD population showing conversion at 1-year follow-up.<br><br>METHODS: multicentre, retrospective, longitudinal study including patients with iAMD at baseline who developed late AMD (nAMD or GA) during the 1-year follow-up. Patients were enroled in three retinal referral institutions: (1) San Raffaele University, Milan, Italy; (2) IRCCS Bietti Foundation, Rome, Italy; (3) University of Paris Est, Creteil, France. Logistic regression model (LRM) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between nAMD and GA conversion.<br><br>RESULTS: We included 154 eyes (154 patients, mean age 80&#x2009;&#xb1;&#x2009;7 years old) with iAMD at the baseline. Eighty-eight eyes(57%) progressed to nAMD, whereas 66 eyes(43%) progressed to GA. Eyes that progressed to nAMD were characterised by a higher double-layer sign(DLS) prevalence (p&#x2009;<&#x2009;0.001), whereas eyes that progressed to GA were characterised by greater height and diameter of the greatest drusen (p&#x2009;<&#x2009;0.001 and p&#x2009;=&#x2009;0.001, respectively), higher presence of HRF(p&#x2009;=&#x2009;0.008), and iRORA(p&#x2009;<&#x2009;0.001). LRM confirmed that DLS is a significant risk factor for nAMD conversion (OR:3.626, p&#x2009;=&#x2009;0.037), whereas height of greatest drusen (OR:0.983, p&#x2009;=&#x2009;0.003), presence of HRF (OR:0.147, p&#x2009;=&#x2009;0.009), and presence of iRORA (OR:0.052, p&#x2009;<&#x2009;0.001) were more associated with GA conversion.<br><br>CONCLUSIONS: Structural OCT biomarkers at the iAMD stage could help clinicians to distinguish between patients who will develop nAMD in comparison to GA. Our findings can contribute to the better management of patients with iAMD.}, }
@article {pmid42271167, year = {2026}, author = {Sleath, B and Zhang, AY and Carpenter, DM and Adjei, A and Annis, I and Garcia, N and Olson, D and Dobbin, K}, title = {Neovascular age-related macular degeneration patient questions for their eye care providers and preferences for education.}, journal = {Optometry and vision science : official publication of the American Academy of Optometry}, volume = {103}, number = {6}, pages = {e70070}, doi = {10.1002/ovs2.70070}, pmid = {42271167}, issn = {1538-9235}, abstract = {PURPOSE: The purpose of this study was to examine: (a) the types of questions that neovascular age-related macular degeneration patients had for their ophthalmologists, and (b) whether the patients thought that a pre-visit neovascular age-related macular degeneration question prompt list and video would be a useful intervention to improve health care provider-patient communication.<br><br>METHODS: Adult neovascular age-related macular degeneration patients attending visits for treatment injections were recruited at two ophthalmology practices and interviewed. They were shown a list of questions and asked to check the ones they had for their eye care provider. They were also asked whether a pre-visit question prompt list and video would be useful to improve provider-patient communication.<br><br>RESULTS: Fifty neovascular age-related macular degeneration patients participated. Patients had a mean of 11.2 questions (standard deviation&#xa0;=&#xa0;7.4; range 0-26) for their eye care providers. The most frequently checked questions included "How likely is it that I am going to go blind?" (70%), "What causes macular degeneration?" (64%), "What can I do to prevent vision loss?" (64%), and "What happens if I miss an injection visit?" (56%). Ninety-eight percent of patients felt completing a question prompt list to use during a visit would be helpful and 96% thought having patients watch a video before completing the question prompt list was a good idea.<br><br>CONCLUSIONS: Neovascular macular degeneration patients have many questions for their eye care providers. Innovative ways to address patient questions should be tested and developed.}, }
@article {pmid42271544, year = {2026}, author = {Adamo, GG and Cartabellotta, A and Talli, PM and Giannaccare, G and Vivarelli, C and Pellegrini, M and Parmeggiani, F and Mura, M}, title = {Combined macular buckle and intraoperative OCT-guided 41-gauge drainage of refractory large bacillary layer detachments in neovascular age-related macular degeneration and diabetic macular edema.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00875-6}, pmid = {42271544}, issn = {2056-9920}, abstract = {BACKGROUND: To describe a novel combined surgical technique for the drainage of large bacillary layer detachment (BLD) in patients with advanced neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) or corticosteroid therapy.<br><br>METHODS: This prospective pilot case series evaluated three eyes of three patients (two nAMD, one DME) with large BLDs runresponsive to intravitreal treatment. The standardized procedure consisted of ab-externo macular buckle placement followed by 23-gauge pars plana vitrectomy (PPV). Intraoperative OCT (iOCT) guided subretinal fluid drainage using a 41-gauge cannula. Primary outcomes were anatomical BLD resolution and changes in best-corrected visual acuity (BCVA) at six-month.<br><br>RESULTS: Immediate and complete anatomical resolution was achieved in all eyes. BCVA modestly improved from 20/400, 20/400, and 20/800 at baseline to 20/200, 20/200 and 20/400 Snellen at six-month follow-up. No intra- or postoperative complications occurred, and no additional anti-VEGF injections were required during follow-up.<br><br>CONCLUSIONS: Combined intraoperative OCT-guided subretinal drainage with macular buckling achieved immediate anatomical resolution of large, chronic bacillary layer detachments refractory to medical therapy. Functional recovery was limited, likely reflecting irreversible outer retinal and retinal pigment epithelium damage in advanced disease. This approach may represent a salvage option in carefully selected cases of refractory exudative macular disease. Further studies with larger cohorts and longer follow-up are required to define its long-term efficacy, optimal timing, and clinical role.}, }
@article {pmid42272620, year = {2026}, author = {Qi, Y and Cheng, A and Xu, J and Zhang, C and Li, S}, title = {Real-World Outcomes of Aflibercept 2 mg Using a Treat-and-Extend Protocol for Neovascular Age-Related Macular Degeneration: A 24-Month Retrospective Study in a Chinese Population.}, journal = {Drug design, development and therapy}, volume = {20}, number = {}, pages = {601668}, pmid = {42272620}, issn = {1177-8881}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; China ; Dose-Response Relationship, Drug ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; Visual Acuity/drug effects ; East Asian People ; }, abstract = {PURPOSE: To evaluate the long-term efficacy of aflibercept using a treat-and-extend (T&amp;E) protocol in Chinese patients with neovascular age-related macular degeneration (nAMD) and to explore baseline imaging predictors of treatment response.<br><br>METHODS: This retrospective, real-world study included patients with treatment-na&#xef;ve nAMD who received intravitreal aflibercept (2.0 mg) under a T&amp;E regimen for 24 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and OCT-derived structural features were assessed. Patients were stratified into effective and non-effective groups based on visual outcomes at 24 months.<br><br>RESULTS: A total of 37 eyes were included. Compared with baseline (0.71&#xb1;0.48 logMAR), BCVA improved significantly at 3 months (0.58&#xb1;0.50, p=0.029), 6 months (0.51&#xb1;0.32, p<0.01), and remained improved at 24 months (0.57&#xb1;0.44, p=0.002). Mean &#x394;BCVA at 24 months was -0.15&#xb1;0.27 logMAR. CMT decreased from 409.89&#xb1;219.24&#xa0;&#x3bc;m at baseline to 277.43&#xb1;113.92&#xa0;&#x3bc;m at 3 months (p<0.001), with sustained reductions throughout follow-up (&#x394;CMT -145.71&#xb1;239.50&#xa0;&#x3bc;m at 24 months). Subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment height (PEDH), resolved significantly during follow-up (all p &#x2264; 0.05), whereas hyperreflective dots (HRD), subretinal hyperreflective exudation (SHE), fibrosis, and macular atrophy (MA) tended to increase progressively. In subgroup analysis, the effective group showed higher baseline CMT (473 vs 293&#xa0;&#x3bc;m, p=0.015), more frequent SRF (70.8% vs 30.8%, p=0.019), and more HRD (79.2% vs 46.2%, p=0.041). Multivariate logistic regression confirmed higher baseline CMT (OR=1.01, p=0.030) and SRF presence (OR=5.40, p=0.028) as independent predictors of visual response.<br><br>CONCLUSION: Intravitreal aflibercept administered under a T&amp;E regimen provides sustained visual and anatomical benefits in Chinese patients with nAMD. Baseline OCT features, particularly CMT and SRF, are valuable predictors of treatment efficacy, supporting their role in individualized therapeutic decision-making.}, }
@article {pmid42274721, year = {2026}, author = {Romano, F and Overbey, K and Durocher-Jean, A and Rojewski, A and St-Hilaire, F and Ding, X and Vingopoulos, F and Stettler, I and Arbour, JD and Rhéaume, MA and Nissan, R and Sorya, P and Santucci, L and Campbell, S and Chevrefils, C and Husain, D and Vavvas, D and Miller, JW and Sylvestre, JP and Miller, JB}, title = {Assessment of Geographic Atrophy Using a Novel Hyperspectral Gradient Imaging Approach.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {6}, pages = {393-399}, doi = {10.3928/23258160-20260323-01}, pmid = {42274721}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: This study describes a novel hyperspectral imaging (HSI) approach for visualizing and measuring geographic atrophy (GA) lesions in age-related macular degeneration.<br><br>PATIENTS AND METHODS: This cross-sectional subanalysis was conducted at Clinique Ophtalmologique 2121 (Montreal, Canada) between November 2022 and August 2023. Participants underwent color fundus photography (CFP), optical coherence tomography (OCT), and HSI using the Optina-4CTM camera. HSI gradient images at 560 nm were generated to visualize melanin depletion within the retinal pigment epithelium.<br><br>RESULTS: Among 152 eyes screened, eight (5.3%) showed GA. All GA lesions identified on OCT appeared as dark areas on HSI, while CFP failed to detect GA in two cases. HSI identified more GA lesions per eye than CFP (P = .001) and yielded larger lesion dimensions compared with OCT (P < .05).<br><br>CONCLUSIONS: HSI at 560 nm provides complementary information for GA visualization and measurement to CFP and OCT, supporting further validation in future studies.}, }
@article {pmid42275976, year = {2026}, author = {Venkataraman, AP and Rosén, R and van der Mooren, M and Alarcón Heredia, A and Romashchenko, D and Cánovas Vidal, C and Lundström, L}, title = {Impact of peripheral optical errors in age-related macular degeneration.}, journal = {Journal of optometry}, volume = {19}, number = {3}, pages = {100618}, doi = {10.1016/j.optom.2026.100618}, pmid = {42275976}, issn = {1989-1342}, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a common ocular condition leading to reduced central visual function and increased dependency on the peripheral field of view for all visual tasks. This study aims to assess the effect of optical errors on peripheral vision in dry form AMD.<br><br>METHODS: High contrast resolution acuity and contrast sensitivity were measured in the 20&#xb0; nasal visual field of fourteen subjects with advanced or early dry AMD. The measurements were performed through an adaptive optics vision simulator to simulate average phakic as well as pseudophakic peripheral optical errors.<br><br>RESULTS: Overall, inducing population average phakic optical errors resulted in better peripheral visual function than average pseudophakic optical errors for all measured subjects, both in high contrast resolution acuity and contrast sensitivity. Specifically, the mean differences between phakic and pseudophakic conditions were 0.16 logMAR in resolution acuity and 0.43 in logarithmic contrast sensitivity. These changes are larger than the results of studies on younger subjects with healthy vision.<br><br>CONCLUSION: The study thereby concludes that reducing peripheral optical errors can improve peripheral vision, although further work is needed to determine how this translates to everyday visual performance. Interestingly, the improvement appears to be larger for AMD patients compared to healthy eyes.}, }
@article {pmid42276413, year = {2026}, author = {Son, S and Kim, Y and Jang, KJ and Kim, DE}, title = {Metformin activates AMPK-TFEB signaling to restore lysosomal and mitochondrial homeostasis and suppress EMT in oxidative stress-injured retinal pigment epithelium.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.05.009}, pmid = {42276413}, issn = {1525-2191}, abstract = {Disruption of lysosomal homeostasis and accumulation of dysfunctional mitochondria contribute to degenerative pathologies including age-related macular degeneration (AMD). Here, we investigated how inhibition of autophagic lysosome reformation (ALR) alters lysosomal dynamics, mitophagy, and downstream stress signaling in retinal pigment epithelial (RPE) cells, and whether these changes are pharmacologically reversible. In ARPE-19 cells, ALR inhibition by nocodazole or siRNA-mediated depletion of kinesin-1 (UKHC) and dynamin-2 (DNM2) induced enlarged lysosomes with reduced degradative capacity, impaired mitophagic turnover, and accumulation of dysfunctional mitochondria. ALR blockade increased reactive oxygen species (ROS) and cytosolic Ca[2+], promoted activation and mitochondrial translocation of protein kinase C (PKC), and triggered phosphorylation of glycogen synthase kinase-3β with subsequent stabilization of SNAIL, consistent with epithelial-to-mesenchymal transition (EMT). Metformin restored lysosomal homeostasis by activating AMPK and enhancing transcription factor EB (TFEB)-dependent lysosome biogenesis, thereby improving autophagic flux, limiting ROS/Ca[2+] accumulation, suppressing PKC activation, and attenuating EMT-associated marker changes. In a sodium iodate-induced oxidative injury model, metformin preserved RPE microtubule architecture and reduced lysosomal and mitochondrial abnormalities. Although these findings rely on a prolonged monolayer culture system and an acute injury model, they support a protective role for AMPK-TFEB-driven lysosome restoration in RPE stress resilience and suggest lysosome-directed repurposing potential for metformin in degenerative retinal disease.}, }
@article {pmid42070633, year = {2026}, author = {Hsu, AY and Kuo, HT and Liu, DY and Hsia, NY and Lai, CT and Chiang, CC and Lin, CJ and Shao, YC and Chen, HS and Wu, BQ and Tseng, H and Hsu, HC and Wang, YH and Bair, H and Tsai, YY and Hsu, MY and Wei, JC}, title = {Nonsteroidal Anti-inflammatory Drug Use and the Risk of Age-Related Macular Degeneration: Insights from a Multicenter Cohort Analysis.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.04.027}, pmid = {42070633}, issn = {1549-4713}, abstract = {PURPOSE: To investigate the effect of nonsteroidal anti-inflammatory drug (NSAID) use and the risk of age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective cohort study using a de-identified multicenter electronic medical records database.<br><br>PARTICIPANTS: This study included patients who received prescriptions for NSAIDs and individuals who did not to assess for the effects of NSAID prescriptions on future AMD risk.<br><br>METHODS: Data from the TriNetX database between January 1, 2015, and December 31, 2024, were used to identify patients who were prescribed NSAIDs with no prior history of AMD. The NSAID patient cohort was propensity score-matched in a 1:1 ratio with a control group of randomly selected patients without a history of NSAID use, based on age, sex, race, and selected comorbidities of interest, including smoking and other common adult comorbidities that potentially could affect future AMD risk.<br><br>MAIN OUTCOME MEASURES: Cumulative incidence and hazard ratio (HR) of AMD.<br><br>RESULTS: Six hundred thirty-four thousand seven hundred ninety-four patients who were prescribed NSAIDs (mean &#xb1; standard deviation age, 59.93 &#xb1; 11.95 years) and 634,794 patients who were not prescribed NSAIDs (mean &#xb1; standard deviation age, 59.68 &#xb1; 12.15 years) were recruited. Among NSAID users, decreased risk of AMD development was seen at 6 months (HR, 0.31; 95% confidence interval [CI], 0.27-0.36), 1 year (HR, 0.36; 95% CI, 0.33-0.39), 3 years (HR, 0.42; 95% CI, 0.40-0.44), and 5 years (HR, 0.48; 95% CI, 0.47-0.50) after the index date compared with nonusers. A protective effect against AMD development was observed (HR, 0.58; 95% CI, 0.56-0.59) among NSAID users compared with nonusers. A protective effect against AMD development was observed among patients who were prescribed aspirin (HR, 0.72; 95% CI, 0.69-0.75) and those prescribed nonselective cyclooxygenase-2 inhibitors (HR, 0.41; 95% CI, 0.36-0.46) compared with their respective nonusers. A decreased risk of AMD was observed for both nonexudative (HR, 0.56; 95% CI, 0.55-0.58) and exudative (HR, 0.62; 95% CI, 0.59-0.65) AMD subtypes after index NSAID prescription compared with nonusers.<br><br>CONCLUSIONS: A protective effect against future AMD development was suggested among patients prescribed NSAIDs compared with nonusers.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42260001, year = {2026}, author = {Zhong, L and Tao, Y and Tao, L}, title = {Arsenic exposure promotes retinal pigment epithelium dysfunction and oxidative stress via NF-κB pathway.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-55608-4}, pmid = {42260001}, issn = {2045-2322}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults and is closely linked to dysfunction of the retinal pigment epithelium (RPE). Arsenic (As), a ubiquitous environmental toxicant present in drinking water and food, has been implicated in multiple chronic diseases. However, its role in AMD remains unclear. This study aimed to investigate the effects of As exposure on AMD-related retinal injury and to elucidate the underlying molecular mechanisms using in vitro and in vivo experimental models. ARPE-19 cells were treated with sodium iodate (NaIO3) to establish an AMD-like injury model and then exposed to 1 µM As to assess cell viability, apoptosis, oxidative stress, mitochondrial dysfunction, autophagy-related changes and epithelial barrier integrity. Evaluation of NF-κB signaling pathway activation using molecular biology techniques. In vivo, a NaIO3-induced mouse model of AMD was established and combined with As exposure at 25 ppm to to validate retinal damage, oxidative stress, mitochondrial impairment, and barrier dysfunction. ShRNA-mediated silencing of NF-κB was further used to confirm pathway involvement. As exposure significantly aggravated NaIO3-induced injury in ARPE-19 cells and mouse retinas. In vitro, As reduced cell viability and enhanced apoptosis, inflammatory responses, reactive oxygen species accumulation, mitochondrial dysfunction, autophagy dysregulation, and epithelial barrier disruption. In vivo, As exacerbated retinal structural damage, increased oxidative stress, impaired mitochondrial function, and further reduced the expression of tight junction proteins in NaIO3-treated mice. Mechanistically, these effects were accompanied by sustained activation of the NF-κB signaling pathway. ShRNA-mediated silencing of NF-κB partially reversed As-induced retinal damage in vivo. Our study found that As exposure exacerbated AMD-like retinal degeneration via NF-κB pathway. These findings identified As as a potentially modifiable environmental risk factor for AMD and suggested that individuals in As-endemic regions may benefit from targeted retinal screening. Moreover, NF-κB pathway targets inhibition emerged as a candidate strategy for mitigating As-exacerbated retinal injury.}, }
@article {pmid42261693, year = {2026}, author = {Lin, H and Hu, Y and Qi, J and Wu, X and Sun, N and Deng, C}, title = {Robust Heterojunction Nanoconstructs Enable Precise Decipherment of Aqueous Humor Metabolic Profiles in Multiple Retinal Diseases.}, journal = {Analytical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.analchem.6c02437}, pmid = {42261693}, issn = {1520-6882}, abstract = {Retinal diseases (RD), which often cause irreversible vision impairment and lack effective treatments, necessitate more attention than common ocular conditions like cataract (CA), and aqueous humor metabolic analysis has proven an invaluable tool for their investigation. In this work, a robust, high-performance heterojunction nanoconstruct (MZ-D) with cost-effectiveness (∼2.7 yuan per gram), streamlined two-step synthesis, high reproducibility, was developed. Combined with high-throughput mass spectrometry and machine learning, aqueous humor metabolic profiles were extracted and analyzed for multiple RD, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). We identified key metabolic features that delivered 92.87% accuracy, 0.9340 AUC, and 92.94% precision for RD recognition against CA, which was used as a control to simulate clinical settings, and 86.59% accuracy, 0.9591 AUC, and 86.59% precision for differentiating AMD, DR, and RVO. Notably, retinaldehyde and 2-hydroxylauroylcarnitine were unveiled as specific metabolic signatures of RD, and beyond playing a pivotal role in robustly distinguishing RD from CA, they exhibited significant discriminatory power across multiple RD subtypes, yielding accuracy and precision both exceeding 80%. This work paves the way for clinical translation of nanomaterial-enabled ocular metabolic diagnostics.}, }
@article {pmid42262492, year = {2026}, author = {Forte, P and Fontana, V and Park, SM and Cattaneo, J and Fazio, E and Forte, G and Scotto, R and Rosa, R and Nicolò, M and Iester, M and Kim, S and Eandi, CM and Kim, JH}, title = {Ethnic Differences in the Presentation Patterns of Type 3 Macular Neovascularization.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004902}, pmid = {42262492}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate differences in the presentation patterns of Type 3 macular neovascularization (T3 MNV) secondary to age-related macular degeneration in Caucasian and Asian populations.<br><br>METHODS: This retrospective, multicenter, comparative case series included treatment-na&#xef;ve T3 MNV patients from Switzerland, Italy, and South Korea. All patients underwent comprehensive multimodal imaging. The topography of T3 MNV foci was mapped relative to the Early Treatment Diabetic Retinopathy Study(ETDRS) grid. Demographic and clinical variables were analyzed with respect to ethnicity, and discriminant score performance was assessed for differentiating Caucasian and Asian populations.<br><br>RESULTS: A total of 301 eyes (181 European and 120 Korean) from 248 patients were included. Asian patients were significantly younger at presentation(76.1&#xb1;6.9 vs. 81.1&#xb1;6.1 years, p<0.001), with T3 MNV lesions located closer to the foveal center (mean distance: 810.7&#xb1;329.0 vs. 1061.4&#xb1;300.8 &#x3bc;m, p<0.001). Central ETDRS circle involvement was observed in Asians (17.5% vs 4.4%; p<0.001). Subfoveal choroidal thickness was similar between groups (154.1&#xb1;72.1 vs. 153.3&#xb1;71.0 &#x3bc;m, p=0.904). The prevalence of reticular pseudodrusen was higher in Caucasians than in Asians(89.0% vs. 74.2%; p=0.001). Multivariable analysis demonstrated that age(&#x3b2;=0.128, p<0.001), mean foveal distance (&#x3b2;=0.003, p<0.001) and RPD (&#x3b2;=1.150, p=0.003) had the strongest associations with ethnicity. In the discriminant model analysis, age and foveal distance emerged as significant discriminant features (&#x394;-C-index decreases=0.03 and 0.04, respectively).<br><br>CONCLUSION: The presentation patterns of T3 MNV in the Caucasian and Asian populations demonstrated both shared and distinct characteristics. These findings suggest that while T3 MNV may involve common pathophysiological mechanisms across ethnicities, certain contributing factors may vary between populations.}, }
@article {pmid42259594, year = {2026}, author = {Iovino, C and Borrelli, E and Coco, G and Viggiano, P and Boscia, F and Hasanreisoglu, M and Kesim, C and Demirel, S and Yanık, &#xd6; and Lucisano, A and Scorcia, V and Vagge, A and Nicolò, M and Proietti, S and Bernabei, F and Rothschild, PR and Farrant, S and Ricardi, F and Pellegrini, M and Mura, M and Cartabellotta, A and Giannaccare, G and Reibaldi, M and Carnevali, A}, title = {12-month outcomes of photobiomodulation in dry age-related macular degeneration: a prospective multicentre randomised double-masked controlled clinical trial.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328389}, pmid = {42259594}, issn = {1468-2079}, abstract = {BACKGROUND: Dry age-related macular degeneration (dAMD) is the leading cause of irreversible vision loss in older adults, with no approved treatment to modify progression in early and intermediate stages. Photobiomodulation (PBM), which targets mitochondrial dysfunction and retinal inflammation, has shown promise in early studies. This study aims to evaluate the anatomical and functional efficacy of PBM in eyes with early and intermediate dAMD.<br><br>METHODS: In this 12-month, multicentre, randomised double-masked controlled trial, 138 eyes from 78 patients with early or intermediate dAMD were included. The primary outcome was change in mean drusen volume (MDV) from baseline to 12 months. Secondary outcomes included change in best-corrected visual acuity (BCVA) and adverse events. Multilevel mixed-effects regression was used to analyse treatment-time interactions.<br><br>RESULTS: MDV decreased significantly in the PBM group (-0.03&#xb1;0.05&#x2009;mm&#xb3;) while increased in the sham group (+0.02 &#xb1; 0.04&#x2009;mm&#xb3;; p<0.001) at 12&#x2009;months. The PBM group also showed a significant improvement in BCVA (+1.31 &#xb1; 6.7 letters) compared with a decline in the sham group (-2.62&#xb1;7.1 letters), yielding a between-group difference of +3.75 letters (95%&#x2009;CI 1.16 to 6.34; p=0.0001). Female sex and higher Age-Related Eye Disease Study (AREDS) category were associated with MDV increase over time (p=0.030&#x2009;and p=0.003; respectively), while older age was associated with MDV reduction (p=0.049). Four eyes in the sham group developed macular neovascularisation, compared with none in the PBM group (p=0.044), while one eye in the PBM group developed geographic atrophy (p=1.00). No cases of retinal phototoxicity were observed.<br><br>CONCLUSION: PBM significantly reduced drusen burden and improved visual function in early and intermediate dAMD over 12&#x2009;months, with an excellent safety profile. These findings support PBM as a promising therapeutic option for patients with non-neovascular age-related macular degeneration, despite further studies with longer follow-up are needed to confirm the role of PBM in potentially slowing the natural course of the disease.}, }
@article {pmid42259595, year = {2026}, author = {Mauschitz, MM and Holz, FG and Schuster, AK and Grabitz, SD and Jonas, JB and Bikbov, MM and Kazakbaeva, GM and Hogg, R and Peto, T and Creuzot-Garcher, CP and Gabrielle, PH and Coimbra, R and Farinha, C and Delcourt, C and Cougnard-Grégoire, A and Brandl, C and Heid, IM and Finger, RP}, title = {Subretinal drusenoid deposits (reticular pseudodrusen) in the general population: a European multicohort study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-329334}, pmid = {42259595}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: To investigate the prevalence and determinants of subretinal drusenoid deposits (SDDs; also known as reticular pseudodrusen, RPDs) in the European general population.<br><br>METHODS: Altogether 18 931 adults from eight population-based studies were included. SDDs/RPDs were determined on optical coherence tomography and/or infrared photography. The prevalence of SDDs/RPDs and associated ocular and systemic determinants using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis were analysed.<br><br>RESULTS: Mean age ranged from 58.7&#xb1;10.6 to 88.4&#xb1;0.0 years in the different studies and prevalence of SDDs/RPDs ranged from 0.6% to 56.0%. Meta-analyses showed that increasing age (OR 1.09 per year, 95% CI 1.04 to 1.13; p<0.001), prevalent early/intermediate and late age-related macular degeneration (AMD) (OR 10.93, 95% CI 5.55 to 21.51; p<0.001 and OR 11.65, 95% CI 4.78 to 28.40; p<0.001, respectively) and AMD genetic risk score (OR 1.21 per unit, 95% CI 1.05 to 1.39; p=0.008) are associated with prevalent SDDs/RPDs. Sex, smoking, education and cardiovascular disease showed borderline association at some cohort levels but not in the meta-analysis. In sensitivity analyses, only age and AMD genetic risk score remained associated with SDDs/RPDs prevalence among participants without any AMD.<br><br>CONCLUSIONS: This multi-cohort analysis emphasises the wide range of SDDs/RPDs prevalence and determinants. Besides age, presence of AMD and AMD genetic risk variants increase the risk of SDDs/RPDs. These cross-sectional findings are compatible with the hypothesis that SDDs/RPDs may not represent a separate disease entity but be an additional sign of retinal pigment epithelium and photoreceptor stress.}, }
@article {pmid42259622, year = {2026}, author = {Chen, KE and Wang, PC and Lin, HA and Lin, SF}, title = {Risk of Age-Related Ocular Diseases in Non-Diabetic Adults With Obesity Using Glucagon-Like Peptide 1 Receptor Agonists.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.70975}, pmid = {42259622}, issn = {1463-1326}, abstract = {AIMS: To assess whether glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with a lower incidence of age-related ocular diseases in non-diabetic older adults with overweight or obesity.<br><br>MATERIALS AND METHODS: We conducted a retrospective, propensity score-matched cohort study using the TriNetX global research network. Non-diabetic, overweight or obese adults aged &#x2265;&#x2009;60&#x2009;years with an ophthalmic disease-na&#xef;ve baseline were enrolled. Patients receiving liraglutide or semaglutide were matched 1:1 with users of alternative weight-loss medications (bupropion-naltrexone, phentermine-topiramate, setmelanotide or orlistat). Outcomes included up to 5-year risks of incident cataract, age-related macular degeneration (AMD), ocular hypertension, primary open-angle glaucoma (POAG) and dry eye syndrome (DES).<br><br>RESULTS: After matching, 68&#x2009;536 patients were included (34&#x2009;268 per group). GLP-1RAs use was significantly associated with a lower 5-year risk of cataract (RR: 0.45; 95% CI, 0.40-0.50), AMD (RR: 0.33; 95% CI, 0.23-0.48), ocular hypertension (RR: 0.56; 95% CI, 0.34-0.91), POAG (RR: 0.50; 95% CI, 0.32-0.78) and DES (RR: 0.36; 95% CI, 0.31-0.42). Sensitivity analyses consistently demonstrated a lower risk across cataract subtypes, including nuclear (RR: 0.42; 95% CI, 0.37-0.48), cortical (RR: 0.37; 95% CI, 0.36-0.55) and posterior subcapsular cataracts (RR: 0.48; 95% CI, 0.26-0.91). Similar reductions were observed in retinal haemorrhage or edema (RR: 0.44; 95% CI, 0.30-0.63) and the use of dry eye-related medication (RR: 0.44; 95% CI, 0.39-0.50).<br><br>CONCLUSIONS: GLP-1RAs were associated with lower risks of multiple age-related ocular conditions in non-diabetic older adults.}, }
@article {pmid42247159, year = {2026}, author = {Hosokawa, MM and Ouchi, C and Matoba, R and Hayashi, J and Morita, T and Kindo, H and Masuda, Y and Akatsuka, R and Tsuji, A and Morizane, Y}, title = {Effects of cataract surgery on eyes with neovascular age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy under a treat-and-extend regimen.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42247159}, issn = {1435-702X}, abstract = {PURPOSE: To evaluate the effects of cataract surgery on eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy under a treat-and-extend (TAE) regimen.<br><br>METHODS: This retrospective observational study included eyes with nAMD receiving anti-VEGF therapy under a TAE regimen and undergoing cataract surgery, with anti-VEGF therapy continued for &#x2265;&#x2009;6 months before and after surgery. Best-corrected visual acuity (BCVA), retinal exudation, central retinal thickness (CRT), and subfoveal choroidal thickness (SFCT) were evaluated at the preoperative baseline and at 1 and 6 months after surgery. Anti-VEGF treatment intervals at the preoperative baseline and at 6 months after surgery were compared, and the number of injections during the 6 months before and after surgery was assessed. Factors associated with treatment-interval shortening at 6 months were analyzed using multivariate logistic regression.<br><br>RESULTS: A total of 85 eyes from 82 patients were included. Median BCVA significantly improved from 0.52 logMAR at baseline to 0.10 at 1 month and 0.05 at 6 months (P&#x2009;<&#x2009;0.001 for both). At 6 months, 53 eyes (62.4%) showed improved BCVA and 32 eyes (37.6%) remained stable; no eyes demonstrated visual deterioration. The proportion of eyes with retinal exudation was 21.2% at baseline, 29.4% at 1 month, and 32.9% at 6 months, with no significant differences. CRT increased significantly at 6 months compared with baseline (P&#x2009;=&#x2009;0.004), and SFCT increased significantly at both 1 and 6 months compared with baseline (P&#x2009;<&#x2009;0.001 for both). Although neither the median anti-VEGF treatment interval nor the median number of injections significantly changed before and after surgery, individually, 31.8% of eyes required shorter treatment intervals and 42.4% achieved longer treatment intervals at 6 months. Greater CRT at the preoperative baseline was a significant factor associated with treatment-interval shortening.<br><br>CONCLUSIONS: Cataract surgery in eyes with nAMD receiving anti-VEGF therapy under a TAE regimen appears beneficial for maintaining or improving visual acuity at 6 months despite the presence of postoperative retinal and choroidal anatomical changes. Changes in anti-VEGF treatment intervals varied among individuals, and greater preoperative CRT may serve as a useful indicator for predicting treatment-interval shortening.<br><br>KEY MESSAGES: WHAT IS KNOWN : Cataract surgery in eyes with neovascular age-related macular degeneration (nAMD) treated under pro re nata (PRN) or mixedregimens has been associated with significant improvements in mean or median visual acuity; however, some individual eyes haveshown postoperative visual deterioration. The effects of cataract surgery on retinal and choroidal morphology and disease activity in nAMD remain controversial.<br><br>WHAT IS NEW: In eyes with nAMD undergoing continuous anti-vascular endothelial growth factor (anti-VEGF) therapy under a treat-and-extend(TAE) regimen, cataract surgery significantly improved median visual acuity at 6 months, with no eyes showing postoperativevisual deterioration. Although central retinal thickness (CRT) and subfoveal choroidal thickness increased after surgery, these anatomical changes didnot lead to visual functional decline under continued TAE management. Changes in anti-VEGF treatment intervals varied among individuals, and greater preoperative CRT was associated with the needfor treatment-interval shortening at 6 months after cataract surgery.}, }
@article {pmid42248210, year = {2026}, author = {Butt, AB and Jeyakumaran, T and Zajner, C and Popovic, MM and Kertes, PJ and Muni, RH and Kohly, RP}, title = {Associations of age-related macular degeneration and statin use: a cross-sectional analysis.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.05.012}, pmid = {42248210}, issn = {1715-3360}, abstract = {OBJECTIVE: To examine the association between self-reported, age-related macular degeneration (AMD), statin use, and sociodemographic factors in a nationally representative sample of U.S. adults.<br><br>DESIGN: Cross-sectional study using 2023 National Health Interview Survey data.<br><br>METHODS: Analyses were restricted to adults aged 50 years and older. The descriptive sample included 16,924 participants, and 7 566 participants with complete covariate data were included in the multivariable analysis. The primary outcome was self-reported AMD. Univariable and multivariable logistic regression models assessed associations between AMD, statin use, and sociodemographic and health-related variables using complex survey weighting.<br><br>RESULTS: The descriptive sample included 16,924 adults aged 50 years and older; 55.41% were female, and 73.52% were non-Hispanic White. In adjusted analysis, statin use was not significantly associated with self-reported AMD (OR: 0.88, 95% CI: 0.66-1.18; p&#x202f;=&#x202f;.401). Older age, female sex, unemployment, and fair self-reported health were associated with higher odds of self-reported AMD, whereas Hispanic ethnicity was associated with lower odds of self-reported AMD.<br><br>CONCLUSIONS: Statin use was not independently associated with self-reported AMD after adjustment. Self-reported AMD was associated with older age, female sex, unemployment, and fair self-reported health, and with lower odds among Hispanic participants.}, }
@article {pmid42249143, year = {2026}, author = {Brown, DM and Berliner, AJ and Rao, R}, title = {Infographic: Study design for ELARA, an open-label, phase 3b trial of aflibercept 8 mg in previously treated patients with neovascular age-related macular degeneration or diabetic macular edema.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42249143}, issn = {1476-5454}, support = {None//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; None//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; None//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; }, }
@article {pmid42251179, year = {2026}, author = {Yang, S and Xin, Z and Li, H and Zhu, Z and Zhu, Z and Chen, Y and Zhang, Y and Xiong, R and Zhou, M and He, M and Wang, W}, title = {Proteomic clocks combined with deep learning phenotypes track eye aging and diseases.}, journal = {NPJ digital medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41746-026-02805-0}, pmid = {42251179}, issn = {2398-6352}, support = {82401298//National Natural Science Foundation of China/ ; 82371086//National Natural Science Foundation of China/ ; 2023YFC2506100//National Key Research and Development Program of China/ ; }, abstract = {Proteomics represents a powerful but underutilized approach for characterizing eye aging. Here, leveraging data from three large-scale, cross-national cohorts of over 55,000 transethnic participants, we demonstrate the ability of high-throughput proteomics combined with deep learning (DL) phenotyping to track eye aging and disease in both discovery and external validation settings. Proteomic aging driven by machine learning modeling closely aligns with signals of eye aging and DL aging phenotypes. We identifiy and validate premature proteomic aging in individuals with major age-related eye diseases (AREDs), including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma, and propose evidence supporting proteomic aging acceleration as a robust biomarker for predicting these conditions beyond chronological age, with adaptability across sexes and ethnicities. We also develop a streamlined, cost-effective proteomic aging clock that preserves predictive performance while reducing assay complexity. By integrating advanced tomographic and angiographic imaging, we derive structural and functional biomarkers through DL-driven pipelines and link accelerated proteomic aging to both neuroretinal degeneration and microvascular rarefaction in the Guangzhou Diabetic Eye Study (GDES) and the High-definition Oculo-Phenomic Evaluation (HOPE) study, highlighting coupled neural-vascular decline in eye aging. Our findings position proteomic aging combined with AI as a scalable tool for tracking eye health and disease, and provides new insights into shared aging pathways underlying multiple ocular pathologies.}, }
@article {pmid42252770, year = {2026}, author = {Desmond, T and Mehta, H and Sehu, W and Cherepanoff, S}, title = {Interpreting Hyperreflective Foci in Age-Related Macular Degeneration: A Critical Review of Cell Origins, Evolving Terminology and Clinical Utility.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.70128}, pmid = {42252770}, issn = {1442-9071}, support = {//Sarks Macular Degeneration Research Foundation (SC)/ ; }, abstract = {BACKGROUND: Hyperreflective foci identified on optical coherence tomography are promising biomarkers in age-related macular degeneration. However, their clinical application is limited by inconsistent definitions and ongoing uncertainty regarding their cellular origin. This review critically evaluates the evidence underlying hyperreflective foci definitions, examines competing hypotheses of cellular origin, and assesses their clinical utility.<br><br>METHODS: A structured critical review was conducted using a systematic search of MEDLINE and Scopus in July 2025, identifying 164 publications reporting hyperreflective foci in age-related macular degeneration. Eligible studies included clinical imaging, clinicopathological, and histological investigations. Given substantial heterogeneity in study design and outcome measures, findings were synthesised interpretively across three domains: imaging definitions, cellular origin, and clinical associations.<br><br>RESULTS: Clinical OCT definitions for hyperreflective foci were heterogeneous across studies. Histologically, hyperreflective foci correspond to pigment-laden epithelioid cells that consistently express monocyte/macrophage markers (CD68, CD163, IBA1) and lack retinal pigment epithelium markers (RPE65, peropsin). These cells are interpreted as pigment-containing macrophages that have ingested RPE-derived material, or as transdifferentiated RPE cells. Clinically, increasing hyperreflective foci burden is associated with disease severity, progression to geographic atrophy, and localised functional deficits, although associations with neovascular conversion and treatment response are inconsistent.<br><br>CONCLUSIONS: The available evidence suggests hyperreflective foci are pigment-containing immune cells, although altered or displaced retinal pigment epithelium cells may also be involved, and independent replication is required. Interpreting hyperreflective foci within this biological context may refine their role in disease monitoring and risk stratification. Establishing consensus imaging criteria, grounded in cellular identity, will be important for clinical translation.}, }
@article {pmid42254804, year = {2026}, author = {Salman, A and Griffiths, H and Garba, K and Lynn, SA and Cree, AJ and Szczepan, M and Jashal, CB and Chozhavel T M, R and Rao, P and Modi, K and MacLaren, RE and Yuen, HM and Lotery, AJ}, title = {Efficacy of anti-VEGF single-chain variable fragment AAV-based gene therapy in a laser-induced choroidal neovascularisation mouse model.}, journal = {Molecular therapy. Advances}, volume = {34}, number = {2}, pages = {201756}, pmid = {42254804}, issn = {3117-387X}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. Neovascular AMD (nAMD) is characterized by abnormal growth of new blood vessels from the choroid (choroidal neovascularization, CNV), with retinal pigment epithelium dysfunction leading to fluid leakage, bleeding, and central vision loss. nAMD is primarily driven by vascular endothelial growth factor (VEGF). Anti-VEGF therapies are widely used, with brolucizumab, a humanized monoclonal single-chain variable fragment (scFv) that inhibits VEGF, showing promise due to its high molar concentration and superior ability to dry the retina. However, concerns over retinal vasculitis have limited its clinical use. In this proof-of-principle study, we evaluated an AAV-delivered anti-VEGF scFv transgene derived from the brolucizumab sequence, packaged into two recombinant adeno-associated virus serotypes (rAAV6 and rAAV8), and delivered via subretinal injections in a laser-induced CNV mouse model. Leakage in 79 mice across seven groups was assessed by fundus fluorescein angiography. Compared with controls, AAV-treatment showed reduced leakage, particularly at week 9 (3.1% for rAAV6 and ∼10% for rAAV8 high doses), compared with controls (71.9%). Vector genomes were detectable by qPCR at 12 weeks, and electroretinography showed no obvious functional deficit. These findings support further evaluation of sustained AAV-mediated anti-VEGF delivery for nAMD.}, }
@article {pmid42255507, year = {2026}, author = {Leung, EH and Ghorayeb, G and Niles, P and Marshall, A and Kolomeyer, AM and Busquets, M and Patel, N and Gong, D and Al-Khersan, H and Emerson, GG and Blim, J and Lai, MM}, title = {Underfunding of a Patient Copay Assistance Program and the Impact on Retinal Disease Care: Survey of ASRS Members.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261442960}, pmid = {42255507}, issn = {2474-1272}, abstract = {Purpose: To assess the impact on treatment patterns resulting from underfunding of a large patient copay assistance program (Good Days) in 2024 and 2025. Methods: A 34-item electronic survey was sent to 1860 US members of the American Society of Retina Specialists (ASRS) in April 2025 to assess the effects of Good Days underfunding. Responses were then stratified based on the social deprivation index and poverty levels of the physicians' office locations. Results: A total of 411 responses (22%) were included. Most physicians (94%) reported significant or moderate disruptions in care after Good Days underfunding, and 90% reported patients being unable to receive their preferred drug therapy. Most physicians (93%) switched patients to off-label bevacizumab, with 84% reporting an increase in injection frequency after switching. Approximately 61% of physicians reported that vision loss was observed in patients due to cost-related delays in treatment, and 63% reported patients being lost to follow-up as a result of financial hardship. Most physicians (77%) believed that the underfunded patient copay assistance program disproportionately affected lower income or underserved communities. Physicians working in lower socioeconomic areas were more likely to report that patients requested to delay or miss therapy (50% vs 37%; P = .019), and patients with geographic atrophy were more likely to request treatment interval extensions (56% vs 44%; P = .033). Conclusions: Physicians were concerned about patients losing access to care, increasing treatment frequency with off-label therapies, and possibly losing vision after a large patient copay assistance program was underfunded. Policy makers, insurance companies, and manufacturers should work together to alleviate the financial burden and barriers to care resulting from high patient copays.}, }
@article {pmid42255749, year = {2026}, author = {Damasceno, NA and Horowitz, SA and Pegado, RS and Damasceno, EF}, title = {Drusen-Like Deposit Choroidopathy in Systemic Lupus Without Glomerulonephritis Treated With a Dexamethasone Implant.}, journal = {Cureus}, volume = {18}, number = {5}, pages = {e108320}, pmid = {42255749}, issn = {2168-8184}, abstract = {We report a case of a 54-year-old woman referred to our clinic with a prior diagnosis of neovascular age-related macular degeneration (nAMD) and who had received three intravitreal aflibercept injections in the left eye (LE). Fundus examination revealed bilateral drusen-like deposits (DLDs) in the posterior pole, along with macular edema in the LE. Optical coherence tomography (OCT) demonstrated subretinal fluid, retinal pigment epithelium detachment (PED) in the LE, and bilateral DLDs and increased choroidal thickness. These findings raised suspicion of an inflammatory condition, prompting laboratory evaluation that supported the diagnosis of systemic lupus erythematosus (SLE). The ocular findings were subsequently reclassified as inflammatory choroiditis associated with DLDs, without evidence of lupus nephritis. Treatment with systemic corticosteroids, mycophenolate mofetil, and dexamethasone intravitreal implant in the LE resulted in progressive clinical improvement.}, }
@article {pmid42255955, year = {2026}, author = {Krakauer, CA and Reilly, L and Su, YR and Walker, RL and Lee, D and Xaiyamuangchanh, VA and Cronkite, DJ and Gatto, NM and Crane, PK and Chew, EY and Arterburn, DE and Lee, CS}, title = {Age-related macular degeneration severity and risk of Alzheimer's disease in older adults in a prospective, community-based cohort study.}, journal = {Alzheimer's &amp; dementia (Amsterdam, Netherlands)}, volume = {18}, number = {2}, pages = {e70368}, pmid = {42255955}, issn = {2352-8729}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is associated with higher risk of Alzheimer's disease (AD), but how AD risk changes as AMD progresses remains unclear.<br><br>METHODS: Among participants in the Adult Changes in Thought study, we characterized the worst dry and wet AMD severities experienced to date on a scale of 0 to 10 and assessed whether they were associated with AD risk.<br><br>RESULTS: Among 2611 participants (550 AD cases, median 6.8 years follow-up), AD hazard was estimated to increase by 4% per one unit increase in dry and wet scores (dry: 95% confidence interval [CI] for hazard ratio [HR] 1.01 to 1.07, p&#xa0;=&#xa0;0.01; wet: 95% CI 1.00 to 1.08, p&#xa0;=&#xa0;0.03). HR estimates were similar among people without diagnosed AMD and were attenuated among those with diagnosed AMD.<br><br>DISCUSSION: Worse AMD severity was associated with higher AD risk, with severity scores potentially offering greater clinical utility for AD risk characterization among individuals without diagnosed AMD.}, }
@article {pmid42256005, year = {2026}, author = {Chujo, S and Quarta, A and Corradetti, G and Chung, YC and Kwak, H and Soylu, C and Abbasgholizadeh, R and Alhelaly, M and Rattu, R and Huang, J and Velaga, S and Nittala, MG and Uji, A and Sadda, SR}, title = {Photoreceptor Density-Dependent Kinetics of Geographic Atrophy Progression.}, journal = {Ophthalmology science}, volume = {6}, number = {7}, pages = {101198}, pmid = {42256005}, issn = {2666-9145}, abstract = {PURPOSE: To investigate whether the spatial distribution of photoreceptor density governs the rate and directionality of geographic atrophy (GA) progression and to propose a photoreceptor density-based metric for biologically informed assessment of GA progression.<br><br>DESIGN: A retrospective longitudinal analysis of untreated fellow eyes from a multicenter, randomized, sham-controlled clinical trial (MAHALO).<br><br>PARTICIPANTS: A total of 103 untreated fellow eyes from 143 eyes enrolled in the MAHALO study, all with GA secondary to age-related macular degeneration.<br><br>METHODS: Fundus autofluorescence images obtained at baseline and 18 months were analyzed. Geographic atrophy lesion area and boundary progression distance ("front") were quantified using rigidly registered images. The retina was divided into concentric eccentricity rings centered on the fovea. Theoretical cone and rod density models derived from histologic data were applied to generate photoreceptor density maps. Photoreceptor loss within GA lesions was estimated, and a photoreceptor-adjusted front was calculated by weighting boundary progression by local photoreceptor density. Directional progression was further evaluated using clock-hour-based analysis and a cosine-based directional metric (cos&#x3b8;).<br><br>MAIN OUTCOME MEASURES: Geographic atrophy area enlargement, front progression distance, photoreceptor-adjusted front, ring-wise photoreceptor loss, and directional variability of lesion expansion.<br><br>RESULTS: Geographic atrophy enlargement differed significantly across eccentricity rings (P < 0.001), demonstrating relatively slower expansion in regions with higher modeled photoreceptor density and greater expansion in lower-density regions. Total photoreceptor loss showed a moderate positive correlation with GA area enlargement (r = 0.48; P = 0.001). Directional variability of progression was significantly reduced when using the photoreceptor-adjusted front compared with the geometric front (coefficient of variation: 0.769 vs. 1.145; P < 0.01). In extrafoveal lesions, conventional front measurements demonstrated more rapid peripheral versus foveal progression, whereas this directional asymmetry was attenuated after photoreceptor density adjustment.<br><br>CONCLUSIONS: Geographic atrophy progression may be partly explained by the spatial distribution of photoreceptor density, among other contributing biological factors. Apparent directional and regional differences in GA expansion may reflect underlying gradients in photoreceptor density in addition to geometric and other biological influences. Photoreceptor density-based metrics provide a biologically informed framework for interpreting GA progression and may serve as complementary measures for natural history studies and clinical trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42257412, year = {2026}, author = {Huang, T and Jiang, D and Wang, D and Dong, Z and Hou, Y and Li, X and Deng, X and Liu, X}, title = {Complement-Modulating Mechanisms of Ginkgo biloba Extract in Dry AMD: Insights From Molecular Docking and Dynamics Simulations.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {6}, pages = {13}, doi = {10.1167/tvst.15.6.13}, pmid = {42257412}, issn = {2164-2591}, abstract = {PURPOSE: To investigate the complement-modulating mechanisms of Ginkgo biloba extract (EGb 761) in dry age-related macular degeneration (dry AMD) through an integrative approach combining bioinformatics, molecular docking, and molecular dynamics (MD) simulations.<br><br>METHODS: Bioinformatics analysis was used to identify dry AMD-related targets, followed by molecular docking and 100-ns MD simulations to evaluate the binding stability and free energy of EGb 761 components with complement proteins C3 and C5.<br><br>RESULTS: Quercetin and ginkgolide B showed the strongest and most stable interactions with complement proteins C3 and C5. Persistent hydrogen bond networks were observed in the C3/ginkgolide B and C3- and C5-quercetin complexes. MM-Poisson-Boltzmann surface area analysis indicated that van der Waals and electrostatic interactions were the main contributors to binding, and key residues (C3: ASP1435, GLU1433, LYS1001, LYS1436; C5: ASP1457, GLU837, GLU932) were identified as critical hotspots.<br><br>CONCLUSIONS: These results suggest that the major active components of G. biloba extract may act as natural complement modulators, stabilizing interactions with C3 and C5 to mitigate inflammation and oxidative injury in dry AMD.<br><br>TRANSLATIONAL RELEVANCE: Because the blood-retinal barrier limits the efficacy of systemic drugs for retinal diseases, nanomaterial-based ocular delivery systems are gaining attention. However, identifying suitable bioactive compounds for nanocarrier encapsulation remains challenging. EGb 761, a standardized and clinically validated G. biloba extract with proven safety and efficacy in ophthalmology, represents a promising candidate. This study provides a mechanistic basis for its potential in dry AMD and offers insights for developing natural complement-targeting therapeutics.}, }
@article {pmid42257918, year = {2026}, author = {Bindewald-Wittich, A and Alkabouni, MW and Wolf, A}, title = {Optical coherence tomography biomarkers for neovascular age-related macular degeneration : Relevance for diagnosis, treatment, and prognosis.}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42257918}, issn = {2731-7218}, abstract = {Comprehensive multimodal imaging is essential for the precise clinical diagnostics of neovascular age-related macular degeneration (nAMD). Noninvasive optical coherence tomography (OCT) is of prime importance regarding the baseline examination, follow-up and monitoring during treatment. OCT imaging in nAMD eyes enables a high-resolution assessment of the retinal micromorphology, which can be considerably disturbed in different layers. A large number of pathological OCT alterations represent distinct micromorphological OCT biomarkers. These should be taken into account in the assessment of OCT images. This article covers the following important biomarkers: intraretinal, subretinal and sub-pigment epithelial fluid, outer retinal tubulations, ellipsoid zone integrity, hyperreflective foci, subretinal drusenoid deposits, onion sign, hyporeflective prechoroidal cleft, double-layer sign, subretinal hyperreflective material and bacillary layer detachment.}, }
@article {pmid42259444, year = {2026}, author = {Xu, H and Pu, J and Yi, C and Deng, W and Yuan, XL and Chen, Z and Xiang, Q and Wang, Q and Wen, F and Chen, M}, title = {Macular Fibrosis Secondary to Neovascular Age-related Macular Degeneration: from Clinic to Biology.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101488}, doi = {10.1016/j.preteyeres.2026.101488}, pmid = {42259444}, issn = {1873-1635}, abstract = {Macular subretinal fibrosis represents the end-stage complication of neovascular age-related macular degeneration (nAMD). Despite the widespread use of anti-VEGF therapy, between 20 and 67% of nAMD patients develop this sight-threatening condition within 2 to 7 years, making fibrosis one of the main reasons responsible for anti-VEGF resistance and irreversible visual loss. Unlike the quiescent scar of a healed skin wound, subretinal fibrosis is a dynamic, vascularised lesion characterised by persistent and active inflammation, a process aptly termed "hot fibrosis". The molecular mechanisms that drive the conversion of neovascularisation into fibrovascular membrane remain poorly defined. This review summarises the clinical features of macular fibrosis in nAMD. It will then detail the pathological insights gained from advanced clinical high-resolution imaging and post-mortem histopathological investigations. We will also explore how advances in our understanding of the pathogenesis of macular fibrosis, as revealed by preclinical models, are uncovering novel therapeutic targets. Promising approaches include dual-targeting agents (e.g., inhibiting VEGF and Ang-2 or complement pathways), as well as repurposing FDA-approved anti-fibrotics, such as pirfenidone or nintedanib, for ocular delivery. The repurposing of drugs with established safety profiles, reformulated for local intraocular use, offers a particularly resource-efficient pathway.}, }
@article {pmid42246240, year = {2026}, author = {Rooks, E and Darrah, S and Rahimi, B and Nakamichi, K and Van Gelder, RN and Mustafi, D}, title = {A novel CAPN5 missense variant associated with autosomal dominant neovascular inflammatory vitreoretinopathy.}, journal = {Ophthalmic genetics}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/13816810.2026.2682399}, pmid = {42246240}, issn = {1744-5094}, abstract = {INTRODUCTION: Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare inherited retinal disorder that often has delayed diagnosis due to overlapping features of intraocular inflammation, retinal degeneration, and retinal neovascularization.<br><br>CASE PRESENTATION: We report a case of a 53-year-old male who presented with progressive panuveitis, peripheral visual field loss, and nyctalopia. Multimodal imaging demonstrated peripheral retinal nonperfusion, vascular leakage, cystoid macular edema, and progressive tractional vitreoretinal changes. Family history was notable for presumed age-related macular degeneration in the patient's father, later found on postmortem evaluation to have features suggestive of ADNIV. To determine the etiology of the clinical presentation, the patient underwent genetic testing using a targeted long-read sequencing inherited retinal disease panel, which identified a heterozygous missense variant in CAPN5, c.728G>A (p.Arg243His).<br><br>DISCUSSION: The overlapping features of intraocular inflammation, retinal degeneration, and vasoproliferative disease frequently lead to delayed or incorrect diagnosis of ADNIV. The potentially causative variant identified has not been reported to cause disease before, but at that amino acid residue, a different missense variant has been identified as the causative variant in ADNIV patients as it localizes to a calcium-sensitive regulatory region adjacent to the catalytic domain, supporting a gain-of-function mechanism. Although currently classified as a variant of uncertain significance, its genomic context, rarity, and biologic plausibility support pathogenicity.<br><br>CONCLUSIONS: This case expands the mutational spectrum of CAPN5-associated ADNIV and highlights the importance of integrating detailed clinical phenotyping with biologically informed genetic interpretation in complex inherited retinal disorders.}, }
@article {pmid42242290, year = {2026}, author = {Al-Burak, SA and Suleiman, A and Voznyy, V and Elganga, M and Zajner, C and Juncal, V and Sheidow, TG and Malvankar-Mehta, MS}, title = {Age-related macular degeneration (AMD) associated with glucagon-like peptide-1 receptor agonist use: a systematic review.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.05.010}, pmid = {42242290}, issn = {1715-3360}, abstract = {BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes.<br><br>METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively.<br><br>RESULTS: Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low.<br><br>CONCLUSIONS: Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships.}, }
@article {pmid42242606, year = {2026}, author = {Boyer, DS and Saad, L and Washington, I and Melamud, A and Graham, KB and O'Malley, AE and DeBartolomeo, GM and Jiang, H and Harris, LD and Kay, CN and Ferrone, PJ and Khan, S and , }, title = {Gildeuretinol Acetate vs Placebo for Geographic Atrophy Secondary to Age-Related Macular Degeneration: The SAGA Randomized Clinical Trial.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.05.018}, pmid = {42242606}, issn = {2468-6530}, abstract = {OBJECTIVE: To assess the effects of gildeuretinol acetate (C20D3-vitamin A) in geographic atrophy (GA).<br><br>DESIGN: 24-month, double-masked, multicenter, randomized, placebo-controlled trial.<br><br>PARTICIPANTS: Participants &#x2265;60 years with GA.<br><br>INTERVENTIONS: Randomized 2:1 to oral gildeuretinol acetate 14 mg daily or placebo.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was GA growth rate from baseline to 24 months. A prespecified sensitivity analysis accounted for a 6-month delay in onset of therapeutic effect. Secondary endpoints included change from baseline in low luminance visual acuity (LLVA), best-corrected visual acuity (BCVA), Visual Function Questionnaire (VFQ)-25, and Functional Reading Independence (FRI) Index.<br><br>RESULTS: Among 198 randomized participants (mean [SD] age 78.4 [7.0] years; 68.7% female), 69.2% completed the 24-month study. In the gildeuretinol and placebo groups, baseline mean (SD) total GA lesion area in mm[2] was 7.72 (6.10) and 7.09 (4.16); BCVA letter scores were 56.2 (21.3) (Snellen equivalent: &#x223c;20/80) and 58.8 (18.0) (&#x223c;20/70); and LLVA letter scores were 31.1 (19.0) (&#x223c;20/200) and 31.6 (17.8) (&#x223c;20/250), respectively. Mean GA growth rates were 1.62 mm[2]/year with gildeuretinol and 1.87 mm[2]/year with placebo (least squares [LS] mean difference: -0.25 mm[2]/year; 95% CI: -0.53, 0.03; P = 0.075), a 13.4% relative reduction for gildeuretinol vs placebo. The LS mean (SE) GA growth rates from 6 to 24 months were 1.90 (0.12) mm[2]/year (placebo) and 1.61 (0.08) mm[2]/year (gildeuretinol), a 15.3% relative reduction (-0.29 mm[2]/year; 95% CI: -0.576, -0.004; nominal P = 0.047). At 24 months, LLVA declined 3.9 and 8.3 ETDRS letters in the gildeuretinol and placebo groups, respectively (difference: 4.4 letters; 95% CI: 0.40, 8.41; nominal P = 0.031). BCVA declined 6.9 letters with gildeuretinol and 10.2 letters with placebo (difference: 3.3 letters; 95% CI: -0.63, 7.23; P = 0.099). VFQ-25 scores declined 4.81 fewer points with gildeuretinol than placebo (95% CI: 0.87, 8.76; nominal P = 0.017) and FRI scores declined 0.35 fewer points (95% CI: 0.11, 0.58; nominal P = 0.004).<br><br>CONCLUSIONS: The prespecified primary endpoint was not met. Prespecified piecewise and secondary functional/patient-reported analyses favored gildeuretinol with nominal P values; these exploratory findings support further evaluation in adequately powered trials.}, }
@article {pmid42243112, year = {2026}, author = {Cui, X and Hui, J and Zhao, Q and Han, Q}, title = {Plant-based diet quality and risk of age-related eye diseases: evidence from multi-cohorts with multi-omics insights.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00919-z}, pmid = {42243112}, issn = {2396-8370}, support = {NKSGZ202305//Nankai University Eye Institute Key Science and Technology Fund/ ; TJYXZDXK-3-004A-3//Tianjin Key Medical Discipline Construction/ ; }, abstract = {Plant-based diets may influence age-related eye diseases (AREDs), but whether ocular benefits depend on diet quality remains unclear. We examined associations of a healthy plant-based diet index (PDI-H) and an unhealthy plant-based diet index (PDI-U) with age-related macular degeneration (AMD), cataract, glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO) using the UK Biobank prospective cohort and an independent Tianjin hospital-based cross-sectional sample. Cox regression, logistic regression, propensity score matching, restricted cubic splines, subgroup analyses, multi-omics profiling, and machine learning were applied. Higher PDI-H was associated with lower risks of AMD, cataract, glaucoma, and DR, whereas higher PDI-U was associated with increased risks of AMD, cataract, and DR. Associations with RVO were weak or absent. Findings from Tianjin were directionally consistent with UK Biobank results and should be interpreted as supportive cross-sectional evidence. Proteomic and metabolomic analyses linked plant-based diet quality to inflammation, lipid metabolism, glycaemic regulation, and hormonal signalling. Predictive models incorporating dietary indices showed good discrimination for AMD and cataract, with modest but consistent AUC improvements after adding PDI-H and PDI-U to traditional risk factors. These findings suggest that plant-based diet quality, rather than plant-based eating alone, may be a modifiable determinant of major AREDs.}, }
@article {pmid42243270, year = {2026}, author = {Pawloff, M and Linhardt, D and Woletz, M and Hollaus, M and Mylonas, G and Holder, GE and Sacu, S and Windischberger, C and Ritter, M}, title = {Robust and reproducible population receptive field mapping in patients with retinal pathologies.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42243270}, issn = {1476-5454}, support = {KLI 670-B30; P35583//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; }, abstract = {PURPOSE: Previous studies have shown high reproducibility of population receptive field (pRF) mapping in young, healthy individuals. The present study examines whether such a level of reproducibility can also be achieved in patients suffering from retinal disease.<br><br>METHODS: Eleven patients with Stargardt disease and eleven patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined in up to four sessions using high-resolution ultra-high field fMRI (Siemens Magnetom 7&#x2009;T) and microperimetry (MP, Nidek MP-3). Reproducibility of the pRF parameters within and between sessions was assessed using Spearman's correlation coefficient.<br><br>RESULTS: Retinotopic maps calculated from ultra-high field MRI had excellent intra- and intersession reproducibility for pRF center position (median correlation between sessions for pRF center eccentricity: r&#x2009;=&#x2009;0.91; polar angle: r&#x2009;=&#x2009;0.90), but only modest reproducibility for pRF size (average correlation r&#x2009;=&#x2009;0.39). Reproducibility was constant across sessions multiple weeks apart, indicating a long-term stability of the method. In addition, the results show that reproducibility is not related to the severity of retinal disease.<br><br>CONCLUSION: The data demonstrate that retinotopic mapping of the primary visual cortex using ultra-high field MRI is a highly reproducible technique for the assessment of macular function in patients with retinal disease. The technique provides an unbiased quantification of retinal function adjunct to conventional clinical assessments and may assist the early diagnosis of retinal disease. In addition, it may be a valuable objective method for monitoring visual deficits during long-term therapeutic interventions or disease progression.}, }
@article {pmid42245065, year = {2026}, author = {Lee, SS and Wang, CA and de Vries, VA and van Hemert, DJ and Schulze, A and Brandl, C and Aman, AM and Alonso-Caneiro, D and Choquet, H and Gorski, M and Hammond, CJ and Heid, IM and Hunter, ML and Hysi, P and Jiang, C and Jonas, J and Klaver, CC and Kneepkens, SC and Konig, S and Lingham, G and Luber, C and Melton, PE and Pennell, CE and Ramdas, WD and Read, SA and Schuster, AK and Wang, YX and Zimmermann, ME and ,  and Khawaja, AP and Gharahkhani, P and MacGregor, S and Guggenheim, JA and Mackey, DA}, title = {Genome-wide discovery reveals 30 loci for choroidal thickness and uncovers potential causal links with angle-closure glaucoma.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.05.26.26354075}, pmid = {42245065}, abstract = {The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.}, }
@article {pmid42232161, year = {2026}, author = {Guo, H and Yan, R and Han, X and Yu, W}, title = {Dysregulated Polarized Secretion of Small Extracellular Vesicles in the Retinal Pigment Epithelium: Mechanisms and Pathological Roles in Age-Related Macular Degeneration.}, journal = {Journal of inflammation research}, volume = {19}, number = {}, pages = {612984}, pmid = {42232161}, issn = {1178-7031}, abstract = {The pathogenesis of age-related macular degeneration (AMD) is intrinsically driven by retinal pigment epithelium (RPE) dysfunction. Under physiological conditions, the strictly polarized secretion of small extracellular vesicles (sEVs) by the RPE dictates outer retinal homeostasis. In response to oxidative and hypoxic stress, this secretory architecture is profoundly disrupted, transforming sEVs into mediators of drusen formation, inflammation, and neovascularization. This review systematically delineates the molecular machinery governing RPE-sEV trafficking, unveiling the distinct protein and miRNA cargo profiles segregated between the apical and basolateral domains. We highlight the unique secretory features of RPE and elucidate how AMD stressors disrupt this polarity via cytoskeletal collapse, secretory autophagy, and Rab GTPase dysregulation. Consequently, this altered sEV secretion abolishes apical neurotrophic support while deteriorating the basolateral microenvironment. Crucially, this establishes a vicious pathological loop where microenvironmental deterioration and sEV dysregulation are mutually causative. Recognizing dysregulated sEV polarity as a contributing factor to AMD, we propose that repairing RPE intracellular trafficking offers a fundamental strategy to restore secretory homeostasis and impede disease progression.}, }
@article {pmid42233695, year = {2026}, author = {Battu, P and Sharma, S and Singh, R and Anand, A}, title = {Circulating biomarker profile and its diagnostic predictive utility in age-related macular degeneration.}, journal = {Biomarkers in medicine}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/17520363.2026.2677199}, pmid = {42233695}, issn = {1752-0371}, abstract = {PURPOSE: We evaluated the serum expression profiles of proteins encoded by AMD-related genes in age-related macular degeneration patients and controls.<br><br>METHODS: In our case-control study, we employed Enzyme-linked immunosorbent assay (ELISA) to analyze the expression of Collagen type X alpha 1 chain (COL10A1), Transforming growth factor-beta receptor type 1(TGF&#x3b2;R1) and Tumor Necrosis Factor Receptor Superfamily (TNFRSF10A) in serum. We have also statistically analyzed the correlations among the biomarkers and further assessed their diagnostic potential using the least absolute shrinkage and selection operator (LASSO) regression.<br><br>RESULTS: Out of three evaluated serum protein levels, two were found to be significantly associated with AMD. The expression of COL10A1 was significantly upregulated (p&#x2009;<&#x2009;0.0001), and TNFRSF10A was significantly downregulated (p&#x2009;<&#x2009;0.0001) in AMD patients compared to controls. The LASSO logistic regression revealed that serum expression of COL10A1 and TNFRSF10A proteins can reliably differentiate AMD cases from controls with predictive accuracy of 87.3%.<br><br>CONCLUSION: Our findings indicate that serum levels of COL10A1 and TNFRSF10A are significantly altered in AMD patients compared to controls. LASSO regression analyses further revealed that these proteins together have a strong ability to differentiate between AMD cases and controls, suggesting their potential as reliable biomarkers for risk prediction of AMD.}, }
@article {pmid42234083, year = {2026}, author = {Saraf, A and Garima, K and Dharwadkar, S and Keshav, S and Patwardhan, SD and Giri, NB and Saxena, M and Phadke, Y and Khare, A and Mishra, A and Kumar, V and Singh, S}, title = {Safety of GBL1204-An Ophthalmic Bevacizumab in Prefilled Syringe for Neovascular Age-Related Macular Degeneration: A Phase I Study.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42234083}, issn = {2193-8245}, abstract = {INTRODUCTION: GBL1204 1.25 mg is an ophthalmic-grade bevacizumab formulation, manufactured in accordance with the stringent ophthalmic quality standards, and supplied in a single-use prefilled syringe (PFS). This clinical trial evaluated the short-term safety and biological activity of a single intravitreal injection of ophthalmic bevacizumab in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This phase&#xa0;I, open-label, single-arm, multicentre trial enrolled 16 participants (aged&#x2009;&#x2265;&#x2009;50&#xa0;years) with best-corrected visual acuity (BCVA) score using Early Treatment of Diabetic Retinopathy Study charts of 20/40-20/320 (approximate Snellen equivalent) at five centres across India. Participants were administered a single intravitreal injection of GBL1204 (1.25&#xa0;mg/0.05&#xa0;mL). The main objective was evaluation of ocular and systemic treatment-emergent adverse events (TEAEs), and laboratory parameters over 4&#xa0;weeks.<br><br>RESULTS: GBL1204 complies with the particulate matter standards specified in the United States Pharmacopeia USP&#x2009;<&#x2009;789&#x2009;>&#x2009;for ophthalmic injectable solutions. GBL1204 was safe and well tolerated by the patients over 4&#xa0;weeks. No ocular or systemic serious adverse events occurred. Nine participants (56.25%) reported 14 TEAEs (13 ocular, 1 non-ocular). Of the 14 adverse events, 8 (57.14%) were considered as mild; all adverse events resolved on their own, and without any sequelae. Mean (standard error mean, SEM) BCVA improvement from baseline was +&#x2009;1.80 (0.76) letters at day&#xa0;7 and +&#x2009;3.0 (1.10) letters at day&#xa0;28. The corresponding mean (SEM) central macular thickness reductions were -&#x2009;41.67&#xa0;&#xb5;m (40.35) and -&#x2009;64.67&#xa0;&#xb5;m (42.74) at days&#xa0;7 and 28, respectively. Serum vascular endothelial growth factor levels showed expected suppression consistent with bevacizumab pharmacodynamics.<br><br>CONCLUSION: A single intravitreal injection of GBL1204 demonstrated favourable short-term safety and tolerability, with evidence of visual and anatomical improvements. These findings support further evaluation of GBL1204 1.25&#xa0;mg PFS in a pivotal phase&#xa0;III trial as a standardized alternative to compounded bevacizumab. Trial Registration Clinical Trial Registry-India (CTRI): Identification no. CTRI/2024/02/063012.}, }
@article {pmid42236129, year = {2026}, author = {Zhang, C and Sonik, NR and Ayoubi, M and AbouKasm, G and Zhu, D and Fan, JC and Albini, TA and Yannuzzi, NA}, title = {Clinical efficacy and safety of aflibercept biosimilars in neovascular age-related macular degeneration: a systematic review and meta-analysis of randomised controlled trials.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328196}, pmid = {42236129}, issn = {1468-2079}, abstract = {BACKGROUND: To evaluate the efficacy and safety of aflibercept biosimilars compared with reference aflibercept in the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD4201069147). Phase 3 randomised controlled trials (RCTs) comparing aflibercept biosimilars to reference aflibercept in treatment-na&#xef;ve nAMD were included. All included studies employed a standardised on-label aflibercept dosing regimen consisting of three initial monthly loading doses followed by injections every 8&#x2009;weeks. The primary outcome was the mean difference (MD) in best-corrected visual acuity (BCVA) at week 8. Secondary outcomes included BCVA at week 52, proportion of patients gaining &#x2265;15 letters or maintaining vision (<15-letter loss), central subfield thickness (CST) and adverse events (AEs).<br><br>RESULTS: Six RCTs (2022-2024)&#x2009;were included, comprising 2029 eyes (1020 biosimilar; 1009 reference). BCVA at week 8 did not differ significantly between groups (MD -0.34 letters; 95% CI -1.12 to 0.44; I&#xb2;=0%; p=0.39), as was BCVA at week 52 (MD -0.04; 95%&#x2009;CI -1.18 to 1.10; I&#xb2;=1%; p=0.94). No differences were observed in the proportion of patients gaining &#x2265;15 letters, maintaining vision, CST changes or AEs.<br><br>CONCLUSIONS: Aflibercept biosimilars demonstrated no significant difference in efficacy at 8&#x2009;weeks and 52&#x2009;weeks as well as safety relative to reference aflibercept in eyes with treatment-na&#xef;ve nAMD following an on-label aflibercept treatment protocol; however, real-world extended durability remains untested. These findings were supported by a low risk of bias and a high-certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations tool.}, }
@article {pmid42237272, year = {2026}, author = {Kong, M and Jin, R and Cheng, T and Sun, L and Tong, N}, title = {Serum microRNA-34a as a circulating biomarker for age-related macular degeneration and short-term anti-VEGF response in neovascular AMD.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04983-7}, pmid = {42237272}, issn = {1471-2415}, abstract = {OBJECTIVE: To evaluate whether serum microRNA-34a (miR-34a) is associated with age-related macular degeneration (AMD) and whether baseline serum miR-34a has the potential to predict short-term response to anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with neovascular AMD (nAMD).<br><br>METHODS: In a cross-sectional cohort recruited at Qingdao Municipal Hospital between January and December 2024, serum miR-34a was quantified in 160 AMD patients and 122 age- and sex-matched healthy controls. AMD was staged according to Age-related Eye Disease Study (AREDS) criteria. Patients with nAMD received three consecutive monthly intravitreal anti-VEGF injections during the loading phase and were classified as good or poor responders according to prespecified anatomical and functional criteria based on optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) after the loading phase. Peripheral blood samples were collected, and serum miR-34a expression was quantified using standard qPCR protocols.<br><br>RESULTS: Serum miR-34a was significantly higher in patients with AMD than in controls (p&#x2009;<&#x2009;0.001). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.740 (95% CI 0.681-0.799; p&#x2009;<&#x2009;0.0001) for discriminating AMD from controls. Across AMD subgroups, serum miR-34a differed significantly overall; patients with geographic atrophy (GA) exhibited higher miR-34a levels than those with nAMD (p&#x2009;<&#x2009;0.05). Among patients with nAMD, baseline serum miR-34a was remarkably higher in good responders than in poor responders after the loading phase (p&#x2009;<&#x2009;0.001). ROC analysis showed an AUC of 0.772 (95% CI 0.687-0.857; p&#x2009;<&#x2009;0.0001) for predicting treatment response, and multivariable logistic regression identified higher serum miR-34a as independently associated with lower odds of poor response (OR 0.143, 95% CI 0.042-0.489; p&#x2009;=&#x2009;0.002).<br><br>CONCLUSION: Elevated serum miR-34a is associated with AMD and may serve as a minimally invasive biomarker for distinguishing AMD from controls. In nAMD, baseline serum miR-34a also showed potential for predicting short-term response to loading-phase anti-VEGF therapy. These findings warrant validation in larger, longitudinal, and preferably multicenter cohorts.}, }
@article {pmid42239431, year = {2026}, author = {Diwedi, B and Neog, A and Baanannou, A and Das, P and Menard, R and Halluin, C and Morse, D and Emmerich, K and Thierer, JH and Patnaude, M and Bonnet, F and Graber, JH and Mumm, JS and Madelaine, R}, title = {Mesenchymal-derived neural progenitors underlie local insulin production and neuronal transdifferentiation during retina regeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.05.20.726251}, pmid = {42239431}, issn = {2692-8205}, abstract = {In humans, retinal-neuron death, optic-nerve injuries, and associated neurodegenerative diseases, such as glaucoma and age-related macular degeneration, often lead to permanent vision loss. While the capacity for regeneration is low in the human nervous system, including the retina, some non-mammalian vertebrate species, including zebrafish, are capable of endogenous neuronal regeneration after injury. Unlike mammals, zebrafish do not form a scar that inhibits axonal and neuronal regeneration after injury. Rather, they harbor neural progenitor and stem-cell populations allowing regeneration of entire parts of the nervous system and restoration of tissue integrity and function. In the zebrafish retina, cycling neural progenitor cells of the ciliary marginal zone and quiescent resident neural stem cells (the latter of which are also called Müller glial cells) participate in neuronal regeneration following different types of injury. In this study, we report the identification of a novel, additional cellular source participating in neuronal regeneration of neurons in the zebrafish retina after genetic ablation of retinal ganglion cells. Before injury, these progenitor cells express molecular markers of neural-crest-cell and/or fibroblast identity, such as sox10 , pdgfrb , and eya2 , while after neuronal ablation they also express proneural factors including the ascl1a and olig2 genes. Combining genetic ablation of neurons with photoconversion or Cre/Lox-dependent genetic lineage tracing of sox10 -expressing cells, we demonstrated that these cells can differentiate into post-mitotic retinal neurons in the ganglion cell layer (GCL) in the absence of cell proliferation. We also showed, surprisingly, that this progenitor population locally produces insulin mRNA, and that insulin signaling is involved in the accumulation of mesenchymal-derived neural progenitors in the GCL and in their subsequent transdifferentiation into RGCs. This work reveals an unexpected and novel cellular mechanism of transdifferentiation, dependent on a neural-crest-derived mesenchymal cell population, participating in neuronal regeneration in the zebrafish retina. The discovery of this plastic cell population could potentially lead to new strategies to promote the formation of new neurons in the mammalian retina.}, }
@article {pmid42239615, year = {2026}, author = {Wang, J and Wang, Q}, title = {IMPG1 Variant Causing Adult-Onset Foveomacular Vitelliform Dystrophy in Chinese: A Case Report.}, journal = {Case reports in ophthalmology}, volume = {17}, number = {1}, pages = {448-454}, pmid = {42239615}, issn = {1663-2699}, abstract = {INTRODUCTION: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare entity and is mostly reported in French individuals. Here, we report a Chinese patient with AOFVD who had IMPG1 mutation and was misdiagnosed with age-related macular degeneration (AMD).<br><br>CASE PRESENTATION: A 59-year-old man complaining of vision loss was misdiagnosed with AMD and treated with intravitreal injections of anti-vascular endothelial growth factor, but with no improvement. Visual acuity was 20/50 in the right eye and 20/40 in the left eye. Fundus examinations revealed a bilateral symmetrical vitelliform "egg yolk" lesion. Spectral-domain optical coherence tomography revealed dome-shaped subretinal hyperreflective materials and cuticular drusen at the retinal pigment epithelium-Bruch's membrane complex in both eyes. No clear neovascularization was observed. Electrooculography revealed a decreased Arden ratio. Based on multimodal imaging analysis and genetic testing, the patient was diagnosed with AOFVD. No therapeutic intervention was administered. One month after the patient's visit, vitelliform "egg yolk" lesion was absorbed in the right eye, and the patient's visual acuity decreased to 20/100 in the right eye.<br><br>CONCLUSION: AOFVD is rare and underdiagnosed. It can disguise as AMD or other similar macular diseases. Clinicians should be alert to this condition, pay attention to its identification, and avoid unnecessary treatments.}, }
@article {pmid42240907, year = {2026}, author = {Güçlü, H and Doğanlar, Z and Şambel Aykutlu, M and Köse, G and Doğanlar, O}, title = {The role of STAT3-targeted therapy created with COLIVELIN in the cross-talk between IL6/JAK2/STAT3 and TGF-β/SMAD2/SMAD3 signaling in a hyperinflammation and ROS-induced in vitro AMD model and its effect on retinal apoptosis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42240907}, issn = {1573-2630}, support = {(T&#xdc;BAP-2021/68)//Republic of T&#xfc;rkiye Trakya University Scientific Research Projects Unit/ ; }, abstract = {This study aimed to investigate the therapeutic potential of Colivelin in modulating the cross-talk between the IL-6/JAK2/STAT3 and TGF-β/SMAD2/SMAD3 signaling pathways and its downstream effects on retinal apoptosis in an in vitro AMD model. An in vitro AMD model was established in ARPE-19 human RPE cells using a sublethal combination of lipopolysaccharide and hydrogen peroxide. Apoptosis was quantified via Tali® image cytometry. Gene expression profiling was performed by qRT- PCR. Protein expressions were assessed by Western blot. Formal mediation analysis was employed to quantify pathway-specific mechanistic contributions. The AMD model exhibited significant upregulation of hypoxia-related genes (HIF-1α, VEGF, MMP3, MMP9), pro-inflammatory cytokines (IL-6, TNF-α), and pro-apoptotic markers (BAX, p53, Caspase- 3), accompanied by markedly elevated ROS levels and reduced cell viability. Low-dose Colivelin (1 µM) significantly enhanced STAT3 phosphorylation, restored antioxidant gene expression (GSS, CAT, SOD2), suppressed hypoxia-associated gene expression, and substantially reduced TGF-β receptor, SMAD2, and SMAD3 expression at both transcriptional and protein levels. Formal mediation analysis revealed that 91-98% of Colivelin's anti-apoptotic effect at the therapeutic dose was mediated through STAT3-driven suppression of TGF-β/SMAD2/3 signaling, rather than through direct STAT3 transcriptional activity on apoptotic target genes. Conversely, high-dose Colivelin (10 µM) paradoxically activated SMAD2/3-independent pro-apoptotic cascades, demonstrating a dose- dependent biphasic response. This study provides the first formal mechanistic evidence that Colivelin exerts its cytoprotective effects in AMD primarily through a STAT3 → SMAD2/3 suppression axis. Low-dose (1 µM) Colivelin demonstrated superior and broader therapeutic efficacy compared to Bevacizumab by simultaneously modulating oxidative stress, hypoxia, angiogenesis, and apoptotic signaling pathways. These findings establish Colivelin as a promising multi-target therapeutic candidate for AMD, with its therapeutic window defined by the capacity of STAT3 activation to selectively suppress TGF-β/SMAD-driven apoptotic signaling without engaging compensatory pro-death mechanisms. Rigorous pharmacokinetic optimization and in vivo validation are warranted to advance Colivelin toward clinical translation.}, }
@article {pmid42240995, year = {2026}, author = {Xue, CC and Chee, ML and Li, H and Tham, YC and Cheng, CY}, title = {Reported Metformin Use and Age-Related Macular Degeneration in Patients With Diabetes.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.1799}, pmid = {42240995}, issn = {2168-6173}, }
@article {pmid42230733, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX}, title = {Presence and associations of retinal pigment epithelium and outer retinal atrophy: the Beijing eye study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-55175-8}, pmid = {42230733}, issn = {2045-2322}, abstract = {The goal of the study was to assess the presence of an incomplete (iRORA) and complete (cRORA) retinal pigment epithelium (RPE) and outer retinal atrophy in a general population and explore their associations with other parameters. Participants of the population-based Beijing Eye Study with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) or those without retinal diseases, underwent optical coherence tomography of the macula. Among 5894 eyes, presence of iRORA and cRORA increased from 0/5117 (0%) and 0/5117 (0%) in the normal group and 0/457 (0%) and 0/457 (0%) in early AMD to 5/277 (1.8%;95%CI:0.3,3.3) and 0/277 (0%) in intermediate AMD, 6/6 (100%) and 6/6 (100%) in geographic atrophy, 0/2 (0%) and 2/2 (100%) in exudative AMD, and 10/30 (33.3%;95%CI:17.8,48.8) and 6/30 (25.0%;95%CI:12.0,38.0) in PCV, respectively. Higher iRORA presence was associated (multivariable analysis) with higher AMD stage (OR:54.7;95%CI:6.68,449;P < 0.001), higher PCV presence (OR:1.523 × 10[5];95%CI:834,2.785 × 10[7];P < 0.001), and higher presence of reticular pseudodrusen (OR:19.2;95%CI:1.94,190;P < 0.001). Drusen number (OR:0.97;95%CI:0.91,1.03;P = 0.27) and subfoveal choroidal thickness (OR:1.003;95%CI:0.994,1.013;P = 0.49) were not associated. Higher cRORA presence correlated with higher PCV presence (OR:48.6;95%CI:4.58,517;P = 0.001) and higher presence of reticular pseudodrusen (OR:120;95%CI:13.1,1094;P < 0.001). iRORAs and cRORAs were spatially associated with ellipsoid zone and external limiting membrane defects and intraretinal hyperreflective foci (iHRFs) in the outer and inner retinal layers. The findings suggest that iRORAs and cRORAs presences were relatively low in our population-based study, and were associated with higher presence of reticular pseudodrusen but not with drusen number or subfoveal choroidal thickness. The spatial association with ellipsoid zone defects and external limiting membrane defects and iHRF in the outer retinal layer and beyond fits with the notion of an RPE cell migration playing a role in the development of iRORAs and cRORAs.}, }
@article {pmid42230802, year = {2026}, author = {Swaroop, A and Roska, B}, title = {Revisiting retinal and macular degeneration in the genomics era.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, pmid = {42230802}, issn = {1471-0064}, abstract = {Retinal and macular degeneration constitute a prominent cause of untreatable vision loss globally. The development of efficacious therapies is impeded by extensive clinical and genetic heterogeneity, poor phenotype-genotype correlation and lack of appropriate disease models. Pioneering advances in next-generation sequencing together with computational methods, human model systems and genetic manipulation technologies have begun to unravel causal genes and variants as well as gene interaction networks. Photoreceptor dysfunction or death represents the end point for both Mendelian and complex traits affecting the retina or its specialized central region, the macula. Here we review the genetic and genomic bases of retinal and macular degeneration and how recent advances are informing therapies to slow the loss of or restore vision.}, }
@article {pmid42230852, year = {2026}, author = {Wu, X and Zhang, X and Jiang, Y and Gu, Z and Li, C and Zhu, X and Huang, Y and Li, B and Ma, M and Zhao, S and Zheng, Z}, title = {Association of high-intensity evening light exposure with risk of incident age-related macular degeneration, cataract, and glaucoma: a prospective cohort study of 82,826 participants.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {42230852}, issn = {2509-2723}, abstract = {Excessive artificial light at night (ALAN) disrupts circadian rhythms and may accelerate ocular aging; however, personal objective dosimetry data linking evening light exposure to specific age-related eye diseases (AREDs) remain sparse. The objective of the study is to determine whether personal high-intensity light exposure during the evening transition window (20:00-23:30) is associated with the risk of incident age-related macular degeneration (AMD), cataracts, and glaucoma. This prospective cohort study utilized data from the UK Biobank. Participants (n = 82,826) were monitored for 7 days via wrist-worn accelerometers equipped with high-resolution light sensors between 2013 and 2015. Individuals with baseline eye diseases were excluded. Average light intensity (lux) during the evening transition period (20:00-23:30) was categorized by percentiles (top 10% threshold ≈1000 lx). Incident AMD, cataract, and glaucoma were identified through linked hospital inpatient records and death registries using ICD-9 and ICD-10 codes. Among 82,826 participants, 6058 incident ARED cases occurred during a median follow-up of 7.85 years. Evening light exposure exceeding 1000 lx (top 10%) was significantly associated with increased hazards of incident AMD (HR, 1.31; 95% CI, 1.06-1.62), cataract (HR, 1.18; 95% CI, 1.08-1.30), and primary open-angle glaucoma (POAG) (HR, 1.47; 95% CI, 1.07-2.03). Significant time-response relationships were observed, with per-hour exposure to > 2250 lx further elevating the risk of overall AREDs (HR, 1.10; 95% CI, 1.04-1.16) and POAG (HR, 1.18; 95% CI, 1.04-1.35). High-intensity artificial light in the evening is an independent, modifiable risk factor for major ocular aging pathologies.}, }
@article {pmid42223803, year = {2026}, author = {Servin, AE and McFadden, I and Esmaeilkhanian, H and Holcomb, D and Lin, J and Awh, CC}, title = {Real-World Utilization and Initial Experience with Aflibercept-ayyh (PAVBLU[®]) for Retinal Disorders in United States Retina Practices: A Descriptive Retrospective Analysis.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42223803}, issn = {2193-8245}, abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) therapies are standards of care for vision-threatening retinal diseases. This retrospective observational study describes demographics, utilization, best recorded visual acuity (BRVA), and safety among eyes with neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), or retinal vein occlusion (RVO) treated with the biosimilar aflibercept-ayyh (PAVBLU[®]) in routine clinical practice.<br><br>METHODS: Electronic medical records from the Retina Consultants of America database of patients receiving aflibercept-ayyh (12/1/2024-10/31/2025) were analyzed, focusing on eyes with &#x2265;&#x2009;84&#xa0;days of follow-up. The index date was defined as the first documented aflibercept-ayyh injection. Post-index data were used to evaluate treatment patterns, changes in BRVA, and adverse events of special interest (AESIs). Within-eye changes in BRVA were assessed using the Wilcoxon signed rank test and summarized as mean change in logarithm of the minimum angle of resolution (&#x394;logMAR).<br><br>RESULTS: A total of 1000 consecutive eyes from 989 patients (55% female, 43% male, 2% unknown) received 3730 injections of aflibercept-ayyh; 91% switched from prior anti-VEGF therapy and 9% were anti-VEGF treatment-na&#xef;ve. Disease distribution was 58% nAMD, 19% RVO, 16% DME, and 7% DR. Among switchers, median (IQR) number of prior injections was 21 (8,&#xa0;46). Median (IQR) follow-up was 6.0&#xa0;months (4.6,&#xa0;7.1). Median (IQR) number of aflibercept-ayyh injections per eye was 4 (3,&#xa0;5). Among eyes with &#x2265;&#x2009;84&#xa0;days of follow-up (n&#x2009;=&#x2009;889), mean BRVA logMAR remained stable for switchers (0.4&#xa0;to&#xa0;0.4; P&#x2009;=&#x2009;0.96) and improved from baseline in anti-VEGF-na&#xef;ve eyes (0.5&#xa0;to&#xa0;0.4; P&#x2009;<&#x2009;0.01). Confirmed AESIs included iritis (n&#x2009;=&#x2009;2; 0.05% of injections), with no events of vitreous cells, endophthalmitis, retinal detachment, retinal vasculitis, or vitreous hemorrhage.<br><br>CONCLUSION: In this descriptive real-world analysis, aflibercept-ayyh was associated with stable visual acuity in previously treated eyes and vision improvement in treatment-na&#xef;ve eyes, with no new or unexpected safety findings, consistent with expectations for aflibercept and the established body of evidence supporting biosimilarity between aflibercept-ayyh and reference aflibercept, EYLEA[&#xae;]).}, }
@article {pmid42224684, year = {2026}, author = {Nadar, D and Shende, P}, title = {Unveiling the Potential of Drug Delivery Systems for Tyrosine Kinase Inhibitors in the Treatment of Neovascular Eye Diseases.}, journal = {Critical reviews in therapeutic drug carrier systems}, volume = {43}, number = {2}, pages = {61-123}, doi = {10.1615/CritRevTherDrugCarrierSyst.2026060256}, pmid = {42224684}, issn = {2162-660X}, abstract = {Tyrosine kinase inhibitors (TKIs) represent a promising category of therapeutic agents for managing edema and neovascular eye diseases (NEDs) such as corneal neovascularization, proliferative diabetic retinopathy and neovascular age-related macular degeneration. By impeding the phosphorylation of receptor tyrosine kinases, TKIs prevent the activation of angiogenic signaling pathways that are vital for cell growth and proliferation. However, the TKIs delivery in ophthalmology presents significant challenges such as toxicity and poor bioavailability. This review discusses emerging TKIs for NEDs, their physicochemical properties, and delivery systems, highlighting strategies such as sustained-release ocular implants, hydrogels, particulate and composite systems. Amid each category, we explore groundbreaking research approaches with a focus on preclinical and clinical studies, providing an in-depth look at the latest advancements in TKI-based delivery systems. Numerous TKI formulations currently under investigation (AXPAXLI, DURAVYU, CLS-AX and D-4517.2) hold the potential to improve therapeutic outcomes and enhance patient adherence, transforming the treatment landscape of NEDs. Advanced TKI delivery platforms, integrated with artificial intelligence-driven tools and minimally invasive technologies may enable more effective and personalized treatment options in the field of eye care.}, }
@article {pmid42225822, year = {2026}, author = {Sun, H and Bu, F and Xin, X and Yan, J and Huang, T}, title = {Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42225822}, issn = {1476-5454}, abstract = {OBJECTIVES: To identify drug-associated risk signals for neovascular age-related macular degeneration (nAMD) and explore their biological basis.<br><br>METHODS: We analysed the US FDA Adverse Event Reporting System (FAERS) to detect drugs with disproportionate nAMD reporting. Drug targets were mapped and causality was assessed by integrating summary-based Mendelian randomisation (SMR) and colocalisation analyses using cis-pQTL data. Single-cell RNA sequencing from nAMD patients evaluated cell type-specific gene expression. Protein-protein interaction and pathway enrichment analyses elucidated underlying mechanisms.<br><br>RESULTS: FAERS analysis identified five drugs (apixaban, carbamazepine, latanoprost, rituximab and semaglutide) significantly associated with higher reporting risks of nAMD. SMR implicated six genes (IGFBP6, MAPKAPK2, NFKB1, RGMA, RNASE1 and WARS1) in nAMD risk, with evidence supporting colocalisation for WARS1. Most candidate genes were predominantly expressed in vascular remodelling endothelial cells, while WARS1 was also highly specific to monocytes. Enrichment analysis highlighted their critical involvement in immune and inflammatory responses, particularly within the Toll-like receptor, TNF and NF-kappa B signalling pathways.<br><br>CONCLUSIONS: This study suggests a potential association between specific drugs and nAMD and reveals six genes as their possible molecular basis, thereby providing prioritised candidate targets and testable biological hypotheses for subsequent experimental validation.}, }
@article {pmid42226100, year = {2026}, author = {He, B and Chen, Y and Cai, P and Xi, R and Shen, X and Guo, S and Chen, J and Li, S and Wu, Y}, title = {Exendin-4 averts all-trans-retinal-driven damage to photoreceptors and the retina via the GLP-1R/PKA/CREB1 signaling axis.}, journal = {Cellular &amp; molecular biology letters}, volume = {}, number = {}, pages = {}, doi = {10.1186/s11658-026-00952-6}, pmid = {42226100}, issn = {1689-1392}, support = {82471093//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Atrophic macular degeneration comprises dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). These disorders lead to irreversible blindness and still lack effective therapies. The rise of all-trans-retinal (atRAL) brought on by visual cycle disruption closely links to retinal atrophy in both conditions, yet the key downstream targets remain obscure. Exendin-4 (EX-4) is a natural glucagon-like peptide-1 receptor (GLP-1R) agonist. Recent clinical retrospective studies indicate that GLP-1R agonists such as exenatide (synthetic EX-4) can markedly lower the 5-year risk of developing dry AMD. Here, we sought to clarify the protective effect of natural EX-4 against retinal degeneration in atrophic macular degeneration linked to impaired clearance of atRAL.<br><br>METHODS: Cell and animal paradigms of STGD1 and dry AMD were generated by atRAL-loaded 661W cells and light-exposed Abca4[-/-]Rdh8[-/-] mice, respectively. RNA-sequencing, cell viability assays, morphometric analysis, annexin V/propidium-iodide staining using flow cytometry, quantitative polymerase chain reaction (qPCR), western blotting, immunofluorescence, electroretinography (ERG), fundus photography, hematoxylin and eosin (H&amp;E) histology, and TUNEL staining were integrated to delineate the anti-apoptotic actions of EX-4 and to uncover its underlying protective mechanism.<br><br>RESULTS: GLP-1R/cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)/cAMP response element-binding protein 1 (CREB1) signaling was markedly downregulated in atRAL-challenged 661W cells and in neural retina of light-exposed Abca4[-/-]Rdh8[-/-] mice. EX-4 reinstated this pathway, suppressed caspase-3 activation and DNA damage, and curtailed apoptosis in both cell and tissue contexts. Silencing of Glp1r or the PKA catalytic subunits by small interfering RNA (siRNA) abrogated EX-4-induced activation of the PKA/CREB1 axis in atRAL-loaded 661W cells. Pharmacologic blockade of CREB1 phosphorylation with the PKA inhibitor H-89 or the CREB1 inhibitor 666-15 largely nullified the DNA-protective and anti-apoptotic benefits conferred by EX-4 in 661W cells following atRAL exposure, suggesting that the GLP-1R/PKA/CREB1 signaling axis contributes to its cytoprotection action. More importantly, intraperitoneal injection of EX-4 significantly preserved retinal structure and function in Abca4[-/-]Rdh8[-/-] mice after exposure to light, and mitigated punctate lesions in the fundus.<br><br>CONCLUSIONS: EX-4 exerted anti-apoptotic and DNA-protective effects against atRAL-induced photoreceptor loss and retinal degeneration at least partially through activating the GLP-1R/PKA/CREB1 pathway. These findings suggest that GLP-1R agonists could serve as potential preventive therapeutics for atrophic macular degeneration associated with atRAL toxicity, including dry AMD and STGD1.}, }
@article {pmid42227867, year = {2026}, author = {Palladino, L and Paglia, L and Meschiari, G and Altieri, F and Cesa, S and Iazzetti, A and Cairone, F}, title = {Structural and thermal stability assessment of repackaged bevacizumab using RT-PCR-based differential scanning fluorimetry and intrinsic fluorescence spectroscopy.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {}, number = {}, pages = {10781552261457538}, doi = {10.1177/10781552261457538}, pmid = {42227867}, issn = {1477-092X}, abstract = {IntroductionBevacizumab is a humanized monoclonal anti-VEGF antibody widely used in oncology and ophthalmology for the treatment of age-related macular degeneration and diabetic macular edema. Its intravitreal administration requires galenic repackaging, raising concerns regarding physicochemical stability and sterility assurance during storage. This study evaluated the structural and thermal stability of repackaged bevacizumab stored at 4 °C for up to four weeks.MethodsStability was assessed using intrinsic fluorescence spectroscopy and differential scanning fluorimetry (DSF) performed on a real-time PCR platform. Structural integrity was monitored through fluorescence emission spectra, while thermal stability was determined by melting temperature (Tm) analysis over time.ResultsIntrinsic fluorescence showed a constant emission maximum at 338 nm throughout the storage period, indicating preservation of the tertiary structure. DSF analysis demonstrated stable thermal unfolding profiles, with no significant variation in Tm values between baseline (67.4 ± 0.3 °C) and four weeks (67.2 ± 0.4 °C; p > 0.05).ConclusionsRepackaged bevacizumab maintained structural integrity and thermal stability for up to four weeks under refrigerated storage conditions. These findings support refrigerated batch preparation under the tested conditions and highlight RT-PCR-based DSF as a practical quality-control tool for hospital pharmacy settings.}, }
@article {pmid42227873, year = {2026}, author = {Karl, NAM and Schuhmayer, AC and Pomberger, L and Eidherr, M and Khalil, H and Kallab, M and Rothbächer, J and Strohmaier, C and Huemer, J and Bolz, M and Reisinger, AS}, title = {Difference in Ocular Perfusion Drop After Intravitreal Aflibercept in Patients with Neovascular AMD and Diabetic Macular Edema.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/02713683.2026.2679143}, pmid = {42227873}, issn = {1460-2202}, abstract = {PURPOSE: Vascular endothelial growth factor (VEGF) is a factor in the pathogenesis of Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME), yet they differ in pathogenesis. It has been shown that only patients with diabetic retinopathy have elevated VEGF levels in the aqueous humor. Intravitreal injections of anti-VEGF substances have been the gold standard in treating diseases for several years, but an impact on ocular perfusion has been assumed. This study aimed to investigate the effects of intravitreal aflibercept injection (IVI) on ocular perfusion in patients with AMD and DME.<br><br>METHODS: This prospective study included 36 eyes of 36 patients, with 18 patients having nAMD (n&#x2009;=&#x2009;18) and 18 patients having DME (n&#x2009;=&#x2009;18), all treated with IVI. Ocular perfusion was measured using Laser Speckle Flowgraphy (LSFG). The parameter Mean Blur Rate (MBR) reflects erythrocyte flow velocity and serves as an indirect marker of perfusion. MBR was measured at the optic nerve head (ONH). The device's software can analyze MBR in areas of major retinal vessels (MV) and in microperfusion areas of the tissue (MT). Measurements were conducted at three time points (before scheduled IVI, as well as 1&#x2009;week and 4&#x2009;weeks after).<br><br>RESULTS: In patients with AMD, significant decrease in MV was observed, while no significant change was noted for MV in patients with DME (Analysis of Variance, ANOVA, p&#x2009;=&#x2009;0.04 vs. p&#x2009;=&#x2009;0.2). However, both groups showed a significant decrease in MT (ANOVA, p&#x2009;<&#x2009;0.001 for both groups).<br><br>CONCLUSION: The results indicate that retinal perfusion as measured with LSFG is less impaired in patients with DME following IVI treatment. This could be related to endothelial dysfunction, which appears to be restricted to retinal endothelial cells, as MT as a surrogate marker of choroidal perfusion showed a significant reduction in the DME group. Responses highlight physiological differences between retinal and choroidal capillaries.}, }
@article {pmid42229813, year = {2026}, author = {Cai, CX and Toy, B and Martin, B and Fan, R and Westlund, E and Tran, D and Nishimura, A and Lee, H and Leng, T and Nagy, P and Mathioudakis, N and Zhang, L and Hribar, M and Chen, A and Armbrust, K and Goetz, K and Baxter, S and Boland, MV and Brown, EN and Tsui, E and Barkmeier, AJ and Wang, S and Mehta, N and Stocking, JC and O'Keefe, G and Lee, CS and Payne, PRO and O'Brien, WJ and DuVall, S and Alshammari, T and Falconer, T and Dorr, DA and Humes, I and McCoy, D and Adibuzzaman, M and Mahmood, R and Morgan-Cooper, H and Desai, P and Kothari, SY and Sena, A and Blacketer, C and Ostropolets, A and Shoaibi, A and Rao, G and Hripcsak, G and Ryan, P and Suchard, MA}, title = {Semaglutide and Neovascular Age-Related Macular Degeneration Among Adults with Type 2 Diabetes: An OHDSI Network Study.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.05.034}, pmid = {42229813}, issn = {1549-4713}, abstract = {OBJECTIVE: or Purpose: To investigate the potential association of semaglutide and neovascular age-related macular degeneration (NVAMD) DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network during the study period from 12/1/2017-12/31/2024 SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Adults with type 2 diabetes (T2D) on semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs) (dulaglutide, exenatide), or non-GLP-1RAs (empagliflozin, sitagliptin, glipizide) METHODS, INTERVENTION OR TESTING: The association between semaglutide and NVAMD was assessed using two approaches: an active-comparator cohort design and a self-controlled case-series (SCCS) analysis. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates.<br><br>MAIN OUTCOME MEASURES: Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) or condition codes and procedures (NVAMD-CP).<br><br>RESULTS: A total of 227,971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to users of dulaglutide (NVAMD-C HR 0.57, 95% CI 0.21 to 1.57, P=.28; NVAMD-CP HR 0.25, 95% CI 0.05 to 1.27, P=.10), empagliflozin (NVAMD-C HR 0.98, 95% CI 0.54 to 1.79, P=.94; NVAMD-CP HR 0.79, 95% CI 0.38 to 1.64, P=.52), sitagliptin (NVAMD-C HR 2.08, 95% CI 0.90 to 4.83, P=.09; NVAMD-CP HR 1.80, 95% CI 0.55 to 5.86, P=.33), and glipizide (NVAMD-C HR 0.83, 95% CI 0.35 to 2.02, P=0.69; NVAMD-CP HR 0.50, 95% CI 0.21 to 1.19, P=.12). There was no evidence of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: incidence rate ratio [IRR] 0.92, 95% CI 0.67 to 1.26, P=.60; NVAMD-CP IRR 1.02, 95% CI 0.76 to 1.36, P=.92) nor any of the other GLP-1RA or non-GLP-1RAs.<br><br>CONCLUSIONS: We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D.}, }
@article {pmid42229850, year = {2026}, author = {Hallaj, S and Nishida, T and Kamalipour, A and Longhurst, CA and Freeman, WR and Baxter, SL and Boussina, A}, title = {Glucagon Like Peptide 1 Receptor Agonists and Age-Related Macular Degeneration Incidence.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.05.016}, pmid = {42229850}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes.<br><br>DESIGN: Retrospective, propensity score-matched cohort study.<br><br>PARTICIPANTS: Adults with diabetes initiating a GLP-1RA or another non-insulin antidiabetic agent. In Epic Cosmos, 2,797,686 GLP-1RA users were matched 1:1 to 2,797,686 active comparators.<br><br>METHODS: We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-vascular endothelial growth factor treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models.<br><br>MAIN OUTCOME MEASURES: Incident any AMD and incident nAMD.<br><br>RESULTS: In the matched Epic Cosmos cohort (total N=5,595,372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% CI, 0.182%-0.192%] vs 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs 6.540% [95% CI, 6.017%-7.108%]); all P<.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs 0.065%), 5 years (0.280% vs 0.340%), and 10 years (1.874% vs 2.393%); all P<.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P<.001) and was not associated with increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P=.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups.<br><br>CONCLUSIONS: Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes.}, }
@article {pmid42218984, year = {2026}, author = {Hyttinen, JMT and Salminen, A and Kauppinen, A and Kaarniranta, K}, title = {The role of Wnt signalling in the pathogenesis and therapy of age-related macular degeneration (AMD).}, journal = {Biochemical pharmacology}, volume = {}, number = {}, pages = {118114}, doi = {10.1016/j.bcp.2026.118114}, pmid = {42218984}, issn = {1873-2968}, abstract = {Age-related macular degeneration (AMD) is an ever-increasing disease which affects the vision of the elderly in the Western world. No preventive therapy exists so far and slowing its progression is only possible for a fraction of the cases, namely neovascular AMD, in which neovascularisation sprouts from the choriocapillaris layer into the retina. Nevertheless, one potential target for modulation as an AMD therapy is the manipulation of Wnt signalling, and especially its canonical type, the Wnt/β-catenin pathway. Wnt signalling is one of the fundamental cellular pathways involved e.g. in morphogenesis, proliferation, cell polarity, tissue maturation, as well as homeostasis, and apoptosis. The rationale of modulating Wnt signalling in AMD therapy, is that weakened autophagy, autophagy, the means of the cell to remove waste material, as well as increased epithelial-mesenchymal cell type transition (EMT), inflammation, and oxidative stress response have been detected in AMD. Corresponding to these, the upregulation of Wnt signalling pathway has been discovered to be related to this disease. Thus, inhibition of Wnt signalling could be used as in therapy, especially in the more common, dry form of AMD in all its stages. On the other hand, the activation of Wnt signalling could be used in the therapy of advanced neovascular AMD, primarily for maintaining the blood-retinal barrier, which preserves the homeostasis of the retinal vasculature. Therefore, several approaches concerning both the inhibition and upregulation of Wnt signaling are discussed in this review, in the context of potentially developing effective therapies against AMD in the future.}, }
@article {pmid42219076, year = {2026}, author = {Mikhail, D and Tao, BK and Yu, P and Calicchia, L and Butt, FR and Dhivagaran, T and Al-Qattan, HM and Feo, A and Quarta, A and Mishra, AV and Seamone, ME and Navajas, EV and Kertes, PJ and Wong, DT and Muni, RH and Kaplan, AJ and Yan, P and Popovic, MM}, title = {Risk of Retinal Detachment After Intravitreal Injection of Anti-VEGF: A Systematic Review and Meta-Analysis.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.05.042}, pmid = {42219076}, issn = {1879-1891}, abstract = {TOPIC: This systematic review and meta-analysis evaluated the literature-pooled risk of retinal detachment (RD) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>CLINICAL RELEVANCE: Intravitreal anti-VEGF injections are the most frequently performed intraocular procedure, with RD remaining a poorly quantified complication. Pooled estimates equip clinicians to contextualize RD risk during informed consent.<br><br>METHODS: This systematic review and meta-analysis followed PRISMA guidelines (PROSPERO: CRD420251175527). MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 18, 2026. Included studies reported RD risk after anti-VEGF IVI for neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema from retinal vein occlusion, proliferative diabetic retinopathy, or myopic choroidal neovascularization. Paired reviewers independently extracted data and assessed risk of bias using ROBINS-I and the Joanna Briggs Institute checklist for case series. A random-effects single-arm meta-analysis of proportions using a generalized linear mixed model generated pooled risk estimates per injection and per eye.<br><br>RESULTS: Twelve studies comprising 834,814 injections and 119 RD events were included. In the meta-analysis of 9 studies (787,849 injections), there were 92 rhegmatogenous RD (RRD) events, with a pooled risk of 0.012% [95% CI (0.009-0.015%), I&#xb2;: 14.4%], equivalent to 1 in 8675 injections. An acute &#x2264;90-day postprocedural sensitivity analysis yielded a consistent RRD risk of 0.013% [95% CI (0.010-0.016%), I&#xb2;: 36.8%] (approximately 1 in 7692 injections). An eye-level sensitivity analysis yielded a per-eye risk of 0.08% [95% CI (0.02-0.31%), I&#xb2;: 66.7%] (approximately 1 in 1250 eyes). Exploratory subgroup analyses showed no differences in RRD risk by injection number (&#x2265;100,000 vs. <100,000; P=0.520), study setting (single-center vs. multicenter; P=0.258), injection indication (nAMD only vs. mixed; P=0.061), injection provider (ophthalmologist vs. mixed; P=0.259), or risk of bias (P=0.356). One study evaluating severe PDR reported tractional RD risk as 3.6% [95% CI (2.3-5.2%)] (approximately 1 in 28 injections), likely reflecting disease-specific fibrovascular contraction.<br><br>CONCLUSION: Low-certainty evidence indicates RRD following anti-VEGF IVI is uncommon, with a per-injection risk of 0.012% (1 in 8675 injections). Per-eye risk was 0.08% (1 in 1250 eyes), which was subject to wider uncertainty but more relevant to patients undergoing long-term treatment; notably, the pooled mean of 13.8 injections per eye in the contributing studies likely underestimates real-world cumulative exposure. Future work should incorporate eye-level denominators and standardized reporting of RD subtypes, ocular characteristics, and injection technique to enable risk stratification and identification of modifiable procedural contributors.}, }
@article {pmid42219104, year = {2026}, author = {Maiti, S and Joseph, J}, title = {From Systemic Disease to the Eye: Why Senescence Deserves Attention in Ocular Infections.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111095}, doi = {10.1016/j.exer.2026.111095}, pmid = {42219104}, issn = {1096-0007}, abstract = {The global increase in life expectancy has led to a growing elderly population, bringing new challenges in managing infectious diseases. Advancing age is accompanied by progressive dysfunction of both innate and adaptive immunity, resulting in impaired responses to pathogens and elevated morbidity and mortality. Cellular senescence, a state of permanent cell-cycle arrest with extensive molecular and phenotypic changes, including chromatin remodeling and the senescence-associated secretory phenotype (SASP), has emerged as a key factor in this process. Though initially protective as a tumor-suppressive mechanism, senescence becomes maladaptive with age, contributing to inflammaging, immune dysregulation, and heightened susceptibility to infection. In ocular diseases, such as age-related macular degeneration and chronic keratitis, senescent cells in retinal pigment epithelium and corneal tissues drive persistent inflammation and fibrosis, exacerbating vulnerability to opportunistic pathogens. Pathogens can exploit senescent cells through virulence factors and persistent inflammatory responses, thereby promoting chronic infection and even age-related diseases. Conversely, senescent cells and their SASP can intensify infection severity, as shown in viral infections such as SARS-CoV-2 and bacterial pathogens including Streptococcus pneumoniae and Mycobacterium tuberculosis. This reciprocal relationship illustrates how infection accelerates cellular aging while aging predisposes individuals to more severe infections. Emerging therapeutic strategies targeting senescence, including senolytics and senomorphics, hold promise for mitigating infection-related pathology. In parallel, vaccines and immunotherapies tailored to the aging immune system will be crucial for reducing infection burden in older populations. This review integrates current evidence on the bidirectional interplay between senescence and infection, emphasizing its clinical relevance and potential for translational intervention.}, }
@article {pmid42221036, year = {2026}, author = {Zhu, Y and Gumustop, SS and Wang, L and Tong, A and Ding, X and Ploumi, I and Romano, F and Chen, C and Nodecker, KN and Shah, SH and Wagner, SL and Vavvas, DG and Husain, D and Miller, JW and Patel, NA and Kim, LA and Wu, DM and Miller, JB}, title = {Influence of Anti-VEGF Injections on Longitudinal Changes in Vascular Metrics Measured by OCTA in Age Related Macular Degeneration: A Retrospective Real-World Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {561121}, pmid = {42221036}, issn = {1177-5467}, abstract = {PURPOSE: To investigate the possible influence of repeated anti-VEGF injections on vascular metrics measured by optical coherence tomography angiography (OCTA) in patients with age-related macular degeneration (AMD).<br><br>METHODS: This retrospective longitudinal study included AMD patients with a follow-up time of at least 18 months from 2019 to 2024. Swept-source OCTA was performed on all eyes. Based on whether an eye received injections or not during follow-up, all eyes were divided into two groups (non-injection group only included non-exudative AMD). Vessel density, Vessel skeleton density in the superficial, deep, and retina slab, as well as foveal avascular zone (FAZ) size, circularity and perimetry of Angio 6mm&#xd7;6mm were calculated. Change in vascular metrics between baseline and last follow-up were compared between the two groups using t-test or Mann-Whitney U-test. Correlation between change in vascular metrics and visual acuity was investigated by Spearman's Rank Correlation test.<br><br>RESULTS: A total of 164 eyes from 107 patients were included. The average follow-up time was 34 months. No statistically significant difference in baseline vascular metrics was detected between the injection group (57 eyes) and non-injection (107 eyes) group. The injection group received 12.56 injections during follow-up. Among all the parameters, only change in FAZ size during follow-up showed a statistically significant difference between the two groups (0.03 vs. 0.02 mm[2], P=0.043). No correlation was found between change in vascular metrics and change in visual acuity (P>0.05).<br><br>CONCLUSION: In this retrospective longitudinal study of 164 eyes, repeated intravitreal anti-VEGF injections were associated with no relevant significant changes in OCTA vascular metrics over time.}, }
@article {pmid42221039, year = {2026}, author = {Swarnkar, PK and Singh Bhangu, J and Stewart, C and Rifat, M and Khalid, S and Winkworth, H and Franklin-Goddard, SL and Awad, MH and Williams, GS}, title = {Challenging the Treatment Threshold: Early Faricimab Prevents Vision Loss in nAMD - A Real-World Welsh Experience.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {604687}, pmid = {42221039}, issn = {1177-5467}, abstract = {PURPOSE: To compare real-world outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients initiated on Faricimab at early (<0.3 logMAR) versus late (0.6-0.7 logMAR) visual thresholds.<br><br>METHODS: Retrospective, single-centre cohort study of 97 patients (53 early, 44 late) treated at a UK centre, with three monthly loading doses followed by treat-and-extend. Outcomes: BCVA change, vision loss (&#x2265;5 letters), stable vision at 6/12/18 months, injection intervals, extension >8&#xa0;weeks, dry macula.<br><br>RESULTS: Baseline VA was 74 &#xb1; 3.5 letters (early) vs 54 &#xb1; 2.0 letters (late), p<0.001. No early patient experienced sustained vision loss at 6, 12, or 18 months compared with 76.7%, 73.3%, and 75.0% of late patients, respectively (p<0.05 for all). At the 7th injection, 67.6% of late patients lost &#x2265;5 letters vs 14.9% of early patients (ARR 52.7%, p<0.001). Cumulatively, 81.8% of late patients experienced &#x2265;5-letter loss vs 41.5% of early patients (ARR 40.3%, NNT 3, p<0.001). Mean injection intervals were similar, but the early cohort sustained extension beyond 8&#xa0;weeks in >50% of eyes from the 4th-5th interval onward. In contrast, the late cohort exhibited a biphasic collapse, with extension rates declining from 62.2% at 6th-7th to only 35.0% by 9th-10th. Despite a significant baseline anatomical disadvantage (18.9% vs 50.0% dry macula, p=0.001), the early cohort achieved 100% dryness by 18 months compared with 96.7% in the late cohort, with crossover occurring by 12 months (95.8% vs 89.7%, p=0.269).<br><br>CONCLUSION: In this retrospective, single-centre study, early faricimab initiation was associated with preservation of high-function vision, a lower risk of clinically significant vision loss, and high rates of anatomical quiescence and durable treatment extension. These findings suggest that proactive early intervention may offer advantages over reactive treatment paradigms, although confirmation in larger, prospective, and multi-centre studies is needed.}, }
@article {pmid42221729, year = {2026}, author = {Zhao, AH and Alam, TA and Das, N and Maatouk, C and Singh, RP and Talcott, KE}, title = {Long-Term Predictive Value of Macular Thickness Fluctuations in Response to Anti-VEGF Treatment for Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261448432}, pmid = {42221729}, issn = {2474-1272}, abstract = {Purpose: To evaluate whether macular thickness fluctuations are predictive of long-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) after treatment initiation with antivascular endothelial growth factor (anti-VEGF). Methods: Patients with nAMD treated with anti-VEGF intravitreal injections for 3 and 5 years were evaluated. Anatomic parameters, including central subfield thickness (CST), were evaluated with optical coherence tomography. The cohort was segregated into quartiles based on CST variability over the initial 12 months of treatment. Kruskal-Wallis tests were used to compare 3- and 5-year final best-corrected visual acuity (BCVA), change in BCVA, final CST, and change in CST among quartiles. Multiple linear regression analyses were subsequently performed. Results: Three hundred sixty-six eyes were included in the 3-year analysis and 275 eyes in the 5-year analysis. Patients received an average of 8.4 injections over 12 months and had a final mean BCVA of 60.7 Early Treatment Diabetic Retinopathy Study letters. Those with the greatest CST variability demonstrated significantly lower baseline and final BCVA compared with other quartiles, alongside lower baseline BCVA values. No difference was found between quartiles for final CST and change in BCVA. Multiple linear regression analyses demonstrated that macular thickness variability characterized by the standard deviation of CST, baseline VA, and age was a significant predictor of VA after 3 and 5 years. Conclusions: Macular thickness variability was a statistically significant correlate and limited predictor of long-term response to visual outcomes at 3 and 5 years after anti-VEGF initiation. Macular thickness variability may be a biomarker with limited long-term predictive value in patients with nAMD.}, }
@article {pmid42221733, year = {2026}, author = {Salabati, M and Mallepally, A and Farhani, K and Mahmoudzadeh, R and Brar, V and Randolph, J}, title = {The Effect of Acetylcholinesterase Inhibitors and N-Methyl-D-Aspartate Receptor Antagonists on the Risk of Development and Progression of Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261450196}, pmid = {42221733}, issn = {2474-1272}, abstract = {Purpose: To investigate whether memantine or acetylcholinesterase inhibitors are associated with reduced risk of developing age-related macular degeneration (AMD) and of progression from nonexudative to exudative AMD. Methods: This retrospective cohort study used data from the TriNetX US Collaborative Network between 2008 and 2023. Adults 50 years and older were included and categorized into AMD-naïve and dry AMD cohorts. Exposure groups were defined by outpatient prescriptions for acetylcholinesterase inhibitors (donepezil, rivastigmine, or galantamine) or memantine. Each exposure group was propensity score-matched 1:1 to unexposed controls based on demographic and clinical characteristics. Outcomes were incident AMD in the AMD-naïve cohort and incident exudative AMD in the dry AMD cohort at least 1 year after the prescription. Risk ratios (RRs) and 95% CIs were estimated, and memantine was compared with acetylcholinesterase inhibitors in a head-to-head analysis. Results: Among AMD-naïve patients, acetylcholinesterase inhibitor use (n = 35 397) and memantine use (n = 13 576) were associated with lower AMD incidence compared with matched controls (RR, 0.490; 95% CI, 0.442-0.543; P < .001; and RR, 0.532; 95% CI, 0.448-0.630; P < .001, respectively). In patients with dry AMD, both acetylcholinesterase inhibitors and memantine were associated with reduced progression to exudative AMD (RR, 0.448; 95% CI, 0.357-0.562; P < .001; and RR, 0.552; 95% CI, 0.362-0.842; P = .005). In head-to-head comparisons, similar risks for incident AMD were seen with memantine and acetylcholinesterase inhibitors (RR, 0.929; 95% CI, 0.762-1.132; P = .46) and progression to exudative AMD (RR, 1.198; 95% CI, 0.720-1.994; P = .49). Conclusions: Memantine and acetylcholinesterase inhibitors were associated with a reduced risk of AMD development and progression. These findings support further investigation into shared neuroprotective pathways and potential drug repurposing.}, }
@article {pmid42222587, year = {2026}, author = {Mercuri, S and Sacu, S and Frank-Publig, S and Schrittwieser, J and Gumpinger, M and Leingang, O and Schmidt-Erfurth, U and Chakravarthy, U and Bogunovic, H and Virgili, G and Reiter, GS}, title = {Fluid Volumes Longitudinal Modeling to Predict Atrophy and Fibrosis in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {6}, pages = {101190}, pmid = {42222587}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the impact of retinal fluid volumes on the development of atrophy and fibrosis in neovascular age-related macular degeneration (nAMD) during routine care.<br><br>DESIGN: Retrospective longitudinal study.<br><br>PARTICIPANTS: Treatment-na&#xef;ve eyes with nAMD from the Vienna Imaging Biomarker Eye Study (2007-2018), initiating anti-VEGF therapy.<br><br>METHODS: Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were automatically quantified on OCT using an approved artificial intelligence algorithm within the 1-, 3-, and 6-mm ETDRS regions. Macular neovascularization (MNV) type and baseline presence of subretinal hyperreflective material (SHRM) were assessed. Fluid volumes were modeled as time-dependent biomarkers using repeated-measure Cox models to evaluate cumulative effects over time on the development of atrophy and fibrosis, with hazard ratios calculated for quartiles (Qs) at each visit. Associations with change in visual acuity (VA) were performed in a subset of eyes with &#x2265;12 months of follow-up.<br><br>MAIN OUTCOME MEASURES: Retinal fluid volumes, development of atrophy and fibrosis, and change in VA.<br><br>RESULTS: A total of 1060 eyes of 998 patients were included. Higher IRF volumes increased the risk of both atrophy and fibrosis (all P < 0.001). Subretinal fluid reduced the risk of atrophy (Q4, P &#x2264; 0.001) and fibrosis (1-mm, P = 0.028) in the 1- and 3-mm regions, but increased the risk of fibrosis in the 6-mm region (P &#x2264; 0.031). Higher PED volumes increased the risk of atrophy in the 6-mm region (P < 0.001), and fibrosis at all locations (P &#x2264; 0.002). Age and baseline presence of SHRM were associated with atrophy (P < 0.001), whereas type 2 and mixed/undefined MNVs were associated with both atrophy (P < 0.001) and fibrosis (P &#x2264;0.004). In 552 eyes, time-related presence of fibrosis was associated with VA decline at all locations (P < 0.001). In all areas, Q4 of IRF was associated with linear VA decline (P <0.001). Larger SRF volumes (Q4) in the 1-mm region were associated with better vision (P <0.05). Higher PED volumes (Q3, Q4) were linked to VA decline at all locations (P < 0.001).<br><br>CONCLUSIONS: Assessment of the cumulative effects of retinal fluid volumes during anti-VEGF therapy using time-dependent biomarker modeling revealed notable associations with risk of atrophy, fibrosis, and VA decline.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42222588, year = {2026}, author = {de Breuk, A and de Jong, S and Bakker, B and Kersten, E and Luttikhuizen, DT and Fauser, S and Klaver, CCW and den Hollander, AI and Hoyng, CB and Lechanteur, YTE}, title = {Geographic Atrophy in Patients with Age-Related Macular Degeneration Is Associated with Rare Variants in Complement Factor H and Complement Factor I.}, journal = {Ophthalmology science}, volume = {6}, number = {6}, pages = {101171}, pmid = {42222588}, issn = {2666-9145}, abstract = {PURPOSE: To describe the phenotype of patients with age-related macular degeneration (AMD) carrying rare genetic variants in the complement factor H (CFH) and complement factor I (CFI) genes.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: Two hundred thirty-four patients with AMD carrying rare variants in CFH (n = 134) and CFI (n = 100) and 234 AMD noncarriers.<br><br>METHODS: Genetic data of patients with AMD from the European Genetic Database were filtered for rare coding and splice-site variants in CFH and CFI. For each carrier, an age-matched (&#xb1;2 years) patient with AMD without rare variants in CFH and CFI (noncarrier) was selected. Phenotypic characteristics on color fundus photographs were graded according to the Rotterdam Classification and compared between carriers and noncarriers by univariate generalized estimating equations with binary logistic regression analyses, applying a Bonferroni correction for multiple comparisons. We performed subanalyses for pathogenic rare variants only, and we analyzed CFH and CFI carriers separately.<br><br>MAIN OUTCOME MEASURES: Phenotypic characteristics on color fundus photographs.<br><br>RESULTS: Geographic atrophy and intermediate AMD, along with features such as predominant drusen type, largest drusen size, and drusen area, were associated with carriership of rare pathogenic variants in CFH (P < 0.001, P = 0.002, P < 0.001, and P < 0.001, respectively). Geographic atrophy and intermediate AMD, along with features such as drusen size, drusen area, and pigmentation, were associated with carriership of rare pathogenic variants in CFI (P = 0.01, P = 0.006, P < 0.001, and P = 0.006, respectively). Furthermore, carriers of rare pathogenic variants in CFH were younger (P < 0.001) and had a lower genetic risk score for common AMD-associated variants compared with noncarriers (mean [standard deviation] genetic risk score 0.83 [1.01] vs. 1.41 [1.21], P = 0.03).<br><br>CONCLUSIONS: In this study, patients with AMD carrying rare variants in CFH and CFI had a more severe drusen phenotype, and a higher frequency of geographic atrophy at a relatively early age. Identifying this distinct phenotype could aid in pinpointing individuals who are more likely to benefit from complement-inhibiting therapies.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42215276, year = {2026}, author = {Guo, X and Chen, Y and Yao, J and Huang, J and Xiong, R and Han, X and Huang, W and Congdon, N and Wang, W}, title = {Trends of blindness and visual impairment in individuals aged 70 and older.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328311}, pmid = {42215276}, issn = {1468-2079}, abstract = {BACKGROUND: The global ageing population has heightened the importance of eye health, yet comprehensive assessments of blindness and vision impairment (BVI) burden among older adults remain limited. Using Global Burden of Disease 2021 data, we analysed trends and disparities in BVI and major eye diseases across 204 countries and territories from 1990 to 2021 among adults aged ≥70 years.<br><br>METHODS: Age-standardised prevalence (ASPR), years lived with disability, and average annual percentage change (AAPC) were estimated for BVI and its leading causes, stratified by age, sex, region and Sociodemographic Index (SDI). Temporal trends were assessed using joinpoint regression.<br><br>RESULTS: Globally, between 1990 and 2021, the number of BVI cases increased 156% (94.5 to 242&#x2009;million) with an AAPC of 0.11%. Women experienced a faster rise in ASPR than men (AAPC 0.16% vs 0.11%). Age-specific analysis revealed divergent trends: prevalence rose in the 70-84&#x2009;age group (peak AAPC 1.02% in 70-74 years) but declined in those &#x2265;85 years (AAPC -0.23% in 85-89 years). With increasing SDI, the prevalence rate for BVI and major blinding eye diseases significantly decreased (p<0.001). Regionally, high-income North America showed the largest ASPR reductions (AAPC -0.30%).<br><br>CONCLUSIONS: Demographic expansion and ageing are the primary drivers of the rise in absolute BVI burden among adults aged &#x2265;70 years since 1990, with persistent inequities across sex and SDI levels. Further country-specific analyses, particularly in settings with limited primary data, will help refine estimates and support future research and service planning.}, }
@article {pmid42215633, year = {2026}, author = {Zhu, J and Zeng, C and Tang, R and Lu, W and Wang, S and Huang, L and Xiong, Z and Deng, A and Zhen, Z and Chen, R and Li, X}, title = {Causal relationship between aspirin use and age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42215633}, issn = {1476-5454}, support = {82220108016//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {OBJECTIVE: Although increasing evidence suggests an association between aspirin use and age-related macular degeneration (AMD), the potential causal relationship between them remains controversial. This study aims to explore the causal genetic association and potential mediators between aspirin use and AMD using Mendelian randomisation (MR) analysis.<br><br>METHODS: A bidirectional, two-sample, two-step MR analysis was performed to assess the potential causal relationships among aspirin use, AMD, and possible mediators. Multivariable MR was additionally performed to estimate the direct effect of aspirin use on AMD after adjusting for mediators. Causal estimates were primarily derived using an inverse variance weighted method. Horizontal pleiotropy, heterogeneity, and stability were evaluated using the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis.<br><br>RESULTS: An MR analysis revealed that aspirin use was associated with an increased risk of both early and dry AMD. A mediation analysis indicated that aspirin use is associated with a lower level of serum low-density lipoprotein cholesterol (LDL-C), an elevated serum apolipoprotein A1 (APOA1) concentration, and an increased risk of early and dry AMD. Multivariable MR analysis further showed that after adjusting for LDL-C and APOA1, the direct effect of aspirin on AMD was attenuated to non-significance.<br><br>CONCLUSION: This study provides robust genetic evidence that aspirin use is associated with an increased risk of early and dry AMD, and demonstrates that this association is fully mediated by decreased serum LDL-C and increased serum APOA1 levels, with no evidence of a direct effect independent of these lipid pathways.}, }
@article {pmid42216114, year = {2026}, author = {Ji, PX and Herman, JE and Sivachandran, N}, title = {Rapid resolution of submacular hemorrhage in neovascular age-related macular degeneration using pneumatic displacement and faricimab.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04978-4}, pmid = {42216114}, issn = {1471-2415}, abstract = {BACKGROUND: Submacular hemorrhage (SMH) is a rare but visually devastating complication of neovascular age-related macular degeneration (nAMD) associated with poor long-term prognosis due to photoreceptor iron toxicity, subretinal fibrosis, and retinal pigment epithelial (RPE) damage. Pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy is an established approach for managing acute SMH; however, the role of faricimab, a novel dual inhibitor of VEGF-A and angiopoietin-2 (Ang-2), in this context has not been previously evaluated.<br><br>CASE PRESENTATION: This study reports the outcomes of PD combined with faricimab injection in a case of a 75-year-old female with acute SMH secondary to nAMD. The patient with dense SMH and a large PED secondary to presumed polypoidal choroidal vasculopathy (PCV) underwent PD with 0.40 mL of sulfur hexafluoride and intravitreal faricimab injection (50 &#xb5;L, 6&#xa0;mg) on the same day as presentation, followed by 5 days of face-down positioning with excellent patient compliance confirmed by verbal verification. Two additional faricimab injections were administered at 4 and 8 weeks, followed by treat-and-extend protocol.<br><br>CONCLUSIONS: The use of timely PD with appropriate head positioning can effectively manage patients with acute large SMH and improve visual outcomes. While the combined approach with serial faricimab injections showed longer-term benefits, the immediate improvement was likely due to mechanical techniques. The potential added benefit of faricimab's dual inhibition mechanism over other anti-VEGF therapies in SMH remains to be investigated through larger, comparative trials.}, }
@article {pmid42217617, year = {2026}, author = {Kaushik, S and Bisen, S and Singh, NK}, title = {Retinal pericytes and their role in proliferative retinopathies.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2026.04.021}, pmid = {42217617}, issn = {1525-2191}, abstract = {Vascular dysfunction and abnormal vascularization are primary characteristics of many proliferative retinopathies. Research on proliferative retinopathies has primarily focused on understanding the role of cells and factors that regulate endothelial cell function in ischemic retinopathies. Pericyte coverage of the retina is deemed essential for the survival of endothelial cells, and recently significant efforts have been made to comprehend the role of pericytes under stress conditions such as diabetes and ischemia. Understanding the significance of retinal pericytes in proliferative retinopathies is essential, particularly because of the often-contradictory findings reported regarding their role in these conditions. This review will not only explore the role of retinal pericytes and their interactions with retinal endothelial cells in physiological vascularization but also highlight its importance in the pathogenesis of retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion. A deeper comprehension of pericyte-endothelial interactions in proliferative retinopathies would aid in diagnosis and the formulation of viable therapeutics to avert vision loss associated with these proliferative retinopathies.}, }
@article {pmid42217724, year = {2026}, author = {Harris, C and Nisar, MA and Amamoo, R and Patel, R and Martin, PM and Jadeja, RN and Thounaojam, MC}, title = {Murine Models of Neovascular AMD Revisited: Mechanistic Pathways, Immune-Metabolic Crosstalk, and the Impact of Aging and Sex.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111094}, doi = {10.1016/j.exer.2026.111094}, pmid = {42217724}, issn = {1096-0007}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Neovascular AMD (nAMD) is characterized by choroidal neovascularization (CNV), vascular leakage, and fibrotic remodeling. Although anti-vascular endothelial growth factor (VEGF) therapy has improved visual outcomes for some patients, emerging findings highlight growing concerns regarding treatment resistance, persistent disease activity, and progression to subretinal fibrosis, which remain major challenges. Growing evidence indicates that nAMD arises from the interplay among metabolic dysfunction, oxidative stress, chronic inflammation, hypoxia signaling, and extracellular matrix remodeling within the outer retina. Disruption of mitochondrial function, lipid handling in the retinal pigment epithelium, complement activation, inflammasome signaling, macrophage immune-metabolic reprogramming, and hypoxia-driven VEGF expression collectively shape angiogenesis and lesion progression. Murine models, including laser-induced CNV, two-stage laser-induced fibrosis, and spontaneous or genetic systems such as JR5558, VLDLR-deficient, and CYP27A1-deficient mice, have provided essential mechanistic insights into these pathways. Aging and biological sex influence metabolism, mitochondrial efficiency, immune responses, hypoxia responsiveness, and wound-healing capacity. However, many widely used experimental models rely on young adult animals and often use a single sex without accounting for sex- or age-based differences, leaving these critical factors understudied and inadequately integrated into preclinical design. This review integrates current mechanistic understanding with a critical evaluation of murine nAMD models and emphasizes the importance of incorporating biological age and sex into experimental systems to improve mechanistic interpretation and translational relevance.}, }
@article {pmid42217973, year = {2026}, author = {Lankry, P and Loewenstein, A and Trivizki, O}, title = {Insights into age-related macular degeneration.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {165-190}, doi = {10.1016/B978-0-443-22212-2.00020-3}, pmid = {42217973}, issn = {0072-9752}, mesh = {Humans ; *Macular Degeneration/epidemiology/therapy/diagnosis ; Risk Factors ; Angiogenesis Inhibitors/therapeutic use ; }, abstract = {Age-related macular degeneration (AMD) is a complex and prevalent ocular condition with significant implications for vision and quality of life in the aging population. This chapter provides a comprehensive exploration of AMD, encompassing its multifactorial pathophysiology, epidemiologic trends, and associated risk factors. A detailed examination of the distinct features and symptoms characterizing neovascular and dry AMD enhances our understanding of the clinical spectrum. Special emphasis is placed on geographic atrophy (GA), an advanced stage of AMD, highlighting its significant impact on visual outcomes. Apart from examining the present diagnostic methods and criteria for AMD, this chapter assesses current therapeutic approaches, with a specific emphasis on antivascular endothelial growth factor (anti-VEGF) treatments. Additionally, the discussion extends to emerging therapies and potential avenues for future research in AMD. Preventative strategies and lifestyle modifications that may influence disease progressions are also reviewed. By consolidating current knowledge, clinical insights, and future prospects, this chapter aims to serve as a valuable resource for clinicians, researchers, and students engaged in the study and management of age-related macular degeneration.}, }
@article {pmid42217980, year = {2026}, author = {Winebrake, JP and Lim, JI}, title = {Retinal imaging and artificial intelligence analysis.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {3-12}, doi = {10.1016/B978-0-443-22212-2.00011-2}, pmid = {42217980}, issn = {0072-9752}, mesh = {Humans ; *Artificial Intelligence ; *Retina/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnostic imaging ; }, abstract = {The retina, uniquely accessible as an extension of the central nervous system, plays a critical role in neurology and ophthalmology. Advances in retinal imaging technologies - including color fundus photography, optical coherence tomography, and OCT angiography - have enabled detailed, noninvasive assessment of ocular and systemic diseases. Artificial intelligence (AI), particularly deep learning, has revolutionized the analysis of these images, facilitating early detection, classification, and prognostication of conditions such as diabetic retinopathy, age-related macular degeneration, optic neuropathies, and inherited retinal diseases. AI applications extend beyond ophthalmology, offering insights into neurologic and cerebrovascular disorders through retinal biomarkers. However, challenges remain regarding dataset bias, generalizability, ethical concerns, and the "black box" nature of AI models. Addressing these limitations, along with integrating multimodal imaging and fostering cross-specialty collaboration, will be pivotal in ensuring that AI technology is adopted effectively and responsibly. The future will be marked by synergistic AI-human workflows to enhance diagnostic accuracy, screening scalability, and personalized patient care. As AI applications evolve, they promise to reshape retinal imaging and its intersection with neurology, expanding opportunities for early intervention and improved outcomes.}, }
@article {pmid42217982, year = {2026}, author = {Jones, BW}, title = {Insights into retinal remodeling in retinal degenerative disease.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {327-339}, doi = {10.1016/B978-0-443-22212-2.00015-X}, pmid = {42217982}, issn = {0072-9752}, mesh = {Humans ; *Retinal Degeneration/pathology/physiopathology ; Animals ; *Neuronal Plasticity/physiology ; *Retina/pathology/physiopathology ; }, abstract = {The retina is a highly organized sensory structure responsible for capturing and processing visual information. Visual computation begins at the first synapse between photoreceptors, bipolar cells, and horizontal cells, before involving amacrine and ganglion cells to generate vision. Retinal degeneration disrupts the precise neural architecture required for vision, initiating a maladaptive process known as retinal remodeling. Photoreceptor degeneration in diseases, like retinitis pigmentosa (RP) and age-related macular degeneration, induces retinal remodeling, but good evidence shows glaucoma and diabetic retinopathy do as well, expanding the clinical significance. Historically, studies relied on histologic measures that assumed photoreceptor degeneration marked disease endpoints. However, retinal remodeling involves extensive structural and functional reorganization across all retinal cell classes, driven by the interdependence between neurons, glia, and the retinal pigment epithelium. Retinal plasticity corrupts normal retinal computations, and recent evidence suggests therapeutic windows close after ∼50% photoreceptor loss. Understanding remodeling mechanisms is critical for effective therapies, as current treatments fail to address the ongoing negative plasticity. Insights from retinal remodeling offer broader implications for neurodegeneration, highlighting the retina as a model for understanding central nervous system diseases like Alzheimer and Parkinson. Advancing knowledge of these processes will be pivotal for developing interventions to preserve vision.}, }
@article {pmid42217985, year = {2026}, author = {Wang, J and Felfeli, T and Ballios, BG}, title = {Stem cell therapy in retinal disease.}, journal = {Handbook of clinical neurology}, volume = {218}, number = {}, pages = {365-385}, doi = {10.1016/B978-0-443-22212-2.00004-5}, pmid = {42217985}, issn = {0072-9752}, mesh = {Humans ; Animals ; *Stem Cell Transplantation/methods ; *Retinal Diseases/therapy/surgery ; Stem Cells/physiology ; }, abstract = {Stem cell therapy presents a new solution to cure degenerative diseases of the retina, which normally have limited ability to regenerate after injury. Stem cells are cells capable of self-renewal and differentiation into more specialized cells, and can be derived from both embryonic and adult sources. This definition encompasses a heterogeneous group of cells possessing varied potency and characteristics. Current attempts in applying stem cell technology to the retina have primarily focused on regenerating the retinal pigment epithelium (RPE) and light-sensing photoreceptor cells. They have not only shown the ability to prevent the death of host photoreceptors, but they can also differentiate into all major retinal cell types to replace lost cells. In vivo experiments, primarily performed in mice, have found that stem cell-derived RPE cells, photoreceptors, and their precursors can survive long-term in animal models without tumorigenicity or immune rejection. Following transplantation, these cells were able to integrate and mature in vivo, forming synapse-like structures with host retinal cells. Furthermore, transplants in mice were able to rescue visual function at a cellular and behavioral level. These promising preclinical results have led to clinical trials testing cell therapy in numerous diseases, including Stargardt macular dystrophy, age-related macular degeneration, retinitis pigmentosa, and central retinal vein occlusion. These trials have demonstrated the safety of cell therapy and have improved visual function in some patients. Scientific advances in the culturing of retinal organoids and the understanding of cell redifferentiation are informing the development of better stem cell therapies, which hold great potential for restoring vision to patients with retinal dystrophies.}, }
@article {pmid42218559, year = {2026}, author = {Zong, Y and Fan, Q and Huang, L}, title = {Biosimilars of anti-VEGF agents in retinal diseases: a narrative review of regulatory, clinical, and pharmacoeconomic aspects.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00872-9}, pmid = {42218559}, issn = {2056-9920}, abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) agents are the cornerstone therapy for retinal vascular diseases including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. With patent expirations of ranibizumab and aflibercept, biosimilars have emerged as cost-effective alternatives. However, vitreoretinal specialists require consolidated evidence on regulatory standards, clinical equivalence, and practical implementation strategies to guide evidence-based integration of biosimilars into clinical practice.<br><br>METHODS: We conducted a narrative review of regulatory documents from the FDA, EMA, and NMPA, as well as Phase III clinical trials, real-world studies, and pharmacoeconomic analyses of approved ophthalmic anti-VEGF biosimilars. Literature searches were performed across PubMed, Embase, and regulatory databases from 2015 to 2025. Studies were included if they reported regulatory approval pathways, clinical efficacy and safety data, interchangeability studies, or pharmacoeconomic evaluations of anti-VEGF biosimilars in retinal diseases.<br><br>RESULTS: Regulatory frameworks demonstrate rigorous biosimilarity assessment through comprehensive analytical characterization, preclinical evaluation, and clinical trials. Pivotal Phase III studies confirm therapeutic equivalence of approved biosimilars (including ranibizumab-nuna and aflibercept-abzv) with comparable visual acuity outcomes, safety profiles, and immunogenicity to originator products. Real-world evidence for ranibizumab biosimilars supports comparable outcomes to originators, while evidence for aflibercept biosimilars remains preliminary and warrants continued pharmacovigilance. Pharmacoeconomic analyses demonstrate 20-40% cost reduction compared to originators, offering substantial healthcare savings and improved patient access. Key implementation considerations include extrapolation principles, switching protocols, and clinic workflow integration.<br><br>CONCLUSIONS: Although real-world data for aflibercept biosimilars are currently limited, emerging evidence for ranibizumab biosimilars supports comparable outcomes. Approved anti-VEGF biosimilars represent safe, effective, and cost-saving alternatives for retinal diseases. With robust analytical and clinical evidence supporting biosimilarity, vitreoretinal specialists can confidently adopt these agents. Successful integration requires understanding of regulatory science, evidence-based switching protocols, and healthcare system collaborations to maximize patient benefits while maintaining treatment standards. Future research should focus on long-term outcomes, broader implementation studies, and pharmacovigilance monitoring.}, }
@article {pmid42206905, year = {2026}, author = {Kayembe-Mulumba, B and Delcourt, C and Delyfer, MN}, title = {Controversial Links Between Cardiometabolic Factors and Age-Related Macular Degeneration: Methodological Perspectives for Future Research.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/02713683.2026.2678294}, pmid = {42206905}, issn = {1460-2202}, abstract = {PURPOSE: Epidemiological studies yielded conflicting results regarding the relationship between cardiometabolic factors and age-related macular degeneration (AMD). However, the methodological characteristics of these studies, which may partly explain this controversy, are not currently addressed. This narrative review aimed to examine current evidence between the six most studied cardiometabolic factors and AMD, focusing on identifying key methodological shortcomings and discussing analytical approaches currently available to address them.<br><br>METHODS: We conducted a rigorous, nonsystematic literature search using targeted MeSH terms and keywords in MEDLINE (PubMed), EMBASE, Web of Science and Scopus, with no language restrictions, up to June 2025. We identified and reviewed epidemiological (cross-sectional, case-control, cohort) studies reporting original data on the six targeted cardiometabolic factors: blood pressure, antihypertensive medications, lipid levels, lipid-lowering medications, diabetes mellitus and antidiabetic treatments. A quantitative synthesis of studies was conducted to describe their methodological characteristics and reported associations.<br><br>RESULTS: Across the 116 reviewed associations, prospective cohorts (41%) and cross-sectional designs (37%) predominated. Most originated from America (35%) and Europe (32%). Lipids (21%) and lipid-lowering agents (20%) were the most frequently studied exposures, while advanced AMD was the predominant outcome (56%). Logistic regression was the main analytic approach (70%), and association conclusions were most often null (42%), followed by increased (36%) and decreased (22%) risk. The most common methodological limitations included cross-sectional study designs, static modeling of dynamic exposures, unaddressed interval censoring, not controlling for confounding by indication, and unstandardized selection of confounders, which are likely to bias the reported associations.<br><br>CONCLUSIONS: Future studies should prioritize robust methodological frameworks, including longitudinal designs, survival bias mitigation, standardized and repeated exposure assessments, distinction between AMD subtypes, propensity scores for medications use, and advanced causal inference techniques wherever feasible. Such an effort is foundational to strengthening the validity and reproducibility of findings linking cardiometabolic factors to AMD, thereby improving AMD prevention strategies.}, }
@article {pmid42207296, year = {2026}, author = {Shaikh, A and Pera, MF}, title = {Cell therapy for age-related macular degeneration.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {37}, number = {1}, pages = {}, pmid = {42207296}, issn = {1432-1777}, mesh = {Humans ; *Macular Degeneration/therapy/pathology/genetics ; Animals ; Retinal Pigment Epithelium/pathology/metabolism ; *Cell- and Tissue-Based Therapy/methods ; }, abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. The disease is caused by deterioration of the retinal pigment epithelium (RPE), a tissue that plays critical roles in the support of the photoreceptors. Cell therapies to replace damaged RPE in the non-exudative form of AMD have been under development for several decades. We review the progress of cell therapy to date and highlight some promising future directions for research in this area.}, }
@article {pmid42207540, year = {2026}, author = {Xiong, R and Tan, S and Li, Y and Li, H and Zhu, Z and Chen, Y and He, M and Chen, S and Wang, W}, title = {Pathologic Myopia Globe Shape and Long-Term Prognosis.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.1561}, pmid = {42207540}, issn = {2168-6173}, abstract = {IMPORTANCE: Three-dimensional (3D) eye shape may play a critical role in predicting long-term structural and functional outcomes in high myopia.<br><br>OBJECTIVE: To determine whether 3D eye shape subtypes defined by high-resolution magnetic resonance imaging (MRI) predict 15-year structural and functional outcomes in high myopia.<br><br>This prospective cohort study involved a subsample of individuals with high myopia (spherical equivalent &#x2264;-6.00 D in both eyes) enrolled in the Zhongshan High Myopia Cohort at a single center in China. Participants underwent biennial ophthalmic examinations over 15 years. Baseline assessments began in August 2011, with biennial follow-ups through September 2025. Data were analyzed from October 2025 through December 2025.<br><br>EXPOSURES: Eye shape was classified into the following 6 categories: spheroidal, ellipsoidal, conical, nasally distorted, temporally distorted, and barrel shaped. Spheroidal and ellipsoidal types were defined as nondeformed and the others as deformed.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcomes were annual axial elongation rate, rapid elongation (&#x2265;0.10 mm/y), macular choroidal thinning (subfoveal choroidal thickness <62 &#xb5;m), progression of myopic macular degeneration (MMD), incidence of posterior staphyloma, visual impairment (best-corrected visual acuity &#x2264;20/40), and visual field defects.<br><br>RESULTS: Of 190 eyes from 95 participants, 152 eyes completed follow-up and were included in the analysis. Of the 152 eyes analyzed, 77 (50.7%) were from female participants, with an overall mean (SD) age of 32.3 (14.1) years. Baseline shapes included spheroidal (83 eyes [54.6%]), nasally distorted (25 [16.4%]), conical (23 [15.1%]), ellipsoidal (11 [7.2%]), temporally distorted (5 [3.3%]), and barrel shaped (5 [3.3%]). Axial elongation followed a morphology-dependent gradient, from slowest in spheroidal eyes (0.045 mm/y) to fastest in nasally distorted eyes (0.095 mm/y). After multivariable adjustment, nasally distorted eyes elongated by 0.050 mm/y (95% CI, 0.020-0.080 mm/y; P&#x2009;=&#x2009;.001) faster and had higher odds of rapid elongation (odds ratio, 5.74; 95% CI, 1.66-19.82; P&#x2009;=&#x2009;.006). Deformed eyes overall had a 7-fold higher risk of macular choroidal thinning (odds ratio, 7.24; 95% CI, 1.77-29.63; P&#x2009;=&#x2009;.006). Nasally distorted and conical eyes showed the greatest risks for both choroidal thinning and MMD progression. For visual field defects, risk was elevated in nasally distorted and conical eyes.<br><br>CONCLUSIONS AND RELEVANCE: Findings from this prospective cohort study suggest that 3D eye shape is an important determinant of long-term outcomes in high myopia. Nasally distorted and conical phenotypes conferred the greatest risks, highlighting the potential value of baseline eye shape stratification for personalized management, risk prediction, or early intervention.<br><br>TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN56368396.}, }
@article {pmid42208846, year = {2026}, author = {Heo, YJ and Bishayee, K and Jhun, JY and Han, SG and Lee, YS and Park, YG and Cho, ML and Park, YS}, title = {Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.}, journal = {Experimental eye research}, volume = {270}, number = {}, pages = {111090}, doi = {10.1016/j.exer.2026.111090}, pmid = {42208846}, issn = {1096-0007}, abstract = {The retinal pigment epithelium (RPE) is the outermost part of the retina, and it is essential for the photoreceptor survival and function. Oxidative stress, aging, accumulation of lipofuscin, and drusen can lead to retinal degenerative diseases such as age-related macular degeneration (AMD). Those stress conditions increase reactive oxygen species (ROS) levels and oxidative stress, which can induce mitochondrial dysfunction and promote RPE cell death during retinal degeneration. We transplanted mitochondria, isolated from C2C12 cells, into cultured RPE cells, and RPE cell injury was induced by NaIO3 treatment. To evaluate the protective effect of mitochondrial transplantation, Annexin V/PI and cell viability assays were performed to measure the cell survival, and ROS levels were measured by flow cytometry to analyze cellular stress. To understand the underlying protective mechanism of mitochondrial transplantation, we measure expression of the antioxidant genes, mitochondrial fusion/fission markers, and mitophagy makers using qRT-PCR and Western blot methods. Mitochondrial transplantation reduced NaIO3-induced cell death and ROS levels, and antioxidant genes related to the Nrf2 pathway were upregulated, providing a protective effect against retinal damage. In addition, mitochondrial fusion was increased, whereas fission was decreased in the NaIO3 model. Furthermore, mitophagy was increased by mitochondrial transplantation, which could clear damaged mitochondria through a cellular protective pathway. In conclusion, mitochondrial transplantation could protect the RPE cells by maintaining mitochondrial homeostasis and promoting the antioxidant pathway via Nrf2 activation. This study suggests that mitochondrial transplantation could be a potential treatment option for improving AMD progress in the future.}, }
@article {pmid42211220, year = {2026}, author = {Peng, Y and Liang, LY and Wei, HL and Huang, Q and Yuan, LM and Xie, YY and Tang, QY and Wang, AQ and Li, JM and Guo, QS and Huang, BL}, title = {Fructus lycii mitigates oxidative stress in dry age-related macular degeneration models via Nrf2/ARE pathway.}, journal = {International journal of ophthalmology}, volume = {19}, number = {6}, pages = {1048-1056}, pmid = {42211220}, issn = {2222-3959}, abstract = {AIM: To evaluate the effect of Fructus lycii (FL) aqueous extract on dry age-related macular degeneration (AMD) in mice via the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway and investigate the protective effect of FL-containing serum on hydrogen peroxide (H2O2)-treated human retinal pigment epithelial cells (ARPE-19) in vitro.<br><br>METHODS: In vivo dry AMD mouse model was established by intraperitoneal injection of NaIO3 solution and treated with aqueous extract of FL. The pathological changes of mouse retinal tissues were observed by electron microscopy; the activity of superoxide dismutase (SOD) and catalase (CAT) in mouse serum was detected by colorimetric method. In vitro dry AMD model was established by H2O2 induction of ARPE-19 cells and treated with FL-containing serum. Methylthiazolyldiphenyl-tetrazolium bromide assay and scratch assay were performed to detect cell activity and proliferation ability. Expression of Nrf2, heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) in retinal tissues and ARPE-19 cells were detected by Western blot and quantitative real-time polymerase chain reaction (Q-PCR).<br><br>RESULTS: The in vivo study revealed severe deposits under the retinal pigment epithelium and thickened Bruch's membrane in dry AMD mice. However, aqueous extract of FL reduced the formation of deposits and decreased the thickness of Bruch's membrane. SOD and CAT activities were significantly reduced in the serum of dry AMD mice, and aqueous extract of FL upregulated SOD and CAT activities. In addition, gene and protein expression of Nrf2, HO-1, and GCLC were significantly downregulated in dry AMD mice, but significantly upregulated by FL aqueous extract treatment. In vitro studies showed that H2O2 inhibited the activity and proliferative capacity of ARPE-19 cells and downregulated the protein and gene expression of Nrf2, HO-1 and GCLC. However, in H2O2-treated ARPE-19 cells, FL-containing serum not only increased cell activity and proliferative capacity, but also upregulated protein and gene expression of Nrf2, HO-1, and GCLC.<br><br>CONCLUSION: FL reduces oxidative stress in an animal model of dry AMD through the Nrf2/ARE signaling pathway and has a protective effect on dry AMD in vitro and in vivo, providing new insights into the therapeutic use of FL for dry AMD.}, }
@article {pmid42211726, year = {2026}, author = {Berni, A and Shen, M and Liu, J and Kastner, JD and El-Mulki, OS and Beqiri, S and Herrera, G and Trivizki, O and Waheed, NK and Usner, DW and Levy, B and O'Brien, R and Gregori, G and Rosenfeld, PJ}, title = {Novel Clinical Trial Designs for Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {6}, pages = {101179}, pmid = {42211726}, issn = {2666-9145}, abstract = {PURPOSE: To develop and model clinical trial designs for intermediate age-related macular degeneration (iAMD) using OCT-based structural biomarkers to define inclusion criteria and estimate sample size requirements for detecting treatment effects over 2 years.<br><br>DESIGN: Retrospective study of a prospectively acquired swept-source OCT cohort.<br><br>SUBJECTS: Patients with iAMD enrolled in a prospective natural history imaging study.<br><br>METHODS: Two clinical trial designs were modeled. The first included eyes with drusen volume (DV) &#x2265;0.20 mm[3] and any hyperreflective foci (HRF). The second included eyes with an area of HRF &#x2265;0.07 mm[2], regardless of DV. Eyes were followed from the time of eligibility and monitored for the onset and growth of large hypertransmission defects (hyperTDs). Power and sample size simulations were performed based on the expected treatment effects.<br><br>MAIN OUTCOME MEASURES: Annual square root growth rates of large hyperTDs and incidence of new large hyperTDs over 2 years.<br><br>RESULTS: In 76 eyes with DV &#x2265;0.20 mm[3] and HRF, the mean annual growth rate of large hyperTDs was 0.153 mm/year (standard deviation [SD] = 0.188), and 35.5% of these iAMD eyes developed hyperTDs by 2 years. In the 79 eyes with HRF area &#x2265;0.07 mm[2], the mean annual growth rate was 0.161 mm/year (SD = 0.172), and 40.5% developed hyperTD by 2 years. With a 2-sided alpha of 0.1, a 50% reduction in the growth rate could be detected with 80% power using &#x2265;89 eyes per arm in the first group and &#x2265;64 eyes per arm in the second group.<br><br>CONCLUSIONS: The growth rate of large hyperTDs is a continuous and reproducible structural endpoint for iAMD trials, influenced by both lesion onset and progression. Drusen volume or the area of HRF serves as high-risk biomarkers for enrolling iAMD eyes. This design allows for a study duration of 1-2 years with no more than 100 subjects per arm.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42212360, year = {2026}, author = {Zhang, W and Chen, J and Zhong, J}, title = {Regulatory mechanisms and therapeutic potential of N6-methyladenosine modification in retinal diseases (Review).}, journal = {Molecular medicine reports}, volume = {34}, number = {1}, pages = {}, doi = {10.3892/mmr.2026.13923}, pmid = {42212360}, issn = {1791-3004}, mesh = {Humans ; *Adenosine/analogs &amp; derivatives/metabolism/genetics ; RNA Methylation ; *Retinal Diseases/metabolism/genetics/drug therapy/therapy/pathology ; Animals ; Epitranscriptome ; Methyltransferases/metabolism/genetics ; RNA, Messenger/metabolism/genetics ; Gene Expression Regulation ; }, abstract = {N6‑Methyladenosine (m6A) modification, the most abundant internal chemical modification in eukaryotic messenger RNA, plays a central role in gene expression by dynamically regulating RNA metabolism. The present review systematically summarizes the regulatory mechanisms and pathological significance of m6A modification in major retinal diseases, including diabetic retinopathy, age‑related macular degeneration, retinoblastoma, uveitis and retinitis pigmentosa. Studies indicate that m6A methyltransferases (METTL3), demethylases (FTO and ALKBH5) and reader proteins (the YTH domain‑containing family of proteins) participate in pathological processes such as angiogenesis, inflammatory responses, pyroptosis and photoreceptor degeneration by modulating the stability, translation efficiency and degradation of key gene mRNAs. Furthermore, this review explores the therapeutic potential of targeting m6A‑modifying enzymes (for example, small‑molecule inhibitors STM2457 and FB23‑2) and highlights challenges in tissue specificity, delivery systems and clinical translation. Future research should integrate multi‑omics technologies and precision intervention strategies to advance the application of m6A modification in the diagnosis and treatment of retinal diseases.}, }
@article {pmid42212881, year = {2026}, author = {Ansari, G and Oertli, J and Mächler, L and Lipsky, T and Jeffrey, BG and Cukras, CA and Feltgen, N and Klaver, CCW and Pfau, K and Pfau, M}, title = {Parafoveal Dark Adaptation in Early and Intermediate Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {74}, doi = {10.1167/iovs.67.5.74}, pmid = {42212881}, issn = {1552-5783}, mesh = {Humans ; *Dark Adaptation/physiology ; *Macular Degeneration/physiopathology/diagnosis ; Female ; Cross-Sectional Studies ; *Fovea Centralis/physiopathology ; Aged ; Male ; *Retinal Rod Photoreceptor Cells/physiology ; ROC Curve ; Middle Aged ; Aged, 80 and over ; }, abstract = {PURPOSE: Rod-mediated dark adaptation delays are among the earliest functional abnormalities in age-related macular degeneration (AMD), preceding photoreceptor loss. This study evaluated whether parafoveal fundus-tracked dark adaptometry at 2 degrees detects earlier rod dysfunction than mid-macular loci (4 degrees and 6 degrees) and assessed the diagnostic performance of dynamic and steady-state parameters across eccentricities.<br><br>METHODS: In this cross-sectional study, 35 patients with predominantly early/intermediate AMD and 35 healthy volunteers across a broad range of ages underwent fundus-controlled dark adaptometry (S-MAIA-2; iCare/CenterVue) and multimodal imaging. After standardized bleaching, Goldmann III sized (0.43 degrees) cyan stimuli were presented 2 degrees, 4 degrees, and 6 degrees temporal to the fovea. Dark-adaptation curves were modeled to derive rod intercept time (RIT), final (rod) threshold (FT), and cone threshold (CT), each compared with normative data. Diagnostic accuracy was quantified using covariate-adjusted receiver operating characteristic (ROC) analyses, to account for age.<br><br>RESULTS: Among 70 analyzed eyes, RIT was abnormal in 86% of AMD eyes at 2 degrees, 69% at 4 degrees, and 60% at 6 degrees, whereas FT and CT were less frequently abnormal (29% to 51% and 17% to 26%, respectively). Median RIT at 2 degrees reached 60 minutes in the AMD cohort, indicating absence of rod function within the test duration in many eyes. RIT achieved the highest diagnostic accuracy, with covariate-adjusted area under the curve (AUC) values of 0.91 (95% credible intervals [CrI] = 0.80-0.97) at 2 degrees, 0.88 (95% CrI = 0.77-0.96) at 4 degrees, and 0.87 (95% CrI = 0.76-0.95) at 6 degrees.<br><br>CONCLUSIONS: Fundus-tracked dark adaptometry enables spatially precise assessment of parafoveal rod recovery. Parafoveal RIT prolongation represents the earliest and most frequent functional abnormality in AMD and demonstrates excellent diagnostic performance, supporting its potential as a sensitive functional biomarker for early disease and therapeutic trials.}, }
@article {pmid42212887, year = {2026}, author = {Tsai, CY and Weng, CH and Tsai, CY and Sheen, YJ and Chen, JP and Chen, HM and Wang, IJ and Chou, CC}, title = {Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {5}, pages = {29}, doi = {10.1167/tvst.15.5.29}, pmid = {42212887}, issn = {2164-2591}, mesh = {Humans ; Male ; *Macular Degeneration/epidemiology/prevention &amp; control ; Retrospective Studies ; Middle Aged ; *PCSK9 Inhibitors ; Aged ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Risk Factors ; Hyperlipidemias/drug therapy ; Incidence ; Proprotein Convertase 9 ; *Anticholesteremic Agents/therapeutic use ; Propensity Score ; Proportional Hazards Models ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) has been linked to systemic lipid imbalance, vascular dysfunction, and inflammation. The ocular effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, have not been established. We evaluated whether PCSK9 inhibitor use is associated with reduced AMD risk compared with statin therapy.<br><br>METHODS: We conducted a retrospective propensity score-matched cohort study using the TriNetX multinational electronic health record database (2015-2024) with up to 5 years of follow-up. Adults aged &#x2265;50 years with hyperlipidemia but no prior retinal disease were included. Participants were assigned to PCSK9 inhibitor or statin therapy groups and matched 1:1 based on demographic, clinical, and laboratory variables. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs), and Kaplan-Meier analyses illustrated cumulative AMD incidence.<br><br>RESULTS: Among 56,660 matched participants, PCSK9 inhibitor use was associated with a significantly lower risk of AMD compared with statin therapy (HR, 0.82; 95% CI, 0.73-0.90). The association remained robust in sensitivity analyses across different follow-up intervals. Stratified analyses showed consistent findings in both age groups (50-75 and &#x2265;75 years), male participants, those without type 2 diabetes, nonobese individuals, and those with <2 years of hyperlipidemia duration.<br><br>CONCLUSIONS: In this large real-world cohort, PCSK9 inhibitor use was associated with a lower AMD risk compared with statin monotherapy. Prospective studies are needed to confirm causality.<br><br>TRANSLATIONAL RELEVANCE: This study supports further evaluation of PCSK9 inhibition as a potential strategy to modify AMD risk.}, }
@article {pmid42213134, year = {2026}, author = {Cinque, F and Brink, SCAT and Shahabi, M and de Breuk, A and Heesterbeek, TJ and Klaver, CCW and Hoyng, CB and Lechanteur, YTE}, title = {Clinical course of non-exudative macular neovascularisations in sustained unilateral neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42213134}, issn = {1435-702X}, abstract = {PURPOSE: To assess the risk of conversion of non-exudative macular neovascularisations (NEMNV) in relation to disease history in sustained unilateral neovascular age-related macular degeneration (AMD).<br><br>METHODS: This exploratory case-only cohort study included six-monthly visits. Fellow-eye NEMNV were identified using fluorescein and indocyanine green angiography. Patients were stratified by time since first-eye exudation:&#x2009;<&#x2009;5&#xa0;years (G1) or&#x2009;&#x2265;&#x2009;5&#xa0;years (G2). The primary outcome was the cumulative annual conversion rate of NEMNV, expressed as conversion rate ratios (CRR) with 95% confidence intervals (CI). Secondary outcomes were independent grading of foveal involvement, core vessel, central core vessel, round shape, sharp borders, and lesion growth.<br><br>RESULTS: A total of 134 patients (65.7% female) were included. Mean age at baseline was 74.2&#xa0;years (SD 8.0). Median time since first-eye exudation was 2.9&#xa0;years (IQR 1.0-6.3). Patients in G2 had an earlier age at first-eye exudation (66.0 [9.1] years) than G1 (72.7 [7.8]; P&#x2009;<&#x2009;.001). Seven NEMNV lesions were identified (G1:2, G2:5). Cumulative conversion rates were 22.1% overall, 14.3% in G1, and 27.1% in G2. CRR were 2.3 (95% CI 0.6-6.2), 1.3 (95% CI 0.0 - 7.8), and 4.0 (95% CI 0.7 - 16.8). All but one NEMNV showed growth.<br><br>CONCLUSION: In this limited sample, most NEMNV show growth time regardless of conversion to exudative AMD and appear at a higher risk of conversion. The rate of conversion varies with the age of onset of first-eye exudation. Evaluating potential predictive signs of conversion may benefit from incorporating disease history with vascular features.}, }
@article {pmid42213331, year = {2026}, author = {La Torre, G and D'Urso, P}, title = {Evaluating synergistic effects among multiple factors in disease causation: a new approach using a generalized synergy index.}, journal = {European journal of epidemiology}, volume = {}, number = {}, pages = {}, pmid = {42213331}, issn = {1573-7284}, abstract = {The methodological objective of the present study is to extend Rothman's additive interaction framework from two factors to three or more factors considered simultaneously, while preserving its original causal interpretation and operational simplicity. we propose a generalized Synergy Index (Sp) that retains the additive logic of Rothman's original formulation while extending it to an arbitrary number of dichotomous factors. For the analysis we used a database of a previous work in which the synergistic factor was calculated for each couples of two factors (alcohol, tobacco smoke and other risk factors) for age-related macular degeneration. The proposed three-factor Sp is sensitive to the underlying structure of the risk factors considered. When a strong susceptibility component such as family history is included, the combined exposure exhibits clear super-additive behavior (Sp = 1.783). Conversely, when hypercholesterolemia replaces family history, the joint effect remains substantial but does not exceed additivity (Sp = 0.756). The generalized multi-factor Synergy Index represents a valuable conceptual and analytical tool for investigating higher-order interactions. It is particularly well suited for the study of complex diseases, where multiple exposures co-occur and interact. It enables the identification of exposure constellations characterized by true superadditivity, with potential implications for etiological research, risk stratification, and targeted prevention strategies.}, }
@article {pmid42201956, year = {2026}, author = {Ly, K and Bhuckory, MB and Pham-Howard, D and Kochnev Goldstein, A and Jensen, N and Palanker, D}, title = {Residual photoreceptors affect the response of a degenerate retina to electrical stimulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {22}, pages = {e2537064123}, doi = {10.1073/pnas.2537064123}, pmid = {42201956}, issn = {1091-6490}, support = {R01-EY- 035227//HHS | NIH (NIH)/ ; P30-EY-026877//HHS | NIH (NIH)/ ; W81XWH-2210933//U.S. Department of Defense (DOD)/ ; FA9550-19-1-0402//DOD | AF | AMC | AFRL | Air Force Office of Scientific Research (AFOSR)/ ; }, mesh = {Animals ; *Electric Stimulation ; Rats, Long-Evans ; *Retinal Degeneration/physiopathology/therapy ; Rats ; Evoked Potentials, Visual/physiology ; *Photoreceptor Cells, Vertebrate/physiology ; *Retina/physiopathology ; Visual Prosthesis ; Retinal Bipolar Cells ; }, abstract = {Photovoltaic subretinal prosthesis can restore central vision in patients blinded by age-related macular degeneration with letter acuity matching its 100 µm pixel size. Improving resolution requires smaller pixels, but to still reach the target neurons, electric field should be less confined. However, wide-spreading field may engage adjacent photoreceptors and alter the visual perception. We studied the effects of residual photoreceptors on retinal responses to electrical stimulation using monopolar and bipolar photovoltaic arrays implanted subretinally in Long Evans rats with local photoreceptor loss, and compared that to RCS rats lacking all photoreceptors. Patterned retinal activation (880 nm, 0.5 to 10 ms) was assessed using visually evoked potentials under scotopic and photopic conditions, with and without the intravitreal injection of neurotransmitter blockers. Results were analyzed using a computational model of photoreceptor activation by various electric field configurations. We observed two mechanisms of photoreceptors engagement in electrical activation of the degenerate retina: 1) Dark-adapted photoreceptors near the implant can be simulated directly by a negative electric potential of the common return electrode along the edge of the array. 2) Light-adapted photoreceptors can reduce the stimulation threshold of bipolar cells within about 100 mm from the implant's edge. Both effects may lead to reduced perceptual uniformity. Bipolar pixels with local return electrodes generate better confined electric fields than monopolar arrays and thus are less affected by the nearby photoreceptors. However, even such implants should be placed a few hundred micrometers from the edge of scotoma to minimize the unintended percepts.}, }
@article {pmid42202045, year = {2026}, author = {Zhang, J and Chen, L and Zhu, X and Cai, Y and Wei, S and Zhou, X and Shi, Y and Liu, C and Huang, C and Bi, S and Wu, F and Zhou, X and Hong, J and Wang, Y}, title = {Coordinated regulation using small-molecule drugs enables controlled therapeutic genome editing and enhanced genomic precision in situ.}, journal = {Science translational medicine}, volume = {18}, number = {851}, pages = {eadx7857}, doi = {10.1126/scitranslmed.adx7857}, pmid = {42202045}, issn = {1946-6242}, mesh = {Humans ; Animals ; *Gene Editing/methods ; CRISPR-Cas Systems/genetics ; Mice ; *Genomics ; Dependovirus/genetics ; }, abstract = {Achieving precise temporal control over genome editing is essential for safety but remains a challenge, especially when using small-molecule drugs as external regulators over systems like clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated systems). Consequently, controlled therapeutic in situ editing that maintains both precision and efficacy has yet to be demonstrated. Here, we report the PRINCE system, in which nuclease proteins and guide RNAs are both inducible, to deliver programmable nucleases under control more effectively. PRINCE demonstrated temporal precision in human cell cultures over a 2-year period, even after stable genomic integration. The design principles of PRINCE were broadly applicable from CRISPR-Cas9 to a prime editor and also compact programmable nucleases, and the latter platform was named "Little Prince." Upon administration of drug inducers, Little Prince, delivered in a single adeno-associated virus vector in situ to humanized mouse models, ameliorated pathological phenotypes of hypercholesterolemia (average reductions of 45 and 47% in serum total cholesterol and low-density lipoprotein cholesterol, respectively) and neovascular age-related macular degeneration, with significantly reduced lesion size and leakage (P < 0.0001). Last, we demonstrated a consistent and marked reduction in off-target activity across the PRINCE and Little Prince systems in comparison with constitutive editors, with fewer off-target sites and substantially lower editing frequencies, irrespective of nuclease type, delivery method, or genomic target. These results position PRINCE and Little Prince as controlled genome editing platforms with potential for in vivo, particularly in situ, therapeutic applications.}, }
@article {pmid42203079, year = {2026}, author = {Koh, TY and Cho, WR and Jeon, HY and Moon, CH and Yoon, JS and Kim, M and Ha, KS}, title = {Sustained human C-peptide protects against retinal neurodegeneration via PEDF restoration and oxidative stress inhibition in a mouse model of age-related macular degeneration.}, journal = {Free radical biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2026.05.327}, pmid = {42203079}, issn = {1873-4596}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. The molecular events that initiate retinal degeneration in dry AMD remain incompletely understood, and effective therapeutic options are limited. Here, we investigated the therapeutic potential of K9-C-peptide against sodium iodate (NaIO3)-induced retinal neurodegeneration and explored its underlying molecular mechanisms. K9-C-peptide markedly attenuated NaIO3-induced retinal apoptosis, thinning, and structural disruption. These protective effects were accompanied by significant suppression of ROS generation, decreased expression of pro-inflammatory cytokines, and inhibition of reactive gliosis. Mechanistically, K9-C-peptide restored NaIO3-induced downregulation of pigment epithelium-derived factor (PEDF). Consistently, intravitreal administration of hydrogel-formulated PEDF similarly reduced oxidative stress and retinal degeneration, supporting a central role for PEDF in mediating the protective effects of K9-C-peptide. Both K9-C-peptide and PEDF improved impaired axonal transport, further confirming their neuroprotective efficacy. Notably, sustained intraocular delivery of human C-peptide or PEDF conferred robust protection against NaIO3-induced retinal neurodegeneration for at least three weeks following a single administration. These findings suggest that K9-C-peptide may serve as a long-acting therapeutic candidate that targets early oxidative and inflammatory events, potentially through PEDF restoration, in NaIO3-induced retinal degeneration. This study provides mechanistic insight into the antioxidative and anti-inflammatory actions of C-peptide-based therapy in dry AMD-like pathology.}, }
@article {pmid42205117, year = {2026}, author = {García-Otero, X and Cuartero-Martínez, A and Fernández-Robredo, P and Antas, SG and Gómez-Lado, N and Otero-Espinar, FJ and Hernández, M and Bezunartea, J and García-Layana, A and Recalde, S and Aguiar, P and Fernández-Ferreiro, A}, title = {Intravitreal faricimab pharmacokinetics assessed by PET imaging in a neovascular Age-related Macular Degeneration rat model.}, journal = {International journal of pharmaceutics: X}, volume = {11}, number = {}, pages = {100567}, pmid = {42205117}, issn = {2590-1567}, abstract = {Age-related Macular Degeneration (AMD) is the leading cause of blindness in the elderly, with its neovascular form characterised by abnormal vessel growth. Current anti-VEGF therapies require frequent intravitreal injections and show variable efficacy. Faricimab, a novel bispecific antibody targeting VEGF-A and ANG-2, offers a dual mechanism with the potential for enhanced efficacy and extended dosing intervals. This study aimed to characterise the intravitreal pharmacokinetics, biodistribution, and ocular localization of faricimab in a rat model of laser-induced choroidal neovascularization (CNV) using non-invasive molecular imaging. Faricimab was conjugated with DFO and radiolabelled with zirconium-89 ([[89]Zr]Zr-DFO-faricimab), maintaining functional binding to VEGF-A and ANG-2. Following intravitreal injection, pharmacokinetics was assessed by PET/CT, blood sampling, and autoradiography, alongside structural retinal evaluation by OCT. Both healthy and CNV-induced rats demonstrated biphasic ocular clearance with similar half-lives, obtaining no significant differences (Control AUC0-∞ = 5587.3 ± 1419.3%·hour and AMD AUC0-∞ = 4079.1 ± 1178.6%·hour). Autoradiography confirmed predominant retention in the posterior segment, with AMD eyes showing higher early accumulation, suggesting altered diffusion, and increased retinal binding. Whole-body biodistribution revealed systemic uptake primarily in the liver and spleen, consistent with antibody catabolism. This work represents the first study to report pharmacokinetic data of faricimab as well as its intraocular distribution in an AMD model. Our findings support its therapeutic potential and highlight PET imaging as a powerful non-invasive tool for longitudinal ocular pharmacokinetic studies.}, }
@article {pmid42190944, year = {2026}, author = {Demirel, R and Irgat, SG and Bike, HI}, title = {Subretinal fluid resolution in the fellow eye after unilateral aflibercept injection in bilateral neovascular age-related macular degeneration: coincidence or systemic effect?.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502585}, doi = {10.1016/j.oftale.2026.502585}, pmid = {42190944}, issn = {2173-5794}, abstract = {We report a case of bilateral neovascular age-related macular degeneration (nAMD) in which a unilateral aflibercept injection led to complete resolution of subretinal fluid (SRF) in the untreated fellow eye. A 63-year-old woman undergoing treat-and-extend therapy for the right eye developed new SRF in the left eye, which maintained good vision (best-corrected visual acuity, 0.8; defined as ≥0.5 Snellen or ≤0.3 logMAR). To avoid injection-related risks in a high-vision eye, only the right eye was treated. Three weeks later, optical coherence tomography demonstrated complete SRF resolution in the left eye, which persisted for 8 weeks before recurrence. This case raises the possibility that systemic absorption of anti-vascular endothelial growth factor (anti-VEGF) may temporarily suppress choroidal neovascularisation activity in the fellow eye. However, this single observation cannot guide clinical practice and requires prospective validation.}, }
@article {pmid42190948, year = {2026}, author = {Kavyasree, PKV and Jayadevan, K and Abdullah, M and Therayil, A}, title = {Redox-inflammation pathways in ocular disease: targets for nutritional modulation.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502581}, doi = {10.1016/j.oftale.2026.502581}, pmid = {42190948}, issn = {2173-5794}, abstract = {Visual impairment remains a major global health burden caused by diverse ocular diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, and ocular surface disorders. Despite differing etiologies, growing evidence identifies oxidative stress and chronic inflammation as a shared pathogenic axis affecting both anterior and posterior ocular segments. High metabolic demand, sustained light exposure, dense mitochondrial content, and limited antioxidant defences render ocular tissues particularly susceptible to redox imbalance. Excess reactive oxygen species induce cellular injury and activate redox-sensitive inflammatory signalling, promoting neurodegeneration, microvascular dysfunction, immune-mediated damage, and progressive vision loss. This review summarises key mechanisms underlying redox-inflammatory crosstalk in ocular tissues, highlighting mitochondrial dysfunction, Nrf2-Keap1 antioxidant responses, NF-κB-driven inflammation, and MAPK and PI3K-Akt signalling as central molecular integrators. Tissue-specific responses in the retina, retinal pigment epithelium, trabecular meshwork, uveal tract, and ocular surface demonstrate how shared mechanisms generate distinct disease phenotypes. The modulatory potential of bioactive nutrients, including omega-3 fatty acids, carotenoids, and polyphenols, is critically discussed. Although preclinical evidence is strong, clinical outcomes remain variable, underscoring the need for precision nutrition strategies and mechanism-based clinical trial design.}, }
@article {pmid42191674, year = {2026}, author = {Sampson, J and Segrè, AV and Bujakowska, KM and Clark, SJ and Bishop, PN and Haynes, S and Baralle, D and Al-Deek, J and Holden, S and Anderson, B and Hayes, A and Kemal, RA and Thomas, HB and O'Keefe, RT and Banka, S and Black, GC and Sergouniotis, PI and Ellingford, JM}, title = {Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {}, pmid = {42191674}, issn = {2041-1723}, mesh = {Humans ; *Retina/metabolism ; Quantitative Trait Loci/genetics ; *Gene Expression Regulation ; Retinal Pigment Epithelium/metabolism ; *Genetic Variation ; Sequence Analysis, RNA ; Polymorphism, Single Nucleotide ; DNA Copy Number Variations ; Whole Genome Sequencing ; }, abstract = {Genetic disorders impacting vision affect millions of individuals worldwide, including age-related macular degeneration (common) and inherited retinal disorders (rare). There is an incomplete understanding of the impact of genetic variation on gene expression in the human retina and its role in genetic disorders. Through the generation of whole genome sequencing and bulk RNA-sequencing of neurosensory retina and retinal pigment epithelium from 201 post-mortem eyes, we uncover common and rare genomic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci impacting 9,959 and 3,699 genes in neurosensory retina and retinal pigment epithelium, respectively, with associated genomic variants enriched to cis-candidate regulatory elements and notable shared eGenes between both tissues. We also detect 1051 expression outliers and prioritise 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.}, }
@article {pmid42193268, year = {2026}, author = {Gopi, S and Prodanoff, GT and Passaglia, CL and Kindy, MS and Sutariya, V and Halade, GV and Lewin, AS and Biswal, MR}, title = {Non-Erythropoietic EPO (EPO-R76E) Protects RPE Cells from Ferroptosis by Modulating the Labile Iron Pool and NRF2-GPX4 Axis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {5}, pages = {}, doi = {10.3390/antiox15050647}, pmid = {42193268}, issn = {2076-3921}, support = {1R00EY027013-04/NH/NIH HHS/United States ; 1R01EY033415-03/NH/NIH HHS/United States ; }, abstract = {Retinal pigment epithelium (RPE) degeneration remains a formidable challenge in dry age-related macular degeneration (AMD) research, primarily due to the toxic interplay between iron overload and ferroptosis. We investigated whether EPO-R76E, a non-erythropoietic modified variant of erythropoietin, could effectively interrupt this destructive cycle. Using ARPE-19 cells challenged with ferric ammonium citrate (FAC) to model iron-induced toxicity, we show that EPO-R76E confers protection against ferroptosis. Our results demonstrate that this variant significantly reduces the intracellular labile iron pool, directly quenching the lipid peroxidation that drives ferroptotic cell death. This resilience is fueled by a robust upregulation of Glutathione Peroxidase 4 (GPX4) and the broad transcriptional activation of the NRF2 (Nuclear factor erythroid 2-related factor 2) NRF2 antioxidant axis. Furthermore, we found that EPO-R76E enhances autophagic flux, ensuring that cells maintain essential proteostasis and "housekeeping" functions even under metabolic crisis. By integrating iron sequestration with reinforced antioxidant signaling and cellular clearing mechanisms, EPO-R76E stands out as a potent candidate for preserving RPE health. These findings uncover a novel molecular framework for protecting the retina against iron-mediated injury, positioning EPO-R76E as a versatile and targeted gene-based therapeutic for addressing the fundamental causes of retinal degeneration.}, }
@article {pmid42193449, year = {2026}, author = {Xiong, C and Zhou, S and Hu, Y and Xu, X}, title = {Exploring Biomarkers and Mechanisms of Action of Adaptive Immune Response in Age-Related Macular Degeneration Based on Transcriptomics.}, journal = {Biomedicines}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/biomedicines14051123}, pmid = {42193449}, issn = {2227-9059}, support = {82374214//National Natural Science Foundation of China/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is a common retinal degenerative disease linked to adaptive immune response dysregulation. This study aimed to identify shared immune-related biomarkers and explore their underlying mechanisms. Methods: GSE29801 and GSE135092 served as training and validation sets. Adaptive immune response-related genes (AIR-RGs) from MSigDB were intersected with AMD-related differentially expressed genes (DEGs) to identify candidate genes. Machine learning algorithms were applied to screen biomarkers, validated in datasets and a mouse model of choroidal neovascularization by qPCR. A nomogram was constructed and assessed. GSEA and immune infiltration analyses explored mechanisms and immune microenvironment associations. Results: A total of 148 DEGs were identified, yielding 15 candidate genes after intersection with AIR-RGs. Machine learning identified C3 and HLA-DOA as potential biomarkers, with their differential expression validated across datasets. A nomogram based on these biomarkers demonstrated good predictive performance for AMD pathology (AUC = 0.795). Biomarkers were associated with some immune-inflammatory pathways. Significant differences in immune cell infiltration were observed between AMD and control groups, with biomarkers positively correlated with differentially infiltrated immune cells, such as natural killer cells. Conclusions: The identification of the established biomarker C3 serves as a proof-of-principle for the analytical approach, rather than a novel discovery, thereby validating the model's capacity to uncover other critical immune targets. Consequently, C3 and HLA-DOA serve as potential biomarkers for AMD, significantly correlated with disease progression via immune pathways and offering insights for immune-based therapeutic strategies.}, }
@article {pmid42193986, year = {2026}, author = {Bhattacharya, S and Ang, C and Soucy, M and Tsang, SH and Chaum, E}, title = {Prominin-1 and Retinal Degenerative Disorders: Expanding the Biology from Photoreceptors to the Retinal Pigment Epithelium.}, journal = {Biomolecules}, volume = {16}, number = {5}, pages = {}, doi = {10.3390/biom16050635}, pmid = {42193986}, issn = {2218-273X}, support = {GF02527//International Retinal Research Foundation/ ; GR020592//Carl Marshall and Mildred Almen Reeves Foundation/ ; Unrestricted Research Grant to the Vanderbilt Eye Institute//Research to Prevent Blindness/ ; Margy Ann and J Donald M. Gass Chair Endowment//Vanderbilt University Medical Center/ ; R24EY028758//Research to Prevent Blindness/ ; R24EY027285//Research to Prevent Blindness/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; *AC133 Antigen/metabolism/genetics ; *Retinal Degeneration/metabolism/pathology/genetics ; Autophagy ; }, abstract = {Prominin-1 (Prom1/CD133) has long been recognized as a structural determinant of photoreceptor outer segment (OS) morphogenesis, yet rapidly accumulating evidence extends its role to retinal pigment epithelium (RPE) homeostasis, encompassing autophagy-lysosomal flux, outer segment phagocytosis, mitochondrial function, and regulation of inflammatory stress. This review synthesizes mechanistic and transcriptomic insights that position PROM1 as a central regulator of photoreceptor and RPE integrity, reframing Prom1 disease as a multi-compartment retinal disorder relevant to both inherited retinal dystrophies (IRDs) and atrophic age-related macular degeneration (aAMD). We develop a dual-axis conceptual model in which Prom1 dysfunction can initiate pathology in either the photoreceptors (OS morphogenesis failure) or the RPE, including impaired autophagic flux, lysosomal activity, defective phagocytosis, and Epithelial-Mesenchymal Transition (EMT)-like de-differentiation, with secondary cross-compartmental degeneration. Clinically, autosomal-dominant missense variants associate with macular or cone-rod dystrophy, whereas biallelic truncating/splice-site mutations drive early-onset rod-cone disease and panretinal/RPE atrophy, illustrating genotype-phenotype diversity. By integrating recent high-resolution transcriptomic data from Prom1-deficient RPE cells with long-standing insights into photoreceptor biology, we highlight converging pathways of degeneration that challenge a photoreceptor-centric view and unify disparate phenotypes within a single molecular framework. These insights broaden the therapeutic landscape, advancing gene augmentation and pathway-targeted strategies to preserve RPE integrity, sustain photoreceptor function, and modify disease course in PROM1-associated IRDs and atrophic AMD.}, }
@article {pmid42194525, year = {2026}, author = {Szymańska, K and Sałasińska, K and Młynarczyk, A and Miszczak, J and Dmoch, W and Maciejewicz, P}, title = {The Gut-Eye Axis and Microbiome in Ophthalmic Diseases: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/jcm15103563}, pmid = {42194525}, issn = {2077-0383}, abstract = {The gut microbiome regulates host metabolism, barrier integrity, and immune homeostasis through microbe-host signaling and bioactive metabolites. Growing evidence suggests that dysbiosis may also influence ocular immune privilege and blood-retinal barrier stability, supporting the emerging concept of the gut-eye axis. This narrative review aimed to integrate retinal, uveal, and ocular surface disorders within a shared functional framework, with emphasis on recurring mechanistic pathways and their translational relevance rather than on single diseases or isolated taxonomic findings. The review was based on a literature search of PubMed and Scopus and primarily included English-language studies published between 2015 and 2025, with earlier seminal papers included when needed. The search was last updated in March 2026, and 101 sources were included in the final narrative synthesis. Across age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, dry eye disease, and Sjögren's syndrome, the most consistent microbiome-related signals were functional rather than taxonomic. Recurrent mechanistic themes included Th17/Treg immune programming, barrier dysfunction with microbial product translocation, and systemic metabolite signaling, particularly involving short-chain fatty acids, bile acid receptor pathways, and tryptophan-derived metabolites. Age-related macular degeneration and diabetic retinopathy showed the strongest multi-layered support, whereas uveitis provided a compelling immune-centered biological model that remains limited by treatment-related confounding in human studies. In glaucoma and ocular surface disease, evidence supports biological plausibility, especially in relation to neuroinflammation, mucosal immune dysregulation, and metabolite-dependent anti-inflammatory pathways, although much of the available human literature remains associative. Overall, current evidence supports dysbiosis as a disease modifier that may influence ocular inflammation, angiogenesis, neurodegeneration, and barrier stability. However, clinical translation remains limited by cohort heterogeneity, methodological variability, and incomplete control of confounding factors. Further progress will depend on longitudinal multi-omics cohorts and controlled intervention trials focused on actionable microbial functions.}, }
@article {pmid42194903, year = {2026}, author = {Benites-Narcizo, G and Juvier-Riesgo, T and Pérez-Negrón, AP and García-Dussán, L and Wang, J and Hong, J and Mendoza-Santiesteban, CE and Lam, BL}, title = {Quantitative Flavoprotein Fluorescence Parameters in Retinal and Optic Nerve Diseases: A Scoping Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/jcm15103942}, pmid = {42194903}, issn = {2077-0383}, abstract = {Background: Retinal and optic nerve disorders remain major causes of visual morbidity worldwide. Ocular fundus flavoprotein fluorescence (FPF) imaging has emerged as a potential noninvasive biomarker of mitochondrial dysfunction for earlier detection and evaluation of disease severity. Methods: We conducted a Systematic Scoping Review of the diagnostic and correlational utility of quantitative FPF parameters in retinal and optic nerve diseases compared with healthy controls. Following PRISMA-ScR guidelines, we searched MEDLINE, Web of Science, Scopus, and CENTRAL for peer-reviewed human studies available online before 31 December 2025. Results: Seventeen studies were included, encompassing 1914 eyes and 1339 participants, and were predominantly cross-sectional. In healthy eyes, mean macular and optic nerve head FPF intensity were reported as 24.1 ± 12.2 gsu and 30.6 ± 14.6 gsu, respectively. Higher signals were reported in several disorders, including diabetes mellitus (76.0 [67.0-92.0] gsu), neovascular age-related macular degeneration (67.47 ± 17.77 gsu), and retinitis pigmentosa (50.5 ± 12.2 gsu). However, lower, unchanged, or stage-dependent signals were also observed within the same disease categories. Interpretation across studies was limited by substantial heterogeneity in patient selection, disease definitions, imaging protocols, control groups, and FPF outcome metrics. The precise cellular and sublayer origin of the detected signal also remains challenging to determine. Conclusions: Ocular fundus FPF imaging provides promising metabolic insight into retinal and optic nerve diseases. However, current evidence remains heterogeneous and largely cross-sectional, limiting clinical interpretability and generalizability. Longitudinal studies, technical standardization, and multimodal integration are needed to define reproducible disease-specific FPF profiles and improve translational applicability.}, }
@article {pmid42195076, year = {2026}, author = {Çatak, O and Keleş, JK and Çatak, Z}, title = {Circulating Claudin-5 and Systemic Inflammatory Indices in Wet and Dry Age-Related Macular Degeneration.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {5}, pages = {}, doi = {10.3390/medicina62050823}, pmid = {42195076}, issn = {1648-9144}, mesh = {Humans ; Female ; *Claudin-5/blood/analysis ; Male ; Case-Control Studies ; Prospective Studies ; Aged ; *Macular Degeneration/blood/physiopathology ; *Inflammation/blood ; Middle Aged ; Biomarkers/blood/analysis ; Aged, 80 and over ; }, abstract = {Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case-control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role.}, }
@article {pmid42195115, year = {2026}, author = {Chang, HL and Wang, LU and Huang, TL and Chang, PY and Ho, WT and Hsu, YR and Chen, FT and Chen, YJ and Lin, CD and Wang, JK}, title = {The Short-Term Outcomes of Intravitreal Faricimab for Treatment-Naïve and -Refractory Neovascular Age-Related Macular Degeneration: A Real-World Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {5}, pages = {}, doi = {10.3390/medicina62050863}, pmid = {42195115}, issn = {1648-9144}, support = {NSTC 114-2221-E-003-037//National Science and Technology Council/ ; }, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections/methods ; Female ; Male ; Treatment Outcome ; Aged ; Visual Acuity/drug effects ; Aged, 80 and over ; *Macular Degeneration/drug therapy ; Polypoidal Choroidal Vasculopathy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Bispecific ; }, abstract = {Background and Objectives: Neovascular age-related macular degeneration (nAMD), including typical nAMD (tAMD) and polypoidal choroidal vasculopathy (PCV), is a leading cause of visual impairment. This study investigated the real-world short-term outcomes of faricimab, a bispecific antibody targeting Ang-2 and VEGF-A, in patients with treatment-naïve or -refractory nAMD. Materials and Methods: This retrospective study analyzed treatment-naïve or -refractory nAMD eyes receiving one, two, or three monthly intravitreal faricimab injections. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) one month after the last injection. Secondary outcomes included the dry macula rate (absence of subretinal and intraretinal fluid) and subgroup comparisons between tAMD and PCV. Results: After a single injection, both treatment-naïve (n = 76) and -refractory (n = 44) eyes showed significant CFT reduction (p < 0.0001) but no significant BCVA improvement (p > 0.05). Dry macula was achieved in 63.2% of treatment-naïve and 71.4% of treatment-refractory eyes. In 38 treatment-naïve eyes receiving three injections, both CFT and BCVA significantly improved from baseline (p < 0.001 and p = 0.02, respectively), with a 94.7% dry macula rate. Subgroup analysis of those receiving three injections revealed that PCV eyes exhibited significant visual improvement, whereas tAMD eyes did not. No serious systemic or ocular adverse events were observed over the short-term follow-up period. Conclusions: Intravitreal faricimab is effective for both treatment-naïve and -refractory nAMD in the short term. While anatomical improvements were comparable between subtypes, the PCV subgroup showed a trend toward greater visual improvement in this small cohort; however, this may be influenced by the significantly younger age of PCV patients. These findings are exploratory and require validation in larger, age-matched prospective studies.}, }
@article {pmid42195150, year = {2026}, author = {Jovanović, M and Milošević, J and Carrasco Guijarro, M and Jovanović, S and Todorović, D and Petrović, N and Paunović, S and Janićijević, K and Živković, MLJ}, title = {Outer Retinal Hyperreflective Foci as a Predictor of Hyperreflective Material Boundary Remodeling and Visual Outcomes in Neovascular Age-Related Macular Degeneration.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {5}, pages = {}, doi = {10.3390/medicina62050895}, pmid = {42195150}, issn = {1648-9144}, mesh = {Humans ; Retrospective Studies ; Bevacizumab/therapeutic use ; Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; Female ; *Macular Degeneration/drug therapy/physiopathology ; Male ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Intravitreal Injections ; Treatment Outcome ; *Retina/physiopathology ; }, abstract = {Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal-Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = -0.300, 95% CI [-0.483, -0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = -0.449, 95% CI [-0.879, -0.020], p = 0.041) and HRM width (β = -0.003, 95% CI [-0.005, -0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling.}, }
@article {pmid42195311, year = {2026}, author = {Hajdari, A and Uka, V}, title = {Real-World Experience with Brolucizumab in Treatment-Naïve nAMD with Low Baseline Visual Acuity: Short-Term Outcomes from a Prospective Single-Institution Study.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, doi = {10.3390/life16050754}, pmid = {42195311}, issn = {2075-1729}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a progressive chronic disease that represents a major cause of irreversible vision loss worldwide. In this study we aim to assess the short-term functional and anatomical outcomes of brolucizumab therapy in treatment-naïve patients with nAMD presenting with low baseline visual acuity in a single institution setting.<br><br>METHODS: This is a prospective non-randomized study that included 154 treatment-na&#xef;ve eyes with low baseline visual acuity. We measured visual outcomes (BCVA, logMAR) and structural outcomes (CST, &#x3bc;m). We also stratified the study population into respective age subgroups to evaluate any possible trend between outcome changes and age differences. BCVA and CST were measured at baseline, at each consecutive month (month 1, 2 and 3) of the loading phase, as well as at the final timepoint (6 months). Intraocular pressure (IOP) before and after injection, as well as the incidence of serious adverse events, were monitored throughout the study.<br><br>RESULTS: Mean BCVA improved by 0.41 logMAR (+20 ETDRS letters) after the first injection, 0.65 logMAR (+32 letters) after the second, and reached a maximum improvement of 0.80 logMAR after the third injection. The most important BCVA improvement was seen in younger patients (<50 years), with mean BCVA decreasing from approximately 1.0 logMAR at baseline to around 0.3-0.4 logMAR at the final measurement. Mean CST declined by 45.5 &#x3bc;m after the first injection, 78.5 &#x3bc;m after the second, 117.8 &#x3bc;m after the third, and 143.6 &#x3bc;m at the final timepoint, indicating a pronounced anatomical response to intravitreal brolucizumab therapy.<br><br>CONCLUSIONS: In conclusion, this study demonstrates that brolucizumab therapy provides significant short-term anatomical and functional improvements in treatment-na&#xef;ve patients with nAMD and poor baseline visual acuity. Baseline visual acuity, treatment-na&#xef;ve status, and patient age appear to be key determinants of visual gain.}, }
@article {pmid42195365, year = {2026}, author = {Skarbek, D and Sochocka, A and Sidło, O and Sapiaszko, A and Drab, A and Baj, J and Rejdak, R and Dolar-Szczasny, J}, title = {Nanocarrier-Based Ocular Drug Delivery Systems for Retinal Diseases: Therapeutic Potential.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, doi = {10.3390/life16050810}, pmid = {42195365}, issn = {2075-1729}, abstract = {BACKGROUND: Posterior segment eye diseases, including age-related macular degeneration and diabetic retinopathy, are preeminent causes of vision loss worldwide. Effective drug delivery to the retina poses an ongoing therapeutic difficulty due to the presence of the anatomical and physiological barriers. Nanotechnology-based drug delivery systems represent a promising strategy to overcome those limitations.<br><br>METHODS: A narrative literature review was conducted using the PubMed, Scopus, and Google Scholar databases, covering publications published between 2019 and 2026. Publications evaluating nanoparticles for the treatment of the vitreoretinal disorders, including pre-clinical in vitro and in vivo studies, were analyzed.<br><br>RESULTS: Nanocarriers, including liposomes, polymeric nanoparticles, and lipid-based systems, established improved drug bioavailability, stability, and targeted delivery. The analyzed systems facilitate sustained drug release and potentially reduce the prevalence of invasive intravitreal injections. The nanocarriers' effectiveness is primarily influenced by their physicochemical properties, such as particle size, surface charge, and encapsulation efficiency. Nonetheless, the production costs and safety aspects, including cytotoxicity, oxidative stress, and inflammatory responses, remain as significant limitations.<br><br>CONCLUSIONS: Nanotechnology-based drug delivery systems serve as an auspicious therapeutic approach for posterior segment eye diseases. However, further standardized preclinical and clinical research is required to assure long-term safety and enable successful clinical transition.}, }
@article {pmid42196569, year = {2026}, author = {De Silva, S and Xu, B}, title = {Beneficial Effects of Natural Bioactive Compounds on Eye Health: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {10}, pages = {}, doi = {10.3390/ijms27104592}, pmid = {42196569}, issn = {1422-0067}, support = {UICR0400015-24B &amp; UICR0400016-24B//Beijing Normal-Hong Kong Baptist University/ ; }, mesh = {Humans ; Animals ; *Eye Diseases/drug therapy/metabolism ; Antioxidants/pharmacology/therapeutic use ; *Biological Products/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Flavonoids/pharmacology/therapeutic use ; *Eye/drug effects/metabolism ; Polyphenols/pharmacology/therapeutic use ; Macular Degeneration/drug therapy ; Fatty Acids, Omega-3/pharmacology/therapeutic use ; Carotenoids/pharmacology/therapeutic use ; }, abstract = {Ocular diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataracts are major causes of visual impairment all over the world and are closely linked to oxidative stress, inflammation and mitochondrial dysfunction. This narrative review critically summarizes the available evidence on how various natural bioactive compounds, such as carotenoids, polyphenols, flavonoids, omega-3 fatty acids and botanical extracts, can affect important molecular pathways associated with ocular degeneration. Their antioxidant, anti-inflammatory, anti-angiogenic and neuroprotective properties are given particular emphasis, especially regarding the Nrf2, NF-κB and VEGF signaling pathways. This review is different from past reviews that simply discuss the potential of bioactives in the general nutritional context; rather, it unfolds the disease-specific mechanisms and compound-specific molecular actions and gives special attention to recent advances in nano-delivery systems and precision nutrition strategies to increase the bioavailability and therapeutic targeting of these nutrients in the eyes. Moreover, it offers a framework for a comparison of evidence between preclinical and clinical studies, as well as identifying current translational gaps, including limited bioavailability and a lack of long-term clinical trials, and suggesting future directions such as genotype-guided nutrition and microbiome-informed interventions. In general, this review provides a mechanistic and translational overview of how dietary bioactive compounds relate to eye health and offers the perspective of their possible use in prevention and complementary treatment for vision-related diseases.}, }
@article {pmid42196841, year = {2026}, author = {Vilkeviciute-Petraite, A and Bruzaite, A and Cebatoriene, D and Zaliuniene, D and Lukosevicius, R and Skieceviciene, J and Kupcinskas, J and Liutkeviciene, R}, title = {The Role of Kynurenine and 5-Hydroxytryptophan in Modulating Microbiota and Their Implications in Exudative Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {10}, pages = {}, doi = {10.3390/diagnostics16101475}, pmid = {42196841}, issn = {2075-4418}, support = {No. S-MIP-23-96//Lietuvos Mokslo Taryba/ ; }, abstract = {Background/Objectives: This study explores the roles of kynurenine and 5-hydroxytryptophan (5-HTP) in modulating gut microbiota and their potential implications for exudative age-related macular degeneration (AMD). By examining the interplay between these metabolites and the microbiome, we aim to uncover novel pathways that may influence the pathogenesis of AMD. Understanding these associations could lead to innovative therapeutic approaches for managing this leading cause of vision loss in the elderly. To investigate the roles of kynurenine and 5-HTP, alongside the composition of the nasopharyngeal microbiota, in patients with exudative AMD. Methods: Blood metabolite profiling was performed using LC-MS-based metabolomics. Metabolites were extracted with cold methanol/water containing internal standards, filtered through a 10 kDa cutoff filter, separated on a ZIC-HILIC HPLC column, and detected using an Orbitrap mass spectrometer. Metabolites were identified using MZmine 2 software. Results: Patients with exudative AMD exhibited a profound systemic shift in tryptophan metabolism, characterized by significantly lower plasma levels of 5-HTP and higher levels of kynurenine compared to control subjects (p < 0.001 for both). Logistic regression analysis confirmed that both metabolites were independent predictors of AMD status; higher kynurenine levels were associated with increased disease probability, while higher 5-HTP levels demonstrated a protective effect. The kynurenine/5-HTP ratio emerged as a robust biomarker, achieving an area under the curve (AUC) of 0.85 with an optimal threshold of 3.43 (74.1% sensitivity, 84.4% specificity). When integrated with age and gender, the diagnostic performance of the model reached an excellent AUC of 0.92. After adjusting for demographic factors, the kynurenine/5-HTP ratio remained a potent independent risk factor, with each unit increase associated with a 6.30-fold increase in the odds of exudative AMD. Conclusions: Exudative AMD is characterized by a shift in tryptophan metabolism toward the kynurenine pathway, with decreased 5-HTP, increased kynurenine, and an elevated kynurenine/5-HTP ratio. This ratio showed a strong independent association with AMD and excellent diagnostic performance, highlighting its potential as a biomarker and its role in disease pathogenesis.}, }
@article {pmid42196921, year = {2026}, author = {Prus-Ludwig, A and Wylęgała, A and Wylęgała, E and Kijonka, M and Wowra, B}, title = {Optical Coherence Tomography Biomarkers Predicting Progression to Atrophy in Non-Exudative Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {10}, pages = {}, doi = {10.3390/diagnostics16101555}, pmid = {42196921}, issn = {2075-4418}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual impairment. Optical coherence tomography (OCT) has revolutionized the diagnosis and monitoring of AMD by enabling in vivo visualization of retinal microstructure and identification of imaging biomarkers associated with progression to late-stage disease. Improved understanding of these lesions may clarify disease pathogenesis and inform the development of new therapeutic strategies and clinical trial endpoints. This review summarizes OCT-based biomarkers reported as predictors of progression to late atrophic forms of AMD, with emphasis on early atrophic changes that precede GA.}, }
@article {pmid42197042, year = {2026}, author = {Azalati, MM and Jiang, H and Zhang, K and Kong, L and Wang, L and Li, Z and Fan, Y and Chen, F and Ma, L and Zhang, W}, title = {Dietary Patterns and Age-Related Macular Degeneration: A Matched Case-Control Study.}, journal = {Nutrients}, volume = {18}, number = {10}, pages = {}, doi = {10.3390/nu18101582}, pmid = {42197042}, issn = {2072-6643}, support = {82373570//The National Natural Science Foundation of China/ ; xtr052023010//The Fundamental Research Funds of Xi'an Jiaotong University/ ; }, mesh = {Humans ; *Macular Degeneration/prevention &amp; control/epidemiology/etiology ; Case-Control Studies ; Female ; Male ; Aged ; *Feeding Behavior ; *Diet ; Odds Ratio ; Logistic Models ; Risk Factors ; Fruit ; Vegetables ; Middle Aged ; Principal Component Analysis ; Multivariate Analysis ; Aged, 80 and over ; Diet, Healthy ; }, abstract = {Background: Previous research on diet and age-related macular degeneration (AMD) has emphasized primarily particular nutrients or foods, and the influence of comprehensive dietary patterns that represent actual eating behaviors is largely unknown. Objective: The aim of this study was to assess the association between dietary patterns and the odds of AMD. Methods: A case-control study involving 246 participants with AMD and 246 controls are individually matched by age and gender. Dietary patterns were identified through principal component analysis using a validated food frequency questionnaire. Multivariable conditional logistic regression models were applied to examine the association between the extracted dietary patterns and the likelihood of AMD. Results: Three major dietary patterns were found, accounting for 50.59% of the total variance explained. The prudent dietary pattern represented a high intake of vegetables, fruits, soybeans and its products, edible fungi and algae, and nuts were associated with reduced odds ratios (ORs) of the highest tertile compared to the lowest tertile (OR, 0.29, 95% confidence interval [CI], 0.14-0.59, p for trend = 0.001). The estimated likelihood for AMD in the highest tertile of egg and milk dietary pattern intake, which is characterized by a high intake of eggs, milk and dairy products, and refined grains, was 0.40 (95% CI, 0.23-0.67, p for trend < 0.001) compared with those in the lowest tertile. No association with AMD was identified for the animal dietary pattern (p > 0.05). Conclusions: Adherence to dietary patterns rich in fruits, vegetables, nuts, refined grains, eggs, milk and dairy products is associated with reduced odds of AMD, emphasizing the potential relevance of dietary habits to visual health among middle-aged and elderly adults.}, }
@article {pmid42198422, year = {2026}, author = {Chakraborty, D and Sinha, TK and Sinha, S and Biswas, RK and Das, A and Maiti, A and Bhattacharya, R and Dan, S and Rungta, D and Das, S}, title = {Real-World Comparison of Biosimilar Ranibizumab (Ranieyes) and Innovator Ranibizumab (Lucentis/Accentrix) Across Multiple Retinal Vascular Diseases (The BRIO Study).}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {5}, pages = {}, doi = {10.3390/ph19050747}, pmid = {42198422}, issn = {1424-8247}, abstract = {Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence.}, }
@article {pmid42198424, year = {2026}, author = {Tsai, HR and Hsu, JZ and Loh, CH and Huang, HK}, title = {PCSK9 Inhibitor Use and the Risk of Age-Related Macular Degeneration in Patients with Atherosclerotic Cardiovascular Disease.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {5}, pages = {}, doi = {10.3390/ph19050750}, pmid = {42198424}, issn = {1424-8247}, support = {TCRD115-012//Hualien Tzu Chi Medical Center/ ; }, abstract = {Background/Objectives: Emerging evidence suggests that alterations in lipid metabolism may play a contributing role in the pathogenesis of age-related macular degeneration (AMD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, offer anti-inflammatory and antioxidant benefits, which may provide protective effects against AMD. We aimed to evaluate the risk of developing AMD among patients with atherosclerotic cardiovascular disease (ASCVD) who were newly treated with PCSK9 inhibitors compared with those receiving statins. Methods: This retrospective cohort study utilized data from the Global Collaborative Network within the TriNetX Research Network. Patients with ASCVD who were newly initiated on PCSK9 inhibitors or statins were identified and matched for age, sex, race, laboratory data, comorbidities, and concomitant medications. The primary outcomes were the hazard ratios (HRs) for developing AMD, dry AMD, and wet AMD. Propensity score matching (PSM) was used to adjust for baseline demographics and comorbidities. Results: After PSM, 50,102 patients were included in each group (PCSK9 inhibitor users vs. statin users). Compared to statin users, PCSK9 inhibitor users had significantly lower risks of AMD (HR, 0.81; 95% confidence interval [CI], 0.72-0.92) and dry AMD (HR, 0.78; 95% CI, 0.65-0.94), but not wet AMD (HR, 0.90; 95% CI, 0.70-1.16). Stratified and subgroup analyses showed reduced AMD risk among patients aged ≥65 years, White patients, female patients, and evolocumab users. Conclusions: In patients with ASCVD, compared with use of statins, use of PCSK9 inhibitors is associated with reduced risks of AMD and dry AMD, suggesting a potential novel strategy for managing a condition with limited therapeutic options.}, }
@article {pmid42199036, year = {2026}, author = {Karunainathan, MG and Lee, C and Zohalinejad, KD and Mæng, MO and Fabrin, NW and Jónsdóttir, S and Hassing, AK and Yde, SK and Wykoff, CC and Vorum, H and Subhi, Y and Ørskov, M and Cehofski, LJ}, title = {Real-world insights on switching aflibercept dosage for enhanced outcomes in age-related macular degeneration (RISE-AMD): Safety data.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70160}, pmid = {42199036}, issn = {1755-3768}, abstract = {PURPOSE: To evaluate real-world safety experience with aflibercept 8 mg in a large case series of patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Due to a high proportion of patients on short treatment intervals, patients with nAMD at a Danish tertiary retina clinic were systematically switched to aflibercept 8&#x2009;mg. Safety data from May 2024 to October 2025 were obtained through a retrospective review of medical records by an experienced retina specialist and an additional reviewer. Symptomatic intraocular pressure (IOP) increase was defined as any symptom (e.g. pain) in conjunction with IOP&#x2009;>&#x2009;21&#x2009;mmHg.<br><br>RESULTS: In total, 8675 intravitreal injections of aflibercept 8&#x2009;mg were administered in 1429 eyes with nAMD, including 139 glaucomatous eyes. A total of 25 AEs were reported (2.88 per 1000 injections). Intraocular inflammation (IOI) was reported in 11 eyes (1.27 per 1000 injections), with 10 eyes being managed with topical dexamethasone, while one case required vitrectomy. Symptomatic IOP increase was observed in 10 cases (1.15 per 1000 injections). The occurrence of symptomatic IOP increase did not differ between glaucomatous and non-glaucomatous eyes (p&#x2009;=&#x2009;0.24). Two cases of bacterial endophthalmitis were registered. No case of retinal vasculitis or retinal vascular occlusion was observed.<br><br>CONCLUSION: Incidence rates of symptomatic IOP increase and IOI were generally low. Despite a large glaucoma cohort, the higher incidence rate of symptomatic IOP increase in glaucomatous eyes did not reach statistical significance.}, }
@article {pmid42199109, year = {2026}, author = {Ni, Y and Li, J and So, KF}, title = {Beyond antioxidation: Retinal neuroprotection by Lycium barbarum polysaccharides via multiple signaling pathways.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01602}, pmid = {42199109}, issn = {1673-5374}, abstract = {Age-related macular degeneration, glaucoma, retinitis pigmentosa, and diabetic retinopathy are the major retinal degenerative disorders, and each ultimately leads to irreversible vision loss. In this context, single-target therapies aimed at isolated pathways have delivered only modest benefits. Lycium barbarum polysaccharides, the predominant bioactive components of goji berries, emerge as far more than simple antioxidants, functioning instead as orchestrators of interconnected signaling networks. Growing evidence shows that Lycium barbarum polysaccharides engages pathways well beyond redox control to interrupt disease-driving cascades: it limits cellular senescence through the SIRT1/p53 axis, preserves blood-retinal barrier integrity by maintaining aquaporin-4 at astrocytic endfeet, and biases microglia from proinflammatory M1 toward reparative M2 states. Beyond immunomodulation, Lycium barbarum polysaccharides promotes clearance of pathogenic protein aggregates and suppresses pathological neovascularization via the miR-15a-5p/ VEGFR2 axis. While antioxidant effects may predominate in early disease, the actions of LBP become more targeted as pathology advances, a stage-dependent selectivity that helps explain its cross-disease efficacy. In age-related macular degeneration, Lycium barbarum polysaccharides sustains metabolic homeostasis in retinal pigment epithelium by tuning autophagic flux through the miR-181/BCL-2 axis. In glaucoma, it safeguards mitochondrial membrane potential in retinal ganglion cells, supporting energy metabolism and survival. Collectively, these properties position Lycium barbarum polysaccharides as a pleiotropic regulator capable of reshaping multiple disease trajectories. Realizing its clinical potential will require precise identification of active metabolites, rigorous in vivo pharmacokinetic profiling, and rational combination with current standard-of-care therapies.}, }
@article {pmid42199324, year = {2026}, author = {Cukurova, F and Ramsey, DJ}, title = {Rapid Macular Thinning as a Biomarker for Geographical Atrophy.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {602755}, pmid = {42199324}, issn = {1177-5467}, abstract = {PURPOSE: To assess the rate of retinal thinning as a biomarker for incident late-stage age-related macular degeneration (AMD).<br><br>METHODS: This retrospective cohort study included patients (aged &#x2265;50 years) with &#x2265;3 optical coherence tomography (OCT) macular scans &#x2265;6 months apart. Eyes that developed &#x2265;250&#xa0;&#x3bc;m of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) with associated hypertransmission through Bruch's membrane on OCT were considered to have developed geographic atrophy (GA). The spatial pattern of macular thinning was assessed using the ETDRS rings centered on the foveola, calculated as a percentage change relative to its baseline value by eye.<br><br>RESULTS: A total of 201 eyes met inclusion criteria. At last follow-up, 17 eyes developed GA (8.5%) at a median observation of 5.2 (2.4) years. The central subfield (1-mm) and inner ring (3-mm ETDRS subfield) thinned faster in eyes that developed incipient GA (central subfield thickness [CST]: -1.59% vs. -0.47% per year, p=0.007; inner ring: -1.48% vs. -0.65% per year, p<0.001), while the outer ring (6-mm ETDRS subfield) thinned less rapidly (-0.75% vs. -0.30% per year, p=0.003). Linear regression identified the rate of inner ring thinning as the most significant predictor of GA, with a receiver operating characteristic curve demonstrating a high predictive accuracy (area under the curve [AUC], 0.821; 95% CI, 0.746-0.896; p<0.001).<br><br>CONCLUSION: Rapid thinning of the inner ETDRS ring is associated with incipient GA. Identifying eyes at risk of late AMD using serial OCT scans would permit personalized monitoring and treatment strategies critical for safeguarding vision.}, }
@article {pmid42200766, year = {2026}, author = {Invernizzi, A and Romano, F and Corvi, F and Cozzi, M and Sadda, SR and Freund, KB and Staurenghi, G}, title = {Real-Time High-Resolution OCT for Imaging Retinal and Choroidal Blood Flow.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {69}, doi = {10.1167/iovs.67.5.69}, pmid = {42200766}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; *Regional Blood Flow/physiology ; Cross-Sectional Studies ; *Retinal Vessels/physiology/diagnostic imaging ; Female ; Male ; Blood Flow Velocity/physiology ; Middle Aged ; Feasibility Studies ; Aged ; *Retinal Diseases/physiopathology ; }, abstract = {PURPOSE: To evaluate the feasibility of visualizing intravascular moving particles within retinal and choroidal vessels using real-time high-resolution optical coherence tomography (High-Res OCT), a prototype device offering 3-µm axial resolution.<br><br>METHODS: In this cross-sectional study, 20 healthy eyes were imaged using both High-Res OCT and the standard SPECTRALIS HRA+OCT. A dedicated in-built research tool enabled ART-1 B-scan movie acquisition with real-time eye-tracking. Two masked graders qualitatively assessed visibility and direction of intravascular moving particles, and intergrader agreement was evaluated using Gwet's agreement coefficient 1 (AC1). Four additional patients with retinal vascular disorders (retinal artery occlusion, diabetic retinopathy, hypertensive retinopathy, and neovascular age-related macular degeneration) were imaged with High-Res OCT to explore illustrative clinical applications.<br><br>RESULTS: High-Res OCT demonstrated superior visualization of intravascular moving particles compared with standard OCT in both arteries (80% vs. 50%; P = 0.01) and veins (90% vs. 60%; P = 0.03). Intergrader agreement was high for High-Res OCT (AC1, 0.82-0.89) and moderate-to-substantial for standard OCT (AC1, 0.53-0.71). Flow direction assessment did not differ significantly between devices, although correct identification was numerically higher with High-Res OCT. In pathological eyes, real-time High-Res OCT enabled dynamic visualization of pulsatile and disturbed flow patterns and distinct intravascular motion across multiple vascular conditions.<br><br>CONCLUSIONS: Real-time High-Res OCT enables direct, non-invasive visualization of intravascular moving particles within retinal and choroidal vessels and improves flow detectability compared with conventional OCT. This technique offers novel qualitative insights into ocular vascular dynamics and may guide future quantitative and translational applications.}, }
@article {pmid42201156, year = {2026}, author = {Fathee, HN and Babayev, R and Sahmoud, S and Ağaoğlu, N}, title = {Advancing AMD Detection: Dataset Design and Deep Learning Optimization for Unconstrained Retinal Images.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/vision10020028}, pmid = {42201156}, issn = {2411-5150}, abstract = {Age-related macular degeneration (AMD) is one of the leading causes of vision impairment worldwide, making early and accurate detection essential for effective clinical intervention. Recent advances in deep learning have demonstrated promising results in automated retinal image analysis; however, most existing approaches rely on datasets acquired under controlled conditions, limiting their generalizability to real-world clinical environments. In this paper, we propose a novel AMD dataset designed to simulate unconstrained imaging conditions, by incorporating noise, luminance variations, and device-related artifacts commonly encountered during retinal scan acquisition. Using this dataset, we conduct a comprehensive comparative evaluation of six widely adopted deep learning architectures: VGG16, VGG19, InceptionV3, MobileNetV2, ResNet50, and DenseNet. Experimental results indicate notable performance variations across models, highlighting the impact of architectural design on robustness to image degradation. Among the evaluated approaches, VGG16 achieved the best overall performance. By further optimizing this architecture through targeted training and fine-tuning strategies, the proposed system reached an accuracy of 88% in AMD detection. These findings demonstrate the effectiveness of the optimized VGG16 model and underline the importance of realistic datasets for developing reliable deep learning-based diagnostic tools for practical clinical settings.}, }
@article {pmid42201157, year = {2026}, author = {Lixi, F and Troisi, M and Calabresi, V and Giagoni, A and Rossi, C and Timofte-Zorila, MM and Tarași, TC and Vitiello, L and Tomi, MI and Gheorghe, AG and Coco, G and Lanzolla, G and Giannaccare, G}, title = {Beyond Glycemic Control: Ocular Effects of Glucagon-like Peptide-1 Receptor Agonists.}, journal = {Vision (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/vision10020029}, pmid = {42201157}, issn = {2411-5150}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events.}, }
@article {pmid42201532, year = {2026}, author = {Mimura, T and Nishijima, Y and Hasegawa, D and Yoshida, Y and Noma, H}, title = {Global association between ambient air pollution and age-related macular degeneration: an ecological analysis across 203 countries.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {42201532}, issn = {1614-7499}, abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, and both environmental and lifestyle factors have been implicated in its development; however, international-scale evidence regarding the impact of air pollution remains limited. We conducted a cross-sectional ecological study to evaluate national-level associations between AMD burden and environmental as well as lifestyle factors using data from the Global Burden of Disease study. Disability-adjusted life years (DALYs), age-standardized DALYs, and age-standardized prevalence of AMD from 1990 to 2020 were analyzed in relation to ambient air pollutants, including particulate matter ≤ 2.5 μm (PM2.5), PM ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide, ozone, household air pollution from solid fuel use, and national smoking prevalence obtained from global databases. Between 1990 and 2020, global DALYs attributable to AMD increased by 26.7%, whereas age-standardized DALYs and age-standardized prevalence decreased by 19.2% and 3.4%, respectively. In 2020, age-standardized AMD prevalence showed significant positive correlations with PM2.5 (r = 0.65, p < 0.001), ozone (r = 0.55, p < 0.001), and household air pollution (r = 0.30, p < 0.001), and a significant negative correlation with smoking prevalence (r = -0.25, p < 0.001). Multivariable regression analyses identified PM2.5 (odds ratio [OR] 8.09, p < 0.001) and ozone (OR 5.42, p < 0.001) as independent predictors of AMD prevalence. These findings suggest that exposure to ambient air pollution, particularly fine particulate matter and ozone, may contribute to the global burden of AMD and represent potentially modifiable risk factors, underscoring the need for further research to clarify causal relationships and to inform public health and environmental policy interventions.}, }
@article {pmid42182542, year = {2026}, author = {Al-Tamimi, NY and Amer, M and Graini, FNE}, title = {Clinical Low Vision Rehabilitation Interventions in Age-Related Macular Degeneration: A Case Report.}, journal = {Cureus}, volume = {18}, number = {5}, pages = {e109419}, pmid = {42182542}, issn = {2168-8184}, abstract = {A 70-year-old female with bilateral age-related macular degeneration (AMD) - wet AMD in the right eye and dry AMD in the left eye - presented with reduced unaided distance visual acuity of 20/200 (6/60) and near visual acuity of 3.2M (20/160, 6/48) OU. Retinoscopy and subjective refraction showed a prescription of -2.25 -2.50 × 175 in the right eye and +0.50 -1.50 × 120 in the left eye, achieving corrected visual acuities of 20/125 (6/37.5) OU. With an additional +3.00 diopters sphere for near tasks, the patient was able to read up to 2.5M (20/125, 6/37.5), indicating a coexisting refractive error. Amsler grid testing revealed central metamorphopsia and scotomas OU. Optical coherence tomography (OCT) confirmed bilateral drusen, retinal pigment epithelium (RPE) atrophy, and vitreomacular adhesion (VMA), with findings consistent with AMD. Functional contrast sensitivity was reduced (20/100, 6/30) OU, and visual field testing showed central scotomas and metamorphopsia. Low vision rehabilitation included the prescription of a 2.5× binocular Galilean telescope (Eschenbach 1639; Eschenbach Optik GmbH, Nuremberg, Germany) for distance, achieving 20/40 (6/12) vision OU, and a 5× illuminated hand magnifier (Eschenbach Mobilux 15105; Eschenbach Optik GmbH) for near tasks, enabling reading of 1.0M print (approximately 20/50, equivalent to 6/18+). Environmental modifications and contrast-enhancing filters were recommended. Nutritional counseling and ongoing monitoring were initiated, and the patient was educated on self-assessment with the Amsler grid. At three-month follow-up, visual function remained stable, and low vision strategies continued to support functional independence. This case underscores the importance of early low vision intervention, multidisciplinary care, and personalized rehabilitation strategies in maintaining quality of life in patients with AMD.}, }
@article {pmid42184268, year = {2026}, author = {Xu, X and Liu, W and Li, H and Wang, Y and Li, Y and Wang, B and Liu, M and Li, Y}, title = {The Trajectory of Retinal Microcirculation Imaging: From Angiography to Artificial Intelligence.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {231}, pages = {}, doi = {10.3791/70115}, pmid = {42184268}, issn = {1940-087X}, mesh = {Humans ; *Artificial Intelligence ; *Retinal Vessels/diagnostic imaging/physiology ; Microcirculation/physiology ; Tomography, Optical Coherence/methods ; Animals ; *Angiography/methods ; }, abstract = {Retinal and choroidal microcirculation are highly specialized vascular networks essential for vision and are increasingly recognized as indicators of systemic diseases. For decades, its assessment relied on invasive dye-based angiography, which infers pathology from secondary effects such as vascular leakage. A paradigm shift is now underway, driven by non-invasive imaging modalities that directly visualize and quantify the microvasculature with unprecedented resolution. Chief among these is optical coherence tomography angiography, which provides depth-resolved, three-dimensional maps of perfused vessels, enabling the generation of objective biomarkers for vascular integrity and ischemia. Complementary techniques further probe absolute blood flow, high-frequency hemodynamics, and cellular-level perfusion, creating a rich, multi-scale dataset. This technological evolution is transforming clinical practice, facilitating preclinical detection of diabetic retinopathy, refining therapeutic strategies for neovascular age-related macular degeneration, and providing new insights into the vascular contributions to glaucoma. Looking ahead, integrating these multimodal data streams with artificial intelligence promises to convert the wealth of information into predictive models of disease risk and progression. This heralds a new era in precision ophthalmology and oculomics (the large-scale, data-driven analysis of ocular imaging biomarkers to assess systemic health and predict disease risk), with transformative gains in processing, quantification, and access.}, }
@article {pmid42184794, year = {2026}, author = {Stitou, B and Hung, J and Tran, THC}, title = {[Comparison between in-person physical examination and telemedicine with portable equipment in elderly fall-risk patients].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {6}, pages = {104901}, doi = {10.1016/j.jfo.2026.104901}, pmid = {42184794}, issn = {1773-0597}, abstract = {PURPOSE: To assess diagnostic and clinical decision concordance between a face-to-face ophthalmological examination using handheld equipment and an asynchronous teleophthalmology assessment in disabled elderly fall-risk patients as well as the feasibility of this approach.<br><br>PATIENTS AND METHODS: This prospective single-center study evaluated a diagnostic method. Disabled elderly fall-risk patients underwent an in-person ophthalmological examination using a handheld slit-lamp followed by an asynchronous teleophthalmology assessment based on videos acquired by handheld anterior segment and fundus cameras. Diagnostic and management concordance were assessed using Cohen's kappa coefficient. Feasibility was evaluated by the rate of readable examinations.<br><br>RESULTS: A total of 142 patients (281 eyes) were included. Concordance was very good for phakic/pseudophakic status assessment (kappa=0.87-0.96), moderate for lens assessment (kappa=0.51-0.58) and macular evaluation (kappa=0.48-0.57), and low for other anterior (cornea, iris) and posterior segment (optic nerve head, retinal vessels) assessment as well as for overall clinical decision-making (kappa=0.15-0.35). Feasibility was excellent for anterior segment examination (90-98%) and acceptable for posterior segment assessment (61-81%). A clinical decision could be proposed via teleophthalmology in 50-72% of cases. The main causes of visual impairment were cataract, age-related macular degeneration, and optic neuropathy.<br><br>CONCLUSION: Asynchronous teleophthalmology using handheld equipment appears feasible in disabled elderly patients, with variable reliability depending on the parameters assessed. Technological, organizational, and methodological improvements are required before broader implementation.}, }
@article {pmid42186202, year = {2026}, author = {Chang, TW and Kuo, CY and Lee, CY and Hung, CH}, title = {GLP-1 Receptor Agonists and Risk of Age-Related Macular Degeneration in Older Adults With Obesity: A Target Trial Emulation.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.70910}, pmid = {42186202}, issn = {1463-1326}, abstract = {AIMS: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. Whilst glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for obesity management, their potential impact on AMD risk in individuals without diabetes remains unclear. This study aimed to evaluate the association between GLP-1RA initiation and the risk of incident AMD in obese adults without diabetes.<br><br>MATERIALS AND METHODS: We conducted a target trial emulation using the TriNetX global health research network (January 2014-June 2025). Eligible participants were adults aged &#x2265;&#x2009;60&#x2009;years with obesity but without diabetes mellitus. New users of GLP-1RAs were compared with new users of other weight-loss medications. Following 1:1 propensity score matching, Cox proportional hazards models estimated hazard ratios (HRs) for incident AMD over a maximum 7-year observation window (median follow-up: 1.11&#x2009;years [IQR: 1.48] in the GLP-1RA group versus 2.56&#x2009;years [IQR: 3.89] in the comparator group).<br><br>RESULTS: In 157&#x2009;880 matched patients (78&#x2009;940 per group), GLP-1RA use was associated with a significantly lower risk of incident AMD (HR 0.82; 95% CI 0.68-0.98) compared with other weight-loss medications. Subtype analyses revealed reduced risk for unspecified AMD (HR 0.70; 95% CI 0.52-0.93) and a potential trend towards a lower risk of nonexudative AMD (HR 0.78; 95% CI 0.60-1.00; p&#x2009;=&#x2009;0.050). Subgroup analyses suggested stronger effects in women and adults aged 60-69&#x2009;years; all subgroup findings should be interpreted as exploratory.<br><br>CONCLUSIONS: GLP-1RA use is associated with a reduced risk of incident AMD-statistically significant for unspecified AMD, with a potential trend towards a lower risk of nonexudative AMD-in obese adults without diabetes. Whether this reflects direct GLP-1RA neuroprotective mechanisms, greater weight-loss magnitude or both remains to be determined. Further mechanistic research and prospective clinical trials are warranted.}, }
@article {pmid42186654, year = {2026}, author = {Kar, SK and Nemivant, K and Sharma, UK and Priya, P and Abbasi, S and Yadav, NK}, title = {Transforming Eye-Care Diagnostics Through Artificial Intelligence, Biometric Evaluation, and Tele-Optometry.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e107620}, pmid = {42186654}, issn = {2168-8184}, abstract = {Visual impairment remains a major global health concern associated with disorders such as diabetic retinopathy, glaucoma, cataract, and age-related macular degeneration. Early detection of ocular abnormalities remains essential for preventing irreversible visual loss. Conventional diagnostic methods rely on clinical examination and specialised imaging, yet limitations in accessibility, diagnostic variability, and delayed detection continue to affect effective eye-care delivery in many settings. Advances in digital technologies have introduced innovative diagnostic approaches integrating artificial intelligence (AI), ocular biometric evaluation, and tele-optometry to improve efficiency and reach of ophthalmic care. The objective of this review involves a comprehensive examination of recent developments in digital ophthalmic diagnostics, focusing on AI-based image analysis, biometric measurement technologies, and tele-optometry platforms. Relevant literature addressing AI applications, ocular biometric assessment, and remote ophthalmic screening systems was evaluated to synthesise current knowledge on diagnostic capability and clinical relevance. Current evidence indicates that AI algorithms enable automated interpretation of retinal images and facilitate early identification of ocular diseases. Biometric evaluation provides precise anatomical measurements that support refractive assessment and surgical planning. Tele-optometry systems expand diagnostic access through remote imaging and consultation services, improving screening coverage in underserved populations. Integration of AI, biometric technologies, and tele-optometry demonstrates strong potential to enhance disease detection, strengthen clinical decision support, and expand accessibility of ophthalmic diagnostic services.}, }
@article {pmid42187268, year = {2026}, author = {Rynjah, H and Sarma, B and Parasar, K}, title = {Comment on "Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion".}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261445283}, doi = {10.1177/11206721261445283}, pmid = {42187268}, issn = {1724-6016}, }
@article {pmid42188557, year = {2026}, author = {Judge, LW and Garcia-Carrillo, E}, title = {Combining Multisensory Cueing and Velocity-Based Training to Enhance Shot Put Performance in an F12 Para-Athlete: A Case Report.}, journal = {Sports (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/sports14050181}, pmid = {42188557}, issn = {2075-4663}, abstract = {This case report documents the multi-season development of a 38-year-old elite F12 shot putter with macular degeneration (<10% functional vision) who improved from 13.00 m to a personal best of 14.41 m between 2021 and 2023. Athletes classified as F11-F13 compete with significant visual impairment that limits spatial feedback during rotational tasks, yet longitudinal evidence describing integrated training frameworks remains scarce. A 12-month macrocycle integrated phase-dependent velocity-based resistance training using mean concentric velocity targets (0.70-1.00 m·s[-1]) monitored via linear position transducers with a 10% velocity loss threshold, combined with structured auditory and tactile cueing, including metronome pacing and environmental anchors. High-volume warm-ups and prehabilitation addressed a prior L4-L5 disk herniation. The athlete achieved 14.41 m at the 2023 U.S. Para Athletics Trials, with TrackMan[®]-verified release velocity of 11.3 m·s[-1]. Bench throw velocity improved by 35.4% (0.65 to 0.88 m·s[-1]) and squat jump velocity improved by 22.9% (1.18 to 1.45 m·s[-1]), while post-session RPE remained manageable, indicating improved neuromuscular readiness and training tolerance. No lumbar symptom recurrence occurred. This case illustrates that integrating velocity autoregulation, multisensory stabilization, and injury-informed preparation can support meaningful performance gains in visually impaired throwers and offers an applied framework for coaches working with F11-F13 athletes.}, }
@article {pmid42190107, year = {2026}, author = {Kim, HM and Bae, Y and Kim, M and Lee, H and Chung, H}, title = {Systemic cancer risk profile in neovascular age-related macular degeneration: insights into shared aging-related mechanisms from a nationwide population-based study.}, journal = {Aging}, volume = {18}, number = {1}, pages = {593-604}, doi = {10.18632/aging.206383}, pmid = {42190107}, issn = {1945-4589}, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults and is increasingly recognized as a manifestation of systemic aging involving vascular and inflammatory pathways. Emerging evidence suggests that nAMD may also be linked to systemic diseases, including malignancies. Using data from the Korean National Health Insurance Service, we conducted a nationwide, population-based cohort study of 334,091 individuals (83,742 with nAMD and 250,349 matched controls) followed for up to 10 years. Patients with nAMD showed a modest but significant increase in overall cancer risk (adjusted hazard ratio [aHR], 1.084; P < 0.001), with selectively elevated risks for pancreatic (aHR, 1.155; P < 0.001), lung (aHR, 1.128; P < 0.001), thyroid (aHR, 1.241; P < 0.001), renal (aHR, 1.177; P = 0.002), bladder (aHR, 1.121; P = 0.002), and prostate (aHR, 1.085; P < 0.001) cancers. No significant associations were observed for other malignancies. These findings indicate that nAMD may serve as a clinical marker of systemic vulnerability to selected cancers, possibly through shared angiogenic, inflammatory, and polygenic mechanisms underlying aging-related disease susceptibility.}, }
@article {pmid42190237, year = {2026}, author = {Lee, C and Karunainathan, MG and Zohalinejad, KD and Mæng, MO and Fabrin, NW and Yde, SK and Wykoff, CC and Abildgaard, SK and Vorum, H and Subhi, Y and Ørskov, M and Cehofski, LJ}, title = {Real-World Outcomes after Switch to Aflibercept 8 mg in Neovascular AMD: Twelve Months Follow-up on 654 Eyes.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004888}, pmid = {42190237}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate 12-month outcomes following systematic switch to aflibercept 8 mg in previously treated eyes with age-related neovascular macular degeneration (nAMD).<br><br>METHODS: Eyes in a plateau phase (&#x2265;10 prior anti-VEGF injections) that were switched to aflibercept 8 mg were retrospectively evaluated. Treatment intervals, best corrected visual acuity (BCVA), central retinal thickness (CRT), and data on intraretinal fluid (IRF) or subretinal fluid (IRF) were assessed at switch and after 3, 6, and 12 months.<br><br>RESULTS: In total, 654 eyes from 567 patients were included (mean [SD] age 82.4 [7.4], 34.5 [21.5] injections per eye before switch). The proportion of eyes with dry maculae increased from 55% at switch to 76% at 3 months (P<0.001), 73% at 6 months (P<0.001), and 69% at 12 months (P<0.05). Eyes treated at 3-5-week intervals declined from 46% to 18% at 12 months (P<0.001). Eyes on 9-12-week intervals increased from 11% to 34% (P<0.001). The mean treatment interval increased from 6.0 (2.1) to 7.8 (2.4) weeks (P<0.001). Eyes with dry maculae at switch were extended by 2.6 (1.8) weeks (P<0.001). The mean CRT decreased from 234.7 (49.7) to 223.5 (46.7) &#xb5;m (P<0.001). BCVA declined from 68.5 (12.2) to 67.3 (13.9) ETDRS letters in the overall cohort, and from 68.5 (12.3) to 66.6 (14.3) ETDRS letters in eyes with a dry macula at switch (P < 0.001).<br><br>CONCLUSION: Switching to aflibercept 8 mg improved anatomical outcomes and reduced the proportion of eyes on short intervals. A slight decline in BCVA was observed, warranting long-term follow-up.}, }
@article {pmid42177487, year = {2026}, author = {Simaku, E and Eddien, AN and Popa, M and Shafei, AE}, title = {Non-infectious occlusive retinal vasculitis following switching from aflibercept 2 mg to aflibercept 8 mg in neovascular age-related macular degeneration: a case report.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04953-z}, pmid = {42177487}, issn = {1471-2415}, abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy represents the standard of care for neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg was recently introduced with extended dosing intervals and favorable safety outcomes in phase III trials. Although no confirmed cases of occlusive retinal vasculitis were reported in pivotal studies, rare inflammatory vascular events may emerge during broader real-world exposure.<br><br>CASE PRESENTATION: A 74-year-old pseudophakic male with active nAMD in the left eye demonstrated significant anatomical and functional improvement following intravitreal aflibercept 2&#xa0;mg. After switching to aflibercept 8&#xa0;mg, the patient presented 26 days later with painful visual deterioration. Fundus examination revealed mild vitritis, segmental arterial sheathing, venous narrowing, and peripheral intraretinal hemorrhages. Fluorescein angiography demonstrated capillary non-perfusion and late vascular leakage. Optical coherence tomography confirmed cystoid macular edema. Extensive infectious and autoimmune investigations were negative. Systemic and local corticosteroid therapy resulted in regression of inflammation with partial visual recovery.<br><br>CONCLUSIONS: Non-infectious occlusive retinal vasculitis may rarely occur following switching to aflibercept 8&#xa0;mg. Early recognition and prompt anti-inflammatory treatment are critical to minimize irreversible ischemic damage. Continued post-marketing pharmacovigilance is warranted.}, }
@article {pmid42177686, year = {2026}, author = {Lains, I and Bhat, R and Mendez, K and Gil, J and Providencia, J and Barreto, P and Sourirajan, K and Kang, H and Nigalye, A and Miller, JB and Kim, I and Vavvas, D and Liang, L and Silva, R and Lasky-Su, J and Miller, JW and Husain, D}, title = {Association of age-related macular degeneration with exposome related metabolomics.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {22}, number = {3}, pages = {}, pmid = {42177686}, issn = {1573-3890}, support = {K12EY016335/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/metabolism/urine/blood ; *Metabolomics/methods ; Male ; Female ; Cross-Sectional Studies ; Aged ; Middle Aged ; *Exposome ; *Metabolome ; Aged, 80 and over ; Biomarkers/blood/urine ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a multifactorial disease, but it remains unclear how external exposures - the exposome - promote its development. Metabolomics can provide insights to better understand AMD pathophysiology. Previous work to date has focused primarily on associations between endogenous metabolites and AMD.<br><br>OBJECTIVES: This study aimed for the first time to investigate associations of exogenous metabolites in plasma and urine and AMD.<br><br>METHODS: Cross-sectional study including patients with AMD and a control group (>&#x2009;50 years) from Boston, US and Coimbra, Portugal (PT). Color fundus photographs (CFP) of all participants were used for AMD staging. Fasting plasma and urine samples were used for metabolomic profiling using Ultrahigh Performance Liquid Chromatography - Mass Spectrometry (Metabolon, Inc). Multivariate and ordinal logistic mixed-effect regression models were computed for each cohort and then combined by meta-analysis. Primary outcome was association of metabolites with AMD (vs. no AMD). False discovery rate (FDR) was used to account for multiple comparisons and significant q-values are reported.<br><br>RESULTS: We included 1023 eyes (823 from the US and 580 from PT). Meta-analysis revealed significant associations of tartronate, thioproline and 2-methoxyhydroquinone sulfate levels with both presence and staging of AMD (q&#x2009;<&#x2009;0.005 for all). Similar trends were seen in urine.<br><br>CONCLUSION: To the best of our knowledge, this is the first study to identify associations between exogenous metabolites and AMD. These findings are crucial for identifying possible targets for preventive strategies for this blinding disease.}, }
@article {pmid42177934, year = {2026}, author = {Gilead, N and Chong, YJ and Cheng, MFS and Kikushima, W and Sherif, M and George, L and Ong, C and Sun, C and Hong, CH and Ibrahim, FNI and Teo, KYC and Cheung, CMG}, title = {Predictors of 1-Year Visual Outcome in Central-Involving Submacular Hemorrhage Secondary to Neovascular AMD.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.05.035}, pmid = {42177934}, issn = {1879-1891}, abstract = {PURPOSE: To identify clinical and imaging predictors of 12-month visual outcome in patients with fovea-involving submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).<br><br>DESIGN: Prospective observational clinical cohort study.<br><br>SUBJECTS: Asian patients with nAMD or PCV presenting with fovea-involving SMH.<br><br>METHODS: Between January 2016 and July 2024, eyes presenting with fovea-involving SMH &#x2265;1 disc diameter with no evidence of blood organization were included. All patients received standard-of-care treatment. Clinical and multimodal imaging parameters were analyzed to identify predictors of visual outcome at 12 months.<br><br>MAIN OUTCOME MEASURES: Good (&#x2264;0.3 logMAR) and poor (&#x2265;1.0 logMAR) visual outcomes at 12 months.<br><br>RESULTS: Among 487 treatment-na&#xef;ve eyes, 75 met inclusion criteria for fovea-involving SMH. Mean (SD) age was 71.40 (9.59) years, 74.4% were male, and 76.0% had PCV. Mean hemorrhage size was 18.92 (22.56) mm&#xb2;. All eyes received anti-VEGF therapy, 2.6% underwent additional pneumatic displacement, and 5.3% received photodynamic therapy. Best-corrected visual acuity (BCVA) improved from 1.04 (0.67) logMAR to 0.69 (0.62) at 12 months. 25 eyes (33.3%) achieved good visual outcome, while 22 eyes (29.3%) had poor visual outcome. On multivariable analysis, younger age (OR=0.47 per decade, 95% CI 0.26-0.86; P=0.02), better baseline BCVA (OR=0.87 per 0.1 logMAR, 95% CI 0.79-0.97; P<0.01), and thicker subfoveal choroid (OR=1.50 per 50 &#xb5;m, 95% CI 1.07-2.10; P=0.02) independently predicted good visual outcome. Conversely, larger hemorrhage size predicted poor visual outcome (OR=1.04 per mm[2], 95% CI 1.01-1.07; P=0.02).<br><br>CONCLUSION: One-third of eyes with SMH achieved 0.3 logMAR (Snellen equivalent 20/40) or better vision. In addition to age, baseline BCVA, and hemorrhage size, we identified choroidal thickness as a biomarker associated with visual outcome.}, }
@article {pmid42179647, year = {2026}, author = {Patel, MJ and Datta, M and Baredes, V and Fuentes-Gonzalez, T and Bass, S and Alba, D and Soloff, AC and Hackam, AS}, title = {Chronic exposure to aerosolized Arizona test dust reduces visual acuity in mice.}, journal = {Toxicology reports}, volume = {16}, number = {}, pages = {102263}, pmid = {42179647}, issn = {2214-7500}, abstract = {Air pollution is associated with increased incidence of age-related macular degeneration (AMD), glaucoma and other retinal diseases. The time course of molecular and cellular changes induced by chronic air pollution exposure that lead to retinal pathology are unknown. In this study, we investigated the effects of moderate levels of air pollution on visual acuity and retinal phenotypes in mice using Arizona test dust (ATD) as a surrogate for ambient air pollution. Mice were exposed to aerosolized standardized test dust for three hours a day, four days a week, for up to four months in a custom-built chamber. Controls were exposed to room air. Visual function was assessed using an optomotor assay and demonstrated reduced visual acuity after one month of exposure that persisted throughout the study. Rod and cone photoreceptors also showed temporarily decreased light-evoked responses that returned to normal levels by four months. Furthermore, reduced cone photoreceptors and retinal ganglion cells were observed whereas markers of retinal stress, including Iba1-positive microglia/macrophage and GFAP expression in macroglia, were not significantly elevated. Molecular analyses indicated elevated expression of genes in the Nrf2-ARE oxidative stress response pathway. Therefore, moderate levels of aerosolized ATD caused a persistent decline in visual acuity, mild retinal degeneration and transient functional changes. This study provides new information into the pathogenesis of pollution-induced retinal damage and establishes a new mouse model for investigating detrimental effects of moderate levels of air pollution in the retina.}, }
@article {pmid42179661, year = {2026}, author = {Uzundede, T and Karatas, G and Yildiz, D and Cakir, A}, title = {The Comparison of Intracystic Hyperreflectivity in Different Macular Edema Etiologies. Is It a New Optical Coherence Tomography Biomarker?.}, journal = {Beyoglu eye journal}, volume = {11}, number = {1}, pages = {50-57}, pmid = {42179661}, issn = {2587-0394}, abstract = {OBJECTIVES: To detect the difference in internal hyperreflectivity of macular cystoid spaces in diabetic retinopathy (DR), exudative (wet) age-related macular degeneration (wet AMD), branch retinal vein occlusion (BRVO).<br><br>METHODS: The medical records of the consecutive patients who were followed up from Prof. Dr. Cemil Ta&#x15f;c&#x131;o&#x11f;lu City Hospital, from 01 April 2023 to 01 June 2023, in the retina department, have been included in this study. The mean gray value (GV) and max-min GV parameters of the cystoid spaces which were detected in the spectral domain optical coherence tomography (OCT) scans, were measured by using the ImageJ program (National Institutes of Health, Bethesda, Maryland, USA). The established diagnosis, baseline best corrected visual acuities (BCVA), OCT biomarkers such as serous macular detachment, hard exudate, hyperreflective foci and central macular thicknesses were also noted. The parameters were compared to each other regarding the different pathologies.<br><br>RESULTS: The mean-max GV of cystoid spaces and the mean-max GV of cystoid/vitreous ratio were found to be highest in the DR, followed by BRVO, and lowest in wet AMD (p<0.001 and p<0.001; respectively). Correlation analyses revealed a positive correlation between OCT biomarkers and intracystic hyperreflectivity (ICH) (p<0.001, respectively). Besides, the max GV cystoid/vitreous ratio is positively correlated with the BCVA (p<0.046; p=0.04, respectively).<br><br>CONCLUSION: This pilot study investigates ICH in macular edema of various etiologies. The ICH was highest in the DR group, followed by the BRVO group, and lowest in the AMD group. It has been observed that there is a high correlation between ICH and OCT biomarkers. Findings support the hypothesis that ICH may reflect underlying inflammatory processes and contribute to individualized treatment approaches in retinal vascular pathologies.}, }
@article {pmid42179664, year = {2026}, author = {Demir, U and Gunturkun, PN and Bozgul, P}, title = {Evaluation of the Association of Senile Macular Degeneration in Patients with Glaucoma.}, journal = {Beyoglu eye journal}, volume = {11}, number = {1}, pages = {42-49}, pmid = {42179664}, issn = {2587-0394}, abstract = {OBJECTIVES: The aim of the study was to evaluate the incidence of senile macular degeneration (SMD) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEG).<br><br>METHODS: The medical files of 2600 patients with glaucoma were analyzed. In this study, 168 patients (90 females and 78 males) with POAG and PEG were included. Patients diagnosed with POAG and PEG with SMD were also recorded. SMD was classified in two categories: Wet type and dry type. Lens status was classified as pseudophakic and phakic. Glaucoma severity was classified according to the Hodapp-Parrish-Anderson criteria. All patients underwent complete ophthalmologic examinations.<br><br>RESULTS: Ninety (53.57%) patients were female, and 78 (46.43%) were male. The mean age was 63&#xb1;8.4 years for women and 66.5&#xb1;7.8 years for men. Sixty-six (73.3%) of women and 60 (76.9%) of men had POAG, 24 (26.7%) of women and 18 (23.1%) of men had PEG. 18 (20.0%) right and 25 (27.8%) left eyes of women and 30 (38.5%) right and 24 (30.8%) left eyes of men were pseudophakic, 72 (80.0%) right and 65 (72.2%) left eyes of women and 48 (61.5%) right and 54 (69.2%) left eyes of men were phakic. SMD was observed in 10 patients (5.95%); four women and five men had dry-type SMD, while one man had wet-type SMD.<br><br>CONCLUSION: In our study, when gender, age, severity of glaucoma, pseudophakic and phakic status of the lens were evaluated in patients with the association of glaucoma and SMD, these variables had no statistically significant effect on the association of glaucoma and SMD.}, }
@article {pmid42179847, year = {2026}, author = {Weiss, ER and Han, Z}, title = {Editorial: Retinitis pigmentosa, macular degeneration and related diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {20}, number = {}, pages = {1856506}, pmid = {42179847}, issn = {1662-5102}, }
@article {pmid42180516, year = {2026}, author = {Sannan, NS}, title = {Genetic determinants of age-related macular degeneration in Middle Eastern populations: a systematic review.}, journal = {Frontiers in genetics}, volume = {17}, number = {}, pages = {1776779}, pmid = {42180516}, issn = {1664-8021}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss, with genetic factors playing a key role in disease susceptibility and progression. While extensive genetic research is being conducted, the genetic architecture of AMD in Middle Eastern populations remains understudied. This systematic review summarizes current evidence on genetic variants associated with AMD in Middle Eastern populations.<br><br>METHODS: A comprehensive literature search was conducted in PubMed, Web of Science Core Collection, and Medline databases. Studies were included if they: (1) examined cohorts from Middle Eastern participants; (2) with clinically diagnosed AMD; (3) explored genetic variants or other genomic markers; (4) no restrictions on year of publication; and (5) were published in English.<br><br>RESULTS: The search yielded 449 articles (PubMed: 164, Web of Science: 99, Medline: 186). After removal of 221 duplicates, 228 unique articles were screened. Of these, 28 studies met the inclusion criteria, covering a total of 4,247 AMD cases and 3,447 controls from five countries: Turkey (n = 11), Iran (n = 11), Israel (n = 4), Jordan (n = 1), and Egypt (n = 1). Most analyses were targeted, with 25 studies targeting one to four genetic loci, two studies examining 12 variants, and one genome-wide association study. The most frequently studied genes were CFH, ARMS2, and HTRA1. The CFH Y402H variant (rs1061170) showed overall positive but heterogeneous associations with AMD risk across studied Middle Eastern populations, with reported odds ratios ranging from 0.36 to 17.34 and statistically significant p values ranging from <0.001 to 0.02 (total AMD cases and controls = 2,079). The ARMS2 A69&#xa0;S variant (rs10490924) and HTRA1 promoter variant (rs11200638) demonstrated strong associations with neovascular AMD.<br><br>CONCLUSION: Few studies have examined genotype-phenotype correlations across this region, and many Middle Eastern countries lack published AMD genetic data. Consequently, the genetic landscape of AMD in the Middle East remains incompletely characterized. Available evidence suggests that variants in CFH, ARMS2, and HTRA1 are important AMD-associated loci in studied Middle Eastern populations, consistent with findings in other population groups.}, }
@article {pmid42181643, year = {2026}, author = {Hu, Y and Liu, S and Liu, Q and Liu, B and Zhang, J and Su, H and Yang, L and Gan, L and Guo, Y and He, Y}, title = {Case Report: A typical triad of Danon disease caused by a LAMP2 splice-donor variant with multilevel functional validation.}, journal = {Frontiers in cardiovascular medicine}, volume = {13}, number = {}, pages = {1695991}, pmid = {42181643}, issn = {2297-055X}, abstract = {Danon disease is a rare X-linked dominant disorder caused by pathogenic variants in LAMP2, typically presenting with cardiomyopathy, skeletal myopathy, and intellectual disability, and showing a severe course in males. In this study, we report the case of a 29-year-old Han Chinese male with the classic triad, plus macular degeneration and a complex neuromuscular phenotype including axonal-demyelinating sensorimotor polyneuropathy. Whole-exome sequencing identified a hemizygous splice-donor variant in LAMP2 (NM_002294.2:c.928 + 1G > A). A functional analysis in peripheral blood with matched controls experimentally confirmed markedly reduced LAMP2 mRNA levels and decreased LAMP2 protein expression, supporting the variant as a loss-of-function allele. The patient rapidly progressed to end-stage heart failure and died 18 months after diagnosis, highlighting the severe multisystem impact of this variant. This case expands the functional evidence for pathogenic LAMP2 splice-site variants and suggests peripheral nervous system involvement in severe multisystem Danon disease.}, }
@article {pmid42181881, year = {2026}, author = {Melecchi, A and Amato, R and Lapi, D and Dal Monte, M and Rusciano, D and Bagnoli, P and Cammalleri, M}, title = {Correction: Increased efficacy of dietary supplement containing wax ester-rich marine oil and xanthophylls in a mouse model of dry macular degeneration.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1850473}, doi = {10.3389/fphar.2026.1850473}, pmid = {42181881}, issn = {1663-9812}, abstract = {[This corrects the article DOI: 10.3389/fphar.2022.1038730.].}, }
@article {pmid42173432, year = {2026}, author = {Namakin, K and Mostafaei, M and Behboodi, S and Dolikhani, M and Boroujerdi, T and Araghi, AS and Masoumi, A and Zolbin, MM}, title = {Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosome on the Retinopathy of Prematurity.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111067}, doi = {10.1016/j.exer.2026.111067}, pmid = {42173432}, issn = {1096-0007}, abstract = {Retinopathy of prematurity is a leading cause of childhood blindness caused by insufficient vascularization of the peripheral retina, which eventually leads to retinal ischemia. In the ischemic state, pro-angiogenic factors such as vascular endothelial growth factor (VEGF), Transforming Growth Factor Beta (TGF-b), and Insulin-like Growth Factor 1 (IGF1) are excessively produced leading to pathological neovascularization. One of the current approaches in regenerative medicine is exosomes, derived from mesenchymal stem cell have shown promise as potential anti-angiogenic agents in various ocular diseases, including macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, autoimmune uveitis (AU), optic nerve crush (ONC), and retinopathy of prematurity (ROP). In this narrative review, we aimed to consolidate the current literature on exosomes as a therapeutic strategy for ROP with a brief overview of the applied exosome and available sources and mechanism of action.}, }
@article {pmid42173886, year = {2026}, author = {Kai, JY and Gong, SY and Li, DL and Lanca, C and Grzybowski, A and Ke, C and Pan, CW}, title = {A multimodal ocular aging index reveals proteomic pathways and predicts incident age-related eye diseases.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00418-1}, pmid = {42173886}, issn = {2731-6068}, support = {2024YFC2510800//National Key R&amp;D Program of China/ ; }, abstract = {Chronological age incompletely captures heterogeneity in biological aging. In this prospective study of 45,819 UK Biobank participants, we developed a multimodal ocular aging index (MOAI) by integrating ophthalmic phenotypes with plasma proteomic and metabolomic profiles using machine learning. The MOAI quantifies divergence between ocular biological and chronological age. Over 13.80 years of follow-up, accelerated ocular aging was significantly associated with higher risks of incident age-related macular degeneration and cataract, even after adjustment for chronological age and established risk factors. Incorporation of the MOAI significantly improved risk reclassification beyond traditional predictors. Explainable modeling and pathway enrichment analyses identified inflammation-related proteins and pathways, including cytokine-cytokine receptor interactions and PI3K-Akt signaling, as key drivers of accelerated ocular aging. These findings establish a multimodal framework for quantifying organ-specific biological aging, link ocular aging to systemic inflammatory processes, and highlight the eye as a sensitive readout of aging biology with implications for healthspan.}, }
@article {pmid42174147, year = {2026}, author = {Fukuda, Y and Shiose, S and Notomi, S and Maehara, Y and Yuge, K and Kiyohara, K and Yasaka, Y and Mori, K and Fujiwara, K and Kano, K and Ishikawa, K and Murakami, Y and Sonoda, KH}, title = {Two-year treatment outcomes in neovascular age-related macular degeneration with type 3 macular neovascularisation.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42174147}, issn = {1476-5454}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularisation (MNV) carries a high risk of macular atrophy (MA) during anti-vascular endothelial growth factor (anti-VEGF) treatment. Previous studies have suggested that a greater injection burden is associated with a higher MA risk. We evaluated 2-year outcomes of patients with nAMD with type 3 MNV following the treat and extend (TAE) and pro re nata (PRN) regimens and identified the risk factors for MA.<br><br>SUBJECTS: This retrospective study included 97 eyes of 68 treatment-na&#xef;ve nAMD patients with type 3 MNV. All eyes received monthly anti-VEGF injections for 3 months as a loading phase and were followed for >2 years. Analyses were performed at the eye level for clinical outcomes; for risk-factor analyses of incident MA, one eye per patient was included. Outcomes included best-corrected visual acuity (BCVA) and central macular thickness (CMT).<br><br>RESULTS: Compared with PRN, TAE achieved better BCVA at 24 months (mean difference, -0.26 logMAR; 95% CI, -0.50 to -0.02). CMT was lower with TAE at 12 months (mean difference, -47.0&#x2009;&#xb5;m; 95% CI, -86.1 to -8.0). Retinal haemorrhage recurrence was less frequent with TAE (16.4% vs. 52.4%; risk difference, -36.0%; 95% CI, -57.8% to -9.5%). In multivariable models, greater injection number and thinner baseline central choroidal thickness were associated with incident MA (P&#x2009;<&#x2009;0.05), whereas regimen type itself was not.<br><br>CONCLUSIONS: Despite a higher injection burden, TAE maintained superior functional outcomes over two years relative to PRN.}, }
@article {pmid42177462, year = {2026}, author = {Nakamura, M and Koido, S and Bito, T and Horiguchi, H and Shimizu, Y and Shimabuku, M and Taguchi, J and Gunji, H and Sugiyama, H and Nakano, T}, title = {WT1-pulsed dendritic cell vaccination for neovascular age-related macular degeneration: a phase I pilot feasibility study.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04946-y}, pmid = {42177462}, issn = {1471-2415}, support = {2022-016SR//The Jikei University Research Fund/ ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss. Although anti-VEGF therapy is effective, frequent injections carry risks and may not fully address the underlying disease process. Wilms' tumor gene 1 (WT1), an upstream regulator of VEGF, is expressed in choroidal neovascular membranes and may represent a biologically relevant adjunctive target in nAMD. This pilot study evaluated the safety, tolerability, and immunogenicity of WT1-targeted dendritic cell (WT1-DC) vaccines and their effects on retinal morphology and visual function in nAMD patients, with secondary endpoints including clinical outcomes and in vitro WT1-specific T-cell responses.<br><br>METHODS: Two patients initially received three monthly intravitreal injections of aflibercept (2&#xa0;mg each), followed by 15 subcutaneous vaccinations with WT1-DCs. The vaccine contained both WT1-specific helper and killer peptides restricted to HLA-A*24:02. In addition, a helper peptide restricted to MHC class II and class I (HLA-A*02:01/02:06) was used.<br><br>RESULTS: WT1-DC vaccination was well tolerated, and adverse events were limited. One patient maintained a stable retinal morphology and visual acuity without additional anti-VEGF therapy, whereas the other experienced recurrent subretinal fluid accumulation requiring intermittent rescue injections and a gradual decline in best-corrected visual acuity. Peripheral blood mononuclear cells from both patients exhibited functional CD4&#x2009;+&#x2009;and CD8&#x2009;+&#x2009;T-cell responses during vaccination and produced IFN-&#x3b3; and TNF-&#x3b1; upon WT1 peptide stimulation in vitro.<br><br>CONCLUSIONS: WT1-DC vaccination was feasible and well tolerated in these two patients who were clinically managed within the nAMD spectrum. Exploratory laboratory findings suggested WT1 peptide-responsive T-cell activity in vitro, but clinically meaningful in vivo immunogenicity was not established. Given the extremely small sample size, the confounding effect of prior anti-VEGF loading therapy, and diagnostic uncertainty regarding CNV etiology in one patient, no conclusions regarding therapeutic efficacy can be drawn. These observations support further investigations of WT1-DC vaccination in larger controlled studies.<br><br>TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTc030210068), registered May 7, 2021.}, }
@article {pmid42171393, year = {2026}, author = {Shen, T and Li, J and Yang, X and Xia, J and Zhou, H and Ma, Q and Wang, Y and Wang, J and Wang, Z and Liu, K and Yan, B}, title = {Genetic and epidemiological analyses of alcohol consumption patterns and age-related macular degeneration risk among current drinkers: a role for TNFRSF10A.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04124}, doi = {10.7189/jogh.16.04124}, pmid = {42171393}, issn = {2047-2986}, mesh = {Humans ; *Alcohol Drinking/epidemiology/genetics/adverse effects ; *Macular Degeneration/genetics/epidemiology ; Female ; Male ; Middle Aged ; Risk Factors ; Aged ; Mendelian Randomization Analysis ; Proportional Hazards Models ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Alcohol intake, a major modifiable lifestyle factor, has been variably associated with age-related macular degeneration (AMD). We aim to investigate the association and potential causal relevance of alcohol consumption with AMD risk using complementary epidemiological and genetic approaches.<br><br>METHODS: We used nonlinear Cox proportional hazards models to evaluate incident AMD associations among 440&#x2009;052 participants of European ancestry with a mean age of 56.7 years and of whom 53.7% were female. We employed two-sample Mendelian randomisation (MR), integrating summary-level genetic associations with cis-expression quantitative trait locus colocalisation between alcohol consumption (UK Biobank n&#x2009;=&#x2009;433&#x2009;353) and AMD (GWAS Catalog n&#x2009;=&#x2009;105&#x2009;248; FinnGen study n&#x2009;=&#x2009;474&#x2009;181), to refine genetic instruments for biologically relevant measures of alcohol consumption. We also used inverse-variance weighting (IVW) and conducted sensitivity analyses. In addition, we integrated publicly available single-cell RNA sequencing (scRNA-seq) data from human retina and retinal pigment epithelium/choroid tissues to assess cell-type-specific expression patterns of genes implicated in AMD.<br><br>RESULTS: Over the follow-up period, 1553 participants were diagnosed with AMD. Alcohol consumption was inversely associated with AMD risk (hazard ratio (HR)&#x2009;=&#x2009;0.83; 95% confidence interval (CI)&#x2009;=&#x2009;0.73&#x2009;-&#x2009;0.95), with the association being most pronounced for wine (HR&#x2009;=&#x2009;0.86; 95% CI&#x2009;=&#x2009;0.76&#x2009;-&#x2009;0.97). Beer consumption showed a positive association with AMD risk. These results were supported by MR analyses (IVW &#x3b2;&#x2009;=&#x2009;-0.13; P&#x2009;=&#x2009;0.02) and remained consistent in sensitivity analyses. Colocalisation analysis highlighted TNFRSF10A (PP.H4&#x2009;=&#x2009;0.98) as a shared locus associated with both alcohol intake and AMD risk. Integration with scRNA-seq data from human samples suggested endothelial cell-enriched expression of TNFRSF10A in AMD tissues, providing functional context for the genetic prioritisation of this locus.<br><br>CONCLUSIONS: Epidemiological and genetic data suggest that TNFRSF10A and its variants may be involved in AMD, with alcohol consumption patterns potentially contributing to this association. This provides new hypotheses for how lifestyle factors may influence disease risk. These findings should not be interpreted as evidence supporting alcohol consumption for AMD prevention, given the potential for residual confounding and the well-established health risks of alcohol.}, }
@article {pmid42171426, year = {2026}, author = {Muqit, MMK and Villani, GM and Dami, M and Druchkiv, V and Spampinato, G and Cadoni, S and Hornig, R and Holz, FG and Bittner, AK}, title = {Patient Preferences for the PRIMA Retinal Prosthesis for Vision Restoration for Dry Age-Related Macular Degeneration: An International Survey Study.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {5}, pages = {18}, doi = {10.1167/tvst.15.5.18}, pmid = {42171426}, issn = {2164-2591}, mesh = {Humans ; Male ; Female ; *Visual Prosthesis ; Aged ; Activities of Daily Living ; *Patient Preference ; Middle Aged ; Aged, 80 and over ; *Macular Degeneration ; Surveys and Questionnaires ; Visual Acuity ; *Geographic Atrophy/rehabilitation/physiopathology ; *Electric Stimulation Therapy ; }, abstract = {PURPOSE: To gauge age-related macular degeneration (AMD) patient opinions on the potential acceptability of the PRIMA neurostimulation device for partial vision restoration during activities of daily living (ADLs).<br><br>METHODS: An international multisite survey study was completed by 196 visually impaired AMD individuals online through a foundation or society (United States, United Kingdom) or via telephone or in-person interviews (Italy, France, Germany) to inquire about ADLs for which retinal implant systems could potentially offer assistance.<br><br>RESULTS: A high level of interest ("very likely") to use a vision restoration device was reported by approximately half of the respondents for completing documents, recognizing people, hobbies, identifying money, reading street signs and store names, and seeing signs in public. The odds of being very likely to use a vision restoration device for these tasks were not statistically significantly related to whether the participant had partial or severe sight loss. Odds of being very likely to use it for completing documents or reading mail (odds ratio = 2.33; 95% confidence interval, 1.2-4.5; P = 0.013) were significantly greater among those who had stopped doing these tasks or relied on others. The majority (66.5%) indicated that they would be comfortable wearing the vision restoration glasses around others. Participation in vision rehabilitation was acceptable if the training duration was not excessive.<br><br>CONCLUSIONS: AMD respondents with varying vision loss indicated interest and acceptability of a vision restoration device for ADLs.<br><br>TRANSLATIONAL RELEVANCE: In support of future research and development efforts, AMD respondents endorsed high levels of willingness to use a vision restoration system involving a surgically implanted device and electronic glasses.}, }
@article {pmid42172633, year = {2026}, author = {Mei, L and Weh, E and Yu, M and Walsh, L and Fahim, AT and Liu, Y and Besirli, CG and Schwendeman, A}, title = {High-Density Lipoprotein Nanoparticles Delivering Liver X Receptor Agonist for the Treatment of Age-Related Macular Degeneration.}, journal = {Molecular pharmaceutics}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.molpharmaceut.5c01852}, pmid = {42172633}, issn = {1543-8392}, abstract = {Liver X nuclear receptor (LXR) agonists are promising therapeutic agents whose efficacy has been demonstrated in vitro and in vivo for the treatment of atherosclerosis. The accumulation of lipids is a common pathogenic mechanism between both atherosclerosis and age-related macular degeneration (AMD). As such, a growing number of studies have implicated LXR agonists as a potential therapeutic option for the treatment of AMD. Unfortunately, the clinical application of LXR agonists has been hindered by their undesirable side effects when administered systemically, as well as their limited aqueous solubility, necessitating a drug delivery system (DDS) for targeted local delivery. Synthetic high-density lipoprotein (sHDL) nanoparticles have intrinsic cholesterol transport and anti-inflammatory functions, making them ideal for the treatment of diseases where cholesterol accumulation and inflammation contribute to the pathology. These nanoparticles also excel as an effective DDS for hydrophobic drugs due to their ability to encapsulate drugs in their hydrophobic core. Thus, we developed a new strategy for AMD treatment by encapsulating an LXR agonist, T0, in sHDL nanoparticles (sHDL-T0). Our in vitro studies showed that sHDL-T0 can effectively upregulate cholesterol transport from mature iPSC-RPE (retinal pigment epithelium) due to increased transcription of cholesterol transporters and by serving as an acceptor for effluxed cholesterol. Encapsulating T0 in sHDL nanoparticles increased the aqueous solubility of T0 significantly, allowing for direct delivery to the eye without organic solvents. In vivo delivery of sHDL-T0 caused upregulation of the Abca1/g1 transporters in the retina and retinal pigment epithelium, suggesting that T0 can escape sHDL nanoparticles and stimulate the LXR pathway. Most importantly, in a murine model of nonexudative (dry) age-related macular degeneration (dAMD), sHDL-T0 administration resulted in the down-regulation of Tnfα, Il-6, and Nlrp3 mRNA expression, and reduced the number of CD45-positive inflammatory cells in comparison to vehicle-treated eyes. Our results provide proof-of-concept for using sHDL nanoparticles to deliver the LXR agonist T0 to restore cholesterol homeostasis and reduce local inflammation in the outer retina, offering a novel therapeutic strategy for dAMD.}, }
@article {pmid42164977, year = {2026}, author = {Dhoot, DS and Garg, SJ and Brown, DM and Suñer, IJ and Rahimy, E and Boyer, DS and Naidu, K and Li, C and Baumal, CR and Guymer, RH}, title = {Efficacy of Continuous Pegcetacoplan Treatment for Subfoveal Geographic Atrophy in Age-Related Macular Degeneration: 36-Month Results from OAKS, DERBY, and GALE Open-Label Extension.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {579237}, pmid = {42164977}, issn = {1177-5467}, abstract = {PURPOSE: To report efficacy of intravitreal pegcetacoplan treatment over 36 months in eyes with subfoveal geographic atrophy (GA).<br><br>PATIENTS AND METHODS: The GALE (NCT04770545) open-label extension trial adds 12 months of results to the 24-month Phase 3 OAKS (NCT03525613) and DERBY (NCT03525600) trials, representing up to 36 months of continuous pegcetacoplan treatment. They included a heterogeneous population of eyes with subfoveal GA (63%). Pegcetacoplan-treated eyes enrolling in GALE continued at the same interval of pegcetacoplan monthly (PM) or every other month (PEOM). Patients' eyes in sham monthly or every-other-month arms crossed over to receive pegcetacoplan in GALE at the same interval (sham crossover). Consequently, projected sham, calculated from prior 24-month GA growth rate of sham-observed eyes in OAKS and DERBY averaged across four 6-month segments, was the comparator for the first 12 months of GALE (months 24-36). This analysis reports results of eyes with subfoveal GA at baseline.<br><br>RESULTS: In eyes with subfoveal GA, 84% had best corrected visual acuity (BCVA) &#x2265;20/200 and 38% had BCVA &#x2265;20/63 at OAKS and DERBY baseline. Pegcetacoplan reduced subfoveal GA growth rate by 21% (p<0.0001) with PM and 19% (p=0.0001) with PEOM over 36 months. Increasing efficacy over time was noted between months 24 and 36; 31% reduction in subfoveal GA growth rate with PM and 25% reduction with PEOM (both p<0.0001) compared with projected sham. Microperimetry demonstrated significant reduction in formation of absolute scotomas with PM at 24 months (-2.5 number of scotomas formed; 95% confidence interval [CI]: -4.5, -0.4; p=0.0205) and 36 months (-4.0 number of scotomas formed; 95% CI: -6.8, -1.2; p=0.0050), compared to sham crossover in subfoveal GA. Safety profile in GALE was consistent with OAKS and DERBY.<br><br>CONCLUSION: Long-term efficacy of pegcetacoplan in slowing GA progression was demonstrated over 36 months in eyes with subfoveal GA.}, }
@article {pmid42165512, year = {2026}, author = {Yeh, TC and Lin, JB and Mruthyunjaya, P and Leng, T and DeBoer, C and Sepah, YJ and Almeida, DRP and Smith, S and Mahajan, VB}, title = {A Simplified Classification for Age-Related Macular Degeneration Based on Optical Coherence Tomography.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-7}, doi = {10.3928/23258160-20260409-02}, pmid = {42165512}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: As optical coherence tomography (OCT) has enabled the identification of an expanding set of age-related macular degeneration (AMD) risk biomarkers and become central to routine clinical practice, there remains a need for a simplified grading scheme that allows physicians to communicate and synchronize AMD grading directly from standard OCT imaging rather than relying on traditional color fundus imaging. This study aims to establish a standardized OCT-based AMD classification that balances diagnostic accuracy with practicality for use across clinical and research settings.<br><br>PATIENTS AND METHODS: Spectral-domain OCT scans were independently graded by two retinal specialists following the newly proposed Stanford OCT-Based AMD Classification (SOAC). Discrepancies were adjudicated by a third independent retinal specialist. Inter-grader agreement was assessed using weighted kappa coefficients.<br><br>RESULTS: Among the 109 eyes from 108 patients (mean age 79.61 &#xb1; 7.57 years; 41.7% men, 58.3% women), AMD staging based on SOAC was distributed as follows: normal aging in nine patients (8.3%), early AMD in 16 (14.7%), intermediate AMD in 32 (29.4%), neovascular AMD (nAMD) in 18 (16.5%), geographic atrophy (GA) in 20 (18.3%), and combined nAMD and GA in 14 (12.8%). The overall intergrader agreement demonstrated robust consistency, with a weighted kappa value of 0.95 (95% CI: 0.92-0.98), signifying excellent intergrader reliability and reinforcing the validity of SOAC.<br><br>CONCLUSION: SOAC provides a standardized, OCT-based framework for AMD grading that demonstrates high intergrader agreement. By enabling consistent classification from commonly acquired OCT scans, SOAC supports reliable disease staging and facilitates integration across clinical studies and translational research. As imaging and molecular data continue to expand, SOAC can serve as a common OCT-based reference for phenotype refinement and longitudinal AMD studies.}, }
@article {pmid42166380, year = {2026}, author = {Prieto-Nevárez, HM and Tarango-García, A and Ollivier-Valenzuela, LI and Álvarez-Cardona, A and Lugo-Reyes, SO}, title = {Immune Privilege of the Eye: A Delicate Balance Between Clarity and Chaos.}, journal = {Ocular immunology and inflammation}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/09273948.2026.2677099}, pmid = {42166380}, issn = {1744-5078}, abstract = {PURPOSE: This review aims to describe the key mechanisms behind ocular immune privilege and how disruption of this immunological balance contributes to ocular disease.<br><br>METHODS: A narrative review of the literature was performed focusing on ocular immune privilege and diseases in which these mechanisms are altered. The review considered evidence related to corneal transplantation, peripheral ulcerative keratitis, age-related macular degeneration, autoimmune uveitis, diabetic retinopathy, ocular tumors, and allergic conjunctivitis.<br><br>RESULTS: The reviewed literature demonstrates how ocular immune privilege is maintained mainly by a combination of anatomical barriers, local immunomodulatory mediators, regulatory immune-cell interactions, and ACAID-mediated systemic tolerance. Across the ocular conditions reviewed, disease was generally associated with partial disruption, remodeling, or exploitation of these mechanisms rather than complete loss of immuneprivilege. These alterations varied according to the affected ocular compartment and clinical context, but recurrently involved disruption of immune homeostasis, increased inflammatory signaling, altered leukocyte activity, impaired barrier integrity, and reduced local immune restraint. Overall, the evidence supports ocular immune privilege as a dynamic system that is not absolute, preserving ocular homeostasis under normal conditions but contributing to disease when its protective mechanisms are disrupted.<br><br>CONCLUSIONS: Ocular immune privilege is best understood as a protective but conditional state. Its disruption does not entirely explain most ocular diseases by itself, but it helps illustrate why inflammation, transplantation, tumors, allergy, and other pathologies can behave differently in ocular tissues. Recognizing which elements are preserved or lost in each setting may improve understanding of ocular pathology and support more precise immune-directed approaches.}, }
@article {pmid42168916, year = {2026}, author = {Wang, YX and Holz, FG and Coenen, M and Sun, X and Xie, W and Panda-Jonas, S and Dong, L and Jonas, JB}, title = {Safety and pharmacokinetics of intravitreally repeatedly injected panitumumab in non-human primates - a study performed under good laboratory practice.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04909-3}, pmid = {42168916}, issn = {1471-2415}, support = {2019-4//Research Development Fund of Beijing Municipal Health Commission/ ; }, abstract = {BACKGROUND: Epidermal growth factor (EGF) has been suggested to play a role in myopic axial elongation, and EGF receptor blockade may be of potential therapeutic benefit. Here we examined the ocular and systemic toxicity of panitumumab, a clinically used EGF receptor blocker in oncology, when repeatedly administered intravitreally in non-human primates.<br><br>METHODS: The experimental study included six non-human cynomolgus primates (3 males) which underwent five (n&#x2009;=&#x2009;1 animal) or three (n&#x2009;=&#x2009;5 animals) 4-weekly intravitreal injections of panitumumab (dose: 0.78&#xa0;mg (78&#xb5;L)) or of phosphate buffered solution (PBS) (78&#xb5;L).<br><br>RESULTS: The study group with panitumumab injections consisted of 7 eyes and the control group with PBS injections of 5 eyes. Two animals of the study group developed on Day 59 (two days after the third injection) signs of a slight intraocular inflammation (cells in anterior chamber and vitreous) and reduction of intraocular pressure, with most of the signs having resolved at study end (Day 86). Panitumumab reached the serum peak concentration at 24&#xa0;h after the first dose (Cmax 18.3 to 946ng/mL; serum exposure 2120 to 37300&#xa0;h*ng/mL). Four weeks after the third injection (Day 86), panitumumab concentrations in aqueous humor ranged from 12.8 ng/mL to 65.0 ng/mL, and in the vitreous from 1.74 ng/mL to 531 ng/mL, with a panitumumab accumulation factor between 0.891 and 0.012. TUNEL staining did not reveal pathological results.<br><br>CONCLUSIONS: Except for mild and reversible intraocular inflammation in some eyes, repeated intravitreal application of 0.78&#xa0;mg panitumumab did not result in ophthalmological or systemic adverse effects in non-human primates.}, }
@article {pmid42156641, year = {2026}, author = {Kuznik, A and Coughlan, A and Pinsent, A and Toro-Diaz, H and Sherman, S and Patel, NA}, title = {Summary of Research: Economic Benefit of Aflibercept 8 mg Versus Faricimab for Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema in the US.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42156641}, issn = {2193-8245}, abstract = {This is a summary of the original article "Economic Benefit of Aflibercept 8 mg Versus Faricimab for Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema in the US". Aflibercept 8 mg and faricimab are medications given by injections into the eye for treating the eye diseases neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Comparing costs of these medications is important for patients, healthcare practitioners, and the people who pay for medications (payers). This research used an economic model to compare the estimated costs of aflibercept 8 mg and faricimab over 5 years in the United States, based on numbers of injections given in clinical trials. The analysis indicated that the lower number of injections needed for aflibercept 8 mg would lead to lower costs compared with faricimab for patients with nAMD or DME, which could benefit patients, healthcare providers, and payers.}, }
@article {pmid42156919, year = {2026}, author = {Singappuli, R and Abeysiri, P and Rahman, W}, title = {Infographic: Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, Phase 3 trial.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42156919}, issn = {1476-5454}, }
@article {pmid42159203, year = {2026}, author = {Yu, HN and Ying, GS}, title = {Associations Between Age-Related Eye Diseases and Mental Health Conditions.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/09286586.2026.2675294}, pmid = {42159203}, issn = {1744-5086}, abstract = {PURPOSE: Age-related eye conditions, including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED), are prevalent and have been linked to mental health disorders, though findings are mixed. This study systematically examines associations between these ocular diseases and mental health conditions using a large real-world dataset.<br><br>METHODS: A retrospective cohort study was conducted using the Global TriNetX database. Five cohorts (aged&#x2009;&#x2265;&#x2009;40&#x2009;years) with diagnoses of cataract, glaucoma, AMD, DR, and DED were propensity score matched 1:1 with controls without these eye diseases based on demographic and clinical covariates. Outcome measures were the incidence of mood, anxiety, and psychotic disorders, identified using ICD-10 codes. Hazard ratios (HRs) and 95% confidence intervals (95% CI) from the Cox proportional hazards models were used to assess associations.<br><br>RESULTS: Study included patients with cataract (N&#x2009;=&#x2009;121,060), glaucoma (N&#x2009;=&#x2009;122,663), AMD (N&#x2009;=&#x2009;39,915), DR (n&#x2009;=&#x2009;43,495), DED (n&#x2009;=&#x2009;148,221), and their median follow-up ranging 1263-2191&#x2009;days. Cataracts, glaucoma, DR, and DED were each associated with mildly increased risks of mood (HR range: 1.05-1.10), anxiety (HR range: 1.04-1.12), and psychotic disorders (HR range: 1.18-1.36). When accompanied by visual impairment, risks were higher: mood (HR range: 1.22-1.57), anxiety (HR range: 1.16-1.32), and psychotic disorders (HR range: 1.54-2.15).<br><br>CONCLUSION: Age-related ocular diseases, particularly when presented with vision impairment, are independently associated with elevated risks of mental health disorders. These findings underscore the need for integrated ophthalmic-psychiatric care and early intervention before vision loss to address the complex needs of affected patients.}, }
@article {pmid42162248, year = {2026}, author = {Korobelnik, JF and Leal, S and Lanzetta, P and , }, title = {Infographic: Efficacy and Safety of HighDdose Intravitreal Aflibercept 8 mg in Patients with Treatment-Naïve Neovascular Age-Related Macular Degeneration: Week 96 Results from the Phase 3 PULSAR Trial.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-026-04486-1}, pmid = {42162248}, issn = {1476-5454}, }
@article {pmid42162254, year = {2026}, author = {Ezzine, S and Gale, R and Bailey, C and Patel, PJ and Sivaprasad, S and Keshk, Z and Eissing, T and Höchel, J and Gilbert, R and Morgan-Warren, P}, title = {Pharmacological principles of intravitreal drug therapy and their implications for clinical practice: a primer for the ophthalmologist.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {42162254}, issn = {1476-5454}, abstract = {Intravitreal (IVT) anti-vascular endothelial growth factor (anti-VEGF) therapies are the standard of care for retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Despite the favourable efficacy and safety profiles of these therapies, decreasing the treatment burden is still an unmet need because frequent injections may be required over many years. The pharmacokinetic and pharmacodynamic properties of IVT therapies, such as ocular half-life and clearance, can affect the duration of VEGF suppression and thus influence clinical outcomes. Although some properties are inherent to the drug molecule (such as molecular weight, binding affinity and potency) and cannot be altered without changing the structure of the molecule, other factors (such as the dose of the drug) can be increased, which may prolong VEGF suppression time in the eye and, in turn, may lead to a more durable effect of the drug. In addition to pharmacokinetic and pharmacodynamic properties, individual patient factors such as age, surgical history and disease status can also affect the pharmacokinetics, pharmacodynamics and observed effectiveness of a drug. This article reviews the key pharmacological properties of IVT anti-VEGF treatments for nAMD and DMO often referred to in the literature, and aims to elucidate their meaning and clinical relevance for managing retinal diseases.}, }
@article {pmid42162902, year = {2026}, author = {Lin, R and Cai, Z and Zheng, T and Wu, Y and Xu, Z and Luo, Y and Liang, F and Zhu, M and Yu, J and Cai, W}, title = {Macrophage-derived SPP1 promotes subretinal fibrosis by YAP1 phase separation in retinal pigment epithelium.}, journal = {Metabolism: clinical and experimental}, volume = {}, number = {}, pages = {156648}, doi = {10.1016/j.metabol.2026.156648}, pmid = {42162902}, issn = {1532-8600}, abstract = {BACKGROUND: Subretinal fibrosis (SRF) is a critical end-stage feature of neovascular age-related macular degeneration (nAMD) with limited treatment options. However, the pathological mechanism during the transformation of choroidal neovascularization (CNV) into SRF remains unclear.<br><br>METHODS: Bulk RNA-seq of mouse macrophages treated with succinate or lactate in acidic hypoxia identified Spp1 as a key fibrosis-associated gene. Dynamic Spp1 expression was tracked by single-cell RNA-seq in a CNV model, while laser-induced CNV and SRF models assessed the pro-fibrotic role of Spp1 in vivo. In vitro, the binding of SPP1 to RPE CD44 was identified through bioinformatics and Co-IP, and Western blotting examined downstream CD44/RhoA/YAP1 pathway proteins. qPCR quantified nine YAP1 isoforms to identify the predominant one after SPP1 intervention. The specific YAP1 isoform undergoing liquid-liquid phase separation (LLPS) was determined by visualizing intracellular localization and biomolecular condensates via EGFP-tagged plasmid transfection, with LLPS characteristics confirmed by live-cell imaging and fluorescence recovery after photobleaching (FRAP). ATAC-seq identified the transcription factors co-activated with YAP1 driving fibrosis, while EMT phenotypes were evaluated using pro-fibrotic gene expression, migration, and collagen contraction assays.<br><br>RESULTS: Succinate and lactate upregulated Spp1 and activated correlated Ca[2+] influx pathways. An expanding Spp1[+] M&#x3c6; population was found in early-to-mid CNV. SRF mice showed elevated Spp1in M&#x3c6;s, and intravitreal Spp1 worsened CNV fibrosis, which blocked by small interfering extracellular matrix receptor III (siCD44). In vitro, SPP1 bound to CD44 activated the RhoA/YAP1 pathway, characterized by a predominant isoform shift from YAP1-1&#x3b1; to YAP1-2&#x3b1;. The nuclear translocation and LLPS of YAP1-2&#x3b1; facilitated pro-fibrotic gene transcription by binding to TEAD4, thereby promoting EMT-like changes in RPE.<br><br>CONCLUSIONS: Under accumulation of acidic metabolites, SPP1-overexpressing M&#x3c6;s promote EMT in the RPE via CD44/RhoA-mediated YAP1-2&#x3b1; LLPS. This process involves binding to TEAD4 to co-activate pro-fibrotic gene transcription, revealing novel pathomechanisms involved in SRF progression.}, }
@article {pmid42163181, year = {2026}, author = {Akkan Aydogmus, FS and Gursoy, T and Ozdemir, O and Elalmis, OU and Kalayci, D}, title = {Outcome and factors affecting prognosis in treat and extend treatment for neovascular age-related macular degeneration-a real world study.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04905-7}, pmid = {42163181}, issn = {1471-2415}, abstract = {BACKGROUND: To evaluate the outcome of treat and extend (T&amp;E) for neovascular age related macular degeneration (nAMD) at 12, 18 and 24 months and the impact of clinical characteristics on treatment success defined as extension of treatment interval to ≥12 weeks and functional improvement or stability.<br><br>METHODS: Visual and anatomical outcomes evaluated by optical coherence tomography (OCT) and extension of treatment interval to &#x2265;12&#x2009;weeks were analyzed retrospectively. Clinical factors effective on extension of the treatment interval and visual outcome were evaluated.<br><br>RESULTS: There were 138 eyes with at least 18&#x2009;months of follow-up. Patients exhibited a significant improvement in visual acuity and reduction in central subfield thickness (CST), subretinal fluid (SRF), intraretinal fluid (IRF) and pigment epithelial detachment (PED) at both the 12[th] and 18[th] months. There was recurrence of IRF and a reduction in gain of visual acuity at 24&#x2009;months. In 15.2%, 36.2% and 40.6% of eyes, the treatment interval could be extended to &#x2265;12-weeks at 12, 18 and 24&#x2009;months. Presence of a large PED was found as the only independent variable effecting extension of treatment interval to 12&#x2009;weeks at 18&#x2009;months. Baseline BCVA of >20/100 and no IRF at baseline were identified as independent predictive factors for better visual acuity at 18&#x2009;months.<br><br>CONCLUSION: Presence of IRF and a visual acuity of &#x2264;20/100 at baseline were found to be negative predictors for visual prognosis, while large PED was a negative predictive factor for less frequent treatment, but it did not affect visual outcome. Treatment interval should be extended cautiously in patients with baseline intraretinal fluid and visual acuity of &#x2264;20/100 in order to balance decreasing the burden of treatment by longer treatment intervals with improvement of visual gain.}, }
@article {pmid42163661, year = {2026}, author = {Liu, S and Zhang, M and Xie, H and Ding, X and Chen, Y and Wang, X and Cui, H and Wang, X}, title = {Neuroprotective Effects of Glucagon-like Peptide-1/glucagon-like Peptide-1 Receptor Agonists on Neurodegenerative Eye Diseases and their Molecular Mechanisms: A Recent Update.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X446766260311123827}, pmid = {42163661}, issn = {1875-6190}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a novel class of glucose-lowering drugs, specifically bind to the glucagon-like peptide-1 receptor and substantially improve glycemic control by mimicking the physiological effects of endogenous glucagon-like peptide-1 (GLP-1). Recent studies have shown multiple beneficial effects of GLP-1 and GLP-1RAs, including anti-inflammatory, antioxidant, and neuroprotective effects, indicating their potential therapeutic applications in treating neurodegenerative diseases. Notably, several ocular disorders, including diabetic retinopathy, glaucoma, age-related macular degeneration, and dry eye disease, also exhibit neurodegeneration-related pathophysiological changes. Hence, it is critical to explore new therapeutic strategies to address the clinical challenges posed by these neurodegenerative ocular diseases. Given this background, we conducted a review of recent preclinical and clinical studies to update and summarize (1) the therapeutic potential of GLP-1/GLP-1RAs for neurodegenerative ocular diseases, (2) clinical evidence supporting the neuroprotective effects of GLP-1/GLP-1RAs in these ocular diseases, and (3) the molecular mechanisms underlying the neuroprotective effects of GLP-1/GLP-1RAs on ocular neural cells, including inflammatory and oxidative stress response inhibition and Ca2+ homeostasis regulation. This review aims to provide a theoretical foundation and research outlook for extending the application of GLP-1RAs to treat neurodegenerative ocular diseases.}, }
@article {pmid42164429, year = {2026}, author = {Raghavendra, AJ and Saeedi, OJ and Hammer, DX and Liu, Z}, title = {Single-scan adaptive optics-enabled quantitative optical coherence tomography angiography for absolute three-dimensional retinal blood flow mapping.}, journal = {Optica}, volume = {13}, number = {1}, pages = {125-134}, pmid = {42164429}, issn = {2334-2536}, abstract = {Accurate measurement of blood flow is critical for understanding metabolic function and disease progression, particularly in the retina, where conditions such as diabetic retinopathy, macular degeneration, and glaucoma are closely linked to impairment in microvascular circulation. However, current imaging techniques, including optical coherence tomography angiography (OCTA) and Doppler OCT, do not generally provide direct and absolute blood flow measurements, particularly at the capillary level. Adoption of adaptive optics (AO) and high-speed swept-source lasers in OCT systems has enabled video-rate volumetric acquisition with the ability to resolve individual red blood cells (RBC). Here, we present a quantitative AO-OCTA approach that enables 3D blood flow mapping by integrating OCTA-based vessel morphology with a 3D Radon transform of RBC streaks to measure cell velocity from the raw spatio-temporal OCT data. We describe a complete post-processing pipeline to determine single-cell velocity, vessel diameter, and flow rate using a single scan. We demonstrate depth-resolved flow rates across retinal vessels with diameters from 5 to 120 μm and velocities ranging from 0.5 to 54 mm/s, capturing the wide range of flow dynamics in the human retina. Our methodology is a powerful tool for quantitative blood flow imaging, establishing a robust method for noninvasive, high-resolution microvascular flow quantification with multiple potential applications in biomedical research and clinical diagnostics.}, }
@article {pmid42164909, year = {2026}, author = {Dihan, QA and Brown, AD and Alshammari, N and Shakarchi, AF and Chauhan, MZ and Sallam, AB}, title = {Eye on the Eclipse: Demographic Trends in Solar Retinopathy From 2012 to 2024.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261447500}, pmid = {42164909}, issn = {2474-1272}, abstract = {Purpose: To characterize demographic, psychiatric, and retinal comorbidities associated with solar retinopathy in the United States from 2012 to 2024 and to evaluate incidence trends in relation to solar eclipse years. Methods: This retrospective, population-based cohort study was conducted using the TriNetX US Collaborative Research Network. Patients with newly diagnosed solar retinopathy (International Classification of Diseases, 10th edition, code H31.02) were identified and included if they had a documented ophthalmology visit and retinal imaging. Annual incidence rates were compared between eclipse and non-eclipse years. Demographic characteristics and the prevalence of psychiatric disorders, substance use disorders, and concurrent retinal conditions were analyzed. Results: Among 1 042 995 patients, 555 were diagnosed with solar retinopathy. The mean annual incidence was 44.5 cases, with a peak observed in 2017 (71 cases). There was no statistically significant difference between eclipse years (51.5 cases/year) and non-eclipse years (37.3 cases/year; P = .062). The median age at diagnosis was 54.1 ± 21.3 years, and 59% of patients were men. Sixty-eight percent of individuals were White, 27% were Black, and 5% were Asian. Psychiatric comorbidities were common, with 32% diagnosed with anxiety disorders, 24% with major depressive episodes, and 10% with psychotic disorders. Substance use disorders were also observed, including nicotine dependence (18%) and cannabis-related disorders (6%). Concurrent retinal conditions included age-related macular degeneration (8%), hereditary retinal dystrophies (7%), and central serous chorioretinopathy (3%). There was no correlation between solar retinopathy incidence and geographic exposure to eclipse totality. Conclusions: The incidence of solar retinopathy remained low over the study period, with no significant increase during eclipse years. However, psychiatric and retinal comorbidities were prevalent among affected individuals. These findings highlight demographic and psychosocial disparities and support the need for targeted, culturally informed preventive education and eye safety initiatives before future eclipses.}, }
@article {pmid42156546, year = {2026}, author = {Ghareeb, AE and Chang, B and Mitchener, L and Yiu, A and Szostkiewicz, CJ and Shved, D and Gyimesi, GJ and Laurent, JM and Wright, SM and Razzak, MT and White, AD and Finnemann, SC and Hinks, MM and Rodriques, SG}, title = {A multi-agent system for automating scientific discovery.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41586-026-10652-y}, pmid = {42156546}, issn = {1476-4687}, abstract = {Scientific discovery is driven by the iterative process of observation, hypothesis generation, experimentation, and data analysis. Despite recent advancements in applying artificial intelligence to biology, no system has yet automated all these stages [1, 2, 3]. Here, we introduce Robin, the first multi-agent system capable of fully automating both hypothesis generation and data analysis for experimental biology. By integrating literature search agents with data analysis agents, Robin can generate hypotheses, propose experiments, interpret experimental results, and generate updated hypotheses, achieving a semi-autonomous approach to scientific discovery. By applying this system, we were able to identify promising therapeutic candidates for dry age-related macular degeneration (dAMD), the major cause of blindness in the developed world [4, 5]. Robin proposed enhancing retinal pigment epithelium phagocytosis as a therapeutic strategy, and identified and confirmed in vitro efficacy for ripasudil and KL001. Ripasudil is a clinically-used Rho kinase (ROCK) inhibitor that has never previously been proposed for treating dAMD. To elucidate the mechanism of ripasudil-induced upregulation of phagocytosis, Robin then proposed and analyzed a follow-up RNA-seq experiment, which revealed upregulation of ABCA1, a lipid efflux pump and possible novel target. All hypotheses, experimental directions, data analyses, and data figures in the main text of this report were produced by Robin. As the first AI system to autonomously discover and validate novel therapeutic candidates within an iterative lab-in-the-loop framework, Robin establishes a new paradigm for AI-driven scientific discovery.}, }
@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 &amp; 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.<br><br>METHODS: We describe four cases of macular telangiectasia type 1 and Coats&#x2019; disease with macular edema, which were treated with intravitreal faricimab injection.<br><br>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&#x2019; disease achieved improved telangiectatic vessel at macula and visual recovery following eight monthly injections of faricimab, with central macular thickness (CMT) reduced from 645&#xa0;&#x3bc;m to 217&#xa0;&#x3bc;m 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&#xa0;&#x3bc;m to 219&#xa0;&#x3bc;m) 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&#x2019; disease demonstrated partial response with reduced macular edema, while in case 4, with a Coats&#x2019; disease, showed no response after two faricimab injections.<br><br>CONCLUSIONS: Faricimab may provide therapeutic benefits in cases of macular telangiectasia type 1 and Coats&#x2019; 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.<br><br>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.<br><br>RESULTS: The patients manifested no resistance to thyroid hormone beta (RTH&#x3b2;) 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 TR&#x3b2;1, producing a deletion of 87 amino acids in the N-terminal domain (TR&#x3b2;1[&#x394;NTD]). In vitro, DNA-binding affinity of TR&#x3b2;1[&#x394;NTD] to DR4-TRE with or without RXR&#x3b1; was comparable to TR&#x3b2;1[WT]. Surprisingly, TR&#x3b2;1[&#x394;NTD] was transcriptionally twice more active than TR&#x3b2;1[WT] with a similar EC50 for T3, demonstrating gain-of-function of TR&#x3b2;1[&#x394;NTD]. THRA expression in leukocytes was increased by 3-fold compared to unrelated controls and different from RTH&#x3b2; patients.<br><br>CONCLUSION: These THRB splice site variants produce TR&#x3b2;1 exon 4 skipping, resulting in a gain-of-function mutant, TR&#x3b2;1[&#x394;NTD]. This explains the dominant ADMD phenotype devoid of RTH&#x3b2; and suggests a TR&#x3b2;1 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.<br><br>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.<br><br>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.<br><br>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.}, }
@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.<br><br>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.<br><br>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 &amp; 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.<br><br>METHODS: We performed subretinal injections of Adeno-Associated Virus-CRISPR/Cas9-Abca4 constructs into postnatal (&#x223c;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.<br><br>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.<br><br>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.}, }
@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).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 83 eyes of 80 consecutive patients with treatment-na&#xef;ve 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.<br><br>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&#xb1;0.7, and the intended injection interval at the last visit was 13.4&#xb1;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.<br><br>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.<br><br>STUDY DESIGN: Interventional study METHODS: This retrospective study included 103 treatment-na&#xef;ve 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.<br><br>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 &#xd7; 10&#x207b;[3]) and remained independently associated with retreatment after adjustment for age, sex, and baseline visual acuity (p = 3.0 &#xd7; 10&#x207b;[3]). Eyes with the TT genotype required significantly more additional injections than those with the TG or GG genotypes (2.4 &#xb1; 1.7 vs. 1.3 &#xb1; 1.6 and 1.3 &#xb1; 1.5, respectively; p = 5.0 &#xd7; 10&#x207b;[3]). Kaplan-Meier analysis demonstrated a significant difference in retreatment-free survival among ARMS2 genotypes (p = 4.1 &#xd7; 10&#x207b;[4]). Visual outcomes did not differ across any genotypes.<br><br>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.<br><br>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&#xa0;weeks. All eyes had received four consecutive intravitreal injections of aflibercept 2&#xa0;mg prior to switching to aflibercept 8&#xa0;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&#xa0;months.<br><br>RESULTS: Fifty patients (50 eyes) were included (mean age 78.4&#x2009;&#xb1;&#x2009;6.9&#xa0;years; 60% female). Median baseline DCVA was 0.19&#xa0;logMAR (IQR 0.12-0.32; 75.5 ETDRS letters), median CST 272&#xa0;&#xb5;m, and median CRT 338&#xa0;&#xb5;m. DCVA improved significantly at months&#xa0;3, 6, and 9 (p&#x2009;&#x2264;&#x2009;0.046) and remained stable at month&#xa0;12. CRT and CST decreased early and remained improved. Over 12&#xa0;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&#xa0;mg as a result of precautionary safety measures. Seventeen (34%) required&#x2009;&#x2264;&#x2009;8 injections per year.<br><br>CONCLUSIONS: In chronically treated patients with nAMD requiring short re-treatment intervals, switching to aflibercept 8&#xa0;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.<br><br>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 &amp; 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).<br><br>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.<br><br>RESULTS: After matching, 126,799 cases comprising 53.1% female patients with a mean age of 74.6 &#xb1; 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).<br><br>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.}, }
@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.}, }
@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).<br><br>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.<br><br>DESIGN: Retrospective case series.<br><br>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&#x2009;mg.<br><br>RESULTS: Forty-eight patients were treated (68.8% women; mean age, 80&#x2009;years). A median of 14&#x2009;days elapsed between SMH onset and surgical intervention (range, 2-120&#x2009;days), with vitrectomy performed after &#x2a7e;30&#x2009;days in 39.6% of patients. A significant improvement from baseline in mean best-corrected visual acuity (BCVA) was observed 6&#x2009;months after SMH treatment (1.6 (baseline) vs 0.9 (Month 6) logMAR; p&#x2009;<&#x2009;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&#x2009;=&#x2009;0.11). The main biomarkers predicting surgical outcome were the state of the retina in the foveal center point and hemorrhage thickness. Treatment &#x2a7e;30&#x2009;days after SMH onset resulted in poorer BCVA at Month 6 compared with treatment occurring <30&#x2009;days after onset (p&#x2009;<&#x2009;0.05).<br><br>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.<br><br>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.<br><br>RESULTS: AMD patients had an increased risk of AMI (adjusted HR&#x2009;=&#x2009;1.45, 95% CI&#x2009;=&#x2009;1.25-1.69) and IS (adjusted HR&#x2009;=&#x2009;1.78, 95% CI&#x2009;=&#x2009;1.52-2.09) compared to controls. CVD patients had a higher risk of AMD (adjusted HR&#x2009;=&#x2009;2.57, 95% CI&#x2009;=&#x2009;1.30-5.09). Aspirin use among CVD patients was associated with a lower risk of AMD (HR&#x2009;=&#x2009;0.69, 95% CI&#x2009;=&#x2009;0.50-0.94). Several comorbidities, including diabetes, hypertension, and chronic kidney disease, further increased risks in both directions.<br><br>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 Yst&#xe4;v&#xe4;t/ ; //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).<br><br>METHODS: This single-centre retrospective study included a cohort of 3831 treatment-na&#xef;ve nAMD patients who were treated with bevacizumab monotherapy using a pro re nata protocol between 2008 and 2023, comprising a total of 79&#x2009;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&#x2009;weeks and &#x2264;8&#x2009;weeks, >8&#x2009;weeks and &#x2264;&#x2009;10&#x2009;weeks and >10&#x2009;weeks.<br><br>RESULTS: After an initial stabilisation in VA during the first treatment year, VA started to decline. The proportion of visits delayed >6&#x2009;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.<br><br>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.<br><br>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 &#xb5;m 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.<br><br>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 &#xb5;m; 95% credible interval [CrI], -25.0, -8.4) and 2 mg (-19.0 &#xb5;m; 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 &#xb5;m; 95% CrI, -35.0, -3.2) and 2 mg (-19.0 &#xb5;m; 95% CrI, -27.0, -12.0).<br><br>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.<br><br>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.<br><br>RESULTS: Mean pairwise Cohen's Kappa was 0.425 (range 0.19-0.73), indicating mild agreement. Agreement with the majority vote ranged from &#x3ba;=0.48&#x2009;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.<br><br>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).<br><br>METHODS: Cross-sectional study including 97 eyes from 70 patients (>55 years) with GA within 1500&#x2009;&#xb5;m 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.<br><br>RESULTS: Participants (age 78.8&#xb1;5.6 years; 70% female) had a median GA size of 4.0&#x2009;mm&#xb2;, with 64% showing subfoveal involvement. Larger GA size and higher %FI were significantly associated with worse VA, AULCSF, CA and CS at 1-12&#x2009;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&#x2009;cpd. GRF analysis identified GA size and %FI as primary predictors of CS loss, with best performance for AULCSF and CS at 3 cpd (R&#xb2;=0.319, 0.314).<br><br>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 &amp; 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 &amp; control ; Animals ; *Aptamers, Nucleotide/pharmacology/therapeutic use ; Humans ; Mice ; *Platelet-Derived Growth Factor/antagonists &amp; inhibitors ; Fibrosis/prevention &amp; control ; Disease Models, Animal ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Lymphokines/antagonists &amp; 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.<br><br>METHODS: A DNA aptamer against PDGF-C (&#x3b1;-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 (PDGFR&#x3b1;) interaction were assessed using surface plasmon resonance. The effects of the &#x3b1;-PC aptamer on PDGF-C-induced proliferation, migration, and PDGFR&#x3b1;, 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.<br><br>RESULTS: The &#x3b1;-PC aptamer specifically bound to PDGF-C and effectively blocked its binding to PDGFR&#x3b1;. The &#x3b1;-PC aptamer significantly inhibited PDGFR&#x3b1;, 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 &#x3b1;-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.<br><br>CONCLUSIONS: These findings suggest that the &#x3b1;-PC aptamer represents a promising therapeutic agent for treating neovascular diseases, especially in patients refractory to anti-VEGF treatment.}, }
@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.<br><br>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).<br><br>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&#xa0;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.<br><br>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 &#xa0;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 &amp; 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).<br><br>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.<br><br>RESULTS: Compared to the controls, the densities of the SCP and DCP were significantly decreased in Group 2 in some regions (p <&#x202f;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 =&#x202f;0.346, p =&#x202f;0.034).<br><br>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 &amp; 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 &amp; 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).<br><br>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 Scheff&#xe9; post hoc testing.<br><br>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 (&#x3b2; = -0.31, P < 0.001) in the regression analysis.<br><br>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.}, }
@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 &amp; 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 &amp; 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.<br><br>METHODS: This multicenter retrospective case series included 156 eyes of 138 treatment-na&#xef;ve 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.<br><br>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.<br><br>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.}, }
@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).<br><br>DESIGN: Evidence-based perspective.<br><br>METHODS: Review of literature and experience of authors.<br><br>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.<br><br>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.<br><br>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&#xb0; to 80&#xb0; anterior to the posterior pole, with a maximum growth at approximately 25&#xb0; anterior to the posterior pole.<br><br>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.<br><br>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 &amp; dosage ; Humans ; Delayed-Action Preparations/administration &amp; dosage ; Temperature ; *Drug Delivery Systems/methods ; Intravitreal Injections ; Drug Liberation ; Animals ; *Vision Disorders/drug therapy ; Ophthalmic Solutions/administration &amp; 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.}, }
@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.}, }
@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.<br><br>METHODS: A narrative review of peer-reviewed literature was conducted using PubMed. Searches combined the following MeSH terms: neuroinflammation, oxidative stress, retinal neurodegeneration, microglia, M&#xfc;ller 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.<br><br>RESULTS: Across all four diseases, persistent microglial and M&#xfc;ller 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.<br><br>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 [...].}, }
@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.<br><br>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.<br><br>RESULTS: The mean number of injections in the first treatment year was 6.79 &#xb1; 2.32. During 2019-2021, annual means were 5.09 &#xb1; 2.33, 5.40 &#xb1; 2.10, and 4.96 &#xb1; 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 &#xb1; 57 ETDRS letters at diagnosis to 62 &#xb1; 57 ETDRS letters by late 2021 (p < 0.0001). In the aflibercept-only subgroup, the decline was smaller and not significant (68 ETDRS letters &#xb1; 55 ETDRS letters to 66 &#xb1; 56 ETDRS letters; p > 0.27). CRT decreased significantly from 388.4 &#xb1; 139.4&#xa0;&#xb5;m at diagnosis to 320.8 &#xb1; 114.7&#xa0;&#xb5;m in 2019 and remained stable thereafter (p < 0.0001 vs. baseline; p > 0.5 between years).<br><br>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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>RESULTS: A total of 3 138 eyes (2 520 patients) were included in the analysis, followed up for 12 (n&#x202f;=&#x202f;2 426; 77.3%), 24 (n&#x202f;=&#x202f;1 793; 57.1%), and 36 months (n&#x202f;=&#x202f;1 167; 37.2%). GVE had significantly better 24-month final VA (71.0 &#xb1; 13.8 vs 52.3 &#xb1; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&#xd7;3 mm and 6&#xd7;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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.}, }
@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.<br><br>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&#x2009;=&#x2009;179). Non-persistence was defined as no visit or treatment for&#x2009;&#x2265;&#x2009;6&#xa0;months. Among patients remaining on therapy, non-adherence was defined as&#x2009;&#x2265;&#x2009;2 visit or injection gaps&#x2009;>&#x2009;16&#xa0;weeks within any 12-month window. Cox proportional-hazards models were used for time-to-event analyses.<br><br>RESULTS: The median age was 78&#xa0;years (IQR 71-86 years), and 26% of patients received bilateral injections. Over a median follow-up of 383&#xa0;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&#x2009;=&#x2009;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.<br><br>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.<br><br>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; &#x2265;3 injections (standard loading), also &#x2265;&#x2009;6 injections.<br><br>RESULTS: For all 622 eyes, presenting BCVA: 1.21&#x2009;&#xb1;&#x2009;0.84 and the final BCVA: 0.91&#x2009;&#xb1;&#x2009;0.80 (P&#x2009;=&#x2009;<&#x2009;0.001). Overall compliance with &#x2265;&#x2009;3 injections was 47.5%, and with &#x2265;&#x2009;6 injections, 10.1%. Compliance to &#x2265;&#x2009;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&#x2009;=&#x2009;0.264) and sex (P&#x2009;=&#x2009;0.870) did not affect compliance to &#x2265;&#x2009;3 injections. Clinic location significantly influenced compliance with &#x2265;&#x2009;3 injections (P&#x2009;=&#x2009;0.000), but not with 6 injections (P&#x2009;=&#x2009;0.173). The highest rates of compliance with &#x2265;&#x2009;3 injections were observed in urban tertiary centers. Injection type and cost were not significant factors (P&#x2009;=&#x2009;0.36). Eyes with &#x2265;&#x2009;3 injections achieved better vision (&#x2265;&#x2009;6/18) across all diagnoses; the most notable improvements were in non-AMD CNVM (+&#x2009;41.4%) and BRVO (+&#x2009;35%). Statistically significant LogMAR improvements were seen in CRVO (p&#x2009;=&#x2009;0.049) and DME (p&#x2009;=&#x2009;0.043). Postoperative endophthalmitis occurred in 2/622 eyes (0.0032) (both Avastin); no other serious adverse event was recorded.<br><br>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, &#xc2;}, 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.<br><br>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).<br><br>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).<br><br>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.}, }
@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).<br><br>METHODS: This is a retrospective, single-center cohort study using chart review and an electronic injection database, including treatment-na&#xef;ve patients with nAMD aged 50 years or older who received three monthly faricimab injections between 1 November 2023 and 31 August 2024.<br><br>RESULTS: Overall, 827 eyes of 742 patients were included in the study. Following the loading dose, the median injection-free interval was 15.0&#xa0;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&#xa0;weeks were 90.9%, 81.1%, 79.1%, 75.5%, 57.1%, 51.1%, 48.6%, and 29.4%, respectively. At 180&#xa0;days, 28.4% (n&#x2009;=&#x2009;235) of eyes remained injection-free, and 21.6% (n&#x2009;=&#x2009;179) were discharged from hospital-based care. At 4&#xa0;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&#x2009;<&#x2009;0.001), corresponding to a gain of approximately 4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters.<br><br>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&#xa0;weeks after loading may be unnecessary in many patients, whereas 8&#xa0;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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.}, }
@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 &amp; 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.}, }
@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.}, }
@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.}, }
@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.<br><br>CASE PRESENTATION: An 84-year-old man with well-controlled type 2 diabetes mellitus received intravitreal bevacizumab (1.25&#x2009;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&#x2009;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.<br><br>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.<br><br>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).<br><br>RESULTS: Drusen accumulate within the central 3&#x2009;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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>FUNDING: None.<br><br>TRIAL REGISTRATION: Not relevant.}, }
@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.<br><br>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.<br><br>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)).<br><br>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.<br><br>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.<br><br>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 &#xb1; 1.30 for knowledge, 43.05 &#xb1; 3.48 for attitude, and 22.36 &#xb1; 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.<br><br>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.}, }
@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.<br><br>METHODS: This population-based prospective cohort study analysed 415&#x2009;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.<br><br>RESULTS: Over a median 13.0-year follow-up, we identified 44&#x2009;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.<br><br>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.<br><br>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.<br><br>RESULTS: PS was independently associated with increased risks of MMD progression (OR 3.39, 95%&#x2009;CI 1.81 to 6.35, p<0.001), MTM (OR 2.25, 95%&#x2009;CI 1.06 to 4.77, p=0.034) and incident plus lesions (OR 3.15, 95%&#x2009;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&#x2009;mm (95% CI 0.114 to 0.145); no PS: 0.066&#x2009;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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>RESULTS: VisionFM with cross-modal transfer learning outperformed ImageNet in classifying different diseases on OCTA (accuracy: 0.8133&#xb1;0.0470&#x2009;vs 0.7600&#xb1;0.0502). RETFound with cross-modal transfer learning outperformed ImageNet in classifying different diseases on OCTA (accuracy: 0.8000&#xb1;0.0507&#x2009;vs 0.7600&#xb1;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.<br><br>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).<br><br>METHODS: This retrospective observational study included 107 treatment na&#xef;ve nAMD eyes who initiated treatment and were followed for 3 years &#xb1; 2 months or until VA deterioration to or below 35 ETDRS letters. Eyes with final VA &#x2264;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.<br><br>RESULTS: Twenty eyes (19%) were presented with a final VA &#x2264;35 ETDRS letters. Mean time from baseline to &#x2264;35 ETDRS letters was 587.7 &#xb1; 330.4 days, with a mean 9.7 &#xb1; 5.3 injections during that period. Mean baseline VA in the maintenance group vs the low VA group were 65.4 &#xb1; 10.8 and 52.0 &#xb1; 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.<br><br>CONCLUSION: After 3 years, 19% had declined to VA &#x2264;35 ETDRS letters. About 25% with &#x2265;1 available OCT follow-ups developed MA. Lower baseline VA predicted a final VA &#x2264;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.<br><br>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 &#x2265;80% agreement and near consensus as 70%-79%.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>CONCLUSIONS: 3D spheroid culture substantially augments the therapeutic efficacy of UC-MSCs by boosting autophagy and suppressing NLRP3 inflammasome signaling, resulting in enhanced protection of RPE cells from oxidative and inflammatory injury. These findings provide preclinical evidence supporting 3D MSCs as a promising therapeutic strategy for AMD.}, }
@article {pmid42070018, year = {2026}, author = {Agarwal, R and Iezhitsa, I and Hombrebueno, JR and Agarwal, P}, title = {Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00846-x}, pmid = {42070018}, issn = {2056-9920}, abstract = {Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.}, }
@article {pmid42072143, year = {2026}, author = {Maggi, MA and Mastromartino, R and Piccardi, M and Minnella, AM and Marangoni, D and Di Marco, S and Falsini, B and Bisti, S}, title = {Saffron as a Retinal Neuroprotectant: A Narrative Review of Preclinical Studies and Clinical Results.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, doi = {10.3390/antiox15040501}, pmid = {42072143}, issn = {2076-3921}, abstract = {The present narrative review reports the main preclinical and clinical results obtained by using supplementation of saffron or its pure components in neurodegeneration, with special emphasis on age-related macular degeneration. Beyond that, this article will address shared pathways between neurodegenerative diseases of the eye and the brain. It will be shown that saffron treatment might counteract oxidative damage in the retina and brain, as well as inflammation and inflammatory mediators that induce neuronal degeneration and death. The ways of action are multiple, and saffron chemical components appear to act in a synergistic manner, inducing tissue resilience. These effects critically depend upon the saffron chemical composition and structure. A well-defined ratio among molecules is linked to a patented batch known as Repron[®] and offers the maximum protection against neurodegeneration.}, }
@article {pmid42072148, year = {2026}, author = {Wiciński, M and Fajkiel-Madajczyk, A and Kurant, Z and Rzepiński, &#x141; and Słupski, M}, title = {Review of Therapeutic Potential of Coenzyme Q10 in Ophthalmology: Focus on Age-Related Macular Degeneration, Glaucoma, and Retinitis Pigmentosa.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, doi = {10.3390/antiox15040506}, pmid = {42072148}, issn = {2076-3921}, abstract = {Coenzyme Q10 (CoQ10), a natural antioxidant produced by the human body, has strong anti-inflammatory properties, reduces oxidative stress, and improves mitochondrial function. It is also known for its strong neuroprotective effects. With age, endogenously produced CoQ10 levels decline, contributing to the development of chronic diseases, including eye disorders. Irreversible ocular diseases that result in blindness present a significant challenge in contemporary medicine, as no fully effective cure exists; current treatments primarily aim to decelerate disease progression, manage symptoms, and preserve residual vision. Our study reviews research on the use of CoQ10 in eye diseases like age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma, which can cause permanent vision loss and are linked to oxidative stress and mitochondrial dysfunction. This article explores whether CoQ10 can be a safe and effective addition to treatment for these conditions. We also outline directions for future research and explain how CoQ10 functions in the studies discussed in this review.}, }
@article {pmid42072314, year = {2026}, author = {Menna, F and De Luca, L and Meduri, A and Baldascino, A and Lupo, S and Vingolo, EM}, title = {New Clinical Trials and Therapeutic Advances with Faricimab and Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration: A Durability-Oriented Comparative Perspective.}, journal = {Biomedicines}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/biomedicines14040773}, pmid = {42072314}, issn = {2227-9059}, abstract = {Neovascular age-related macular degeneration (nAMD) remains a major cause of visual morbidity worldwide, although its contribution to blindness in developed healthcare systems has declined in the era of anti-VEGF therapy. Although randomized clinical trials have consistently demonstrated meaningful visual gains under structured retreatment protocols, real-world outcomes frequently decline over time due to undertreatment, limited durability, and persistent disease activity. Recent therapeutic advances have shifted the focus from maximizing short-term efficacy to engineering sustained disease control. Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2, introduces dual-pathway vascular modulation, while high-dose aflibercept (8 mg) enhances VEGF suppression through pharmacokinetic intensification. This perspective critically examines the biological rationale, clinical evidence, real-world implications, and strategic positioning of these agents, proposing a durability-centered framework for next-generation management of nAMD.}, }
@article {pmid42072323, year = {2026}, author = {Menna, F and Pinelli, C and De Luca, L and Meduri, A and Baldascino, A and Lupo, S and Vingolo, EM}, title = {From Genetic Diagnosis to Therapeutic Implementation in Retinal Diseases: Translational Advances and Persistent Bottlenecks.}, journal = {Biomedicines}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/biomedicines14040782}, pmid = {42072323}, issn = {2227-9059}, abstract = {Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics-including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies-have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70-80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology.}, }
@article {pmid42072770, year = {2026}, author = {Unlu, BH and Durmaz Engin, C and Ozturk, AT}, title = {The Role of Systemic Inflammation in Age-Related Macular Degeneration Subtypes: Exploring Novel Biomarkers.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {8}, pages = {}, doi = {10.3390/diagnostics16081144}, pmid = {42072770}, issn = {2075-4418}, abstract = {Background/Objectives: This study aimed to compare hematological and inflammatory markers among patients with dry and wet age-related macular degeneration (AMD) and healthy controls, and to evaluate the influence of geographic atrophy (GA) in dry AMD and treatment response (TR) in wet AMD on these markers. Methods: The study included patients with dry AMD (n = 54), wet AMD (n = 53), and age- and sex-matched controls (n = 55). Hematological parameters, serum albumin, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), and hemoglobin, albumin, lymphocyte, and platelet index (HALP), were compared among the groups. Results: Age and sex distributions did not differ significantly between groups. Compared to controls, the wet AMD group had significantly higher neutrophil counts (p = 0.013), red cell distribution width (RDW) (p = 0.033), and inflammatory indices, including NLR, PLR, SII, SIRI, and PIV (all p < 0.01). HALP levels were significantly lower in wet AMD (p < 0.001). Dry AMD patients also had higher PLR (p = 0.045) and RDW (p = 0.005) than controls. When comparing wet and dry AMD groups directly, SIRI (p = 0.041) and PIV (p = 0.029) were significantly elevated in wet AMD, indicating stronger systemic inflammatory burden. In the dry AMD subgroup, patients with GA had significantly lower hemoglobin (p = 0.002) and erythrocyte counts (p = 0.039) than those without GA. No significant differences were observed between TR-positive and TR-negative wet AMD patients. Conclusions: Patients with wet AMD exhibit a more pronounced systemic inflammatory profile than both dry AMD patients and healthy controls. These findings support the hypothesis that systemic inflammation may contribute to AMD pathogenesis. Geographic atrophy in dry AMD may also be associated with additional hematologic alterations, whereas treatment response in wet AMD is not reflected in systemic markers.}, }
@article {pmid42074336, year = {2026}, author = {Bruzaite, A and Vilkeviciute-Petraite, A and Cebatoriene, D and Zaliuniene, D and Ciapiene, I and Smalinskiene, A and Kriauciuniene, L and Liutkeviciene, R}, title = {Metabolic and Genetic Alterations in Early and Exudative Age-Related Macular Degeneration: Inosine, Amino Acids, and COL2A1 Gene Variant.}, journal = {International journal of molecular sciences}, volume = {27}, number = {8}, pages = {}, doi = {10.3390/ijms27083697}, pmid = {42074336}, issn = {1422-0067}, support = {S-MIP-23-96//Research Council of Lithuania/ ; }, mesh = {Humans ; Female ; Male ; Aged ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/metabolism ; *Inosine/metabolism ; *Amino Acids/metabolism ; *Collagen Type II/genetics/metabolism ; Genetic Predisposition to Disease ; Middle Aged ; Genotype ; Case-Control Studies ; Alleles ; Aged, 80 and over ; }, abstract = {Age-related macular degeneration (AMD) is a complex retinal disease influenced by genetic and metabolic factors. Genetic variants impact disease susceptibility, while alterations in amino acid and purine metabolism are involved in AMD development. This study aimed to examine the association between the COL2A1 rs1635529 polymorphism and AMD, as well as its relation to specific metabolites. The study comprised 919 participants: 261 with early AMD, 229 with exudative AMD, and 429 controls. DNA was extracted using the salting-out method, and genotyping was performed using real-time PCR. Metabolite levels were analysed with liquid chromatography-mass spectrometry. Statistical analysis was conducted using IBM SPSS Statistics 27.0. Logistic regression revealed that carriers of the GT + TT genotypes had a 1.63-fold higher risk of early AMD (p = 0.046). The T allele was also linked to a 1.67-fold elevated risk (p = 0.033). No significant associations were observed in exudative AMD. Furthermore, lower leucine levels were noted in exudative AMD patients, and inosine levels were reduced in GT genotype carriers within the early AMD group. The COL2A1 rs1635529 polymorphism showed a nominal association with early AMD, but not exudative AMD. Differences in leucine and inosine levels were observed, suggesting a potential link between genetic variation and metabolic alterations. These findings indicate possible involvement of collagen-related and metabolic pathways in early disease development; however, the results should be interpreted with caution and require validation in larger studies.}, }
@article {pmid42074510, year = {2026}, author = {Rowe, LW and Becerra, SP and MacLaren, RE and Avery, RL and Wykoff, CC and Ho, AC and Regillo, CD and Eliott, D and Osborne, A and Binley, KM and Ciulla, TA}, title = {Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.}, journal = {Genes}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/genes17040392}, pmid = {42074510}, issn = {2073-4425}, mesh = {Humans ; *Genetic Therapy/methods ; *Retinal Diseases/genetics/therapy ; *Neuroprotection/genetics ; *Immunomodulation/genetics ; Animals ; Nerve Growth Factors/genetics ; }, abstract = {Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors-including pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF), rod-derived cone viability factor (RdCVF), brain-derived neurotrophic factor (BDNF), fibroblast growth factors (FGFs), glial cell line-derived neurotrophic factor (GDNF), and proinsulin-have demonstrated photoreceptor preservation across multiple preclinical IRD models regardless of the underlying genetic mutation. The recent FDA approval of CNTF cell-based gene therapy (Encelto) for macular telangiectasia type 2 validates this therapeutic paradigm. Complement system inhibition represents another gene-agnostic strategy, with intravitreal complement inhibitors approved for geographic atrophy secondary to age-related macular degeneration and gene therapy approaches targeting C3, C5, or delivering soluble complement regulators under investigation for IRDs. Combination strategies simultaneously addressing multiple pathogenic pathways may offer synergistic benefits. Conclusions: Gene-agnostic approaches targeting neuroprotection and immunomodulation offer a therapeutic paradigm capable of benefiting patients across the spectrum of IRD genotypes, potentially transforming treatment for conditions where mutation-specific therapies remain unavailable.}, }
@article {pmid42074639, year = {2026}, author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S}, title = {Five-Year Changes in Pachydrusen with Late-Phase Hyperfluorescence on Indocyanine Green Angiography.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082836}, pmid = {42074639}, issn = {2077-0383}, abstract = {Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA-hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen.}, }
@article {pmid42074670, year = {2026}, author = {Sanders, FWB and Acton, JH and Ryan, B and McAlinden, C}, title = {Psychometric Assessment of the Metamorphopsia Questionnaire in Patients with Macular Diseases Receiving Anti-Vascular Endothelial Growth Factor Treatment.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082867}, pmid = {42074670}, issn = {2077-0383}, support = {2023/2024(ER)-ER-23-07-Dr Francis William Barwise Sanders//HCRW/ ; }, abstract = {Background: The metamorphopsia questionnaire (MeMoQ) is an established patient-reported outcome measure (PROM) in the context of macular disease. However, its performance has not been proved in those being treated for various macular conditions with intravitreal anti-vascular endothelial growth factor (Anti-VEGF). The objective was to eliminate misfitting items, enhance measurement precision, and ensure optimal response categorisation. Methods: Rasch analysis was performed iteratively on 2286 responses from patients with macular diseases being treated with Anti-VEGF to optimise the MeMoQ. Fit statistics, reliability indices, person and item separation measures, and principal component analysis (PCA) of residuals were assessed to determine the optimal model. This study was conducted in an outpatient clinic specialising in retinal diseases in Hywel Dda University Health Board. Results: Misfitting items were removed in successive iterations, leading to optimised category probability curves and stable fit statistics for the MeMoQ. The resulting model for all responses included two final items, with person separation remaining inadequate reducing from 1.23 to 1.12 and reliability from 0.60 to 0.56. Category probability curves demonstrated good ordering of response variables with Andrich thresholds separated by >1.2 logits. In the subgroups of neovascular age-related macular degeneration and diabetic macular oedema person separation remained below two and reliability remained low. Conclusions: Rasch analysis demonstrated that the MeMoQ was not a valid or reliable PROM in this patient population. Therefore, the MeMoQ may not provide a reliable index of patient's perception and visual experience when undergoing Anti-VEGF treatment.}, }
@article {pmid42074763, year = {2026}, author = {Dmoch, W and Sawicka, J and Żelichowska, N and Kępczyńska, Z and Maciejewicz, P and Kęcik, D}, title = {Statins and Fibrates in Age-Related Macular Degeneration: A Contemporary Clinical Narrative Review (2020-2025).}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082960}, pmid = {42074763}, issn = {2077-0383}, abstract = {Age-related macular degeneration (AMD) remains the leading cause of irreversible central vision loss in the elderly. Increasing attention has been directed toward lipid metabolism as a potential contributor to disease onset and progression. The overlap between AMD and atherosclerosis-particularly regarding lipid accumulation, endothelial dysfunction, and chronic inflammation-has prompted interest in lipid-lowering therapies. This narrative review synthesizes the clinical evidence published between 2020 and 2025 on the potential role of statins and fenofibrate in AMD risk modification and disease progression. A structured literature search was conducted in PubMed, Scopus, and Web of Science using combined MeSH and free-text terms related to lipid-lowering agents and AMD. Human studies evaluating clinical incidence or progression outcomes were considered alongside contextual evidence from prior evidence syntheses. Overall, findings remain heterogeneous. Most studies did not demonstrate a consistent association between statin therapy and AMD incidence or progression in unselected populations. However, selected reports suggested a potential delay in dry AMD onset or slower disease progression among patients receiving prolonged or higher-intensity statin treatment. Evidence regarding fenofibrate was more limited and heterogeneous, with only a tentative protective signal observed in adherent users, particularly for non-exudative AMD. The current literature does not support lipid-lowering therapy as a universal preventive strategy for AMD. Nonetheless, subgroup-specific benefits cannot be excluded, especially in early disease stages or metabolically high-risk populations. Further well-designed prospective and randomized studies are needed to clarify therapeutic relevance and identify the patients who are most likely to benefit.}, }
@article {pmid42074798, year = {2026}, author = {Nagano, N and Kanemori, E and Hirano, Y and Hojo, T and Sakaeda, Y and Yuguchi, T and Kuwayama, S and Ogura, S and Kimura, M and Morita, H and Uemura, K and Yasukawa, T}, title = {Assessing the Validity of the Fellow Eye as an Internal Control in Early-Phase Clinical Trials for Myopic Chorioretinal Atrophy.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15082997}, pmid = {42074798}, issn = {2077-0383}, support = {Not applicable//PharmaBio Corporation/ ; }, abstract = {Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as an internal control in early-phase clinical trials for myopic CRA. Methods: This exploratory and methodological retrospective study included eight patients (16 eyes) with myopic CRA who visited the Department of Ophthalmology at Nagoya City University Hospital between January 2010 and August 2023. Atrophic areas in both eyes were measured, and the longitudinal changes were analyzed. Three mixed-effects models were compared to assess the impact of inter-individual and inter-ocular variability on atrophic area progression. Subsequently, fixed-effects and mixed-effects models were compared using the Akaike Information Criterion (AIC). Finally, the square root of the variance ratio was calculated to quantify the contribution of inter-ocular variability to atrophic area progression. Results: In all eyes, the square root of the atrophic area increased over time. The model including random intercepts and slopes for each eye nested within patients had the lowest AIC of 69.4, suggesting that accounting for both inter-individual and inter-ocular variability improved model accuracy. The mixed-effects model had a lower AIC than the fixed-effects model, indicating a better fit. The square root of the variance ratio was 0.34 in the mixed-effects model, indicating that the inter-ocular variability was lower than the inter-individual variability, though it remained appreciable. Conclusions: This study quantitatively supports the feasibility and methodological validity of inter-ocular comparison designs for early-phase clinical trials in myopic CRA.}, }
@article {pmid42074899, year = {2026}, author = {Ahmad, NU and Mir, TA}, title = {Advances in Gene Therapy for Age-Related Macular Degeneration: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/jcm15083097}, pmid = {42074899}, issn = {2077-0383}, abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness and vision impairment in individuals over 60 years of age in the United States (US). Despite this, current treatment options have limitations related to drug efficacy and durability. Gene therapy provides a potential solution by providing a more durable and longer- acting treatment option that can decrease treatment burden and improve long-term visual outcomes. This review presents the current treatment approaches, routes of administration, and vectors being investigated for gene therapy delivery in AMD. It also provides an update on the ongoing gene therapy clinical trials for dry and wet AMD. As these therapies advance into later-stage clinical trials, ophthalmologists need to be mindful of the many challenges pertaining to gene therapy delivery, including safety, limitations related to immunogenicity, long-term ocular and systemic side effects, and potential barriers to drug manufacturing and access. Continued efforts are required to improve precision, safety, and efficacy, including identifying the safest and most effective vectors and delivery routes, and minimizing potential adverse effects. In addition, guidelines need to be established to guide appropriate patient selection before gene therapy can be integrated into clinical practice.}, }
@article {pmid42079735, year = {2026}, author = {Yu, B and Liu, L and Yang, N and Xu, L and Wu, H}, title = {Visual acuity and stereopsis across the parafoveal and perifoveal retina in young adults: an eccentricity and meridian analysis.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e21251}, pmid = {42079735}, issn = {2167-8359}, mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Adult ; *Depth Perception/physiology ; Young Adult ; *Retina/physiology ; *Fovea Centralis/physiology ; Vision, Binocular/physiology ; }, abstract = {BACKGROUND: Visual acuity (VA) and stereoacuity (SVA) are fundamental visual functions that decline with increasing retinal eccentricity. Patients with macular degeneration and other central vision disorders often rely on paracentral vision, yet location-specific reference data for VA and SVA across the parafoveal and perifoveal retina remain limited. This study aimed to quantify the distribution of binocular VA and SVA across eccentricity and meridian in young adults, develop prediction equations with 95% prediction intervals, and examine the relationship between these two visual functions in the paracentral retina.<br><br>METHODS: Thirty-five healthy young adults (13 males, 22 females; mean age 27.23&#xa0;&#xb1;&#xa0;2.43 years) were recruited. Binocular VA and SVA were measured at 48 test positions across eight meridians (0&#xb0;, 45&#xb0;, 90&#xb0;, 135&#xb0;, 180&#xb0;, 225&#xb0;, 270&#xb0;, 315&#xb0;) and six eccentricities (2.5&#xb0; to 15&#xb0; in 2.5&#xb0; increments) using a polarized 3D display system. A four-alternative forced-choice task was employed with tumbling E optotypes for VA and random-dot stereograms for SVA. Eye tracking ensured fixation stability throughout testing. Generalized estimating equations were used to analyze the effects of eccentricity and meridian. Linear mixed-effects models and Bayesian Tobit models were employed to develop prediction equations. Ten-fold cross-validation assessed model generalizability.<br><br>RESULTS: Both VA and SVA significantly declined with increasing eccentricity (P&#xa0;<&#xa0;0.001). VA decreased from a median of 0.40 logMAR at 2.5&#xb0; to 1.20 logMAR at 15.0&#xb0;, at a rate of 0.057 logMAR per degree. SVA increased from 2.1 log arcsec at 2.5&#xb0; to 2.9 log arcsec at 7.5&#xb0;, declining approximately three times faster than VA (0.154 log arcsec per degree). Both functions showed significant meridional anisotropy (P&#xa0;<&#xa0;0.001), with the horizontal meridian demonstrating 0.058 logMAR better VA and 0.106 log arcsec better SVA compared to the vertical meridian. Despite parallel declines with eccentricity, no significant correlations were observed between VA and SVA at any test position within 7.5&#xb0; eccentricity (P&#xa0;>&#xa0;0.05).<br><br>CONCLUSIONS: VA and SVA deteriorate with increasing eccentricity in the paracentral retina, with stereopsis declining approximately three times faster and demonstrating a more pronounced horizontal-over-vertical advantage. The absence of correlation between VA and SVA suggests distinct neural mechanisms underlying these functions. The prediction equations with 95% prediction intervals provide reference benchmarks for healthy young adults, facilitating clinical interpretation of patient measurements and enabling objective assessment of disease-related changes in paracentral visual function.}, }
@article {pmid42079755, year = {2026}, author = {Zhu, S and Yang, T and Sheng, L and Shi, L}, title = {TREM2 in age-related macular degeneration: a microglia-centered perspective in the retinal myeloid landscape.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1804578}, pmid = {42079755}, issn = {2674-0826}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Advanced AMD comprises an atrophic ("dry") form characterized by retinal pigment epithelium (RPE) and photoreceptor degeneration and a neovascular ("wet") form driven by choroidal neovascularization (CNV). Beyond genetic predisposition and environmental stressors, chronic dysregulation of innate immunity is increasingly recognized as a convergent mechanism linking drusen/Bruch's membrane alterations to outer retinal cell death and pathological angiogenesis. Retinal myeloid cells-including resident microglia and, in specific disease contexts, recruited monocyte-derived macrophages-can support homeostasis by clearing lipids and cellular debris, yet may also exacerbate inflammation, matrix remodeling, and neovascularization. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia and other myeloid cells that regulates phagocytosis, lipid handling, migration, survival, immunometabolism, and inflammatory tone. Recent retinal studies suggest that TREM2-associated programs can restrain lesion expansion in outer retinal degeneration models and modulate CNV severity in experimental neovascularization; however, interpretation remains limited by disease stage, anatomical niche, and the difficulty of cleanly separating microglia from infiltrating macrophages in vivo. Here, we synthesize current evidence on retinal myeloid contributions to dry and neovascular AMD, provide an updated mechanistic framework for TREM2 signaling, and discuss therapeutic strategies and translational challenges for targeting TREM2 in AMD.}, }
@article {pmid42080790, year = {2026}, author = {Piroozmand, S and Latifi-Navid, H and Soheili, ZS and Hosseinkhani, S and Samiei, S and Barzegar Behrooz, A and Ahmadieh, H and Leonardi, A and Ghavami, S and Sheibani, N}, title = {Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {5}, pages = {4}, doi = {10.1167/iovs.67.5.4}, pmid = {42080790}, issn = {1552-5783}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Aging/physiology ; Signal Transduction ; *Retinal Diseases/drug therapy/metabolism ; }, abstract = {PURPOSE: Vision-threatening ocular diseases are impacted by aging-associated molecular changes, including mitochondrial dysfunction, cellular senescence, and chronic inflammation. Anti-VEGF therapies targeting VEGF-A/VEGFR2 signaling remain the frontline standard of care, but many patients exhibit suboptimal or nondurable responses, often due to compensatory and/or compromised antiangiogenic and anti-inflammatory pathways. We aimed to elucidate shared mechanisms underlying treatment failure and disease progression.<br><br>METHODS: We applied an integrative systems biology framework that combined multiomics datasets, network-based machine learning, and disease-specific pathway mapping. A comprehensive literature review of conditions, including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and aging, identified 14 core genes consistently associated with angiogenesis, inflammation, and immune signaling. Multialgorithm centrality and enrichment analyses reconstructed disease-specific interaction networks, revealing consensus mechanistic axes. Integration of cell-type-specific single-cell RNA sequencing data from AMD-RPE clusters identified cluster-specific gene hubs and vertical signaling axes, leading to VEGF blockade failure.<br><br>RESULTS: EGFR, HSP90AA1, SIRT1, and STAT3 emerged as central resistance hubs linking angiogenesis and inflammatory processes. Pathway enrichment analyses revealed 21 conserved core signaling cascades, grouped into six functional categories, with AGE-RAGE, PI3K-Akt, HIF-1, MAPK, and chemokine pathways playing central roles. A MiRGD-based peptide nanocomplex delivering htsFLT01 achieved efficient RPE transfection and controlled gene activation under basal conditions.<br><br>CONCLUSIONS: This systems-level framework clarifies mechanisms of VEGF blockade resistance and provides a rational basis for next-generation, combinatorial therapeutic strategies requiring validation in disease-relevant models.}, }
@article {pmid42080917, year = {2026}, author = {Haroon, MM and Akram, L and Jalal, L and Ahmed, A and Haider, S}, title = {Granzyme B in age-related macular degeneration: mechanistic insights and therapeutic perspectives.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42080917}, issn = {1435-702X}, abstract = {Granzyme B (GzmB), beyond its established role in corneal and conjunctival disease, is increasingly recognized in the retinal and choroidal distribution of several pathologies. GzmB targets tight-junction proteins (e.g., ZO-1, JAM-A) and extracellular proteins such as fibronectin and laminin within the retinal pigment epithelium (RPE) and Bruch's membrane, thereby disrupting the outer blood-retinal barrier and contributing to the pathogenesis of age-related macular degeneration (AMD) and Macular neovascularization (MNV). This mini review highlights recent mechanistic insights into how GzmB drives extracellular matrix breakdown, inflammation, and angiogenesis; summarizes experimental and clinical evidence supporting its role in AMD; and discusses emerging therapeutic approaches, limitations, and translational potential for targeted therapy.}, }
@article {pmid42081160, year = {2026}, author = {Lin, Y and Han, Z and Zhang, Y and Yuan, R and Huang, M and Liu, Y and Wang, J and Xu, C and Liu, L and Yu, P and Yang, Q and Zeng, L and Li, S}, title = {The aging eye: navigating molecular mechanisms and innovative interventions.}, journal = {Biogerontology}, volume = {27}, number = {3}, pages = {}, pmid = {42081160}, issn = {1573-6768}, mesh = {Humans ; *Aging/pathology/metabolism ; Oxidative Stress ; Animals ; Cellular Senescence ; *Eye/metabolism/pathology ; *Eye Diseases/therapy/metabolism ; Autophagy ; }, abstract = {The global demographic shift toward aging has precipitated a surge in age-related ocular pathologies, imposing a formidable public health challenge that demands urgent intervention. Blinding disorders such as age-related macular degeneration (AMD), cataracts, and dry eye disease exemplify this crisis, with their pathogenesis being intrinsically linked to tissue-specific aging processes in the eye. At the molecular level, core pathways including telomere attrition, oxidative stress, cellular senescence, and autophagic dysregulation orchestrate this degenerative cascade. This review systematically delineates the dynamic interplay network of these pathways during ocular aging, with particular emphasis on four pivotal mechanisms: oxidative stress-driven reactive oxygen species (ROS) accumulation, senescence-associated secretory phenotype (SASP)-mediated inflammatory cascades, autophagic flux dysfunction, and epigenetic remodeling aberrations. We further evaluate recent advancements in translational therapies, emphasizing the clinical potential of targeted gene-editing technologies, stem cell-derived regenerative approaches, and novel senolytic agents. Additionally, artificial intelligence (AI) -assisted diagnostics are explored as pivotal tools for precision medicine, particularly in early disease detection via retinal imaging and biomarker analysis. Future research priorities should focus on the integration of aging-specific biomarkers including methylation signatures, the advancement of tissue-selective drug delivery systems tailored to anterior and posterior ocular compartments. Collectively, these initiatives will propel the development of targeted interventions to address age-related visual decline, positioning precision medicine as the cornerstone of next-generation geriatric ophthalmic care.}, }
@article {pmid42081293, year = {2026}, author = {Procyk, CA and Melati, A and Tariq, M and Liu, J and Branch, MJ and Delicata, JD and Harding, P and Khazim, M and Moshtagh Khorasani, M and Ladino, B and Lanning, EP and Margari, M and Mahamoud, I and Mofidi, C and Kumar, KN and Van Heerden, S and Smith, AJ and West, EL and Ali, RR and Pearson, RA}, title = {Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged rd1 mice with advanced retinal degeneration.}, journal = {Stem cells (Dayton, Ohio)}, volume = {}, number = {}, pages = {}, doi = {10.1093/stmcls/sxag023}, pmid = {42081293}, issn = {1549-4918}, abstract = {Targeted photoreceptor replacement therapy is a promising, potentially disease-agnostic approach for reversing sight-loss associated with advanced retinal degenerations, including age-related macular degeneration. We have previously shown that transplantation of human stem cell-derived cone photoreceptors (hCones) into young adult (3-month-old) mouse models of advanced retinal degeneration can restore retinal function. However, substantial remodeling of the remaining inner retinal circuitry continues long after complete photoreceptor loss, raising the critical question of whether photoreceptor transplantation can effectively rescue function at very late-stage degeneration. rd1 mice received transplants at 12-15 months of age and were examined ∼3 months later. Transplanted hCones survived in large numbers, while host inner retinal neurons exhibited significant plasticity, extending dendrites to transplanted hCones, and making synapse-like contacts. Host Müller glia undergo notable remodeling, apparently incorporating the donor cells within the retinal structure. Multielectrode array recordings showed robust rescue of light-evoked activity across the normal photopic range intensities and evidence of inner retinal processing, while some treated mice showed improvements in visually-evoked optokinetic head tracking behavior. Together, these data indicate that effective rescue following photoreceptor replacement therapy is feasible long after complete photoreceptor loss and extensive inner retinal remodeling.}, }
@article {pmid42082070, year = {2026}, author = {Tran, J and Chhablani, J}, title = {Unsuccessful Clinical Trials in Retina: Lessons Learned.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.04.028}, pmid = {42082070}, issn = {1879-1891}, abstract = {OBJECTIVE: To analyze patterns of non-success in phase 2 and 3 interventional retinal clinical trials conducted in the United States between 2015 and 2025.<br><br>DESIGN: Perspective based on retrospective analysis of unsuccessful clinical trials.<br><br>METHODS: Unsuccessful trials that were terminated, withdrawn, or completed without meeting primary endpoints were evaluated across indications, trial phases, intervention classes, and mechanisms of action to identify recurring design, feasibility, and operational challenges.<br><br>RESULTS: High attrition rates were observed across diabetic macular edema, diabetic retinopathy, neovascular age-related macular degeneration, and geographic atrophy. Phase 2 trials were more frequently discontinued following interim analyses, whereas phase 3 trials more often failed to meet primary efficacy endpoints. Later-phase studies were associated with increased sample size, geographic dispersion, follow-up duration, and assessment burden. Differences in endpoint selection, comparator choice, and population heterogeneity may contribute to attenuation of treatment effects. Operational and sponsor-level factors, including strategic and financial considerations, were also associated with trial discontinuation.<br><br>CONCLUSION: Translating early-stage findings into successful late-phase outcomes remains challenging in retinal drug development. Improved alignment of biological rationale, endpoint selection, and operational feasibility may enhance trial success.}, }
@article {pmid42082131, year = {2026}, author = {Duo, L and Cheng, P and Jiang, W and Lin, Q}, title = {Free-standing chondroitin sulfate/collagen multilayered films as preliminary Bruch's membrane-mimetic platform for retinal pigment epithelial cell culture.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {152359}, doi = {10.1016/j.ijbiomac.2026.152359}, pmid = {42082131}, issn = {1879-0003}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, primarily associated with retinal pigment epithelial (RPE) cell degeneration. Although RPE cell therapy has emerged as a promising strategy for AMD, maintaining RPE cell attachment, organization, and functional characteristics remains a major challenge. In this study, free-standing chondroitin sulfate (CS)/collagen (Col) multilayered films were fabricated via spin-coating-assisted layer-by-layer (LbL) assembly and evaluated in vitro as preliminary Bruch's membrane (BM)-mimetic platform for supporting RPE growth and preserving cellular functionality. Genipin cross-linking improved the mechanical stability of the films and reduced their swelling behavior. ARPE-19 cells cultured on the 2 h cross-linked films showed improved attachment and proliferation compared with uncross-linked films, together with detectable RPE65 expression and several RPE-related functional features, including apical-basal differences in pigment epithelium-derived factor (PEDF) secretion, phagocytosis of labeled photoreceptor outer segments (POS), and formation of microvilli-like structures. Collectively, these findings suggest that CS/Col free-standing films can support ARPE-19 cell growth and maintain several RPE-related phenotypic and functional features in vitro, providing a preliminary BM-mimetic platform for future RPE culture studies.}, }
@article {pmid42082322, year = {2026}, author = {Kortuem, KU and Zarranz-Ventura, J and Bandello, F and Duval, R and O'Toole, L and De Zanet, S and Blair, JPM and Seaman, J and Zvolanek, M and Jaeger, K and Gmeiner, B and Holz, FG}, title = {Impact of AI-enhanced three-dimensional OCT scans on disease activity assessment in patients with nAMD: the RAZORBILL study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2024-327060}, pmid = {42082322}, issn = {1468-2079}, abstract = {BACKGROUND: The standard of care for neovascular age-related macular degeneration (nAMD) is repeated intravitreal injection with anti-vascular endothelial growth factor agents. Real world evidence suggests that some patients are undertreated, which might be linked with the retreatment decisions made by physicians. Therefore, this multicentre observational study aimed to investigate the extent to which enrichment of optical coherence tomography (OCT) images with segmentation information could influence and support disease activity assessment (DAA) in patients treated for nAMD.<br><br>METHODS: Descriptive statistics were tabulated for the demographic and clinical characteristics and outcome variables. To assess the influence of automated OCT image enrichment with segmentation information on DAA, a generalised linear mixed model was employed. The degree of agreement in classification of disease activity across reviewers was assessed by Krippendorff's alpha.<br><br>RESULTS: The odds estimate for DAA regarding enriched OCT images was 0.759 and for non-enriched OCT images 0.772. The OR for enriched versus non-enriched OCT images was 1.078 with a p value of 0.229. No difference in the odds of DAA between automated OCT image enrichment with segmentation and DAA was noted. Krippendorff's alpha coefficient was 0.416 for enriched and 0.402 for non-enriched OCT images. Thus, the inter-reviewer reliability/agreement was similarly low between enriched and non-enriched OCT images.<br><br>CONCLUSIONS: OCT image enrichment did not appear to impact the likelihood of adequately detecting disease activity, nor did it have an impact on agreement between reviewers of images in this study. No new safety signals in products involved in the study were detected.<br><br>TRIAL REGISTRATION NUMBER: NCT04662944.}, }
@article {pmid42066985, year = {2026}, author = {Cui, X and Zhao, Q and Yuan, J and Yu-Wai-Man, P}, title = {Integrated plasma proteomics and metabolomics reveal immunometabolic pathways and predictive signatures for age-related eye diseases.}, journal = {Metabolism: clinical and experimental}, volume = {180}, number = {}, pages = {156624}, doi = {10.1016/j.metabol.2026.156624}, pmid = {42066985}, issn = {1532-8600}, abstract = {BACKGROUND AND AIMS: Age-related eye diseases (AREDs) share aging as a major risk factor, but the systemic molecular changes preceding disease onset remain incompletely understood. We aimed to define the shared and disease-specific immunometabolic architecture of major AREDs and to examine how circulating molecular features relate to retinal phenotypes, pre-diagnostic patterns, and disease risk.<br><br>METHODS: We performed a large-scale prospective multi-omics study in the UK Biobank integrating baseline plasma proteomics, metabolomics, retinal imaging-derived phenotypes, and longitudinal follow-up across five major AREDs: age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal vascular occlusion. Cox regression, functional enrichment, protein-metabolite correlation, mediation analysis, trajectory analysis, and machine-learning models were applied.<br><br>RESULTS: Proteome-wide analyses identified both shared and disease-specific circulating signatures, mainly involving immune, extracellular matrix, vascular, and stress-response pathways. Reconstructed population-level molecular patterns diverged from controls up to 15&#xa0;years before diagnosis, with marked heterogeneity across diseases. Integration with retinal imaging linked immune- and matrix-related proteins to retinal neurodegenerative and microvascular phenotypes. Metabolite clustering and mediation analyses highlighted recurrent lipoprotein-related pathways, particularly HDL-related structure and composition, as cross-layer features associated with systemic protein signals, metabolic states, and disease risk. Combined proteomic-metabolomic models improved prediction of incident disease compared with protein-only models.<br><br>CONCLUSIONS: Major AREDs share a systemic immunometabolic aging architecture while retaining substantial disease-specific molecular features. Circulating molecular alterations are detectable years before clinical onset and may support future biological stratification and risk prediction.}, }
@article {pmid42067026, year = {2026}, author = {González Escobar, AB and Baquero Aranda, IM and Valera Ávila, JC and Barco Moreno, E and Galván Cano, JM and Luque Aranda, R}, title = {Bilateral peripheral exudative hemorrhagic chorioretinopathy treated with intravitreal injections of ranibizumab.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502539}, doi = {10.1016/j.oftale.2026.502539}, pmid = {42067026}, issn = {2173-5794}, abstract = {Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare entity consisting of lesions similar to those of age-related macular degeneration (AMD) and type 1 aneurysmal neovascularization (N1a), but located outside the macular region in the peripheral retina. We present the case of an 89-year-old woman who presented to the emergency department with loss of visual acuity (VA) in both eyes (OU) due to a massive macular subretinal hemorrhage in the right eye (OD) and a vitreous hemorrhage in her left eye (OS), accompanied in both eyes by peripheral hemorrhagic retinal pigment epithelium detachments (HPED). Ophthalmological examination and multimodal imaging led to the diagnosis of PEHCR. This case highlights the importance of the differential diagnosis of PEHCR from other vascular and neoplastic pathologies in order to avoid unnecessary tests and treatments. Early recognition and diagnosis are essential for establishing appropriate management, with intravitreal injections of anti-vascular endotelial groth factors (anti-VEGF) being recommended in cases with loss of VA or threat thereof. This case also contributes to the limited published literature on bilateral PEHCR, reinforcing the need to consider this pathology in elderly patients with peripheral hemorrhagic lesions.}, }
@article {pmid42068401, year = {2026}, author = {Kaplan, E and Segal, O and Moisseiev, E and Allon, G}, title = {Switch to faricimab in various retinal diseases: real-world data.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {42068401}, issn = {1573-2630}, mesh = {Humans ; Male ; Female ; Intravitreal Injections ; *Retinal Diseases/drug therapy/diagnosis ; Aged ; Retrospective Studies ; *Visual Acuity ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence ; Treatment Outcome ; Fluorescein Angiography ; *Drug Substitution ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Antibodies, Bispecific ; }, abstract = {OBJECTIVE: To evaluate the efficacy of faricimab in various retinal conditions in previously treated patients.<br><br>METHODS: This study included patients who received at least three faricimab injections at a large medical center between April 2023 and October 2024, all of whom were not naive to treatment.<br><br>RESULTS: A total of 242 eyes from 219 patients were included in the analysis. The diagnoses were: 139 eyes with neovascular age-related macular degeneration (NVAMD), 63 eyes with diabetic macular edema (DME), 24 eyes with polypoidal choroidal vasculopathy (PCV), 5 eyes with choroidal neovascularization (CNV) secondary to central serous retinopathy (CSR), 5 eyes with branch retinal vein occlusion (BRVO) accompanied by cystoid macular edema (CME), 3 eyes with central retinal vein occlusion (CRVO) with CME, and 3 eyes with myopic CNV. Patients had previously received intravitreal injections of medications including bevacizumab, ranibizumab, aflibercept 2&#xa0;mg, brolucizumab, triamcinolone, and Ozurdex. Following treatment with faricimab, the proportion of eyes with no intraretinal or subretinal fluid increased across all retinal diseases. Additionally, the average central subfield thickness decreased, the interval between injections was extended, and average visual acuity improved in every retinal condition. The average height of the pigment epithelium detachment (PED) decreased in cases of NVAMD and PCV.<br><br>CONCLUSIONS: Faricimab appears to be effective after the failure of other treatment options.}, }
@article {pmid42068868, year = {2026}, author = {Hammond, BR and Buch, J}, title = {The evidentiary basis and challenges associated with studying the role of light damage on ocular health.}, journal = {Journal of optometry}, volume = {19}, number = {3}, pages = {100616}, doi = {10.1016/j.optom.2026.100616}, pmid = {42068868}, issn = {1989-1342}, abstract = {The interaction between light and the eye is both essential and potentially harmful. Light regulates ocular development, supports vision, and influences systemic physiology, yet it can also induce photochemical damage. Determining whether chronic exposure to high-energy visible (HEV) light contributes to age-related ocular disease remains challenging. Randomized clinical trials, the gold standard for medical evidence, are largely infeasible for exposures that are lifelong, ubiquitous, and potentially harmful. Instead, researchers rely on a spectrum of evidence, from cellular and animal models to case studies, cohort studies, and expert consensus, each with unique advantages and limitations. This review categorizes existing evidence according to study design, evaluates its strengths and weaknesses, and considers how converging findings might inform clinical practice. We conclude that while acute light injury is well established, the long-term impact of low-level HEV exposure remains largely and necessarily inferential. Definitive evidence is difficult to obtain but improvements in exposure assessment and integration across different categories of evidence have led to a cautious but reasonable conclusion on the potential harms of long-term exposure.}, }
@article {pmid42069034, year = {2026}, author = {Hekimsoy, HK and Şekeroğlu, MA and Ateşoğlu, H&#x130; and Doğuizi, S}, title = {The Foveal Microvasculature of Adult Offspring of Patients with Neovascular Age-Related Macular Degeneration.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105497}, doi = {10.1016/j.pdpdt.2026.105497}, pmid = {42069034}, issn = {1873-1597}, abstract = {AIM: To assess the foveal microvasculature in adult offspring of patients with neovascular age-related macular degeneration (nAMD) who exhibit no clinical or imaging signs of AMD, and to compare these parameters with those of healthy controls without a family history of AMD.<br><br>METHODS: This cross-sectional study included 82 adult offspring of patients with nAMD and 85 age- and sex-matched controls. Optical coherence tomography angiography (OCTA) was used to evaluate vessel densities of the superficial and deep capillary plexuses (SCP and DCP), the foveal avascular zone (FAZ), outer retinal flow, and choriocapillaris (CCP) flow area.<br><br>RESULTS: There were no significant differences in demographic or visual parameters between groups, nor in FAZ area, perimeter, or acircularity index. However, vessel densities in all SCP and DCP zones, as well as outer retinal and CCP flow areas, were significantly reduced in the nAMD offspring group (all p < 0.05).<br><br>CONCLUSION: Subclinical microvascular alterations in SCP, DCP, and CCP were identified in clinically unaffected adult offspring of patients with nAMD. These findings suggest a potential heritable vascular component in early AMD pathogenesis and support the use of OCTA as a tool for risk stratification.}, }
@article {pmid42062331, year = {2026}, author = {Zhong, L and Liu, S and Lu, W and Wu, Q and Lv, Y and Yi, S and Wang, X and Wu, Z and Yan, J}, title = {Assessment of quality, reliability, and interactive characteristics of age-related macular degeneration short videos on TikTok: a cross-sectional study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44509-1}, pmid = {42062331}, issn = {2045-2322}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Short-video platforms like TikTok are increasingly important sources of health information, yet concerns persist regarding content quality and reliability. To systematically evaluate the quality, reliability, and user engagement characteristics of AMD-related videos on TikTok. We systematically searched TikTok for AMD-related videos. Quality and reliability were assessed using JAMA benchmark, modified DISCERN, Global Quality Scale (GQS), and Patient Education Materials Assessment Tool (PEMAT). Entropy weight method and cluster analysis were applied to engagement data. Among 145 videos, overall quality was poor. Median scores were 1 for JAMA, 2 for mDISCERN, and 3 for GQS. Understandability was limited (median PEMAT-U: 43%), while actionability was moderate (median PEMAT-A: 60%). High-quality videos were characterized by creation by Western medicine ophthalmologists, inclusion of prognostic information, and monologue narration; physician title showed no association with quality. "Saves" carried the highest engagement weight (35.71%). "Self-test and screening" themes achieved the highest engagement rate (62.5%). Media accounts attained the highest PEMAT-U scores and interaction metrics. Video format and presenter attire showed no significant impact on quality or engagement. AMD-related health information on TikTok is generally poor quality. Information quality and user engagement are driven by distinct factors, highlighting the need for targeted strategies to improve content accuracy and understandability.}, }
@article {pmid42063159, year = {2026}, author = {Yuan, XL and Hughes, D and Cui, X and Zhou, R and Qi, J and Yi, C and Liu, J and McFetridge, S and Silva, JD and Naderi-Meshkin, H and Krasnodembskaya, AD and Xu, H and Chen, M}, title = {MSC-EVs attenuate subretinal fibrosis in choroidal neovascularization through miR-21-5p-mediated inhibition of EMT and MMT and suppression of inflammation.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-026-03836-w}, pmid = {42063159}, issn = {1742-2094}, support = {AIM2301D02//Science Research Foundation of Aier Eye Hospital Group/ ; KY24002//Philanthropy Foundation of Xiangjiang Public Welfare Fund/ ; 2023JJ70047//Hunan Provincial Natural Science Fund/ ; }, abstract = {BACKGROUND: Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (nAMD). Sustained macular inflammation drives the initiation and progression of fibrosis by activating profibrotic cells and perpetuating tissue damage. This study investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in mitigating nAMD-associated subretinal fibrosis.<br><br>METHODS: MSC-EVs were prepared from human bone marrow-derived MSCs and characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western Blotting. Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced model. MSC-EVs were injected either intravitreally (1&#x2009;&#xd7;&#x2009;10[8] particles/eye, single injection) or retro-orbitally (1&#x2009;&#xd7;&#x2009;10[8] particles, two injections four days apart) immediately after the second laser. Eyes were collected 10 days post-second laser for immunostaining of collagen-1 and CD31 or iso-lectin B4. In vitro, primary human RPE and ARPE-19 cells were treated with TGF-&#x3b2;2 (10 ng/mL) to induce epithelial-mesenchymal transition (EMT); peritoneal macrophages were treated with TGF-&#x3b2;1 (10 ng/mL) to induce macrophage-to-myofibroblast transition (MMT). After 48&#xa0;h, cells were treated with MSC-EVs (cell-to-MSC-EV ratio&#x2009;=&#x2009;1:2000) for 3 days. Myofibroblast markers (&#x3b1;SMA, fibronectin, and collagen-1) were examined by immunocytochemistry and quantitative PCR (qPCR). Human iPCS-derived macrophages (iMACs), bone-marrow-derived macrophages, peritoneal macrophages, and BV2 microglia were treated with LPS (100 ng/mL) and IFN-&#x3b3; (20 ng/mL) for 24&#xa0;h with or without MSC-EVs (1:2000). Small RNA sequencing was used to identify specific functional molecules within MSC-EVs. Immune-related gene expressions were evaluated by qPCR.<br><br>RESULTS: Intravitreal and retroorbital administration of MSC-EVs reduced collagen-1[+] fibrotic lesions by 46% and 30%, respectively, and significantly inhibited infiltrating Iba-1[+] cells. In vitro, MSC-EVs attenuated TGF-&#x3b2;2-induced upregulation of &#x3b1;SMA, fibronectin, and collagen-1 at both protein and mRNA levels in RPE cells. Similarly, the expression of Acta2, Fn1, and Col1a1 in TGF-&#x3b2;1-treated macrophages was also significantly reduced following MSC-EV treatment. In LPS&#x2009;+&#x2009;IFN-&#x3b3;-stimulated immune cells, MSC-EVs significantly suppressed the expression of Il6 and Il1b in all cell types, and reduced the expression of Inos, Tnfa, and Cd86 in iMACs, peritoneal macrophages, and BV2 cells. Enriched hsa-miR-21-5p was identified in MSC-EVs and involved in the TGF-&#x3b2;-related signaling pathway. Overexpression of miR-21-5p mimic abrogated the TGF-&#x3b2;1-driven upregulation of pro-fibrotic markers in RPE and macrophages.<br><br>CONCLUSIONS: Local administration of MSC-EVs effectively mitigated subretinal fibrosis and reduced inflammation in the mouse model of nAMD, potentially via miR-21-5p-mediated attenuation of EMT and MMT, and suppression of inflammation. MSC-EVs represent a novel cell-free therapeutic strategy for macular fibrosis in nAMD.}, }
@article {pmid42063162, year = {2026}, author = {Huang, M and Lin, Y and Zhang, H and Yuan, R and Zeng, L and Li, S and Yang, Q and Gong, M and Xiao, R and Jia, P and Yuan, L and Guo, Q and Han, Z and Xie, L}, title = {The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.}, journal = {Biology direct}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13062-026-00821-4}, pmid = {42063162}, issn = {1745-6150}, abstract = {Autophagy is a self-digestive process in which cellular components are degraded and recycled to maintain homeostasis and cope with stress. When cells are in a state of stress, autophagy will degrade proteins, lipids and damaged organelles, and convert them into key nutrients and building cornerstones needed to maintain cell homeosis. More and more evidence shows that there is a link between autophagy process damage and the development of a variety of ophthalmic diseases that seriously threaten vision, including age-related macular degeneration, glaucoma and the formation of cataracts. Through a systematic review, we integrate experimental data covering basic biological mechanisms, genetic models and clinical evidence to clarify these pathological associations. With a focus on the mechanisms and regulation of autophagy in various ocular tissues and diseases, we analyzed research on autophagy in the lens, retina, cornea, and trabecular meshwork. Key findings elucidate the specific mechanisms of autophagy in maintaining lens transparency, promoting retinal ganglion cell survival, and regulating ocular immunity, demonstrating its critical role in preserving cellular equilibrium in ocular tissues. Furthermore, we evaluated potential therapeutic strategies targeting autophagic pathways, including mammalian target of rapamycin (mTOR) inhibition, transcription factor EB(TFEB) activation, noncoding RNA regulation, gene editing, and artificial intelligence-assisted diagnostics, which show significant promise for modulating autophagy to treat ocular diseases. The results of this review underscore the importance of autophagy in ocular health and disease.}, }
@article {pmid42063165, year = {2026}, author = {Ruiz-Medrano, J and Su, A and Mao, Z and Akiba, M and Ruiz-Moreno, JM}, title = {Exploratory study on a novel automatic quantification software by artificial intelligence for geographic atrophy associated to age-related macular degeneration.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00862-x}, pmid = {42063165}, issn = {2056-9920}, }
@article {pmid42064470, year = {2026}, author = {Afridi, R and Senaldi, G and Hwang, JJ and Nguyen, N and Inoue, T and Berger, B and Patel, S and Fazal, ZZ and Nguyen, QD and Sepah, Y}, title = {Assessing the Safety and Efficacy of Agonistic Monoclonal Antibody against Robo4 versus Ranibizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Phase I, Open-Label, Multicenter Study.}, journal = {Ophthalmology science}, volume = {6}, number = {5}, pages = {101084}, pmid = {42064470}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the safety and efficacy of agonistic monoclonal antibody against roundabout receptor 4 (DS-7080a) in eyes with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) alone or in combination with ranibizumab.<br><br>DESIGN: This was a phase I dose escalation and expansion study registered on clinicaltrials.gov (NCT02530918) and conducted in 3 parts. Parts 1 (first phase of the study [P1]) and 2 (second phase of the study [P2]) involved dose escalation and expansion for patients with nAMD, while part 3 (third phase of the study [P3]) involved dose expansion only for DME subjects.<br><br>SUBJECTS: Patients with nAMD or DME.<br><br>METHODS: In P1, eligible patients were randomized into 3 sequential dose-level cohorts to establish a maximum tolerated dose for DS-7080a as 4.0 mg and assess its safety and tolerability. The study then proceeded to P2, where 27 nAMD subjects were randomized to one of the 3 treatment arms: DS-7080a, 4.0 mg only; ranibizumab, 0.5 mg only; or DS-7080a, 4.0 mg plus ranibizumab, 0.5 mg. In P3, 20 subjects with DME were randomized to one of the 2 arms: DS-7080a, 4.0 mg or ranibizumab, 0.3 mg injected thrice. The treatment period was 12 weeks.<br><br>MAIN OUTCOME OUTCOMES: The primary endpoints were treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). The secondary endpoints were changes in central retinal thickness (central subfield thickness [CST]) and best-corrected visual acuity (BCVA).<br><br>RESULTS: A total of 56 patients were enrolled. Agonistic monoclonal antibody against Robo4, administered as monotherapy or in combination with ranibizumab, was generally well tolerated. Six drug-related TEAEs were observed, 4 of which were ocular events that led to treatment discontinuation. No drug-related SAEs or deaths occurred. As expected, ranibizumab was associated with improvements in BCVA and CST, whereas DS-7080a, alone or in combination, did not show clinically meaningful functional or anatomical benefit.<br><br>CONCLUSIONS: Agonistic monoclonal antibody against Robo4 was generally well tolerated in eyes with nAMD and DME; however, drug-related TEAEs, including ocular events leading to discontinuation, were observed. In terms of efficacy outcomes, DS-7080a does not show BCVA improvement and CST decrease when administered alone or in conjunction with ranibizumab. These findings are inconsistent with nonclinical studies supporting DS-7080a as a therapeutic agent for nAMD and DME.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42058402, year = {2026}, author = {Ameli, S and Ní Dhubhghaill, S and Vidal-Aroca, F and Fasolino, G}, title = {Surgical repositioning of a SING IMT following haptic dislocation: Restoration of alignment and visual function.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102583}, pmid = {42058402}, issn = {2451-9936}, abstract = {PURPOSE: The Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT) is an IOL designed to enhance central vision in patients with bilateral late-stage AMD. This report describes a case of successful surgical repositioning of a tilted SING IMT following haptic displacement out of the capsular bag.<br><br>OBSERVATIONS: A 77-year-old man with bilateral geographic atrophy and baseline CDVA (Corrected Distance Visual Acuity) of logMAR 0.96 (Snellen 20/200) underwent uncomplicated implantation of a SING IMT in the right eye. Six weeks postoperatively, CDVA showed no improvement, and the patient reported monocular diplopia with off-axis visual perception. Retinal morphology remained stable. Slit-lamp and anterior segment OCT revealed pronounced optic tilt caused by inferior haptic dislocation out of the capsular bag. The haptic was successfully repositioned by performing superior traction with a push-pull hook, resulting in restoration of straight, diplopia-free vision and an improvement in CDVA to logMAR 0.52 (Snellen 20/63).<br><br>CONCLUSIONS AND IMPORTANCE: Prompt surgical correction of haptic displacement may fully restore the optical and functional benefits of the SING IMT without compromising corneal health.}, }
@article {pmid42058595, year = {2026}, author = {Bettelheim, EC and Liu, J and Dazzan, P and Turkheimer, F}, title = {Self images: an empirical enquiry into Rembrandt's self-portraits.}, journal = {Frontiers in psychiatry}, volume = {17}, number = {}, pages = {1631373}, pmid = {42058595}, issn = {1664-0640}, abstract = {Many have speculated that events of personal and financial loss in the life of Rembrandt van Rijn (Rembrandt) caused depression and that this is revealed by examination of his work particularly self-portraits painted in old age. Some report detecting various physiological diseases associated with aging, including vision impairment, which may have affected his mood and work. Aging and neurodegenerative disease which often accompanies it, are both associated with depression. Depression is characterised by visual deficits including perception of reduced contrast and colour. Age-related neurological disorders are associated in artists with reduced complexity. Recent advances in imaging and computer technology make it possible to empirically examine changes in artistic style which can contribute to understanding artists' physical and mental health. Previous studies have identified associations between adverse events in artists' lives and altered contrast and colour in their self-portraits. In the current study changes in contrast, colour and fractal dimension were measured in the entire corpus of Rembrandt's painted self-portraits and portraits to determine whether changes in style indicate depression, cognitive decline, or neurological disease and whether differences in style can be detected between self-portraits and portraits of related and unrelated others. Productivity was also examined as an indirect indicator. The results suggest that it is unlikely that Rembrandt suffered from unipolar or bipolar depression, age-related cognitive decline, or neurodegenerative disease. The data are consistent with someone experiencing episodes of low mood associated with normal grieving and adversity followed by resilient recovery. There is evidence of a gradient in saliency and complexity between self-portraits and related and unrelated portraits and of a 'late' style identified by leading art historians consistent with macular degeneration.}, }
@article {pmid42059115, year = {2026}, author = {Song, SJ and Kim, E}, title = {Glucagon-Like Peptide-1 Receptor Agonists and Ocular Outcomes: Metabolic Transition, Retinal Vulnerability, and Risk-Stratified Monitoring.}, journal = {Journal of obesity &amp; metabolic syndrome}, volume = {35}, number = {2}, pages = {164-175}, doi = {10.7570/jomes26012}, pmid = {42059115}, issn = {2508-7576}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin-based therapies provide marked reductions in glycosylated hemoglobin (HbA1c), body weight, and cardiovascular risk. As global adoption expands and recognition of their broad metabolic benefits grows, clinical attention is shifting toward potential secondary complications, including ocular manifestations, during rapid metabolic improvement. This narrative review synthesizes evidence from randomized trials, meta-analyses, and observational studies up to 2026 to evaluate the effects of GLP-1-based therapies on various ocular outcomes. Recent meta-analyses demonstrate an overall neutral long-term risk for diabetic retinopathy (DR) and macular edema. Transient early worsening of DR occurs primarily in patients with advanced baseline disease and rapid HbA1c reductions, reflecting a metabolic transition phenomenon rather than intrinsic retinal toxicity. This interpretation is supported by 2024 cardiovascular outcome data in a non-diabetic population (e.g., Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT] trial) that showed no increased ocular risk. Observational data suggest protective associations with glaucoma via intraocular pressure-independent neuroprotection and a reduced risk of incident age-related macular degeneration, but a potential safety signal for nonarteritic anterior ischemic optic neuropathy has emerged in recent datasets. Although the absolute incidence remains low, risk with a delayed temporal pattern appears to be increased in specific cohorts. Emerging evidence also suggests potential benefits in ocular surface homeostasis and uveitis. Accordingly, following a 2025 multidisciplinary expert consensus, risk-stratified ophthalmic monitoring, rather than routine treatment avoidance, is recommended during the early metabolic transition in high-risk diabetic patients.}, }
@article {pmid42059902, year = {2026}, author = {Vahldiek, B and Heine, L and Vahldiek, A and Schröter, J and Wolf, JN and Swora, M and Reissberg, L and Pauleikhoff, L and Kleesiek, J and Pauleikhoff, D}, title = {Choroidal vascularity across aging and the spectrum of age-related macular degeneration: an AI-based OCT study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42059902}, issn = {1435-702X}, abstract = {PURPOSE: To characterize the choroidal morphology across a spectrum of participants affected by normal aging as well as age-related macular degeneration (AMD) using various metrics.<br><br>METHODS: Four cohorts were analyzed: healthy young (n&#x2009;=&#x2009;42), healthy elderly (n&#x2009;=&#x2009;19), iAMD (n&#x2009;=&#x2009;20), and treatment-naive nAMD eyes (n&#x2009;=&#x2009;79). Quantification of choroidal volume (CV) and choroidal vessel volume (VV) resulting in choroidal vascularity index (CVI) as well as mean choroidal thickness (CT), vessel thickness (VT) and foveal vessel area (FVA) and vessel count (FVC) were derived from spectral-domain optical coherence tomography using an artificial intelligence (AI)-based semantic segmentation model with manual validation. Cohort differences were statistically assessed.<br><br>RESULTS: All choroidal parameters were reduced in healthy elderly, iAMD and nAMD eyes compared with young controls. While most of these reduced choroidal measurements were largely similar between healthy elderly, iAMD and nAMD eyes, only CVI and FVA showed a specific reduction in nAMD eyes.<br><br>CONCLUSIONS: This study demonstrates a decline in several choroidal parameters with age, which can be quantified using AI-based segmentations. While age-related reductions were comparable between elderly and iAMD eyes, a significantly higher reduction of the CVI and FVA was observed in eyes with nAMD which may indicate a more pronounced alteration of choroidal structure in this condition.}, }
@article {pmid42060220, year = {2024}, author = {Kim, BS and Choi, RY and Kweon, H and Lee, JH and Kim, IW and Seo, M}, title = {Oxya chinensis sinuosa (OC) Extracts Protects ARPE-19 Cells against Oxidative Stress via Activation of the Mitogen-Activated Protein Kinases (MAPKs)/ Nuclear Factor-κB (NF-κB) Pathway.}, journal = {Food science of animal resources}, volume = {44}, number = {3}, pages = {699-709}, doi = {10.5851/kosfa.2024.e15}, pmid = {42060220}, issn = {2636-0780}, abstract = {Oxya chinensis sinuosa (OC) is a well-known edible insect. Several researches on the health benefits of OC consumption have been performed to date; however, their effect on eye health remains largely unknown. This study aimed to assess the protective effects of OC extracts on the oxidative stress on the retinal pigment epithelium (RPE) cells. Oxidative damage has been identified as one of the key regulatory factors in age-related macular degeneration. H2O2-induced reactive oxygen species (ROS) production, a well-known oxidative stress factor, can cause cell death in retinal pigment epithelia cells. In this study, we found that three OC extracts effectively prevented H2O2-induced ROS production and subsequent death of ARPE-19 cells in a dose-dependent manner. In addition, the OC extracts inhibited the phosphorylation of mitogen-activated protein kinases including p38, JNK, and ERK. The OC extracts restored IκBα degradation induced by H2O2, indicating that OC extracts suppressed the activation of nuclear factor-κB. Furthermore, the three OC extracts were shown to have antioxidant effects by up-regulating the intracellular expression of key antioxidant proteins such as SOD, NQO, and HO-1. Here we demonstrated the antioxidant and anti-apoptotic effects of the OC extracts on ARPE-19, indicating their potential role in improving eye health. These results suggest that three OC extracts plays a critical role in oxidative stress-induced cell death protects in ARPE-19 cells.}, }
@article {pmid42060349, year = {2026}, author = {Verma, L and Singh, S and Ramachandran, O}, title = {Peep into anti-vascular endothelial growth factor.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {635-638}, doi = {10.4103/IJO.IJO_385_26}, pmid = {42060349}, issn = {1998-3689}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor ; Ranibizumab/therapeutic use ; }, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed the management of retinal vascular diseases over the past two decades. Beginning with the foundational identification of VEGF as the principal driver of ocular neovascularization, the field has evolved from early agents such as pegaptanib and bevacizumab to more potent molecules including ranibizumab, aflibercept, brolucizumab, and faricimab. In India, the landscape is shaped by unique economic and epidemiological factors, including a high burden of diabetic retinopathy and age-related macular degeneration, limited healthcare reimbursement, and the significant role of biosimilar ranibizumab products in expanding access. This article provides a comprehensive overview of the historical development, pharmacology, regulatory milestones, safety considerations, and current clinical use of anti-VEGF agents in the Indian context, with emphasis on strategies to deliver equitable, high quality retinal care across a diverse population.}, }
@article {pmid42060351, year = {2026}, author = {Sharma, D and Gupta, T}, title = {Anti-vascular endothelial growth factor therapy in clinical practice: Real-world scenarios, limitations, and outcomes.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {643-652}, doi = {10.4103/IJO.IJO_185_26}, pmid = {42060351}, issn = {1998-3689}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; *Visual Acuity ; *Retinal Vein Occlusion/drug therapy ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/drug therapy ; *Wet Macular Degeneration/drug therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {This narrative review examines the "efficacy-effectiveness gap" in anti-vascular endothelial growth factor (anti-VEGF) therapy by comparing outcomes from randomized controlled trials (RCTs) with global and Indian real-world evidence (RWE) in neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Across all three conditions, real-world outcomes consistently fall short of those observed in RCTs. In nAMD, studies such as AURA report minimal visual gains by Year 2 (+0.6 letters) compared to +8 to +10 letters in RCTs, largely attributable to fewer injections administered in practice. Indian data, including the ARMOUR study, reflect similarly reduced injection frequencies alongside issues such as delayed presentation. For DME, global RWE demonstrates modest improvements in visual acuity with fewer injections per year than in RCTs, while Indian cohorts show even lower treatment intensity, resulting in anatomical stabilization without meaningful visual gains. Outcomes in RVO are also compromised by incomplete loading doses and inadequate follow-up. The primary drivers of this gap include undertreatment, variability in patient populations, and socioeconomic barriers that affect adherence and access to care. Overall, the discrepancy appears to stem more from real-world treatment challenges than from limitations of the therapies themselves. Addressing this gap will require practical approaches such as implementing Treat-and-Extend regimens, promoting earlier diagnosis and intervention, enhancing patient engagement, and increasing the use of cost-effective or longer-acting treatment options, particularly in resource-constrained settings like India.}, }
@article {pmid42060352, year = {2026}, author = {Singh, S and Kala, U and Bamel, A and Agarwal, M}, title = {Expanding horizons of intravitreal anti-vascular endothelial growth factor therapy in retinal diseases.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {661-668}, doi = {10.4103/IJO.IJO_3035_25}, pmid = {42060352}, issn = {1998-3689}, mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy/diagnosis ; }, abstract = {Vascular endothelial growth factor (VEGF) plays a central role in the pathogenesis of retinal and choroidal neovascularization, as well as macular edema (ME), in retinal disorders such as diabetic retinopathy, retinal vein occlusion (RVO), and age-related macular degeneration (ARMD). The advent of intravitreal anti-VEGF therapy has revolutionized their management. More recently, these agents have been explored in several other retinal pathologies characterized by secondary neovascularization, either in vascular or non-vascular disorders. This review summarizes current evidence on the role of anti-VEGF agents in retinal disorders other than ARMD, including central serous chorioretinopathy (CSCR), macular telangiectasia type 2 (MacTel), choroidal osteoma, retinopathy of prematurity (ROP), tubercular granuloma, inherited retinal dystrophies, Coats' disease, angioid streaks, and retinal vasoproliferative tumors (RVPTs).}, }
@article {pmid42061620, year = {2026}, author = {Zieneldien, T and Ma, S and Kim, J and Grant-Kels, JM}, title = {Dermatologic Care Amid Vision Loss: Preventing Harm While Preserving Autonomy.}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2026.04.1969}, pmid = {42061620}, issn = {1097-6787}, }
@article {pmid42050639, year = {2026}, author = {Rezende, MP and Faria, FA and Beraldo, DP and Polido, J and Belfort, R and Cabral, T}, title = {Correlations between SS-OCT and OCT angiography biomarkers in treatment-naïve neovascular AMD during aflibercept therapy: a prospective study.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00854-x}, pmid = {42050639}, issn = {2056-9920}, }
@article {pmid42050899, year = {2026}, author = {Sano, H and Yanai, R and Mitamura, Y}, title = {Hemolytic Glaucoma Following Intravitreal Aflibercept Injection for Age-Related Macular Degeneration: A Case Report.}, journal = {The American journal of case reports}, volume = {27}, number = {}, pages = {e952247}, doi = {10.12659/AJCR.952247}, pmid = {42050899}, issn = {1941-5923}, mesh = {Humans ; Male ; *Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Middle Aged ; Intravitreal Injections/adverse effects ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Glaucoma/etiology/chemically induced ; *Macular Degeneration/drug therapy ; *Hemolysis ; }, abstract = {BACKGROUND Intraocular pressure (IOP) elevation secondary to intraocular hemorrhage after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection for age-related macular degeneration (AMD) is exceedingly rare. Although mild, transient hyphema has been reported, secondary glaucoma caused by hemolysis or ghost cell formation has not previously been documented in this setting. CASE REPORT A 54-year-old man presented with decreased vision and was diagnosed with exudative AMD in the right eye. Baseline evaluation showed subretinal hemorrhage and macular neovascularization, and intravitreal aflibercept injections were initiated and continued for 1 year. Three days after the tenth injection, the patient developed blurred vision, progressing to hand-motion vision by day 4. Slit-lamp examination revealed hyphema with a fluid level, and IOP increased to 50 mmHg despite conservative therapy. The patient underwent anterior chamber irrigation and phacoemulsification with pars plana vitrectomy. Intraoperatively, mild vitreous hemorrhage was observed, and temporal scleral indentation revealed a localized blood clot adherent to the pars plana and vitreous base at the injection site. Postoperatively, IOP normalized, without recurrence of vitreous hemorrhage or exudative activity during 1-year follow-up. CONCLUSIONS This case demonstrates that hemolytic glaucoma can develop even after intravitreal anti-VEGF injection in AMD, a context in which intraocular bleeding is uncommon. Clinicians should remain vigilant to postinjection IOP elevation, and timely surgical intervention can yield favorable visual and pressure outcomes.}, }
@article {pmid42051690, year = {2026}, author = {Reiter, RJ and Sharma, R and Blasiak, J and Rosales-Corral, S and Loh, D}, title = {Retinal pigment epithelium pathology in age-related macular degeneration: mitigation with melatonin.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1813015}, pmid = {42051690}, issn = {2296-858X}, abstract = {Approximately 1.5 million Americans over the age of 40 suffer from vision-threatening age-related macular degeneration (AMD), a number expected to rise with aging demographics. AMD exists in two defined forms: dry (non-exudative) which accounts for up to 90% of cases, and wet (exudative). Dry AMD is characterized by the slow buildup of drusen under the retina, eventually leading to geographical atrophy. Wet AMD involves vascular endothelial growth factor (VEGF)-induced blood vessel formation from the choriocapillaris into the subretinal space, a process referred to as neovascularization. These newly formed blood vessels leak fluid into the subretinal space leading to atrophy of the retinal pigment epithelium (RPE) and associated photoreceptors. Despite clinical distinctions, dry and wet AMD share overlapping pathophysiological features, marked by degeneration of the RPE and the overlying photoreceptors. A major feature of the RPE and photoreceptors are their high metabolically activity and their large numbers of mitochondria, which generate reactive oxygen species (ROS) during ATP production. ROS-induced oxidative stress damages lipids, proteins and DNA, resulting in cellular degradation which contributes to AMD. Because of the elevated oxidative stress levels, antioxidants which neutralize ROS are often recommended as a treatment for AMD. A major objective of this review is to examine the role of melatonin, a powerful and multifunctional antioxidant, in altering the trajectory of AMD progression. Melatonin is synthesized in the RPE and photoreceptors of young individuals but its expression declines with age. As shown in an epidemiological report, its loss contributes to age-related degeneration of the RPE and photoreceptors. Moreover, melatonin inhibits VEGF, suggesting that it would be useful as a treatment for wet AMD. This review explores melatonin-mediated protective mechanisms in the retina, a likely mechanistic basis for the already published findings showing that melatonin use by humans is associated with delayed AMD, and potential clinical applications.}, }
@article {pmid42052023, year = {2026}, author = {Tang, M and Liu, Y and Dong, L}, title = {Unveiling the non-linear synergistic effects of smoking and aging on cataract-AMD comorbidity: an explainable artificial intelligence approach.}, journal = {Frontiers in public health}, volume = {14}, number = {}, pages = {1784189}, pmid = {42052023}, issn = {2296-2565}, mesh = {Humans ; *Cataract/epidemiology ; Male ; Female ; *Macular Degeneration/epidemiology ; Aged ; Retrospective Studies ; Case-Control Studies ; Comorbidity ; *Smoking/adverse effects/epidemiology ; *Artificial Intelligence ; Risk Factors ; *Aging/physiology ; Middle Aged ; Machine Learning ; Aged, 80 and over ; }, abstract = {BACKGROUND: The comorbidity of cataract and age-related macular degeneration (AMD) poses a significant public health burden. Traditional linear statistical models often fail to capture complex, non-linear interactions among risk factors. This study aimed to develop an interpretable machine learning framework to predict comorbidity risk and elucidate the synergistic effects of systemic and ocular factors.<br><br>METHODS: A retrospective case-control study was conducted involving 640 participants (264 comorbidity cases and 376 controls). Fifteen multi-dimensional clinical features were extracted. Four machine learning algorithms-Logistic Regression, Random Forest, SVM, and XGBoost-were trained and validated. Model performance was assessed via AUROC, AUPRC, and calibration curves. SHapley Additive exPlanations (SHAP) and LIME were employed to visualize global and local interpretability.<br><br>RESULTS: The XGBoost model demonstrated robust discriminative performance (AUC = 0.895, 95% CI: 0.85-0.93) and calibration compared to other algorithms. SHAP analysis identified drusen severity and lens opacity (LOCS III) as dominant ocular predictors, while C-reactive protein (CRP) and smoking were critical systemic contributors. Notably, interaction analysis revealed a non-linear synergistic effect: smoking was associated with an exponentially higher comorbidity risk in individuals aged >75 years, whereas CRP exhibited a distinct saturation threshold effect. Decision curve analysis confirmed the model's high net clinical benefit across a wide range of threshold probabilities.<br><br>CONCLUSION: This study establishes a robust, clinically applicable risk stratification tool for cataract and AMD comorbidity. By uncovering non-linear interactions between aging, lifestyle, and inflammation, it provides valuable evidence-based support for personalized screening and preventive intervention.}, }
@article {pmid42052781, year = {2026}, author = {Chen, X and Hao, P and Lu, P and Han, R and Jiang, Z and Jiang, L and Wang, L and Liu, Z and Li, X}, title = {Proteomic insights into nepetin-mediated protection against oxidative stress in ARPE-19 cells.}, journal = {Free radical research}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/10715762.2026.2667438}, pmid = {42052781}, issn = {1029-2470}, abstract = {Oxidative stress is one of the crucial factors associated with the pathogenesis of age-related macular degeneration (AMD), particularly the degeneration of retinal pigment epithelium (RPE) cells. In this study, we identified nepetin, a natural flavonoid compound, as a potential inhibitor of hydrogen peroxide (H2O2)-induced ARPE-19 cell death. Pretreatment of nepetin significantly reduced intracellular generation of reactive oxygen species (ROS). Quantitative proteomics was applied to explore the underlying molecular response, revealing that 77 proteins were up-regulated, and 198 proteins were down-regulated significantly after nepetin treatment. Gene ontology (GO) analysis and the protein-protein interaction (PPI) network analysis showed that heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP1), Sequestosome 1 (SQSTM1)/p62, and glucose-regulated protein 78 (GRP78) were associated with nepetin-mediated antioxidative responses. Western blotting confirmed the altered expression of these key proteins, with HO-1, p62, and GRP78 being upregulated and KEAP1 being downregulated. Immunofluorescence further showed nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, suggesting the involvement of Nrf2-related antioxidant signaling in nepetin-treated ARPE-19 cells. Although direct causal interactions were not established, the proteomic and bioinformatic analyses provide correlative and suggestive evidence that nepetin modulates key proteins within the oxidative stress response network. Based on our previous research and the current study, nepetin exhibits both anti-inflammatory and antioxidative properties in RPE cells, and may have potential implications for the prophylaxis and treatment of AMD, particularly dry AMD.}, }
@article {pmid42052818, year = {2026}, author = {Zhao, TT and Chang, MK and Shen, BY and Guo, HR and Han, YT and Wang, WF}, title = {Effect of Endogenous FGF21 Deficiency on the Inflammatory Microenvironment of the Retina.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {4}, pages = {47702}, doi = {10.31083/FBL47702}, pmid = {42052818}, issn = {2768-6698}, support = {2025GXNSFAA069182//Guangxi Natural Science Foundation Project/ ; 2023JJ70050//Natural Science Foundation of Hunan Province/ ; Z-A20251080//Guangxi Zhuang Autonomous Region Health Commission Self-funded Scientific Research Project/ ; }, mesh = {Animals ; *Fibroblast Growth Factors/deficiency/genetics ; Mice, Knockout ; Mice ; *Retina/metabolism/immunology/pathology/diagnostic imaging ; *Inflammation/genetics/metabolism/pathology ; Macrophages/immunology/metabolism ; Mice, Inbred C57BL ; Transcriptome ; *Cellular Microenvironment ; Tomography, Optical Coherence ; Signal Transduction ; Gene Expression Profiling ; }, abstract = {BACKGROUND: While the systemic metabolic role of fibroblast growth factor 21 (FGF21) is well-established, its function in retinal homeostasis and its link to retinal diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) remains poorly understood. This study investigated the impact of endogenous FGF21 deficiency on the retinal immune microenvironment.<br><br>METHODS: Retinal structure was assessed in FGF21 KO and wild-type mice using spectral-domain optical coherence tomography. Transcriptomic profiles of the retina/choroid were analyzed by RNA-seq. Differentially expressed genes (DEGs) were identified (DESeq2, FDR <0.05), clustered, and interrogated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Immune-cell composition was inferred with ImmuCellAI.<br><br>RESULTS: FGF21 KO mice showed no overt retinal structural defects under baseline conditions. Nevertheless, 449 DEGs were identified (293 up, 156 down in knockout). Pathway analysis revealed significant enrichment of cytokine-cytokine receptor interaction, chemokine signaling, and Jak-STAT cascades. Immune deconvolution indicated a significant increase in M2-polarised macrophages (p < 0.01) without change in total macrophage number. Expression of key inflammatory mediators including Il1b was concordantly altered.<br><br>CONCLUSIONS: This work establishes endogenous FGF21 as a crucial local immunomodulator and defines a novel mechanistic link to retinal disease susceptibility, supporting its further exploration as a therapeutic target.}, }
@article {pmid42052823, year = {2026}, author = {Ke, X and Liang, S and Qu, T and Li, S and Lei, J and Han, H and Guo, Y and Xing, M and Wang, X and He, S and Liao, M and Zhou, D and Yan, H}, title = {Platelet Factor 4: A Novel Therapeutic Inhibitor for Experimental Neovascular Age-Related Macular Degeneration.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {31}, number = {4}, pages = {49564}, doi = {10.31083/FBL49564}, pmid = {42052823}, issn = {2768-6698}, support = {82530032//National Natural Science Foundation of China/ ; 82330031//National Natural Science Foundation of China/ ; 82401296//National Natural Science Foundation of China/ ; 25JCZDJC00390//Natural Science Foundation of Tianjin/ ; 25JCQNJC00680//Natural Science Foundation of Tianjin/ ; 23JCQNJC01180//Natural Science Foundation of Tianjin/ ; TJYXZDXK-3-004A//Tianjin Key Medical Discipline Construction Project/ ; }, mesh = {Animals ; Humans ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Mice ; *Platelet Factor 4/pharmacology/therapeutic use/metabolism/administration &amp; dosage/genetics ; Disease Models, Animal ; *Macular Degeneration/drug therapy/metabolism/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Cell Proliferation/drug effects ; Mice, Knockout ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Cell Movement/drug effects ; Signal Transduction/drug effects ; Endothelial Cells/drug effects/metabolism ; Male ; Intravitreal Injections ; Receptors, LDL ; }, abstract = {BACKGROUND: Platelet factor 4 (PF4/CXCL4) is a chemokine with reported anti-angiogenic and immunomodulatory properties; however, the role of PF4 in neovascular age-related macular degeneration (nAMD) remains unclear. Thus, this study aimed to evaluate the therapeutic potential of PF4 in experimental models of ocular pathological neovascularization and explored the underlying mechanisms.<br><br>METHODS: PF4 expression was assessed in a laser-induced choroidal neovascularization (CNV) mouse model using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Recombinant PF4 was administered intravitreally in laser-induced CNV mice and very low-density lipoprotein receptor knockout (Vldlr&#x207b;/&#x207b;) mice, a model of spontaneous retinal neovascularization with retinal angiomatous proliferation (RAP)-like lesions. Pathological neovascularization and vascular leakage were quantified by fundus fluorescein angiography and choroidal/retinal flat-mount analyses. Immunofluorescence, qRT-PCR, and RNA sequencing were employed to evaluate inflammatory responses. Moreover, the effects of PF4 on vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human retinal microvascular endothelial cells were examined in vitro, and VEGF-mediated signaling was analyzed by Western blotting. Ocular safety was assessed by optical coherence tomography (OCT), electroretinography (ERG), hematoxylin and eosin (H&amp;E) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.<br><br>RESULTS: Intravitreal PF4 significantly reduced pathological neovascularization and vascular leakage in both models and attenuated intraocular inflammation, as indicated by decreased expression of proinflammatory cytokines and reduced microglial/macrophage recruitment. PF4 inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation in vitro. Mechanistically, PF4 downregulated VEGF expression in CNV lesions in vivo and suppressed VEGF-induced activation of vascular endothelial growth factor receptor 2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and signal transducer and activator of transcription 3 (STAT3) signaling in vivo and in vitro. PF4 administration was well tolerated, with no detectable adverse effects on retinal structure or function.<br><br>CONCLUSIONS: PF4 effectively inhibits ocular pathological neovascularization and inflammation by modulating the VEGF/VEGFR2 signaling pathway. These findings support PF4 as a promising therapeutic candidate for nAMD and warrant further investigation.}, }
@article {pmid42053093, year = {2026}, author = {Li, H and Xu, J and Wang, J and Cheng, L and Fan, J}, title = {Mapping ophthalmic research on glycosylation and glycation: a PRISMA-compliant bibliometric and co‑citation analysis.}, journal = {Future science OA}, volume = {12}, number = {1}, pages = {2663167}, doi = {10.1080/20565623.2026.2663167}, pmid = {42053093}, issn = {2056-5623}, abstract = {BACKGROUND: Enzymatic glycosylation and non-enzymatic glycation contribute significantly to the pathogenesis of major ocular diseases, particularly diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and cataract. However, the knowledge structure and developmental trajectory of glycosylation-related research in ophthalmology remain unclear.<br><br>METHODS: The literature on the role of enzymatic glycosylation and non-enzymatic glycation modification in ophthalmic diseases from 1997 to 2024 was searched in the core database of Web of Science. Bibliometrics analysis software VOS viewer (version 1.6.20), Citespace (version 6.1.R1), Scimago Graphica (version 6.1.R1), Microsoft Excel 2021.<br><br>RESULTS: This study analyzed 3,221 publications, all results are available on January 4, 2025. Biochemistry &amp; Molecular Biology was the primary subject area. Research has evolved from early exploration of advanced glycation end products and protein kinase C pathways toward inflammation, biomarker discovery, and risk prediction in specific ocular disorders. Increasing attention has also been directed toward glycosylation-based diagnostic markers and potential therapeutic targets.<br><br>CONCLUSION: This bibliometric analysis provides an ophthalmology-centered overview of glycosylation and glycation research, identifying DR as the primary research hub while highlighting emerging translational directions in retinal and other ocular diseases.}, }
@article {pmid42053221, year = {2026}, author = {Nitzan, I and Jaskoll, S and Kramer, A and Shmueli, O and Levy, J and Chowers, I}, title = {High-Density Lipoprotein Cholesterol Levels and Risk of Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {69}, doi = {10.1167/iovs.67.4.69}, pmid = {42053221}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Cholesterol, HDL/blood ; Aged ; *Macular Degeneration/blood/epidemiology ; Risk Factors ; Middle Aged ; Incidence ; Follow-Up Studies ; United States/epidemiology ; Aged, 80 and over ; Biomarkers/blood ; }, abstract = {PURPOSE: To evaluate the association between high-density lipoprotein cholesterol (HDL-C) levels and incident age-related macular degeneration (AMD) in a large cohort.<br><br>METHODS: This retrospective cohort study used electronic health records from 70 U.S. healthcare organizations in the TriNetX network from 2005 to 2025. Adults with at least two HDL-C measurements obtained at least three months apart were classified as having high HDL-C (all values &#x2265;60 mg/dL) or low HDL-C (all values &#x2264;39 mg/dL). Groups were matched 1:1 on demographics, comorbidities, medications, laboratory values, and healthcare utilization. Follow-up began at the second qualifying HDL-C measurement and continued for up to 10 years. Incident nonexudative and exudative AMD were evaluated using Kaplan-Meier and Cox proportional hazards analyses, with robustness assessed through nested matching, subgroup and sensitivity analyses, and positive and negative control outcomes.<br><br>RESULTS: Over 1.29 million person-years of follow-up, high HDL-C was associated with increased risk of nonexudative AMD (hazard ratio [HR] = 1.53; 95% confidence interval [CI], 1.32-1.78) and exudative AMD (HR = 1.37; 95% CI, 1.09-1.73). For nonexudative AMD, risk was elevated across early (HR = 1.55; 95% CI, 1.26-1.91), intermediate (HR = 1.82; 95% CI, 1.42-2.33), and advanced atrophic (HR = 1.85; 95% CI, 1.16-2.97) stages. Associations for nonexudative AMD were robust across washout periods, follow-up intervals, mortality exclusion, and stepwise matching. Associations for exudative AMD were consistently positive but less stable. Control outcomes supported the specificity and internal validity of the findings.<br><br>CONCLUSIONS: Higher HDL-C levels were associated with increased risk of incident nonexudative AMD and a weaker, less consistent association with exudative AMD. These findings suggest that sustained HDL-C levels may be relevant to AMD risk assessment and warrant further investigation.}, }
@article {pmid42053222, year = {2026}, author = {Kuchernig, L and Reiter, GS and Schrittwieser, J and Eidenberger, A and Jeremic, N and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Sacu, S}, title = {Choriocapillaris Flow Deficits Are Spatially Linked to Retinal Pigment Epithelium and Photoreceptor Integrity in Geographic Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {68}, doi = {10.1167/iovs.67.4.68}, pmid = {42053222}, issn = {1552-5783}, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; *Geographic Atrophy/physiopathology/diagnosis ; Male ; Female ; Aged ; *Choroid/blood supply ; Fluorescein Angiography/methods ; Middle Aged ; Aged, 80 and over ; Regional Blood Flow/physiology ; Fundus Oculi ; *Photoreceptor Cells, Vertebrate/pathology ; }, abstract = {PURPOSE: To assess the correlation between choriocapillaris (CC) flow deficits and structural biomarkers of outer retinal degeneration in eyes with geographic atrophy (GA) secondary to nonexudative age-related macular degeneration, using a novel histology-informed binarization method and multimodal image registration.<br><br>METHODS: Patients with GA underwent spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA + OCT) and swept-source optical coherence tomography angiography (SS-OCT-A; PLEX Elite 9000) imaging. Flow deficit percentage (FD%) was quantified via a novel histology-informed binarization approach. Retinal pigment epithelium loss (RPEL), ellipsoid zone loss (EZL), and ellipsoid zone (EZ) thickness were derived from SD-OCT using previously validated segmentation algorithms. Exact interdevice registration enabled spatial mapping. Linear mixed-effects models assessed global and local FD% associations with structural biomarkers.<br><br>RESULTS: We analyzed 115 eyes of 64 patients. Global FD% predicted RPEL (&#x3b2;, estimated effect = 0.16 mm/%FD; 95% confidence interval [CI], 0.10-0.22; P < 0.001) and EZL (&#x3b2; = 0.11 mm/%FD; 95% CI, 0.07-0.15; P < 0.001). Local FD% was elevated in RPEL (&#x3b2; = 22.95%FD; 95% CI, 20.86-25.04; P < 0.001) and EZL (&#x3b2; = 12.03%FD; 95% CI, 9.94-14.12; P < 0.001) regions. FD% negatively correlated with EZ thickness independent of drusen (&#x3b2; = -0.05&#xa0;&#xb5;m/%FD; 95% CI, -0.05 to -0.05; P < 0.001).<br><br>CONCLUSIONS: Using a novel multimodal pipeline combining structural SD-OCT, SS-OCT-A, and histology-informed choriocapillaris binarization, we demonstrate that CC flow deficits are spatially correlated with outer retinal degeneration and independently associated with photoreceptor integrity, supporting their potential as predictive biomarkers for GA severity. These findings support a model in which choriocapillaris hypoperfusion contributes to metabolic stress in the retinal pigment epithelium and compromises photoreceptor outer segment integrity in geographic atrophy.}, }
@article {pmid42053269, year = {2026}, author = {Monteiro, A and Mugisho, OO and de Souza, A and Liu, L and Agban, Y and Agarwal, P and Shome, A and Rupenthal, ID and Sheardown, H}, title = {A Cationic Block Co-Polymer for Gene Delivery in the Posterior Segment of the Eye.}, journal = {Journal of biomedical materials research. Part A}, volume = {114}, number = {5}, pages = {e70078}, doi = {10.1002/jbm.a.70078}, pmid = {42053269}, issn = {1552-4965}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; *Gene Transfer Techniques ; *Polymers/chemistry ; Animals ; Cell Line ; Cations/chemistry ; *Oligonucleotides, Antisense/pharmacology/administration &amp; dosage ; Retinal Pigment Epithelium/metabolism/cytology ; *Posterior Eye Segment/metabolism ; Cell Survival/drug effects ; }, abstract = {Diseases of the back of the eye such as neovascular age-related macular degeneration (nAMD) are vision threatening and treatment is burdensome for patients, often requiring ocular injections every other month. Injection risks and logistics lower patient compliance; however, even patients receiving optimal treatment can deteriorate. Gene silencing has shown great potential as a therapeutic alternative but is often limited by instability of the genetic payload, reducing efficacy. In the current work, a cationic block co-polymer was developed and investigated as a delivery system for an antisense oligonucleotide (ASO) to the posterior segment of the eye. This work details the synthesis, characterization, in vitro, and ex vivo testing of the polymer and the subsequent polyplexes formed between the polymer and ASO. pH-dependent polyplexes were formed which fully complexed the ASO at 1:1 and 10:1 ratios of polymer amine groups to ASO phosphate groups (N/P ratio). Neither formulation displayed a significant reduction in the viability of human retinal pigment epithelial (ARPE-19) cells. The polyplexes were under 150 nm in diameter, with a slightly negative zeta potential. In comparison to the naked ASO, the 10:1 polyplexes achieved superior transfection into ARPE-19 cells. After 24 h, the ASO delivered by the 10:1 polyplexes displayed significant knockdown of the target protein. Polyplexes were well distributed throughout the vitreous humor, retina, and choroid within 4 h of intravitreal administration in an ex vivo porcine eye. These materials show potential for gene delivery in the treatment of various posterior segment conditions including nAMD.}, }
@article {pmid42054085, year = {2026}, author = {Ayachit, A and Rao, S and Eqbal, S and Vibhute, G and Fatima, F and Joshi, S and Ayachit, G and Chhablani, J}, title = {Neovascular age-related macular degeneration management - Beyond anti-VEGF.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {653-660}, doi = {10.4103/IJO.IJO_3274_25}, pmid = {42054085}, issn = {1998-3689}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Disease Management ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; }, abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed neovascular age-related macular degeneration (nAMD) into a chronic, treatable condition. However, real-world outcomes remain limited by treatment burden, limited durability, variable response, and progression of atrophy or fibrosis, highlighting the need for strategies beyond VEGF-A suppression. This narrative review summarizes emerging therapeutic approaches aimed at addressing these unmet needs. Adjunctive pharmacologic targets, including angiopoietin/Tie2 signaling, VEGF-C/D, integrins, hypoxia-inducible pathways, and intracellular tyrosine kinase inhibition, are discussed. Gene-based therapies offering the potential for prolonged intraocular VEGF suppression are discussed, though challenges related to inflammation, irreversibility, and patient selection persist. Finally, surgical and regenerative strategies such as retinal pigment epithelium monolayer transplantation are reviewed as investigational options for highly selected patients. Collectively, these developments signal a shift toward individualized, multipronged nAMD management, with anti-VEGF therapy remaining foundational, while biomarkers, intraocular biochemical milieu, and patient adherence may guide future care.}, }
@article {pmid42054086, year = {2026}, author = {Giridhar, A and Lekha, T and Chandran, K}, title = {Anti-vascular endothelial growth factor therapy in polypoidal choroidal vasculopathy.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {669-680}, doi = {10.4103/IJO.IJO_3237_25}, pmid = {42054086}, issn = {1998-3689}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Polyps/drug therapy/diagnosis ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Choroid/blood supply ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage ; Fundus Oculi ; *Choroidal Neovascularization/drug therapy/diagnosis ; *Choroid Diseases/drug therapy/diagnosis ; Polypoidal Choroidal Vasculopathy ; }, abstract = {The diagnosis and management of polypoidal choroidal vasculopathy (PCV), a complex chorioretinal disease which constitutes 60% of neovascular age-related macular degeneration cases among Asians, have evolved significantly in the last decade. SD-OCT biomarkers can reliably diagnose and monitor PCV, restricting the role of invasive indocyanine green angiography to situations like suboptimal responders to therapy where it helps to clarify the diagnosis and explore other treatment options like laser. The introduction of Aflibercept resulted in a paradigm shift in the treatment from combination therapy (photodynamic therapy plus injection of anti-VEGF drugs) to anti-VEGF monotherapy after it was proven noninferior to the former in the PLANET trial. The limited availability of PDT also favored this shift. The longer half-life of Aflibercept led to adoption of proactive treatment regimens like treat and extend guided by fluid markers on OCT, reducing the treatment burden. Newer molecules with more potency and durability like Brolucizumab and Faricimab demonstrated superior drying effects and achieved a longer treatment interval of up to 16 weeks, offering additional options for anti-VEGF monotherapy. HAWK and HARRIER trials proved the noninferiority of Brolucizumab to Aflibercept, though there were safety concerns of inflammation. Interim analysis of the on-going SALWEEN trial for Faricimab in PCV has also shown favorable outcomes. Characterizing the different phenotypes of PCV based on OCT and choosing the appropriate drug and treatment regimen are important to maximize visual outcome while reducing the treatment burden. This article reviews the evolution of anti-VEGF therapy in PCV and provides recommendations for optimal management in the real world.}, }
@article {pmid42054089, year = {2026}, author = {Chakraborty, D and Sinha, TK and Boral, S and Das, A}, title = {Biosimilar anti-vascular endothelial growth factor agents: Clinical outcomes, safety, and cost-effectiveness in India.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {5}, pages = {760-766}, doi = {10.4103/IJO.IJO_3222_25}, pmid = {42054089}, issn = {1998-3689}, mesh = {Humans ; India/epidemiology ; Cost-Benefit Analysis ; *Biosimilar Pharmaceuticals/economics/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/economics/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Ranibizumab/therapeutic use/economics ; *Retinal Diseases/drug therapy/economics/epidemiology ; Treatment Outcome ; }, abstract = {Retinal vascular diseases, including neovascular age-related macular degeneration, diabetic macular edema, retinal vein occlusion, myopic choroidal neovascularization, and retinopathy of prematurity, are a major cause of visual morbidity in India. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed the management of these conditions, long-term outcomes in real-world Indian practice are frequently limited by affordability-related undertreatment. The introduction of biosimilar anti-VEGF agents, particularly ranibizumab biosimilars, has therefore assumed critical importance in improving access to sustained retinal care. This narrative review synthesizes the available Indian evidence on the clinical efficacy, safety, immunogenicity, and cost-effectiveness of biosimilar anti-VEGF agents. A comprehensive literature search was conducted in PubMed, MEDLINE, EMBASE, and Scopus from inception through September 2025 using predefined keywords related to biosimilar ranibizumab, retinal vascular diseases, safety, immunogenicity, real-world evidence, and cost-effectiveness. Additional studies were identified through manual screening of reference lists. Peer-reviewed English-language randomized trials, phase 3 studies, post-marketing surveillance reports, and large real-world cohorts from India were included. Across major retinal indications, phase 3 trials consistently demonstrated equivalence or noninferiority of biosimilars to the reference molecule in visual and anatomical outcomes, with comparable safety and low immunogenicity. Large real-world datasets further corroborate these findings and provide reassurance regarding ophthalmic use of biosimilar anti-VEGF. Importantly, reduced treatment costs have translated into improved treatment initiation and adherence. Overall, current evidence supports biosimilar ranibizumab as a safe, effective, and cost-effective alternative for retinal diseases in resource-limited settings.}, }
@article {pmid42054256, year = {2026}, author = {Gruszka-Goh, MH and Donachie, PHJ and Chhabra, RR and McKibbin, M}, title = {The Royal College of Ophthalmologists National Ophthalmology Database Age-related Macular Degeneration (AMD) Audit, Report 2: Baseline characteristics, the care pathway and 12-month visual acuity and safety outcomes for 54,882 eyes starting treatment for neovascular AMD.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-16}, doi = {10.1159/000552289}, pmid = {42054256}, issn = {1423-0267}, abstract = {AIMS: To report aggregate data from the United Kingdom AMD (age-related macular degeneration) Audit, focussing on baseline characteristics, treatment and one year acuity and safety outcomes for eyes starting treatment for neovascular AMD between April 2021 and March 2023.<br><br>METHODS: Anonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at participating centres providing NHS-funded treatment. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation.<br><br>RESULTS: Analysis included 54,882 eyes of 48,371 patients from 78 participating treatment centres. Just over 60% were female and the median age at the start of treatment was 79.9 years for first treated eyes and 82.2 years for second treated eyes. Median baseline acuity was 60 ETDRS letters (interquartile range (IQR)= 44-70) and 28.1% of eyes had "good" acuity, defined as &#x2265; 70 ETDRS letters. The initial three injections, during the loading phase of monthly treatment, were given within 10 weeks in 64% of eyes and the median number of injections in the first 12 months was 6 (IQR 4-8). The median interval between injections at the end of the first year of treatment was 8 weeks (IQR 6-12 weeks). Trained non-medical healthcare professionals administered at least 72% of injections. Median acuity after 12 months was 65 ETDRS letters (IQR 48-75) and 43.1% had "good" visual acuity. The incidence of intra-ocular inflammation and presumed infectious endophthalmitis after each injection were 0.03% (1 in 3,176) and 0.014% (1 in 7,013) respectively. There was no difference in the incidence of either complication by profession of the injector.<br><br>CONCLUSIONS: Aggregate data from the UK AMD Audit provides real-world evidence and a benchmark against which other countries and centres can compare local performance and outcomes. Almost 91% of eyes retained stable acuity and avoided moderate visual loss after 12 months of treatment. The best acuity outcomes were obtained in younger patients and in eyes treated second, with good baseline acuity, prompt completion of the loading phase of treatment and receiving more injections during the first 12 months of treatment.}, }
@article {pmid42054488, year = {2026}, author = {Zhou, Y and Xu, M and Xu, Y and Shao, A and Cui, W and Shen, W and He, Y and Chen, Z and Zhang, Y and Miao, Q and Han, H and Ye, J}, title = {Iron Homeostasis Restoration via Triple-Pool-Targeted Nanotherapy for Enhanced Amelioration of Age-Related Macular Degeneration.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.6c00302}, pmid = {42054488}, issn = {1936-086X}, abstract = {Oxidative stress-induced retinal pigment epithelium (RPE) damage and ferroptosis are critical in retinal degenerative diseases, particularly in age-related macular degeneration (AMD)─a major cause of irreversible blindness. Current clinical AMD treatment is predominantly dependent on intravitreal anti-VEGF administration targeting only late-stage choroidal neovascularization (CNV), with limitations of incomplete response and adverse effects. Herein, a facile synthesis of Nuci@PAM-BR, which was designed by modification of antioxidant bilirubin to the surface and encapsulation of antiferroptosis nuciferine in the hydrophobic cavity of polyamidoamine dendrimers, was reported, thus achieving iron homeostasis restoration via triple-pool-targeted scavenging properties for eradicating CNV in AMD management. Our results demonstrated that Nuci@PAM-BR could significantly attenuate CNV by targeting the detrimental "triple pool" in damaged RPE cells, exhibiting excellent antioxidant and anti-inflammatory properties that contributed to its excellent antiangiogenic effect, achieving an over 80% reduction in leakage area and an over 85% decline in neovascular lesion. Such triple-pool-targeted nanotherapy offers a promising alternative and holds significant potential for the future clinical treatment of diverse fundus neovascularization diseases, including AMD.}, }
@article {pmid42054989, year = {2026}, author = {Wang, T and Xu, Y}, title = {RetinalFRNet: retinal vessel segmentation in OCTA images using the feature reconstruction network.}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {}, number = {}, pages = {}, pmid = {42054989}, issn = {1862-278X}, abstract = {OBJECTIVES: Automated segmentation of retinal blood vessels in optical coherence tomography angiography (OCTA) images is essential for early diagnosis of ocular diseases such as diabetic retinopathy, myopia, and macular degeneration. This study evaluates the performance of the Retinal Feature Reconstruction Network (RetinalFRNet), a full-resolution deep learning architecture designed for OCTA retinal vessel segmentation.<br><br>METHODS: RetinalFRNet integrates recurrent neural network modules within a ConvNeXt backbone while preserving full spatial resolution without downsampling. Its performance was compared with five algorithms&#xa0;-&#xa0;fuzzy C-means (FCM), U-Net, ResUnet, Vision Transformer (ViT), and VM-Unet&#xa0;-&#xa0;using three publicly available datasets (OCTA-3&#xa0;mm, OCTA-6&#xa0;mm, and ROSSA). All models were trained using the Adam optimizer for 100 epochs and evaluated using seven standard metrics including Accuracy, Dice coefficient, Sensitivity, and mean Intersection over Union (IoU).<br><br>RESULTS: RetinalFRNet achieved the highest overall performance across all datasets, reaching a Dice coefficient of 91.72&#x202f;% and mean IoU of 84.93&#x202f;% on the ROSSA dataset, improving performance by up to 30.66&#x202f;% over the FCM baseline.<br><br>CONCLUSIONS: RetinalFRNet demonstrates superior accuracy and robustness for OCTA retinal vessel segmentation. Its downsampling-free architecture enables improved detection of fine vascular structures critical for ophthalmic diagnosis. Further multi-center validation is recommended prior to clinical deployment.}, }
@article {pmid42055007, year = {2026}, author = {Arduini, BL and Blenkinsop, TA and Naimark, M and Borden, S and Charniga, C and Campbell, M and Rugenstein, N and Davis, RJ and Alam, N and Prusky, G and Frye, AM and Mazzoni, F and Finnemann, SC and Zhao, C and Lederman, P and Saini, JS and Kiehl, TR and Renga, N and Kozak, JA and Rocchio, PA and Salero, E and Boles, NC and Goderie, SK and Lotz, S and Adamo, JE and Zaccaglino, S and Onanuga, K and Fiske, M and Capela, A and Temple, S and Stern, JH}, title = {IND-enabling safety and efficacy of RPESC-RPE-4W, an adult RPE progenitor cell therapy for dry age-related macular degeneration.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102779}, doi = {10.1016/j.xcrm.2026.102779}, pmid = {42055007}, issn = {2666-3791}, abstract = {Dry age-related macular degeneration (AMD) is a prevalent blinding disorder characterized by loss of retinal pigment epithelium (RPE) cells and resulting central vision impairment. Here, we describe preclinical studies supporting an investigational new drug (IND) application for adult RPE stem cell-derived RPE (RPESC-RPE) cell replacement therapy. We establish donor-to-donor reproducibility and Good Manufacturing Practice (GMP) processes and evaluate the GMP cell product in preclinical studies conducted in accordance with Good Laboratory Practice principles. Efficacy experiments in Royal College of Surgeons rats show that subretinal implantation of the 4-week, postmitotic, progenitor-stage product (RPESC-RPE-4W) produces significant and durable vision rescue compared to vehicle control. Biodistribution and safety studies in immunocompromised Rowett Nude rats demonstrate a favorable safety profile, with no adverse effects related to the cell product. These studies underpin allowance of an ongoing phase 1/2a clinical trial.}, }
@article {pmid41851876, year = {2026}, author = {Zhang, J and Zhang, F and Wang, P and Lin, B and Yang, M and Chen, Q}, title = {Fellow-eye effect of intravitreal aflibercept 8mg in a patient with bilateral refractory nAMD: a case report and literature review.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41851876}, issn = {1471-2415}, support = {No. 82171062//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy remains first-line therapy for the treatment of neovascular age-related macular degeneration (nAMD), but the high frequency of injections imposes a substantial burden on elderly patients. High-dose aflibercept 8 mg has been shown to extend dosing intervals while maintaining anatomical control. Fellow-eye effects have been reported with other anti-VEGF agents but not with aflibercept 8 mg.<br><br>CASE PRESENTATION: An 89-year-old woman with bilateral refractory nAMD had received 23 prior anti-VEGF injections in the right eye. Owing to financial constraints, she underwent unilateral aflibercept 8&#xa0;mg injection in the right eye only. Baseline best-corrected visual acuity (BCVA) was 0.82 the logarithm of the minimum angle of resolution (logMAR) in the right eye and 1.0 logMAR in the left eye. One week after intravitreal injection, optical coherence tomography (OCT) showed marked bilateral improvement: central subfield thickness (CST) decreased from 629 to 327&#xa0;&#x3bc;m in the treated eye and from 357 to 308&#xa0;&#x3bc;m in the untreated fellow eye. BCVA remained stable in the treated eye, while improved to 0.70 logMAR in the fellow eye.<br><br>CONCLUSION: This is the first reported case of a fellow-eye effect associated with aflibercept 8&#xa0;mg. The findings suggest a potential systemic effect of high-dose aflibercept, but it should be noted that, for patients with bilateral nAMD, bilateral treatment is still necessary to avoid insufficient treatment of the contralateral eye.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-026-04751-7.}, }
@article {pmid42046820, year = {2026}, author = {Karpecki, P and Ayres, B and Donnenfeld, E and Farid, M and Gaddie, IB and Gupta, PK and Koetting, C and Lindstrom, R and McGee, S and Nichols, KK and Periman, LM and Pflugfelder, S and Starr, C and Venkateswaran, N and Yeu, E}, title = {Lotilaner ophthalmic solution 0.25% in the treatment of Demodex blepharitis: A case report.}, journal = {SAGE open medical case reports}, volume = {14}, number = {}, pages = {2050313X261443128}, pmid = {42046820}, issn = {2050-313X}, abstract = {Demodex blepharitis is a chronic inflammatory ocular condition caused by Demodex mite infestation of the eyelid that can negatively impact quality of life. Currently, lotilaner ophthalmic solution 0.25% is the only FDA-approved treatment for Demodex blepharitis. The Demodex Expert Panel on Treatment and Eyelid Health has established consensus that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis. We report a patient who presented with collarettes, the pathognomonic sign of Demodex blepharitis, meibomian gland dysfunction, and poor visual acuity. The patient also had a history of neovascular age-related macular degeneration. Consistent with the Demodex Expert Panel on Treatment and Eyelid Health consensus recommendations, the patient was treated with lotilaner ophthalmic solution 0.25%, lid scrubs, and warm compresses. At the 2-month follow-up, collarettes had resolved, and signs of meibomian gland dysfunction had improved. This case supports the Demodex Expert Panel on Treatment and Eyelid Health recommendation that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis.}, }
@article {pmid42046926, year = {2026}, author = {Çalışkan, B and Demir, Y}, title = {Serum Cholinesterases as Indicators of Cholinergic Dysfunction in Exudative Age-Related Macular Degeneration.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/02713683.2026.2664597}, pmid = {42046926}, issn = {1460-2202}, abstract = {PURPOSE: The aim of this study was to measure serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in order to evaluate the potential role of the cholinergic system in exudative type age-related macular degeneration (AMD).<br><br>METHODS: This case-control study involved 38 individuals diagnosed with exudative AMD and 41 healthy individuals with similar characteristics in terms of age and gender. The Ellman method was used to evaluate serum AChE and BChE activity after each subject underwent an ophthalmological examination. Multivariate logistic regression, ROC curve analysis, t-tests, and Mann-Whitney U tests were used in the statistical studies.<br><br>RESULTS: Serum AChE activity levels were higher in the AMD-diagnosed group compared to the control group (1.155&#x2009;&#xb1;&#x2009;0.178&#x2009;&#xb5;mol/mL vs. 1.029&#x2009;&#xb1;&#x2009;0.150&#x2009;&#xb5;mol/mL; p&#x2009;=&#x2009;0.002). There was no statistically significant difference in BChE activity levels (p&#x2009;=&#x2009;0.24). AChE activity showed moderate diagnostic performance according to ROC analysis (AUC = 0.697; 95% CI: 0.580-0.814; optimal threshold &#x2265;1.106&#x2009;&#xb5;mol/mL; sensitivity 63.2%; specificity 70.7%). According to logistic regression analysis, AChE activity levels were considered an independent predictor of AMD (OR = 89.34; p&#x2009;=&#x2009;0.005).<br><br>CONCLUSIONS: The increased serum AChE activity observed in exudative AMD suggests that the cholinergic system plays a role in retinal degeneration. AChE levels could be considered as potential AMD pathogenesis biomarkers and as a potential treatment target.}, }
@article {pmid42047667, year = {2026}, author = {Sun, N and Li, J and Wang, J and Wang, J and Chen, T and Wang, Y and Liu, C and Yang, S and Yao, T and Feng, H and Wang, Z}, title = {Endothelial TRPV1 Drives Choroidal Neovascularization in Wet Age-Related Macular Degeneration via NF-κB Signaling.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {64}, doi = {10.1167/iovs.67.4.64}, pmid = {42047667}, issn = {1552-5783}, mesh = {Animals ; *TRPV Cation Channels/genetics/metabolism/biosynthesis ; *Choroidal Neovascularization/metabolism/etiology/genetics/pathology ; *NF-kappa B/metabolism ; Mice ; Humans ; *Wet Macular Degeneration/metabolism/complications/genetics ; Signal Transduction/physiology ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; Tomography, Optical Coherence ; Fluorescein Angiography ; Male ; Real-Time Polymerase Chain Reaction ; Blotting, Western ; Human Umbilical Vein Endothelial Cells/metabolism ; Cells, Cultured ; Female ; Aged ; Endothelial Cells/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; }, abstract = {PURPOSE: We investigated the effects of endothelial cell transient receptor potential vanilloid 1 (TRPV1) activation on neovascularization and endothelial cell-microglial crosstalk, aiming to clarify the mechanisms underlying choroidal neovascularization (CNV) in wet age-related macular degeneration (wAMD).<br><br>METHODS: We performed bioinformatics analysis on transcriptomes of retinal pigment epithelium-choroidal tissues from wAMD patients. Vascular leakage was assessed in laser-induced CNV and TRPV1 knockout (TRPV1-/-) mice using fundus fluorescein angiography, optical coherence tomography, hematoxylin and eosin staining, and isolectin B4 staining. TRPV1 expression in CNV mice was determined via immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction analyses. Angiogenesis and microglial activation were examined via pharmacological intervention, siRNA silencing, and co-culture assays. Physiological TRPV1 agonists were analyzed by public metabolomics datasets.<br><br>RESULTS: TRPV1 was upregulated in patients with wAMD and mice with laser-induced CNV. TRPV1 activation exacerbated vascular leakage in CNV mice, whereas inhibition or knockout had the opposite effects. In human umbilical vein and retinal microvascular endothelial cells, TRPV1 activation promoted tube formation, with no measurable effects on proliferation or migration. TRPV1 promoted the release of inflammatory factors from endothelial cells by regulating the nuclear factor kappa B (NF-&#x3ba;B) pathway, which in turn induced pro-inflammatory polarization of microglia and the secretion of angiogenic factors from microglia, further facilitating angiogenesis. Moreover, linoleic acid, a physiological ligand of TRPV1, activated the endothelial TRPV1/NF-&#x3ba;B pathway to promote angiogenesis.<br><br>CONCLUSIONS: Endothelial TRPV1 mediated endothelial dysfunction and microglial activation via NF-&#x3ba;B, thereby promoting CNV, with linoleic acid serving as a key activator. TRPV1 can be considered a potential therapeutic target for treating wAMD.}, }
@article {pmid42048095, year = {2026}, author = {Shadrichev, FE and Strunina, YV}, title = {[Cost analysis of aflibercept 8 mg versus other anti-VEGF agents].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {2}, pages = {40-48}, doi = {10.17116/oftalma202614202140}, pmid = {42048095}, issn = {0042-465X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/economics ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Intravitreal Injections/economics/methods ; Russia ; Angiogenesis Inhibitors/economics/administration &amp; dosage ; *Macular Edema/drug therapy/economics/etiology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/economics/administration &amp; dosage ; Male ; Cost-Benefit Analysis ; Female ; Treatment Outcome ; Costs and Cost Analysis ; *Diabetic Retinopathy/drug therapy/economics/diagnosis/complications ; Aged ; Antibodies, Monoclonal, Humanized ; }, abstract = {PURPOSE: This study aimed to assess the economic impact of aflibercept 8 mg (114.3 mg/ml, 0.263 ml; hereinafter aflibercept 8 mg) compared with alternative anti-VEGF agents in adult patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) over a 2-year treatment period.<br><br>MATERIAL AND METHODS: The study compared different anti-VEGF therapies (aflibercept 8 mg; aflibercept 2 mg - 40 mg/ml, 0.278 ml; brolucizumab 6 mg - 120 mg/ml, 0.23 ml; ranibizumab 0.5 mg - 10 mg/ml, 0.23 ml) from the perspective of the healthcare system of the Russian Federation over a 2-year horizon. The number of intravitreal injections was determined based on an indirect comparative analysis; the number of administrations was reconstructed using an anchor value for aflibercept 8 mg and published differences in injection frequencies. Costs were calculated using the weighted average procurement price per package. The burden on the compulsory health insurance (CHI) system was estimated based on the average cost per insurance case (Diagnosis-Related Group, DRG, for "Intravitreal drug administration") of 47 459.63 RUB.<br><br>RESULTS: The costs over 2 years were lower with aflibercept 8 mg, resulting in savings of 99 713-140 434 RUB per patient with nAMD and 98 305-173 196 RUB with DME, depending on the comparator drug. When assessing the burden on the CHI system, savings amounted to 142 378-489 783 RUB per patient with nAMD and 119 598-541 039 RUB per patient with DME.<br><br>CONCLUSION: The use of aflibercept 8 mg in nAMD and DME reduces both direct treatment costs and expenditures of the CHI system in the first and second years of therapy, as well as cumulatively over 2 years. The results remain robust under price reductions and support the economic feasibility of the use of aflibercept 8 mg.}, }
@article {pmid42048097, year = {2026}, author = {Litvina, EA and Illarionova, AR and Potapova, OM}, title = {[Antiangiogenic therapy after cataract surgery in neovascular age-related macular degeneration (clinical observation)].}, journal = {Vestnik oftalmologii}, volume = {142}, number = {2}, pages = {57-62}, doi = {10.17116/oftalma202614202157}, pmid = {42048097}, issn = {0042-465X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; Female ; Male ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Visual Acuity ; Tomography, Optical Coherence/methods ; Treatment Outcome ; *Phacoemulsification/methods/adverse effects ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Retrospective Studies ; *Cataract/complications/diagnosis ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Intravitreal Injections ; Aged, 80 and over ; }, abstract = {UNLABELLED: The combination of age-related cataract and neovascular age-related macular degeneration (nAMD) presents a clinically challenging scenario, as it requires continuation of anti-angiogenic therapy during the perioperative period. The impact of cataract phacoemulsification (PE) on nAMD activity and the need for continued anti-VEGF treatment remains a subject of debate.<br><br>PURPOSE: This study assessed the safety profile and progression of nAMD over 12 months following phacoemulsification in patients undergoing treatment with aflibercept and brolucizumab.<br><br>MATERIAL AND METHODS: This retrospective-prospective study included 24 patients (24 eyes) with nAMD and age-related cataract. Two groups were formed: the brolucizumab group (n=12) and the aflibercept group (n=12). All patients underwent PE with intraocular lens (IOL) implantation. The examination protocol included best-corrected visual acuity (BCVA) assessment, biomicroscopy, fundus photography, optical coherence tomography (OCT), and OCT angiography. Outcomes were evaluated over 12 months preoperatively and 12 months postoperatively. The analysis included BCVA, central retinal thickness (CRT), presence of intra-, subretinal, and subpigment epithelial fluid, and the number of anti-VEGF injections.<br><br>RESULTS: The number of injections did not increase during the 12 months after surgery amounting to 3.1&#xb1;1.1 in the brolucizumab group and 3.8&#xb1;1.4 in the aflibercept group (p=0.22). BCVA improved by 0.10 in the brolucizumab group and by 0.05 in the aflibercept group. CRT decreased by 46 &#xb5;m and 29 &#xb5;m, respectively. Patients treated with brolucizumab demonstrated more pronounced positive structural dynamics, including a reduction in the frequency of subretinal and intraretinal fluid occurrence. No postoperative adverse events were recorded.<br><br>CONCLUSION: Phacoemulsification does not negatively affect the course of nAMD and does not require increased frequency of anti-VEGF therapy. The data confirm the safety of continuing treatment after cataract surgery. Brolucizumab demonstrated more pronounced functional and morphological improvements compared with aflibercept.}, }
@article {pmid42048983, year = {2026}, author = {Trinquet, L and Matonti, F and Chavane, F and Lorenceau, J and David, T}, title = {[Functional assessment of maculopathies and diabetic retinopathy by chromatic multifocal pupillometry].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {6}, pages = {104878}, doi = {10.1016/j.jfo.2026.104878}, pmid = {42048983}, issn = {1773-0597}, abstract = {PURPOSE: To evaluate the performance of an innovative, noninvasive, rapid chromatic multifocal dynamic pupillometry protocol (mPFTCo) in detecting functional retinal changes in three chronic diseases: age-related maculopathy (ARM), age-related macular degeneration (AMD), and diabetic retinopathy (DR).<br><br>METHODS: A cohort of 222 participants (68 controls, 18 ARM, 79 AMD, 57 DR) was tested with mPFTCo. This one-minute test per eye used a multifocal stimulus covering 40&#xb0; of the visual field, divided into nine regions, each periodically modulated in luminance, with chromatic alternation (blue, red, green, gray) every 15s. Regional and spectral pupillary responses were analyzed to characterize functional deficits. Group comparisons were performed using Student's t-tests and ROC curve analyses.<br><br>RESULTS: Compared with controls, significant regional alterations were observed in all three diseases. In AMD, pupillary responses were reduced in central and paracentral regions, particularly under red stimulation (P<0.001). In ARM, a moderate paracentral deficit was observed with blue and green stimulation (P<0.005). In DR, a diffuse deficit affected the entire visual field across all colors (P<0.001). This brief, objective, well-tolerated test showed excellent diagnostic performance (AUC=1).<br><br>CONCLUSION: mPFTCo enables rapid, noninvasive topographic assessment of retinal function. It effectively discriminates between pathological profiles and identifies subclinical alterations not detected by conventional visual tests, representing a promising tool for screening, monitoring, and functional evaluation of treatments in routine clinical practice.}, }
@article {pmid42049512, year = {2026}, author = {Wienbar, SR and Bryman, GS and Do, MTH}, title = {HIGH-FIDELITY backpropagation through primate foveal cones.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.0085-26.2026}, pmid = {42049512}, issn = {1529-2401}, abstract = {Primate vision has exceptionally high spatial acuity and contrast sensitivity. This performance originates in specialized photoreceptors of the fovea. These cones transduce light into electrical signals in the outer segment, and convey these signals to the presynaptic terminal for transmission. Backpropagating signals are also possible, as the terminal receives inputs. Such signals could influence phototransduction itself. To test this idea, we recorded electrophysiologically from both ends of single cones dissociated from the macaque fovea (either sex). We found that backpropagation was effective despite the extreme slenderness and length of these cells. Backpropagation was also effective in a passive compartmental model, indicating that amplification by voltage-gated channels is not required. We then modeled foveal cones receiving terminal inputs from retinal networks. Despite faithful backpropagation of these inputs, they appear unlikely to influence phototransduction. Thus, even though foveal cones exhibit effective backpropagation, their encoding of visual information may remain compartmentalized.Significance Statement Humans, like other primates, see a fineness of detail that eludes other mammals. This capability is used for tasks like reading and recognizing faces. It is lost in leading forms of vision impairment, such as age-related macular degeneration. Investigating it therefore provides insight into the origin of exceptional sensory performance while strengthening the foundation for preserving and restoring sight. This study examines cells that initiate high-acuity vision, the foveal cones, which produce electrical signals from light and send them forward. It reveals that electrical signals also travel effectively in reverse, from the site of transmission to that of production, and how the production of light responses may be independent nonetheless.}, }
@article {pmid42038919, year = {2025}, author = {Bokhary, KA}, title = {Narrative Review of Artificial Intelligence in Ophthalmic Disease Detection : Artificial Intelligence in Ophthalmic Diseases Detection.}, journal = {Galen medical journal}, volume = {14}, number = {}, pages = {e3979}, pmid = {42038919}, issn = {2322-2379}, abstract = {BACKGROUND: Artificial intelligence (AI) is revolutionizing ophthalmology and optometry by utilizing high-resolution imaging modalities such as optical coherence tomography (OCT), fundus photography, and corneal topography. These modalities generate quantifiable data suitable for machine learning (ML), facilitating automated diagnosis of ocular conditions like diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD), which are leading causes of visual impairment worldwide. This narrative review evaluates the role of ML in improving diagnostic accuracy and accessibility in eye care, focusing on methodological complexities, supervised and unsupervised learning approaches, and challenges in clinical integration.<br><br>MATERIALS AND METHODS: A comprehensive narrative literature review was conducted, analyzing ML applications in ophthalmology.<br><br>RESULTS: AI systems exhibit high sensitivity and specificity, often outperforming human graders in diabetic retinopathy screening and early detection of glaucoma and AMD using OCT and fundus imaging. Anterior segment diseases benefit from AI-driven corneal topography analysis. Challenges include image quality, dataset imbalances, and variability in imaging protocols, necessitating fine-tuning for diverse clinical environments. Unsupervised learning shows potential for identifying novel biomarkers but requires further validation.<br><br>CONCLUSION: AI-driven ML models significantly enhance eye disease diagnostics, improving accuracy and accessibility, particularly in resource-limited settings. However, challenges like data standardization and model generalizability must be addressed to ensure robust clinical adoption.}, }
@article {pmid42038949, year = {2026}, author = {Almusib, RBA and Awad, AH and Ghandorah, AM and AnbarSerry, AOM and Aljumah, HK and Albarrak, AI and Alghanmi, RM and Alshami, FME and Alhejaili, BFR and Alboqami, AFF and Mohayya, EMH and Almatrafi, AM and Alzuwayr, MA}, title = {Relationship of Atropine in Controlling Myopia Progression Among Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {590501}, pmid = {42038949}, issn = {1177-5467}, abstract = {PURPOSE: Myopia is a refractive error where light focuses in front of the retina, causing blurred distance vision. It is linked to complications such as macular degeneration, retinal detachment, glaucoma, and cataracts, potentially resulting in irreversible vision loss. Controlling myopia progression is critical to reduce long-term impairment. This systematic review evaluate and compare different atropine concentrations for slowing myopia progression in pediatric patients.<br><br>PATIENTS AND METHODS: A comprehensive electronic search was conducted in PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials for studies published between June 1, 2006, and September 1, 2024. Included studies enrolled participants aged <18 years, used a randomized placebo-controlled design, and evaluated atropine effects on myopia progression in individuals with spherical equivalent &#x2264; 0.25 D. Primary outcomes, spherical equivalent refractive error (SER) and axial length (AL), were analyzed via meta-analysis using mean differences (MDs) with 95% confidence intervals (CIs).<br><br>RESULTS: This meta-analysis included 10 studies (2006-2024) evaluating atropine effects on myopia progression. Atropine significantly slowed progression versus placebo. At 6 and 12 months, MD in SER was 0.26 (95% CI, 0.17-0.34) and 0.54 (95% CI, 0.26-0.82), respectively, (p < 0.001). Atropine also significantly reduced AL growth at 6 months (MD -0.09, 95% CI, -0.14 to -0.04).<br><br>CONCLUSION: Atropine effectively reduced AL growth and myopia progression. Heterogeneity across studies suggests variability. Further research is essential to clarify its mechanism.}, }
@article {pmid42039586, year = {2026}, author = {Ghosh, S and Koontz, V and Xin, Y and Bammidi, S and Meyer, D and Wang, H and Babu, VS and Dutta, P and Cherukaraveedu, D and Mohanakrishnan, SA and Mondal, AK and Das, J and Nguyen, J and Soundararajan, A and Adekale, IA and Bhaumik, D and Hose, S and Rowan, S and Pattabiraman, PP and Kannan, RM and Handa, JT and Yi, J and Sripathi, SR and Qian, J and Sinha, D}, title = {Gut-derived metabolic reprogramming drives immune aging and tissue degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.14.718497}, pmid = {42039586}, issn = {2692-8205}, abstract = {Aging is characterized by changes in gut microbiome, metabolic imbalance and chronic inflammation, yet how these processes integrate to drive tissue degeneration remains poorly defined. Using age-related macular degeneration (AMD) as a model of tissue aging, we identify a diet-induced metabolic-immune axis that promotes systemic and retinal degeneration. In mice, a high-fat, cholesterol-enriched (HFC) diet induced perturbations in the gut structural integrity and microbiome repertoire, as well as systemic metabolic aging signatures, prominently marked by reduced circulating histidine. Plasma histidine levels were similarly decreased in AMD patients and inversely correlated with body mass index (BMI) in control donors. These diet-induced gut microbiome changes and subsequent metabolic alterations promoted peripheral innate immune reprogramming, with expansion of inflammatory neutrophils and monocytes that infiltrated the outer retina in a mouse model. Mechanistically, the gut-derived IGF1R/AKT2 signaling acts as a central regulator of global epigenetic remodeling and systemic immune aging under high-fat conditions in C. elegans . In a mouse model with an age-dependent dry AMD-like pathology, distinct retinal pigment epithelium (RPE) subpopulations exhibited downregulation of the histidine transporter SLC7A5, linking metabolic stress to activation of MIF/CD74-dependent inflammatory signaling between RPE and infiltrating immune cells. Histidine supplementation or AKT2 phospho-state modulation attenuated systemic immune activation and rescued retinal degeneration. These findings identify histidine-axis dysregulation as a mechanistic bridge between diet-induced microbiome changes, metabolic stress, immune aging, and retinal degeneration.}, }
@article {pmid42040622, year = {2026}, author = {Zhang, X and Cui, B and Liu, Y and Ji, X and Tian, X and Hou, S and Yang, L and Yang, J}, title = {Psychosocial determinants of anti-VEGF treatment adherence in AMD patients: optimization of one-stop intravitreal injection service model.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1745453}, pmid = {42040622}, issn = {2296-858X}, abstract = {OBJECTIVE: To investigate modifiable psychosocial determinants of anti-VEGF treatment adherence in patients with neovascular age-related macular degeneration (nAMD) and evaluate the optimization effects of a one-stop intravitreal injection service model.<br><br>METHODS: This historical control mixed-methods study included patients receiving anti-VEGF treatment at Cangzhou Regional Ophthalmology Center from August 2022 to October 2024. Patients were divided into three groups based on service models: traditional multiple-visit group (historical control, n = 165), one-stop standard group (n = 161), and one-stop AI-enhanced group (n = 162). The Hospital Anxiety and Depression Scale (HADS) was used to assess psychological status, and geographic information systems analyzed spatial accessibility impacts. Primary outcome measures included 12-month retention rate, early discontinuation rate (within 6 months), and appointment adherence rate. In-depth semi-structured interviews were conducted with patients from the one-stop standard and AI-enhanced groups, using thematic analysis to identify key influencing factors. Logistic regression analysis was used to analyze adherence predictors.<br><br>RESULTS: Compared to the historical control group, the one-stop standard and AI-enhanced groups showed significantly reduced clinic-to-injection time (23.87 vs. 6.47 vs. 6.01 h, P < 0.05), significantly improved 12-month retention rates (52.12 vs. 73.29 vs. 85.80%, P < 0.05), and significantly reduced early discontinuation rates (29.09 vs. 17.39 vs. 9.88%, P < 0.05). Regarding clinical outcomes, patients in the AI-enhanced group showed more significant best-corrected visual acuity (BCVA) improvement (logMAR change: -0.08 vs. -0.12 vs. -0.17, P < 0.05) and more pronounced central retinal thickness reduction (57.83 vs. 86.92 vs. 111.75 &#x3bc;m, P < 0.05). Multifactorial analysis showed that residential distance >38 km, baseline high anxiety levels, and baseline depressive symptoms were independent risk factors for treatment discontinuation. AI-enhanced intervention significantly reduced early discontinuation risk (P < 0.05). Qualitative analysis identified five main themes: treatment anxiety, service experience, expectation management, social support, and service improvement needs. Safety event incidence rates showed no significant differences between groups (P > 0.05).<br><br>CONCLUSION: The one-stop intravitreal injection service model significantly improved treatment adherence in nAMD patients, with AI-enhanced intervention further optimizing outcomes. Baseline anxiety and depression levels, along with geographic distance, are important modifiable determinants of treatment adherence. Personalized service models integrating psychosocial interventions provide new insights for precision management of chronic eye diseases.}, }
@article {pmid42040936, year = {2026}, author = {Azargui, S and Lisker-Cervantes, A and Patnaik, JL and Gnanaraj, R and Mehta, N and Gange, B and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Mandava, N and Forest, TEC}, title = {Imaging Biomarkers To Predict Progression of Intermediate AMD with Avascular Pigment Epithelial Detachment in the University of Colorado AMD Registry.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-9193520/v1}, pmid = {42040936}, issn = {2693-5015}, abstract = {Purpose: To investigate whether specific imaging biomarkers predict progression to neovascular AMD (nAMD) or geographic atrophy (GA) in eyes with high-risk intermediate age-related macular degeneration (iAMD) and avascular pigment epithelial detachment (PED). Methods: Prospective longitudinal cohort study of eyes with iAMD and avascular PED from the University of Colorado AMD registry (August 2014 - August 2023) with ≥1 month of follow-up through February 2024. Multimodal imaging, including color fundus photos (CFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT), was graded by two reviewers for presence of specific imaging biomarkers. Time-to-progression survival analysis was conducted with hazard ratios calculated. Results: Over a median follow-up period of 35 months, 224 eyes (142 patients) were included. 31 (13.8%) eyes progressed to nAMD, and 63 (28.1%) to GA. Progression to nAMD was significantly predicted by pigmentary changes on CFP (HR=4.43 (95%CI: 1.77, 11.1), p=0.001) and intraretinal hyperreflective foci (iHRF) on OCT (HR=4.90 (95%CI: 2.02, 11.9), p=0.0005). Progression to GA was significantly predicted by pigmentary changes on CFP (HR=3.60 (95%CI: 1.94, 6.67), p<0.0001), iHRF (HR=4.13 (95%CI: 2.14, 7.94), p<0.0001), acquired vitelliform lesions (AVL; (HR=2.97 (95%CI: 1.55, 5.68), p=0.001)) and incomplete retinal pigment epithelium and outer retina atrophy (iRORA; (HR=4.18 (95%CI: 1.52, 11.4), p=0.006)). No other biomarkers demonstrated significance. Conclusion: In eyes with avascular PED, pigmentary changes and iHRF were significantly associated with progression to nAMD and GA, while AVL and iRORA were specifically to GA. We highlight in this study important imaging biomarkers that help identify high-risk eyes that may warrant closer monitoring to ensure timely therapeutic intervention.}, }
@article {pmid42041185, year = {2026}, author = {Ju, H and Jin, L and Qin, X and Tian, Y and Peng, H and Wang, X}, title = {Associations of Frailty Index and Composite Dietary Antioxidant Index With Major Ocular Diseases and Analysis of Component Contributions: A Cross-Sectional Study.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {4}, pages = {25}, doi = {10.1167/tvst.15.4.25}, pmid = {42041185}, issn = {2164-2591}, mesh = {Humans ; Cross-Sectional Studies ; Male ; *Antioxidants/metabolism ; Middle Aged ; Female ; *Frailty/epidemiology ; *Eye Diseases/epidemiology ; Aged ; Nutrition Surveys ; *Diet ; Adult ; United States/epidemiology ; }, abstract = {PURPOSE: To evaluate the independent and joint effects of the frailty index (FI) and composite dietary antioxidant index (CDAI) with major ocular diseases and quantify contributions of their components.<br><br>METHODS: We analyzed 4455 U.S. adults aged &#x2265;40 years from NHANES 2005-2008. Frailty was defined using a 49-item deficit accumulation FI (FI > 0.21 considered frail), and CDAI was derived from six antioxidants (carotenoids, vitamins A, C, E, selenium, zinc). Weighted multivariable logistic regression, variable importance, restricted cubic spline analyses, and sensitivity analyses assessed associations with retinopathy, cataract, diabetic retinopathy (DR), glaucoma, and age-related macular degeneration.<br><br>RESULTS: Higher FI was associated with higher odds of all major ocular diseases (any ocular disease: odds ratio [OR] = 1.35; DR: OR = 2.21; glaucoma: OR = 1.34), whereas higher CDAI was associated with lower odds (any ocular disease: OR = 0.97; glaucoma: OR = 0.91). Participants with high FI and low CDAI had the highest odds, based on predefined cutoff categories (any ocular disease: OR = 2.22; DR: OR = 4.92; cataract: OR = 2.50; glaucoma: OR = 3.18; all P < 0.05). Exploratory analyses showed that CDAI contributions varied by disease, whereas chronic disease burden dominated among FI domains.<br><br>CONCLUSIONS: Higher FI and lower CDAI were independently and in combination associated with major ocular diseases, highlighting the relevance of considering frailty status and dietary antioxidant profiles together in ocular health.<br><br>TRANSLATIONAL RELEVANCE: Higher FI and lower CDAI show combined associations with major ocular diseases, emphasizing their relevance to vision-related health.}, }
@article {pmid42041592, year = {2026}, author = {Yang, Y and Liu, P and Li, J and Deng, Y and Xiao, L and Peng, Q and Peng, J}, title = {Retinal Pigment Epithelium Ageing: Cellular and Molecular Mechanisms of Long-Term Homeostasis and Age-Related Dysfunction.}, journal = {Cells}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/cells15080725}, pmid = {42041592}, issn = {2073-4409}, support = {82274341, 82405487//National Natural Science Foundation of China/ ; 2024JJ5304, 2025JJ60633//Natural Science Foundation of Hunan Province/ ; 2024JK2122//Key Research and Development Program of Hunan Province/ ; 23A0278, 23B0346//Scientific research project of Hunan Provincial Department of Education/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *Homeostasis ; *Aging/pathology/metabolism ; Animals ; Macular Degeneration/pathology/metabolism ; Mitochondria/metabolism ; *Cellular Senescence ; }, abstract = {The retinal pigment epithelium (RPE) is a long-lived, highly polarised epithelial monolayer that performs essential functions in retinal homeostasis, including outer blood-retina barrier maintenance, visual cycle activity, metabolic exchange, phagocytic clearance of photoreceptor outer segments, and regulation of oxidative and immune balance. Because RPE cells persist for decades under conditions of sustained oxidative, metabolic, and phagocytic stress, this tissue provides a valuable model for examining how long-lived post-mitotic cells preserve function over time and how age-related dysfunction emerges when that balance weakens. Although much of the current literature on RPE ageing has been shaped by age-related macular degeneration (AMD), age-dependent change in the RPE should not be understood solely as a preclinical stage of disease. Rather, the ageing RPE offers a broader framework for studying cellular maintenance under chronic physiological load. In this review, we synthesise current evidence on RPE ageing across four interrelated domains: structural remodelling, mitochondrial and metabolic imbalance, proteostatic and lysosomal burden, and chronic inflammatory dysregulation. Across these processes, ageing in the RPE is expressed less as widespread cell loss than as progressive decline in cellular organisation, buffering capacity, and functional precision. Structural irregularity, altered mitochondrial regulation, incomplete degradative clearance, and persistent low-grade inflammatory signalling together reduce the ability of the RPE to maintain long-term homeostasis and increase vulnerability to age-related retinal dysfunction. We further argue that ageing in the RPE is best understood not as abrupt failure of isolated pathways, but as gradual loss of system coherence among interacting homeostatic systems that remain active while operating under increasing constraint. This view helps integrate diverse cellular and molecular findings and highlights the RPE as an informative model for understanding ageing in long-lived post-mitotic tissues.}, }
@article {pmid41840594, year = {2026}, author = {Liu, Y and Zhao, J and Huang, J and Qin, Y and Huang, Y and Fan, H and Zhou, W and Han, H and You, C and Cui, Z and Belfort Junior, R and Fernandes, RAB and Yan, H}, title = {Real-world cost evaluation of conbercept vs. ranibizumab for retinal and choroidal vascular diseases from 2021 to 2024: evidence from societal and medical insurance perspectives.}, journal = {BMC public health}, volume = {26}, number = {1}, pages = {}, pmid = {41840594}, issn = {1471-2458}, support = {22ZYYYQ05//Tianjin Medical University General Hospital Excellent Youth Science Fund/ ; 23JCQNJC01180//Tianjin Natural Science Foundation Youth Project/ ; 23JCZXJC00140//Beijing-Tianjin-Hebei Special Project/ ; 82530032&#xff0c;82330031//National Natural Science Foundation of China/ ; 25JCZDJC00390//Natural Science Foundation of Tianjin/ ; NO. TJYXZDXK-3-004A//The Tianjin Key Medical Discipline Construction Project/ ; }, abstract = {BACKGROUND: Retinal and choroidal vascular diseases including age-related macular degeneration (AMD), branch and central retinal vein occlusion (BRVO, CRVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) are important causes of blindness. Their treatments by anti-VEGF agents imply heavy economic impact.<br><br>METHODS: The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies and medical costs of 15,266 patients in Tianjin (2021&#x2013;2024), utility values, and transition probabilities derived from clinical trials. Costs and outcomes were calculated separately under societal and medical insurance perspectives. Incremental cost-effectiveness ratios (ICERs) were computed, and sensitivity analyses (one-way, two-way and probabilistic) were conducted to assess result robustness.<br><br>RESULTS: From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with ICERs as -442,423.176, -2,429,628.701, -69,339.384, -410,661.276 as Chinese Yuan/quality-adjusted life year (RMB/QALY) under the societal perspective, and&#x2009;-370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept&#x2019;s ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. Sensitivity analyses confirmed the robustness of these findings.<br><br>CONCLUSION: Conbercept is a cost-effective alternative to ranibizumab in RVO, DME, and PM from societal and medical insurance perspectives. In AMD, ranibizumab remains more clinically effective option. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-026-26994-1.}, }
@article {pmid42033410, year = {2026}, author = {Gu, X and Terebuh, P and Xu, R and Kaelber, DC and Davis, PB}, title = {Age-related macular degeneration and dementia: Association through pathogenesis or visual impairment?.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877261438849}, doi = {10.1177/13872877261438849}, pmid = {42033410}, issn = {1875-8908}, abstract = {BackgroundStudies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship between AMD and dementia.ObjectiveTo evaluate the association between AMD and 5-year dementia risk in non-blind patients.MethodsThis retrospective cohort study used TriNetX to compare non-blind patients with exudative AMD (n = 35,021) and non-exudative AMD (n = 96,809) to those without AMD (n = 1,801,879) for five-year dementia risk. Blind (n = 90,615) and non-blind (n = 800,737) patients were compared. Cohorts were propensity-matched for confounding factors.ResultsNon-blind AMD patients had decreased Alzheimer's disease risk, while blindness showed a strong positive association. Exudative AMD had HR of 0.84 (95% CI = [0.72, 0.97]), non-exudative AMD had HR of 0.95 (95% CI = [0.87, 1.04]), but blindness increased Alzheimer's disease risk (95% HR = 1.29, CI = [1.17, 1.41]).ConclusionsThese findings suggest that previously reported associations between AMD and dementia may be partially mediated by visual impairment. The modest reduction in dementia risk in non-blind AMD patients may reflect differences in healthcare utilization or treatment exposure among AMD patients.}, }
@article {pmid42033485, year = {2026}, author = {Desmettre, T and Ledesma-Gil, G and Paques, M}, title = {Bidirectional Retro mode differential imaging improves drusen boundary depiction in early and intermediate AMD: a pilot study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42033485}, issn = {1435-702X}, }
@article {pmid42033607, year = {2026}, author = {Zhang, R and Tunon-Robinson, I and Nguyen, AK}, title = {Visual Outcomes Following Infectious Endophthalmitis from Intravitreal Injections of Biologic Drugs: An Intelligent Research in Sight Registry Retrospective Analysis.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42033607}, issn = {2193-8245}, abstract = {INTRODUCTION: Intravitreal (IVT) injections are now among the most frequently performed intraocular procedures globally. Evidence regarding post-IVT-injection infectious endophthalmitis is primarily derived from a limited number of randomized controlled trials and retrospective case series. This study assesses visual acuity outcomes after IVT biologic therapy utilizing data from a large-scale ophthalmic registry, with the objective of elucidating the real-world effects of post-IVT-injection infectious endophthalmitis on patient visual function.<br><br>METHODS: Data were obtained from the Intelligent Research in Sight[&#xae;] (IRIS[&#xae;]) Registry, focusing on subjects who received commercially available IVT anti-VEGF and anti-complement biologic drugs.<br><br>RESULTS: As of 31 December 2024, 1,998,399 individuals received at least one IVT injection in one or both eyes, and 13,074 subjects (affecting 13,317 eyes) were diagnosed with infectious endophthalmitis. Incidence of infectious endophthalmitis per IVT injection was 0.052%. The cumulative rate of infectious endophthalmitis per subject rose from 0.31% after 10 IVT injections to 0.58% after 60 injections. The proportion of subjects who were legally blind (defined as&#x2009;&#x2264;&#x2009;35 letters or&#x2009;&#x2264;&#x2009;20/200) increased from 19.4% before the infectious endophthalmitis event to 46.1% afterward. In total, 94 eyes affected by infectious endophthalmitis underwent evisceration or enucleation. Subjects with retinal vein occlusion and myopic choroidal neovascularization had the highest incidence rates of infectious endophthalmitis compared with those with neovascular (wet) age-related macular degeneration and diabetic macular edema/diabetic retinopathy.<br><br>CONCLUSIONS: In the real world, the cumulative incidence of infectious endophthalmitis per subject is positively correlated with the total number of IVT injections administered. While the incidence of post-IVT-injection infectious endophthalmitis was comparable to literature values reported after cataract surgery, visual acuity outcomes were worse in the post-IVT injection group. Implementing strategies aimed at reducing IVT injection frequency may have the potential to lower the incidence of infectious endophthalmitis and the consequent risk of significant vision loss.}, }
@article {pmid42033608, year = {2026}, author = {Haase, M and Wittenborn, E}, title = {Rapid Effects on Anatomical and Functional Outcomes following Upload with Faricimab in Treatment-Naïve nAMD: German Single-Center Study 45DRY.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {42033608}, issn = {2193-8245}, abstract = {INTRODUCTION: The bispecific antibody faricimab inhibits vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2), two key mediators in the pathophysiology of neovascular age-related macular degeneration (nAMD), which is characterized by choroidal neovascularization, vascular instability, leakage, and intra/subretinal fluid with consequent vision loss. The aim of our study was to assess the effectiveness of faricimab at week 16 versus baseline in patients with treatment-naïve nAMD managed under real-world conditions in Germany.<br><br>METHODS: 45DRY was a retrospective, single-center analysis of consecutive patients with treatment-na&#xef;ve nAMD initiating faricimab (four monthly injections at weeks 0, 4, 8, and 12). Outcomes were evaluated at baseline and week 16 (&#xb1;&#x2009;14&#xa0;days). The&#xa0;primary endpoint was change from baseline in central retinal thickness (CRT); secondary endpoints were change in best-corrected visual acuity (BCVA) and presence/absence of intraretinal fluid (IRF), subretinal fluid (SRF), combined IRF&#x2009;+&#x2009;SRF, and subretinal pigment epithelium (sub-RPE) fluid. Analyses were descriptive.<br><br>RESULTS: A total of 45 eyes from 45 patients were included (mean age 82.1&#xa0;years; 51.1% female). Mean CRT decreased by&#x2009;-140.8&#xa0;&#x3bc;m from 343.1&#xa0;&#xb5;m at baseline to 202.4&#xa0;&#xb5;m at week 16 [95% confidence interval (CI)&#x2009;-178.2 to&#x2009;-103.3]. Mean BCVA improved by -0.15 logMAR at week 16. Among eyes with retinal fluid at baseline, IRF resolved in 100% (24/24), SRF in 94.1% (32/34), combined IRF&#x2009;+&#x2009;SRF in 100% (17/17), and sub-RPE fluid in 90% (9/10). Maintenance of fluid-free status was universal in eyes negative at baseline for IRF (21/21), SRF (11/11), and combined IRF&#x2009;+&#x2009;SRF (28/28); sub-RPE fluid remained absent in 100% (35/35).<br><br>CONCLUSIONS: In routine clinical practice, a four-dose faricimab upload per label at the time of study conduct led to a rapid and substantial anatomical drying effect at week 16 with improvement in BCVA and marked CRT reduction. These real-world findings confirm that faricimab rapidly and effectively reduces retinal fluid, in line with post hoc analyses of the pivotal TENAYA and LUCERNE trials.}, }
@article {pmid42036126, year = {2026}, author = {Turnbull, PRK and Acosta, ML and Lee, A and Solanki, B}, title = {Optometrist attitudes towards delivering intravitreal injections in Aotearoa New Zealand.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/08164622.2026.2652580}, pmid = {42036126}, issn = {1444-0938}, }
@article {pmid42027463, year = {2026}, author = {Drago, L and De La Motte, LR}, title = {The eye's coral reef: toward a planetary-health agenda for ocular-microbiome stewardship.}, journal = {Frontiers in microbiology}, volume = {17}, number = {}, pages = {1816460}, pmid = {42027463}, issn = {1664-302X}, abstract = {Coral reefs and the human ocular surface represent ecologically distinct yet structurally comparable microbial ecosystems in which resilience depends on finely regulated host-microbe interactions. In coral reef science, microbial shifts precede visible bleaching and ecosystem collapse, enabling the development of predictive stress indices such as Degree Heating Weeks (DHW). Comparable principles are emerging in host-associated, low-biomass microbiomes, where subtle perturbations may trigger disproportionate functional consequences. Here, we propose a systems-level conceptual framework linking coral reef holobionts and the ocular surface as sentinel ecosystems governed by cumulative stress, threshold dynamics, and microbial instability. We introduce two heuristic constructs-the Cumulative Desiccating Load (CDL) and the Ocular Dysbiosis Sentinel Index (ODSI)-to frame dysbiosis as a trajectory of resilience loss driven by cumulative perturbations. Aging-related conditions such as age-related macular degeneration are discussed as examples of microbial and metabolic senescence within the human holobiont, conceptually paralleling coral reef decline under chronic sublethal stress. By integrating environmental and host-associated microbiome research within a planetary-health perspective, this article advances a resilience-oriented systems framework applicable across biological scales.}, }
@article {pmid42027954, year = {2026}, author = {Li, J and Yan, Z and Mao, D and Liu, X and Lee, P and Lyu, Y and Feng, N}, title = {Microneedle technology in the treatment of ocular diseases: Advances and applications.}, journal = {Asian journal of pharmaceutical sciences}, volume = {21}, number = {2}, pages = {101129}, pmid = {42027954}, issn = {2221-285X}, abstract = {Microneedle (MN) technology has emerged as a transformative approach for treating ocular diseases, addressing the limitations of conventional drug delivery methods such as low bioavailability and poor patient compliance. This review highlights the advancements and applications of MNs in managing both anterior and posterior segment ocular diseases. MNs overcome physiological barriers, enabling precise, minimally invasive drug delivery with enhanced efficacy. Various MN designs, such as solid, coated, soluble, hollow, hydrogel and cryo-MNs, are tailored for specific therapeutic needs, offering rapid or sustained drug release. Applications include treating keratitis, glaucoma, age-related macular degeneration and diabetic retinopathy, demonstrating improved drug penetration and reduced side effects. Despite challenges in manufacturing and clinical translation, MN technology holds promise for revolutionizing ocular therapeutics through innovations in materials, design, and personalized medicine.}, }
@article {pmid42028099, year = {2026}, author = {Shah, SH and Zhu, Y and Bennett, C and Tracy, J and Ploumi, I and Barton, KM and Gumustop, S and Nodecker, K and Wagner, S and Chen, C and Ding, X and Stevanovic, M and Lains, I and Miller, JB}, title = {Standardized Ultra-Widefield Swept-Source OCT Imaging: A Reproducible Protocol for Peripheral Retinal Assessment.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {581561}, pmid = {42028099}, issn = {1177-5467}, abstract = {BACKGROUND: The utilization of ultra-widefield (UWF) photography and, more recently, UWF-OCT has increased greatly in retina clinic. The most widely available UWF-OCT uses navigated swept-source OCT (SS-OCT), which lacks a standardized protocol, consequently limiting comparisons across patient visits or larger population-based studies. We present a structured imaging protocol to address this limitation.<br><br>TECHNIQUE: A universal template standardizes the number, type, and anatomical positioning of seven scans per patient, including three 21 mm line scans and four UWF volume scans. Scans are automatically positioned per protocol and ultimately stitched into a composite image, which is optimized for longitudinal and inter-patient comparisons.<br><br>DISCUSSION: This protocol enhances efficiency and ensures reproducible assessment of peripheral retinal findings. It may be adapted for other UWF systems and is currently being evaluated for clinical applications.}, }
@article {pmid42028334, year = {2026}, author = {Wang, WX and Wang, CC and Hsu, WC and Peng, YJ}, title = {From Supplements to Sight: Quantifying the Impact of Lutein and Carotenoid on Age-Related Macular Degeneration-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {2155378}, pmid = {42028334}, issn = {2090-004X}, abstract = {PURPOSE: To quantify the effects of lutein-containing supplementation on structural and functional visual outcomes in patients with age-related macular degeneration (AMD), with particular focus on disease stage and treatment exposure.<br><br>METHODS: A meta-analysis of randomized, placebo-controlled trials was conducted. Nine RCTs involving 860 participants were included. Eligible studies evaluated oral lutein alone or in combination with zeaxanthin or epilutein and reported pre- and post-treatment measurements of macular pigment optical density (MPOD) and best-corrected visual acuity (BCVA). Random-effects models were applied to calculate pooled effect sizes using Hedges' g. Subgroup and meta-regression analyses were performed to explore stage-specific responses and dose-duration associations.<br><br>RESULTS: Across the 9 RCTs, lutein-containing supplementation significantly improved MPOD (Hedges' g&#x2009;=&#x2009;-0.589, p < 0.001) and BCVA (Hedges' g&#x2009;=&#x2009;-0.827, p = 0.001). Improvements were predominantly observed in early-stage AMD, whereas no statistically significant benefit was detected in late-stage disease. Lutein monotherapy demonstrated greater visual benefit than combination regimens. Meta-regression analyses revealed significant positive associations between treatment effect and both supplementation duration and total lutein exposure. Contrast sensitivity and serum lutein concentrations also improved significantly.<br><br>CONCLUSION: Lutein-based supplementation is associated with measurable structural and functional visual benefits in early-stage AMD. Treatment effects appear dose- and duration-dependent, while evidence in late-stage AMD remains limited. These findings support early intervention strategies and warrant further investigation into long-term therapeutic impact.}, }
@article {pmid42029948, year = {2026}, author = {Labishetty, SC and Kumar, N and Kumari, S}, title = {Comment on "Conjunctival microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion".}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261445275}, doi = {10.1177/11206721261445275}, pmid = {42029948}, issn = {1724-6016}, }
@article {pmid42030193, year = {2026}, author = {Molins, B and Nabaes Jodar, MS and de Oliveira, E and Estanyol, JM and Peña, E and Bezunartea, J and Hernández, M and Figueras-Roca, M and Adan, A}, title = {Decellularized Aged Bruch's Membrane Confers Unique Biochemical Cues to Retinal Pigment Epithelium for In Vitro Modeling of Age-Related Macular Degeneration.}, journal = {Aging cell}, volume = {25}, number = {5}, pages = {e70501}, doi = {10.1111/acel.70501}, pmid = {42030193}, issn = {1474-9726}, support = {PI22/00782//Instituto de Salud Carlos III/ ; //Novartis Farmac&#xe9;utica/ ; }, mesh = {Humans ; *Bruch Membrane/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/pathology/metabolism ; Aged ; *Models, Biological ; Male ; Female ; Proteomics ; }, abstract = {Age-related macular degeneration (AMD), a chronic inflammatory disease, is a major cause of irreversible blindness worldwide. It involves the degeneration of the retinal pigment epithelium (RPE) and the accumulation of deposits between the RPE and the Bruch's membrane (BrM), ultimately leading to photoreceptor death. The multifactorial and chronic nature of AMD makes it challenging to model in vitro. We developed a biomaterial based on decellularized BrM (dECM-BrM) from aged donors to evaluate its ability to induce an AMD-like phenotype in RPE monolayers. BrM from 5 young and 5 aged human donors was decellularized and the protein profile analyzed by LC-MS/MS. dECM-BrM was then used as a coating substrate for RPE culture. A total of 281 proteins were identified and proteomic analysis screened 49 differentially expressed proteins in aged dECM-BrM. Gene Ontology analysis showed that they were associated with extracellular region, antioxidant activity, lipid metabolism and transport. Moreover, the KEGG pathway related to complement and coagulation cascade was significantly enriched. RPE culture on aged dECM-BrM allowed RPE polarization and after 60 days, transepithelial electrical resistance significantly decreased compared to RPE grown on young dECM-BrM, accompanied by increased IL-33 secretion and marked expression of drusen components such as vitronectin and apolipoprotein E, lipid deposition and complement factors C3 and C9. We showed a successful approach to obtain a BrM mimic based on decellularized BrM that ensured cellular removal while preserving ECM structure and identified differentially expressed proteins in aged dECM-BrM that may provide specific biochemical cues fundamental to model AMD in vitro.}, }
@article {pmid42030962, year = {2026}, author = {Beiner, D and Zhu, H and Bosholm, CC and Wang, HC and Criswell, T and Atala, A and Ma, JX and Zhang, Y}, title = {Derivation and characterization of retinal pigment epithelium from urine-derived iPSCs.}, journal = {FEBS open bio}, volume = {}, number = {}, pages = {}, doi = {10.1002/2211-5463.70246}, pmid = {42030962}, issn = {2211-5463}, support = {NIH/HIAID R21 AI152832//National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH)/ ; NIH/NEI R21 EY0358332024//National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH)/ ; R03 AI165170/AI/NIAID NIH HHS/United States ; 2024 Pilot Research Grant//Eye Bank Association of America (EBAA)/ ; HT94252510856//Department of Defense/ ; 2025 Ignition Fund Pilot Award//Wake Forest School of Medicine (WFSM)/ ; 2025 Translational Team Science Pilot Award//Translational Eye and Vision Research Center (TrEVR), Wake Forest School of Medicine (WFSM)/ ; }, abstract = {Age-related macular degeneration (AMD), particularly its dry form, is a leading cause of irreversible vision loss due to retinal pigment epithelium (RPE) dysfunction and loss. Addressing this unmet therapeutic need requires non-invasive strategies for generating patient-specific RPE cells. This study reports the successful generation and initial characterization of RPE cells derived from urine-derived induced pluripotent stem cells (u-iPSC-RPE). Urine-derived stem cells (USCs) were isolated from healthy individuals and comprehensively characterized, confirming strong expression of renal progenitor makers and mesenchymal stem cell markers, while lacking standard hematopoietic markers. USCs were reprogrammed into iPSCs using the integration-free Sendai virus expressing the Yamanaka factors. The reprogrammed u-iPSC clones displayed characteristic pluripotency marker expression and demonstrated clearance of the Sendai virus by later passages. Subsequently, these u-iPSCs were efficiently differentiated into RPE cells, exhibiting characteristic hexagonal morphology and pigmentation which was confirmed by the expression of key RPE-specific proteins. Our findings demonstrate the feasibility and reliability of generating patient-specific u-iPSC-RPE cells from readily accessible USCs providing a foundation for future studies to investigate their functional potential for retinal disease modeling and therapeutic applications for AMD.}, }
@article {pmid42031005, year = {2026}, author = {Palakkan, AA and Shankar, G and Vignesh, TP and Kim, R}, title = {A tunable, biofabricated light-delivery platform for in vitro modelling of age-related macular degeneration using iPSC-derived RPE cells.}, journal = {Biomedical materials (Bristol, England)}, volume = {}, number = {}, pages = {}, doi = {10.1088/1748-605X/ae6498}, pmid = {42031005}, issn = {1748-605X}, abstract = {The lack of physiologically relevant and controllable experimental systems has limited mechanistic understanding of age-related macular degeneration (AMD) and the development of effective therapeutic strategies. Here, we present a tunable in vitro retinal pigment epithelium (RPE) stress model that integrates engineered light delivery with lipid modulation to reproduce early AMD-like cellular pathology under standard culture conditions. Human RPE cells (ARPE-19 and iPSC-derived RPE) were exposed to precisely controlled, low-intensity light-induced oxidative stress in the presence of docosahexaenoic acid (DHA), a highly unsaturated retinal lipid, or palmitic acid (PA) as a saturated lipid control. Cellular responses were assessed using functional and structural readouts including lysosomal and mitochondrial activity, membrane integrity, epithelial morphology, tight junction organization, and lipid peroxidation. A programmable LED-based exposure system enabled fine control over light intensity, duration, and cycling, allowing delivery of sub-lethal, chronic oxidative stress. Combined light and DHA exposure selectively induced lipid peroxidation, disruption of ZO-1-defined tight junctions, and progressive loss of RPE viability, while PA-treated cells and non-retinal HuH7 hepatocytes showed minimal sensitivity. ARPE-19 cells responded rapidly, whereas iPSC-derived RPE cells exhibited delayed but comparable pathological changes, reflecting differences in cellular maturity and stress resilience. Pharmacological inhibition of ferroptosis using ferrostatin-1 significantly reduced lipid peroxidation and rescued epithelial integrity and cell viability, identifying ferroptosis as a key mechanism underlying RPE vulnerability in this system. By enabling programmable and reproducible delivery of oxidative lipid stress, this modular light-based platform provides a biofabrication-compatible framework for modeling early AMD, with potential for integration into more complex retinal constructs, co-culture systems, and high-throughput therapeutic screening pipelines.}, }
@article {pmid42031134, year = {2026}, author = {Anegondi, N and Lam, D and Guymer, RH and Steffen, V and Cukras, CA and Ferrara, D and Wu, Z}, title = {Vision-Related Quality of Life in Geographic Atrophy: Association with Topographic Lesion Distribution.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.04.019}, pmid = {42031134}, issn = {1549-4713}, abstract = {PURPOSE: To understand the associations between the topographic lesion distribution and vision-related quality of life (VR-QoL) in individuals with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Analysis of data from Chroma (NCT02247479) and Spectri (NCT02247531), which are two identically designed Phase III clinical trials of lampalizumab.<br><br>PARTICIPANTS: Eight-hundred and fifty-six participants that were &#x2265;50 years old with bilateral GA who completed the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) at baseline.<br><br>METHODS: The NEI VFQ-25 was used to determine estimates of VR-QoL in the visual functioning (NEI VFQ-VF) domain, using calibrated item measures and rating category thresholds from Rasch analysis. GA were automatically segmented on combined fundus autofluorescence and near-infrared reflectance images, and its extent in central regions across varying diameters (from 0.25- to 6.00-mm, in 0.25-mm intervals) relative to the fovea were then derived.<br><br>MAIN OUTCOME MEASURES: Association between NEI VFQ-VF person measures and the minimum eye-level GA extent in the region evaluated within an individual (referred to as the minimum GA extent).<br><br>RESULTS: Minimum GA extent within the central region across varying diameters between 0.25- to 6.00-mm were all significantly associated with the NEI VFQ-VF person measures (P &#x2264; 0.001 for all), but the highest proportion of variance explained was seen when evaluating the central 2.50-mm diameter region (R[2] = 0.11). A multivariable analysis showed that only the minimum GA extent within the central 2.50-mm region (P < 0.001), but not the 2.50- to 6.00-mm annulus (P = 0.541), was independently associated with NEI VFQ-VF person measures.<br><br>CONCLUSIONS: In this cohort, VR-QoL is most strongly associated with minimum eye-level GA extent within the central 2.50-mm region within an individual. These findings underscore the importance of evaluating GA extent in this region, beyond simply considering foveal GA involvement, when seeking to evaluate structural changes most closely associated with self-reported impairments in visual functioning.}, }
@article {pmid42031505, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Pan, Z and Xu, J and Jonas, RA and Wang, YX}, title = {Prevalence and associations of intraretinal hyperreflective foci in age-related macular degeneration: the Beijing Eye Study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328004}, pmid = {42031505}, issn = {1468-2079}, abstract = {BACKGROUND: To assess prevalence and associations of intraretinal hyperreflective foci (HRFs) in a general population.<br><br>METHODS: Participants of the population-based Beijing Eye Study underwent optical coherence tomography and macula photography.<br><br>RESULTS: The study cohort included 1641 eyes (mean age: 62.8&#xb1;9.1 years; range: 50-93 years). Prevalence of any HRF or HRFs located only above the ellipsoid zone (EZ) increased from 33/590 (5.6%; 95%&#x2009;CI 4.0 to 7.0) and 22/590 (3.7%; 95%&#x2009;CI 2.2 to 5.2), respectively, in normal eyes to 371/725 (51.2%; 95%&#x2009;CI 47.7 to 54.7) and 246/725 (33.9%; 95%&#x2009;CI 30.4 to 37.4), respectively, in eyes with early age-related macular degeneration (AMD), to 283/314 (90.1%; 95%&#x2009;CI 87.1 to 93.1) and 260/314 (82.8%; 95%&#x2009;CI 78.8 to 86.8), respectively, in eyes with intermediate AMD, and to 12/12 (100%) and 12/12 (100%), respectively, in late AMD. HRFs above the EZ were spatially associated with EZ defects in 298/540 (55.2%) eyes and external limiting membrane (ELM) defects in 203/540 (37.6%) eyes. 52 (96%) of 54 eyes with macular hyperpigmentations showed HRFs above the EZ, and 52 (9.6%) of 540 eyes with HRFs above the EZ had corresponding macular hyperpigmentations. Higher HRF prevalence was associated (multivariable analysis) with higher AMD stage (OR: 1.75; 95%&#x2009;CI 1.36 to 2.26; p<0.001), and higher prevalences of EZ defects (OR: 36.6; 95%&#x2009;CI 8.56 to 157; p<0.001), reticular pseudodrusen (OR: 1.91; 95%&#x2009;CI 1.29 to 2.82; p<0.001), retinal pigment epithelium (RPE) elevations (OR: 34.5; 95%&#x2009;CI 10.4 to 111; p<0.001) and interdigitation zone thinnings (OR: 4.22; 95%&#x2009;CI 1.90 to 9.35; p<0.001).<br><br>CONCLUSIONS: The HRF prevalence was relatively high in early AMD and increased to late AMD. HRF location and shape suggested intraretinally migrated RPE cells as their equivalent. The majority of HRFs were not associated with an ophthalmoscopically detected macular hyperpigmentation. HRFs can also be found in locations with a localised interdigitation zone thinning with spatially corresponding EZ defects and ELM defects.}, }
@article {pmid41933583, year = {2026}, author = {Zhou, Y and Liu, Y and Chen, H and Yu, Y and Li, Y and Sun, Z and Han, X and Li, H and Zou, X and Sui, R}, title = {Expanding the Clinical and Genetic Spectrum of TTLL5-Associated Retinal Dystrophy: A Single-Center Cohort Study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.03.017}, pmid = {41933583}, issn = {2468-6530}, abstract = {PURPOSE: To characterize the clinical and genetic spectrum of TTLL5-related retinal dystrophy.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Twenty-one affected individuals from 19 unrelated families carrying biallelic TTLL5 variants.<br><br>METHODS: Patients with inherited retinal dystrophy and confirmed biallelic TTLL5 variants were retrospectively reviewed. Genetic diagnosis was established using whole-exome sequencing followed by Sanger confirmation and cosegregation analysis. Clinical assessments included best-corrected visual acuity, multimodal retinal imaging, visual field testing, and full-field electroretinography.<br><br>MAIN OUTCOME MEASURES: Visual function, retinal structural and functional characteristics, and genotype-phenotype correlation.<br><br>RESULTS: The cohort included 10 males and 11 females, aged 6 to 66 years. Based on phenotypic classification, 2 patients were diagnosed with cone dystrophy (CD), 12 with cone-rod dystrophy (CRD), and 7 with rod-cone dystrophy (RCD). Best-corrected visual acuity ranged from 0 to 2.70 logarithm of the minimum angle of resolution (LogMAR) (median, 0.6 LogMAR; interquartile range, 1.55) and was significantly correlated with age (Spearman R = 0.704; P < 0.001). All patients were myopic, with spherical equivalent values ranging from -1.13 to -18.00 diopters, and 14 of 21 (66.67%) had bilateral high myopia (&#x2264;-6.0 diopters). Retinal involvement was characterized by macular degeneration with progressive extension beyond the posterior pole. Fundus autofluorescence demonstrated parafoveal or macular hyperautofluorescent rings followed by expanding hypoautofluorescent areas, whereas OCT revealed parafoveal-to-diffuse disruption or loss of the ellipsoid zone with outer nuclear layer thinning. Genetic analysis identified 24 pathogenic variants, of which 19 (79.17%) were novel. The recurrent missense variant c.437G>A (p.Gly146Glu) was the most frequent allele in this cohort and was consistently associated with a CRD phenotype. Extraocular manifestations were uncommon, with sensorineural hearing loss observed in 1 patient.<br><br>CONCLUSIONS: TTLL5-associated retinal dystrophy exhibits a broad clinical spectrum encompassing CD, CRD, and RCD, with a high prevalence of myopia as a shared feature. The recurrent p.Gly146Glu variant showed a consistent association with the CRD phenotype, suggesting specific allele-phenotype correlations. These findings expand the recognized phenotypic and genetic spectrum of TTLL5-related disease and provide an important clinical framework for diagnosis, counseling, natural history, and future therapeutic studies.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42021400, year = {2026}, author = {Kniggendorf, V and Silveira, TC and Costa, VDM and Soriano, DS and Regatieri, CV and Sugai, RF and Bordon, A and Nutels, GS and Peixoto, AL and Moreira-Neto, CA and Miranda, JVC and Nehemy, MB and Damico, FM and Zacharias, LC and Lavinsky, D and Machado, CG and Veloso, CED and Cyrino, FV and Cella, W and Roisman, L and Brasil, OF and Andrade, GC and Stefanini, F and Malerbi, FK and Penha, FM and , }, title = {Real-world performance of faricimab for neovascular age-related macular degeneration and diabetic macular edema: experience from the BrazilRetNet multicenter study. Report 1.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00860-z}, pmid = {42021400}, issn = {2056-9920}, }
@article {pmid42021792, year = {2025}, author = {Iztleuov, M and Abugaliyeva, N and Ryzhkin, S and Iztleuov, Y and Saparbaev, S and Smagulova, G}, title = {Current Insights into Plausible Mechanisms of Chromium (VI) Neurotoxicity in the Brain and Future Perspectives.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {39}, number = {}, pages = {157}, pmid = {42021792}, issn = {1016-1430}, abstract = {BACKGROUND: Hexavalent chromium (Cr (VI)) is a known neurotoxin and environmental contaminant. Despite its recognition, the underlying mechanisms by which Cr (VI) induces neurological damage remain insufficiently explored. The complexities of the Central Nervous System (CNS), including the Blood Brain Barrier (BBB) and supporting brain cells, contribute to regions-specific susceptibility within the brain. Understanding Cr (VI) neurotoxicity is crucial for its potential role in neurodegenerative diseases.<br><br>METHODS: A Systematic Review was conducted using international databases (PubMed, Medline, Scopus, and Web of Science) and Google Scholar. Only open-access, free full-text articles published in English between 2010 and 2025 were included. Following PRISMA 2020 guidelines, a total of 19 relevant studies were selected, comprising 12 animal-based and 7 human cohort studies.<br><br>RESULTS: Animal studies investigated the effects of Cr (VI) via various administration methods and doses, revealed evidence of oxidative stress, inflammatory markers, and apoptotic changes in the brain. Interventional studies showed delayed toxicity when antioxidant agents were used prior to Cr (VI) exposure, including PDC (Potassium Dichromate), SA (Sodium Alginate), and TNG (Tangeretin). Human studies, including autopsies and cell culture analyses, demonstrated neurotoxic effects in conditions such as ALS (Amyotrophic Lateral Sclerosis), nAMD (Neovascular Age-Related Macular Degeneration).<br><br>CONCLUSION: Animal studies have clarified the role of oxidative stress in Cr (VI)-induced neurotoxicity. Human cohort studies have identified Cr (VI) as an environmental risk factor for both neurodegenerative and neurobehavioral disorders. Future research should focus on defining harmful levels of Cr (VI) and exploring potential antioxidant therapies.}, }
@article {pmid42022797, year = {2026}, author = {Sannan, NS and Ramadan, M and Malli, I and Ishgi, L and Al Johani, R and Abualjamal, R}, title = {Frequency and comorbidities of age-related macular degeneration in KSA: A retrospective multiregional study.}, journal = {Journal of Taibah University Medical Sciences}, volume = {21}, number = {3}, pages = {411-419}, pmid = {42022797}, issn = {1658-3612}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. In this study, we characterized the frequency of AMD and its comorbidities in understudied regions.<br><br>METHODS: A retrospective cohort study was conducted using medical records from tertiary care hospitals in KSA (2016-2022). Patients aged &#x2265;40 years with a confirmed AMD diagnosis were included. Demographic and clinical data were analyzed, including comorbidities. Logistic regression analyses were performed.<br><br>RESULTS: Among the 335 patients diagnosed, 66.9% had the exudative form and 33.1% had the non-exudative form. The cohort had a mean age of 71.17 &#xb1; 10.12 years, and there was no significant difference in age between AMD subtypes (p = 0.29). High prevalences of diabetes (66.3%) and hypertension (65.1%) were observed. Estimation of annual case counts revealed a significant temporal variation in diagnosed AMD cases, peaking in 2019 and increasing again by 2021-2022. Logistic regression identified female gender (Exp(B) = 1.03; p = 0.009) and age at diagnosis of diabetes mellitus (Exp(B) = 0.93; p < 0.001) as significant predictors of age at AMD onset. Diabetes mellitus was independently associated with later AMD diagnosis (Exp(B) = 1.03; p = 0.02). Conversely, stroke history was linked to earlier AMD onset (Exp(B) = 0.94; p = 0.002). Other comorbidities, including hypertension, dyslipidemia, and heart failure, had no significant associations.<br><br>CONCLUSION: Our findings highlight the burden of AMD and its comorbidities in KSA. Diabetes and stroke are key predictors, demonstrating the need for integrated chronic disease management strategies.}, }
@article {pmid42023256, year = {2026}, author = {Sun, RS and Huo, SX and Zhang, TL and Ying, HJ and Wang, JH and Xu, LN and Luo, XL and Yang, Y and Hu, YD}, title = {Development of a predictive model for depressive symptoms in type 2 diabetes mellitus patients under community management: Based on visual function index.}, journal = {Ibrain}, volume = {12}, number = {1}, pages = {123-136}, pmid = {42023256}, issn = {2769-2795}, abstract = {Visual impairment has been recognized as a potential risk factor for depressive symptoms (DS) in diabetes patients, yet the role of visual function in predicting DS remains unexplored. This study aims to develop and validate a predictive model for DS risk in type 2 diabetes mellitus (T2DM) patients in community health settings, incorporating a visual function index (VF14). We conducted a cross-sectional study involving 542 T2DM patients from four community health centers in Guiyang. Univariate and multivariate logistic regressions identified significant predictors, while 10 machine learning algorithms were employed to construct the predictive model. Model performance was assessed using such metrics as receiver operating characteristic curves, accuracy, sensitivity, specificity, F1 score, Brier score, C-index, calibration curves, and decision curve analysis. A restricted cubic spline (RCS) analysis evaluated the score-dependent risk profiles between the VF14 and DS. Key predictors included body mass index (BMI), self-reported glycemic status, age-related macular degeneration, glycated hemoglobin (HbA1c), and VF14. Among the models, the gradient boosting machine exhibited the robust predictive performance, with an area under the curve of 0.73 and sensitivity of 0.72. The Shapley additive explanations analysis identified VF14, BMI, and HbA1c as the top risk factors. RCS analysis revealed a score-dependent risk profile between VF14 and DS risk. This study introduces a clinically interpretable tool for early DS risk stratification in T2DM patients, offering potential for improved risk assessment and timely intervention in community health settings.}, }
@article {pmid42024166, year = {2026}, author = {Gregori, G and Sahoo, NK and Lall, SR and Sadeghi, E and Schulman, A and Hasan, N and Chhablani, J}, title = {High choroidal vascularity index zones favor the distribution of drusenoid pigment epithelial detachment in intermediate age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42024166}, issn = {1435-702X}, }
@article {pmid42025255, year = {2026}, author = {Sagnard, M and Valero, B and D'aiello, A and Agard, E and El Chehab, H}, title = {Ocular risks related to light overexposure in maritime professionals in the Provence-Alpes-Côte d'Azur Region, France: The PHOTOPPA study.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {5}, pages = {104885}, doi = {10.1016/j.jfo.2026.104885}, pmid = {42025255}, issn = {1773-0597}, abstract = {PURPOSE: To assess the prevalence of light-induced toxic effects on the ocular and palpebral regions in maritime professionals chronically exposed to light radiation in the Provence-Alpes-Côte d'Azur region and to compare the results to a non-overexposed population. The study also investigates risk factors for and protective factors against ocular phototoxicity in exposed individuals.<br><br>DESIGN: Single-center, cross-sectional comparative analysis.<br><br>PARTICIPANTS: The study included 77 maritime professionals (overexposed group) and 70 non-overexposed individuals (control group). Participants were examined between July 2023 and June 2024 at the ophthalmology department of Sainte-Anne Military Hospital.<br><br>METHODS: Cross-sectional comparative analysis was performed between the two groups. Participants underwent a clinical examination, including ocular imaging, focused on ocular conditions such as conjunctival lesions, cataracts, and macular changes linked to light overexposure, and completed questionnaires on sun exposure.<br><br>RESULTS: The study found no connection between age-related macular degeneration (AMD) and solar overexposure but highlighted the significant role of light reflection from water in other ocular conditions. Four basal cell carcinomas were found in the exposed group, consistent with the pathogenesis of these skin cancers. A higher risk of conjunctival lesions (pinguecula and/or pterygium) and cortical cataracts was noted. Macular epithelial damage was linked to increased light exposure. Protective solar equipment reduced the risk of ocular damage in certain conditions.<br><br>CONCLUSIONS: The PHOTOPPA study is the first to compare ocular pathologies related to light overexposure in maritime professionals. It confirms the increased risk of ocular conditions, emphasizing the importance of comprehensive sun protection to reduce light-induced ocular damage and possibly prevent AMD development.}, }
@article {pmid42025869, year = {2026}, author = {Abdouh, M and Sebag, W and Abdouh, N and Goyeneche, A and Burnier, MN}, title = {Differential protective effects of blue light (BL)-exposed retinal pigment epithelial cells by selective BL-filtering lenses.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {111034}, doi = {10.1016/j.exer.2026.111034}, pmid = {42025869}, issn = {1096-0007}, abstract = {Blue light (BL) is harmful to eye posterior segment structures. It induces accelerated retina aging and the progression of retinal diseases. We reported that BL is cytotoxic to retinal pigment epithelial (RPE) cell through oxidative damage. Herein, we investigated the potential of selective BL-filtering intraocular lenses (BL-IOL) to mitigate these deleterious effects. Human RPE cells were exposed to BL in the absence or presence of a panel of BL-IOLs having different pigment compositions and BL-filtering potentials. Cells were analyzed for their oxidative status (levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨM)), and growth (proliferation, metabolic activity and viability). Exposure of RPE cells to BL significantly increased the levels of cellular ROS and mitochondrial superoxide anion. While these effects did not affect cell proliferation, they triggered a collapse of the ΔΨM, a decrease in cell metabolic activity and an increase of cell death. Independent of the BL-IOL used in the BL beam, there was a drop in oxidative stress and ensuing protection of cells from the BL-mediated cytotoxic effects. Notably, BL-IOL with higher filtration potential of high-energy BL provided better photoprotection to exposed cells. This study highlights the need to selectively filter BL radiation wavelengths from light reaching the eye. It will help to define the best filtering devices to prevent RPE cell damage and eye posterior segment structure-related disease progression, such as during age-related macular degeneration.}, }
@article {pmid42026508, year = {2026}, author = {Chi, SC and Hwang, DK and Chen, SJ and Weng, CC and Huang, YM and Chou, YB and Lin, TC}, title = {Short-term efficacy of aflibercept 8 mg in refractory neovascular age-related macular degeneration: a retrospective case series from Taiwan.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04848-z}, pmid = {42026508}, issn = {1471-2415}, support = {(CI-113-26)//Yen Tjing Ling Medical Foundation/ ; V114C-191//Taipei Veterans General Hospital/ ; }, }
@article {pmid42015048, year = {2026}, author = {Ma, Q and Liu, X and Li, J and Bai, Y and Mu, W and Li, N and Yan, B and Wang, Z}, title = {AMD-UPerNet: a tool for retinal layer and fluid assessment in age-related macular degeneration.}, journal = {BMC medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12880-026-02349-5}, pmid = {42015048}, issn = {1471-2342}, }
@article {pmid42017182, year = {2026}, author = {Sivachandran, N and Ji, PX and Khan, H and Pickel, L and Mojumder, O and Aziz, AA and Khan, H and Sulahria, H and Gahn, GM and Khanani, AM}, title = {Visual and Anatomic Outcomes of Faricimab in Naïve Neovascular Age-Related Macular Degeneration with Subretinal Hemorrhage: A Multi-Centre Retrospective Analysis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {589703}, pmid = {42017182}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate functional and anatomical outcomes of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) presenting with subretinal hemorrhage (SRH).<br><br>SUBJECTS AND METHODS: A multicenter retrospective chart review was completed in retina practices in Canada and the United States from June 2022 to September 2025. Treatment-na&#xef;ve nAMD patients with SRH receiving faricimab were evaluated. Standardized imaging protocols and treat-and-extend guidelines were employed. Primary outcome was visual acuity (VA) change; secondary outcomes included central subfield thickness (CST), pigment epithelial detachment (PED) height, and qualitative assessment of subretinal hyperreflective material (SHRM) and subretinal fibrosis. Outcomes were analyzed following three consecutive loading doses using Friedman statistics for repeated measures. Paired analysis was performed using Wilcoxon signed rank test. Detailed characterization of SRH included measurements of hemorrhage size in disc diameters (DD), location in terms of subfoveal versus extrafoveal, and duration from symptom onset to treatment initiation. Univariate regression analysis was performed to identify predictors of SRH resolution (effect ratio and 95% CI) and visual acuity improvement (odds ratio and 95% CI).<br><br>RESULTS: This study included 63 treatment-na&#xef;ve patients with nAMD and SRH (mean age was 81.6 &#xb1; 8.2 years; 58.2% females; n = 28 from Canada and n = 35 from United States; mean total follow-up duration was 17.5 &#xb1; 6.0 months). Significant VA improvement was observed (Friedman statistic: 26.3, p < 0.00001), with 42.6% of patients gaining &#x2265;3 lines of vision after loading doses. CST decreased substantially from 391.8&#xa0;&#xb5;m to 249.4&#xa0;&#xb5;m (p < 0.00001, z = -5.48) and mean PED height reduced from 309.6&#xa0;&#xb5;m to 110.7&#xa0;&#xb5;m (p < 0.00001, z = -3.51). SHRM and subretinal fibrosis were noted in 81.6% and 25.4% of cases, respectively, at baseline. Of this, 70% had resolution of SHRM and 50% had improvement in fibrosis, at last follow up visit. Univariate analysis of predictors of faricimab injection account to achieve SRH resolution in n = 33 patients identified three significant predictors: SHRM-presence at baseline (effect ratio = 0.531, 95% CI 0.399-0.707, p < 0.0001), combined intraretinal fluid (IRF) and subretinal fluid (SRF) (effect ratio = 1.43, 95% CI 1.09-1.87, p = 0.011), and non-Caucasian ethnicity (effect ratio = 1.45, 95% CI 1.03-2.04, p = 0.031). Analysis of predictors of VA improvement >3 lines did not reveal any clinically meaningful associations.<br><br>CONCLUSION: This study demonstrates faricimab's efficacy in nAMD with SRH, a challenging phenotype traditionally associated with poor visual prognosis. The dual-pathway inhibition of VEGF-A and Ang-2 achieved rapid hemorrhage clearance and meaningful vision gains, offering clinical hope for this high-risk population.}, }
@article {pmid42017838, year = {2026}, author = {Cui, X and Yuan, J and Zhao, Q and Yu-Wai-Man, P and Zheng, T}, title = {Sleep Regularity and Age-Related Eye Diseases: Prospective Analyses with Retinal Imaging and Multimorbidity Assessment in the UK Biobank.}, journal = {Sleep}, volume = {}, number = {}, pages = {}, doi = {10.1093/sleep/zsag111}, pmid = {42017838}, issn = {1550-9109}, abstract = {STUDY OBJECTIVES: Sleep regularity, a key circadian dimension of sleep health, has been linked to cardiometabolic and neurodegenerative outcomes, yet its relevance to ocular ageing remains unclear. The retina is a metabolically active, circadian-regulated neural tissue, suggesting that irregular sleep may contribute to the development of age-related eye diseases.<br><br>METHODS: We studied 78,839 adults in the UK Biobank. Sleep regularity was quantified using the Sleep Regularity Index (SRI). Associations with age-related macular degeneration (AMD), cataract, glaucoma, retinal vein occlusion (RVO), and diabetic retinopathy (DR) were examined using Cox models, restricted cubic splines, subgroup analyses, and propensity-score matching. Retinal structural and vascular metrics were additionally evaluated. Nomogram models integrating SRI with clinical risk factors were developed.<br><br>RESULTS: Lower SRI was consistently associated with higher risks of AMD (HR=0.87), cataract (HR=0.95), and glaucoma (HR=0.89), with clear dose-response patterns; no robust associations were found for RVO or DR. Higher SRI correlated with greater macular, retinal ganglion cell (RGC), and retinal nerve fiber layer (RNFL) thicknesses, and with more favourable retinal vascular geometry. Incorporating SRI improved prediction performance for AMD, cataract, and glaucoma (AUC 0.72-0.74). SRI also declined markedly with increasing ocular multimorbidity.<br><br>CONCLUSIONS: Sleep regularity was consistently associated with major age-related eye diseases, ocular multimorbidity, and retinal structural and vascular characteristics. These findings highlight sleep regularity as a clinically relevant behavioural correlate of ocular ageing and a potential adjunctive marker for prevention-oriented risk stratification.}, }
@article {pmid42018151, year = {2026}, author = {Nielsen, MA and Bjerager, J and Citirak, G and Subhi, Y and Holm, LM and Singh, A}, title = {Charles Bonnet syndrome in patients referred for cataract surgery.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42018151}, issn = {1435-702X}, abstract = {PURPOSE: To investigate the prevalence and clinical characteristics of Charles Bonnet Syndrome (CBS) in patients referred for bilateral cataract surgery.<br><br>METHODS: This prospective, cross-sectional clinical trial included 391 patients attending cataract assessment at a single-center tertiary cataract clinic. After clinical examination, participants were screened for presence of visual hallucinations (VHs). Participants experiencing complex VHs were further questioned regarding characteristics of their hallucinatory experiences to properly determine if they were attributable to CBS. CBS was defined as complex visual hallucinations with retained insight, no medical history or medication known to cause hallucinations and not limited to hypnagogic or hypnopompic states (hallucinations happening shortly before falling asleep and/or shortly after waking up).<br><br>RESULTS: Nineteen (4.9%) patients experienced complex VHs. Of these, 11 (2.8%) were diagnosed with CBS while 8 (2.1%) had complex hypnagogic and/or hypnopompic VHs. Multivariable logistic regression analysis identified lower best-corrected visual acuity (BCVA) in the better seeing eye as&#xa0;a significant predictor of CBS. When excluding participants with a BCVA>0.3, prevalence of complex VHs rose to 10.0%. Three of the patients with CBS (27.3%) had ocular comorbidities: two had exudative age-related macular degeneration (AMD), and one had drusenoid AMD. In the overall cohort, twenty-four patients (6.1%) reported prior knowledge of CBS.&#xa0; CONCLUSION: CBS was observed in a clinically relevant minority of cataract patients requiring bilateral surgical intervention. Given the high prevalence of cataract among the elderly, this study highlights the importance of healthcare personnel being aware of CBS and other complex VHs and their potential consequences for cataract patients.}, }
@article {pmid42018574, year = {2026}, author = {Vavvas, DG}, title = {Photobiomodulation in Dry Age-Related Macular Degeneration: Promising Signal, Familiar Questions.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {5}, pages = {765-767}, doi = {10.1097/IAE.0000000000004823}, pmid = {42018574}, issn = {1539-2864}, }
@article {pmid42019353, year = {2026}, author = {Deng, Q and Kishimoto, K and Sugiyama, O and Miyake, M and Tamura, H}, title = {Automatic selection of optical coherence tomography images for prognostic prediction models in age-related macular degeneration.}, journal = {Computer methods and programs in biomedicine}, volume = {282}, number = {}, pages = {109384}, doi = {10.1016/j.cmpb.2026.109384}, pmid = {42019353}, issn = {1872-7565}, abstract = {BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) is a leading cause of blindness. Current standard treatments require frequent intravitreal injections and entail high costs, placing a heavy burden on patients and healthcare providers. These challenges often lead to treatment discontinuation or overtreatment, highlighting the need for personalized AMD management. Accurate early prediction of long-term treatment outcomes is critical for optimizing these strategies. However, most existing prognostic models rely heavily on manual image selection by ophthalmologists. This labor-intensive process, which requires carefully selecting suitable images from large volumes of electronic medical record (EMR) data, significantly hinders real-world implementation. This study proposes an automated deep learning framework to select appropriate images from extensive EMR-stored optical coherence tomography (OCT) reports, thereby reducing the reliance on manual curation.<br><br>METHODS: We developed a vision transformer (ViT)-based architecture to perform automated image selection. The model integrates features from the fundus infrared reflectance (IR) images and the corresponding OCT images presented in the clinical reports.<br><br>RESULTS: Compared to related works using a single OCT image input, the proposed method outperformed to the baseline. At training the pretrained ViT framework achieved an overall accuracy of 89% in identifying suitable images. Furthermore, using the images selected by our method improved the downstream prognostic prediction accuracy by an average of 3.1 percentage points. Confidence scores showed a statistically significant difference between the proposed method and the baseline (p = 0.026). The 95% confidence interval (CI) of the performance difference was [0.002, 0.066].<br><br>CONCLUSIONS: These results demonstrate the feasibility of an automated module capable of reliably identifying suitable images for AMD prognosis. By streamlining image selection workflows, this approach can enhance clinical efficiency, support the accurate estimation of long-term treatment effects, and facilitate treatment planning.}, }
@article {pmid42019593, year = {2026}, author = {Goncalves, L and Hashimoto, Y and Barthelmes, D and Barry, R and Pollreisz, A and Wolff, B and Toole, LO and Ponsioen, TL and Morros, HB and Creuzot-Garcher, C and Gillies, M and Gabrielle, PH}, title = {Real-World Outcomes in Neovascular AMD with Visit Gaps under Anti-VEGF Therapy: Data from the FRB! Registry.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.04.007}, pmid = {42019593}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate visual outcomes observed across visit gaps in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) therapy in routine clinical practice.<br><br>DESIGN: Retrospective data analysis from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! (FRB!).<br><br>PARTICIPANTS: Treatment-na&#xef;ve nAMD eyes receiving intravitreal anti-VEGF therapy (&#x2265;1 injection), monitored at least quarterly during the first treatment year, and experiencing a visit gap of &#x2265;6 to 12 months, with subsequent follow-up over the next 9 months (&#x2265;3 visits).<br><br>METHODS: Visual outcomes were assessed using a segmented linear mixed-effect model. Cumulative incidence and risk factors for visit gaps were evaluated using Aalen-Johansen estimators and Cox regression models.<br><br>MAIN OUTCOME MEASURES: The main outcome was the mean estimated change in VA immediately after the visit gap. Secondary outcomes included the cumulative incidence and associated risk factors of visit gaps.<br><br>RESULTS: From 3694 eligible eyes for the survival analysis, we tracked 262 (7.1%) eligible eyes experiencing a visit gap for the visual outcome analysis. nAMD-treated eyes experiencing a 6-12 month visit gap had a significant drop in vision immediately after the visit gap, with a mean (95% confidence interval [CI]) estimated change in VA of -4.9 letters (-6.0 to -3.7; P < 0.001). Eyes with active choroidal neovascularization (CNV) lesions (difference -3.9 [-7.1 to -0.3] letters vs. inactive CNV) and without subfoveal macular atrophy (MA) (difference 3.4 [-0.3 to 7.0] letters vs. subfoveal MA) at the last visit before the gap experienced a greater decline in VA after the visit gap. A quarter of the eyes experienced a 6-12 month visit gap at 6.5 years. nAMD eyes with a longer time interval since last injection were more likely to experience a visit gap, while eyes with better VA and that had active CNV with subretinal fluid only at follow-up visits were less likely.<br><br>CONCLUSIONS: Visit gaps were common and associated with a significant visual decline across the visit gap in nAMD eyes treated with anti-VEGF therapy in routine clinical practice.}, }
@article {pmid42020899, year = {2026}, author = {Kumar, S and Zhao, D and Wong, VHY and Bui, BV and Liu, GS}, title = {Evaluation of CRISPR/CasRx-Mediated VEGF mRNA Knockdown in Mouse Retina.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3023}, number = {}, pages = {25-37}, pmid = {42020899}, issn = {1940-6029}, abstract = {Neovascular eye diseases (NEDs) are a group of diseases caused by the abnormal overgrowth of blood vessels in the eye. Normal vasculature is maintained through a dynamic balance of the vascular endothelial growth factor (VEGF). In diseases such as advanced diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD), an overexpression of VEGF leads to the formation of structurally weak and leaky blood vessels, resulting in vision impairment and, without intervention, legal blindness. In the clinic, NEDs are presently managed through anti-VEGF agents that specifically bind and neutralize VEGF signaling. While effective, this approach requires invasive intravitreal injections monthly and places a heavy burden on patients and healthcare providers. A flexible, long-lasting therapeutic that can reduce or eliminate frequent anti-VEGF treatment will significantly advance NED management.RNA editing with clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) is an emerging strategy to achieve reversible gene editing. The CRISPR-Cas13 system exclusively targets single-stranded RNA and allows gene silencing in a safe manner through RNA knockdown, as the genome is left intact. In addition, the compact CasRx enzyme (930aa) allows RNA silencing to be achieved through the delivery of a single adeno-associated virus (AAV), ideal for gene therapy applications. Herein, we outline methods to target VEGFA mRNA using CRISPR/CasRx in a mammalian cell line and humanized VEGFA transgenic mice.}, }
@article {pmid42020902, year = {2026}, author = {Hall, J and Cheung, S and Shobhana, K and Cho, E and Lidgerwood, GE and Paull, D and Pébay, A}, title = {Quantification of Drusen-Like Deposits in Human Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cells Using Confocal Microscopy.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3023}, number = {}, pages = {59-80}, pmid = {42020902}, issn = {1940-6029}, abstract = {Accessing pathologically relevant models of human retinal degeneration is crucial for understanding, screening, and developing accurate treatment strategies that prevent or slow progression of blinding diseases. Human pluripotent stem cells (hPSCs) are a powerful tool to investigate retinal disease, as cells from selected individuals or specific genetic background can be differentiated into cell types of interest. hPSC-derived retinal pigment epithelium (RPE) cells can produce drusen-like deposits that accumulate between the RPE and the underlying Bruch's membrane. These key pathological markers of specific retinal disorders are detectable using simple microscopy techniques. However, quantification of these deposits often requires slow, low-throughput manual counting of images. This further lends itself to issues including sampling biases while ignoring critical data parameters such as deposit volume and precise localization. To overcome these issues, we developed two methods for quantifying the presence of drusen-like deposits in vitro, using hPSC-derived RPE cultures. Both methods accurately quantify drusen-like deposit numbers, and the mid-throughput pipeline allows for quantification of drusen-like deposit volume, as well as discerns their apical or basal localization on RPE cells. The platform's ability to track changes in drusen-like deposits supports screening experimentation and personalized medicine initiatives, including for gene therapy optimization.}, }
@article {pmid42020908, year = {2026}, author = {Miller, AL and Bhatt, Y and Carvalho, LS}, title = {Intravitreal Injections in Mouse Models of Eye Disease.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {3023}, number = {}, pages = {167-176}, pmid = {42020908}, issn = {1940-6029}, abstract = {Intravitreal injections are a commonly used technique in the treatment of some vitreoretinal diseases. In clinical situations, intravitreal injections are often used to deliver drugs that treat diseases such as age-related macular degeneration, retinal vein occlusion, and uveitis. Many preclinical studies in animals such as mice utilize intravitreal injections to test neuroprotective treatments and gene therapies before clinical use can be indicated. Herein, we describe our method and favorable practices for intravitreal injection into the eye of both preweaned and adult mice.}, }
@article {pmid42008990, year = {2026}, author = {Said, S and Knecht-Bösch, M and Knecht-Bosch, P}, title = {Switching to the Biosimilar Ranibizumab-nuna for the Intravitreal Treatment of Retinal Diseases - a Real-World Study.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {243}, number = {4}, pages = {434-439}, doi = {10.1055/a-2803-9757}, pmid = {42008990}, issn = {1439-3999}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/adverse effects/therapeutic use ; Female ; Male ; Retrospective Studies ; Aged ; Middle Aged ; Intravitreal Injections ; Aged, 80 and over ; *Biosimilar Pharmaceuticals/administration &amp; dosage/adverse effects/therapeutic use ; *Drug Substitution ; Tomography, Optical Coherence ; *Retinal Diseases/drug therapy ; Visual Acuity/drug effects ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {ABSTRACT: INTRODUCTION: Following the expiration of ranibizumab's (Lucentis) patent, the biosimilar ranibizumab-nuna (Byooviz) offers an alternative intravitreal medication with identical indications. However, real-world data on its efficacy remain limited. This study aimed to investigate the efficacy and safety of retinal disorders in patients who were switched from Lucentis to Byooviz.<br><br>ABSTRACT: METHODS: This retrospective, single-center study assessed adult patients previously treated with intravitreal Lucentis and switched to Byooviz. We evaluated structural and functional outcomes based on Snellen visual acuity (VA), fundoscopy, and optical coherence tomography (OCT) parameters, and treatment safety. Disease activity was classified as active or inactive, with neovascular activity defined as retinal pigment epithelial detachments, intra- or subretinal fluid, subretinal hyperreflective material, or macular hemorrhage on OCT or fundoscopy.<br><br>ABSTRACT: RESULTS: Between June 2021 and December 2024, we identified 31 patients, 21 (67.7%) of whom were female. Median (IQR, range) age was 82 (76.5 to 85.5, 49 to 91) years. The most common indication was neovascular age-related macular degeneration (61.3%), followed by macular edema (ME) due to retinal vein occlusion (22.6%), diabetic ME (9.7%), and secondary choroidal neovascularization (6.5%). Right and left eyes were nearly equally represented (48.4% vs. 51.6%). The median (IQR) injection numbers were 15 (10 to 40) for Lucentis and 8 (5 to 10.5) for Byooviz. After the switch, VA improved in 8 eyes (25.8%), was unchanged in 10 (32.3%), and worsened in 13 (41.9%). Disease activity decreased in 6 eyes (20%), increased in 3 (10%), and remained stable in 22 (70%). Treatment intervals shortened in 8 (25.8%) patients and extended in 14 (45.2%). No cases of endophthalmitis or other complications occurred.<br><br>ABSTRACT: DISCUSSION: Switching from Lucentis to Byooviz was generally well tolerated, with anatomical disease stability maintained in most patients. Certain decline in VA is also be observed in real-world outcomes for Lucentis and may reflect underlying disease progression rather than reduced efficacy of the biosimilar. Overall, Byooviz seems to be a viable alternative for patients previously treated with Lucentis.}, }
@article {pmid42008992, year = {2026}, author = {Gabathuler, F and Cozzi, M and Fasler, K and Maloca, PM and Blaser, F and Zweifel, S}, title = {Real-World Case Series of Intravitreal Pegcetacoplan for Geographic Atrophy Secondary to Age-related Macular Degeneration in Switzerland.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {243}, number = {4}, pages = {461-464}, doi = {10.1055/a-2825-0926}, pmid = {42008992}, issn = {1439-3999}, mesh = {Humans ; *Geographic Atrophy/drug therapy/etiology/diagnosis ; Male ; Female ; Switzerland ; Intravitreal Injections ; Aged ; Retrospective Studies ; *Macular Degeneration/complications/drug therapy ; Aged, 80 and over ; Treatment Outcome ; Visual Acuity/drug effects ; Tomography, Optical Coherence/methods ; }, abstract = {ABSTRACT: PURPOSE: To report early real-world experience with intravitreal pegcetacoplan for geographic atrophy secondary to age-related macular degeneration in Switzerland.<br><br>ABSTRACT: METHODS: This retrospective case series included patients with geographic atrophy secondary to age-related macular degeneration treated with intravitreal pegcetacoplan. Treatment exposure, best-corrected visual acuity, adverse events, and follow-up were assessed. Geographic atrophy was quantified on macula-centred OCT scans using the RetinAI Discovery platform, based on automated segmentation of total photoreceptor and RPE atrophy.<br><br>ABSTRACT: RESULTS: Seven eyes from six patients were included, receiving a total of 37 intravitreal pegcetacoplan injections. The median number of injections per eye was five (range 3&#x200a;-&#x200a;8), with a mean injection interval of 9.5&#x2009;&#xb1;&#x2009;2.4 weeks. Follow-up duration ranged from 4.4 to 14.0 months. Median best-corrected visual acuity declined by 7 ETDRS letters over the observation period. Mean geographic atrophy area increased from 7.6&#x2009;mm[2] at baseline to 8.7&#x2009;mm[2] at last follow-up. No severe adverse events were recorded.<br><br>ABSTRACT: CONCLUSIONS: In this real-world case series, intravitreal pegcetacoplan was well tolerated without severe adverse events during short-term follow-up, while visual acuity decline and continued geographic atrophy progression were observed.}, }
@article {pmid42009153, year = {2026}, author = {Ge, Z and Jia, Z and Liu, Y and Zhang, H}, title = {Injectable hyaluronic acid hydrogels for the treatment of ocular diseases: A review.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {152112}, doi = {10.1016/j.ijbiomac.2026.152112}, pmid = {42009153}, issn = {1879-0003}, abstract = {Globally, an increasing number of individuals suffer from ocular diseases, including dry eye syndrome, corneal injuries, and age-related macular degeneration (AMD), ultimately leading to visual impairment or complete blindness. The complex anatomy and physiological barriers of the eye limit the efficacy of conventional therapies such as eye drops and intraocular injections, while also posing challenges including frequent dosing requirements and inflammatory risks. Injectable hyaluronic acid (HA) hydrogels present a promising strategy to address the limitations of current ocular therapies, owing to their excellent biocompatibility, tunable physicochemical properties (including optical transparency and mechanical modulus), and sustained drug release capabilities. Recent research continues to explore the potential of functionalized injectable HA hydrogels to advance ophthalmic treatment paradigms. This review summarizes recent advances in the chemical modification and crosslinking strategies of HA, as well as innovative design concepts for functionalized injectable HA hydrogels in treating ocular disorders such as corneal injuries and age-related macular degeneration (AMD). Injectable HA hydrogels show considerable promise for improving therapeutic outcomes, reducing treatment frequency and side effects, lowering healthcare costs, and enhancing patient compliance. This review aims to provide theoretical support for the future development of emerging HA hydrogel-based platforms for ocular care.}, }
@article {pmid42009803, year = {2026}, author = {Zeng, Q and Hua, X and Liu, Y and Wang, S}, title = {Oxidative stress promotes the progression of age-related macular degeneration by up-regulating Spp1 to activate the JAK/STAT signaling pathway.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-48556-6}, pmid = {42009803}, issn = {2045-2322}, }
@article {pmid42011167, year = {2026}, author = {Ching, K and Meng, J and Wang, L and Cheng, K and He, W and Zhang, K and Lu, Y and Zhu, X}, title = {Swept-source OCTA assessment of iris vasculature as a biomarker for myopic macular degeneration severity.}, journal = {Advances in ophthalmology practice and research}, volume = {6}, number = {2}, pages = {139-145}, pmid = {42011167}, issn = {2667-3762}, abstract = {BACKGROUND: To investigate the vessel area density (VAD) and morphological features of the iris in patients at different stages of myopic macular degeneration (MMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: In this retrospective case-control study, 106 eyes of 106 high myopia patients (axial length (AL) &#x2265;26 mm) were included and classified into different MMD categories according to the International META-PM Classification. The VAD of iris, iris volume (IV), area of anterior iris surface (IS), area of posterior IS, and average iris thickness (IT) were evaluated using SS-OCTA. Associations among iris vasculature, iris morphology, and MMD categories were investigated.<br><br>RESULTS: Full-range, inner-region, and intermediate-region VAD of the iris decreased significantly with increasing MMD severity (all P-trend <0.001), whereas outer-region VAD did not show a significant linear trend. The area of IS was larger in eyes with MMD 2 and MMD 4 compared to the other two groups (all P <0.05). The full-range and outer-region VAD of iris was negatively correlated with AL, while the inner-region VAD of iris was positively correlated with the area of anterior and posterior IS, especially in eyes with MMD 2 (all P <0.05). Multivariate linear regression revealed that greater full-range, inner-region and intermediate-region VAD were all significantly associated with milder MMD, whereas greater outer-region VAD was significantly associated with shorter AL.<br><br>CONCLUSIONS: Iris blood flow, quantified by VAD, decreased with increasing MMD severity. Iris VAD may represent a promising candidate biomarker for non-invasive monitoring of MMD severity. Additionally, the association between VAD and AL or iris morphology varied across MMD categories.}, }
@article {pmid42011205, year = {2026}, author = {Chen, ZJ and Yu, J and Ng, DSC and Ho, M and Zhu, X and Brelen, ME and Young, AL and Yam, JC and Tham, CC and Pang, CP and Chen, LJ}, title = {Associations of TNFRSF10A with Central Serous Chorioretinopathy, Polypoidal Choroidal Vasculopathy, and Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {5}, pages = {101161}, pmid = {42011205}, issn = {2666-9145}, abstract = {PURPOSE: To investigate the role of tumour necrosis factor receptor superfamily member 10A (TNFRSF10A) in chronic central serous chorioretinopathy (cCSCR), polypoidal choroidal vasculopathy (PCV), and neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Case-control genetic association study.<br><br>PARTICIPANTS: A total of 1478 Chinese participants were recruited, including 217 patients with cCSCR (174 without and 43 with macular neovascularization [MNV]), 288 patients with PCV, 341 patients with nAMD, and 632 healthy controls.<br><br>METHODS: Thirteen single-nucleotide polymorphisms (SNPs) in TNFRSF10A that covered both the promoter and coding regions were genotyped, including 12 haplotype-tagging SNPs and a manually selected reference SNP, rs13278062. Two variants showing significant deviation from Hardy-Weinberg equilibrium were excluded, leaving 11 SNPs for the final analysis. Logistic regression, adjusted for age and sex, was applied to assess both allelic and haplotype associations. Conditional analyses were conducted to evaluate independent effects. Single-nucleotide polymorphisms were annotated based on TNFRSF10A domains defined by UniProtKB.<br><br>MAIN OUTCOME MEASURES: Associations between individual SNPs and haplotypes in the TNFRSF10A with nAMD, PCV, and cCSCR (with or without MNV), respectively.<br><br>RESULTS: For cCSCR without MNV, 4 tagging SNPs showed significant associations: rs59693001 (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.12 - 2.33; P = 0.0043), rs3808530 (OR = 1.91, 95% CI: 1.22 - 2.83; P = 0.0013), rs2235126 (OR = 1.74, 95% CI: 1.22 - 2.41; P = 7.50 &#xd7; 10[-4]), and rs7814465 (OR = 1.66, 95% CI: 1.22 - 2.28; P = 0.0016). The reference SNP, rs13278062, also showed a significant association (OR = 1.81, 95% CI: 1.31 - 2.51; P = 3.64 &#xd7; 10[-4]). In addition, 4 haplotypes within 2 blocks from a continuous region also showed significant associations. For PCV, only rs36005462 in an independent domain showed a marginally significant association (OR = 0.58; P = 0.0050). No significant association was identified for nAMD or cCSCR with MNV.<br><br>CONCLUSIONS: This study identified multiple TNFRSF10A variants associated with cCSCR without MNV, while a distinct protective SNP was linked to PCV. These findings provide preliminary evidence for varying TNFRSF10A association patterns across the pachychoroid disease spectrum.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid42011963, year = {2026}, author = {Posnic, A and Yagoub, S and Lebastard, C and Vaast, M and Poinas, A and Pabic, EL and Bellamy, JP and Delhay, C and Faure, S and Rouic, JL and Henry, A and Lebreton, O and Masse, H and Susini, F and Guillaumie, T and Fournier, I and Mainguy, A and Lez, ML and Khanna, RK and Mortemousque, G and George, A and Pipelart, V and Bernard, Y and Grimbert, P and Mazhar, D and Benzerroug, M and Briend, B and Clement, M and Jammes-Veaux, HP and Posnic, MP and Bonissent, A and Guyot, C and Rousseau, N and Dam, BTV and Bellot, L and Ferron, R and Meur, GL and Mouriaux, F and Weber, M and Maucourant, Y and Ducloyer, JB}, title = {Predictive factors for injection interval extension after switching to faricimab in neovascular AMD: The FAR WEST multicentre study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70134}, pmid = {42011963}, issn = {1755-3768}, support = {//Centre Hospitalier Universitaire de Nantes/ ; }, abstract = {PURPOSE: To assess whether switching to faricimab allowed extending injection intervals after 12 months (M12) in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.<br><br>DESIGN: FAR WEST was a multicentre, observational, retrospective cohort study.<br><br>PARTICIPANTS: Patients with nAMD treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for at least 1&#x2009;year before switching to faricimab.<br><br>METHODS: The reason for switching (clinician's intent to extend the interval in the absence or presence of a recurrence or refractory status), and the switch strategy (whether an induction phase comprising 2, 3 or 4 injections was performed using the same or a shorter interval, or whether the interval was immediately extended from the second injection without induction) were left to the physician's discretion.<br><br>MAIN OUTCOME MEASURES: The following data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M12 follow-up visit: recurrence-free interval, last injection interval, best-corrected visual acuity (BCVA), central macular thickness (CMT), exudation status and intraocular inflammation events.<br><br>RESULTS: A total of 845 eyes of 718 patients were included in 23 centres. The recurrence-free injection interval increased significantly from 5.7&#x2009;weeks at M0 to 8.6&#x2009;weeks at M12 (difference: +2.9&#x2009;weeks, p&#x2009;<&#x2009;0.001). The proportion of exudative patients decreased from 571 (68%) to 337 (42%) (- 41%, p&#x2009;<&#x2009;0.001). BCVA decreased from 0.33 (20/40) to 0.35 logMAR (20/40) (p&#x2009;=&#x2009;0.0038). Among 238 refractory cases at M0, 84 (35%) achieved a dry macula at M12. In multivariable analysis, absence of an induction phase was associated with greater injection interval gain. (p&#x2009;<&#x2009;0.001). There were no differences according to time since the first injection, type of neovascularization. The number of injections per year decreased from 8.7 at M0 to 6.1 at M12 (-2.6, p&#x2009;<&#x2009;0.001), and the number of consultations decreased from 6.1 at M0 to 5.2 at M12 (-0.9, p&#x2009;<&#x2009;0.001). The intraocular inflammation rate was 1.6% (n&#x2009;=&#x2009;14).<br><br>CONCLUSION: Switching to faricimab allowed significantly extending the recurrence-free injection interval, decreasing the proportion of exudative patients and reducing the therapeutic burden in nAMD patients. Further studies are needed to determine the most appropriate switching modalities and which patients actually require an induction phase.}, }
@article {pmid42012273, year = {2026}, author = {Shi, J and Xu, H and Zhao, H and Zhao, J and Chen, L and Xu, P and Jia, D and Jiang, C}, title = {Safety and Efficacy of cceAAV-aflibercept-Fc-YTE (F-CRG-B191): A Gene Therapy for Neovascular Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {47}, doi = {10.1167/iovs.67.4.47}, pmid = {42012273}, issn = {1552-5783}, mesh = {Animals ; *Genetic Therapy/methods ; *Recombinant Fusion Proteins/therapeutic use/genetics ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/genetics ; Mice ; Disease Models, Animal ; Humans ; Dependovirus/genetics ; *Choroidal Neovascularization/therapy ; Genetic Vectors ; Female ; Male ; *Wet Macular Degeneration/therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Treatment Outcome ; Visual Acuity ; Mice, Inbred C57BL ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: To evaluate the safety and efficacy of a novel gene therapy vector, covalently closed-end double-stranded adeno-associated virus-aflibercept-Fc-YTE (cceAAV-aflibercept-Fc-YTE; clinical trial name F-CRG-B191), designed for sustained anti-vascular endothelial growth factor (VEGF) expression in the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We developed cceAAV-aflibercept-Fc-YTE. The therapeutic efficacy of cceAAV-aflibercept-Fc-YTE was evaluated in both mice and non-human primate (NHP) models with laser-induced choroidal neovascularization (CNV). The incidence of grade IV CNV lesions was quantified. A first-in-human administration of F-CRG-B191 was conducted to assess anatomical and functional outcomes, as well as safety. Immune responses and retinal toxicity were monitored in NHPs and the patient post-injection.<br><br>RESULTS: Compared to conventional AAV vectors expressing aflibercept, cceAAV-aflibercept-Fc-YTE significantly reduced the incidence of grade IV CNV lesions in both mice and NHP models. In the human subject, F-CRG-B191 administration led to a sustained reduction in CNV area and improvement in visual acuity. No significant immune response or retinal toxicity was observed in either preclinical models or the treated patient.<br><br>CONCLUSIONS: cceAAV-aflibercept-Fc-YTE (F-CRG-B191) is a promising gene therapy candidate for nAMD, demonstrating potent anti-VEGF efficacy, durable therapeutic effects, and favorable safety profiles in both preclinical and early clinical settings.}, }
@article {pmid42012371, year = {2026}, author = {Cha, E and Youn, J and Yun, C and Kim, SW and Choi, M}, title = {Impact of Phacoemulsification on Neovascular Age-Related Macular Degeneration Activity: Predictive Role of Choroidal Vascularity and MNV Subtypes.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004864}, pmid = {42012371}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the impact of cataract surgery on disease activity in neovascular age-related macular degeneration (nAMD) and determine whether choroidal biomarkers and macular neovascularization (MNV) subtypes predict increased postoperative treatment requirements.<br><br>METHODS: This retrospective study included 84 eyes from 84 patients with nAMD who underwent phacoemulsification while receiving intravitreal anti-VEGF therapy. Increased treatment need was defined as a shortened injection interval or occurrence of submacular hemorrhage. Pre-and postoperative choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), and central subfield thickness (CST) were analyzed using EDI-OCT within 1 month before and after surgery. MNV subtypes were classified as type 1, type 2, retinal angiomatous proliferation (RAP), and polypoidal choroidal vasculopathy (PCV).<br><br>RESULTS: Best-corrected visual acuity remained stable after cataract surgery (from 0.39 &#xb1; 0.27 [20/50] to 0.38 &#xb1; 0.28 logMAR [20/50]; p = 0.907), with no significant differences among MNV subtypes. Increased treatment need occurred in 45.2% of eyes. Both CVI and SFCT increased significantly postoperatively (p < 0.001). Eyes with increased treatment need showed significantly higher preoperative and postoperative CVI (p = 0.003 and p = 0.032, respectively). The PCV subtype demonstrated the highest rates of increased treatment need and the shortest injection intervals. Higher preoperative CVI independently predicted increased postoperative treatment need (OR = 1.13; p = 0.019).<br><br>CONCLUSIONS: Cataract surgery may affect disease activity in a subset of patients with nAMD, particularly those with PCV and increased CVI. Preoperative choroidal characteristics such as CVI and SFCT may provide valuable insights for risk stratification and postoperative management.}, }
@article {pmid42012698, year = {2026}, author = {Herold, TR and Finger, RP and Bauer-Steinhusen, U and Lommatzsch, A and Ziemssen, F}, title = {Opportunities to Improve Management of Neovascular Age-related Macular Degeneration: Communication at Diagnosis and Beyond : Insights from the German nAMD Barometer Survey.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {42012698}, issn = {1435-702X}, }
@article {pmid42013734, year = {2026}, author = {Casablanca-Piñera, A and Alforja-Castiella, MS and Casaroli-Marano, RP}, title = {Changes on imaging after 10years of follow-up for concurrent melanocytoma and congenital hypertrophy of the retinal pigment epithelium in a patient treated with anti-VEGF intravitreal therapy for neovascular age-related macular degeneration.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {6}, pages = {104876}, doi = {10.1016/j.jfo.2026.104876}, pmid = {42013734}, issn = {1773-0597}, }
@article {pmid42014412, year = {2026}, author = {Raul, P and Lee, T and Barry, R and Sabeti, F and van Boxtel, JJA}, title = {Visual noise in augmented reality improves vision in age-related macular degeneration.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00389-3}, pmid = {42014412}, issn = {2731-6068}, support = {DP220100406//Australian Research Council/ ; }, abstract = {Exudative age-related macular degeneration (eAMD) is a degenerative eye disease of the central retina that results in central vision loss, significantly affecting the daily functioning and quality of life of affected individuals. Although first-line treatments are quite effective in improving vision in eAMD, they are invasive and not suitable or efficacious for everyone. The non-invasive methods to enhance visual acuity (VA) in eAMD, are often limited in scope and burdensome for patients. Stochastic resonance (SR), a phenomenon in which optimal noise improves sensory perception, offers a promising non-invasive strategy with broad clinical potential. In this study, we tested whether visual noise delivered via an augmented reality (AR) headset enhanced binocular VA in binocular eAMD (N = 12) and in healthy individuals (N = 17) via the SR effect. Using a standard clinical letter chart, we observed an immediate improvement in vision, without the need for any training. Improvements were 2.5 letters and 2 letters at optimal noise levels for eAMD and healthy individuals, respectively. These findings demonstrate the potential of noise-based AR as a practical, wearable visual aid for individuals with eAMD or other visual disorders, offering enhancements that may complement or extend the benefits of current first-line treatments.}, }
@article {pmid42002030, year = {2026}, author = {Fernández-Vigo, JI and Gallego-Pinazo, R and Montero Hernández, J and Arias-Barquet, L and Arévalo, FJ and García-Layana, A}, title = {Photodynamic therapy in neovascular age-related macular degeneration: Past or present in the era of second-generation anti-VEGF agents?.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502558}, doi = {10.1016/j.oftale.2026.502558}, pmid = {42002030}, issn = {2173-5794}, }
@article {pmid42002032, year = {2026}, author = {Benedictus, B and Tsania, S and Ronik, HK and Dwinastiti, YA and Priscilla, B and Nova, E}, title = {Associations of Dose Adjustment with Efficacy and Safety of Faricimab for Age-related Macular Degeneration Disorders: A Systematic Review and Meta-analysis.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502562}, doi = {10.1016/j.oftale.2026.502562}, pmid = {42002032}, issn = {2173-5794}, abstract = {This paper reviews the efficacy and safety of various dosing regimens and treatment cycles of intravitreal faricimab as therapy for Age-related macular degeneration (ARMD). The included studies were randomized controlled trials (RCTs) or post-hoc analyses of RCTs involving a population of ARMD or macular related disorder patients receiving faricimab therapy. Study outcomes were assessed by best-corrected visual acuity (BCVA) or central macular subfield thickness (CST). Data extracted from the journals included characteristics of the patient population, subgroup population, treatment used, therapeutic dose, treatment cycle, BCVA, CVA, number of populations with severe adverse events, and severe ocular adverse events. Study heterogeneity was assessed using the I[2] statistic, with values ≤40% considered homogeneous. A random effects model was applied when effect estimates crossed the line of no effect. Effect sizes were reported as mean differences with 95% confidence intervals. We included eight studies with a total of 8458 study populations. There are several doses that can be given (1.5 mg and 6 mg) and several cycles of administration (every 4, 8, 12, 16 weeks and personalized treatment interval). Faricimab 6 mg every sixteen weeks has shown a better effect than aflibercept and ranibizumab. These findings suggest that faricimab 6 mg administered every sixteen weeks demonstrated superior outcomes in improving best-corrected visual acuity (BCVA) and greater reductions in central subfield thickness (CST) compared to aflibercept 2 mg every eight weeks. However, a more frequent regimens were associated with significantly higher severe adverse events, especially ocular severe adverse events.}, }
@article {pmid42003716, year = {2026}, author = {Airody, A and Hanson, RLW and Bunola-Hadfield, I and Sivaprasad, S and Morland, AB and Chakravarthy, U and Gale, RP and , }, title = {The long-term impact of neovascular age-related macular degeneration undergoing routine treatment in first and second eyes on vision-related quality-of-life: FASBAT Report 3.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70150}, pmid = {42003716}, issn = {1755-3768}, support = {OAP030A2401T//Novartis Pharmaceuticals Corporation/ ; }, abstract = {PURPOSE: The study evaluated the long-term effect on vision-related quality-of-life (VRQoL) of routinely treated neovascular age-related macular degeneration (nAMD) in first and second eyes.<br><br>METHODS: The FASBAT (Observing Fibrosis, macular Atrophy and Subretinal highly reflective material Before and After Treatment with anti-VEGF treatment) study followed individuals with new unilateral nAMD (first eye) undergoing routine treatment for up to 4.5&#x2009;years. Visual acuity (VA) was measured as part of routine care and VRQoL was assessed using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25).<br><br>RESULTS: Of the 424 participants, 307 had only the first eye affected by nAMD (mean age&#x2009;=&#x2009;76.5, SD&#x2009;=&#x2009;8.4&#x2009;years). The mean VA was 58.1 (SD&#x2009;=&#x2009;15.5) and 79.4 (SD&#x2009;=&#x2009;5.6) letters at baseline, and 58.4 (SD&#x2009;=&#x2009;20.9)/78.5 (SD&#x2009;=&#x2009;7.8) letters at 36-months in the affected and unaffected eyes, respectively. The mean composite NEI-VFQ-25 score was 87.1 (SD&#x2009;=&#x2009;11.9) at baseline and 85.2 (SD&#x2009;=&#x2009;13.5) at 36-months. One hundred and seventeen participants (mean age&#x2009;=&#x2009;77.6, SD&#x2009;=&#x2009;7.3&#x2009;years) developed second eye nAMD, with a mean of 18.9 (SD&#x2009;=&#x2009;10.2) months following the first eye. Mean VA in first and second eye was 56.3 (SD&#x2009;=&#x2009;19.3)/74.1 (SD&#x2009;=&#x2009;9.9) letters at the time of second eye development, and 51.1 (SD&#x2009;=&#x2009;22.5)/73.6 (SD&#x2009;=&#x2009;8.9) letters after 24-months. Mean composite NEI-VFQ-25 score was 81.4 (SD&#x2009;=&#x2009;14.6) and 79.1 (SD&#x2009;=&#x2009;17.2) at these time points.<br><br>CONCLUSIONS: Long-term VRQoL remains stable in unilateral treated nAMD. However, a clinically meaningful reduction in VRQoL occurs following development and treatment in the second eye which does not recover. It is important to offer appropriate support when the first and then second eye develop nAMD.}, }
@article {pmid42005206, year = {2026}, author = {Faustine, G and Bastion, MC}, title = {A Case Series of Familial Macular Drusen: Clinical, Imaging, and Diagnostic Considerations in the Spectrum Between Age-Related Macular Degeneration (AMD) and Other Macular Disorders.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e105478}, pmid = {42005206}, issn = {2168-8184}, abstract = {Familial clustering of macular drusen in younger adults can mimic age-related macular degeneration (AMD) but may reflect an underlying inherited macular disorder. We describe a 72-year-old Chinese woman with high myopia and advanced neovascular AMD in one eye, who presented with progressive visual decline. Despite anti-vascular endothelial growth factor therapy, vision remained poor. Concerned about familial risk, her three adult children were examined. All three adult children (aged 46, 38, and 36 years) were asymptomatic despite drusen being detected on examination. This multigenerational clustering of drusen at relatively young ages raises suspicion for a possible hereditary macular disorder. This case highlights the need for family screening and genetic evaluation in atypical AMD presentations.}, }
@article {pmid42005909, year = {2026}, author = {Lim, JI and Ambresin, A and Avery, RL and Chaikitmongkol, V and Eter, N and Gomi, F and Khanani, AM and London, NJS and Harrell, E and Margaron, P and Patel, S and Souverain, A and Yang, M and Lai, TYY}, title = {Reduction in Pigment Epithelial Detachment Thickness with Faricimab versus Aflibercept 2 mg during Head-to-Head Dosing in TENAYA/LUCERNE.}, journal = {Ophthalmology science}, volume = {6}, number = {5}, pages = {101148}, pmid = {42005909}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the effects of dual angiopoietin-2 (Ang-2)/VEGF-A pathway inhibition with faricimab versus VEGF pathway inhibition with aflibercept 2 mg on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: TENAYA/LUCERNE (NCT03823287/NCT03823300) post hoc analysis.<br><br>PARTICIPANTS: Patients with treatment-na&#xef;ve nAMD.<br><br>METHODS: Patients were randomized 1:1 to faricimab 6 mg up to every 16 weeks (n = 665) after 4 initial every-4-week (Q4W) doses or aflibercept 2 mg every 8 weeks (n = 664) after 3 Q4W doses. Pigment epithelial detachment was defined as retinal pigment epithelium (RPE) elevation width &#x2265;350 &#x3bc;m and graded as predominantly/purely serous (serous PED) or predominantly/only fibrovascular (fibrovascular PED). Large PED definition: thickness &#x2265;125 &#x3bc;m.<br><br>MAIN OUTCOME MEASURES: Pigment epithelial detachment thickness change from baseline during initial 12-week head-to-head dosing, proportion of patients with serous PED at the end of head-to-head dosing, and time to first reduction of maximum PED thickness by 50%.<br><br>RESULTS: Baseline PED characteristics were similar between arms. At week 12, the adjusted mean decrease from baseline in maximum PED thickness was greater with faricimab than aflibercept 2 mg in eyes with large (-119.1 [n = 500] vs. -101.4 &#x3bc;m [n = 496]; nominal P = 0.0028), serous (-136.1 [n = 128] vs. -108.2 &#x3bc;m [n = 114]; nominal P = 0.0147), and any type (-87.9 [n = 644] vs. -74.5 &#x3bc;m [n = 638]; nominal P = 0.0067) PED at baseline. The proportion of eyes with serous PED at baseline remaining serous at week 12 was lower with faricimab than aflibercept 2 mg (4.7% vs. 13.4%; nominal P = 0.0258). In eyes with large PED at baseline, the cumulative incidence of PEDs achieving time to first reduction of maximum PED thickness by 50% at week 12 was 35.3% with faricimab versus 25.7% with aflibercept 2 mg. The corresponding incidence in eyes with serous PED at baseline was 61.1% with faricimab versus 51.8% with aflibercept 2 mg. The incidence of RPE tears was low (faricimab, 2.9%; aflibercept 2 mg, 1.5%).<br><br>CONCLUSIONS: In TENAYA/LUCERNE, dual Ang-2/VEGF-A inhibition with faricimab elicited greater improvements in PED outcomes versus aflibercept 2 mg during head-to-head dosing. These findings are consistent with the greater drying of retinal fluid with faricimab during head-to-head dosing, which may allow for rapid treatment interval extension.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid42005954, year = {2026}, author = {Seddon, JM and De, D}, title = {The Macular Degeneration Preventive Diet and Lifestyle for Providers and Patients: From Evidence to Action.}, journal = {American journal of lifestyle medicine}, volume = {}, number = {}, pages = {15598276261438371}, pmid = {42005954}, issn = {1559-8284}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults, with both genetic and modifiable risk factors contributing to disease progression. Robust prospective evidence demonstrates that dietary patterns rich in lutein, zeaxanthin, and omega-3 fatty acids-particularly through green leafy vegetables, fatty fish, and Mediterranean diet adherence-reduce AMD progression risk by 20-56% across disease stages. Lifestyle factors including smoking cessation, weight management, and regular physical activity also confer protective benefits. Despite ample evidence, counseling about the benefits of these dietary and lifestyle behaviors remains underutilized in ophthalmic practice, largely due to inadequate medical education in preventive medicine and perceived barriers to implementation of such recommendations. This perspective examines the current evidence, highlights the gap between scientific evidence and clinical implementation, and proposes a framework for systematic reform. Recommendations include embedding nutrition education into medical school and residency training, establishing ocular nutrition as a continuing education requirement, and equipping clinicians with tools for incorporating these guidelines into routine AMD clinical care. Aligning ophthalmic practice with the recommended nutritional guidelines and other behavioral changes through the Macular Degeneration Preventive Diet and Lifestyle, represents a timely opportunity to translate evidence into interventions that preserve vision.}, }
@article {pmid42007660, year = {2026}, author = {Le, VH and El-Mulki, OS and Zhang, Y and Pan, H and Kumar, S and Shen, M and Beqiri, S and Badla, O and Berni, A and Kastner, J and Gregori, G and Rosenfeld, PJ and Wang, RK}, title = {Hyporeflective Core Drusen Cause an Artifactual Bending of Bruch's Membrane on OCT Images: Optical Mechanism and Proposed Quantitative Metrics.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {43}, doi = {10.1167/iovs.67.4.43}, pmid = {42007660}, issn = {1552-5783}, abstract = {PURPOSE: To investigate the optical mechanism and impact of the artifactual bending of Bruch's membrane (BM) beneath hyporeflective core drusen (hypoRCD) on optical coherence tomography (OCT).<br><br>METHODS: This observational and experimental laboratory study analyzed volumetric OCT scans with hypoRCD from an age-related macular degeneration (AMD) cohort. The optical mechanism underlying BM bending was examined using tissue phantoms with different oil droplets to model different refractive indices (RIs) of hyporeflective cores (hypoRCs). Three metrics were proposed to quantify hypoRCD: (1) hypocore bending index (CoreBI), (2) drusen bending index (DruBI), and (3) maximum bending index (Bmax). The impact of BM bending on choriocapillaris flow deficit (CCFD) analysis was assessed by comparing CCFD measurements before and after correcting BM segmentation under hypoRCD.<br><br>RESULTS: BM bending was consistently observed beneath the core region of hypoRCD in both structural OCT and optical attenuation coefficient (OAC) B-scans. Phantom experiments demonstrated that the bending was associated with differences in the RIs of the hypoRCs. The degree of bending, quantified by the CoreBI, increased with the RI of the core material (P < 0.001). The CCFD percentage beneath hypoRCD was significantly reduced by 25.9% &#xb1; 7.7% (P = 0.005) after correcting the BM segmentation. Morphological changes associated with the bending could be quantified using the three proposed metrics.<br><br>CONCLUSIONS: BM bending induced by hypoRCD is an artifactual OCT feature that reflects the optical properties of the hypoRCs. This morphological characteristic may improve our understanding of hypoRCD, raise cautions in quantitation of CCFDs under hypoRCD, and provide additional insights into their role in AMD.}, }
@article {pmid41999267, year = {2026}, author = {Delcourt, C and Hucteau, E and Gattoussi, S and Pérès, K and Delyfer, MN and Helmer, C and Korobelnik, JF}, title = {Association of treated neovascular AMD with disability and mood disorders: A longitudinal nationwide study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70130}, pmid = {41999267}, issn = {1755-3768}, support = {//Bayer Healthcare (Lille, France)/ ; }, abstract = {PURPOSE: To describe the associations of treated neovascular AMD with the risk of disability, falls, fractures and mood disorders in a large sample representative of the French population.<br><br>METHODS: Analyses were based on 77&#x2009;582 individuals belonging to the 'Echantillon G&#xe9;n&#xe9;raliste des B&#xe9;n&#xe9;ficiaires', a 1/97 random sample of the French population, aged 65&#x2009;years or more on 1 April 2009 and followed until 31 December 2019. Treated neovascular AMD (nAMD) was identified through the reimbursement of anti-VEGF drugs, intravitreal injections and after exclusion of other pathologies requiring the use of intravitreal anti-VEGFs. Activities of daily living (ADL) disability was identified using a previously developed algorithm, while falls, fractures, head trauma and mood disorders were identified using relevant ICD codes and medications. Associations of nAMD with outcomes were assessed using Cox models with nAMD as a time-dependent variable and adjustment for confounders.<br><br>RESULTS: During the study period, 1662 cases of incident nAMD were identified. After adjustment for age, sex, Charlson comorbidity index and number of drugs, nAMD was significantly associated with the occurrence of ADL disability (Hazard ratio (HR): 1.19, 95% confidence interval (CI): 1.08-1.30; p&#x2009;=&#x2009;0.0002) and of mood disorders (HR: 1.19, 95%CI: 1.07-1.32; p&#x2009;=&#x2009;0.002). Associations with falls, fractures and head trauma were not statistically significant.<br><br>CONCLUSION: Treated neovascular AMD remains associated with a 19% increased risk of disability and mood disorders, while no association was detected with falls, fractures and head trauma. These results are consistent with a major improvement in functional outcomes, with respect to the pre-anti-VEGF era.}, }
@article {pmid41999355, year = {2026}, author = {Thomsen, AK and Villarruel Hinnerskov, JM and Maung, M and Mutschler, A and Sadda, S and Sørensen, TL}, title = {Junctional sensitivity and atrophy progression rate of geographic atrophy secondary to age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70151}, pmid = {41999355}, issn = {1755-3768}, support = {00024226//Velux Fonden/ ; R29-A1337//Region Sj&#xe6;lland/ ; //Fight for Sight Denmark/ ; //Synoptik-Fonden/ ; //Dagmar Marshalls Fond/ ; //Grosserer L. F. Foghts Fond/ ; }, abstract = {PURPOSE: To determine the relationship between the baseline junctional retinal sensitivity measured with microperimetry and the atrophy progression rate in eyes with geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: In this prospective cohort study, patients with GA were examined with fundus autofluorescence (FAF) to determine the atrophy area at baseline and at follow-up of 13.1&#x2009;&#xb1;&#x2009;2.5&#x2009;months in order to determine the atrophy progression rate. Microperimetry and optical coherence tomography (OCT) were evaluated at baseline. Microperimetry was superimposed on the baseline FAF image to determine mean junctional sensitivity. Multivariable linear regression was performed adjusting for age, presence of junctional intraretinal hyperreflective foci (HRF), subretinal drusenoid deposits (SDD) and FAF pattern.<br><br>RESULTS: Fifty-six eyes with GA of 56 patients were included. There was a significant association between baseline junctional sensitivity and the atrophy progression rate in GA eyes (&#x3b2;, -8.84&#x2009;&#x3bc;m/year/dB; 95% CI, -16.56 to -1.11; p&#x2009;=&#x2009;0.026) tested with simple linear regression. However, when adjusting for age, structural factors and junctional FAF patterns in a multivariable linear regression model, the association between junctional sensitivity and atrophy progression rate was no longer statistically significant (&#x3b2;, -6.40&#x2009;&#x3bc;m/year/dB; 95% CI, -16.04 to 3.25; p&#x2009;=&#x2009;0.18). The diffuse trickling FAF pattern was independently and significantly associated with progression rate (p&#x2009;=&#x2009;0.019).<br><br>CONCLUSIONS: Microperimetric junctional sensitivity may have relevance in predicting atrophy progression rate in eyes with GA, although the FAF pattern may be of greater importance. Larger, longitudinal studies are necessary to further elucidate this relationship.}, }
@article {pmid41999445, year = {2026}, author = {Pearce, I and Dinah, C and Downey, L and Patwardhan, A and Vardarinos, A and Williams, G}, title = {Faricimab in Treatment-Naïve nAMD: Regional UK Real-World Experience.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, pmid = {41999445}, issn = {1865-8652}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease leading to significant vision loss. Previous standard of care, anti-vascular endothelial growth factor (anti-VEGF) monotherapy, requires frequent injections to maintain efficacy. Faricimab, which targets angiopoietin-2 and VEGF-A, has shown efficacy in patients with nAMD with extended dosing intervals in randomised controlled trials (RCTs). However, results from RCTs are often challenging to replicate in real-world practice. This study aimed to explore outcomes in patients with nAMD treated with faricimab in real-world settings in the UK.<br><br>METHODS: Newly diagnosed patients with nAMD receiving first-line faricimab between 2022 and 2024 were examined across six UK sites in England and Wales. Patients were generally treated per the National Institute of Health and Care Excellence (NICE)-recommended protocol for approximately 1&#xa0;year, with some deviations at individual sites. Outcomes reported included best-corrected visual acuity (BCVA), optical coherence tomography (OCT) fluid, retinal thickness, treatment intervals and safety. Data were analysed separately for each site; adverse event incidence was pooled.<br><br>RESULTS: The total number of eyes treated was 505 from 473 patients. Baseline characteristics were similar across sites, with a mean age of 77.0-82.0&#xa0;years. BCVA, OCT fluid and retinal thickness improvements from baseline were observed across all sites, irrespective of timepoint or treatment protocol. BCVA improvements from baseline ranged from&#x2009;+&#x2009;5.1 to&#x2009;+&#x2009;7.7 letters at the first post-loading visit and from&#x2009;+&#x2009;5.0 to&#x2009;+&#x2009;8.2 letters at 12&#xa0;months. Mean change in retinal thickness from baseline ranged from&#x2009;-&#x2009;92.3 to&#x2009;-&#x2009;127.7&#xa0;&#x3bc;m at 12&#xa0;months. Most patients received faricimab at intervals of&#x2009;&#x2265;&#x2009;8&#xa0;weeks following the loading phase. The pooled incidence of adverse events was low.<br><br>CONCLUSION: Faricimab demonstrated consistent visual and anatomical improvements in real-world UK settings across a heterogeneous group of patients with nAMD. Further real-world studies will be essential to confirm long-term safety and effectiveness in clinical practice.}, }
@article {pmid41999903, year = {2026}, author = {Domalpally, A and Chew, EY and Eydelman, MB and Keenan, TDL and Keane, PA and Lee, AY and Lee, CS and Lad, EM and Lim, JI and Lowenstein, A and Schmidt-Erfurth, U and Abramoff, MD and , }, title = {Reference Standard for Validation of Age-Related Macular Degeneration Screening Algorithms.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.04.013}, pmid = {41999903}, issn = {1549-4713}, abstract = {PURPOSE: Artificial intelligence (AI)-based screening models hold promise for identifying individuals with undiagnosed age-related macular degeneration (AMD) in non-specialist settings. A standardized reference framework for image labeling is needed to enable consistent training, validation, and deployment of AI based screening algorithms.The goal of the present study is to establish expert consensus on image -based reference standard for labeling AMD DESIGN: Modified Delphi consensus study Subjects/ Participants: fellowship-trained retina specialists, ophthalmologists, AI specialists, and imaging specialists METHODS: A prespecified Delphi process was conducted using structured surveys . Over two rounds, panelists assessed opinions on existing reference standards, including the AREDS scale and Beckman scale, as well as imaging modalities such as color, optical coherence tomography (OCT), and autofluorescence. The surveys also evaluated imaging features of AMD, including drusen, pseudodrusen, and pigment changes, as well as referral criteria. Consensus was defined using a 9-point Likert scale, with predefined statistical thresholds for agreement.<br><br>MAIN OUTCOME MEASURES: Agreement on key elements of a reference standard RESULTS: Consensus was reached on adopting the Beckman Classification as the level 1 reference standard (median score 8; agreement). OCT use for identifying key AMD features, including drusen, GA, and CNV, also reached consensus (median scores 8.5-9; agreement). Pigment change detection did not reach consensus (median 7.5; uncertain), and screening age thresholds showed non-consensus (median 8; uncertain). Referral thresholds reached consensus, including urgent referral for neovascular AMD and non-urgent referral for GA and intermediate AMD (median 9; agreement).<br><br>CONCLUSIONS: This study defines a consensus-based reference standard for labeling AMD from images for AI based screening. These recommendations are intended to support consistent AI model development and evaluation, while remaining distinct from clinical practice guidelines.}, }
@article {pmid41814412, year = {2026}, author = {Yin, W and Xu, M and Niu, Z and Gao, Y and Su, N and Song, Y and Liu, Q}, title = {Targeting CDH13 as a therapeutic strategy to mitigate pathological ocular angiogenesis.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41814412}, issn = {1479-5876}, support = {82471096//National Natural Science Foundation of China/ ; 82271100//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Anti-angiogenic therapies, which suppress pathological vessel growth in neovascular diseases such as diabetic retinopathy and neovascular age-related macular degeneration (nAMD), have transformed the clinical landscape. However, a critical unmet challenge is to shift the therapeutic paradigm from broad inhibition towards achieving vascular normalization, as non-selective angiogenic blockade can result in detrimental off-target effects. Consequently, the identification of novel molecular targets is imperative for developing more precise and effective treatment strategies.<br><br>METHODS: We evaluated CDH13 expression in fibrovascular membranes (FVMs) and nAMD derived from human using bioinformatics analysis and confirmed its presence in mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) via western blot, RT-PCR, and immunostaining. We then investigated CDH13 function through in vitro transwell, wound healing, and EdU assays following its knockdown, and extended our analysis in vivo using isolectin B4 staining, fundus fluorescein angiography, and immunofluorescent staining in mice subjected to CDH13 knockdown or treated with the oral inhibitor GW3965. Finally, we employed dual-luciferase reporter assays, RT-PCR, and western blot to elucidate the underlying molecular mechanisms.<br><br>RESULTS: We observed substantial CDH13 expression in endothelial cells of human nAMD fibrovascular membranes and mouse models of OIR and CNV. CDH13 knockdown inhibited pathological vessel growth, promoted vascular normalization, and induced a pro-regenerative environment. Mechanistically, hypoxia inhibits NR2F2, thereby de-repressing CDH13 transcription and activating the NF-&#x3ba;B pathway to drive vascular dysfunction. Additionally, oral GW3965 treatment reduced LDL deposition and alleviated pathological neovascularization through LXR activation, countering CDH13-mediated effects.<br><br>CONCLUSION: Together, these findings establish CDH13 as a promising therapeutic target for driving vascular normalization in neovascular retinal diseases.<br><br>GRAPHICAL ABSTRACT: [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07972-y.}, }
@article {pmid41992419, year = {2026}, author = {Chen, YS and Chang, HC and Chi, SC and Tanaka, K and Chen, SJ and Lin, TC}, title = {Different aflibercept regimens for wet age-related macular degeneration: A systematic review and network meta-analysis.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001379}, pmid = {41992419}, issn = {1728-7731}, abstract = {BACKGROUND: Intravitreal aflibercept injection for wet age-related macular degeneration (AMD) was initially approved with a regimen consisting of three monthly loading doses followed by maintenance doses every 8 weeks. Alternative regimens with a reduced treatment burden have been explored. The treat-and-extend (TAE) regimen involves gradually extending the treatment interval in accordance with disease activity, and the pro re nata (PRN) regimen involves administering injections only when signs of disease activity are observed during follow-up visits. This study evaluated these alternative regimens aimed at reducing treatment burden in real-world clinical practice.<br><br>METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant randomized controlled trials (RCTs). A random-effects model was adopted for network meta-analysis. Results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Methodological quality of the included RCTs was assessed using the Cochrane risk-of-bias 2.0 tool.<br><br>RESULTS: Seven RCTs (1,683 patients with wet AMD) were included in the network meta-analysis. No significant interregimen differences were observed in visual acuity or central retinal thickness. The TAE and PRN regimens required significantly fewer injections than did bimonthly and monthly regimens, respectively (TAE vs. bimonthly: SMD -1.091, 95% CI -2.030 to -0.153; TAE vs. monthly: SMD -3.024, 95% CI -4.584 to -1.465; PRN vs. Bimonthly: SMD -1.919, 95% CI -3.307 to -0.532; PRN vs. Monthly: SMD -3.852, 95% CI -5.717 to -1.988). However, injection count did not differ significantly between the TAE and PRN regimens (TAE vs. PRN: SMD 0.828, 95% CI -0.847 to 2.503). Nonetheless, the TAE regimen was associated with fewer clinic visits than the PRN regimen.<br><br>CONCLUSION: The TAE regimen maintains efficacy while reducing treatment burden in patients with wet AMD receiving intravitreal aflibercept.}, }
@article {pmid41993457, year = {2026}, author = {Cakir, B and Yeh, TC and Lin, CH and Wu, MR and Boilard, &#xc9; and Pelletier, M and Singh, AM and Breton, Y and Patel, S and Benson, T and Almeida, DR and Wang, S and Mahajan, VB}, title = {Mitochondrial Transplantation in the Eye: A Review and Evaluation of Surgical Approaches.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.04.06.716722}, pmid = {41993457}, issn = {2692-8205}, abstract = {PURPOSE: Mitochondrial dysfunction contributes to major blinding diseases, including age-related macular degeneration and glaucoma. Although mitochondrial transplantation has shown therapeutic potential in multiple organ systems, translation to the eye remains limited, partly due to uncertainty regarding optimal delivery. We summarize the biologic rationale and preclinical evidence supporting ocular mitochondrial transplantation and present feasibility data evaluating clinically relevant delivery routes.<br><br>METHODS: We conducted a focused narrative review of ocular mitochondrial transplantation. For feasibility experiments, mitochondria with an endogenous fluorescent dye were isolated from liver donor mice. Postnatal day 7 pups received subretinal injections, and adult CD1 mice received intravitreal injections, including optic nerve head directed delivery. Eyes were analyzed using fluorescence microscopy and immunohistochemistry. Mitochondrial uptake was assessed in cultured retinal pigmental epithelial (RPE) cells using co-incubation assays. Suprachoroidal delivery feasibility was evaluated in cadaveric human near-real surgical specimens using a novel dedicated suprachoroidal injector.<br><br>RESULTS: The literature on ocular mitochondrial transplantation remains limited and consists primarily of small preclinical studies using intravitreal delivery and imaging-based detection. In our experiments, intravitreal delivery produced donor signals predominantly within inner retinal layers, with enrichment along retinal nerve fiber bundles when directed toward the optic nerve head. Cultured RPE cells demonstrated dose-dependent uptake of exogenous mitochondria. Subretinal delivery localized donors signal to the RPE and adjacent outer retina. Suprachoroidal injections demonstrated procedural feasibility with reliable access to the suprachoroidal space and visible injectate distribution.<br><br>CONCLUSIONS: Ocular mitochondrial transplantation is in an early stage of investigation. Our feasibility data indicate that established posterior-segment delivery routes expose distinct retinal compartments and that route selection strongly influences anatomic distribution. Further studies are needed to verify intracellular uptake, define dosing and durability, and evaluate safety in disease-relevant models.}, }
@article {pmid41993761, year = {2026}, author = {Bousamri, A and Al-Shehri, M and Mestarihi, M and Almutairi, TB and Alaredhi, M and Mahanna, B and Alharbi, F}, title = {Clinical Outcomes of High-Dose Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {18}, number = {4}, pages = {e106769}, pmid = {41993761}, issn = {2168-8184}, abstract = {Polypoidal choroidal vasculopathy (PCV) is a distinct subtype of neovascular macular disease with variable responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. This systematic review and meta-analysis evaluated the visual, anatomical, and lesion-regression outcomes of intravitreal aflibercept 8 mg, a formulation developed to extend dosing intervals while maintaining efficacy, in patients with PCV. PubMed, Embase, Scopus, Web of Science, and Google Scholar were searched from inception to March 12, 2026 (PROSPERO: CRD420261339679). Eligible studies enrolled adults with indocyanine green angiography (ICGA)-confirmed PCV treated with aflibercept 8 mg and reported at least one co-primary outcome: change in best-corrected visual acuity (BCVA), central retinal or subfield thickness (CRT/CST), or complete polyp regression. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2), Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and Joanna Briggs Institute (JBI) appraisal tools. Complete polyp regression was analyzed using a generalized linear mixed model with a logit link; continuous outcomes were pooled using restricted maximum likelihood estimation with the Hartung-Knapp-Sidik-Jonkman correction. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Five studies encompassing 362 eyes (245 treated with aflibercept 8 mg) were included. The pooled complete polyp regression rate was 57% (95% confidence interval (CI), 39%-73%; I[2]=55.9%; k=3). The pooled mean CRT/CST change was -157.8 µm (95% CI, -176.9 to -138.7 µm; I[2]=0%; k=2), though the estimate was predominantly driven by a single study contributing 95.5% of the inverse-variance weight. BCVA outcomes were not pooled due to metric incompatibility and clinical heterogeneity; however, individual study results were directionally favorable, with Early Treatment Diabetic Retinopathy Study (ETDRS) gains of +8.4 to +9.5 letters at 48 weeks in the largest contributing study. Extended dosing intervals were maintained in 80.5% (q12) and 86.5% (q16) of treated eyes at 48 weeks. One study reported intraocular inflammation in 10.8% of the overall neovascular age-related macular degeneration (AMD) cohort in that study, a safety signal not observed in the remaining studies. The certainty of evidence was low for CRT/CST change and very low for polyp regression and BCVA. Available evidence suggests that aflibercept 8 mg may produce clinically relevant polyp regression and substantial anatomical improvement in PCV, with a potential reduction in injection frequency. However, given the low to very low certainty of the current evidence base across all co-primary outcomes, definitive efficacy and safety conclusions cannot yet be drawn. Prospective, PCV-specific trials with standardized outcome reporting are needed.}, }
@article {pmid41994559, year = {2026}, author = {Cheng, CK and Tsai, CJ and Bai, CH}, title = {Reassessing high-dose ranibizumab in the era of durable anti-VEGF therapy.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1802903}, pmid = {41994559}, issn = {2674-0826}, }
@article {pmid41995082, year = {2026}, author = {Patel, MK and Piedade, WP and Famulski, JK}, title = {Cdhr1a and pcdh15b may link photoreceptor outer segments with calyceal processes revealing a potential mechanism for cone-rod dystrophy.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, doi = {10.7554/eLife.102258}, pmid = {41995082}, issn = {2050-084X}, support = {P20GM103436//KYINBRE core facility voucher/ ; }, mesh = {Animals ; *Cadherins/metabolism/genetics ; Zebrafish ; Humans ; *Cone-Rod Dystrophies/pathology/genetics/metabolism ; Cadherin Related Proteins ; *Zebrafish Proteins/metabolism/genetics ; Mice ; *Retinal Photoreceptor Cell Outer Segment/metabolism ; }, abstract = {Cone-rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell degeneration. Mutations in CDHR1, a photoreceptor-specific cadherin, have been found to be associated with the incidence of CRD. While studying the function of CDHR1, we observed that the localization of the zebrafish homologue, cdhr1a, resembles that of calyceal process (CPs). When co-labeling CPs using pcdh15b, we observed that cdhr1a, in the outer segment (OS), juxtaposes with pcdh15b, found in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, gerbil, and mouse. Using immunoprecipitation and K652 cell aggregation assays, we demonstrate that pcdh15b and cdhr1a can interact and thus potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a cdhr1a mutant line (cdhr1a[fs*146]). Homozygous cdhr1a[fs*146] mutants exhibit minor cone OS defects starting at 15 dpf and severe OS disruption and cell loss by 3 months. Shortening of CPs coincided with cone OS defects which were significantly exacerbated when combined with the loss of pcdh15b. Rod OS defects were mild and delayed until 3-6 months. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs and maintain OS integrity.}, }
@article {pmid41995436, year = {2026}, author = {Pu, J and Zhuang, X and Hao, X and Li, M and Su, Y and He, G and He, Y and Zhang, G and Wen, F}, title = {Longitudinal Tracking of Photoreceptor Integrity in Neovascular AMD: Early Restoration Predicts 24-Month Structural and Visual Outcomes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {41}, doi = {10.1167/iovs.67.4.41}, pmid = {41995436}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Follow-Up Studies ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Fluorescein Angiography ; *Photoreceptor Cells, Vertebrate/pathology ; Ranibizumab/therapeutic use/administration &amp; dosage ; Time Factors ; }, abstract = {PURPOSE: The purpose of this study was to longitudinally characterize photoreceptor band changes over 24 months and determine whether early restoration predicts long-term outcomes in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study enrolled treatment-na&#xef;ve patients with nAMD receiving anti-vascular endothelial growth factor therapy following 3 + pro re nata (PRN) regimen. Impaired areas of outer nuclear layer (ONL), ellipsoid zone (EZ), external limiting membrane (ELM), and interdigitation zone (IZ) were quantified at baseline, 1 week, 1, 2, 3, 12, and 24 months, and associations between early restoration and long-term structural and visual outcomes were assessed.<br><br>RESULTS: Eighty-two eyes from 82 patients (mean age = 65.15 &#xb1; 7.47 years) completed a 24-month follow-up. All bands showed significant changes over 2 years (P < 0.05 for all). Only EZ demonstrated significant early restoration at 1 week and 1 month (P = 0.041 and 0.004, respectively). Month 3 restoration of all bands predicted corresponding 1- and 2-year structural changes (Std&#x3b2; = 0.432-0.912, P < 0.05, except for 2-year ONL and IZ: P = 0.201 and 0.304, respectively). Moreover, month 2 ONL changes also independently predicted long-term ONL changes (P = 0.011 and P < 0.001 for 1 and 2 years, respectively). For visual outcomes, month 3 IZ restoration predicted 1-year BCVA improvement (Std&#x3b2; = -0.334, P = 0.032), whereas month 2 ONL restoration predicted 2-year BCVA improvement (Std&#x3b2; = -0.378, P = 0.003).<br><br>CONCLUSIONS: Photoreceptor bands showed layer-specific restoration patterns, with EZ responding earliest. Early restoration at months 2 to 3 predicted long-term outcomes, with ONL and IZ as independent visual predictors.}, }
@article {pmid41998200, year = {2026}, author = {Cheah, IK and Fong, ZW and Chen, L and Tang, RMY and Zhou, L and Yanagi, Y and Cheng, CY and Su, X and Li, X and Teo, KYC and Cheung, CMG and Tan, TE and Halliwell, B}, title = {Ergothioneine as a potential protective agent against macular degeneration and other eye disorders.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-48438-x}, pmid = {41998200}, issn = {2045-2322}, support = {OFYIRG22jul-0027//National Medical Research Council/ ; R1752/75/2020//SERI Lee Foundation Grant/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO3, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye. These findings identify a strong association between low ET levels and AMD, warranting further studies to determine whether ET supplementation can modify AMD risk or progression.}, }
@article {pmid41998289, year = {2026}, author = {Küçükerdönmez, C and Tedford, SE}, title = {Response to "Letter to the Editor Regarding 'Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration'".}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-026-01383-4}, pmid = {41998289}, issn = {2193-8245}, }
@article {pmid41998290, year = {2026}, author = {Karakosta, C and MacLaren, RE}, title = {Letter to the Editor Regarding "Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration".}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41998290}, issn = {2193-8245}, }
@article {pmid41987023, year = {2026}, author = {Horita, S and Saki, M and Takigawa, S and Kanai, Y and Murotani, K and Gomi, F}, title = {Ocular pharmacokinetics of tivozanib eye drops in patients with neovascular age-related macular degeneration: comparison with phase 1 trials of oral tivozanib in solid tumors.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41987023}, issn = {2056-9920}, abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD) but is invasive and burdensome for patients. To overcome these obstacles, tivozanib, a pan-VEGF receptor inhibitor approved for renal cell carcinoma, is in development as eye drops. The phase 1 study of a 3-week administration of tivozanib eye drops showed a preferable safety profile and exploratory efficacy signs in Japanese patients with nAMD. During eye drop administration, two drug delivery pathways affect ocular pharmacokinetics, either directly through the ocular tissues or through systemic circulation. To assess the ocular pharmacokinetics of tivozanib eye drops, we conducted an integrated analysis of systemic adverse event occurrence and systemic exposure in patients with nAMD treated with tivozanib eye drops and in patients with cancer treated with oral tivozanib, using previous phase 1 study results. Systemic exposure was significantly lower with tivozanib eye drops versus oral tivozanib, with no drug-related hypertension due to the systemic pan-VEGF receptor inhibition observed, suggesting systemic VEGF receptors are not fully inhibited by tivozanib. Exploratory efficacy signs in patients with nAMD after short-term use of tivozanib eye drops also suggest tivozanib might reach the retina and inhibit VEGF receptors, although further long-term efficacy studies are warranted. Given the integrated analysis, we hypothesize that tivozanib eye drops could predominantly be delivered to the posterior eye segment through the ocular tissues, with limited contribution by the systemic drug delivery pathway. This hypothesis provides meaningful insights into the ocular pharmacokinetics of tivozanib eye drops.}, }
@article {pmid41987034, year = {2026}, author = {Mohamed, MI and Halwag, MI and Mahmoud, NH and Salib, M and Nada, MA}, title = {Migraine as a risk factor for retinal vascular events and maculopathies: a systematic review and meta-analysis of 47 million individuals.}, journal = {The journal of headache and pain}, volume = {}, number = {}, pages = {}, doi = {10.1186/s10194-026-02353-8}, pmid = {41987034}, issn = {1129-2377}, }
@article {pmid41987176, year = {2026}, author = {Zhang, Y and He, W and Wang, C and Liu, B and Wen, J and Zhao, Y and Zhang, Y and Liu, L and Yang, Q and Li, J and Dong, Y and Zhang, X and Xu, Q and Zhai, G and Ye, L and Qu, Y}, title = {A sequential dual-drug delivery system for multi-target inhibition of subretinal fibrosis.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04390-6}, pmid = {41987176}, issn = {1477-3155}, abstract = {BACKGROUND: Subretinal fibrosis (SRF), a severe vision-threatening complication secondary to neovascular age-related macular degeneration (nAMD), remains a major clinical challenge due to its complex pathogenesis and prolonged disease course. The fibrotic process is driven by multiple synergistic factors, including chronic inflammation, hypoxia, epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and pathological neovascularization, which collectively lead to the ineffectiveness of conventional anti-vascular endothelial growth factor (VEGF) monotherapies in halting disease progression.<br><br>RESULTS: This study developed a sequential dual-drug delivery system based on the terpolymer P(NIPAM-co-AA-co-HEMA) hydrogel (NAHGel), designed to achieve multi-targeted regulation from the pathological microenvironment to downstream fibrotic processes. NAHGel exhibits excellent thermal responsiveness, biomechanical stability, and biodegradability, and is co-loaded with matrine (MT) and cRGD-modified sorafenib liposomes (SF/cLP). The hydrogel undergoes thermal contraction to enable the rapid release of hydrophilic MT, exerting anti-inflammatory and anti-hypoxic effects. As the hydrogel progressively degrades, SF/cLP is released in a delayed manner and, under cRGD mediation, is targeted to RPE cells and vascular endothelial cells. This enables modulation of key pathways including TGF-&#x3b2;2/MEK1/2/ERK1/2 and HIF-&#x3b1;/VEGF/PDGF, thereby inhibiting EMT and endothelial proliferation. In a laser-induced SRF mouse model, MT&#x2009;+&#x2009;SF/cLP@NAHGel formed a stable in situ gel within 24&#xa0;h after intravitreal injection and remained structurally intact in the dynamic vitreous environment, enabling sustained retention for up to 8 months. Imaging and histological analyses demonstrated that, compared with aflibercept and other group, this system significantly reduced choroidal neovascularization and fibrotic lesion areas. Transcriptomic analysis further confirmed its broad inhibition of signaling pathways related to inflammation, angiogenesis, and fibrosis, with marked downregulation of key mediators including VEGFA, TGF-&#x3b2;2, TNF-&#x3b1;, and HIF-1&#x3b1;.<br><br>CONCLUSION: MT&#x2009;+&#x2009;SF/cLP@NAHGel achieves sequential drug release and multi-targeted synergy to intervene in key pathological processes such as inflammation, hypoxia, EMT, and pathological neovascularization, thereby effectively halting SRF progression. Combining sustained therapeutic efficacy with excellent biosafety, this system holds strong translational potential as a long-acting treatment strategy for SRF and other multifactorial retinal diseases.}, }
@article {pmid41987778, year = {2026}, author = {Li, M and Gu, A and Li, H and Li, Y and Liang, R and Su, T and Wu, Y}, title = {Machine-learning for age-related macular degeneration using multimodal fundus data.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1756787}, pmid = {41987778}, issn = {2296-858X}, abstract = {OBJECTIVE: To develop an integrated model that combines multimodal fundus image features for accurately predicting the individualized risk of progression from early to late stages of age-related macular degeneration (AMD).<br><br>METHODS: A retrospective analysis was conducted on the data of 324 patients with AMD. The patients were randomly divided into a training set (n = 227) and a validation set (n = 97) at a ratio of 7:3. The follow-up period was 3 years, and patients with disease progression were defined as the progression group. In the training set, indicators related to prognosis were screened through univariate analysis. After variable compression by LASSO regression, independent influencing factors for poor prognosis were determined using multivariate logistic regression. Random Forest, Support Vector Machine, XG BOOST, and K-Nearest Neighbor algorithm prediction models were constructed using Python software. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC), and the optimal model was selected.<br><br>RESULTS: There were no significant differences in the baseline characteristics between the training set and the validation set patients (P > 0.05), indicating comparability. In the training set, multivariate logistic regression analysis showed that pigmentary abnormalities, the total area of drusen in the macular area, and the ellipsoid zone were independent risk factors for disease progression (P < 0.05), while subfoveal choroidal thickness and choroidal capillary blood flow density were independent protective factors (P < 0.05). The AUC values of the Random Forest model (0.779 in the training set and 0.700 in the validation set) were significantly higher than those of the K-Nearest Neighbor algorithm (0.717 in the training set and 0.596 in the validation set), the Support Vector Machine model (0.768 in the training set and 0.646 in the validation set), and XG BOOST (0.702 in the training set and 0.762 in the validation set), making it the optimal prediction model.<br><br>CONCLUSION: In this study, an AMD progression prediction model based on multimodal fundus images was successfully developed, which can effectively identify patients at high risk of progression and provide a new paradigm for clinical individualized precision medicine.}, }
@article {pmid41987800, year = {2026}, author = {Garcia-Atutxa, I and Martinez-Baliu, L and Villanueva-Flores, F}, title = {Robust benchmarking of DeepLabv3 hybrid models for multiclass fundus screening and referable-disease triage on the FIVES dataset.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1771083}, pmid = {41987800}, issn = {2296-858X}, abstract = {BACKGROUND: Automated analysis of color fundus photographs can support scalable screening for diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, but single-run reporting and accuracy-only summaries can mask clinically relevant instabilities and failure modes.<br><br>METHODS: Using the public FIVES dataset, we benchmarked six deep learning configurations for four-class fundus screening (AMD, DR, glaucoma, normal): three DeepLabv3-backbone hybrids (ResNet50, DenseNet121, EfficientNet-B0) and three backbone-only classifiers. All experiments were evaluated using five independent stratified splits generated with different random seeds (n = 5 runs), each defining a distinct 20% held-out test set. Models were trained on the remaining 80% (training/validation), and all reported metrics are computed on the 20% test set of each run and summarized as mean &#xb1; SD across runs. Performance was summarized with accuracy, sensitivity, specificity, and one-vs.-rest AUC; we further characterized clinical behavior via row-normalized confusion matrices, per-class precision/recall/F1, and a screening-style binary triage setting (referable = AMD &#x222a; DR &#x222a; glaucoma vs. normal).<br><br>RESULTS: Hybrid models consistently achieved higher discrimination than simple classifiers (AUC 0.969-0.979 vs. 0.908-0.920), despite similar accuracies (0.924-0.941). The selected model, DeepLabv3-DenseNet121, reached the highest AUC (0.979 &#xb1; 0.009). Class-wise analysis revealed strong performance for Normal (F1 0.970 &#xb1; 0.014) and Glaucoma (F1 0.896 &#xb1; 0.048), while DR was the main bottleneck (sensitivity 0.738 &#xb1; 0.117), with most DR errors redistributed to AMD (13.6%) and Glaucoma (12.0%) and minimal confusion with Normal (0.5%). In binary triage, the model achieved sensitivity 0.993 &#xb1; 0.011 and specificity 0.963 &#xb1; 0.034, with PPV 0.987 &#xb1; 0.013 and NPV 0.980 &#xb1; 0.032, and a stable referral rate (&#x223c;0.73-0.77) across runs.<br><br>CONCLUSION: DeepLabv3-based hybrids provide a robust advantage in AUC for multiclass fundus screening on FIVES. The residual risk concentrates in the DR-AMD-Glaucoma decision boundary, suggesting that deployment-oriented policies should prioritize conservative handling of DR-adjacent cases while leveraging the stability of Normal predictions for screening workflows.}, }
@article {pmid41988431, year = {2026}, author = {Auer, EA and Gnanaraj, R and Lynch, AM and Mandava, N and Palestine, AG and Mathias, MT and Manoharan, N and Lisker-Cervantes, A and de Carlo Forest, TE and Kohrt, WM and Patnaik, JL}, title = {Menopausal Hormone Therapy and Conversion from Intermediate to Advanced Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261428770}, pmid = {41988431}, issn = {2474-1272}, abstract = {Purpose: To evaluate the relationship between self-reported menopausal hormone replacement therapy use and conversion to an advanced form of AMD among female patients with intermediate AMD (iAMD). Methods: Female patients with iAMD enrolled in the University of Colorado AMD Registry between July 2014 and July 2024 were included in this prospective cohort study, with follow-up through November 2024. Conversion to an advanced form of AMD, either advanced non-neovascular AMD or neovascular AMD, was assessed by review of patients' multimodal imaging. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess time to conversion. Hazard ratios (HRs) with 95% CIs are presented for multivariable models. Results: Among 285 female patients with iAMD, the mean (±SD) follow-up time was 36.3 ± 26.7 months. In a total of 82 patients (28.8%), conversion to advanced AMD occurred during follow-up. In univariate analysis, a history of ever having used hormone replacement therapy (55.4%), compared with never having used hormone replacement therapy (44.6%), was not associated with conversion to either of the advanced forms of AMD. In multivariable analysis, patients who had ever used hormone replacement therapy did not have significantly elevated risks of conversion to advanced non-neovascular AMD (HR, 1.03, 95% CI, 0.54-1.96; P = .94) or neovascular AMD (HR, 2.10, 95% CI, 0.86-5.02; P = .10). Conclusions: Among female patients with iAMD, self-reported use of hormone replacement therapy was not associated with an increased risk of conversion to either of the advanced forms of AMD.}, }
@article {pmid41988735, year = {2026}, author = {Sun, H and Gao, E and Li, Y and Xiang, D and Lu, F and Zhou, Y and Zhu, W and Shi, F and Nie, B and Chen, X and Zhang, L and Cai, J and Peng, D and Peng, T}, title = {Refining feature representation for accurate fundus lesion segmentation.}, journal = {Medical physics}, volume = {53}, number = {4}, pages = {e70441}, doi = {10.1002/mp.70441}, pmid = {41988735}, issn = {2473-4209}, support = {62371328//National Nature Science Foundation of China/ ; 61971298//National Nature Science Foundation of China/ ; 62371326//National Nature Science Foundation of China/ ; 62271337//National Nature Science Foundation of China/ ; 62471326//National Nature Science Foundation of China/ ; BK20231310//Natural Science Foundation of Jiangsu Province/ ; 24KJB510042//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; JSTJ-2024-434//Technology Young Science and Technology Talent Support Project/ ; PRJ2022008//DKU Education Development Fund/ ; }, mesh = {*Image Processing, Computer-Assisted/methods ; Humans ; *Fundus Oculi ; Deep Learning ; Choroidal Neovascularization/diagnostic imaging ; Macular Degeneration/diagnostic imaging ; Retina/diagnostic imaging ; }, abstract = {BACKGROUND: Accurate segmentation of retinal lesions is essential for early detection of age-related macular degeneration (AMD), particularly its key indicators, choroidal neovascularization (CNV) and choroidal non-perfusion (CNP). However, the highly variable shapes and appearances of lesions pose substantial challenges for automated segmentation.<br><br>PURPOSE: To tackle these challenges, we propose a deep-learning model, the Retinal Feature Enhancement Network (RFENet), designed to improve the accuracy and robustness of retinal lesion segmentation under challenging imaging&#xa0;conditions.<br><br>METHODS: RFENet builds upon the UNeXt backbone and introduces two modules tailored for retinal lesion segmentation: an Adaptive Feature Refinement Unit (AFRU), which selectively emphasizes informative features, and an Optimized Channel-Wise Convolution Unit (OCCU), which captures fine structural details in irregular lesions. Two expert-annotated datasets were used: 1070 OCT B-scans from 83 CNV patients and 184 FFA images from 107 CNP patients. Images were split at the patient level into training (70%), validation (10%), and test (20%) sets. Performance was compared against state-of-the-art segmentation models, including UNet++, Swin-UNet, SelfReg-UNet, DAEFormer, and Mamba-UNet. Evaluation metrics included Dice coefficient and Intersection over Union (IoU). Statistical significance was assessed using paired two-tailed t-tests (&#x3b1; = 0.05 $\alpha = 0.05$), and effect sizes were reported with Cohen's d $d$ .<br><br>RESULTS: On the CNV dataset, RFENet achieved a Dice of 82.50% and an IoU of 71.66%, with clear improvements over competing models. On the CNP dataset, RFENet achieved a Dice of 74.43% and an IoU of 60.80%, slightly surpassing the best benchmark. Most pairwise comparisons were statistically significant, including CNV compared with Swin-UNet and SelfReg-UNet (p < $<$ 0.001) and CNP compared with DAEFormer (p = $=$ 0.035). Statistical analyses, including effect size evaluation, further confirmed the robustness of these improvements, with the most notable gains observed in the CNV&#xa0;dataset.<br><br>CONCLUSIONS: RFENet demonstrated consistent improvements over strong benchmarks on both CNV and CNP tasks, with statistical evidence supporting the reliability of these gains. These results indicate that RFENet provides a reliable technical advance for automated segmentation of CNV and CNP lesions associated with AMD. To facilitate reproducibility and further research, the source code is publicly available at https://github.com/HaoSun223/RFENet.}, }
@article {pmid41989239, year = {2026}, author = {Jonas, JB and Panda-Jonas, S and Jonas, RA and Wang, YX}, title = {Prevalence and associations of hyper-reflective bodies in the posterior vitreous: The Beijing eye study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70139}, pmid = {41989239}, issn = {1755-3768}, support = {82271086//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: To assess prevalence and associations of intra-vitreal hyper-reflective bodies (vHRBs) in the posterior vitreous in a general population.<br><br>METHODS: Participants of the population-based Beijing Eye Study underwent systemic and ophthalmological examinations. We included into this study a randomly selected group of normal eyes without retinal diseases and a randomly selected group of eyes with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PVC) or central serous choroidopathy (CSC). Using serial optical coherence tomography scans of the posterior fundus region, we searched for vHRBs in the posterior vitreous compartment.<br><br>RESULTS: The study consisted of 1347 eyes (age: 64.3&#x2009;&#xb1;&#x2009;9.8&#x2009;years, range: 50-91&#x2009;years; axial length: 23.04&#x2009;&#xb1;&#x2009;1.00&#x2009;mm, range: 19.39-28.93&#x2009;mm). vHRB were detected in 314/1347 eyes (23.3%; 95% confidence interval [CI]: 21.1, 25.6), that is, in 137 out of 447 normal eyes (28.9%; 95% CI: 24.8, 33.0), 110/458 eyes with early AMD (24.0%; 95% CI: 20.1, 27.9), 45/278 eyes with intermediate AMD (16.2%; 95% CI: 11.8, 20.5), 3/35 eyes with PCV (8.6%; 95% CI: 0.00, 18.3), and in 19/94 eyes with CSC (20.2%; 95% CI: 11.9, 28.5). In multivariable analysis, higher vHRB prevalence was associated with younger age (OR: 0.93; 95% CI: 0.91, 0.95; p&#x2009;<&#x2009;0.001), shorter axial length (OR: 0.69; 95% CI:0.56, 0.84; p&#x2009;<&#x2009;0.001), and lower stage of posterior vitreous detachment (OR: 0.53; 95% CI: 0.44, 0.64; p&#x2009;<&#x2009;0.001). It was independent of AMD stage (p&#x2009;=&#x2009;0.87), and prevalence of PCV (p&#x2009;=&#x2009;0.67) and CSC (p&#x2009;=&#x2009;0.40). Higher amount of vHRBs (multivariable linear regression analysis) correlated with younger age (beta: -0.21; B: -0.02; 95% CI: -0.03, -0.02; p&#x2009;<&#x2009;0.001), shorter axial length (beta: -0.07; B: -0.09; 95% CI: -0.16, -0.02; p&#x2009;=&#x2009;0.009) and lower stage of posterior vitreous detachment (beta: -0.15; B: -0.13; 95% CI: -0.19, -0.08; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: vHRBs were detected in one out of four normal eyes of individuals aged 50+ years, in dependence on younger age, shorter axial length and lower degree of posterior vitreous detachment. They were independent of a concurrence of AMD, PCV and CSC.}, }
@article {pmid41989896, year = {2026}, author = {Wen, Y and Zeng, Y and Bi, L and Zhao, X and Shi, W and Fu, H and Sheng, B}, title = {M2Net: Multimodal Multitask Mutual Learning for Anti-VEGF Efficacy Prediction.}, journal = {IEEE transactions on medical imaging}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TMI.2026.3684331}, pmid = {41989896}, issn = {1558-254X}, abstract = {Age-related macular degeneration with abnormal blood vessel growth (neovascular AMD) is the leading cause of vision loss in elderly populations. While anti-VEGF injections are the standard treatment, they present financial burdens for patients and vary in effectiveness. Predicting treatment efficacy is therefore crucial for patient care. Current prediction methods fail to fully integrate information from different imaging techniques, typically focusing on either forecasting vision improvements or generating post-treatment images-but not both simultaneously. This approach overlooks the important relationship between these tasks. We present M2Net, a novel joint generation and classification network based on Multimodal Multitask Mutual learning, to simultaneously predict changes in visual acuity and generate post-treatment retinal images. M2Net employs a dual-branch structure that processes both fundus photographs and Optical Coherence Tomography (OCT) scans to improve prediction accuracy. Our framework includes two key innovations: the Multimodal Collaborative Treatment Efficacy Prediction module, which interacts the features between the two modalities and provides initial visual acuity change classification to guide the generation of post-treatment images; and the Pre-Post Treatment Image Joint Analysis module, which identifies both common and changing features between pre-treatment and post-treatment images to enhance prediction accuracy. To validate our approach, we created the dataset (MMPD) containing paired multimodal retinal images with corresponding visual acuity measurements. Experiments on the dataset demonstrate that M2Net achieves superior performance compared to existing methods, with a classification accuracy of 96.03%, an SSIM of 0.6377 on the OCT modality, and an SSIM of 0.8347 on the fundus modality. Our code will be available at https://github.com/zengying123/M2Net.}, }
@article {pmid41990324, year = {2026}, author = {Rhodes, EY and Xia, JL and de Carlo Forest, TE and Manoharan, N and Palestine, AG and Reddy, AK}, title = {Hypertensive Anterior Uveitis Following Intravitreal Faricimab.}, journal = {Ocular immunology and inflammation}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/09273948.2026.2658753}, pmid = {41990324}, issn = {1744-5078}, abstract = {PURPOSE: Describe findings of three cases of culture and PCR negative hypertensive anterior uveitis following intravitreal faricimab.<br><br>METHODS: This is a case series of three patients undergoing treatment for diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). Data collected included visual acuity, intraocular pressure (IOP), slit lamp examination (SLE), anterior chamber (AC) tap, vitreous tap with culture, and fluorescein angiography (FA).<br><br>RESULTS: Three patients developed hypertensive uveitis following repeated intravitreal faricimab injections for DME or nAMD. All presented within 2-5&#x2009;weeks of injection with ocular pain and redness. Exam revealed elevated intraocular pressure (22-52&#x2009;mmHg), and keratic precipitates with anterior chamber inflammation. Infectious and inflammatory workups, including aqueous and/or vitreous PCR for HSV, VZV, and CMV, were negative in all cases. Faricimab was discontinued and topical and/or local corticosteroids initiated, with adjunctive IOP-lowering therapy as indicated. Inflammation resolved in all patients within 3&#x2009;months without recurrence after switching intravitreal anti-VEGF agents. Final visual acuity ranged from 20/25 to count fingers, limited by glaucomatous optic neuropathy in one case.<br><br>CONCLUSIONS: Hypertensive anterior uveitis with diffuse KPs is a potential rare complication of intravitreal faricimab and must be considered in patients presenting with new ocular inflammation or IOP elevation while undergoing treatment with faricimab. The intraocular inflammation appears to respond well to discontinuation of faricimab and treatment with local corticosteroids.}, }
@article {pmid41990841, year = {2026}, author = {Grün, M and Faatz, H}, title = {[Optical coherence tomography angiography].}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2729-1450}, pmid = {41990841}, issn = {1439-3999}, abstract = {Optical coherence tomography angiography (OCTA) has become increasingly established as a diagnostic procedure in clinical practice in recent years. In the field of medical retina in particular, it serves as a useful aid to the morphological assessment of vascular diseases such as neovascular age-related macular degeneration and diabetic retinopathy. Technically speaking, it is a further development of optical coherence tomography (OCT) and therefore offers the advantage of being non-invasive. Even though other imaging modalities still need to be used for certain clinical matters, OCTA offers a suitable alternative to invasive procedures in some situations or can be a helpful supplement in cases of unclear findings. In addition, OCTA has led to a better understanding of the pathophysiology and course of vascular diseases in a scientific context. Recent developments have already reduced or eliminated some of the limitations of OCTA and further improvements for use in clinical practice can be expected in the future.}, }
@article {pmid41990981, year = {2026}, author = {Keenan, TDL and Hébert, M and Chew, EY and Johnson, MW}, title = {What Should Patients with Age-Related Macular Degeneration Eat?.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.04.003}, pmid = {41990981}, issn = {1879-1891}, abstract = {PURPOSE: To summarize relevant data on what individuals with age-related macular degeneration (AMD) should eat and to propose simple, evidence-based, dietary and micronutrient supplement guidelines that can be shared with patients and physicians.<br><br>DESIGN: Focused literature review with interpretation and clinical perspective METHODS: We selectively reviewed literature on the associations between diet, oral micronutrient supplementation, and AMD progression, synthesizing evidence by disease stage. Sources included the Age-Related Eye Disease Studies (AREDS/AREDS2) in the United States, and major epidemiologic and cohort studies in Europe and North America.<br><br>RESULTS: Across disease stages, closer adherence to a Mediterranean diet is consistently associated with substantially slower AMD progression. In AREDS, individuals with early AMD who adhered more closely to a Mediterranean diet were significantly less likely to develop intermediate AMD. In AREDS/AREDS2 participants with intermediate AMD, higher Mediterranean diet adherence was strongly associated with decreased risk of progression to late AMD, especially for geographic atrophy (GA). Specific dietary components were particularly influential: higher fish intake was most protective, followed by higher vegetable and lower red meat intake. For individuals with geographic atrophy (GA), a Mediterranean diet was associated with markedly slower GA enlargement, including slower expansion towards the fovea. Higher intake of fruit and vegetables, lower intake of red meat, and avoidance of heavy alcohol consumption were most important in the modulation of GA expansion. Oral micronutrient supplementation with the AREDS2 formulation decreased progression to late AMD for individuals with intermediate AMD (or advanced disease in one eye) and slowed expansion of extrafoveal GA towards the fovea. Notably, the benefits of healthy diet and AREDS2 supplementation were found to be complementary and non-redundant.<br><br>CONCLUSION: Individuals with AMD should adopt a Mediterranean diet (or similar pattern), which appears beneficial at all disease stages. Dietary emphasis may vary by stage. A predominantly plant-based diet appears preferable to an animal-based diet, particularly for late AMD with GA. The AREDS2 formulation is recommended for individuals with intermediate or advanced AMD, and may be especially helpful for those with extrafoveal GA. A Mediterranean diet and micronutrient supplementation have complementary actions, so should be used together for maximal benefit.}, }
@article {pmid41787550, year = {2026}, author = {Spero, V and Escher, P and Braga-Lagache, S and Enzmann, V and Zinkernagel, M}, title = {Systemic inflammation triggers local complement production in the mouse retina and RPE.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {}, pmid = {41787550}, issn = {1742-2094}, abstract = {UNLABELLED: Systemic inflammation is increasingly recognized as a potential contributor in sight threatening retinal diseases such as Age-related Macular Degeneration (AMD). Yet, its impact on local eye immune responses and further pathological processes remains poorly understood. This study aims to elucidate the effect of peripheral immune activation on the local complement system, a central component of innate immunity with a dual role in maintaining ocular homeostasis and mediating inflammation, in the mouse retina and retinal pigment epithelium (RPE). Using a systemic lipopolysaccharide (LPS) challenge and a high-resolution proteomic approach, we observed a significant increase in complement factor 3 (C3) production in the RPE and retina 24 h post-injection. Further analysis confirmed the local source of complement signaling in resident cells such as astrocytes and RPE, independently from blood-retina barrier disruption. These findings reveal a direct cross-talk between systemic immune activation and ocular complement activation, and highlight the potential implications of systemic inflammation in the pathogenesis of ocular diseases, underlining the importance of future research into targeted therapies for inflammation-driven conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03737-y.}, }
@article {pmid41982839, year = {2025}, author = {Agarwal, K and Sadeghi, E and Mehrotra, K and Bollepalli, SC and Vupparaboina, KK and Chhablani, J}, title = {Uncomplicated Cataract Surgery and Neovascular Conversion of Age-Related Macular Degeneration: Fifteen-Year Follow-Up Study.}, journal = {Journal of current ophthalmology}, volume = {37}, number = {3}, pages = {346-351}, pmid = {41982839}, issn = {2452-2325}, abstract = {PURPOSE: To evaluate the impact of cataract surgery on neovascular age-related macular degeneration (nAMD) conversion over a 15-year follow-up period.<br><br>METHODS: This 15-year retrospective study on dry AMD patients compared Group A (cataract surgery) and Group B (no surgery). It assessed nAMD conversion rates, mean logMAR best-corrected visual acuity (BCVA), and final central macular thickness (CMT) changes. Kaplan-Meier survival curves and log-rank tests evaluated the impact of cataract surgery on time to conversion.<br><br>RESULTS: This study included 73 eyes from 46 patients, with a mean baseline age of 68.78 &#xb1; 8.62 years. Among them, 31 (67.39%) were female. Final analyses comprised 43 eyes in Group A and 30 eyes in Group B. Group A had a higher baseline age (70.3 &#xb1; 8.58 vs. 65.6 &#xb1; 7.24; P = 0.01), but baseline BCVA was similar (0.26 &#xb1; 0.33 vs. 0.29 &#xb1; 0.40; P = 0.61). The nAMD conversion rate showed no difference (32.55% vs. 36.66%; P = 0.491), as well as mean age at conversion (77.5 &#xb1; 8.10 vs. 77 &#xb1; 3.66; P = 0.80). The mean interval of conversion from cataract surgery was 5.24 &#xb1; 3.22 years. Final logMAR BCVA (0.78 &#xb1; 0.73 vs. 0.8 &#xb1; 0.76; P = 0.61) and mean CMT at final follow-up (167.6 &#xb1; 77.26 vs. 187 &#xb1; 85.19; P = 0.90) were also similar. The log-rank test showed no association between cataract surgery and conversion rate (P = 0.789).<br><br>CONCLUSIONS: The present study did not find a significant difference in conversion from dry to wet AMD between patients who underwent cataract surgery and who did not. No significant difference was noted in the age at the time of conversion between the two groups.}, }
@article {pmid41984164, year = {2026}, author = {Mauschitz, MM and Goerdt, L and Helbig, H and Holz, FG and Finger, RP and Brandl, C}, title = {Nutrition and dietary supplements in age-related macular degeneration.}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41984164}, issn = {2731-7218}, abstract = {BACKGROUND: Nutrition has an influence on the condition of our retina and appears to play a role in the complex, multifactorial pathogenesis of age-related macular degeneration (AMD).<br><br>OBJECTIVES: This article summarizes the current epidemiological evidence on nutrition and AMD and discusses the intake of specific nutrients as well as nutritional supplements and their potential role in prevention and disease modification.<br><br>MATERIAL AND METHODS: A&#xa0;narrative literature review of epidemiological studies, clinical trials and experimental work on the role of individual micronutrients, supplements and dietary patterns in AMD was carried out.<br><br>RESULTS: There is evidence of a&#xa0;protective effect for individual nutrients such as lutein, zeaxanthin, zinc and omega&#x2011;3 fatty acids. The AREDS studies in particular show a&#xa0;reduction in the progression of intermediate AMD to late stages through defined supplements. In addition, a&#xa0;Mediterranean diet correlates with a&#xa0;reduced risk of AMD. Nevertheless, the study results remain contradictory in some cases, which is due to methodological limitations and the complex pathogenesis of AMD.<br><br>DISCUSSION: Nutrition can potentially influence and reduce the risk for and progression of AMD. The existing literature underlines the potential of nutrition-based approaches, which must be further investigated in the future.}, }
@article {pmid41984830, year = {2026}, author = {Brillante, S and Volpe, M and Diana, A and Negueruela, S and Molinari, M and Saurino, R and Cipollaro, E and Polishchuk, E and Tenderini, E and Damiano, C and Tornabene, P and Polishchuk, R and Parenti, G and Tarallo, A and Banfi, S and Trapani, I and Carrella, S and Indrieri, A}, title = {Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {16}, pages = {e2504764123}, doi = {10.1073/pnas.2504764123}, pmid = {41984830}, issn = {1091-6490}, support = {M2020184//BrightFocus Foundation (BFF)/ ; PRIN2020 grant 2020XBCMHJ//Ministero dell'Universit&#xe0; e della Ricerca (MUR)/ ; TGM22MT01//Fondazione Telethon (FT)/ ; }, mesh = {Animals ; *Stargardt Disease/genetics/therapy/pathology/metabolism ; MicroRNAs/genetics/metabolism ; *Mitochondria/metabolism/pathology/genetics ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; ATP-Binding Cassette Transporters/genetics/metabolism ; *Macular Degeneration/congenital/genetics/pathology/therapy/metabolism ; GTP Phosphohydrolases/metabolism/genetics ; Mice, Knockout ; Disease Models, Animal ; Organoids/metabolism/pathology ; *Photoreceptor Cells, Vertebrate/metabolism/pathology ; }, abstract = {Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in ABCA4, which result in the progressive degeneration of the retinal pigment epithelium (RPE), ultimately leading to photoreceptor loss. Despite extensive efforts, STGD1 currently lacks effective treatments. Here, we first identified mitochondrial defects in the photoreceptors of Abca4[-/-] mice and STGD1 patient-derived retinal organoids. Specifically, we found reduced mitochondrial content, defective cristae morphology, and downregulation of OPA1, a critical regulator of mitochondrial integrity, demonstrating that photoreceptor defects in STGD1 also have a cell-autonomous origin, besides the RPE dysfunction. Importantly, we also demonstrated that correcting this pathological phenotype through the modulation of microRNAs 181a and b (miR-181a/b), key regulators of mitochondrial function, ameliorates the STGD1 phenotype. Indeed, genetic inactivation and adeno-associated viral vector-mediated silencing of miR-181a/b in STGD1 models restored OPA1 levels, improved mitochondrial phenotype, and reduced lipofuscin accumulation in the RPE. Our study demonstrates that mitochondrial dysfunction in photoreceptors is an important contributor to STGD1 pathology, opening promising therapeutic avenues for this disorder.}, }
@article {pmid41985834, year = {2026}, author = {Chen, KY and Chan, HC and Hwang, YS and Lin, WW and Chan, CM}, title = {Are Müller Glial Cells Gatekeepers of Neuroprotection and Regeneration in Age-Related Macular Degeneration? Unraveling Their Roles in Pathophysiology and Therapeutic Innovation.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101471}, doi = {10.1016/j.preteyeres.2026.101471}, pmid = {41985834}, issn = {1873-1635}, abstract = {Age-related macular degeneration (AMD) is traditionally conceptualized as a disorder of the retinal pigment epithelium (RPE)-photoreceptor axis; however, this paradigm incompletely explains early disease dynamics and therapeutic failure in geographic atrophy (GA). This review aims to redefine AMD progression through a Müller glial cell-centered framework that integrates cellular homeostasis, structural transitions, and stage-dependent therapeutic implications. Emerging transcriptomic, histologic, and functional evidence demonstrates that Müller glial cells actively participate in AMD pathobiology, including complement regulation, metabolic coupling, redox control, and inflammatory signaling. In early AMD, Müller glial cells exhibit adaptive responses that preserve retinal integrity despite increasing metabolic and extracellular stress. Progressive accumulation of basal laminar deposits and extracellular remodeling imposes diffusion constraints and inflammatory burden, promoting glial reprogramming. A critical transition occurs at external limiting membrane (ELM) descent, which corresponds to loss of photoreceptor support, disruption of retinal compartmentalization, and onset of irreversible degeneration. Beyond this threshold, Müller glial cells undergo structural remodeling and contribute to formation of subretinal glial membranes, reflecting a shift from homeostatic support to containment. This framework proposes a biologically testable staging axis from preserved Müller glial cell function to progressive dysfunction, aligning disease progression with therapeutic windows. Pre-ELM stages are characterized by retained plasticity and suitability for neuroprotective and metabolic interventions, whereas post-ELM stages require strategies focused on stabilization and limiting degeneration. Importantly, current clinical trials do not incorporate Müller glial cell state or ELM integrity as stratification variables, contributing to outcome insensitivity. In conclusion, Müller glial cells function as central regulators of retinal homeostasis and disease progression in AMD. Integrating glial biology with structural biomarkers may enable stage-specific precision therapies and improve clinical trial design.}, }
@article {pmid41986091, year = {2026}, author = {Lee, JH and Bae, K and Lee, EK and Yoon, CK and Park, KH and Park, UC}, title = {Effect of intraocular pressure-lowering agents in highly myopic eyes.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327484}, pmid = {41986091}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: To evaluate the effects of intraocular pressure (IOP)-lowering agents in highly myopic eyes.<br><br>METHODS: Highly myopic patients with axial length (AL) data for longer than 5 years were included. The changes in IOP, AL and myopic macular complications during the study period were compared between the eyes treated with IOP-lowering agents (treatment group) and those never treated (control group).<br><br>RESULTS: The treatment (30 eyes of 30 patients) and control (90 eyes of 90 patients) groups had comparable baseline characteristics except for IOP, which was significantly higher in the treatment group (p=0.020). During the study period, the treatment group showed a greater mean percentage decrease in IOP per year compared with the control group (-2.13&#xb1;2.51%&#x2009;/year vs+0.30 &#xb1; 2.31%&#x2009;/year; p<0.001). The mean change in AL per year was +0.032 &#xb1; 0.050&#x2009;mm/year in the treatment group and +0.058 &#xb1; 0.054&#x2009;mm/year in the control group (p=0.022), and the difference was more pronounced in eyes with posterior staphyloma or without dome-shaped macula. The progression of myopic macular degeneration (MMD), myopic retinoschisis and myopic choroidal neovascularisation during the study period was comparable between groups, but the increase in MMD category was significantly less frequent in the treatment group (3.3% vs 20.0%; p=0.040). In the multivariate analysis, use of IOP-lowering agents was associated with both decreased axial elongation and lower likelihood of MMD category increase.<br><br>CONCLUSION: IOP-lowering agents may be effective in alleviating axial elongation and progression of myopic maculopathy in highly myopic eyes.}, }
@article {pmid41975624, year = {2026}, author = {Miranda, M and Gupta, P and Sukkar, B and Cantó Catalá, A and Hosseinzadeh, Z}, title = {Müller glial cells for regeneration, retinal organoids, cell transplantation, and neuroprotection.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01256}, pmid = {41975624}, issn = {1673-5374}, abstract = {Müller glial cells are essential for retinal structure and homeostasis and increasingly recognized as dual regulators of retinal degeneration and regeneration. Beyond providing metabolic and structural support, Müller glial cells actively shape disease progression while retaining latent regenerative potential. Growing evidence highlights their roles in retinal degeneration, development, and neuroprotection, particularly in age-related macular degeneration, diabetic retinopathy, and inherited retinal disorders. This review integrates recent advances across five key areas: (1) Müller glial cell dysfunction in retinal disease pathology, including gliosis, inflammatory signaling, and vascular dysregulation; (2) their regenerative capacity, with a critical appraisal of efforts to reprogram Müller glial cells into retinal progenitors in mammalian models and the ongoing controversy surrounding functional neuronal replacement; (3) their contribution to the maturation of induced pluripotent stem cells-derived retinal organoids; (4) their neuroprotective roles through antioxidant, immunomodulatory, and trophic mechanisms; and (5) their emerging applications in cell-based therapies. By highlighting unresolved knowledge gaps-particularly the molecular barriers limiting Müller glial cell reprogramming and the signals governing their switch between protective and pathogenic states, this review positions Müller glial cells as central targets for future retinal regenerative and therapeutic strategies.}, }
@article {pmid41976951, year = {2026}, author = {Ciszewska, K and Winiarczyk, M and Winiarczyk, D and Mackiewicz, J}, title = {Microperimetry-Based Fixation Training in Patients with Age-Related Macular Degeneration (AMD).}, journal = {Journal of clinical medicine}, volume = {15}, number = {7}, pages = {}, pmid = {41976951}, issn = {2077-0383}, abstract = {Background: Age-related macular degeneration (AMD) is the primary cause of severe visual acuity loss in individuals over 60 with increasing prevalence. Currently, no effective treatments exist for geographic atrophy and macular scarring, highlighting the need for visual rehabilitation in these patients. Microperimetry offers functional assessment at any AMD stage and employs fixation training to help patients utilize the most effective retinal areas for vision. Methods: A prospective study involving 25 patients (50 eyes) aged 67 to 90. The MAIA II microperimeter assessed scotoma size and location, retinal sensitivity, macular integrity, fixation parameters (P1, P2, 63%BCEA, 95%BCEA), fixation stability, and preferred retinal locus. Quality of life was evaluated using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). A subgroup with inactive AMD-related macular changes, either bilateral geographic atrophy (13 patients, 26 eyes) or bilateral scarring (12 patients, 24 eyes), was identified, all exhibiting bilateral absolute central scotomas of at least 2 degrees. Each patient completed 10 fixation training sessions with a microperimeter, training the eye with better acuity weekly. One-week post-training, a functional assessment was performed on both trained and untrained eyes. Results: Fixation training significantly improved best corrected visual acuity (BCVA) in trained eyes (mean change -0.14 logMAR, p < 0.001, large effect size) and also in fellow untrained eyes (-0.16 logMAR, p < 0.001). BNVA improved from 2.25 to 1.86 in trained eyes (p < 0.001) and from 2.96 to 2.76 in untrained eyes (p = 0.004). Fixation stability parameters improved significantly, including increases in P1 and P2 and reductions in Bivariate Contour Ellipse Area (BCEA). Quality of life measured using the NEI-VFQ-25 questionnaire improved significantly in 9 of 11 domains. Conclusions: Microperimetry may be a valuable tool for assessing visual function in AMD patients. Fixation training with the MAIA II microperimeter is both safe and effective for vision rehabilitation in those with geographic atrophy and macular scarring.}, }
@article {pmid41977310, year = {2026}, author = {Yang, JY and Choi, JS and Park, TK}, title = {AAV2.7m8-Mediated MicroRNA Expression Suppresses VEGF-Induced Angiogenic Responses in HUVEC.}, journal = {International journal of molecular sciences}, volume = {27}, number = {7}, pages = {}, doi = {10.3390/ijms27073123}, pmid = {41977310}, issn = {1422-0067}, support = {RS-2025-02217948//National Research Foundation of Korea/ ; RS-2024-00452984//National Research Foundation of Korea/ ; }, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Human Umbilical Vein Endothelial Cells/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/pharmacology/genetics ; *Dependovirus/genetics ; Cell Proliferation ; Cell Movement/genetics ; Genetic Vectors/genetics ; *Neovascularization, Physiologic/genetics ; *Neovascularization, Pathologic/genetics/metabolism ; Signal Transduction ; }, abstract = {Vascular endothelial growth factor (VEGF)-driven pathological angiogenesis constitutes a primary driver of neovascular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Although anti-VEGF agents demonstrate clinical efficacy, their limited intraocular half-life mandates repeated intravitreal injections, thereby highlighting the imperative for long-term therapeutic strategies. In the present study, we assessed the anti-angiogenic potential of retinal organoid-derived microRNAs (miRNA) delivered via an engineered adeno-associated virus vector. Human umbilical vein endothelial cells (HUVEC) were transduced with AAV2.7m8 vectors to overexpress three candidate miRNA (miR-26a, miR-122, and let-7a), followed by VEGF stimulation to evaluate downstream signaling pathways and angiogenic responses. AAV2.7m8-mediated transduction of HUVEC demonstrated high efficiency without inducing detectable cytotoxicity. Overexpression of these miRNA markedly attenuated VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Functional assays demonstrated suppression of endothelial cell proliferation and cell cycle progression, with miR-122-5p additionally inhibiting migration. All three miRNA substantially inhibited capillary-like tube formation. In aggregate, these results affirm that AAV2.7m8-mediated delivery of retinal organoid-derived miRNA -namely miR-26a-5p, miR-122-5p, and let-7a-5p-markedly suppresses VEGF-induced angiogenic signaling cascades and endothelial cell activation in vitro, thereby establishing their viability as a sustained therapeutic approach for pathological retinal neovascularization.}, }
@article {pmid41977482, year = {2026}, author = {Phillips, R}, title = {Nutrition, Cell Signalling, Mitochondrial Function, and Chronic Non-Communicable Disease.}, journal = {International journal of molecular sciences}, volume = {27}, number = {7}, pages = {}, doi = {10.3390/ijms27073303}, pmid = {41977482}, issn = {1422-0067}, mesh = {Humans ; *Mitochondria/metabolism ; *Signal Transduction ; Animals ; *Noncommunicable Diseases ; Chronic Disease ; Homeostasis ; Energy Metabolism ; }, abstract = {Cellular homeostasis is a dynamic process which balances anabolic processes with catabolic and recycling processes. These processes require nutrients, which are converted to energy to fuel the complex interactions of intracellular signalling. Cellular health requires that, on average, energy input and energy requirements are matched. Cells contain a nutrient-sensing mechanism which controls the balance between anabolism and catabolism. Normal intracellular functions generate products which regulate signalling pathways, and health at a cellular level requires a fluctuation between relative nutrient abundance and relative nutrient scarcity. This allows clearance of damaged intracellular molecules and organelles. When nutrient supply exceeds cellular requirements, adaptations to intracellular signalling occur, resulting in energy being stored as glycogen in muscle and the liver and fatty acids in adipose tissue. Overfuelling and aberrant fuelling of mitochondria result in oxidative stress, which not only disrupts cellular homeostasis but can alter epigenetic expression, with intergenerational effects. If the recycling mechanisms of the cell are insufficient to clear metabolic products, apoptosis may result or expression of Damage-Associated Molecular Patterns (DAMPs) on the cell surface may occur, activating immunity and inflammation at a systemic level. Disrupted cellular signalling affects cells with different "professional" functions in different organs, and it is the mechanism which underlies the associations between chronic non-communicable diseases such as cancer, type 2 diabetes, cardiovascular disease, neurodegenerative disease, autoimmune diseases, and macular degeneration. Mitochondria are the controllers of energy production and are pivotal in cell signalling. Mitochondrial function governs health at cellular and organismal levels. This paper reviews the influence of nutrition on mitochondrial function, nutrient sensing, autophagy, insulin signalling, and apoptosis-the key pathways in cellular homeostasis.}, }
@article {pmid41979251, year = {2026}, author = {Zhao, Z and Ou, Q and Zhu, J and He, Z and Yang, Y and Jiang, J and Wang, Q and Zhou, Y and Liu, Y and Zhu, X and Cui, T and Liu, Y and Xu, J and Gao, F and Jin, C and Wang, J and Lu, L and Bi, Y and Xu, GT and Xu, JY and Tian, H}, title = {Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {30}, doi = {10.1167/iovs.67.4.30}, pmid = {41979251}, issn = {1552-5783}, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Cellular Senescence/drug effects/physiology ; Mice ; *Glucose/metabolism ; Reactive Oxygen Species/metabolism ; Humans ; Blotting, Western ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Ferric Compounds/toxicity/pharmacology ; Cells, Cultured ; Induced Pluripotent Stem Cells/metabolism ; Electroretinography ; Disease Models, Animal ; Quaternary Ammonium Compounds/toxicity ; Metabolic Reprogramming ; }, abstract = {PURPOSE: This study aimed to investigate whether iron overload induces retinal pigment epithelial (RPE) cell senescence through glucose metabolic reprogramming and to evaluate the therapeutic potential of targeting this metabolic pathway.<br><br>METHODS: We utilized human-induced pluripotent stem cell-derived RPE cells and induced RPE cells, along with mouse models with intravitreal or intraperitoneal injection of ferric ammonium citrate (FAC), to evaluate the effect of iron overload on RPE senescence. Proteomics, targeted metabolomics, reactive oxygen species (ROS) assay kits, JC-1 assay kit, reverse-transcription polymerase chain reaction, SA-&#x3b2;-gal staining, and western blot were used to assess mitochondrial function, ROS, and senescence markers. 2-Deoxy-d-glucose (2-DG), pyruvate kinase M2 inhibitor-1 (PKM2-IN-1), and sodium oxamate (SO) were used to modulate glucose metabolism flux. Flash electroretinography recording was used to assess visual function.<br><br>RESULTS: Iron overload triggered significant glucose metabolic reprogramming in RPE cells, characterized by a time-dependent metabolic shift. Early exposure to FAC induced a transient surge in glucose metabolic flux, which elevated mitochondrial ROS production and disrupted mitochondrial homeostasis, ultimately leading to cellular senescence. Importantly, early inhibition of this metabolic surge with 2-DG or PKM2-IN-1 effectively attenuated senescence by reducing ROS levels and preserving mitochondrial function. Conversely, enhancing pyruvate flux with SO exacerbated senescence. The protective effect of 2-DG against iron-induced RPE senescence was further confirmed in a mouse model, where it preserved visual function and reduced senescence markers.<br><br>CONCLUSIONS: Glucose metabolic reprogramming mediates iron-induced RPE senescence, with transient glucose flux surge driving pathology via ROS-related mitochondrial damage. Targeting glucose metabolism may preserve mitochondria homeostasis and prevent RPE degeneration in age-related macular degeneration.}, }
@article {pmid41979253, year = {2026}, author = {Foshe, S and Anderson, BD and Song, Y and Shi, S and Lee, S and Bell, BA and Park, HG and Brenna, JT and Shchepinov, M and Dunaief, JL}, title = {Oral Deuterated Docosahexaenoic Acid Protects Against Onset and Progression of RPE Degeneration in a Mouse Model of Chronic Oxidative Stress.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {28}, doi = {10.1167/iovs.67.4.28}, pmid = {41979253}, issn = {1552-5783}, mesh = {Animals ; *Oxidative Stress/drug effects ; *Docosahexaenoic Acids/administration &amp; dosage ; *Retinal Pigment Epithelium/pathology/drug effects/metabolism/ultrastructure ; Mice ; Disease Models, Animal ; Mice, Knockout ; Tomography, Optical Coherence ; Disease Progression ; Mice, Inbred C57BL ; Administration, Oral ; Electroretinography ; Female ; *Macular Degeneration/prevention &amp; control ; Ophthalmoscopy ; Hepcidins/genetics ; }, abstract = {PURPOSE: Oxidative stress is associated with many retinal diseases, including age-related macular degeneration (AMD). The purpose of this study is to investigate the efficacy of oral deuterated docosahexaenoic acid (D-DHA), an oxidation-resistant lipid, in a mouse model with features of dry AMD. We also evaluated whether long-term D-DHA dosing affects normal retinal structure or function.<br><br>METHODS: Liver-specific hepcidin (Hepc) and ceruloplasmin/hepcidin (Cp/Hepc) knock-out (KO) mice were fed experimental diet containing 0.25% D-DHA or control containing normal H-DHA during various stages of disease progression. Retinal pigment epithelium (RPE) damage was assessed with in vivo scanning laser ophthalmoscopy (SLO) imaging and histology. For the safety study, wild-type mice were fed the diets beginning in utero or at 3 months of age, continuing for 12 months. These mice were analyzed to assess retinal structure (SLO, optical coherence tomography [OCT], and transmission electron microscopy [TEM]), function (ERG), and gene expression (qPCR).<br><br>RESULTS: KO mice fed control diet developed expanding autofluorescent patches of hypertrophic RPE cells. This damage was markedly prevented or halted by diet with D-DHA, depending on age at diet onset. Wild-type mice administered diet with D-DHA from age 3 to 15 months had no retinal abnormalities. Mice administered D-DHA beginning in utero had normal retinal development and structure but minor deficits in ERG amplitudes and Rpe65 expression by age 12 months.<br><br>CONCLUSIONS: Oral D-DHA was strongly protective against RPE ferroptosis, with minimal side effects. This study suggests that DHA oxidation is a key mechanism of retinal iron toxicity and supports the potential clinical application of D-DHA for diseases involving retinal oxidative stress.}, }
@article {pmid41979423, year = {2026}, author = {Jiang, H and Wang, X and Wang, L and Fan, Y and Li, Z and Ma, M and Liu, S and Li, B and Shi, J and Li, C and Ma, L and Li, J and Zhang, W}, title = {Association of dietary calcium and its food sources with age-related macular degeneration in China: a population-based case-control study.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo04327a}, pmid = {41979423}, issn = {2042-650X}, abstract = {Background &amp; aims: Recent studies, primarily in developed countries, suggest that higher dietary calcium intake is associated with lower odds of age-related macular degeneration (AMD). However, evidence on this association is lacking in China, where the population has unique dietary patterns and relatively low calcium intake. The aim of this study was to investigate the association of dietary calcium and its major sources with the likelihood of AMD in a Chinese population. Methods: A case-control study was performed within the frame of the Xi'an Eye Study. A total of 284 AMD cases and 284 matched controls who completed the eye examination and a detailed semi-quantitative food frequency questionnaire were included in the present analysis. Multivariable-adjusted conditional logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of dietary calcium and its main sources. Results: In the multivariable adjusted model, an increasing amount of dietary calcium intake was associated with significantly lower odds of AMD, especially among participants with a dietary calcium intake of less than 800 mg per 2000 kcal per day. The OR for the comparison of the top with the bottom tertile of dietary calcium intake was 0.46 (95%CI: 0.23, 0.90; P-trend = 0.02). Regarding major sources of calcium, a significant inverse association was only observed for dairy-based calcium intake, with an OR of 0.45 (95%CI: 0.23, 0.89; P-trend = 0.02). Consumption of dairy products, particularly milk (OR: 0.45 from a comparison of ≥4 servings per week with never/rarely; 95%CI: 0.22, 0.90; P-trend = 0.05) and yogurt (OR: 0.38 from a comparison of ≥2 servings per week with never/rarely; 95%CI: 0.19, 0.78; P-trend = 0.01), was also associated with lower odds of AMD. No significant associations were found for milk powder or dietary intake of calcium from vegetables or legumes. Conclusions: Higher intake of calcium and its major food sources, such as milk and yogurt, was associated with a significantly decreased likelihood of AMD in a Chinese population with relatively low dietary calcium intake. These findings align with current public health recommendations for maintaining adequate calcium status and emphasize that the health implications of calcium may depend on its dietary sources.}, }
@article {pmid41979761, year = {2026}, author = {Brandl, C and Heid, IM and Helbig, H and Holz, FG and Finger, RP and Mauschitz, MM}, title = {Risk factors for age-related macular degeneration.}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41979761}, issn = {2731-7218}, }
@article {pmid41981257, year = {2026}, author = {Janmohamed, IK and Harahn, H and Carr, B and Sahbi, S and Ahmed, H and Farahat, A and Hannan, S and Membrey, L}, title = {Early real-world outcomes of aflibercept 8 mg in previously treated neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41981257}, issn = {1476-5454}, abstract = {BACKGROUND: Real-world evidence of aflibercept 8 mg in treatment-experienced patients remains limited. This study evaluated early outcomes of switching treatment-refractory patients with neovascular age-related macular degeneration (nAMD) to aflibercept 8 mg.<br><br>METHODS: This retrospective cohort study analysed previously-treated patients who switched to aflibercept 8&#x2009;mg between January and June 2025. Best-corrected visual acuity (BCVA), central macular thickness (CMT), pigment epithelial detachment (PED) height, macular fluid status and treatment intervals were evaluated at baseline, 3 months, 6 months and final visit.<br><br>RESULTS: 58 patients (66 eyes) were included. Patients received a mean 24.98&#x2009;&#xb1;&#x2009;18.04 anti-VEGF injections per eye over 49.41&#x2009;&#xb1;&#x2009;35.74 months pre-switch. Mean 5.15&#x2009;&#xb1;&#x2009;1.51 aflibercept 8&#x2009;mg injections were administered per eye over a mean follow-up period of 25.86&#x2009;&#xb1;&#x2009;8.34 weeks. Median treatment intervals increased significantly from baseline to final visit (4&#xa0;to 6 weeks, p&#x2009;<&#x2009;0.001). 23 eyes (34.8%) achieved &#x2265;8-week intervals by final follow-up. Median BCVA remained stable (70 ETDRS letters, interquartile range [IQR] 62-76 baseline and final follow-up, p&#x2009;=&#x2009;0.571), as did median CMT (230.5&#x2009;&#x3bc;m (IQR 189.5-281.2) at baseline to 226.5&#x2009;&#x3bc;m (IQR 195-257) at final follow-up, p&#x2009;=&#x2009;0.494). Median PED height showed a significant reduction (175&#x2009;&#x3bc;m (IQR 106-287) at baseline to 173&#x2009;&#x3bc;m (IQR 105-251) at final follow-up, p&#x2009;=&#x2009;0.045). Complete macular fluid resolution occurred in 23.9% of eyes with baseline fluid at the final visit. No serious ocular adverse events occurred in this cohort.<br><br>DISCUSSION: Aflibercept 8&#x2009;mg demonstrated modest interval extension with stable functional and anatomical outcomes in heavily pre-treated nAMD patients. Long-term studies are needed to establish durability.}, }
@article {pmid41971199, year = {2025}, author = {Shakeel, A and Bhatt, D and Sripriya, S and Ratra, D}, title = {Early-onset drusen in Malattia Leventinese with EFEMP1 mutation differ from drusen in age-related macular degeneration.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {4}, pages = {598-605}, pmid = {41971199}, issn = {2501-2533}, mesh = {Humans ; Male ; Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/genetics ; *Extracellular Matrix Proteins/genetics/metabolism ; *Macular Degeneration/diagnosis/genetics ; Fluorescein Angiography/methods ; *Mutation ; Female ; Pedigree ; Middle Aged ; Fundus Oculi ; Age of Onset ; DNA Mutational Analysis ; Diagnosis, Differential ; Adult ; Phenotype ; *DNA/genetics ; Visual Acuity ; Optic Disk Drusen/congenital ; }, abstract = {PURPOSE: To study the clinical, genetic, and phenotypic aspects of Malattia Leventinese (ML)/Doyne honeycomb retinal dystrophy (DHRD) and to differentiate it from age-related macular degeneration (AMD).<br><br>METHODS: Three cases of ML/DHRD from the Indian population were evaluated, including fundus examination, fundus autofluorescence (FAF), and swept-source optical coherence tomography (SSOCT). Genetic investigations involved screening for an inherited retinal gene panel using the Illumina MiSeq platform for one case. Pedigree charting, blood collection, DNA extraction, and variant annotation were performed, followed by pathogenicity assessment of the identified variants using multiple bioinformatics tools.<br><br>RESULTS: All cases exhibited early-onset central vision loss and small, radially distributed drusen, consistent with ML/DHRD. Genetic analysis done in patient one revealed a heterozygous, autosomal dominant, pathogenic mutation (c.1033C>T p.ARG345Trp) in the EFEMP1 gene, confirming the ML diagnosis. Patient 1 had no late-stage complications, whereas patients 2 and 3 developed macular neovascularization (MNV). OCT showed gross thickening of the retinal pigment epithelium with hyperreflectivity, along with outer retinal tubulations (ORT) and interlaminar bridges, indicating outer retinal degeneration.<br><br>DISCUSSION: Malattia Leventinese is a rare autosomal dominant macular dystrophy caused by a single EFEMP1 missense mutation (R345W), leading to early-onset radial or honeycomb drusen and central vision loss in the third decade. In this series, all patients showed typical radial drusen, with macular neovascularization in two cases, and demonstrated interlaminar bridges and ORTs on OCT. The mutant EFEMP1 protein misfolds and accumulates abnormally between the RPE and Bruch's membrane, accelerating drusen formation. Some phenotypic variability, including intrafamilial differences, likely reflects additional genetic or environmental modifiers. The presence of the R345W mutation, age at onset, and drusen distribution pattern are crucial for differentiating ML/DHRD from AMD.<br><br>CONCLUSION: The identified pathogenic EFEMP1 mutation (R345W) established a molecular link to ML/DHRD. Typical phenotypic patterns and drusen characteristics can differentiate ML/DHRD from AMD.}, }
@article {pmid41971250, year = {2026}, author = {Rowe, LW and Macha, NN and Aggarwal, N and Singh, RP and Maturi, RK}, title = {Visual Acuity and Durability Outcomes of Faricimab Compared With Other Antivascular Endothelial Growth Factor Agents Within Routine Clinical Practice for Neovascular Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261428749}, pmid = {41971250}, issn = {2474-1272}, abstract = {Purpose: To compare the visual acuity (VA) outcomes and dosing intervals of faricimab with those of other antivascular endothelial growth factor agents in treatment-naïve and treatment-experienced eyes with neovascular age-related macular degeneration (nAMD). Methods: De-identified electronic medical records (Vestrum Health treatment and outcomes database) of patients with nAMD treated with bevacizumab, ranibizumab, aflibercept, or faricimab between January 2021 and December 2023 were included. Mean VA change and mean number of days between injections were collected through 6 injections for treatment-naïve eyes and through 2 injections for treatment-switched eyes. Results: A total of 736 treatment-naïve eyes receiving faricimab experienced nonsignificantly lower VA gains than all other drugs; 5467 eyes switched to faricimab demonstrated lower VA gains relative to other drugs. This includes significantly lower gains than aflibercept or bevacizumab when switched from ranibizumab (P < .01). Bevacizumab achieved the highest VA gains-significantly more than aflibercept (P < .01) in the treatment-naïve cohort and significantly more than faricimab and aflibercept when switched from ranibizumab (P < .01). After adjusting for significant VA differences at baseline and at the switch date, all drugs displayed similar VA gains in both cohorts. Compared with all other drugs, faricimab provided up to 4 additional days on average between injections and had the highest proportion of eyes extended over 50 days between the final 2 injections for both cohorts. Relative to aflibercept and ranibizumab, these injection frequencies for faricimab were significantly longer (P < .01). Conclusions: Treatment-naïve and treatment-experienced nAMD eyes receiving faricimab demonstrated VA gains and minimally longer injection intervals, comparable to other antivascular endothelial growth factor agents.}, }
@article {pmid41972930, year = {2026}, author = {Fasler, K and Multone, E and Stahel, M and Gabathuler, F and Blaser, F and Zweifel, SA}, title = {Misfolded Proteins in the Eye - Vitreous Amyloidosis.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001927}, pmid = {41972930}, issn = {1937-1578}, abstract = {PURPOSE: The aim of this study was to describe a case of vitreous amyloidosis as a rare aetiology of vitreous opacities and to show diagnostic value of vitreous biopsy in the diagnostic process as well as show a potiential new non-invasive diagnostic for vitreous amyloidosis.<br><br>METHODS: Retrospective case report with presentation of medical record data, clinical imaging, and pathological work-up.<br><br>RESULTS: A 82-year-old man underwent diagnostic vitrectomy due to dense vitreous opacities in the right eye. While visual acuity did not improve much due to an underlying advanced fibrotic age related macular degeneration, pathology confirmed amyloid material in the vitreous. The patient was diagnosed with hereditary amyloid transthyretin amyloidosis (ATTRv) and offered a transthyretin stabilising therapy (tafamidis, vindaqel&#xae;).<br><br>DISCUSSION: While vitreous opacities are a common usually benign phenomenon, it is important to recognise atypical presentation. Diagnostic work-up may include diagnostic vitrectomy, which can aid in diagnosing relevant underlying systemic disease such as ATTRv amyloidosis. While pathologic work-up of vitreous material is the current gold standard, there may be novel non-invasive imaging techniques to aid in diagnosis of vitreous amyloidosis.}, }
@article {pmid41973161, year = {2026}, author = {Chang, CW and Liu, PK and Cheng, KC and Lai, HC and Wu, HJ and Lee, DY and Lo, MW and Chen, KJ and Lin, HC and Chang, YC}, title = {Anatomic and functional outcomes of intravitreal faricimab for polypoidal choroidal vasculopathy: a review.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41973161}, issn = {1573-2630}, mesh = {Humans ; Intravitreal Injections ; *Choroid/blood supply/pathology ; *Visual Acuity ; *Antibodies, Bispecific/administration &amp; dosage ; *Polyps/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence ; Fluorescein Angiography ; Treatment Outcome ; *Choroidal Neovascularization/drug therapy/physiopathology/diagnosis ; Fundus Oculi ; Polypoidal Choroidal Vasculopathy ; }, abstract = {PURPOSE: This review examines anatomic and functional outcomes of intravitreal faricimab for treating polypoidal choroidal vasculopathy (PCV), a neovascular age-related macular degeneration subtype common in Asian populations. Faricimab is a bispecific antibody targeting both VEGF-A and Ang-2, potentially offering more durable effects than standard anti-VEGF monotherapy.<br><br>METHODS: A narrative review was conducted by searching PubMed, Embase, and Web of Science through July 2024. Keywords included faricimab, polypoidal choroidal vasculopathy, and anti-VEGF. Eligible studies comprised English-language, peer-reviewed human trials (prospective, retrospective, case series, and reports). Conference abstracts and non-peer-reviewed sources were excluded.<br><br>RESULTS: In treatment-na&#xef;ve patients, preliminary data suggest that faricimab may yield favorable results, though findings are largely derived from small retrospective studies. Functionally, a one-year study reported significant improvement in mean best-corrected visual acuity (BCVA), from 0.30&#xb1;0.33 logMAR at baseline to 0.16&#xb1;0.26 logMAR at final visit. However, some studies note visual gains may not be statistically significant during initial loading phase. Anatomically, high polyp regression rates are key findings, with one study reporting 61.1% rate after three monthly injections. High rates of dry macula (60-80%) and significant reductions in central foveal thickness (CFT) and central choroidal thickness (CCT) are consistently observed. For patients with suboptimal response to prior anti-VEGF therapies, switching to faricimab presents mixed picture. While a prospective cohort study found no significant average improvement in visual acuity for switched PCV eyes, a case report showed dramatic improvement from 20/100 to 20/60 after two injections in a ranibizumab-refractory case. Anatomically, switched patients show significant reduction in choroidal thickness and serous pigment epithelial detachments (PEDs). However, the presence of polypoidal lesions was identified as a negative predictive factor for successfully extending the treatment interval.<br><br>CONCLUSIONS: Based on limited retrospective evidence, faricimab may represent a promising therapeutic candidate for PCV, with several studies reporting anatomical improvements. The dual mechanism of action targeting both VEGF-A and Ang-2 may help address certain pathological features of the disease; however, confirmation from larger prospective studies is needed.}, }
@article {pmid41973601, year = {2026}, author = {Tse, DY and Ma, MM and Hon, Y and Ho, LM and Lam, WC and Shih, KC and Zhang, X and Lam, DMK and Kong, ACW and Lam, TC and Lam, CSY and Lian, TJ and Morgan, I and To, CH and Chun, RKM and Leung, CKS}, title = {Effectiveness of Low-Dose Atropine Combined With Bright Light Therapy for Controlling Myopic Eye Growth in Schoolchildren: Study Protocol for a Randomized Controlled Trial.}, journal = {JMIR research protocols}, volume = {15}, number = {}, pages = {e90893}, doi = {10.2196/90893}, pmid = {41973601}, issn = {1929-0748}, mesh = {Humans ; *Atropine/administration &amp; dosage/therapeutic use ; *Myopia/therapy/drug therapy ; Child ; Female ; Male ; *Phototherapy/methods ; Treatment Outcome ; Single-Blind Method ; Disease Progression ; Randomized Controlled Trials as Topic ; Hong Kong ; }, abstract = {BACKGROUND: Myopia is increasingly prevalent worldwide, with projections indicating that nearly 50% of the global population may have myopia by 2050. This surge poses significant concerns due to its impact on vision and quality of life and its link to a range of blinding diseases, including myopic macular degeneration, glaucoma, and retinal detachment. Current pharmacologic and optical interventions offer limited effectiveness in slowing myopia progression, highlighting the urgent need for more effective treatments.<br><br>OBJECTIVE: This study aims to examine the combined effect of bright light therapy and low-dose atropine on myopic progression.<br><br>METHODS: This is a single-site, 2-arm, single-masked (examiner-masked) randomized controlled trial to compare the effectiveness of low-dose atropine alone and its combination with bright light therapy in retarding myopia progression. The study protocol has been approved by the institutional review boards of Hong Kong Polytechnic University (HSEARS 20180829002-05) and the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 20-362). Schoolchildren with myopia aged 7 to 12 years who have not undergone any previous myopic control intervention will be recruited and randomly allocated into 2 groups (n=67 per group) after baseline measurements. Both groups will receive 0.01% atropine twice daily for 24 months. The combination treatment group will also receive a high-intensity lamp for bright light therapy. The primary and secondary outcome measures will be the changes in cycloplegic autorefraction in spherical equivalent refraction and axial length, respectively, measured every 6 months over 2 years from baseline.<br><br>RESULTS: The project was funded in January 2019. The recruitment process started on March 21, 2023, and was completed on February 2, 2024. Data collection is expected to be completed in April 2026.<br><br>CONCLUSIONS: This study will provide new information on whether the combination of bright light therapy and low-dose atropine is more effective than atropine alone in slowing down myopia progression. It will also assess the effectiveness of low-dose atropine used twice daily. Combining bright light therapy and atropine could become a new treatment option if shown to be effective. New data on the effectiveness of using atropine twice daily might also expand available treatment options.}, }
@article {pmid41974662, year = {2026}, author = {Parween, S and Saviola, AJ and Howell, AC and Varghese, S and Galindo, DC and Vergara, MN}, title = {Human retinal organoid model of disease-relevant photoreceptor cell death amenable to drug screening.}, journal = {Cell death &amp; disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08724-y}, pmid = {41974662}, issn = {2041-4889}, abstract = {Dry age-related macular degeneration (AMD) is characterized by the progressive loss of retinal pigment epithelium cells in the macula, leading to photoreceptor degeneration and loss of central vision. Current treatments only modestly delay disease progression, but once photoreceptors are damaged, vision loss becomes irreversible. Therefore, there is an urgent need to develop therapies that prevent photoreceptor cell death and that may complement current and emerging treatment strategies. A critical step toward this goal is establishing pathophysiologically relevant human disease models for therapeutic testing. In this study, we developed a human induced pluripotent stem cell-derived retinal organoid (RO) model that recapitulates key aspects of AMD-associated photoreceptor degeneration. To mimic environmental stressors relevant to AMD, we treated mature ROs with cigarette smoke extract (CSE), a known oxidative agent and major modifiable risk factor for the disease. CSE exposure induced oxidative stress, mitochondrial membrane depolarization, and cell death primarily in the outer nuclear layer. Photoreceptor degeneration in this model involves the activation of the intrinsic apoptotic pathway and ferroptosis, which is accompanied by lipid peroxidation and dysregulation of the glutathione system. Proteomic profiling confirmed alterations in metabolic, redox, and cell death pathways consistent with AMD pathophysiology, and offered further insight into the mechanistic interplay among these pathways. Furthermore, we integrated this model with robust, quantitative outcome measures in live ROs, offering a powerful platform for preclinical therapeutic screening in dry AMD.}, }
@article {pmid41963383, year = {2026}, author = {Zhang, F and Wang, C and Tang, Q and Ao, T and Li, J and Liu, Y}, title = {Integrated transcriptomic and metabolomic analyses reveal distinct energy metabolic signatures and functional properties of RPE cells under two culture conditions.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41963383}, issn = {2045-2322}, support = {CSTB2024NSCQ-BSX0015//Chongqing Natural Science Foundation - Doctoral "Fast Track" Project/ ; JFLKYXM202203AZ-217//Jinfeng Lab Fundamental Research Funds/ ; CQERC-OIBM20241005//Open Project of Chongqing Engineering Research Center of Organ Intelligent Bio-Manufacturing/ ; }, abstract = {UNLABELLED: Retinal pigment epithelium (RPE) degeneration is a major cause of vision loss in multiple retinal diseases, including age-related macular degeneration, Bietti crystalline dystrophy and Stargardt disease. Induced pluripotent stem cell (iPSC)-derived RPE cells hold promise for regenerative therapies. B27- and KSR-based media are among the most commonly used for RPE culture; however, how these culture conditions shape RPE cell identity and features remain incompletely understood. Here, we performed comprehensive transcriptomic and metabolomic profiling of iPSC-derived RPE cells cultured in B27 or KSR media to systematically compare their gene expression and metabolic features. B27- and KSR-cultured RPE cells exhibited distinct morphologies and barrier properties. Integrated multi-omics analyses revealed that KSR-cultured RPE cells displayed a relative bias toward fatty acid oxidation and oxidative phosphorylation, whereas B27-cultured RPE cells showed a relative bias toward glycolytic metabolism. The glycolytic tendency observed in B27-RPE cells was accompanied by increased expression of extracellular matrix–related genes and higher transepithelial resistance. In contrast, KSR-RPE cells exhibited comparable tricarboxylic acid cycle activity but higher expression of oxidative phosphorylation–related genes compared with B27-RPE cells. Together, these results demonstrate that RPE cells cultured under different conditions adopt distinct but partially overlapping metabolic and transcriptional states, which are associated with differences in RPE-related features and barrier properties. Our findings highlight the importance of metabolic balance between glycolysis and fatty acid oxidation in shaping in vitro RPE phenotypes.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-39689-9.}, }
@article {pmid41967781, year = {2026}, author = {Sha, C and Wei, D and Xu, W and Sun, H and Yin, Y and Su, S and Zhao, M and Duan, JA}, title = {Zhujing Pill ameliorates age-related macular degeneration by regulating lipid metabolism, complement activation, and inflammatory responses: an integrated network pharmacology and metabolomics study.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121674}, doi = {10.1016/j.jep.2026.121674}, pmid = {41967781}, issn = {1872-7573}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, with particularly limited therapeutic options for dry AMD. Zhujing Pill (ZJP), a traditional Chinese medicinal formula recorded in Taiping Sheng Hui Fang of the Northern Song Dynasty, has historically been prescribed for visual disorders attributed to age-related "liver and kidney deficiency", a traditional syndrome sharing core clinical features with AMD. However, the pharmacological basis and molecular mechanisms underlying its therapeutic effects remain largely unexplored.<br><br>AIM OF THE STUDY: To systematically elucidate the bioactive constituents and therapeutic mechanisms of ZJP in AMD using an integrated strategy combining network pharmacology, molecular docking, metabolomics, and experimental validation.<br><br>MATERIALS AND METHODS: The chemical profiles and principal constituents of ZJP and ZJP-medicated serum (ZJW) were characterized by UHPLC-MS analysis. Network pharmacology and molecular docking were applied to identify key compounds and potential molecular targets. Protective effects were evaluated using lysophosphatidylcholine (LPC)-induced ARPE-19 cell injury and sodium iodate-induced AMD mouse models. Retinal structure and function were assessed by behavioral testing, optical coherence tomography (OCT), and histopathology. Serum and intracellular metabolomics were performed using UPLC-QTOF-MS. The expression of inflammatory, complement-related, and lipid and cholesterol metabolism-associated genes were analyzed by RT-qPCR.<br><br>RESULTS: A total of 386 constituents were identified in ZJP, and 222 compounds were detected in ZJP-medicated serum, predominantly flavonoids, iridoids, phenylethanoid glycosides, and bile acid-related metabolites. Network pharmacology highlighted quercetin, kaempferol, isorhamnetin, and sophoranol as key active compounds targeting core proteins such as AKT3, HSP90AA1, and PIK3CA. In in vivo evaluations, compared with the AMD model group, high-dose ZJP treatment increased the time spent in the dark chamber by 90.51% (P < 0.001), significantly restored retinal thickness by 84.76% (P < 0.001), and improved the histopathological score by 52.88% (P < 0.001). In ARPE-19 cells, ZJP increased LPC-induced cell viability by 105.56% (P < 0.001), inhibited complement overactivation, and suppressed inflammatory cytokine. Metabolomic analyses demonstrated that ZJP markedly corrected lipid metabolism, bile acid biosynthesis, energy metabolism, and inflammatory eicosanoid pathways, and promote retinal cholesterol efflux via upregulation of LXR&#x3b1; and ABCA1, and modulate LDLR-mediated cholesterol uptake.<br><br>CONCLUSIONS: Rooted in the TCM theory of 'nourishing liver and kidney to benefit eyesight', ZJP (composed of Cuscutae Semen, Plantaginis Semen, and Rehmanniae Radix) ameliorates AMD by regulating LXR&#x3b1;/ABCA1-mediated cholesterol efflux, suppressing complement activation, and normalizing lipid and bile acid metabolism. These findings provide mechanistic support for the traditional use of ZJP in ocular disorders and highlight its potential as a therapeutic candidate for AMD.}, }
@article {pmid41958546, year = {2026}, author = {Bautista-Hernández, MA and Torres-Rosas, R and Argueta-Figueroa, L and Moreno-Rodríguez, A and Pérez-Cervera, Y and Acevedo-Mascarúa, AE and Martínez-Martínez, EA}, title = {Acupuncture in the treatment of inflammation-related ocular degenerations: a systematic review.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1749297}, pmid = {41958546}, issn = {2296-858X}, abstract = {BACKGROUND: Inflammation-related ocular degenerations include dry eye syndrome, diabetic retinopathy, age-related macular degeneration, and glaucoma. Until now, there are no efficient protocols for treating inflammation-related ocular degenerations. On the other hand, acupuncture therapy modulates the inflammatory and oxidative stress responses in several inflammatory diseases and has been proposed as an emerging therapy for the potential treatment of ocular pathologies.<br><br>OBJECTIVE: This work aimed to conduct a comprehensive systematic review to address the efficacy of acupuncture therapy for Inflammation-related ocular degenerations.<br><br>METHODS: The designs of the included studies were clinical trials and observational studies, whereas case series, in vivo, and in vitro studies were excluded. The search was performed in five databases. Relevant data from all included studies were recorded, the outcomes analyzed were intraocular pressure and visual acuity for glaucoma; score of symptoms, pain, tear-film breakup time, and mm of Schirmer test for dry eye syndrome; visual acuity, retinal structure or disease progression for diabetic retinopathy; and finally visual acuity and scores of symptoms for age-related macular degeneration. Risk of bias (using the RoB 2 tool) and quality (using the Grading of Recommendations Assessment, Development, and Evaluation [GRADE] tool) assessments were conducted.<br><br>RESULTS: The included studies showed heterogeneity, risk of bias, inconsistency, and very low certainty of evidence.<br><br>CONCLUSION: There is no conclusive evidence to support that acupuncture is an effective therapy in patients with inflammation-related ocular degeneration disease.<br><br>https://www.crd.york.ac.uk/PROSPERO/view/CRD42022368882, identifier PROSPERO (CRD42022368882).}, }
@article {pmid41959212, year = {2026}, author = {Voigt, AP and Mullin, NK and Mulfaul, K and Lozano, LP and Navratil, EM and Flamme-Wiese, MJ and Lavine, JA and Fingert, JH and Tucker, BA and Stone, EM and Scheetz, TE and Mullins, RF}, title = {Single-Cell Gene Expression and eQTL Analyses in the Human Retina, RPE, and Choroid in Macular Degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.30.714946}, pmid = {41959212}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD) is a common, complex disease affecting older individuals that can lead to severe vision loss. It is characterized by early anatomical changes in the retina, retinal pigment epithelium (RPE), and choroid, especially in the central (macular) region. AMD can progress to severe atrophy and/or pathologic angiogenesis that leads to visual decline. Over 30 genetic loci have been identified as contributing to AMD risk; however, the mechanisms by which genetic variants affect pathology has not been thoroughly explored. In this report we examined single-nucleus gene expression in the retina, RPE and choroid of 88 individuals categorized by AMD stage, as well as 37 previously published samples. Genotyping was performed on 1.8 million SNPs, with additional SNPs imputed, on each donor to identify expression quantitative trait loci (eQTLs). We found that two AMD-risk loci (PILRB and ARMS2/HTRA1) affected the expression of PILRB and HTRA1, respectively. The risk allele of PILRB was associated with increased PILRB RNA in cones, fibroblasts, choroidal macrophages, and RPE, whereas the HTRA1 risk locus was associated with decreased HTRA1 RNA in the RPE. We also identified an age-related decrease in complement inhibitors in the choriocapillaris, a tissue susceptible to complement mediated damage in AMD.}, }
@article {pmid41959804, year = {2026}, author = {Yeh, TC and Lin, JB and Mruthyunjaya, P and Leng, T and DeBoer, C and Sepah, YJ and Almeida, DR and Smith, S and Mahajan, VB}, title = {A Simplified Classification for Age-Related Macular Degeneration Based on Optical Coherence Tomography.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.29.26349635}, pmid = {41959804}, abstract = {BACKGROUND AND OBJECTIVE: As optical coherence tomography (OCT) has enabled the identification of an expanding set of age-related macular degeneration (AMD) risk biomarkers and become central to routine clinical practice, there remains a need for a simplified grading scheme that allows physicians to communicate and synchronize AMD grading directly from standard OCT imaging rather than relying on traditional color fundus imaging. This study aims to establish a standardized OCT-based AMD classification that balances diagnostic accuracy with practicality for use across clinical and research settings.<br><br>PATIENTS AND METHODS: Spectral-domain optical coherence tomography scans were independently graded by two retinal specialists following the newly proposed Stanford OCT-Based AMD Classification (SOAC). Discrepancies were adjudicated by a third independent retinal specialist. Intergrader agreement was assessed using weighted kappa coefficients.<br><br>RESULTS: Among the 109 eyes from 108 patients (mean age 79.61&#x25a1;&#xb1;&#x25a1;7.57 years; 41.7% male, 58.3% female), AMD staging based on SOAC was distributed as follows: normal aging in 9 patients (8.3%), early AMD in 16 (14.7%), intermediate AMD in 32 (29.4%), neovascular AMD (nAMD) in 18 (16.5%), geographic atrophy (GA) in 20 (18.3%), and combined nAMD and GA in 14 (12.8%). The overall intergrader agreement demonstrated robust consistency, with a weighted kappa value of 0.95 (95% CI: 0.92-0.98), signifying excellent intergrader reliability and reinforcing the validity of SOAC.<br><br>CONCLUSION: SOAC provides a standardized, OCT-based framework for AMD grading that demonstrates high intergrader agreement. By enabling consistent classification from commonly acquired OCT scans, SOAC supports reliable disease staging and facilitates integration across clinical studies and translational research. As imaging and molecular data continue to expand, SOAC can serve as a common OCT-based reference for phenotype refinement and longitudinal AMD studies.<br><br>KEY QUESTIONS: What is already known on this topic? Existing classifications of age-related macular degeneration (AMD) rely heavily on color fundus photography and inconsistently incorporate optical coherence tomography (OCT) biomarkers, despite OCT's superior resolution for detecting subclinical structural changes. What this study adds? This study introduces an OCT-based classification framework that consolidates key biomarkers with proven prognostic relevance into a simplified, tiered staging protocol. By prioritizing a curated set of evidence-supported, high-risk OCT biomarkers, the Stanford OCT-Based AMD Classification (SOAC) provides a common framework and shared language for OCT-based AMD staging, facilitates longitudinal monitoring, and reduces intergrader variability through standardized reporting guidelines. The framework deliberately balances clinical practicality with scientific rigor, excluding less significant or potentially confusing features to ensure scalability across diverse clinical and research settings. How this study might affect research, practice or policy? SOAC provides an OCT-based framework for AMD staging with high inter-physician agreement. This is particularly important in real-world clinical and translational research settings, where color fundus photography is not always available. By offering a common OCT-based reference, SOAC reduces diagnostic variability and supports more consistent AMD staging across clinicians and studies. The classification incorporates up-to-date, evidence-based, high-risk OCT features associated with disease progression and is designed to be scalable, allowing integration with emerging multimodal data, including AI-driven imaging analysis and molecular profiling. By bridging advances in retinal imaging with practical clinical application, SOAC lays the groundwork for improved risk stratification, longitudinal outcome studies, and more standardized reporting in AMD.}, }
@article {pmid41960189, year = {2026}, author = {Ryu, Y and Jeong, D and Kim, JH and Kim, YK}, title = {CircAFF3 modulation of p53-ID2 signaling in the retinal pigment epithelium links inflammation with cell death in dry age-related macular degeneration.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1733888}, pmid = {41960189}, issn = {2296-634X}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) represents a multifactorial disease that is influenced by age, genetic, and environmental factors. AMD is characterized by dysfunction of the retinal pigment epithelium (RPE) resulting from oxidative stress, inflammation, and complement activation. As the disease progresses, the loss of the RPE and photoreceptors leads to geographic atrophy, which is a hallmark of dry AMD. Although research is ongoing, there is currently no established effective treatment for dry AMD. Notably, circular RNAs (circRNAs) have been studied in various diseases; however, the role of circRNAs in eye diseases remains poorly understood. To fill this gap, this study aimed to investigate circRNAs as potential therapeutic targets for dry AMD.<br><br>METHODS: We identified candidate circRNAs using a laser-induced choroidal neovascularization (CNV) model. The function of circAFF3 was investigated through knockdown experiments in ARPE-19 cells, followed by transcriptomic analysis, pathway enrichment, and functional assays, including qPCR, western blotting, immunofluorescence, monocyte adhesion, and measurements of ROS, iron, lipid peroxidation, and apoptosis. Interaction between circAFF3 and p53 was explored using binding prediction, RNA-binding protein immunoprecipitation, and cycloheximide chase assay.<br><br>RESULTS: We found that circAff3 levels were downregulated in RPE samples at day 3 after laser injury. Moreover, silencing circAFF3 induced an inflammatory response in ARPE-19 cells. Based on these results, a subsequent transcriptomic analysis of circAFF3 knockdown in ARPE-19 cells was conducted to further elucidate its function. These analyses showed that genes downregulated by circAFF3 knockdown in ARPE-19 cells were significantly associated with retinal degeneration. Additionally, reduced circAFF3 expression promoted a decrease in ID2 levels, resulting in increased oxidative stress and cell death. Our study further demonstrated that circAFF3 directly interacts with p53, thereby regulating ID2 expression in ARPE-19 cells.<br><br>CONCLUSION: Collectively, our study reveals that circAFF3 plays a crucial role in RPE dysfunction by modulating a circAFF3/p53/ID2 pathway, suggesting that circAFF3 can serve as a key regulator with therapeutic potential in dry AMD.}, }
@article {pmid41960651, year = {2026}, author = {Zeender, G and Moulin, A and Rizzuto, P and Elbany, S and Gascon, P and Allaix, K and Feldman, A and De Bats, F and Wolff, B and Bassouamina-Kinanga, E and Dot, C and Kodjikian, L and Mathis, T}, title = {Recurrence after treat-and-extend suspension in neovascular age-related macular degeneration: A real-world analysis by macular neovascularization subtype.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70132}, pmid = {41960651}, issn = {1755-3768}, }
@article {pmid41960966, year = {2026}, author = {Akada, M and Ideyama, M and Kido, A and Miyata, M and Ueda-Arakawa, N and Tamura, H and Ooto, S and Miyake, M and Tsujikawa, A and Hata, M}, title = {Age-Specific Increases in the Prevalence and Treatment Burden of Neovascular Age-Related Macular Degeneration in a Super-Aged Society.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {19}, doi = {10.1167/iovs.67.4.19}, pmid = {41960966}, issn = {1552-5783}, mesh = {Humans ; Aged ; Male ; Female ; Prevalence ; Cross-Sectional Studies ; Japan/epidemiology ; Aged, 80 and over ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/epidemiology/drug therapy ; Adult ; Databases, Factual ; *Cost of Illness ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Comorbidity ; Age Distribution ; Recombinant Fusion Proteins/therapeutic use ; }, abstract = {PURPOSE: To characterize age-specific changes in the prevalence and treatment burden of neovascular AMD (nAMD) from 2014 to 2019 in a super-aged society and to assess whether comorbidities contribute to this increase.<br><br>METHODS: We performed a nationwide repeated cross-sectional study using Japan's national claims database (>95% population coverage). Adults aged &#x2265;40 years in 2014 and 2019 were included to estimate age-stratified nAMD prevalence. Treatment burden was evaluated as the total number of nAMD-related treatment claims and mean administrations among users of each agent. Diabetes, hypertension, and dyslipidemia were identified from claims. Multivariable logistic regression compared nAMD cases with controls and assessed whether comorbidity adjustment attenuated the odds of nAMD in 2019 versus 2014.<br><br>RESULTS: We identified 76,125 cases in 2014 and 125,190 in 2019; age-standardized prevalence increased from 101.3 to 152.4 per 100,000. Prevalence peaked at ages 80-84 in both years but increased most steeply among those &#x2265;75 years (62.9%). Total treatment claims increased markedly, driven primarily by aflibercept. Among users of each agent, mean administrations increased modestly. Comorbidities were associated with higher odds of nAMD, but adjusting for them did not change the higher odds of nAMD in 2019 compared with in 2014.<br><br>CONCLUSIONS: Between 2014 and 2019, the prevalence and treatment burden of nAMD increased substantially in Japan, with a disproportionate rise among older age groups in a super-aged population. Comorbidities did not account for the temporal increase, suggesting that factors beyond aging and comorbidity are contributing to the growing burden.}, }
@article {pmid41961694, year = {2026}, author = {Dugiełło, B and Bolek, B and Walasz, K and Kijonka, M and Wylęgała, E and Wylęgała, A}, title = {OCT angiography-derived biomarkers of retinal and choroidal microvascular changes in dry age-related macular degeneration.}, journal = {Medicine}, volume = {105}, number = {15}, pages = {e48033}, doi = {10.1097/MD.0000000000048033}, pmid = {41961694}, issn = {1536-5964}, mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Aged ; *Retinal Vessels/diagnostic imaging/pathology ; Biomarkers ; Middle Aged ; *Macular Degeneration/diagnostic imaging ; Fluorescein Angiography/methods ; *Microvessels/diagnostic imaging/pathology ; Aged, 80 and over ; }, abstract = {This study aimed to identify optical coherence tomography angiography (OCTA) biomarkers associated with disease severity in dry age-related macular degeneration (dAMD). This cross-sectional study included 142 eyes (104 patients) with dAMD, classified as early (n = 34), intermediate (n = 40), or late stage (n = 37) according to the Beckman Classification, and 30 control eyes without AMD. OCTA-images were obtained using the ZEISS PLEX Elite 9000, vascular metrics such as vessel density, total number of junctions, total and average vessel length, junction density, total number of endpoints, and lacunarity were assessed in the superficial capillary plexus, deep capillary plexus (DCP), and choriocapillaris (CC) using AngioTool software. The CC showed the most pronounced changes, with vessel percentage area reduced from 58.98 ± 4.86% in controls to 52.14 ± 10.30% in intermediate and 31.34 ± 11.27% in late AMD (P <.001). Total vessel length declined from 407.52 ± 16.33 mm to 367.09 ± 49.18 mm and 217.23 ± 86.88 mm, respectively (P <.001), while lacunarity increased nearly 50-fold in late AMD (0.56 ± 0.91 vs 0.01 ± 0.00; P <.001). In the DCP, vessel percentage area decreased from 45.68 ± 4.92% in controls to 41.95 ± 5.08% in intermediate and 38.24 ± 6.71% in late AMD (P <.001). Vessel length dropped from 275.21 ± 21.82 mm to 254.13 ± 28.78 mm and 224.68 ± 36.37 mm (P <.001), with increased lacunarity in intermediate and late stages (P <.01). The superficial capillary plexus showed early alterations, with vessel percentage area reduced from 41.46 ± 1.58% in controls to 39.42 ± 3.45% in early AMD (P = .017) and total vessel length decreased from 202.85 ± 10.65 mm to 191.42 ± 18.67 mm and 185.92 ± 18.09 mm in intermediate AMD (P <.001). Mean lacunarity was elevated in all AMD stages (P <.001). OCTA reveals distinct, layer-specific microvascular changes in AMD mainly within DCP and CC. Vessel percentage area, total vessel length, and lacunarity represent sensitive, noninvasive OCTA biomarkers of microvascular impairment in dry AMD, with potential applicability for longitudinal disease monitoring and as quantitative imaging endpoints in future interventional trials.}, }
@article {pmid41962145, year = {2026}, author = {Basyal, D and Bhandari, SK and Kim, HJ}, title = {Targeting retinal degeneration: zeaxanthin dipalmitate from Lycium barbarum L. prevents A2E photooxidation under blue light.}, journal = {Natural product research}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/14786419.2026.2654653}, pmid = {41962145}, issn = {1478-6427}, abstract = {The accumulation of the toxic byproduct A2E in retinal pigment epithelial cells, coupled with blue-light-induced photooxidation, is a key driver of oxidative damage in early age-related macular degeneration (AMD). Zeaxanthin dipalmitate (ZD), the esterified carotenoid abundant in goji berries, has higher lipophilicity and stability. In this study, ZD was isolated from the berries using its fat-soluble nature and purified using medium-pressure liquid chromatography. Isolated ZD and synthesised A2E were structurally characterised using HPLC, NMR, and positive mode LC-ESI-TQ-MS. An acellular photo-oxidation assay revealed that ZD significantly suppressed A2E degradation under blue light with higher efficacy than vitamin E, a standard antioxidant control. This indicates ZD's potent ability to filter blue light and scavenge reactive oxygen species, mitigating A2E photooxidation and phototoxicity. These findings highlight ZD's unique structural advantages for sustained retinal protection. The findings also support further in vivo and clinical studies of ZD as a natural photoprotective agent that targets early events in AMD.}, }
@article {pmid41962545, year = {2026}, author = {Copland, DA and Liu, J and Chan, YK and Dick, AD and Clare, AJ}, title = {Can NRF2 provide a gene-agnostic approach to treating age-related macular degeneration?.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.03.029}, pmid = {41962545}, issn = {1525-0024}, }
@article {pmid41952808, year = {2026}, author = {Gad El Sayed, M and Vu Pham, N and Bandaru, D and Abboud, I and Zakhary, MB and Zakhary, M and Bishay, RGE and Rezaei, K and Khaksar, P and Enciso, J and Tran, K and Martinez, SJ and Mikhail, K and Glendrange, RR and Fouad, Y}, title = {Smoking and Risk of Vision Threatening Complications: A Global Database Analysis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {596936}, pmid = {41952808}, issn = {1177-5467}, abstract = {PURPOSE: To investigate the association between smoking and the incidence of vision-threatening conditions, including cataract, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vascular occlusion, uveitis, and ischemic optic neuropathy (ION) in a large real-world database to provide quantitative risk estimates to inform smoking cessation counseling.<br><br>METHODS: A retrospective cohort study was conducted using the TriNetX electronic health records platform, analyzing 12,183,254 patients. Patients were categorized into smokers (n = 304,823) and non-smokers (n = 11,878,431), and then a propensity score matching was utilized to balance both groups for demographic features and vascular risk factors. The incidence rates of the studied ocular conditions were then compared over a ten-year period using risk ratios (RR).<br><br>RESULTS: Matched cohorts included 300,867 patients per group. Smokers exhibited a significantly higher 10-year risk for all studied ophthalmic outcomes (p < 0.0001). The strongest associations were observed for posterior subcapsular cataract (RR 2.60; 95% CI, 2.41-2.82), uveitis (RR 2.43 [2.25-2.63]), and retinal vascular occlusions (CRAO: RR 2.35; CRVO: RR 2.16). Increased risks were also consistent across glaucoma subtypes (RR 1.57-2.47), AMD (RR 1.85), and diabetic retinopathy (RR 1.21).<br><br>CONCLUSION: Smoking is significantly associated with an increased risk of multiple vision-threatening ocular diseases. These findings highlight the need for ophthalmologists and public health professionals to incorporate smoking history into risk stratification and screening programs and to emphasize ocular health during smoking cessation counseling.}, }
@article {pmid41952906, year = {2026}, author = {Chen, Q and Zhang, J and Xu, K and Liu, X and Liang, L}, title = {Qiju Granule alleviates retinal damage in a mouse model of age-related macular degeneration.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1781217}, pmid = {41952906}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Despite recent advances, the pathophysiology of AMD remains incompletely understood, and current therapies are limited. Qiju Granule is a traditional herbal formulation with therapeutic potential; however, its efficacy and mechanisms in AMD remain unclear.<br><br>OBJECTIVE: The aim of this study was to evaluate the protective effects of Qiju Granule in a mouse model of AMD and investigate potential underlying mechanisms.<br><br>METHODS: AMD-like retinal injury was induced in C57BL/6J mice by chronic light exposure combined with hydroquinone feeding. Retinal function and structure were assessed using electroretinography and histomorphological analyses. Retinal cell apoptosis and the expression of key angiogenic factors (VEGF and CD31) were assessed to explore underlying mechanisms.<br><br>RESULTS: Qiju Granule treatment significantly preserved retinal function, as reflected by improved electroretinographic responses, and maintained structural integrity of the retina and RPE layer. Mechanistically, Qiju Granule exerted potent anti-apoptotic effects, evidenced by a marked reduction in TUNEL-positive retinal cells. Furthermore, it downregulated VEGF and CD31 expression, indicating suppression of aberrant angiogenic signaling.<br><br>CONCLUSION: Our findings identified a protective role of Qiju Granule in mitigating AMD-related retinal damage and suggested its potential as a therapeutic candidate to prevent progression to advanced AMD.}, }
@article {pmid41953649, year = {2026}, author = {Armendariz, BG and Kent, D}, title = {Submacular tissue repair and fibrosis in neovascular macular degeneration: A predictable outcome secondary to a chronic age-related endotheliopathy.}, journal = {Molecular vision}, volume = {32}, number = {}, pages = {22-32}, pmid = {41953649}, issn = {1090-0535}, mesh = {Humans ; Fibrosis ; *Macular Degeneration/pathology/metabolism/drug therapy/physiopathology ; Animals ; Extracellular Matrix/metabolism/pathology ; Chronic Disease ; *Aging/pathology ; Endothelial Cells/pathology/metabolism ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Capillary Permeability ; }, abstract = {Fibrosis is strictly a histopathological term that refers to the replacement of functional tissue with permanent deposition of nonfunctional extracellular matrix (ECM), following an injury or disease, and can occur in any tissue in the body. In this histological setting, there is no overt difference between fibrosis and scarring. However, in the clinical context, fibrosis tends to be associated with chronic disease, as it ensures ongoing ECM deposition. This could be considered "excessive" when compared to ECM deposition in acute or end-stage chronic disease. This perspective highlights how fibrosis in neovascular age-related macular degeneration follows a stereotypical tissue repair process similar to that seen in other tissues and how salient biologic processes, such as aging and metabolic health, impact fibrosis development. In addition, we highlight the emerging and pivotal profibrogenic role played by progressive endothelial cell (EC) dysfunction, together with secondary blood flow impedance in the neovasculature. This results in abnormal vascular permeability, endothelial-to-mesenchymal transition, and EC senescence-associated secretory phenotype, processes that could potentially be targeted therapeutically. Finally, the dramatic impact of anti-vascular endothelial growth factor therapy, by primarily targeting permeability of the nascent microvasculature, on the natural history of fibrosis in neovascular age-related macular degeneration indirectly highlights the potentially significant role of ECs in fibrosis development and points toward how novel future targeting of these cells could further modulate the development of fibrosis.}, }
@article {pmid41954091, year = {2026}, author = {Lin, Y and Du, Y and Shu, Q and Su, W and Peng, H and Wang, X}, title = {Belzutifan Attenuates Choroidal Neovascularization by Suppressing the HIF-2α/PAI-1 Axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {7}, pages = {e71740}, doi = {10.1096/fj.202503954RR}, pmid = {41954091}, issn = {1530-6860}, support = {CSTB2024NSCQ-MSX0705//CSTC | Natural Science Foundation of Chongqing Municipality ()/ ; CSTB2024NSCQ-MSX1234//CSTC | Natural Science Foundation of Chongqing Municipality ()/ ; //Chongqing Medical University/ ; }, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Rats ; Humans ; *Basic Helix-Loop-Helix Proteins/metabolism/antagonists &amp; inhibitors/genetics ; *Plasminogen Activator Inhibitor 1/metabolism/genetics ; Rats, Sprague-Dawley ; Male ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Indenes ; }, abstract = {Choroidal neovascularization (CNV) is the hallmark pathology of exudative age-related macular degeneration (AMD). Although anti-vascular endothelial growth factor (VEGF) therapy is widely used, its limitations, including drug resistance and treatment burden, necessitate alternative targets. This study aimed to investigate the role of hypoxia-inducible factor-2α (HIF-2α) in CNV pathogenesis and evaluate the therapeutic potential of its inhibitor Belzutifan, with a particular focus on validating the functional significance of the HIF-2α/plasminogen activator inhibitor-1 (PAI-1) axis. The efficacies of Belzutifan were assessed in a laser-induced CNV rat model using H&amp;E staining, OCT, fundus photography, and immunofluorescence. Network pharmacology identified potential therapeutic pathways. In vitro, CoCl2-injured HUVECs were used to evaluate the effects of drugs on proliferation, migration, and tube formation. The expression levels of HIF-2α, PAI-1, VEGF-A, Ve-cadherin, and inflammatory factors were assessed by ELISA, immunofluorescence, and Western blot analysis. This study demonstrated that Belzutifan inhibits CNV by targeting the HIF-2α/PAI-1 axis. It also showed that Belzutifan can markedly reduce the expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). Both the HIF-2α inhibitor and the PAI-1 inhibitor suppressed the proliferation, migration, and tube formation of HUVECs. Intravitreal injection of both inhibitors effectively reduced neovascularization from Day 14 to Day 21 in the laser-induced CNV rat model. Collectively, these findings provide a novel therapeutic strategy for exudative AMD and highlight its significant clinical translational value.}, }
@article {pmid41954492, year = {2026}, author = {Spaide, RF and Lee, K and Kuo, JW and Akiba, M and Durbin, M and Naderi, A and Ko, TH and Tafreshi, A}, title = {Retinal Blood Velocity after Intravitreal Injection for Neovascular Age-Related Macular Degeneration with Optical Coherence Tomography Using Speckle Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004851}, pmid = {41954492}, issn = {1539-2864}, abstract = {PURPOSE: To quantify the effect of transient intraocular pressure (IOP) elevation after intravitreal injection on retinal blood flow using a validated speckle-based optical coherence tomography (OCT) method.<br><br>METHODS: Nineteen eyes of 19 patients with neovascular age-related macular degeneration underwent OCT imaging and IOP measurement before, immediately after, and for &#x223c;15 minutes after anti-VEGF injection. Retinal blood flow was quantified using a speckle-derived flow index proportional to the erythrocyte velocity. Flow changes were analyzed with linear mixed-effects models incorporating IOP, age, and vessel type.<br><br>RESULTS: Mean pre-injection IOP was 14.1 mm Hg, rising to 54.4 mm Hg immediately post-injection and decreasing to 24.1 mm Hg after 15.4 minutes. Flow remained stable for IOPs &#x2264; 40 mm Hg but declined by 3.6% per mm Hg above this threshold (P < 0.001). Older patients exhibited less arterial flow reduction at higher pressures, a modest effect observed only in arteries, not veins. In a limited comparison of the youngest and oldest participants, the arteriolar walls in older eyes appeared thicker and more reflective, consistent with arteriolosclerosis.<br><br>CONCLUSIONS: Speckle-based OCT enables direct, quantitative assessment of retinal blood flow in vivo. Retinal perfusion remains stable through transient IOP elevations up to about 40 mm Hg, likely reflecting autoregulatory reserve, but declines at higher pressures. The relative flow preservation in older eyes may result from increased vascular wall rigidity. Speckle-based OCT provides a practical, quantitative method to assess retinal blood flow dynamics in vivo.}, }
@article {pmid41954837, year = {2026}, author = {Eker, S and Erdem, A and Acar, U and Gönül, &#x15e;}, title = {Evaluation of the triglyceride-glucose index, serum inflammatory biomarkers and lipid profile in patients with neovascular age-related macular degeneration.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41954837}, issn = {1573-2630}, mesh = {Humans ; Female ; Male ; Biomarkers/blood ; Retrospective Studies ; Aged ; *Triglycerides/blood ; *Blood Glucose/metabolism ; Case-Control Studies ; *Lipids/blood ; *Wet Macular Degeneration/blood/diagnosis ; Middle Aged ; Inflammation/blood ; Aged, 80 and over ; }, abstract = {PURPOSE: To evaluate the triglyceride-glucose index (TyG), novel systemic inflammatory biomarkers, and lipid profile in patients with neovascular age-related macular degeneration (nAMD), and to investigate their potential relationship with disease presence.<br><br>METHODS: This retrospective case-control study included 59 patients diagnosed with nAMD and 67 age- and sex-matched healthy controls. Demographic characteristics, fasting biochemical tests, lipid profile, complete blood count, and serum inflammatory indices were recorded. Triglyceride-glucose index, systemic inflammatory indices derived from various hematological parameters and lipid levels were calculated. Laboratory parameters and calculated indexes were compared between the two groups using Statistical Package for the Social Sciences (SPSS).<br><br>RESULTS: Triglyceride-glucose index was significantly higher in the nAMD group than in controls (4.84&#x2009;&#xb1;&#x2009;0.27 vs. 4.69&#x2009;&#xb1;&#x2009;0.17, p&#x2009;=&#x2009;0.0001). Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels were also elevated in the nAMD group (p&#x2009;=&#x2009;0.0001 for both). Among hematological markers, white blood count (WBC), neutrophil, and monocyte counts were significantly increased in nAMD patients (p&#x2009;=&#x2009;0.012, p&#x2009;=&#x2009;0.001, p&#x2009;=&#x2009;0.015, respectively). Inflammatory indices including neutrophil/lymphocyte ratio (NLR) (p&#x2009;=&#x2009;0.015), monocyte/HDL-C ratio (MHR) (p&#x2009;=&#x2009;0.003), systemic inflammation aggregate index (AISI) (p&#x2009;=&#x2009;0.025), and C reactive protein/albumine ratio (CAR) (p&#x2009;=&#x2009;0.006) were significantly higher in the nAMD group, whereas the systemic immune inflammation index (SII), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) showed no significant differences (p&#x2009;>&#x2009;0.05). Serum lipid levels and atherogenic lipid ratios did not differ between the groups.<br><br>DISCUSSION: Patients with nAMD exhibit increased systemic inflammatory activity and metabolic stress, reflected by elevated NLR, MHR, AISI, and CAR levels. In addition, TyG, a novel indicator of systemic insulin resistance, was found to be elevated in nAMD patients. These findings suggest that metabolic dysregulation and chronic low-grade systemic inflammation may contribute to nAMD pathogenesis independently of serum lipid levels. The TyG and inflammation-derived biomarkers may serve as potential systemic indicators for nAMD risk or disease activity.}, }
@article {pmid41954906, year = {2026}, author = {Thottarath, S and Gurudas, S and Kubravi, S and Kazantzis, D and Keskin, AM and Sivaprasad, S and , }, title = {Nonexudative Macular Neovascularization in Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaophthalmol.2026.0459}, pmid = {41954906}, issn = {2168-6173}, abstract = {IMPORTANCE: Nonexudative macular neovascularization (neMNV) is a risk factor for exudation in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD). Accurate estimation of prevalence of neMNV is required for sample size calculations for clinical trials evaluating novel interventions to delay exudation from neMNV. Certain dimensions of double-layer sign (DLS) on optical coherence tomography (OCT) are often regarded as a surrogate for neMNV.<br><br>OBJECTIVE: To assess the prevalence of fellow-eye neMNV on OCT angiography (OCT-A) in eyes with AMD with DLS on OCT among patients with unilateral new-exudative AMD in the first eye.<br><br>This prospective observational cohort multicenter study took place in the United Kingdom from January 2021 through June 2025. The study included 862 participants with OCT and OCT-A within 3 months of initiation of anti-vascular endothelial growth factor (VEGF) therapy, of whom 550 (63.8%) had both OCT and OCT-A performed within 30 days of the date of the first anti-VEGF injection to the fellow eye. These data were analyzed from July 2025 through October 2025.<br><br>MAIN OUTCOMES AND MEASURES: Prevalence of DLS, neMNV, and assessment of univariable and adjusted associations with neMNV and DLS were assessed using logistic regression models.<br><br>RESULTS: Among 550 eyes (mean [SD] participant age, 78.0 [7.6] years; 315 female [57.3%] and 235 male [42.7%]), 112 (20.4%; 95% CI [Wilson score], 17.1%-24.0%) had DLS and 47 eyes (8.5%; 95% CI [Wilson score], 6.4%-11.3%) had neMNV at baseline, including 42 (89.36%) within DLS, 3 (6.4%) in fibrovascular irregular shallow-pigment epithelial detachment, and 2 (4.3%) below drusen. Prevalence of neMNV was higher among eyes with thick DLS (n&#x2009;=&#x2009;36 [48%]) compared with those with thin DLS (16.2%; n&#x2009;=&#x2009;6; difference&#x2009;=&#x2009;-31.8%; 95% CI [Wilson score], -46.9% to -11.7%; P&#x2009;=&#x2009;.002).<br><br>CONCLUSIONS AND RELEVANCE: While 1 in 5 fellow eyes had DLS on OCT among patients with unilateral new-onset exudative AMD in the first eye, the prevalence of neMNV on OCT-A was only 40% among these eyes with DLS. These results suggest DLS on OCT in fellow eyes of patients with new-onset exudative AMD in the first eye is not a good surrogate for neMNV.<br><br>TRIAL REGISTRATION: ISRCTN registry Identifier: ISRTCTN13798759.}, }
@article {pmid41955658, year = {2026}, author = {Desmettre, T and Paques, M}, title = {[Retro mode imaging and early-stage AMD].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {5}, pages = {104859}, doi = {10.1016/j.jfo.2026.104859}, pmid = {41955658}, issn = {1773-0597}, abstract = {Age-related macular degeneration (AMD) is a chronic disease whose progression toward advanced stages is closely related to the phenotype observed at the early and intermediate stages. The detection and characterization of drusen and pigmentary abnormalities are central to the stratification of progression risk. Retro mode imaging, based on indirect infrared retro-illumination, enhances the visualization of retinal surface elevation, depth-related features, and variations in pigment density. This review examines the contribution of the various retro mode configurations (deviated left [DL]; deviated right [DR]; and ring aperture [RA]) in AMD, based on recent data in the literature as well as our clinical experience. When integrated into a multimodal imaging strategy, the combined use of DL and DR modes improves the detection and morphological assessment of drusen, while the ring aperture mode facilitates the identification of subtle pigment migration at the onset of the disease. A more precise characterization of these lesions allows refinement of AMD staging and provides clinically meaningful prognostic information.}, }
@article {pmid41955664, year = {2026}, author = {Mathis, T and Devin, F and Gabrielle, PH and Grenet, T and Gualino, V and El Khatib, N and Del Rio, M and Balez, S and Souied, E}, title = {PICCTURE: Survey of French ophthalmologists' practices for the treatment of neovascular age-related macular degeneration patients currently treated with anti-VEGF.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {5}, pages = {104861}, doi = {10.1016/j.jfo.2026.104861}, pmid = {41955664}, issn = {1773-0597}, abstract = {PURPOSE: To evaluate the practices of French ophthalmologists in the management of neovascular age-related macular degeneration (nAMD) with regard to the identification of criteria influencing therapeutic decision-making and motivating the need for a new molecule.<br><br>METHODS: A survey of practices based on the validated case-vignette method was conducted from January to September 2023 and included 110 ophthalmologists throughout France. A total of 480 clinical cases were developed based on disease progression (worsening, stability, improvement), the presence or absence of exudative signs (intraretinal fluid, subretinal fluid, or subretinal hyperreflective material), and the volume of retinal fluid (obvious or subtle). For each case, ophthalmologists assessed whether to continue the current anti-VEGF treatment or change the injection interval and/or molecule, and they assessed the benefit of having a new molecule available.<br><br>RESULTS: In 76.9% of cases, clinical cases showed disease activity (56.5% worsening and 20.4% disease stability). The fluid present was mostly subtle in 55% of the cases and obvious in 38.8% of the cases. Among the responding physicians, 82.5% intended to change the treatment entirely, and 71.8% opted to change only one parameter (molecule or treatment interval). The common criterion for a change in treatment was disease worsening. For the same clinical case, 92% of those who opted for a single change and 87% of those who opted for a change in interval and molecule would consider it relevant to propose a new anti-VEGF. Among the physicians, 55.8% would maintain the treatment interval identical to that of the previous treatment. The most common criteria for the need for a new molecule was the obvious presence of exudative signs (P<0.001), treatment every&#x2264;6weeks (P<0.001), initial treatment for 3-6months (P<0.001), and visual acuity of 20/200 (P<0.001).<br><br>CONCLUSION: This survey provides an overview of current management strategies for patients with nAMD in France and identifies criteria influencing therapeutic decision-making based on different patient profiles. This highlights the interest of ophthalmologists in having new molecules to treat insufficiently controlled patients.}, }
@article {pmid41956945, year = {2026}, author = {Li, S and Gao, T and Wang, Y and He, Q and Ma, H and Ye, H and Shen, Y and Wang, Y and Wang, Y and Li, X and Fang, S and Chen, Q and Liu, Q and Sun, G and Xin, H and Xue, J and Liu, S and Zhu, M and Xu, W and Wang, Z and Shao, J and Xie, M}, title = {Rationally designed light-inducible RNA-releasing protein for translational regulation and optogenetic control of gene therapies.}, journal = {Trends in biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tibtech.2026.03.004}, pmid = {41956945}, issn = {1879-3096}, abstract = {In this study, we describe a rationally designed light-inducible RNA-releasing protein (LIRP) capable of inhibiting mRNA translation in the dark while permitting gene expression upon exposure to blue or ambient light. This LIRP-dependent gene switch is compatible with various delivery routes of gene- and cell-based therapy, such as subcutaneous implantation of microencapsulated light-sensitive cells or expression in various light-accessible body sites using single adeno-associated virus (AAV) vectors. To exemplify a gene therapy approach that directly harnesses ambient light as a natural illumination source to induce therapeutic action, we show how intradermal delivery of AAV2 vectors carrying a LIRP-regulated gene switch controlling murine thymic stromal lymphopoietin expression was effective in enabling light-dependent prevention and treatment of diet-induced obesity. To describe another therapeutic scenario, we engineered AAV2 vectors for LIRP-dependent expression of Vascular endothelial growth factor (VEGF) inhibitors for the treatment of retinal neovascular diseases. Upon intravitreal delivery into mice suffering from wet macular degeneration, VEGF inhibitors were constantly produced when animals were exposed to daylight, but therapeutic actions could be flexibly interrupted either by exposure to dark environments or by administration of a selective blue light filter at any point in time. When compared to conventional treatment strategies based on constitutive VEGF inhibition over the course of 3 months, we show that a regulated gene therapy approach through LIRP-dependent optogenetics was advantageous in maintaining a normal retina thickness. This work not only provides a valuable addition to the optogenetic toolbox but also offers a perspective to translate light-dependent gene switches toward therapeutic usage.}, }
@article {pmid41957251, year = {2026}, author = {Koh, A and Staurenghi, G and Chhablani, J and Panos, GD and Tan, CS and Yamaguchi, TCN and Empeslidis, T}, title = {Long-Term Management of Polypoidal Choroidal Vasculopathy: A Narrative Review.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41957251}, issn = {2193-8245}, abstract = {Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (nAMD), characterised by polypoidal lesions. Prevalence data indicate that PCV is more common in people of Asian ethnicity, although it also occurs in non-Asian individuals. However, because of a lack of globally agreed diagnostic criteria and routine screening programmes, PCV is likely to be under-diagnosed in some populations. Recent consensus suggests that PCV is a form of type 1 macular neovascularisation and should be classified as a subtype of nAMD. Anti-vascular endothelial growth factor (VEGF) monotherapy has demonstrated short-term efficacy in terms of visual acuity in PCV, and outcomes may be further improved by combining anti-VEGF therapy with photodynamic therapy. However, data on the long-term (≥ 5 years) efficacy of these treatments are limited and often conflicting. Although some people with PCV can achieve long-term remission following initial treatment (21.7-51.5%), eventual lesion reactivation is reported for approximately four-fifths of patients (81.3%). The socioeconomic impact of long-term PCV management could be reduced by identifying and characterising the subpopulations least likely to require chronic treatment. Large, global, randomised, placebo-controlled studies with long-term follow-up periods are needed in addition to real-world evidence to allow clinicians to reliably stratify people with PCV and support the stopping of anti-VEGF therapy in people at low risk of disease reactivation.}, }
@article {pmid41948241, year = {2026}, author = {Neupane, R and Rance, J and McKenna, T and Kesselman, MM}, title = {Effects of Metformin on Mitochondrial Health and Oxidative Stress in Age-Related Macular Degeneration: A Systematic Review.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e104820}, pmid = {41948241}, issn = {2168-8184}, abstract = {Age-related macular degeneration (AMD) is a chronic, progressive condition and a leading cause of irreversible central vision loss in older patients. It is driven by oxidative stress, mitochondrial dysfunction, chronic inflammation, and degeneration of retinal pigment epithelium (RPE) cells. Current AMD treatments include lifestyle modifications, nutritional supplements, and/or anti-vascular endothelial growth factor therapies and primarily aim to slow disease progression. As a result, interest has grown in repurposing established medications with potential cytoprotective properties. Metformin, a widely-used anti-diabetic agent, has been proposed as a candidate due to its anti-inflammatory and mitochondrial-modulating effects. We conducted a systematic review to identify studies published between January 2015 and November 2025 that evaluate metformin therapy in (1) adults with AMD and (2) experimental retinal models designed to replicate AMD-related degeneration or pathogenesis. Comparators included individuals with AMD who were not taking metformin therapy, were untreated, and/or were given standard treatment therapy. Outcomes of interest included in the review focused on clinical endpoints of AMD incidence and severity and mechanistic endpoints of mitochondrial function, oxidative stress markers, and cellular senescence. This systematic review includes evidence from epidemiologic, clinical, and experimental studies to link molecular mechanisms with observed disease progression. A total of 10 studies published met the inclusion criteria and demonstrated that metformin is associated with cytoprotective effects in RPE cells by reducing oxidative stress (ROS) and upregulating antioxidant enzymes through activation of the Nrf2 pathway. The drug was also shown to preserve mitochondrial function via activation of AMP-activated protein kinase by enhancing mitophagy, supporting DNA repair, and promoting mitochondrial biogenesis. Observational studies suggested that metformin use was associated with a lower risk of AMD development, particularly dry AMD, with stronger associations observed with a longer duration and higher cumulative exposure. However, findings were context-dependent. Under certain stress conditions, such as sodium iodate exposure, metformin-mediated inhibition of mitochondrial complex I appeared to increase oxidative stress, highlighting a potential "double-edged" effect. Overall, current preclinical and observational studies suggest a possible association between metformin use and mitochondrial modulation in AMD. Prospective studies are needed to clarify dosing, safety, and therapeutic relevance before clinical recommendations can be made.}, }
@article {pmid41948417, year = {2026}, author = {Takebayashi, K and Iemura, Y and Yamauchi, M and Hara, K and Tsuchiya, T and Machida, S and Hashimoto, K}, title = {Acute onset of neovascular age-related macular degeneration after initiation of tirzepatide.}, journal = {Diabetology international}, volume = {17}, number = {2}, pages = {37}, pmid = {41948417}, issn = {2190-1678}, abstract = {Recent retrospective cohort studies showed that use of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) increased the incident risk of diabetic retinopathy and nonarteritic anterior ischemic optic neuropathy (NAION). Furthermore, it was recently reported that use of GLP-1RAs for more than 6 months increased the risk of neovascular age-related macular degeneration (nAMD) by about twofold, although the association between a gastric inhibitory polypeptide (GIP)/GLP-1 receptor dual agonist (GIP/GLP-1RA) and nAMD is not clearly established. We describe the case of a middle-aged male patient with type 2 diabetes without apparent diabetic retinopathy. Due to poor glycemic control, tirzepatide (a GIP/GLP-1RA) was started instead of sitagliptin (a dipeptidyl peptidase-4 inhibitor). After switching from sitagliptin to tirzepatide, glycemic control rapidly improved, but the patient felt haziness with distortion of the central part of the left eye. A diagnosis of neovascular age-related degeneration (nAMD) was made by ophthalmologists in our hospital. The basis for the possible association of tirzepatide administration with onset of nAMD is unknown. However, clinicians should pay attention to potential visual impairments after achieving acute glycemic control with incretin-related drugs, including tirzepatide.}, }
@article {pmid41943786, year = {2026}, author = {Aldaher, KE and Azmeh, A and Wehby, B and Alhalabi, N}, title = {Retinal Angiomatous Proliferation and Pachychoroid: A Case Report.}, journal = {Cureus}, volume = {18}, number = {3}, pages = {e104749}, pmid = {41943786}, issn = {2168-8184}, abstract = {Retinal angiomatous proliferation (RAP), also known as type 3 macular neovascularization (MNV), is a distinct and less common subtype of neovascular age-related macular degeneration (nAMD). This condition is typically associated with a thinner subfoveal choroid than in age-matched control eyes. However, the coexistence of RAP and pachychoroid, which is characterized by increased choroidal thickness and choriocapillaris attenuation, is rarely documented in the literature. In this report, we present the case of a 56-year-old male patient diagnosed with RAP in conjunction with pachychoroid. This case highlights the importance of multimodal imaging techniques, including optical coherence tomography (OCT), fluorescein angiography (FA), and optical coherence tomography angiography (OCT-A), to achieve a comprehensive assessment. Additionally, we emphasize the need for a thorough differential diagnosis to accurately identify and manage such overlapping retinal disorders. We hypothesize that choroidal ischemia secondary to compression of choriocapillaris by choroidal pachyvessels led to outer retinal ischemia and upregulation of vascular endothelial growth factor (VEGF), which caused RAP formation starting at the level of retinal superficial and deep capillary plexus and extended to the outer retina. Thus, our hypothesis supports that choriocapillaris atrophy is a common pathology between these two entities and may explain their coexistence.}, }
@article {pmid41944257, year = {2026}, author = {Alshaikhsalama, A and Thompson, K and Hashim, H and Patel, KG}, title = {Analyzing the association between age-related macular degeneration, retinal vascular occlusions, and dementia.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261438587}, doi = {10.1177/11206721261438587}, pmid = {41944257}, issn = {1724-6016}, abstract = {PurposeTo investigate the association between age-related macular degeneration (AMD), retinal artery occlusion (RAO), and retinal vein occlusion (RVO) and the future development of Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia (ACD).MethodsRetrospective propensity score-matched cohort study using TriNetX, a confederated healthcare network. The study population included 91,296 AMD, 15,372 RAO, 35,862 RVO, and 3,076,291 population control (PC) patients aged 65 and older. Propensity score matching was applied to control for baseline demographics and health characteristics. The primary outcome was the measured risk of developing AD, VaD, and ACD following incident diagnosis of AMD, RAO, or RVO.Major FindingsAMD was associated with a significantly elevated risk of AD (HR, 1.25; 95% CI, 1.17-1.34; P < 0.001), VaD (HR, 1.20; 95% CI, 1.11-1.31; P < 0.001), and ACD (HR, 1.12; 95% CI, 1.08-1.16; P < 0.001) following diagnosis with an average follow up of 45.0 ± 36.7 months. RVO patients also displayed higher risks across all dementia types (AD: HR, 1.46; 95% CI, 1.22-1.74; P < 0.001; VaD: HR, 1.51; 95% CI, 1.23-1.87; P < 0.001; ACD: HR, 1.34; 95% CI, 1.22-1.47; P < 0.001) with an average follow up of 46.6 ± 37.9 months.ConclusionsRetinal disease diagnoses may correlate with increased dementia risk. While AMD and RVO are associated with all dementias (AD, VaD, and ACD), RAO did not increase dementia risk.}, }
@article {pmid41944542, year = {2026}, author = {Francis, JH and Abramson, DH}, title = {Ocular Glymphatic System: Its Modulation and Role in Intraocular Tumors.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {11}, doi = {10.1167/iovs.67.4.11}, pmid = {41944542}, issn = {1552-5783}, mesh = {Humans ; *Glymphatic System/physiology/physiopathology ; *Eye Neoplasms/physiopathology ; Animals ; Glaucoma/physiopathology ; }, abstract = {The glymphatic system is a glial-based perivascular network that clears metabolic waste from the central nervous system (CNS), and its dysfunction is related to neurodegenerative disease. This review describes a correlate ocular glymphatic system in the eye and describes how this might relate to ophthalmic diseases. This review article summarizes the published literature on the CNS and ophthalmic glymphatic system and how its dysfunction relates to disease. There are associations in the pathogenesis among neurodegeneration, glaucoma, and age-related macular degeneration (AMD), which could be explained through glymphatic dysfunction in the CNS and eye, respectively. The protective effects of exercise and sleep further demonstrate associations among neurodegeneration, glaucoma, and AMD. We provide new insights on the role of the glymphatic system and intraocular tumors, proposing that tumors may hijack the glymphatic system as a bidirectional pathway of communication between the eye and the brain. New therapies for enhancing CNS glymphatic flow are discussed. Dysfunction of the glymphatic system may be a unifying pathogenesis among neurodegeneration, glaucoma, and AMD. Future research should analyze whether CNS-focused therapeutics may improve ocular disease. The role of the glymphatic system in the pathogenesis of intraocular tumors warrants further investigation.}, }
@article {pmid41944612, year = {2026}, author = {Jacob, N and Chhablani, J and Chandra Behera, U and Narayanan, R and Sahoo, NK}, title = {Large and medium choroidal vessel remodelling in progressive age-related macular degeneration and polypoidal choroidal vasculopathy.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001925}, pmid = {41944612}, issn = {1937-1578}, abstract = {PURPOSE: To describe the long-term follow-up of large and medium-sized choroidal vessels in eyes with age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This was a retrospective, observational analysis of eyes with AMD or PCV, with a minimum of five years of follow-up of indocyanine green angiography (ICGA). Qualitative analysis of the choroidal vessels was carried out at baseline until the final visit.<br><br>RESULTS: We analysed ten eyes of five patients diagnosed with either AMD or PCV with a follow-up duration ranging from seven to sixteen years. Eyes with active disease received various treatment modalities. On serial follow-up of ICGA images, remodelling of medium and large choroidal vessels was seen. The changes included large choroidal vessel attenuation, prominence/ dilatation of pre-existing choroidal vessels connecting the neovascular complex and formation of new anastomotic channels. These changes appeared adjacent to present or future neovascular complex locations. One uninvolved fellow eye showed minimal changes on follow-up.<br><br>CONCLUSION: We report the long-term changes in large and medium-sized choroidal vessels in eyes with AMD and PCV with serial ICGA images. These vascular alterations suggest the possible role played by these vessels in the pathogenesis of choroidal neovascular complexes.}, }
@article {pmid41937714, year = {2026}, author = {Samman, M and Khan, H and Aziz, AA and Patel, R and Khanani, AM}, title = {An update on the port delivery system with ranibizumab for retinal diseases.}, journal = {Expert opinion on drug delivery}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17425247.2026.2652029}, pmid = {41937714}, issn = {1744-7593}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME) are among the leading causes of irreversible vision loss globally. Anti-vascular endothelial growth factor (VEGF) therapeutics have revolutionized the treatment and management of retinal vascular diseases. Management of these retinal diseases is highly individualized, with treatment intervals ranging from 4 to 16 weeks. The port-delivery system (PDS) with ranibizumab is a refillable implant that has demonstrated safety and efficacy while also improving treatment burden by decreasing the need for frequent injections.<br><br>AREAS COVERED: Multiple FDA-approved therapeutics are available to physicians for treating and managing retinal diseases. The ultimate goal is to achieve optimal visual and anatomic outcomes while also ensuring individualized treatment. A literature search was conducted across PubMed, Google Scholar, and pharmaceutical companies' websites from 2005 to December 2025 to review clinical data, highlight the utility of the PDS, and detail the improved structure following the voluntary class III recall.<br><br>EXPERT OPINION: The PDS provides a medium to maintain treatment of retinal vascular disease over an extended period of time. Although physicians may feel hesitant to implant the device, refinements in surgical technique and the refill-exchange procedure, along with improvements to the device, may encourage more clinical uptake of PDS in appropriate patients.}, }
@article {pmid41939091, year = {2026}, author = {Hossain, B and Rahmatullah, S and Ahmed, T}, title = {Efficacy of brolucizumab and ranibizumab in diabetic macular edema and neovascular age-related macular degeneration: insights from a case series.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {4}, pages = {2477-2483}, pmid = {41939091}, issn = {2049-0801}, abstract = {BACKGROUND: The effectiveness of various anti-vascular endothelial growth factors in treating patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) in Bangladesh lacks comprehensive information.<br><br>OBJECTIVE: We evaluated the efficacy of brolucizumab and ranibizumab and assessed the incidence of drug-related adverse events in nAMD and DME patients of Bangladesh.<br><br>METHODS: In this retrospective case series, 20 patients who had received either intravitreal brolucizumab (n&#xa0;=&#xa0;10) or ranibizumab (n&#xa0;=&#xa0;10) were included. Demographic and clinical characteristics, data on best-corrected visual acuity (BCVA), and optical coherence tomography (OCT) measurements, including macular volume (MV) and central subfield retinal thickness (CSRT), were recorded for each patient at baseline and follow-up visits. In addition, brolucizumab was compared with ranibizumab in terms of above mentioned parameters.<br><br>RESULTS: Both brolucizumab and ranibizumab induced changes in patient parameters, including BCVA, OCT measurements, and MV, relative to baseline values. At the 12-week follow-up, neither drug demonstrated statistically significant superiority over the other (P > 0.05 in all cases). However, over the course of treatment, the mean BCVA showed a significant improvement following the initiation of brolucizumab therapy (P =&#xa0;0.042). In terms of OCT findings, the mean CSRT significantly decreased from 508.5&#xa0;&#xb1;&#xa0;101.1&#xa0;&#xb5;m at baseline to 241&#xa0;&#xb1;&#xa0;40.4&#xa0;&#xb5;m at week 12, while the mean MV was significantly reduced from 10.3&#xa0;&#xb1;&#xa0;1.0 mm[3] to 8.2&#xa0;&#xb1;&#xa0;1.6 mm[3] (P < 0.05).<br><br>CONCLUSION: Intravitreal brolucizumab appeared to be an effective option for patients with nAMD and DME.}, }
@article {pmid41941161, year = {2026}, author = {Yuan, R and Zhang, Y and Liu, Z and Xu, P and Li, K}, title = {A Study of the Causal Association Between Autoimmune Diseases and Blinding Eye Diseases.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673409616260128140543}, pmid = {41941161}, issn = {1875-533X}, abstract = {INTRODUCTION: Autoimmune diseases (ADs) are known to affect multiple organs, including the eyes. This study aims to evaluate the causal associations of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) with cataracts, age-related macular degeneration (AMD), and glaucoma using Mendelian randomization (MR).<br><br>METHODS: Genome-wide association study (GWAS) data were utilized to identify single- nucleotide polymorphisms (SNPs) strongly associated with AS, SLE, RA, cataracts, AMD, and glaucoma, which served as instrumental variables (IVs). The basic analysis was performed via inverse variance weighting (IVW), complemented by weighted median (WM), MR-Egger regression, weighted mode, simple mode, and MR-Robust Adjusted contour scoring technique (RAPS). The Cochran Q test, MR-Egger intercept test, MR-Steiger test, leave-one-out analysis, funnel plot, and MR-PRESSO model were used to assess the robustness of doing sensitivity analysis.<br><br>RESULT: IVW estimated that primary angle-closure glaucoma (PACG) (OR=1.265), AMD (OR=1.063), DRY-AMD (OR=1.088), and cataracts were significantly related to RA. SLE is associated with drug-induced cataract (OR=1.113) and senile cataract (OR=1.012). AS is being linked with glaucoma (OR=1.265), PACG (OR=2.436), and primary open-angle glaucoma (POAG) (OR=1.400).<br><br>DISCUSSION: RA, SLE, and AS can directly contribute to the development of cataracts, AMD, and glaucoma. These results endorse the interdisciplinary interventions approach that can incorporate rheumatology and ophthalmology. All investigations were restricted to individuals of European descent. These findings should be verified and expanded by performing multi-ethnic studies.<br><br>CONCLUSION: The study is generally reliable in establishing the causal relationship between AS, SLE, RA, and selective blinding eye illnesses, with the rationale of applying clinical screening techniques and specific intervention strategies.}, }
@article {pmid41941273, year = {2026}, author = {Park, JH and Liu, RJY and Sun, X and Mahalingan, KK and Hiriyanna, S and Li, T and Roll-Mecak, A}, title = {Insights into retinal disease and non-tubulin glutamylation from a RPGR-TTLL5 complex structure.}, journal = {The Journal of cell biology}, volume = {225}, number = {6}, pages = {}, doi = {10.1083/jcb.202508020}, pmid = {41941273}, issn = {1540-8140}, support = {ZIAEY000490/NH/NIH HHS/United States ; 1ZIANS003163/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Eye Proteins/metabolism/chemistry/genetics ; Mice ; Crystallography, X-Ray ; Mutation ; *Retinitis Pigmentosa/genetics/metabolism ; *Peptide Synthases/metabolism/chemistry/genetics ; Protein Binding ; Models, Molecular ; Tubulin/metabolism ; }, abstract = {Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause photoreceptor degeneration, vision loss, and eventual blindness. RPGR function requires glutamylation by tubulin tyrosine ligase-like 5 (TTLL5) whose mutation is also linked to severe forms of retinal degeneration. How TTLL5 targets RPGR and how mutations in either protein cause disease are unknown. Here we report the 2.8-Å X-ray crystal structure of the coactivator interacting domain (CID) of human TTLL5 in complex with the RPGR C terminus, both required for glutamylation. The RPGR C terminus forms a helix that intercalates through aromatic interactions into the CID helical bundle of novel fold. Interfacial residues are mutated in retinitis pigmentosa, as well as macular degeneration of unknown etiology. Key mutations at this interface abolish RPGR-TTLL5 interaction in vitro and RPGR glutamylation in mouse photoreceptors. Our work reveals mechanisms of non-tubulin substrate recognition by TTLL glutamylases, increasingly recognized as broad regulators of the proteome, and sheds light on mechanisms of disease associated with TTLL5 and RPGR mutations.}, }
@article {pmid41941952, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can Gene Therapy Revolutionize Treatment of Neovascular Age-Related Macular Degeneration.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.04.001}, pmid = {41941952}, issn = {1879-1891}, abstract = {TOPIC: This systematic review and meta-analysis (PROSPERO: CRD42024619992) evaluated whether gene therapy provides safe and clinically meaningful efficacy for patients with neovascular age-related macular degeneration (nAMD). The clinical question addressed outcomes in patients with nAMD receiving gene therapy (primarily adeno-associated virus-based anti-VEGF constructs) compared with baseline or standard care contexts, focusing on visual acuity, anatomical response, treatment burden, and safety. Anti-VEGF intravitreal injections remain the current standard of care but require frequent administration and long-term adherence.<br><br>CLINICAL RELEVANCE: nAMD is a major cause of irreversible vision loss in older adults and imposes substantial treatment burden due to repeated injections. Gene therapy aims to achieve sustained intraocular therapeutic protein expression after a single or infrequent administration, potentially reducing injection frequency while maintaining disease control. Establishing safety and functional efficacy is critical before translation into routine retinal practice.<br><br>METHODS: Following PRISMA guidelines, databases (PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane Library) were searched from inception to February 1, 2026. Eligible studies were prospective interventional clinical trials evaluating gene therapy in nAMD, including randomized and early-phase dose-escalation designs. Primary outcomes included best-corrected visual acuity (BCVA), central subfield thickness (CST), rescue anti-VEGF requirement, mortality, and adverse events. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Multilevel random-effects meta-analyses using restricted maximum likelihood accounted for clustering of multi-arm cohorts.<br><br>RESULTS: Eight trials (7 randomized, 1 nonrandomized) comprising 203 treated participants were included. Multilevel REML analysis showed no significant pooled BCVA improvement (MD 0.54 letters; 95% CI -7.38 to 8.46) despite favorable fixed-effect estimates. CST demonstrated significant anatomical reduction (MD 37.13 &#xb5;m; 95% CI 26.63-47.62). Approximately 44% of eyes required rescue anti-VEGF injections. Safety outcomes demonstrated generally low-to-moderate event probabilities: mortality approximately 8%, serious adverse events approximately 21-38%, inflammation approximately 20%, and retinal hemorrhage approximately 12%, with negligible heterogeneity across most endpoints. Publication bias was detected for BCVA and CST but was minimal for safety outcomes.<br><br>CONCLUSION: Gene therapy for nAMD demonstrates encouraging safety and anatomical efficacy signals but lacks consistent functional visual improvement. Current evidence supports a treatment-burden-reducing adjunctive role rather than replacement of anti-VEGF therapy. Evidence strength is limited by early-phase designs, small sample sizes, and clinical heterogeneity; ongoing phase 3 trials are required to define long-term efficacy and clinical positioning.}, }
@article {pmid41943094, year = {2026}, author = {Jorge, R and Rego, MGB and Zupelli, AS and Calado, RT}, title = {Off-label intravitreal eculizumab for geographic atrophy: report of the first two cases.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41943094}, issn = {2056-9920}, }
@article {pmid41934603, year = {2026}, author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, N}, title = {Correction: Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-026-01377-2}, pmid = {41934603}, issn = {2193-8245}, }
@article {pmid41934654, year = {2026}, author = {Asanad, S and Boyer, DS}, title = {Gene therapy for wet AMD: a paradigm shift in the standard of care.}, journal = {Expert opinion on emerging drugs}, volume = {}, number = {}, pages = {}, doi = {10.1080/14728214.2026.2651330}, pmid = {41934654}, issn = {1744-7623}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD), or wet AMD, remains a leading cause of vision loss in older adults. Current standard of care relies on repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, which create significant treatment burdens for patients and healthcare systems. Emerging gene therapies aim to address these challenges by delivering sustained therapeutic effects via single administration.<br><br>AREAS COVERED: Next-generation gene therapies are transforming AMD treatment by enabling sustained, autonomous production of therapeutic proteins within ocular tissues, enabling the eye to synthesize its own anti-VEGF agents. A comprehensive literature search was performed using both PubMed and ClinicalTrials.gov to identify pertinent manuscripts and clinical trials for this narrative review. Keywords utilized included: Gene therapy, wet AMD, neovascular AMD, Viral Vectors, Adeno-associated viral vectors, Subretinal, Suprachoroidal, and Retinal Pigment Epithelium.<br><br>EXPERT OPINION: Advances in gene therapy for wet AMD may revolutionize treatment by enabling sustained intraocular anti-VEGF protein, reducing frequent injections, improving patient adherence, and potentially lowering long-term healthcare costs. Although promising, challenges including long-term safety, complex delivery procedures, immune responses, regulatory hurdles, and the need for optimized vectors and clinical protocols must be addressed before widespread adoption and integration into standard care.}, }
@article {pmid41935142, year = {2026}, author = {Mehta, H}, title = {Social deprivation in neovascular age-related macular degeneration: when equal treatment does not deliver equal vision.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41935142}, issn = {1476-5454}, }
@article {pmid41935371, year = {2026}, author = {Moftakhar-Bazkiaei, A and Farzaneh, M}, title = {Network-based Transcriptomic Profiling of Fetal Astrocyte Differentiation Reveals Therapeutic Targets for Neurodegenerative Disease.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240412373260224061022}, pmid = {41935371}, issn = {1875-5666}, abstract = {INTRODUCTION: Neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Age-related Macular Degeneration (AMD), are marked by the progressive loss of specific neuronal populations. Astrocytes, the glial cells surrounding neurons, play a critical role in maintaining neuronal health by providing neurotrophic support, producing antioxidants, and clearing waste. Dysfunctional astrocytes contribute to disease progression, yet their developmental trajectory and molecular regulation remain incompletely understood.<br><br>METHOD: This study aims to computationally characterize transcriptional differences between fetal astrocytes and neural stem cell lines to identify key regulatory genes, pathways, and therapeutic targets relevant to astrocyte-linked neurodegeneration. Using microarray data and bioinformatics pipelines, 359 Differentially Expressed Genes (DEGs) were identified, including 249 upregulated and 110 downregulated transcripts.<br><br>RESULTS: Protein-Protein Interaction (PPI) network analysis revealed ten hub genes- COL1A1, TIMP1, LOX, COL6A1, COL6A3, COL5A1, CD44, LTBP2, ACTA2, and PLAU-central to extracellular matrix remodeling and cell adhesion. Drug-gene interaction analysis linked these genes to compounds such as Estradiol valerate, Retinoic acid, and Calcitriol, suggesting therapeutic relevance.<br><br>DISCUSSION: Enrichment analysis highlighted transcriptional regulation, apoptosis, and ECM-receptor interaction as dominant biological themes. Key miRNA-mRNA interactions, including hsa-miR-877-5p and hsa-miR-767-5p targeting LOX and COL6A3 were also identified.<br><br>CONCLUSION: Overall, this study integrates transcriptomic profiling, network modeling, and drug-gene interaction analysis to uncover astrocyte-specific molecular targets, offering a computational framework for therapeutic exploration in neurodegenerative disease.}, }
@article {pmid41935442, year = {2025}, author = {Chen, KY and Chan, HC and Lin, WW and Chan, CM}, title = {Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review.}, journal = {Redox biology}, volume = {93}, number = {}, pages = {103976}, doi = {10.1016/j.redox.2025.103976}, pmid = {41935442}, issn = {2213-2317}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly and has a multifactorial etiology involving advanced age, genetic susceptibility, and environmental risk factors. Accumulating evidence suggests that mitochondrial dysfunction is a central pathogenic mechanism in AMD, particularly in the retinal pigment epithelium (RPE). The RPE is critical for retinal homeostasis, and its high metabolic activity renders it vulnerable to age-related mitochondrial dysfunction. In AMD, the core processes of mitochondrial dynamics-fission, fusion, biogenesis, and mitophagy-are profoundly dysregulated, leading to a fragmented and dysfunctional mitochondrial network. This failure of quality control results in bioenergetic deficits, excessive oxidative stress, and the release of damage-associated molecular patterns that fuel chronic inflammation and complement-mediated damage. Experimental models and human tissue studies have strengthened the link between mitochondrial dysfunction and AMD pathology, revealing structural abnormalities, mitochondrial DNA (mtDNA) damage, and altered metabolic signatures. Therapeutic strategies targeting mitochondrial pathways, including mitochondria-targeted antioxidants, dynamic modulators, and enhancers of biogenesis and mitophagy, such as agents that restore defective mitophagosome formation, represent promising avenues for intervention. As the field advances, the integration of biomarker development and personalized approaches holds the potential to transform the clinical landscape of AMD by addressing the root causes of cellular dysfunction.}, }
@article {pmid41936183, year = {2026}, author = {Ju, Y and Lu, H and Liu, S and Chen, X and Ni, N and Su, Y and Liu, Y and Zhang, D and Chen, M and Huang, R and Zhang, J and Xiang, H and Chen, Y and Tang, Z and Gu, P}, title = {Molybdenum-based antioxidative nanomedicine fighting against retinal pigment epithelium degeneration.}, journal = {Biomaterials}, volume = {333}, number = {}, pages = {124192}, doi = {10.1016/j.biomaterials.2026.124192}, pmid = {41936183}, issn = {1878-5905}, abstract = {Oxidative stress-induced retinal pigment epithelium (RPE) degeneration is the pathologic basis of most retinal degenerative diseases, especially dry age-related macular degeneration (AMD), for which corresponding therapeutic strategies currently were still in their infancy and lack optimal efficacy. In the present study, cerium-doped molybdenum-based polyoxometalate (MoCe) nanoclusters (NCs) are designed as antioxidative nanocatalysts to inhibit oxidative stress-induced RPE degeneration and subsequent retinal damage. The synthesized MoCe NCs display prominent reactive oxygen species (ROS) scavenging efficacy with excellent in vivo biocompatibility. In RPE degeneration mice model, a single intravitreal administration of MoCe NCs effectively inhibit RPE oxidative degeneration and substantially protect retinal structure and visual function. Upon high-throughput sequencing combined with bioinformatics analysis, MoCe administration predominantly restores the expression of DNA repair-related genes and inhibits oxidative stress-induced apoptosis by suppressing the JNK/c-Jun signaling pathway. The ideal biocompatibility and remarkable protective effect render MoCe NCs as the promising nanomedicines combating RPE degeneration-associated retinal diseases especially AMD.}, }
@article {pmid41936993, year = {2026}, author = {Lizard, G and Sassi, K and Mackrill, JJ and Ghzaiel, I and Meziane, S and Hassen, E and Abdelkarim, M and Masmoudi-Kouki, O and Ghrairi, T and Brahmi, F and Gargouri, A and Rezig, L and Benkalifa, R and Khallouki, F and El Midaoui, A and Pincemail, J and Atanasov, AG and Vejux, A and Millot, N}, title = {7-ketocholesterol as a theranostic target: potential applications and future perspectives.}, journal = {Chemistry and physics of lipids}, volume = {}, number = {}, pages = {105588}, doi = {10.1016/j.chemphyslip.2026.105588}, pmid = {41936993}, issn = {1873-2941}, abstract = {7-Ketocholesterol (7KC) is mainly formed by cholesterol autoxidation and is a pro-oxidant and pro-inflammatory bioactive lipid that also induces different types of cell death, including oxiapoptophagy. It is frequently associated with major age-related diseases, such as cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease. 7KC can therefore be considered a biomarker for these diseases, offering the possibility of developing theranostic strategies combining diagnosis and treatment. Currently, all the elements are in place to develop tools for the design of theranostic therapies targeting 7KC in diseased organs: antibodies, nanoparticles used as nanoplatforms, molecules that neutralize 7KC such as enzymes which degrade it, as well as natural or synthetic compounds that inhibit the cytotoxic signaling pathways associated with oxidative stress, inflammation and cell death activated by 7KC. Identifying and neutralizing 7KC biological activities using a theranostic approach could also be of interest for growing medical fields such as space medicine widely concerned by oxidative stress, aging and age-related diseases, driven by microgravity. This review supports that most of key tools are now available to develop theranostic treatments targeting 7KC in age-related pathologies, especially in cardiovascular diseases associated with atheroma, but also in age-related macular degeneration and Alzheimer's disease. Discovery of effective treatments for these diseases is a major challenge and will answer an important need for both patients and caregivers.}, }
@article {pmid41937011, year = {2026}, author = {Bagewadi, S and Parameswaran, S and Sethuraman, S and Subramanian, A}, title = {Hyaluronic acid-poly (vinyl alcohol) composite hydrogels with self-assembled peptide nanofibers as Bruch's membrane mimics for age-related macular degeneration treatment.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {151748}, doi = {10.1016/j.ijbiomac.2026.151748}, pmid = {41937011}, issn = {1879-0003}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and effective curative therapies are not available. This study presents a tissue-engineering strategy for retinal regeneration using an injectable, in situ-forming hydrogel composed of thiol-functionalized hyaluronic acid (HA-SH) and polyvinyl alcohol (PVA), reinforced with peptide nanofibers. Decellularized Bruch's membrane derived from goat eyes was used as a control and exhibited a fiber diameter of 75.09 ± 12.99 nm, thickness of 6.26 ± 1.12 μm, and hydrophilic properties (contact angle: 39.46° ± 0.46). In comparison, the GAGA-YIGSR-based hydrogel membrane demonstrated comparable structural features with a fiber diameter of 92.38 ± 16.37 nm, a thickness of 13.43 ± 3.64 μm, and a contact angle of 72.13° ± 2.98. The HA-SH/PVA hydrogel incorporating peptide nanofibers significantly enhanced retinal pigment epithelium (RPE) cell viability, adhesion, proliferation, phagocytosis, and RPE-specific gene expression compared to the peptide-free hydrogel. In vivo functional evaluation using H&amp;E-stained retinal sections revealed that the HA-SH/PVA hydrogel containing the GAGA-YIGSR peptide markedly improved RPE cell organization, ONL nuclei density (1578.22 ± 187.03), ONL cell rows (9.02 ± 1.74), linear RPE cell count (10.6 ± 2.6), and ONL thickness (35.52 ± 4.44 μm) relative to saline controls. Furthermore, the hydrogel preserved retinal barrier integrity and ultrastructural parameters, including tight-junctions, subretinal pigment epithelium space (7.26 ± 4.92 μm), BM thickness (5.91 ± 1.07 μm), collagen area (21.74 ± 3.48%), collagen thickness (81.8 ± 24.17 μm), and collagen pore area (17.72 ± 9.19%), which were comparable to those of healthy controls. In conclusion, this study successfully developed and evaluated an injectable peptide-functionalized hydrogel as a promising therapeutic scaffold for retinal tissue regeneration in AMD.}, }
@article {pmid41933659, year = {2026}, author = {von der Emde, L and Reiter, GS and Mallwitz, M and Jauch, AS and Wall, K and Holz, FG and Pollreisz, A and Ach, T}, title = {Quantitative fundus autofluorescence in age-related macular degeneration.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.03.018}, pmid = {41933659}, issn = {1879-3304}, abstract = {Fundus autofluorescence captures the fluorescence of the retina, specifically the retinal pigment epithelium (RPE). Within the RPE, fluorophores, including lipofuscin, melanolipofuscin, and melanosomes, fluoresce when excited by light of varying wavelengths. Quantitative fundus autofluorescence (QAF), which has been implemented using blue excitation light, enables mapping and quantifying lipofuscin and melanolipofuscin fluorescence. This is achieved by using a reference bar to standardize measurements. The technical functionality of QAF relies on repeatability and high image quality. Multicenter studies, however, indicate variability. Age-related lens opacities also affect QAF, necessitating individualized correction formulas for accuracy. Accordingly, this review focuses on the development and application of QAF, addressing technical considerations and its relevance to structural and cellular changes in age-related macular degeneration (AMD), and highlighting how QAF can provide clinically meaningful information for AMD diagnosis and therapy monitoring. In AMD, numerous independent studies have found reduced autofluorescence at the posterior pole and as AMD progresses autofluorescence further decreases. Typical AMD lesions, such as subretinal drusenoid deposits, have been associated with significant QAF reduction. On a cellular level, granule aggregation and degranulation are identified as histological correlates. Subcellularly, technologies like serial block-face scanning electron and structured illumination microscopy have revealed a reduced lipofuscin volumetric density and RPE dysmorphia associated with AMD's reduced autofluorescence. New software tools enhance QAF's potential for detailed lesion analysis. Future advancements in QAF include integrating new excitation wavelengths and combining quantified emission spectra and fluorescence lifetimes to improve early detection of AMD-related changes. Despite challenges, QAF continues to evolve, promising better insights into retinal health and disease.}, }
@article {pmid41929012, year = {2026}, author = {Navratil, EM and Liu, X and Wiley, LA and Anderson, MG and Meyer, KJ and Brown, RF and Evans, IA and Taylor, EB and Stone, EM and Tucker, BA and Mullins, RF}, title = {Metabolic Analysis of Human Retinal Pigment Epithelium and Choroid Tissue in Aging and Macular Degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.24.713982}, pmid = {41929012}, issn = {2692-8205}, abstract = {Age-related macular degeneration is a common ocular disease that causes vision loss in the elderly, with a complex set of risk factors and proposed mechanisms of pathogenesis. A powerful method for investigating changes in disease is metabolomics, by which small molecules can be identified and quantified simultaneously. We report here the metabolic analysis of human RPE-choroid tissue in aging and macular degeneration (AMD), as well as comparisons of human macular and extramacular RPE-choroid and neural retina. Levels of 215 metabolites were determined in young donors, AMD donors (early/intermediate, geographic atrophy, and neovascularization) and age-matched controls. The largest number of metabolite differences were observed between young and healthy aged controls, as opposed to between aged controls and any stage of AMD. Two notable metabolites found to be increased in aging choroids are trimethylamine N-oxide and uric acid, both of which were significant after Bonferroni correction. A mouse endothelial cell line treated with a high concentration of uric acid exhibited reduced migration in a wound closure assay. This study provides initial insights into the metabolome of human choroids in varying states of age and macular degeneration, as well as functional implications of these changes in the aging choroid.}, }
@article {pmid41929144, year = {2026}, author = {Mir, HA and Mahesh, G and Palanimuthu, A and Cioffi, CL and Petrukhin, K}, title = {Loss of Lamp2a-dependent chaperone-mediated autophagy drives dry AMD-like retinal pathology in mice and is rescued by BK channel activation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.19.712761}, pmid = {41929144}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in elderly individuals for which no effective treatments are currently available. The photoreceptor loss in dry AMD is secondary to the demise of the retinal pigment epithelium (RPE) cells. The accumulation of extracellular deposits, known as drusen, resulting in part from deficient lysosomal and autophagosomal degradation, is a key feature of dry AMD pathogenesis. Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that maintains proteostasis by targeting specific cytosolic proteins for lysosomal translocation and degradation. LAMP2A (lysosome-associated membrane protein 2A) functions as the key lysosomal receptor required for CMA. Using Lamp2a knockout mouse, we show that selective CMA dysfunction recapitulates AMD-like pathologies, including sub-RPE lipid and protein deposits, RPE atrophy, Bruch's membrane thickening, and impaired autophagic activity. Furthermore, we identify large-conductance Ca[2+]-activated K[+] (BK) channels as a therapeutic target for restoring autophagic activity. Mechanistically, pharmacological activation of BK channels with the small-molecule agonist GLA-1-1 enhances macroautophagy and stimulates autophagic flux by promoting autophagosome-lysosome fusion. Importantly, oral administration of GLA-1-1 in markedly attenuates structural, functional, and molecular retinal abnormalities in Lamp2a -deficient mice, suggesting that pharmacological activation of macroautophagy through facilitating autophagosome-lysosome fusion can partially compensate for CMA deficiency. Together, these findings demonstrate that pharmacological activation of macroautophagy can ameliorate the retinal phenotype resulting from CMA dysfunction and support BK channel activation by GLA-1-1 as a promising therapeutic strategy for dry AMD.}, }
@article {pmid41929345, year = {2026}, author = {Chau, K and Allison, K and Braithwaite, T and Harley, ITW and Hassman, LM}, title = {Genomic network analysis links uveitis with systemic inflammatory diseases.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.24.26349228}, pmid = {41929345}, abstract = {OBJECTIVE: To determine whether uveitis shares genetic similarity with extraocular immune-mediated inflammatory diseases (IMIDs), we performed network analysis of putative causal genes associated with ocular inflammatory disease, IMIDs and eye-specific diseases, including age-related macular degeneration and monogenic disorders.<br><br>METHODS: We identified putative causal genes for genome-wide significance variants from uveitis, IMIDs and ocular diseases using OpenTargets and published studies. To assess the gene-level pleiotropy between disease groups, we quantified the causal gene overlap between groups, and the Jaccard Similarity Indices for individual disease pairs. We then used a network approach to assess the molecular genetic similarity between diseases at a biological pathway level and comparative statistics to identify diseases with greater network similarity to uveitis.<br><br>RESULTS: Seventy-five percent of the putative causal genes for uveitis are also causal for IMIDs, while no uveitis genes are shared with primary ocular disorders. Network analysis revealed that 1) uveitis genes are more closely networked with systemic IMIDs disease genes than with ocular-specific disease genes; and 2) significant network similarity links uveitis and specific IMIDs, such as ankylosing spondylitis and sarcoidosis.<br><br>CONCLUSIONS: Overlapping causal genes and network similarity indicate that uveitis is predominantly an inflammatory disease, sharing genetic architecture with other IMIDs. Future studies aimed at dissecting genetic heterogeneity within uveitis may determine whether subgroups share common immune pathways that could nominate endotype-specific therapeutic approaches.}, }
@article {pmid41931001, year = {2026}, author = {Easton, CA and Wilmarth, PA and Criss, M and Kim, K and Reddy, AP and Tanne, S and Boone, JQ and Tran, KD}, title = {Comparison of Transcript and Protein Abundance in Human Donor Retinas Support Extending Postmortem Interval From 12 to 18 Hours to Expand the Donor Pool for Biomedical Research.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {4}, pages = {9}, doi = {10.1167/iovs.67.4.9}, pmid = {41931001}, issn = {1552-5783}, mesh = {Humans ; *Tissue Donors ; Proteomics/methods ; *Retina/metabolism ; Female ; *Eye Proteins/genetics/metabolism ; Middle Aged ; Male ; Aged ; *Biomedical Research ; *Postmortem Changes ; Adult ; Tandem Mass Spectrometry ; Time Factors ; Organ Preservation/methods ; *RNA, Messenger/genetics ; }, abstract = {PURPOSE: To evaluate whether extending the postmortem interval (PMI) from 12 to 18 hours affects transcript and protein abundances in the human retina.<br><br>METHODS: Donor eyes were recovered from postmortem donors (n = 7 pairs) and stored at 2&#xb0;C-8&#xb0;C. Only donor eyes with ocular cooling within eight hours of death were examined. The OD retina was preserved at 12 hours and the OS retina at 18 hours postmortem. Retinas were flash frozen with liquid nitrogen. The macular region superior to the fovea was used for RNA sequencing (RNA-seq), whereas the inferior region was processed for tandem mass tag (TMT) quantitative proteomics. RNA library preparations were performed simultaneously, and the sequencing of all samples were conducted on the same chip. Proteins were isolated and labeled with 16-plex TMTPro isobaric tags, and all samples were analyzed in a 20-fraction TMT-mass spectrometry experiment. RNA-seq data were processed using DESeq2 (Bioconductor) and proteomic data were analyzed using the previously published PAW pipeline.<br><br>RESULTS: RNA-seq identified 22,446 transcripts, with only five transcripts showing significant differential expression (adjusted P < 0.1 and a Log2FoldChange > 1) between 12 and 18 hours. No enriched pathways were associated with these changes. Proteomic analysis identified 6,109 proteins, with no significant differences in abundance (all adjusted P > 0.05). Retinal cell-type specific markers and markers relevant for disease research, such as age-related macular degeneration and glaucoma, remained stable across both time points.<br><br>CONCLUSIONS: Extending the PMI cutoff from 12 to 18 hours did not significantly impact transcriptomic or proteomic integrity in human donor retinas. This PMI extension greatly increases the availability of donor eyes for biomedical research.}, }
@article {pmid41932376, year = {2026}, author = {Cui, X and Hui, J and Han, Q}, title = {Traffic Noise, Air Pollution, and Greenness in Relation to Age-Related Macular Degeneration: Evidence from a Cross-National Cohort Study.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {128042}, doi = {10.1016/j.envpol.2026.128042}, pmid = {41932376}, issn = {1873-6424}, abstract = {Age-related macular degeneration (AMD) is influenced not only by biological factors but also by the broader urban environment, yet evidence integrating multiple environmental exposures remains limited. We examined the associations of residential road traffic noise, fine particulate air pollution (PM2.5), and green space with AMD risk using data from the UK Biobank (207,859 controls and 5,571 incident AMD cases) and an independent hospital-based cohort from Tianjin, China (286 controls and 233 cases). Environmental exposures were assessed using harmonized metrics, and associations were estimated using Cox proportional hazards models in the UK Biobank and multivariable logistic regression in the Tianjin cohort. Restricted cubic splines were applied to evaluate non-linear exposure-response relationships, and joint exposure analyses assessed combined environmental effects. Higher levels of Lden, Lnight, and PM2.5 were consistently associated with increased AMD risk, whereas greater residential green space was associated with lower risk across both cohorts. Non-linear analyses revealed steep risk increases at moderate-to-high noise and PM2.5 levels and a J-shaped association for green space. Individuals exposed to both high noise and high PM2.5 exhibited the greatest risk. Feature selection using Boruta and LASSO identified environmental exposures alongside age, C-reactive protein, and HbA1c as key predictors. Machine-learning models integrating environmental exposures with inflammatory and metabolic biomarkers achieved good discrimination (XGBoost AUC = 0.81). Quantile g-computation further indicated that the combined burden of urban environmental exposures was strongly associated with AMD risk, with traffic noise contributing the largest share of the mixture effect. These findings suggest that traffic noise and air pollution are important, potentially modifiable environmental risk factors for AMD, while residential green space may help mitigate risk.}, }
@article {pmid41932381, year = {2026}, author = {Hjæresen, S and Gramkow, ET and Zhang, M and Svenningsen, &#xc5;F}, title = {HTRA1 and Brain Disorders: A Balancing Act Across Neurodegeneration and Repair.}, journal = {Progress in neurobiology}, volume = {}, number = {}, pages = {102914}, doi = {10.1016/j.pneurobio.2026.102914}, pmid = {41932381}, issn = {1873-5118}, abstract = {High temperature requirement protein A1 (HTRA1) is a trypsin-like serine protease increasingly recognized as a central regulator of brain homeostasis. HTRA1 is broadly expressed in the brain, where it regulates proteostasis, extracellular matrix (ECM) remodeling, and important signaling pathways such as: TGF-β, Wnt, and Notch. These functions are essential for maintaining blood-brain barrier integrity, supporting tissue repair, and restraining inflammation. HTRA1 is a double-edged sword, as both insufficient and excessive activity can lead to neurodegenerative and vascular pathology. Reduced HTRA1 levels are linked to ECM accumulation and vascular fibrosis, while elevated activity contributes to tissue breakdown, inflammation, and impaired repair. This dual role is implicated in a range of disorders, including cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, small vessel disease, age-related macular degeneration, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We review recent insights into HTRA1's interactions with ApoE and tau, its roles in lipid and cytoskeletal regulation, and its modulation by inhibitors such as: Macrophage Migration Inhibitory Factor. Finally, we explore its biomarker potential and therapeutic targeting strategies. Understanding the mechanisms behind HTRA1's shift from protective to pathological is crucial for developing targeted therapies that preserve its beneficial roles.}, }
@article {pmid41736120, year = {2026}, author = {Xiang, Y and Zuo, G and He, X and Wang, K and Zhu, Y and Cheng, S}, title = {Therapeutic potential of mesenchymal stem cells in ocular degenerative disorders.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41736120}, issn = {1479-5876}, abstract = {BACKGROUND: Mesenchymal stem cells (MSCs), with their regenerative, anti‑inflammatory, and immunomodulatory properties, represent a promising therapeutic strategy for degenerative retinal diseases. Current treatments fail to address core pathologies-such as inflammation, oxidative stress, and apoptosis-in conditions including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and glaucoma, underscoring the need for regenerative approaches.<br><br>METHODS: This review summarizes the signaling pathways through which MSCs and their exosomes promote tissue repair and neuroprotection in ocular disorders. It evaluates published preclinical and clinical data to outline the current therapeutic applications, efficacy, and safety profiles of MSC-based therapies in ophthalmology.<br><br>RESULTS: MSC-based interventions show potential in alleviating key pathogenic processes in retinal degeneration. Clinical trials indicate their ability to reduce inflammation, oxidative stress, and apoptotic cell death, thereby supporting retinal cell survival and function. These benefits are primarily mediated through paracrine signaling via extracellular vesicles such as exosomes.<br><br>CONCLUSION: MSCs constitute a significant advance toward retinal repair and functional restoration. However, translation of these findings is hindered by the lack of standardized and regulated treatment protocols. Future efforts should focus on establishing optimized delivery methods, safety standards, and a deeper understanding of molecular mechanisms to bridge the gap between promising experimental outcomes and reliable clinical application.}, }
@article {pmid41924198, year = {2026}, author = {Mizuma, R and Mizuki, Y and Kamata, A and Onishi, J and Sakono, T and Suzuki, M and Mizuki, N}, title = {One-Year Real-World Outcomes of Intravitreal Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration in Japan: A Multicenter Retrospective Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {596218}, pmid = {41924198}, issn = {1177-5467}, abstract = {BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has improved outcomes in neovascular age-related macular degeneration (nAMD), but treatment burden remains substantial in real-world practice. High-dose aflibercept 8 mg was developed to extend dosing intervals; however, one-year real-world evidence in Japanese patients is limited.<br><br>OBJECTIVE: To evaluate one-year real-world efficacy, durability, and safety of aflibercept 8 mg for nAMD in Japan.<br><br>METHODS: This multicenter retrospective study was conducted across five institutions in Japan and included consecutive eyes with nAMD treated with aflibercept 8 mg between April and December 2024 and followed for at least 12 months. Visual acuity (VA; logMAR) and central subfield thickness (CST) were assessed at baseline and follow-up visits. Treatment followed an individualized treat-and-extend approach; 19, 1, and 20 eyes received 1, 2, and 3 loading injections, respectively. Durability was evaluated by comparing pre-switch and 12-month dosing intervals in eyes with paired data.<br><br>RESULTS: Forty eyes (36 patients) were analyzed: 35 previously treated eyes switched to aflibercept 8 mg and 5 treatment-na&#xef;ve eyes. Median baseline VA was 0.155 logMAR and CST was 284&#xa0;&#xb5;m. VA at 12 months did not differ significantly from baseline (Hodges-Lehmann -0.0395 logMAR; 95% CI, -0.111 to 0.0141; p = 0.148), whereas CST decreased significantly (-62.0&#xa0;&#xb5;m; 95% CI, -106 to -32.0; p = 0.000538). Among eyes with paired pre-switch interval data (n = 35), injection intervals increased from 8&#xa0;weeks (IQR, 7-12) to 12&#xa0;weeks (IQR, 8-14) at 12 months (median change +2&#xa0;weeks; p = 0.00471). No ocular or systemic adverse events potentially related to aflibercept 8 mg were observed.<br><br>CONCLUSION: In this Japanese real-world nAMD cohort, significant CST reduction was observed over 12 months, while visual acuity remained stable. Longer dosing intervals were also observed after switching.}, }
@article {pmid41925707, year = {2026}, author = {Allon, G and Sarrabia, G and Goren, L and Moisseiev, E and Segal, O}, title = {Assessing patients who are treated with intravitreal injections by ultra-wide field imaging versus slit lamp biomicroscopy.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261438854}, doi = {10.1177/11206721261438854}, pmid = {41925707}, issn = {1724-6016}, abstract = {PurposeTo evaluate the agreement between a virtual clinic model based on ultra-widefield imaging (UWFI) and spectral-domain optical coherence tomography (SD-OCT) and conventional face-to-face (F2F) slit-lamp fundus examination with SD-OCT for treatment decision-making in patients receiving intravitreal injections.MethodsIn this retrospective masked paired comparative study, consecutive patients receiving intravitreal injections underwent F2F evaluation by a retina specialist using slit-lamp biomicroscopy and SD-OCT. F2F examination was predefined as the reference standard. During the same clinical encounter, UWFI was obtained. A second retina specialist, masked to the clinical findings and decisions, independently reviewed the SD-OCT and UWFI images in a virtual setting and made management decisions.ResultsA total of 426 eyes from 304 patients were included. Of these, 217 eyes (50.94%) had neovascular age-related macular degeneration (NVAMD), 151 (35.45%) diabetic macular edema (DME), and 56 (13.15%) retinal vein occlusion (RVO; 36 branch RVO, 14 central RVO, and 6 hemi-retinal RVO). One eye (0.23%) had myopic choroidal neovascularization (CNV), and one (0.23%) had Sorsby macular dystrophy with CNV.The virtual assessment demonstrated 98.12% agreement with the F2F examination for treatment decisions (Cohen's κ = 0.90; 95% CI, 0.83-0.97). Recognition of NVAMD-associated macular hemorrhages was comparable between modalities. UWFI identified additional cases of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE), all of which were subsequently confirmed on slit-lamp examination. The mean virtual review time was more than twofold shorter than the F2F evaluation (P < 0.001).ConclusionsVirtual assessment using ultra-widefield imaging demonstrated high agreement with F2F slit-lamp examination for treatment decision-making in patients receiving intravitreal injections. This approach may represent an efficient alternative for selected follow-up visits in which anterior segment evaluation is not required.}, }
@article {pmid41925898, year = {2026}, author = {Faiz Turan, M and Ozkaya, A}, title = {Imaging biomarkers associated with visual acuity in central serous chorioretinopathy: a multimodal analysis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41925898}, issn = {1573-2630}, mesh = {Humans ; *Central Serous Chorioretinopathy/physiopathology/diagnosis ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; *Fluorescein Angiography/methods ; *Multimodal Imaging/methods ; Middle Aged ; Adult ; Fundus Oculi ; Biomarkers ; Indocyanine Green/administration &amp; dosage ; Follow-Up Studies ; Aged ; Macula Lutea/pathology ; }, abstract = {OBJECTIVE: To assess the relationship between best-corrected visual acuity (BCVA) and multimodal imaging findings including optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) in patients diagnosed with central serous chorioretinopathy (CSC).<br><br>METHODS AND MATERIALS: We retrospectively analyzed 249 eyes of 164 patients with CSC. OCT parameters included central macular thickness (CMT), neurosensory and pigment epithelial detachments, outer retinal integrity, and degenerative changes. FA and ICGA findings were also evaluated. Associations between multimodal imaging features and BCVA were analyzed.<br><br>RESULTS: BCVA differed significantly among CSC subgroups (p&#x2009;<&#x2009;0.001), with the sequelae group showing the best visual acuity. CMT varied across subgroups (p&#x2009;<&#x2009;0.001) and was negatively correlated with BCVA in the overall cohort, driven primarily by acute cases. Outer retinal alterations on OCT and angiographic markers of disease activity were associated with worse BCVA. In multivariable analysis, intraretinal and/or subretinal hyperreflective dots, cystoid macular degeneration, FA leakage, and choroidal neovascularization remained independent predictors of poorer visual acuity.<br><br>CONCLUSION: Visual acuity in CSC varies across disease subtypes and is associated with distinct OCT, FA, and ICGA features. These findings highlight the value of multimodal imaging in the assessment of visual prognosis and in supporting individualized follow-up and treatment strategies in CSC.}, }
@article {pmid41927600, year = {2026}, author = {Kim, HM and Woo, SJ}, title = {Association between screening duration and treatment outcomes in the clinical trials of ranibizumab and aflibercept for neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41200-3}, pmid = {41927600}, issn = {2045-2322}, abstract = {The clinical implications of screening duration prior to treatment initiation in neovascular age-related macular degeneration (nAMD) are not well understood. This post hoc analysis investigated whether screening duration influences treatment outcomes in two multinational phase 3 randomized clinical trials, SB11 (ranibizumab biosimilar) and SB15 (aflibercept biosimilar), comprising a total of 1,152 participants (704 from the SB11 trial and 448 from the SB15 trial) with nAMD. Screening duration was assessed in relation to changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at weeks 8 and 48. Multiple linear and logistic regression analyses, adjusted for age and baseline BCVA/CST, showed no significant associations between screening duration and either visual or anatomical outcomes at both time points. Linear regression coefficients for screening duration were not statistically significant for BCVA or CST at week 8 (BCVA: B = - 0.058, P = 0.242; CST: B = - 0.050, P = 0.908) or at week 48 (BCVA: B = - 0.015, P = 0.843; CST: B = 0.036, P = 0.930). These findings suggest that a screening period of up to 21 days does not adversely affect treatment efficacy in clinical trial settings and support the clinical feasibility of short pre-treatment delays.}, }
@article {pmid41918827, year = {2026}, author = {Stewart, C and Bhangu, JS and Swarnkar, PK and Rifat, M and Khalid, S and Al-Janabi, A and Awad, MH and Williams, GS}, title = {Real-World Outcomes of Switching to Faricimab in Treatment-Experienced and Resistant Neovascular Age-Related Macular Degeneration: A Single-Centre Retrospective Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {591029}, pmid = {41918827}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate anatomical, functional, and treatment burden outcomes of Faricimab in neovascular age-related macular degeneration (nAMD) patients with persistent disease activity despite prior anti-VEGF therapy.<br><br>PATIENTS AND METHODS: Single-centre retrospective study of 67 eyes switched to Faricimab (November 2022-December 2024). This cohort was unable to be extended beyond 4-6-week intervals on existing anti-VEGF therapy. All patients received three monthly loading doses followed by treat-and-extend regimen. Primary outcomes: central macular thickness (CMT), best-corrected visual acuity (BCVA), macular dryness over eight injections, and treatment interval extension.<br><br>RESULTS: The cohort had received mean 33 (range 10-78) prior anti-VEGF. Baseline mean BCVA was 0.42 logMAR (SD &#xb1; 0.28) and mean CMT was 244.5&#xa0;&#x3bc;m (SD &#xb1; 62.2). Statistically significant CMT reduction occurred by injection 8 (-16.9&#xa0;&#x3bc;m, p=0.0084). Complete macular dryness peaked by the time of third injection (43.3%) then declined to 32.8% at injection 8 (p=0.0089). Visual acuity remained unchanged (p=0.6043) with no correlation to CMT change (p=0.172). Treatment interval extension was achieved in 46.3% of patients (p=0.002). Dryness at injection 3 after switching to Faricimab did not predict treatment extension (p=0.217). Two patients (0.36% of total injections, 2/548) developed sterile intraocular inflammation requiring discontinuation.<br><br>CONCLUSION: Faricimab switching achieves statistically significant but modest anatomical improvement in heavily pretreated nAMD with meaningful treatment burden reduction in 46.3% of eyes. Our analysis revealed treatment burden did not indicate the potential for treatment interval extension.}, }
@article {pmid41918832, year = {2026}, author = {Wang, R and Durrani, AK}, title = {Severe Pancytopenia Secondary to Zinc Toxicity from Age-Related Eye Disease Study Vitamin Supplementation.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261436350}, pmid = {41918832}, issn = {2474-1272}, abstract = {Purpose: To report a case of zinc-induced hypocupremia associated with Age-Related Eye Disease Study 2 supplementation presenting with pancytopenia. Methods: A single case was retrospectively reviewed. Results: An 86-year-old woman taking Age-Related Eye Disease Study 2 supplementation presented to a hematology-oncology clinic with severe fatigue and pancytopenia. Laboratory evaluation demonstrated elevated zinc levels and low copper levels consistent with zinc-induced hypocupremia. Age-Related Eye Disease Study supplementation was discontinued, and the patient was started on copper supplementation. At the 4-month follow-up, the patient demonstrated near normalization of hematologic parameters and resolution of symptoms. Conclusions: Zinc-induced hypocupremia is a rare but potentially fatal complication of Age-Related Eye Disease Study 2 supplementation and may present with pancytopenia. Clinicians should consider this diagnosis in patients taking zinc-containing supplements who present with unexplained cytopenias.}, }
@article {pmid41919172, year = {2026}, author = {Ambrosio, L and Cammalleri, M and Panariello, S and Califano, G and Scala, A and Improta, G and Pisani, A and Rejdak, R and Ostrowski, I and Filippi, L and Bagnoli, P and Dal Monte, M and Toro, MD}, title = {Mirabegron in patients with age-related macular degeneration treated for overactive bladder: a study protocol for a prospective observational non-randomized trial.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1761473}, pmid = {41919172}, issn = {2296-858X}, abstract = {UNLABELLED: Although anti-vascular endothelial growth factor drugs have revolutionized the treatment of neovascular age-related macular degeneration (wet AMD), preventing eyes from converting from dry to wet AMD provides better long-term prognosis for sight and overall health. Mirabegron, an agonist at beta 3 adrenoceptors (β3-ARs), is licensed for the treatment of overactive bladder (OAB), but has potential effects on angiogenic proliferation in the retina, and therefore may reduce risk of conversion from dry to wet AMD. Both OAB and AMD are more common in older adults and share risk factors suggesting a potential link between these two conditions, thus highlighting the need for common therapy for the two diseases. Mirabegron use in AMD patients is supported by its rather safe profile at the eye level as macular and choriocapillary parameters do not seem to be affected in OAB patients. The purpose of this study will be to investigate the effects of mirabegron in patients concomitantly affected by OAB and dry AMD to evaluate its impact on slowing down AMD progression from the dry to the neovascular form.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT07305298, identifier NCT07305298.}, }
@article {pmid41922489, year = {2026}, author = {Morsy, MS and Dutta, NA and Eldessouky, EI and Kabil, MM and El-Koumy, HAEA and Mehta, NN and Ali, AL and Jena, S and Zhang, H and Bartsch, DU and Cheng, L and An, C and Nguyen, T and Freeman, WR}, title = {Artificial intelligence based assessment of treatment response in wet age related macular degeneration using paired OCT angiography.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-42999-7}, pmid = {41922489}, issn = {2045-2322}, support = {P30EY022589//UCSD Vision Research Center Core Grant/ ; R01EY033847,//NIH grant/ ; }, }
@article {pmid41913248, year = {2026}, author = {Hanhart, J and Celi, LA and Blumenthal, EZ and Almog, R and Behar, J}, title = {Artificial intelligence in retinal care: transforming the doctor-patient partnership.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00837-y}, pmid = {41913248}, issn = {2056-9920}, abstract = {BACKGROUND: The integration of artificial intelligence into retinal practice represents more than a technological advancement; it constitutes an anthropological shift fundamentally redefining the centuries-old therapeutic partnership between physician and patient.<br><br>OBJECTIVE: To examine how artificial intelligence integration into retinal care transforms the therapeutic partnership, revealing what this transformation illuminates about the nature of medical knowledge itself and identifying frameworks for conscious implementation.<br><br>METHODS: We conducted a structured narrative review examining AI-based diagnosis and monitoring of diabetic retinopathy and age-related macular degeneration (2018-2025), synthesizing clinical deployment evidence with qualitative implementation studies, adopting an anthropological interpretive stance to examine technology as a mediator of human relationships.<br><br>RESULTS: FDA-approved AI systems demonstrate robust diagnostic performance for diabetic retinopathy and age-related macular degeneration. AI integration shifts encounters from examination-based to screen-mediated, clinical reasoning from individual to algorithm-guided, and physicians from diagnosticians to interpreters. Three insights emerge. First, AI reveals that medical practice always combined mechanistic reasoning with pattern recognition, now separated algorithmically. Second, accountability operates asymmetrically: while all stakeholders derive benefits from algorithmic integration, authority over system selection and deployment remains concentrated among vendors and institutions rather than distributed to frontline clinicians or patients. Third, impact diverges along existing stratification: transformation may create access for excluded populations while potentially eroding relationships for those who had comprehensive care, raising fundamental questions about equitable distribution.<br><br>CONCLUSIONS: The AI transformation of retinal care offers a revealing mirror of medicine's algorithmic future. Success demands epistemological rigor, robust evaluation competencies and establishing frameworks for shared accountability among the various stakeholders. Our framework maps six fundamental dimensions where synthesis supersedes substitution: expanding algorithmic capabilities while preserving healing relationships, creating access while maintaining continuity. Medicine can embrace algorithmic intelligence while preserving its humanistic core through conscious choices about epistemology, equity, and the character of practice we create.}, }
@article {pmid41914966, year = {2026}, author = {Trinh, M and Nguyen, J and Lee, M and Wang, J and Tee, YG and Nivison-Smith, L}, title = {Eccentricity-Dependent Reflectivity Rates-of-Change Across the Retina in Intermediate Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {62}, doi = {10.1167/iovs.67.3.62}, pmid = {41914966}, issn = {1552-5783}, mesh = {Humans ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis ; *Retinal Ganglion Cells/pathology ; Bruch Membrane/pathology ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Nerve Fibers/pathology ; Middle Aged ; *Retina/pathology ; Longitudinal Studies ; Disease Progression ; Visual Acuity ; Follow-Up Studies ; }, abstract = {PURPOSE: The purpose of this study was to characterize reflectivity rates-of-change and eccentricity patterns across all retinal layers and bands in intermediate age-related macular degeneration (iAMD), using topographical optical coherence tomography (OCT) analysis.<br><br>METHODS: This retrospective, longitudinal study included 58 consecutive individuals with iAMD and no progression to late AMD. Linear reflectivity was derived from manually segmented OCT macular cubes (25 &#xd7; 25 degrees) across 60 &#xd7; 60 grids and normalized to vitreous reflectivity, for each reflective retinal layer from the retinal nerve fiber layer (RNFL) to Bruch's membrane (BM). This included the outer retinal bands, that is, the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), and the drusen layer (RPE-BM). Grids below large blood vessels, the optic nerve head, and above drusen were excluded. Reflectivity rates-of-change (median, interquartile range [IQR], %/year) and eccentricity patterns were evaluated, then compared with colocalized thickness using regression coefficient ratios.<br><br>RESULTS: RNFL and ganglion cell layer reflectivity decreased up to -10.2%/year, with para-foveal troughs at 1.5 to 1.6 mm eccentricity. Inner plexiform and outer plexiform layers showed more uniform decreases without eccentricity dependence. In the outer retina, EZ band reflectivity decreased with a parafoveal trough of -11.1%/year at 1.4 mm, whereas ELM band, RPE band, and drusen layer changes were smaller and spatially uniform (within &#xb1;3%/year). Reflectivity rates-of-change were up to 15 &#xd7; [IQR = 1.47-28.53] faster than thickness (P < 0.05), although relationships (R2) were weak.<br><br>CONCLUSIONS: In iAMD, reflectivity changes across all retinal layers, most prominently para-/centrally, and show minimal colocalization with thickness. Faster rates-of-change and distinct spatial profiles support reflectivity as a sensitive biomarker for early disease change over time.}, }
@article {pmid41915734, year = {2026}, author = {Bordon, AF and Kaiser, PK and Wolf, A and Cen, L and Heyn, J and Urosevic, D and Dodeller, F and Allmannsberger, L and Silva, R}, title = {Efficacy and Safety of the Proposed Biosimilar Aflibercept, SDZ-AFL, in Patients With Neovascular Age-Related Macular Degeneration: 52-Week Results From the Phase 3 Mylight Study: Erratum.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004832}, pmid = {41915734}, issn = {1539-2864}, }
@article {pmid41916277, year = {2026}, author = {Spirig, SE and Herrero-Navarro, &#xc1; and Utz, L and Arteaga-Moreta, VJ and Raics, Z and Posada-Céspedes, S and Chreng, S and Galuba, O and Galuba, I and Claerr, I and Renner, S and Boldogkoi, M and Moreno-Juan, V and Kleindienst, PT and Volak, A and Imbach, J and Malysheva, S and Siwicki, RA and Hahaut, V and Hou, Y and Rodrigues, TM and Picelli, S and Cattaneo, M and Jüttner, J and Cowan, CS and Duckely, M and Baeschlin, DK and Renner, M and Unterreiner, V and Roska, B}, title = {Cell-type-focused compound screen in human organoids reveals CK1 inhibition protects cone photoreceptors from death.}, journal = {Neuron}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuron.2026.02.024}, pmid = {41916277}, issn = {1097-4199}, abstract = {Human organoids that mirror their corresponding organs in cell-type diversity present an opportunity to perform large-scale screens for compounds that protect disease-affected or damaged healthy cell types. Here, we generated 20,000 human retinal organoids with green fluorescent protein (GFP)-labeled cone photoreceptors. Since degeneration of cones is a leading cause of blindness, we induced cone death and screened 2,707 compounds with known targets for those that saved cones or those that further damaged cones. We identified inhibitors of casein kinase 1 (CK1) that protected cones, heat shock protein 90 (HSP90) inhibitors that saved cones in the short term but damaged them in the longer term, and broad histone deacetylase (HDAC) inhibition by many compounds that significantly damaged cones. Finally, we confirmed the protective effects of identified compounds in a mouse model of photoreceptor degeneration. This work provides a database for cone-damaging compounds and describes compounds and targets that can be starting points to develop neuroprotection for cones in diseases such as macular degeneration.}, }
@article {pmid41916527, year = {2026}, author = {Chen, Y and Zhang, Z and Wu, J and Wang, Y and Lin, S}, title = {MiR-335-5p as a potential biomarker of wet age-related macular degeneration.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/08164622.2026.2639834}, pmid = {41916527}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Early diagnosis and intervention are of vital importance in delaying the irreversible vision loss caused by wet age-related macular degeneration (wAMD).<br><br>BACKGROUND: wAMD can lead to blindness in severe cases. At present, the pathogenesis of wAMD is still unclear, so a new biomarker is needed to study wAMD.<br><br>METHODS: A total of 190 subjects were included in this study, including the control group (n&#x2009;=&#x2009;90) and the wAMD group (n&#x2009;=&#x2009;100). The expression of miR-335-5p and the diagnostic value of miR-335-5p in wAMD were analysed. ARPE-19 cells treated with 300&#x2009;&#xb5;M t-BHP for 24&#x2009;h or 600&#x2009;&#xb5;M H2O2 for 24&#x2009;h were selected as oxidative damage models. MiR-335-5p mimic and miR-335-5p inhibitor were transfected into oxidative damage models to up-regulate and down-regulate miR-335-5p, and then proliferation and apoptosis were measured. Targetscan was used to forecast the target of miR-335-5p and gain VEGFA, which was confirmed by the dual-luciferase reporter system. MiR-335-5p and VEGFA were overexpressed in oxidative damage models to detect the role of both in wAMD.<br><br>RESULTS: MiR-335-5p was reduced and may have high diagnostic value in wAMD. MiR-335-5p was a risk factor for wAMD. In the oxidative damage models, overexpressed miR-335-5p increased the cell viability and decreased the apoptosis, while the inhibition of miR-335-5p was reversed. VEGFA was the target of miR-335-5p and was negatively regulated by miR-335-5p in the oxidative damage models. VEGFA and miR-335-5p were negatively correlated in wAMD.<br><br>CONCLUSION: MiR-335-5p may have a high diagnostic value in wAMD, suggesting that miR-335-5p might be a biomarker of wAMD. VEGFA was the target of miR-335-5p, and the two were negative correlation in wAMD. MiR-335-5p regulates VEGFA secretion in RPE cells, thereby indirectly participating in the core pathological process of wAMD.}, }
@article {pmid41907382, year = {2026}, author = {Hwang, S and Kang, SW and Kim, SJ and Park, KH and Oh, J and Jo, YJ and Byeon, SH and Kim, JH and Son, KY and Choi, J and Sagong, M and Kim, K and Yu, SY and Hwang, DD and Park, YH and Lee, H and Choi, EJ and Lee, J and , }, title = {Design and Baseline Characteristics of the Korean Age-Related Maculopathy Study (KARMS): A Nationwide Multicenter Prospective Observational Study.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101121}, pmid = {41907382}, issn = {2666-9145}, abstract = {PURPOSE: To describe the design and baseline characteristics of the Korean Age-Related Maculopathy Study, a nationwide prospective cohort investigating age-related macular degeneration (AMD) in Koreans.<br><br>DESIGN: A 5-year prospective observational study conducted across 33 tertiary hospitals and ophthalmology clinics in Korea.<br><br>PARTICIPANTS: A total of 1159 Korean participants diagnosed with nonexudative or exudative AMD.<br><br>METHODS: Participants aged 50 to 80 years were assigned to the A Study for Intermediate AMD Natural Outcome (ASIANO) arm (nonexudative) or Korean Exudative AMD Treatment Study (KEATS) arm (newly diagnosed exudative AMD). A Study for Intermediate AMD Natural Outcome arm 1 included bilateral intermediate AMD with classic drusen (soft, reticular pseudodrusen, cuticular, or calcified drusen) without advanced AMD. A Study for Intermediate AMD Natural Outcome arm 2 included pachychoroid spectrum disease with unilateral or bilateral findings such as pachydrusen with retinal pigment epithelium undulation, focal attenuation of inner choroidal vessel, and dilated outer choroidal vessels or pigmentary abnormalities corresponding retinal pigment epithelium elevation or disruption in OCT, without significant classic drusen. The KEATS arm comprised active exudative AMD, including typical exudative macular neovascularization, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. All underwent standardized multimodal imaging at baseline and are followed annually.<br><br>MAIN OUTCOME MEASURES: Baseline demographic, behavioral, and ocular characteristics across drusen-driven, pachychoroid-driven, and exudative AMD phenotypes.<br><br>RESULTS: Of the 1409 individuals screened, 1159 were enrolled (ASIANO 1: 551; ASIANO 2: 317; KEATS: 291). A Study for Intermediate AMD Natural Outcome arm 1 participants were older, predominantly female, and universally bilateral; arm 2 participants were younger, more often male, and frequently unilateral. Korean Exudative AMD Treatment Study showed a high proportion of patients with polypodal choroidal vasculopathy (39.5%, patient-based) and male predominance. Behavioral profiles also differed: the KEATS arm had lower eye-supplement use, higher smoking exposure, and less frequent sunglasses/sun-visor use. Exploratory follow-up analyses suggested differing rates of exudative conversion between ASIANO arm 1 and arm 2.<br><br>CONCLUSIONS: Korean Age-Related Maculopathy Study is the first large-scale, nationally representative prospective cohort in Koreans, distinguishing drusen-driven and pachychoroid-driven maculopathy phenotypes and detailing exudative subtypes. These baseline data provide a foundation for future phenotype-specific progression analyses and management strategies in Asian populations.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41910764, year = {2026}, author = {Savastano, MC and Fossataro, C and Hu, L and Mottola, F and D'Onofrio, NC and Cestrone, V and Giannuzzi, F and Rizzo, S}, title = {Non neovascular Age - related macular degeneration - Review on clinical and imaging advances.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41910764}, issn = {1435-702X}, }
@article {pmid41912546, year = {2026}, author = {Mani, P and Ramachandran, N and Sowmya, V and Ravi, V and Ramesh, PV and Alahmadi, TJ}, title = {Multi-scale adaptive fusion network for retinal layer and fluid segmentation in optical coherence tomography B-scans.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-44006-5}, pmid = {41912546}, issn = {2045-2322}, abstract = {Major treats to visual health includes diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO), which require prompt and correct interpretation for effective treatment. Optical coherence tomography (OCT) is an imaging modality, providing intense cross-sectional views of the retina to aid in diagnosis. Diagnosis and localization of retinal diseases were complicated by the structure of retinal fluids. In order to cope with these challenges, a deep learning architecture, the Adaptive Multi-Domain Fusion Network (AMDF-Net), is initiated to improve the detection of retinal diseases. AMDF-Net assimilates state of the art modules like Hybrid Spectral-Spatial Transformer (HSST) to gain insight about global and local features effectively. Moreover, the Dynamic Attention Fusion (DAF) module enhances the work of the network by specifying the features unique to retinal fluids, and Disease-Inclusive Segmentation (DIS) module makes it easier to accurately diagnose primary fluids. Extensive analyses of publicly available and real-time data reveal that AMDF-Net shows notable results with Dice coefficient of 98. 87% and classification accuracy of 98. 12%. These remarks highlight the potential of AMDF-Net to elevate automated retinal disease analysis and provide valuable assistance in the development of decisions focused on treatment.}, }
@article {pmid41904432, year = {2026}, author = {Bulut, M and Reyhan, AH}, title = {A comparison of GPT-4V's capability in optical coherence tomography images of age-related macular degeneration with expert assessments.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04777-x}, pmid = {41904432}, issn = {1471-2415}, }
@article {pmid41896965, year = {2026}, author = {Kochnev Goldstein, A and Park, J and Zhou, Y and Jensen, N and Palanker, D}, title = {Simulation of prosthetic vision with the PRIMA system and enhancement of face representation.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12984-026-01958-z}, pmid = {41896965}, issn = {1743-0003}, support = {R01-EY-035227/NH/NIH HHS/United States ; W81XWH-22-1-0933//Department of Defense/ ; FA9550-19-1-0402//Air Force Office of Scientific Research/ ; }, abstract = {OBJECTIVE: Patients implanted with the PRIMA photovoltaic subretinal prosthesis in geographic atrophy report form vision with the average acuity matching the 100 μm pixel size. Although this remarkable outcome enables them to read and write, they report difficulty with perceiving faces. Despite the pixelated stimulation, patients report seeing smooth patterns rather than dots. This paper provides a novel, non-pixelated algorithm for simulating prosthetic vision the way it is experienced by PRIMA patients, compares the algorithm's predictions to clinical perceptual outcomes, and offers computer vision and machine learning (ML) methods to improve face representation.<br><br>APPROACH: Our simulation algorithm (ProViSim) integrates a grayscale filter, spatial resolution filter, and contrast filter. This accounts for the limited sampling density of the retinal implant (pixel pitch), as well as the reduced contrast sensitivity of prosthetic vision. Patterns of Landolt C and faces created using this simulator are compared to reports from actual PRIMA users. To recover the facial features lost in prosthetic vision due to limited resolution or contrast, we apply an ML facial landmarking model, as well as contrast-adjusting tone curves to the image prior to its projection onto the photovoltaic retinal implant.<br><br>MAIN RESULTS: Prosthetic vision simulated using the above algorithm matches the maximum letter acuity observed in clinical studies, as well as the patients' subjective descriptions of perceived facial features. Applying the inversed contrast filter to the image prior to its projection onto the implant and accentuating the facial features using an ML facial landmarking model helps preserve the contrast in prosthetic vision, improves emotion recognition and reduces the response time.<br><br>SIGNIFICANCE: Spatial and contrast constraints of prosthetic vision limit resolvable features and degrade natural images. ML based methods and contrast adjustments prior to image projection onto the implant mitigate some limitations and improve face representation. Even though higher spatial resolution can be expected with implants having smaller pixels, contrast enhancement still remains essential for face recognition.}, }
@article {pmid41897380, year = {2026}, author = {Kaštelan, S and Antunica, AG and Konjevoda, S and Tomić, Z and Sarić, A and Kulaš, M and Kulaš, L and Begović, EK and Čanović, S and Kovačević, P and Ivanković, M}, title = {Mitochondrial ROS in Retinal Neurodegeneration: Thresholds, Quality Control Failure, and Precision Therapeutic Windows.}, journal = {Biomolecules}, volume = {16}, number = {3}, pages = {}, doi = {10.3390/biom16030445}, pmid = {41897380}, issn = {2218-273X}, mesh = {Humans ; *Reactive Oxygen Species/metabolism ; *Mitochondria/metabolism/pathology ; Animals ; Oxidative Stress ; Oxidation-Reduction ; *Neurodegenerative Diseases/metabolism/pathology ; *Retina/metabolism/pathology ; }, abstract = {Mitochondrial reactive oxygen species (mtROS) play a dual role in retinal physiology, acting as essential redox signalling mediators under homeostatic conditions but driving oxidative damage and neurodegeneration once regulatory thresholds are exceeded. Owing to the exceptionally high energetic demands of retinal neurons and supporting cells, even subtle perturbations in mitochondrial redox balance can precipitate progressive retinal dysfunction. Increasing evidence indicates that retinal neurodegenerative diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and inherited optic neuropathies, are characterised not by uniform oxidative stress, but by disease- and stage-specific mtROS signatures shaped by mitochondrial quality control capacity. This review synthesises current insights into the sources, regulation, and signalling functions of mtROS in the retina, with particular emphasis on threshold-dependent redox transitions, reverse electron transport, and the progressive failure of mitochondrial quality control mechanisms, including mitophagy, mitochondrial dynamics, and redox-responsive transcriptional networks. The limitations of non-selective antioxidant strategies are critically examined, highlighting why indiscriminate ROS suppression has yielded limited clinical benefit. In contrast, emerging therapeutic approaches aimed at recalibrating mitochondrial redox homeostasis, rather than abolishing physiological signalling, are discussed in the context of disease stage, metabolic state, and mitochondrial competence. By integrating redox biology with mitochondrial quality control and precision medicine concepts, this review proposes a unifying framework in which retinal neurodegeneration is governed by regulated mtROS signalling and the progressive exhaustion of mitochondrial resilience. This model defines critical therapeutic windows for mitochondria-targeted intervention and provides a framework for biomarker-guided patient stratification.}, }
@article {pmid41897428, year = {2026}, author = {Roberson, JK and Bauer, AN and Lopez-Ramirez, A and Jenness, DB and Cruz Zayas, S and Cooke Bailey, JN and Woodlief, TL}, title = {Environmental Exposures and Oxidative Stress in Retinal and Optic Nerve Diseases: Mechanisms, Consequences, and Therapeutic Opportunities.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/antiox15030281}, pmid = {41897428}, issn = {2076-3921}, support = {Institutional Startup Funds//East Carolina University Brody School of Medicine/ ; }, abstract = {Oxidative stress is a key contributing and convergent pathogenic mechanism linked to retinal and optic nerve diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma. The retina is highly susceptible to redox imbalance due to intense mitochondrial activity, oxygen consumption, and light exposure. While endogenous drivers are well recognized, the contribution of environmental exposure to retinal oxidative injury remains incompletely defined. This review uniquely integrates emerging environmental contaminants with canonical oxidative stress pathways. We examine how cigarette smoke, ultraviolet radiation, heavy metals, microplastics, and per- and polyfluoroalkyl substances (PFASs) promote oxidative injury through mitochondrial dysfunction, inflammatory signaling, impaired antioxidant responses, and ferroptotic pathways. We also highlight therapeutic strategies targeting oxidative pathways and emphasize the importance of exposure-informed retinal and optic nerve disease research.}, }
@article {pmid41898716, year = {2026}, author = {Calbay, O and Hsieh, CL and Lu, C and Ghosh, S and Vijaykumar, V and Watts, I and Sweigard, H and Gandhi, J and den Hollander, AI}, title = {Mapping the Hypoxic Fitness Landscape of Retinal Pigment Epithelial Cells.}, journal = {International journal of molecular sciences}, volume = {27}, number = {6}, pages = {}, doi = {10.3390/ijms27062857}, pmid = {41898716}, issn = {1422-0067}, mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; Humans ; Cell Hypoxia/genetics ; Gene Expression Profiling ; Cell Line ; Transcriptome ; Macular Degeneration/genetics/metabolism/pathology ; CRISPR-Cas Systems ; *Epithelial Cells/metabolism ; Mitochondria/metabolism ; *Hypoxia/genetics ; Oxygen/metabolism ; }, abstract = {Chronic hypoxia is a hallmark of aging and retinal diseases such as age-related macular degeneration (AMD), yet the molecular mechanisms that enable retinal pigment epithelium (RPE) cells to survive under sustained low-oxygen conditions remain poorly understood. To address this, we conducted transcriptomic profiling and a genome-wide CRISPR-Cas9 loss-of-function screen in ARPE-19 cells exposed to chronic hypoxia (1% and 5% O2), mimicking the retinal disease environment. The CRISPR screen identified genes whose loss compromises RPE viability or fitness under hypoxia, while transcriptomic profiling revealed oxygen-dependent shifts in key functional modules. These findings converged on pathways related to mitochondrial function, extracellular matrix remodeling, vascular signaling, and cell cycle regulation, identifying unique functional nodes specific to RPE cells. These core processes are also implicated in retinal diseases, such as AMD. Together, these complementary approaches provide an integrated view of the molecular networks driving RPE adaptation to hypoxic stress and highlight novel gene candidates that may serve as therapeutic targets in retinal disease.}, }
@article {pmid41901080, year = {2026}, author = {Baek, HI and Kim, I and Bae, J and Kwon, JE and Kang, SC}, title = {Effects of Long-Term Supplementation with Centella asiatica (L.) Urb. Extract (CA-HE50) on Macular Pigment Optical Density: A Randomized, Double-Blind, Placebo-Controlled Trial.}, journal = {Nutrients}, volume = {18}, number = {6}, pages = {}, doi = {10.3390/nu18060905}, pmid = {41901080}, issn = {2072-6643}, support = {117050-3//Ministry of Agriculture, Food and Rural Affairs/ ; }, mesh = {Humans ; Double-Blind Method ; Female ; Middle Aged ; Male ; *Plant Extracts/administration &amp; dosage/pharmacology ; *Dietary Supplements ; *Centella/chemistry ; Aged ; *Triterpenes/administration &amp; dosage/pharmacology ; *Macular Pigment/metabolism ; Antioxidants ; *Macula Lutea/drug effects/metabolism ; }, abstract = {Background/Objectives: Macular pigment optical density (MPOD) is a nutrition-responsive biomarker that indicates the antioxidant status of the macula. This study aimed to evaluate the effects of long-term supplementation with a standardized Centella asiatica (L.) Urb. extract (CA-HE50) on MPOD in a randomized, double-blind, placebo-controlled clinical trial. Methods: Eighty men and women aged 45-65 years, with baseline MPOD values between 0.2 and 0.4, were randomly assigned to receive either CA-HE50 (300 mg/day, n = 40) or a placebo (n = 40) for 6 months. Efficacy was assessed by measuring MPOD at baseline and on Days 60, 120, and 180. The primary efficacy endpoint was the change in MPOD from baseline to Day 180. Safety was evaluated through monitoring adverse events, vital signs, and clinical laboratory tests. Results: By Day 180, supplementation with CA-HE50 resulted in a statistically significant increase in MPOD compared to the placebo in the right eye, left eye, and the average of both eyes (all p < 0.001). Significant between-group differences were also observed at Day 120, indicating a time-dependent improvement in MPOD. Additionally, the proportion of responders was significantly higher in the CA-HE50 group compared to the placebo group (p < 0.001). CA-HE50 was well tolerated, with no serious adverse events or clinically relevant safety concerns identified during the intervention period. Conclusions: Long-term supplementation with C. asiatica extract significantly improved MPOD, supporting its potential role in enhancing macular nutritional status. These findings suggest that CA-HE50 may serve as a beneficial dietary intervention for maintaining macular health.}, }
@article {pmid41888298, year = {2026}, author = {Krasniakova, M and Pansell, T and Gustafsson, J}, title = {Impact of individualized colored spectacle filters on photophobia and visual comfort in central visual field defect patients: a one-year study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-45302-w}, pmid = {41888298}, issn = {2045-2322}, abstract = {Visual comfort is a critical yet often overlooked aspect in managing patients with central visual field defects and photophobia. This study investigates the long-term effects of individualized colored spectacle filters on visual comfort and function in patients with Age-related Macular Degeneration and Leber Hereditary Optic Neuropathy. Patients were fitted with individualized precision tint spectacles tailored to improve vision comfort for one year. The study involved a comprehensive evaluation of visual acuity, contrast sensitivity, and photophobia symptoms alongside qualitative feedback from patient interviews. Results indicate significant improvements in subjective visual comfort and function, with a notable reduction in photophobia symptoms among patients with Leber Hereditary Optic Neuropathy. Colored filters, particularly those in the blue-green spectrum, were preferred by most patients and had a positive impact on comfort. Statistical analysis revealed trends in color preferences and subjective enhancements in visual function, underscoring the potential benefits of comfort-tint filters and the importance of personalized treatment approaches. The findings suggest that individualized colored spectacle filters can be valuable in enhancing visual comfort and function for patients with central visual field defects. This study shows the importance of integrating visual comfort considerations into clinical practice for a comprehensive approach to patient care.}, }
@article {pmid41888985, year = {2026}, author = {Helland-Hansen, BA and Sverstad, A and Petrovski, G and Larsen, SE}, title = {Eye-tracking-derived foveal biomarkers and functional alterations in dry AMD: findings from a controlled clinical study.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00838-x}, pmid = {41888985}, issn = {2056-9920}, support = {333925//Norges Forskningsr&#xe5;d/ ; 333925//Norges Forskningsr&#xe5;d/ ; 333925//Norges Forskningsr&#xe5;d/ ; 333925//Norges Forskningsr&#xe5;d/ ; }, }
@article {pmid41889981, year = {2026}, author = {Meng, R and Kenney, RC and Pan, M and Gupta, AK and Modi, YS and Chauhan, P and Curcio, CA and Srinivasan, VJ}, title = {Visible Light Optical Coherence Tomography Reveals Aging at the Retinal Pigment Epithelium-Bruch's Membrane Interface.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.18.712487}, pmid = {41889981}, issn = {2692-8205}, abstract = {UNLABELLED: Landmark histological studies have shown that as the retina ages, lipids and other debris accumulate within Bruch's membrane (BM) and in spaces introduced between BM and the retinal pigment epithelium (RPE). These deposits grow with age, increasing the risk of age-related macular degeneration (AMD), the leading cause of irreversible vision loss for older adults globally. Current in vivo imaging lacks specificity to study BM and the important spaces at the RPE/BM interface in living human eyes, while histological techniques suffer from processing artifacts that distort photoreceptors. Here we employ visible light Optical Coherence Tomography (OCT), with 1 micrometer depth resolution, to quantitatively analyze these tissues in living eyes. We identify age-related changes in a human cohort without retinal pathology: thickening and loss of contrast of the hyper-reflective BM band, and thickening of the RPE together with the sub-RPE basal laminar space (RPE+sBL). Both forms of thickening were locally coupled depending on eccentricity, suggesting related biosynthetic mechanisms. A thicker BM and RPE+sBL were locally associated with anomalies in the overlying photoreceptors. Thus, sub-clinical changes in aging eyes detected by visible light OCT resemble early versions of deposits found in AMD. Visible light OCT depicts the relationship between RPE+sBL, BM, and photoreceptors in aging, holding promise to precisely and non-invasively grade ocular phenotypes ranging from normal aging to early AMD.<br><br>SIGNIFICANCE STATEMENT: As humans age, lipids and other debris deposit in Bruch's membrane (BM) of the human eye (1) and spaces introduced between the retinal pigment epithelium (RPE) and BM. These deposition processes are linked to the eventual development of age-related macular degeneration (AMD), the leading blinding disease amongst older adults. Here we investigate these deposits with visible light OCT imaging in living human subjects without overt retinal pathology. Whereas early RPE/BM deposits were previously assessed only in donor eyes postmortem via preparations that distort photoreceptors, our results shed light on these AMD precursors and overlying photoreceptor changes in living human eyes.}, }
@article {pmid41890681, year = {2026}, author = {Agius, D and Mamo, J and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F}, title = {Prevalence of Refractive Errors, Myopic Macular Degeneration, and Associated Risk Factors in a Maltese Population-Based Study.}, journal = {Clinical optometry}, volume = {18}, number = {}, pages = {561426}, pmid = {41890681}, issn = {1179-2752}, abstract = {PURPOSE: To estimate the prevalence of refractive error and myopic macular degeneration in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors.<br><br>PATIENTS AND METHODS: This population-based cross-sectional study included 1,794 participants aged 50-80 years from Malta, recruited as part of The Malta Eye Study (response rate 44.8%). Demographic, medical, behavioral, and ocular data were collected using structured questionnaires. Standardized ophthalmic examinations were performed, including autorefraction and retinal imaging with optical coherence tomography. Refractive error was classified by spherical equivalent as myopia (< -0.50 D) and hyperopia (> +0.50 D), while astigmatism was defined as &#x2264; -0.75 D. Myopic macular degeneration was graded using the meta-analysis for pathologic myopia classification. Associations were assessed using multivariable logistic regression.<br><br>RESULTS: Among right phakic, surgically untouched eyes, the prevalence of emmetropia, myopia, and hyperopia was 20.0% (95% CI 18.0-22.1%), 25.1% (95% CI 23.0-27.4%), and 54.8% (95% CI 52.3-57.3%), respectively. Vector-derived average astigmatism prevalence in both eyes was 44.3% (95% CI 41.6-46.9%), with against-the-rule astigmatism being the most common pattern. Effective refractive error coverage exceeded 90% for both distance and near vision. The prevalence of any myopic degeneration in either eye was 2.6% (95% CI 1.9-3.4%). Myopia prevalence among individuals aged 50-59 years was lower than that reported in other European populations, and use of long-acting anti-muscarinic agents was associated with myopic degeneration (OR 25.70, 95% CI 1.55-426.04, p=0.023).<br><br>CONCLUSION: This study reports refractive error and myopic macular degeneration prevalence broadly comparable to other European settings. Lower myopia prevalence among individuals aged 50-59 years may reflect complex gene-environment-behavior interactions. Further investigation of these interactions, as well as the potential impact of long-acting anti-muscarinic agents on myopic macular degeneration, is warranted, particularly in light of the wide confidence interval.}, }
@article {pmid41891014, year = {2026}, author = {Yeh, TC and Velez, G and Prasad, A and Lee, SH and Rasmussen, DK and Kumar, A and Chadha, M and Dabaja, MZ and Singh, AM and Sanislo, S and Smith, S and Mryuthyunjaya, P and Montague, A and Bassuk, AG and Almeida, D and Dufour, A and Mahajan, VB}, title = {Multi-omics liquid biopsy identifies mitochondrial dysfunction in geographic atrophy and supports the longevity-associated metabolite α-ketoglutarate as a therapeutic strategy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.12.26347263}, pmid = {41891014}, abstract = {BACKGROUND: Mitochondrial dysfunction is an emerging metabolic hallmark of age-related diseases, yet tools to directly profile mitochondrial pathways and test metabolic interventions in the living human eye remain limited. Multi-omics ocular liquid biopsy enables real-time proteomic and metabolomic profiling of the intraocular microenvironment, complementing systemic biomarkers and imaging surrogates. Here, we used this approach to define mitochondrial and tricarboxylic acid (TCA) cycle dysregulation in geographic atrophy (GA) and to assess whether oral α-ketoglutarate (α-KG) supplementation can modulate mitochondrial metabolites within the eye.<br><br>METHODS: Mitochondrial and TCA cycle-related proteins were profiled in aqueous humor (AH) samples from patients with GA using DNA-aptamer-based proteomics. In a phase 0 study, a second cohort undergoing sequential cataract surgery provided paired AH samples collected at first-eye surgery and at second-eye surgery after interim &#x3b1;-KG supplementation. These samples underwent targeted metabolomic profiling using hydrophilic interaction liquid chromatography coupled with mass spectrometry.<br><br>RESULTS: In GA, 64 mitochondrial proteins were differentially expressed, including coordinated TCA-cycle deficiencies marked by reduced expression of enzymes regulating TCA entry and flux, including PDHB and DLST. In the phase 0 cohort, oral &#x3b1;-KG supplementation significantly increased intraocular &#x3b1;-KG levels and the &#x3b1;-KG-to-succinate ratio (P < 0.05), with coordinated shifts across TCA intermediates consistent with enhanced TCA cycle flux.<br><br>CONCLUSIONS: AH proteomics demonstrated mitochondrial pathway depletion in GA, consistent with reduced oxidative bioenergetic capacity. AH metabolomics provided first-in-human in vivo evidence that systemic &#x3b1;-KG supplementation can modify intraocular metabolites and may enhance intraocular energy metabolism. These findings support ocular liquid biopsy as a precision-health framework for per-patient biomarker-guided metabolic trials in GA.<br><br>PLAIN LANGUAGE SUMMARY: Geographic atrophy (GA) is an advanced form of age-related macular degeneration and a major cause of irreversible vision loss. To better understand the biology of GA, we studied proteins and small molecules in aqueous humor, the fluid inside the eye. We found that eyes with GA showed clear signs of mitochondrial dysfunction, including disruptions in the tricarboxylic acid (TCA) cycle, a key pathway for energy production. This suggests that impaired cellular metabolism is an important feature of the disease. We then tested whether oral &#x3b1;-ketoglutarate (&#x3b1;-KG), a metabolite involved in mitochondrial function and previously shown to have life-extending effects in preclinical studies, could alter these metabolic pathways in the human eye. We found that &#x3b1;-KG supplementation not only increased intraocular &#x3b1;-KG levels but changed metabolic markers linked to mitochondrial activity, providing the first direct evidence that oral supplementation can reach the eye and measurably modify metabolism inside the living human eye. Together, these findings show that liquid biopsy can provide a direct molecular snapshot of the living human eye and may help accelerate the development of biomarker-guided therapies for ocular diseases.<br><br>KEY POINTS: Questions: What specific mitochondrial and TCA-cycle dysfunctions occur in the aqueous humor (AH) of patients with geographic atrophy (GA), and can oral &#x3b1;-ketoglutarate (&#x3b1;-KG) supplementation measurably remodel these metabolic pathways in the living human eye?Findings: AH proteomics in GA patients revealed significant mitochondrial disruption and a coordinated depletion of TCA-cycle enzymes. In a paired-eye interventional metabolomics study, oral &#x3b1;-KG significantly increased intraocular &#x3b1;-KG levels and the &#x3b1;-KG-to-succinate ratio, proving that systemic therapy can drive measurable metabolic modulation within the human eye.Meaning: Multi-omics liquid biopsy provides a direct, eye-specific readout of mitochondrial metabolism in GA and offers early human proof-of-concept that a systemic metabolic therapy can successfully reach and modify intraocular pathways, paving the way for biomarker-guided clinical trials in AMD.}, }
@article {pmid41891097, year = {2026}, author = {Gallardo, MJ and Porter, M and Vincent, L and Sandrosyan, A and Koch, B and Kasuga, DT}, title = {Outcomes of Ab-Interno Canaloplasty and Gonioscopy-Assisted Transluminal Trabeculotomy in Eyes with Sustained Intraocular Pressure Elevation Following Intravitreal Injections.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {563035}, pmid = {41891097}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the long-term efficacy and safety of combined ab-interno canaloplasty (ABiC) and gonioscopy-assisted transluminal trabeculotomy (GATT) with the iTrack microcatheter in patients with sustained intraocular pressure (IOP) elevation following intravitreal anti-VEGF or steroid injections.<br><br>PATIENTS AND METHODS: This was a retrospective, single-center study of patients who underwent ABiC and GATT with the iTrack microcatheter between 2017 and 2021 for secondary open-angle glaucoma or ocular hypertension following intravitreal injections. Eligible eyes had a preoperative IOP of &#x2265;18&#xa0;mmHg while on maximal tolerated medical therapy. Primary outcomes included IOP and glaucoma medication burden. Surgical success was defined using American Academy of Ophthalmology (AAO) criteria. Subgroup analyses were conducted by etiology (anti-VEGF vs steroid-induced). Kaplan-Meier analysis estimated cumulative success rates.<br><br>RESULTS: Thirty-four eyes from 30 patients were included, with a mean last follow-up of 15.3&#xb1;9.8 months. Mean IOP was reduced by 46%, from 28.1&#xb1;6.0&#xa0;mmHg at baseline to 14.3&#xb1;5.6&#xa0;mmHg (p<0.001) at the last follow-up, while the number of medications decreased from 2.79&#xb1;0.9 to 1.76&#xb1;1.5 (p=0.001). Surgical success was achieved in 71% of eyes. Medication-free status was reached in 29% of eyes, compared with none at baseline, and 26% achieved IOP &#x2264;15&#xa0;mmHg without medications. Additional glaucoma procedures were needed in 11.8% of eyes. Combined ABiC and GATT remained effective in eyes receiving post-procedure intravitreal reinjections or prolonged topical steroid use. Kaplan-Meier analysis showed a survival probability above 70% at 25 months.<br><br>CONCLUSION: Combined ab-interno canaloplasty and GATT using the iTrack microcatheter is a safe surgical option for selected eyes with sustained IOP elevation following intravitreal injections. The procedure achieved meaningful reductions in IOP and medication use, including in eyes requiring continued intravitreal therapy, supporting a primary surgical effect. Careful patient selection and long-term follow-up remain essential, as a subset of eyes may require additional intervention.}, }
@article {pmid41891889, year = {2026}, author = {Tabano, DC and Ali, FS and Borkar, DS and Leng, T and Ahmed, A and Ko, S and Myrick, A and Zwick, E and Downey, A and Barteselli, G and Singh, RP}, title = {One-year Real-world Outcomes With Faricimab in Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-9}, doi = {10.3928/23258160-20260302-02}, pmid = {41891889}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: This study evaluated real-world treatment patterns and 1-year outcomes in patients with neovascular age-related macular degeneration (nAMD) initiating faricimab.<br><br>PATIENTS AND METHODS: FARETINA-AMD was a retrospective study using data from the IRIS[&#xae;] Registry for patients diagnosed with nAMD initiating faricimab from February 2022 to March 2023.<br><br>RESULTS: Included in the study were 2,025 treatment-naive patients (2,184 eyes) and 22,253 patients (26,851 eyes) previously treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Visual acuity improved by 2.0 &#xb1; 15.0 (mean &#xb1; SD) letters in treatment-naive eyes (P < .001) and was maintained in previously treated eyes at injection 7. Central subfield thickness (CST) improved by -53.1 &#xb1; 64.8 &#x3bc;m in treatment-naive and -28.5 &#xb1; 79.7 &#x3bc;m in previously treated eyes (both P < .0001); 78.4% and 66.8%, respectively, had achieved/maintained CST &#x2264; 280 &#x3bc;m at injection 7. Dosing frequency was reduced in the second 6 months (mean 2.4-3.2 injections) versus the first 6 months (4.0-4.2) of treatment.<br><br>CONCLUSION: Outcomes among patients with nAMD receiving faricimab over 1-year follow-up support the real-world effectiveness and extended durability of treatment.}, }
@article {pmid41891912, year = {2026}, author = {Antonietti, M and Mercado, C and Fortun, JA and Albini, TA and Dubovy, SR and Smiddy, WE and Schwartz, SG and Kovach, JL}, title = {Real-world Safety Profile of Avacincaptad Pegol in the Management of Geographic Atrophy.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-5}, doi = {10.3928/23258160-20260305-01}, pmid = {41891912}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: This study evaluated the safety of intravitreal avacincaptad pegol in treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>PATIENTS AND METHODS: A retrospective review was conducted of patients treated with avacincaptad pegol at Bascom Palmer Eye Institute from January 2024 to January 2025. Adverse events, side effects, and potential risk factors were recorded.<br><br>RESULTS: The study analyzed 124 eyes from 83 patients (mean age 81.8 &#xb1; 6.4 years; 49.4% male; 91.6% White) who received 409 injections in total. Injection intervals varied: 54 eyes monthly, 55 every other month, and others less frequently. The variability in injection frequency was mostly due to patient difficulty with follow-up. Follow-up ranged 3 to 12 months (median: 5 months). Baseline visual acuity averaged 0.40 (approx. 20/50 Snellen) decreasing slightly to 0.38 (20/53 Snellen)-not statistically significant (P = .628). Most eyes (85.2%) were pseudophakic; 47% of patients had prior neovascular AMD treated with anti-vascular endothelial growth factor (anti-VEGF), and 24.2% were simultaneously being treated for active neovascular AMD in the eye receiving avacincaptad pegol. Sixteen eyes had prior pegcetacoplan treatment. Adverse events were rare. One patient developed culture-negative endophthalmitis 4 days after the third injection, presenting with vision loss to hand motion but improving after intravitreal antibiotics. Side effects occurred in 14 eyes (13.8%) across 10 patients, including intraocular pressure elevation (seven eyes), discomfort (four eyes), visual disturbance (two eyes), and subconjunctival hemorrhage (one eye). Five patients discontinued treatment, and one eye (0.8%) had reactivation of neovascular AMD.<br><br>CONCLUSION: Our study highlights the safety profile of avacincaptad pegol for GA, with a low incidence of conversion to neovascular AMD, few adverse events, and manageable side effects.}, }
@article {pmid41892574, year = {2026}, author = {Kim, SJ and Kim, DY and Jeong, D and Lee, C and Cho, HD and Kim, MP}, title = {Food-Grade Microgels for Age-Related Macular Degeneration: Design, Fabrication, and Targeted Delivery.}, journal = {Gels (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, doi = {10.3390/gels12030252}, pmid = {41892574}, issn = {2310-2861}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions-particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients-have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut-eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD.}, }
@article {pmid41893318, year = {2026}, author = {Greiner, JV and Glonek, T}, title = {Metabolomics of Ocular Tissues with High and Low Metabolic Activity.}, journal = {Metabolites}, volume = {16}, number = {3}, pages = {}, doi = {10.3390/metabo16030167}, pmid = {41893318}, issn = {2218-1989}, support = {EY-03988/EY/NEI NIH HHS/United States ; Grant 533181//Valerie and Walter Winchester Grant/ ; }, abstract = {BACKGROUND/OBJECTIVES: An unexplainably high millimolar (~3 mM) concentration of adenosine triphosphate (ATP), herein designated as nucleoside triphosphate (NTP), exists in the crystalline lens even though all of the known functions of NTP combined require only micromolar (μM) concentrations. Since the lens is one of the most metabolically quiescent tissues in the body and the retina is one of the most metabolically active tissues in the body, we compared their phosphorus metabolomics and related metabolic indices that measure their metabolic health status. As such, the purpose of this report was to compare the NTP concentrations in lenticular and retinal tissues and the metabolic indices that include NTP as well as their phosphorus-31 spectral modulus (PSM).<br><br>METHODS: Known phosphatic metabolic profiles of rat lenses and retinas were compared and quantified in mole % phosphorus using phosphorus-31 nuclear magnetic resonance spectroscopy. Metabolic indices measuring health status, where ATP is a principal component, were calculated, including the PSM.<br><br>RESULTS: In this secondary analysis, the NTP concentration calculated in the lens was 41.0% of the total phosphate detected, whereas it was similarly 37.6% in the sensory retina. The PSM values were 1.28 for the lens and similarly 1.42 for the retina.<br><br>CONCLUSIONS: Due to the lens tissue's low quiescent metabolic activity, one might expect the NTP concentration to be lower in the lens than in the highly metabolically active retina: a similar difference is expected in the PSM. However, this was not the case with the mM concentrations of NTP in both the lens (&#x2265;2.3 mM) and the retina (2.4 mM). The similarly high mM NTP concentration coupled with the PSM-calculated measure of metabolic health in these tissues is a novel finding. The novel findings of such similarly high concentrations of NTP in these metabolically diverse eye tissues further support and are consistent with the hypothesized role of NTP as a hydrotrope, preventing protein aggregation resulting in age-related cataractogenesis and age-related macular degeneration.}, }
@article {pmid41893888, year = {2026}, author = {Azizmohammad Looha, M and Amanollahi, M and Hashemi, E and Jameie, M and Mohammadpoor, A and Mozafar, M and Samiee, R and Jalalinejad, M and Arevalo, JF}, title = {Global burden of age-related macular degeneration: Trends, regional disparities, and projections from the Global Burden of Disease study 2021.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41893888}, issn = {1435-702X}, }
@article {pmid41893991, year = {2026}, author = {Venugopal, D and Wood, J and Black, A and Bradley, C and Bentley, S}, title = {Development and Validation of the Assessment of Low Luminance Vision-Related Activities.}, journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)}, volume = {46}, number = {1}, pages = {81-89}, pmid = {41893991}, issn = {1475-1313}, mesh = {Humans ; Cross-Sectional Studies ; Aged ; Male ; Female ; *Visual Acuity/physiology ; Reproducibility of Results ; *Vision, Low/physiopathology/diagnosis ; Middle Aged ; *Vision, Binocular/physiology ; Aged, 80 and over ; *Vision Tests/methods ; Adult ; Psychometrics ; }, abstract = {PURPOSE: To develop a new comprehensive vision-related low luminance performance-based measure, the 'Assessment of Low Luminance Vision-Related Activities' (ALLVA), and evaluate its construct validity and test-retest reliability using Rasch analysis.<br><br>METHODS: A cross-sectional observational study of 75 adults with vision impairment from various ocular conditions (mean age 70 years [SD: 15 years]; mean binocular visual acuity 0.63 logMAR [SD: 0.45 logMAR]) was conducted. Seventeen tasks were developed as items and administered to participants under low luminance, with completion time and number of errors recorded. As some items could not be completed by all participants, five categories of completion time were created for analysis (quartiles and a fifth category representing non-completion). The 'method of successive dichotomisations'-a polytomous Rasch model that always estimates ordered response category thresholds, enabling its application to binned continuous data-was applied to create a single combined measure of performance. Errors were not analysed as they occurred infrequently and generally increased completion time. Eleven participants with age-related macular degeneration were retested after 2-4 weeks. Clinical vision measures, including visual acuity, contrast sensitivity and visual fields, were also collected.<br><br>RESULTS: Initial analysis of the 17-task ALLVA led to removal of one item, walking a mobility course, due to infit and outfit mean square statistics being outside the acceptable range. For the remaining 16 tasks, item difficulty was well targeted to person ability, with only a minor floor effect. Item and person reliability values were 0.98 and 0.93, respectively. Clinical vision measures were significantly correlated with person measures. Bland-Altman analysis indicated a mean difference between test and retest person measures of -0.08 logits (95% limits of agreement 2.16 to -2.32 logits).<br><br>CONCLUSION: The ALLVA is the first comprehensive vision-related low luminance performance-based measure. It demonstrated strong Rasch psychometric properties, validity and good test-retest reliability.}, }
@article {pmid41896032, year = {2026}, author = {Chen, F and Shi, Y}, title = {Lipid peroxidation as a driver of oxidative and neuroinflammatory damage in ocular disease: review and perspectives.}, journal = {Archives of physiology and biochemistry}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/13813455.2026.2628183}, pmid = {41896032}, issn = {1744-4160}, abstract = {Context: Lipid peroxidation (LPO) causes oxidative stress and neuroinflammation in eye diseases. Malondialdehyde and 4-hydroxy-2-nonenal are produced in the eye via polyunsaturated fatty acid oxidation. Objective: Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. Materials and Methods: LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. Results: Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. Conclusion: Understanding how lipid peroxidation, oxidative stress, and neuroinflammation interact is crucial to developing effective eye health and vision loss therapies.}, }
@article {pmid41896127, year = {2027}, author = {Zhao, X and Wen, Y and Yang, Z and Gu, X and Zeng, Y and Lai, A and Cao, W and He, M and Shi, Z and Zhang, W and Zhao, Q and Cheng, T and Meng, L and Wang, Y and Cheng, S and Wang, C and Liu, X and Yu, Q and Cai, X and Liu, G and Lu, L and Lv, L and Wei, W and Yuan, D and Zhang, J and Cun, Y and Chen, M and Zhang, T and Li, Z and Zeng, Q and Xiao, Z and Wang, C and Su, Y and Wang, Z and Sha, Q and Sheng, B and Chen, Y}, title = {Development and validation of a deep learning model to predict visual and anatomical prognosis of anti-VEGF therapy for neovascular age-related macular degeneration (KongMing Study): a prospective, nationwide, multicentre study.}, journal = {The Lancet. Digital health}, volume = {}, number = {}, pages = {100971}, doi = {10.1016/j.landig.2025.100971}, pmid = {41896127}, issn = {2589-7500}, abstract = {BACKGROUND: The financial burden and the uncertain response of the anti-vascular endothelial growth factor (anti-VEGF) treatment often cause hesitation among patients with neovascular age-related macular degeneration (nAMD), highlighting the need for a reliable method to predict treatment outcomes. We aimed to develop and validate a deep learning model that can predict the visual and anatomical prognosis of patients with nAMD undergoing anti-VEGF therapy.<br><br>METHODS: This prospective, nationwide, multicentre study involved 18 tertiary referral hospitals from 12 provinces across China. A large dataset of patients (aged 50-85 years) with nAMD treated with anti-VEGF therapy (Conbercept, 0&#xb7;5&#x2009;mg/0&#xb7;05&#x2009;mL, Chengdu, China) under a 3+PRN regimen was established. All participants underwent comprehensive ophthalmological examinations, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography (OCT) imaging at baseline, follow-up, and 4-6 weeks after treatment. Patients with other ocular diseases that could confound the diagnosis or prognosis of nAMD were excluded. A Structural-Attention Guided Therapeutic Response Predicting Model (KongMing Model) was developed based on the lesion-aware, transformer-based multitask architecture to facilitate post-single-injection (4-6 weeks after any single injection during the treatment), post-three-loading-injections (4-6 weeks after the first three consecutive injections), and 1-year-post-three doses plus pro re nata (3+PRN; 1-year after treatment) dual predictions of visual and anatomical prognoses. For the prediction of BCVA changes, model performance was evaluated with the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, average precision, and human-machine comparison. The prediction of BCVA values was evaluated with mean absolute error (MAE) and coefficient of determination (R[2]). The prediction of post-treatment OCT images was evaluated by the structural similarity index measure (SSIM) compared with the true post-treatment OCT images. Heatmaps and Shapley additive explanation images were used to identify features related to the prognosis of nAMD.<br><br>FINDINGS: From July 1, 2020, to Dec 31, 2023, we collected 29&#x2009;772 OCT images from 1226 participants after screening to form the internal dataset. From Jan 1, 2023, to May 1, 2024, we collected 3308 OCT images from 172 participants after screening to form the external dataset. In total, we included 603 (43&#xb7;1%) women and 795 (56&#xb7;9%) men. For the prediction of post-single-injection, post-three-loading-injections, and 1-year-post-3+PRN BCVA changes, our model achieved AUCs of 0&#xb7;948 (95% CI 0&#xb7;942-0&#xb7;954) in the internal test and 0&#xb7;941 (0&#xb7;934-0&#xb7;948) in the external test, also significantly outperforming ophthalmologists with different levels of experience in the human-machine comparison (all p<0&#xb7;0001). For the prediction of the post-treatment BCVA values, our model had a remarkably low MAE across the three predictions (range 0&#xb7;048 [0&#xb7;039-0&#xb7;057] to 0&#xb7;058 [0&#xb7;044-0&#xb7;072]) and high R[2] (range 0&#xb7;7140-0&#xb7;9012) across both internal and external tests. The model achieved an SSIM exceeding 0&#xb7;57, indicating a close similarity between the predicted and true post-treatment OCT images. In all aspects, our model outperformed the convolutional neural network-based models. Heatmaps and SHAP plots precisely located the features related to the prognosis of nAMD.<br><br>INTERPRETATION: The KongMing Model, developed and tested by a nationwide, multicentre dataset, showed excellent performance in predicting the post-single-injection, post-three-loading-injections, and 1-year-post-3+PRN visual and anatomical prognosis of patients with nAMD undergoing anti-VEGF therapy. It provides a robust and non-invasive method for more informed personalised treatment planning, potentially improving treatment adherence and avoiding unnecessary interventions.<br><br>FUNDING: National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Lumitin Vision to Brightness Research Funding for the Young and middle-aged Ophthalmologists, Peking Union Medical College Hospital Talent Cultivation Program, Fundamental Research Funds for the Central Universities, Peking Union Medical College, National High-Level Hospital Clinical Research Funding, Beijing Students' Funding for Innovation and Entrepreneurship Training Program, Guangdong Basic and Applied Basic Research Foundation, Guangdong Provincial Key Laboratory.}, }
@article {pmid41896129, year = {2027}, author = {Tsai, CY and Lai, TT}, title = {Artificial intelligence for post-treatment prediction in age-related macular degeneration.}, journal = {The Lancet. Digital health}, volume = {}, number = {}, pages = {100997}, doi = {10.1016/j.landig.2026.100997}, pmid = {41896129}, issn = {2589-7500}, }
@article {pmid41883753, year = {2026}, author = {Vidal-Alaball, J and Arocas Bonache, A and Solé-Casals, J and Royo Fibla, D and Marin-Gomez, FX and Distéfano, LN and Boixadera, A and Casado-García, &#xc1; and García-Domínguez, M and Inés, A and Heras, J and Zapata, MA}, title = {Clinical validation of artificial intelligence algorithms for the detection of different central-involved retinal pathologies and glaucoma from non-mydriatic images.}, journal = {Frontiers in artificial intelligence}, volume = {9}, number = {}, pages = {1754682}, pmid = {41883753}, issn = {2624-8212}, abstract = {UNLABELLED: The use of Artificial intelligence (AI) algorithms for detecting different ophthalmic diseases, especially diabetic retinopathy (DR), has become increasingly popular. In this paper, we evaluate the screening performance of different AI algorithms based on convolutional neural networks (CNNs) in a real-world scenario. To that aim, we conducted an observational and cross-sectional study on patients aged ≥18 years with type-2 diabetes mellitus, who had undergone fundus examination for DR screening using a teleophthalmology program. We used the UPRETINA diagnostic system, which consists of 8 AI algorithms based on CNNs. A total of 1,652 eyes from 871 patients were analyzed. The AI algorithms had a sensitivity/specificity of 86.8%/95.6% for detecting DR; 94.9%/94.3% for detecting age-related macular degeneration (AMD); 82.7%/92.4% for detecting glaucomatous optic neuropathy (GON); 87.0%/87.5% for detecting epiretinal membrane; and 89.7%/98.0% for detecting nevus. Additionally, the sensitivity/specificity for correctly classifying images as right eye/left eye and to correctly classifying images gradeability (medium or high quality) were 100% /100 and 92.9%/90.5%, respectively. The AUROC of the AI algorithms ranged between 0.9777 (AMD) and 0.9122 (GON). UPRETINA system was capable of automatically and accurately classifying the screening retinographies, reducing workload and leading to a scenario of more efficient optimization of resources.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04132401 NCT04132401.}, }
@article {pmid41885533, year = {2026}, author = {Michaud, C and Faurite, C and Guénot, J and Gallice, M and Chiquet, C and Vayssière, N and Berry, I and Trotter, Y and Baurès, R and Rosito, M and Soler, V and Peyrin, C and Cottereau, BR}, title = {Perceptual Learning as a Rehabilitation Approach to Enhance Motion Processing in Maculopathy Patients.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {52}, doi = {10.1167/iovs.67.3.52}, pmid = {41885533}, issn = {1552-5783}, mesh = {Humans ; Male ; *Motion Perception/physiology ; Female ; *Macular Degeneration/rehabilitation/physiopathology ; Magnetic Resonance Imaging ; Aged ; *Learning/physiology ; Middle Aged ; Visual Acuity/physiology ; }, abstract = {PURPOSE: Macular degeneration (MD) is a disease affecting the central retina and significantly impairing vision. Given the absence of a cure, rehabilitation strategies are vital for enhancing visual perception.<br><br>METHODS: This study introduces a perceptual learning (PL) protocol for MD patients, focusing on improving motion perception, a key ability for navigating environments and social interactions. Patients underwent four weeks of motion discrimination training, with pretraining and post-training functional magnetic resonance imaging scans to study the underlying neural mechanisms. We also assessed generalization to an untrained multiobject tracking task in a subset of participants. A control group, matched by age and gender with simulated scotomata, followed the same procedures.<br><br>RESULTS: Results in both groups indicated improved motion discrimination and increased responses in the human middle temporal complex (hMT+), a critical neural hub for motion processing. Improvements in the multiobject tracking task suggested transferable learning effects.<br><br>CONCLUSIONS: These findings highlight perceptual learning as a promising rehabilitation strategy for MD and potentially other eye conditions.}, }
@article {pmid41885545, year = {2026}, author = {Zhang, K and Jia, L and Zhao, C and Wang, Y and Wei, P and Han, G}, title = {Genetic Evidence for Causal Effects of Blood Metabolites on Age-Related Macular Degeneration and its Subtypes.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {31}, doi = {10.1167/tvst.15.3.31}, pmid = {41885545}, issn = {2164-2591}, mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics/blood/metabolism/classification ; Aged ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a predominant cause of permanent vision impairment among older individuals. Despite available treatments for advanced disease, a comprehensive understanding of the pathogenesis, specifically the pivotal causal pathways, remains elusive. This study aims to assess the causal effects of 1400 serum metabolites and their ratios on 3 AMD subtypes using Mendelian randomization (MR).<br><br>METHODS: This study leveraged an integrated MR analytical framework to systematically investigate the causal relationships of 1400 circulating metabolites and metabolite ratios with 3 AMD subtypes: early, dry, and wet AMD. The robustness and consistency of the findings were validated via comprehensive sensitivity analyses, alongside assessments for heterogeneity and horizontal pleiotropy.<br><br>RESULTS: Of the 1400 metabolites and metabolite ratios examined, inverse variance weighting identified 77, 62, and 80 metabolites with statistically significant causal associations with early, dry, wet AMD, respectively. Most of these associations demonstrated consistency across complementary MR methodologies. Furthermore, most of the identified metabolites did not show significant evidence of heterogeneity or horizontal pleiotropy. Notably, among lipid classes, glycerophosphoethanolamine (GPE) metabolites consistently exhibited protective effects.<br><br>CONCLUSIONS: Multiple metabolite classes, including glycerophospholipids, fatty acids, steroid hormones, and energy metabolism intermediates, are involved in AMD pathogenesis. These findings confirm that metabolic dysregulation is the principal driver of AMD at the causal level, in addition to revealing heterogeneous effect sizes of distinct metabolic pathways across disease subtypes. This study reveals potential molecular targets for developing strategies based on metabolism for AMD prevention, diagnosis, and precision therapeutics.<br><br>TRANSLATIONAL RELEVANCE: This work bridges fundamental metabolic discoveries to clinical application by identifying causal metabolites as novel therapeutic targets and informing strategies specific to disease subtypes for precision medicine and diagnostics in AMD.}, }
@article {pmid41887320, year = {2026}, author = {Boscia, G and Feo, A and Quarta, A and Stradiotto, E and Forte, P and Termite, AC and Mastropasqua, R and Savastano, A and Reibaldi, M and Eandi, CM and Boscia, F and Cicinelli, MV and Au, A and Tsui, E and Vujosevic, S and Schmidt-Erfurth, U and Sarraf, D and Sadda, SR and Romano, MR and Borrelli, E and Viggiano, P}, title = {Intraretinal Hyperreflective Foci: Pathophysiology, Imaging Features, and Clinical Implications Across Retinal Diseases.}, journal = {Progress in retinal and eye research}, volume = {}, number = {}, pages = {101464}, doi = {10.1016/j.preteyeres.2026.101464}, pmid = {41887320}, issn = {1873-1635}, abstract = {Intraretinal hyperreflective foci (IHRF) are a common but pathologically diverse optical coherence tomography (OCT) finding, increasingly recognized as a hallmark of retinal disease activity. IHRF have been described in age-related macular degeneration (AMD), where they may represent migrating retinal pigment epithelium cells, in diabetic retinopathy, retinal vein and artery occlusions, pachychoroid spectrum disorders, inherited retinal dystrophies, and ocular inflammatory diseases. Their appearance reflects a spectrum of underlying processes, including inflammatory cell recruitment, lipid or proteinaceous material deposition, and degenerative tissue remodeling. Advances in OCT technology and multimodal imaging have refined the characterization of IHRF, enabling correlations with histopathology, cytokine profiles, and genetic risk variants. Across diseases, their presence, number, distribution, and temporal evolution have been linked to structural progression, functional decline, and treatment response-serving as early indicators of atrophy or neovascularization in AMD, markers of inflammation and therapeutic responsiveness in vascular retinopathies, and predictors of recurrence or complication in pachychoroid disease. This review provides a comprehensive synthesis of the current literature on IHRF, summarizing their proposed histopathological correlates, multimodal imaging features, molecular associations, prognostic significance, and potential role as biomarkers in a wide range of retinal disorders.}, }
@article {pmid41879246, year = {2026}, author = {Pu, J and Gao, L and Thomas, TN and Goerdt, L and Corradetti, G and Kar, D and McGwin, G and Crosson, JN and Owsley, C and Curcio, CA}, title = {Choriocapillaris Flow Signal Deficits Are Associated With AMD Onset and Early Progression Over Three Years: ALSTAR2 Follow-Up.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {51}, doi = {10.1167/iovs.67.3.51}, pmid = {41879246}, issn = {1552-5783}, mesh = {Humans ; Disease Progression ; Male ; Female ; Aged ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fluorescein Angiography/methods ; Middle Aged ; *Macular Degeneration/physiopathology/diagnosis ; Regional Blood Flow/physiology ; Aged, 80 and over ; *Capillaries/physiopathology ; *Retinal Vessels/physiopathology ; }, abstract = {PURPOSE: To determine if a baseline choriocapillaris flow signal deficits (CCFD%), as a marker of impaired transport, is associated with age-related macular degeneration (AMD) onset and progression at the 3-year follow-up.<br><br>METHODS: Participants &#x2265; 60 years old with normal macular health, early AMD (eAMD), and intermediate AMD (iAMD) were staged at baseline and follow-up with the Age-Related Eye Disease Study (AREDS) 9-step classification system and were then classified as stable and progressing based on whether their stage advanced. Spectral-domain optical coherence tomography angiography (OCTA) quantified baseline CCFD% across the Early Treatment Diabetic Retinopathy Study (ETDRS) central subfield (CS), inner ring (IR), and an outer area (OA, extending superiorly). Adjusted baseline CCFD% values were compared between stable and progressing eyes.<br><br>RESULTS: Of 332 included eyes at baseline (mean age, 71.1 &#xb1; 5.8 years), 173 eyes were normal, 101 were eAMD, and 58 were iAMD. Over 3 years, 284 eyes remained stable (85.5%), and 48 eyes progressed (14.5%). In the overall cohort, progressing eyes demonstrated significantly higher baseline CCFD% than stable eyes in the CS (57.7% vs. 53.5%; P = 0.007) and IR (56.1% vs. 53.9%; P = 0.045), but not in the OA. When stratified by baseline AMD stage, stable versus progressor differences were exclusively observed in eAMD (51.4% vs. 60.7% and 52.6 vs. 58.0% for CS and IR, respectively) but not in OA or in normal eyes (all P > 0.05).<br><br>CONCLUSIONS: CCFD% in the CS and IR, one aspect of impaired transport between circulation and photoreceptors, is associated with AMD progression in early-stage disease; this spatial specificity implicates the fovea.}, }
@article {pmid41879420, year = {2026}, author = {Lishinsky-Fischer, N and Jaskoll, S and Kramer, A and Grunin, M and Elbaz-Hayoun, S and Rinsky, B and Chowers, I and Levy, J}, title = {Distinct Genetic Profiles Associated With Subretinal Drusenoid Deposits and Cardiovascular Risk in Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {27}, doi = {10.1167/tvst.15.3.27}, pmid = {41879420}, issn = {2164-2591}, mesh = {Humans ; *Macular Degeneration/genetics/complications ; Female ; *Retinal Drusen/genetics ; Male ; Aged ; Retrospective Studies ; *Polymorphism, Single Nucleotide ; *Cardiovascular Diseases/genetics ; Aged, 80 and over ; Middle Aged ; Tomography, Optical Coherence ; Genetic Predisposition to Disease ; Gene Frequency ; Genotype ; Risk Factors ; Phenotype ; }, abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are increasingly recognized as a distinct phenotype in age-related macular degeneration (AMD) and may be linked to cardiovascular disease (CVD). This study aims to explore whether AMD patients with SDDs carry a distinct genetic profile related to CVD risk compared to those without SDDs.<br><br>METHODS: In a retrospective cohort of 459 AMD patients with genotyping and spectral-domain OCT data, we annotated SDD status and extracted cardiovascular diagnoses and procedures from electronic medical records. Fifty-two AMD-associated single-nucleotide polymorphisms (SNPs) were used to calculate weighted genetic risk scores (GRSs), and minor allele frequencies (MAFs) were compared between groups. Principal component analysis (PCA) was performed to assess clustering by SDD status within CVD subgroups.<br><br>RESULTS: Patients with SDDs exhibited distinct MAFs in several SNPs, including CFH, ARMS2, COL4A3, and ARHGAP21. Certain variants were more strongly associated with cardiovascular subtypes in patients with SDDs compared to those without. GRSs related to lipid metabolism and complement pathways were higher among SDD-positive patients within selected CVD subgroups. PCA suggested modest but significant separation between genetic profiles of patients with and without SDDs.<br><br>CONCLUSIONS: AMD patients with SDDs show distinct genetic signatures potentially relevant to cardiovascular health. These findings suggest that SDDs may represent a genetically and systemically unique AMD phenotype. Further investigation is warranted to understand the shared pathophysiology and potential for systemic risk stratification.<br><br>TRANSLATIONAL RELEVANCE: Integrating OCT phenotyping and genomic profiling in AMD may uncover systemic disease associations with implications for precision medicine.}, }
@article {pmid41879644, year = {2026}, author = {Capuano, V and Fragiotta, S and Abadou, J and Sacconi, R and Miere, A and Amoroso, F and Souied, EH and Querques, G}, title = {Centenarian patients with neovascular age-related macular degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004837}, pmid = {41879644}, issn = {1539-2864}, abstract = {PURPOSE: To report clinical characteristics of exudative neovascular age-related macular degeneration (AMD) in centenarian patients.<br><br>METHODS: A retrospective, longitudinal study conducted in two retinal referral centers in Europe. Clinical characteristics of neovascular AMD patients having at last follow up at least &#x2265; 100 years were reviewed.<br><br>RESULTS: Twenty-eight eyes from 14 patients (13 females), with a mean baseline age of 95.7 (SD 4.1) years and a mean follow-up duration of 89 months (39.9). The mean age at last follow-up was 102.4 (1.7) years. Most eyes (86%) presented type 1 macular neovascularization (MNV). At the last follow-up, best corrected visual acuity (BCVA) was stable or improved in 57% of eyes, with a mean final BCVA of 53 letters (21.8) Snellen equivalent 20/100. Eyes with better visual outcomes (>50 letters) had significantly higher baseline BCVA (p<0.001) and thicker subfoveal choroidal thickness (p=0.03). Macular hemorrhage (25%) and macular atrophy (53.6%) were associated with poorer BCVA.<br><br>CONCLUSION: Centenarian patients with neovascular AMD can maintain vision with long-term anti-VEGF therapy. These findings underscore the need for tailored management strategies for the challenges faced by centenarians with neovascular AMD.}, }
@article {pmid41880726, year = {2026}, author = {Karapapak, M and Özal, E and Ermiş, S and Önal, I and Gül, C and Özal, SA}, title = {Prevalence and progression of non-exudative macular neovascularization in age-related macular degeneration.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {4}, pages = {104835}, doi = {10.1016/j.jfo.2026.104835}, pmid = {41880726}, issn = {1773-0597}, abstract = {PURPOSE: To determine the prevalence of non-exudative macular neovascularization (neMNV) in age-related macular degeneration (AMD) and to identify potential markers for activation and disease progression using findings from optical coherence tomography angiography (OCTA).<br><br>MATERIALS AND METHODS: This retrospective longitudinal study included patients with treatment-na&#xef;ve neMNV secondary to AMD who presented to a tertiary retina clinic between January 2021 and July 2024. Patients were evaluated using OCT and OCTA at each visit, with a definitive diagnosis of neMNV established using OCTA. Exclusion criteria included prior anti-VEGF therapy, pachychoroid spectrum diseases, vitreoretinal surgery, chorioretinal conditions, and unreliable OCTA images. Parameters assessed included best-corrected visual acuity (BCVA), and lens status.<br><br>RESULTS: neMNV was identified in 186 out of 3119 patients (5.96%). The mean age was 72.73&#xb1;8.60 years, with a mean follow-up of 22.11&#xb1;7.51&#xa0;months. Transition from the non-exudative to the exudative form occurred in 34 (18.3%) patients, with an average activation duration of 14.71&#xb1;8.42 months. BCVA improved significantly in neMNV eyes over time (P<0.01) but remained stable in fellow eyes. No significant correlations were found between activation time and age, gender, or laterality. The prevalence of exudative MNV in fellow eyes was 67%.<br><br>CONCLUSIONS: neMNV is relatively common among AMD patients, with a prevalence of 5.96%. Regular monitoring using OCTA is essential for early detection and management, given the significant potential for these lesions to progress to an exudative state. Future research should focus on identifying specific biomarkers and imaging characteristics predictive of neMNV activation.}, }
@article {pmid41881234, year = {2026}, author = {Goerdt, L and Basten, V and Terheyden, JH and Dunbar, H and Luhmann, U and Zakaria, N and Leal, S and Moll, KP and Poor, S and Tufail, A and Schmid, M and Finger, RP and Schmitz-Valckenberg, S and Holz, FG and Saßmannshausen, M and , }, title = {Hyperreflective foci contiguous with the RPE associate with visual function in aging, early and intermediate AMD: MACUSTAR study report.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.03.020}, pmid = {41881234}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early (e) age-related macular degeneration (AMD), and intermediate (i) AMD.<br><br>DESIGN: Prospective cohort study.<br><br>SUBJECTS: Participants of the MACUSTAR study.<br><br>METHODS: MACUSTAR participants underwent color fundus photography, optical coherence tomography (OCT) imaging, best-corrected visual acuity (BCVA), low luminance VA (LLVA), rod-mediated dark adaptation (RMDA) at 12&#xb0;, contrast sensitivity (CS), mesopic, and scotopic pointwise sensitivity deviation (mesPSD, scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using ANOVA, linear regression, and Spearman correlation.<br><br>MAIN OUTCOME MEASURES: Presence, burden, topographic distribution of rpeHRF; association with functional parameters.<br><br>RESULTS: Fifty-six normal aged (33 female (f), mean age 68.1 &#xb1; 6.4 years), 34 eAMD (27 f, 71.7 &#xb1; 6.4 years), and 583 iAMD eyes (387 f, 72.0 &#xb1; 7.0 years) were included. rpeHRF counts were 0.16 &#xb1; 0.85 in normals, 0.33 &#xb1; 0.96 in eAMD, and 1.61 &#xb1; 2.49 in iAMD (p < 0.001). BCVA, LLVA, CS (all p < 0.001), and scPSD (p&#x202f;=&#x202f;0.001) differed between disease groups. Whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all p < 0.001), and mesPSD (p&#x202f;=&#x202f;0.02). rpeHRF cound associated modestly with only CS, scPSD, LLVA, and BCVA.<br><br>CONCLUSIONS: Presence and burden of rpeHRF were independently associated with impaired visual function and may thus serve as a prognostic biomarker for disease progression and enrichment criterion for future interventional trials.}, }
@article {pmid41881262, year = {2026}, author = {Yasuda, H and Nakamura, S and Shirakawa, A and Kuse, Y and Mori, K and Shimazawa, M}, title = {Age-dependent induction of ER stress in retinal pigment epithelium impairs phagocytosis via ADAM17-dependent MERTK shedding.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {111397}, doi = {10.1016/j.jbc.2026.111397}, pmid = {41881262}, issn = {1083-351X}, abstract = {Retinal pigment epithelium (RPE) plays a crucial role in maintaining visual function by phagocytosing photoreceptor outer segments (POS). Age-related decline in RPE phagocytic activity has been linked to the development of degenerative retinal diseases, including age-related macular degeneration (AMD). However, the underlying mechanisms of RPE phagocytic dysfunction remain poorly understood. In this study, we examined age-related induction of endoplasmic reticulum (ER) stress in RPE cells and its association with POS phagocytosis using tissues from middle-aged mice and cultured RPE cells. In the RPE-choroid complex of 12-month-old mice, ER stress marker proteins were significantly upregulated compared to younger mice. Notably, this increase was absent in the neural retina at the same age. In cultured RPE cells, pharmacological induction of ER stress by tunicamycin (Tm) significantly reduced both phagocytic activity and lysosomal function. Treatment with sodium 4-phenylbutyrate, a chemical chaperone, and transfection with chaperone protein-inducible plasmids alleviated the ER stress-induced phagocytic dysfunction in RPE cells. In the lysates of ER stress-induced RPE cells, the extracellular domain of Mer tyrosine kinase receptor (MERTK) and phosphorylation of focal adhesion kinase were significantly decreased. Mechanistically, ER stress promoted the maturation of a disintegrin and metalloprotease 17 (ADAM17) through Ca[2+]-dependent activation of the Furin protease, leading to MERTK shedding. Furthermore, ADAM17 knockdown attenuated the Tm-induced impairment of POS internalization. Collectively, our findings suggest that ER stress impairs RPE phagocytosis through an integrated mechanism and may contribute to the pathogenesis of AMD.}, }
@article {pmid41881267, year = {2026}, author = {Dong, H and Ding, Q and Liu, M}, title = {Exploring the causal link between long-term elevated plasma caffeine levels and age-related eye diseases using Mendelian randomization.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {113106}, doi = {10.1016/j.exger.2026.113106}, pmid = {41881267}, issn = {1873-6815}, abstract = {OBJECTIVE: Experimental evidence suggests that caffeine has the potential to reduce the risk of age-related eye diseases (AREDs). However, there is a lack of population-based evidence directly assessing whether long-term caffeine exposure benefits these conditions. In this study, we employ Mendelian randomization (MR) to evaluate the causal effects of long-term elevated plasma caffeine levels (PCL) on AREDs, including age-related macular degeneration (AMD), age-related cataract (ARC), and glaucoma.<br><br>METHODS AND ANALYSIS: Single-nucleotide polymorphisms strongly associated with PCL and located near the CYP1A2 and AHR genes, both key in caffeine metabolism, were selected as instrumental variables. The MR analyses then calculated the Wald ratio for each variant, with variant-specific estimates combined through a multiplicative random effects meta-analysis.<br><br>RESULTS: Our MR analysis showed that higher genetically predicted PCL were significantly associated with a reduced risk of dry AMD (odds ratio [OR], 0.651; 95% confidence interval [CI], 0.527-0.805; pFDR&#x202f;<&#x202f;0.001), wet AMD (OR, 0.582; 95% CI, 0.433-0.781; pFDR&#x202f;=&#x202f;0.001), ARC (OR, 0.812; 95% CI, 0.720-0.916; pFDR&#x202f;=&#x202f;0.001), and primary open-angle glaucoma (POAG) (OR, 0.753; 95% CI, 0.633-0.896; pFDR&#x202f;=&#x202f;0.002). Notably, an estimated 54.05% (95% CI: 19.25%-88.84%) of the protective effect of PCL on POAG was mediated through reduced intraocular pressure (IOP).<br><br>CONCLUSION: This MR study provides evidence that long-term higher plasma caffeine levels may reduce the risk of age-related eye diseases, including AMD, ARC, and POAG. Notably, approximately half of the protective effect of PCL on POAG is mediated through IOP reduction.<br><br>This study provides novel evidence on the long-term effects of caffeine on age-related eye diseases, including age-related macular degeneration (AMD), age-related cataract (ARC), and primary open-angle glaucoma (POAG). Unlike previous studies that used imprecise measures of caffeine exposure, such as caffeinated beverage intake, we utilized fasting plasma caffeine levels, offering a more accurate assessment of individual exposure. Through Mendelian randomization, we demonstrate that long-term caffeine exposure is independently associated with reduced risks of AMD and ARC, and is also linked to a lower risk of POAG, with approximately half of this effect mediated through intraocular pressure (IOP) reduction. Our findings suggest that caffeine could play a protective role in ocular health, offering new insights into potential prevention strategies for age-related eye diseases.}, }
@article {pmid41108153, year = {2025}, author = {Beckers, D and Lockington, D and Kretz, F and Beckers, L}, title = {Beyond the Label: Inconsistencies in AREDS2 Eye Supplements and a Call for Standardisation.}, journal = {Seminars in ophthalmology}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/08820538.2025.2577391}, pmid = {41108153}, issn = {1744-5205}, abstract = {PURPOSE: Age-related macular degeneration (AMD) remains a major cause of vision impairment among older adults globally. While treatment exists for the more aggressive, exudative form, options for managing nonexudative AMD are limited. One of the few interventions with scientific backing is the AREDS2 micronutrient formula, which has demonstrated an ability to slow disease progression in patients with intermediate AMD.This investigation set out to systematically assess over-the-counter supplements in the UK that are promoted for macular support, measuring how closely their contents align with the evidence-based AREDS2 formulation.<br><br>METHODS: Products marketed as beneficial for AMD were collected and analyzed. Their labeled ingredients and dosages were directly compared with the standardized nutrient profile outlined in the AREDS2 clinical trials.<br><br>RESULTS: The analysis revealed that most commercially available supplements deviated markedly from the AREDS2 formula. On average, vitamin C levels were 52.3% lower than recommended, vitamin E levels were 61.2% lower, and zinc content was reduced by 40.1%. Only a small subset of products fully matched both the composition and dosage of the reference formulation.<br><br>CONCLUSION: These findings highlight a significant gap between marketed claims and clinical evidence. Most supplements do not meet the established AREDS2 standards, potentially limiting their efficacy. Some were promoted specifically for AMD, while others used general "macular health" claims, adding to patient confusion. This inconsistency underscores the need for regulatory measures to enforce standardized labeling and formulation requirements to ensure informed clinical recommendations.}, }
@article {pmid41108452, year = {2025}, author = {Shen, LL and Applegate, CA and Rubin, GS and Sunness, JS}, title = {Patient-reported visual difficulties associated with geographic atrophy from age-related macular degeneration.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {412}, pmid = {41108452}, issn = {1573-2630}, support = {R01EY08552/NH/NIH HHS/United States ; }, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/complications/etiology ; Male ; Female ; *Visual Acuity/physiology ; Prospective Studies ; Aged ; *Macular Degeneration/complications/diagnosis/physiopathology ; *Vision Disorders/etiology/physiopathology/diagnosis ; Tomography, Optical Coherence/methods ; Surveys and Questionnaires ; Cross-Sectional Studies ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; }, abstract = {PURPOSE: To characterize visual difficulties associated with geographic atrophy (GA).<br><br>METHODS: A prospective study included 91 participants with bilateral GA. A visual activities questionnaire was administered at baseline and annually for 2&#xa0;years along with best-corrected visual acuity (BCVA) and GA size. Baseline questionnaire responses were compared using logistic regressions, and longitudinal changes were analyzed with generalized linear mixed-effect models. A small group of 12 participants with drusen without GA served as a comparison to participants with GA and good VA.<br><br>RESULTS: Compared to drusen participants, bilateral GA participants with BCVA of 20/50 or better reported significantly more difficulties in 8 vision-specific tasks. The frequencies of difficulty in reading small print, trouble with face recognition, and stopping driving were positively associated with GA severity cross-sectionally, measured by either BCVA or GA size, and increased over 2&#xa0;years (P&#x2009;<&#x2009;0.05 for each). Additional significant longitudinal changes included difficulty seeing in dim light (P&#x2009;=&#x2009;0.005) and locating a sign (P&#x2009;=&#x2009;0.008).<br><br>CONCLUSION: Reading, vision in dim illumination, face recognition, locating signs, and driving worsen over 2&#xa0;years in patients with GA, and may be the appropriate self-reported items to monitor in a clinical trial. These findings highlight the need for therapies addressing both GA enlargement and visual function decline.}, }
@article {pmid41109779, year = {2025}, author = {Lai, TYY and Kataoka, K and Hsieh, YT and Apte, RS and Bhende, M and Chang, A and Chaikitmongkol, V and Chen, Y and Chen, LJ and Cheung, GCM and Chhablani, J and Fong, KCS and Guymer, RH and Gomi, F and Huang, SS and Kim, JE and Kokame, GT and Koh, A and Li, X and Lim, JI and Ng, DSC and Okada, AA and Radke, NV and Sadda, SR and Sasaki, M and Sivaprasad, S and Shanmugam, MP and Verma, L and Wong, TY and Zhang, X and Lam, DSC}, title = {Corrigendum to "International consensuses and guidelines on etiology, diagnosis, treatment, and future developments of neovascular age-related macular degeneration (nAMD) by the Asia-Pacific Vitreo-retina Society (APVRS), the Asia-Pacific Ocular Imaging Society (APOIS) and the Academy of the Asia-Pacific Professors of Ophthalmology (AAPPO)" [Asia-Pac J Ophthalmol, Available online 29 August 2025, 100242 (2025) DOI:10.1016/j.apjo.2025.100242].}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100249}, doi = {10.1016/j.apjo.2025.100249}, pmid = {41109779}, issn = {2162-0989}, }
@article {pmid41110782, year = {2025}, author = {Liu, H and Wong, DSL and Parikh, BH and Hao, M and Tan, QSW and Chee, PL and Lou, X and Kai, D and Lingam, G and Huang, D and Su, X and Liu, Z}, title = {Single-cell-pore-sized 3D printed scaffolds for retinal pigment epithelial cell therapy.}, journal = {Acta biomaterialia}, volume = {207}, number = {}, pages = {294-310}, doi = {10.1016/j.actbio.2025.10.033}, pmid = {41110782}, issn = {1878-7568}, mesh = {*Printing, Three-Dimensional ; *Tissue Scaffolds/chemistry ; *Retinal Pigment Epithelium/cytology/metabolism ; Humans ; Animals ; Rabbits ; Polyesters/chemistry ; Swine ; Porosity ; *Human Embryonic Stem Cells/cytology/metabolism ; *Cell- and Tissue-Based Therapy ; }, abstract = {Cell therapy is one of the most promising methods to treat retinal degenerative diseases, and crucial to its success is optimizing biomaterials to facilitate the delivery of retinal pigment epithelial (RPE) cells. This study explores the application of single-cell-pore-sized 3D printed polycaprolactone (PCL) scaffolds for cultivating human embryonic stem cell-derived RPE cell sheets. It compares them with track-etched polyethylene terephthalate (PET) membranes, the commercial products used in clinical trials for RPE cell delivery. We engineered two types of scaffolds at the microscale to optimize cell culture conditions, specifically focusing on pore size and fiber spacing. Protein expression analysis demonstrated that one scaffold with a pore size of ∼10 µm facilitated superior cellular integrity and function. Functional assessments, including barrier integrity, permeability, and phagocytosis assays, indicated that this scaffold enhanced nutrient exchange and maintained effective RPE functions akin to PET membranes. In an in vivo study, color fundus, optical coherence tomography, immunohistochemistry, and electroretinography revealed that 3D printed scaffolds exhibited biocompatibility, stability, and minimal inflammatory responses in the subretinal space of porcine models for 2 months and rabbit models for 14 months, with no adverse impact on retinal structure or function over either period. The findings suggest that 3D-printed biodegradable scaffolds present a viable alternative for RPE cell delivery, potentially advancing therapies for retinal degenerative conditions. STATEMENT OF SIGNIFICANCE: Cell therapy shows great promise for treating eye diseases that lead to vision loss. A crucial aspect of this therapy is delivering specialized retinal pigment epithelial (RPE) cells effectively. Our research presents a 3D-printed scaffold made from polycaprolactone (PCL), designed to carry RPE cells derived from human stem cells and dissolve after placement in the eye. We tested this scaffold in rabbits and pigs to evaluate its surgical handling, cell delivery effectiveness, and safety for human application. Our results refine implant design, paving the way for safer and more effective treatments for retinal diseases. Overall, this research enhances the application of cell therapy with scaffolds and offers valuable insights for future medical practices.}, }
@article {pmid41111635, year = {2025}, author = {Koksaldi, S and Karti, O and Saatci, AO}, title = {Anti-vascular endothelial growth factor therapies in ophthalmology.}, journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal}, volume = {14}, number = {3}, pages = {107-135}, pmid = {41111635}, issn = {2322-3219}, abstract = {BACKGROUND: Retinal diseases, including neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, are leading causes of vision loss worldwide. The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies has dramatically changed the management of these conditions, offering targeted treatment that can preserve and even improve vision. We aimed to provide a comprehensive review of the development, clinical applications, and emerging indications of anti-VEGF therapies in ophthalmology, including biosimilar agents.<br><br>METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE for English-language articles published up to 31 July 2025. Additional sources were identified through manual screening of reference lists. Included studies spanned various designs: clinical trials, meta-analyses, observational studies, and preclinical research. Keywords used in the search strategy included terms such as "anti-VEGF therapy", "biosimilar pharmaceuticals", "intravitreal and intrastromal anti-VEGF injections", "retinal diseases" including "macular degeneration" and "retinal neovascularization", "ranibizumab", and "bevacizumab", as well as relevant MeSH terms where applicable.<br><br>RESULTS: Anti-VEGF agents have transformed the management of retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Newer agents such as brolucizumab and faricimab offer prolonged durability and enhanced anatomic outcomes, while biosimilars provide cost-effective alternatives. Anti-VEGF therapy has also shown promise in off-label or emerging indications such as neovascular glaucoma, corneal neovascularization, and other retinal or choroidal disorders including secondary macular edema and/or macular neovascularization associated with various forms of uveitis, diffuse choroidal hemangioma in Sturge-Weber Syndrome, hereditary retinal disorders such as fundus flavimaculatus, Coats-Like retinitis pigmentosa, Peripherin-2-associated retinopathy, immune checkpoint inhibitor use, radiation retinopathy, retinitis pigmentosa, Bietti crystalline dystrophy, autosomal recessive bestrophinopathy, melanocytoma-associated macular neovascular membrane, Best disease, Wyburn-Mason syndrome, choroidal osteoma, peripheral exudative hemorrhagic chorioretinopathy, traumatic choroidal rupture, torpedo maculopathy, optic disc melanocytoma, type 2 proliferative macular telangiectasia, and Coats disease. High-dose formulations and innovative delivery systems are under active investigation to reduce the treatment burden and extend dosing intervals.<br><br>CONCLUSIONS: Anti-VEGF therapies have revolutionized the field of ophthalmology, providing sight-saving treatment for a range of retinal diseases that were once considered untreatable or inevitably blinding. Today, anti-VEGF drugs are the go-to option for managing neovascular retinal disorders, thanks to their proven efficacy, favorable safety profile, and transformative impact on modern eye care.}, }
@article {pmid41111640, year = {2025}, author = {Abukhaled, Y}, title = {Reactive oxygen species and oxidative stress in ocular disease: from molecular mechanisms to targeted therapies.}, journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal}, volume = {14}, number = {3}, pages = {136-145}, pmid = {41111640}, issn = {2322-3219}, abstract = {BACKGROUND: Reactive oxygen species and oxidative stress are increasingly recognized as central drivers in the development of major ocular diseases, including cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. The eye's unique environment-continuous light exposure, high oxygen tension, and abundant photosensitizers-renders it particularly vulnerable to ROS-mediated damage. This narrative review aims to synthesize current evidence on the molecular mechanisms of oxidative stress in ocular disease and highlight emerging therapeutic approaches.<br><br>METHODS: Targeted searches of PubMed, Scopus, and Google Scholar for literature published between 2000 and June 2025 were conducted. Keywords included "oxidative stress", "reactive oxygen species", "ocular disease", "cataract", "age-related macular degeneration", "glaucoma", and "diabetic retinopathy". Only English-language, peer-reviewed articles were considered. Relevant primary studies, clinical trials, reviews, and experimental reports were selectively incorporated, with an emphasis on recent publications and high-impact contributions to the field.<br><br>RESULTS: Evidence consistently demonstrates that ROS induce lipid peroxidation, protein oxidation, DNA damage, mitochondrial dysfunction, and disruption of redox-sensitive cellular signaling pathways across ocular tissues. In cataracts, oxidation of crystalline proteins and glutathione depletion are primary drivers of lens opacification. In age-related macular degeneration, mitochondrial dysfunction and lipofuscin accumulation promote retinal pigment epithelium degeneration and neovascularization. Glaucoma involves both trabecular meshwork oxidative injury, contributing to elevated intraocular pressure, and mitochondrial-driven retinal ganglion cell apoptosis. In diabetic retinopathy, hyperglycemia-induced ROS overload activates pathogenic pathways, leading to microvascular damage and neuronal dysfunction. Clinical and experimental studies support antioxidant therapies as adjunctive strategies, with the strongest evidence for Age-Related Eye Disease Study-based formulations in age-related macular degeneration and promising results for agents such as Coenzyme Q10 in glaucoma and sulforaphane in diabetic retinopathy. For cataracts, supplementation trials have yielded mixed outcomes and surgery remains the definitive treatment.<br><br>CONCLUSIONS: Oxidative stress represents a unifying mechanism in the pathogenesis of vision-threatening ocular diseases. Antioxidant-based interventions show potential, particularly when integrated with existing treatment regimens, but their translation into routine practice remains limited by heterogeneous trial results and the absence of robust biomarkers for patient selection. Future research should focus on precision antioxidant therapy, leveraging stage-specific interventions, novel delivery systems, and pathway-targeted compounds, to transform ocular care from reactive management toward prevention.}, }
@article {pmid41112795, year = {2025}, author = {Dhaliwal, KK and Simmons, J and Wong, A and Hudson, C and Wright, T and Ballios, BG and Bizheva, K}, title = {Visual stimulus-evoked transient blood flow and blood vessel diameter changes in the healthy human retina measured with a combined OCT+ERG system.}, journal = {Biomedical optics express}, volume = {16}, number = {10}, pages = {3958-3976}, pmid = {41112795}, issn = {2156-7085}, abstract = {Neurodegenerative retinal diseases, such as glaucoma, age-related macular degeneration and diabetic retinopathy, cause gradual damage to the retinal morphology, blood vasculature, and neuronal function, and ultimately lead to blindness. In this study, a retinal OCT system was combined with a clinical electroretinography (ERG) system to investigate visually-evoked transient changes in the retinal blood flow (RBF) and blood vessel diameter (BVD) in the healthy human retina. The OCT system offered 2.7 µm axial resolution in retinal tissue and 98 dB sensitivity for 1.1 mW imaging power and 250 kHz image acquisition rate. Doppler OCT (double circular scans around the optic nerve head) and ERG traces were acquired from healthy subjects in response to 10 Hz, white light flicker stimuli and different stimulus intensities. The ERG system was used to generate visual stimuli of precise timing, duration, luminance, and flicker frequency, as well as to confirm the retinal neuronal response to the visual stimulation. MATLAB-based custom algorithms were developed to track time-dependent changes in the RBF and BVD from the OCT images. Results from this study revealed a rapid transient increase in the RBF accompanied by transient vasoconstriction and vasodilation of the retinal blood vessels in response to the flicker stimulation. The amplitude and latency of the RBF and BVD responses were dependent on the stimulus intensity as well as the blood vessel type (arteries or veins).}, }
@article {pmid41114788, year = {2026}, author = {Zhou, Y and Liu, C and Yin, J and Zhao, D and Xue, F}, title = {From environmental exposure to retinal pathology: epidemiological and mechanistic insights into multi-metal driven ocular diseases.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {39}, number = {1}, pages = {181-202}, pmid = {41114788}, issn = {1572-8773}, mesh = {Humans ; *Environmental Exposure/adverse effects ; Male ; *Macular Degeneration/epidemiology/chemically induced/pathology ; Female ; Middle Aged ; *Cataract/epidemiology/chemically induced ; *Cadmium/urine/toxicity ; Aged ; *Diabetic Retinopathy/epidemiology/chemically induced ; *Glaucoma/epidemiology/chemically induced ; *Retina/pathology/drug effects ; }, abstract = {With aging and environmental pollution, heavy metal exposure has become a growing concern for age-related eye diseases. However, the relationship between heavy metals and age-related macular degeneration (AMD), cataracts, glaucoma, and diabetic retinopathy (DR) remains unclear. This study investigates the association between urinary heavy metals and these eye diseases, focusing on the molecular mechanisms of cadmium (Cd) in driving AMD. Data from the 2005-2008 NHANES (n = 1865) were analyzed using multivariable logistic regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS) modeling, and sensitivity analyses. Potential molecular mechanisms of Cd in AMD were explored via intersection gene screening, protein-protein interaction network construction, and GO/KEGG enrichment analyses. In single-metal exposure models, Cd was significantly associated with AMD (OR = 1.563, 95% CI: 1.177-2.077, P = 0.00205), Co with cataract (OR = 1.386), U with glaucoma (OR = 1.300), and As with DR (OR = 1.214). In the WQS model, only AMD remained significantly associated with the overall metal mixture (OR = 1.89, 95% CI: 1.22-2.91, P = 0.0041). BKMR identified Cd as the most influential contributor to AMD (PIP = 0.523). The exposure-response curve for Cd and AMD demonstrated an upward trend, with the risk of AMD increasing as Cd exposure levels rose. Additionally, the overall metal mixture was positively associated with AMD risk. Subgroup and RCS analyses confirmed the stability of results, with no significant interaction across demographic subgroups. Sensitivity analyses further validated the findings: the highest quartile of Cd exposure was associated with increased AMD risk (OR = 2.45), and a significant dose-response trend was observed (P for trend = 0.0187). The association remained robust after excluding outliers (OR = 1.31, P = 0.0483).Mechanistically, Cd may induce retinal pigment epithelium damage via oxidative stress (SIRT1/TP53 axis), inflammation (TLR4/NF-κB pathway and pro-inflammatory cytokines), dysregulated apoptosis (BCL2/BAX imbalance), and hypoxia-induced metabolic disruption (HIF-1 signaling). Cd is an independent risk factor for AMD, likely acting through multiple toxic pathways. The effects of U, Co, and As may depend on exposure thresholds or confounders. These findings highlight the need for stricter Cd control and targeted antioxidant or anti-inflammatory strategies for age-related eye disease prevention and treatment.}, }
@article {pmid41117141, year = {2026}, author = {Chen, C and Zhu, M and Fan, X and Lv, K and Jiang, K and Zhang, Y and Zhang, H and Qi, X and Lee, BT and Wan, Y and Wei, G and Liu, K and Xu, X}, title = {Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {1}, pages = {e04660}, pmid = {41117141}, issn = {2198-3844}, support = {82271096//National Natural Science Foundation of China/ ; 81800835//National Natural Science Foundation of China/ ; 82273864//National Natural Science Foundation of China/ ; 21S11905300//Shanghai Science and Technology Program/ ; 21ZR1407100//Shanghai Science and Technology Program/ ; 18YF1419700//Shanghai Sailing Program/ ; //Shanghai Talent Development Fund/ ; //Shanghai Jiao Tong University K. C. Wong Medical Fellowship Fund/ ; //Lumitin Vision to Brightness Research Funding/ ; }, mesh = {Animals ; Macaca fascicularis ; *Choroidal Neovascularization/drug therapy/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Disease Models, Animal ; *Single-Domain Antibodies/administration &amp; dosage/pharmacology ; *Retinal Neovascularization/drug therapy/pathology ; Ophthalmic Solutions ; Angiogenesis Inhibitors/pharmacology/administration &amp; dosage ; Retina/drug effects ; }, abstract = {Pathological retinal and choroidal neovascularization is a hallmark of several blinding diseases, including diabetic retinopathy and age-related macular degeneration. While intravitreal anti-VEGF therapies remain the standard of care, they necessitate frequent injections, posing risks such as endophthalmitis and elevated intraocular pressure, alongside economic and adherence challenges. Here, we present Pene/LQ015, a novel eye drop formulation comprising the anti-VEGFA nanobody (LQ015) and a proprietary penetratin analog for noninvasive delivery. LQ015 demonstrates superior VEGF-blocking activity, broad binding specificity across species, and robust stability and scalability using a yeast expression system. Topical administration of Pene/LQ015 achieved effective retinal-choroid complex drug levels and suppressed neovascularization in preclinical models. Notably, in the cynomolgus monkey laser-induced choroidal neovascularization model, 30 days of continuous topical application significantly reduced neovascularization and vascular leakage, with excellent safety and tolerability. These findings highlight Pene/LQ015's potential as a game-changer in treating neovascular eye diseases. It offers a groundbreaking, noninvasive alternative to intravitreal injections, addressing key limitations of current therapies by enabling continuous dosing, improving patient adherence, and reducing treatment burden. These findings underscore its potential to transform the management of neovascular retinal and choroidal diseases, with promising implications for clinical application.}, }
@article {pmid41117255, year = {2025}, author = {Yang, W and Jia, J and Liu, X and Wan, P}, title = {Evaluating the Impact of Age-Related Macular Degeneration on Seasonal Affective Disorder: A Retrospective Cohort Study in a Chinese Population.}, journal = {Actas espanolas de psiquiatria}, volume = {53}, number = {5}, pages = {939-946}, pmid = {41117255}, issn = {1578-2735}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Seasonal Affective Disorder/complications/psychology/epidemiology ; *Macular Degeneration/complications/psychology ; China/epidemiology ; Aged ; Middle Aged ; Life Style ; East Asian People ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) usually affects the macular region of the retina, while seasonal affective disorder (SAD) is a complex mental disorder. However, the interaction between these two clinical conditions remains unexplored. Therefore, this study aimed to explore the influence of AMD on SAD and to assess the correlation of ocular pathology with lifestyle and mental health factors.<br><br>METHODS: This study recruited 158 AMD patients admitted to the Second Affiliated Hospital of Xi'an Medical University, China, between January 2020 and October 2023. Based on their affection status, the patients were divided into two groups: the SAD group (n = 58) and the non-SAD group (n = 100). Baseline characteristics, including blood pressure, hematological parameters, ocular parameters, and lifestyle factors, were compared between the two groups to evaluate the potential influence of AMD on SAD.<br><br>RESULTS: We observed specific differences in the family history of mental illness between the non-SAD and SAD groups (p < 0.001). However, the two groups' other baseline characteristics, such as blood pressure and hematological parameters, were comparable (p > 0.05). Additionally, significant differences were also observed in central retinal thickness (CRT), choroidal thickness, lesion atrophy area, and macular volume between the two groups (p < 0.001). Moreover, intraocular pressure (IOP) did not reveal a~significant difference between the two groups (p > 0.05). Compared with the SAD group, the non-SAD group had significantly better vision, longer exercise duration, sunlight exposure time, outdoor activity, and lower sedentary behavior (all p < 0.001). The logistic regression analysis indicated that increased macular volume (odds ratio (OR) = 3.054, p = 0.008) and sedentary behavior (OR = 4.382, p < 0.001) significantly increased SAD risk. Additionally, the absence of a family history of mental illness did not reach statistical significance (OR = 0.375, p = 0.129), but a specific correlation was still observed.<br><br>CONCLUSION: This study shows a correlation between SAD and AMD. The significant differences in ocular pathological characteristics, lifestyle factors, and mental health status between the SAD and non-SAD groups suggest the crucial role of visual function and lifestyle in regulating mood and circadian rhythm in AMD patients.}, }
@article {pmid41117364, year = {2026}, author = {García-Serrano Fuertes, R and Romero Martínez, A and Suarez Pérez, J and López Herrero, F and Cabanás Jiménez, M and Flores Córdoba, A and Sánchez Vicente, JL}, title = {Cost-effectiveness analysis of Brolucizumab compared to Aflibercept and Ranibizumab in nAMD with persistent retinal fluid.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {231-239}, pmid = {41117364}, issn = {1724-6016}, mesh = {Humans ; *Recombinant Fusion Proteins/economics/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Cost-Benefit Analysis ; *Ranibizumab/economics/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/economics/diagnosis ; *Angiogenesis Inhibitors/economics/therapeutic use ; Aged ; Female ; Male ; Visual Acuity ; *Antibodies, Monoclonal, Humanized/economics/therapeutic use ; *Subretinal Fluid ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Drug Costs ; Aged, 80 and over ; Cost-Effectiveness Analysis ; }, abstract = {Purpose of the researchThis study aimed to evaluate the cost-effectiveness of Brolucizumab in patients with exudative age-related macular degeneration (AMD) and persistent retinal fluid unresponsive to previous therapies, within the context of a real-world clinical practice setting in a Spanish referral hospital. Furthermore, the study examined the probabilities of transitioning between therapies.Major findingsA 6-month treatment projection demonstrated that Brolucizumab was not cost-effective compared to Ranibizumab (incremental cost-effectiveness ratio [ICER]: -12.98) and Aflibercept (ICER: -47.64). Conversely, when assessing only drug and administration visit costs, Brolucizumab appeared cost-effective (ICER of 9.14 versus Aflibercept and 35.01 versus Ranibizumab). The increased burden of follow-up costs, which were €348.96 higher than those for Ranibizumab and €174.48 higher than Aflibercept, likely drove the trend towards non-cost-effectiveness. Additionally, the analysis indicated a 43% probability of transitioning to Faricimab within the studied population.ConclusionsBrolucizumab was determined to be not cost-effective compared to Ranibizumab and Aflibercept in patients with exudative AMD and persistent retinal fluid, primarily due to a higher number of follow-up visits necessitated by its safety profile. Furthermore, newly observed vitreous opacities and a tendency towards the use of Faricimab were noted.}, }
@article {pmid41120131, year = {2025}, author = {Phan, LT and Hong, T and Chang, JH and Mehta, H and Fraser-Bell, S and Cheung, GCM and Broadhead, GK and Chang, AA}, title = {A prospective, open-label, single-arm, investigator-initiated clinical trial to assess the efficacy, safety and durability of faricimab in patients with inadequate response to current treatment for neovascular age-related macular degeneration: protocol design and rationale for the FURGGHORN Study.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41120131}, issn = {2397-3269}, mesh = {Aged ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Multicenter Studies as Topic ; Prospective Studies ; Research Design ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Clinical Trials, Phase IV as Topic ; Antibodies, Bispecific ; }, abstract = {INTRODUCTION: Anti-vascular endothelial growth factor therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). However, some patients face recurrent and persistent disease activity despite ongoing treatment. Faricimab (trade name: Vabysmo) is a recently approved therapy which targets two pathways involved in nAMD. This study aims to assess changes in best-corrected visual acuity (BCVA) and treatment frequency among patients currently treated for nAMD who switch to intravitreal faricimab therapy under a treat-and-extend regimen.<br><br>METHODS AND ANALYSIS: The FURGGHORN Study is a prospective, open-label, single-arm, multicentre investigator-initiated clinical trial. 102 patients with nAMD meeting inclusion criteria were recruited from 12 clinical sites across Australia and Singapore. Following 4&#x2009;monthly loading doses of faricimab, treatment intervals were adjusted according to a regimen developed based on real-world practice patterns and consensus guidelines. The primary endpoint is the change from BCVA at week 52. Secondary endpoints include the proportions of patients at different treatment intervals, changes in central macular thickness and retinal fluid dimensions.<br><br>ETHICS AND DISSEMINATION: This study was designed, implemented and reported in accordance with the International Conference on Harmonisation Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. Ethics approval was obtained from Bellberry Limited (2022-12-1388), St Vincent's Hospital Human Research Ethics Committee (2023/STE01568) and Singhealth Centralized Institutional Review Board (2023-2190). Results will be disseminated at scientific meetings and through peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12623000215628.}, }
@article {pmid41122382, year = {2025}, author = {Wang, W}, title = {LLM-based multi-agent system for neuro-ophthalmic diagnosis and personalized treatment planning.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1688509}, pmid = {41122382}, issn = {1662-4548}, abstract = {INTRODUCTION: Ophthalmic findings can non-invasively reflect nervous-system status. We present an LLM-based multi-agent framework that preserves diagnostic uncertainty to support neuro-ophthalmic screening and referral.<br><br>METHODS: Heterogeneous inputs (clinical text/PDFs and optional fundus/OCT images) are normalized by an Information Collection Agent. A Diagnosis Agent ensembles multiple LLMs and, when available, a CNN image branch; outputs are aggregated with an uncertainty-aware fusion.<br><br>RESULTS: Across a curated ophthalmic corpus, the multi-agent framework improves robustness over single-model baselines and produces multi-candidate distributions suitable for downstream triage and monitoring.<br><br>DISCUSSION: Uncertainty-aware, multi-candidate predictions align with clinical decision-making under ambiguity and suggest future work on calibration and knowledge-layer fusion.}, }
@article {pmid41122527, year = {2025}, author = {Bates, BA and Mansour, HA and Al-Khersan, H and Wood, E and Momenaei, B and Schneider, E and Richards, CJ and DeYoung, C and Wykoff, CC and Quinn, K and Hsu, J and Regillo, CD and Ho, AC and Fineman, MS and Klufas, MA and Storey, PP}, title = {The Efficacy and Safety of Intravitreal Aflibercept 8 mg in Clinical Practice.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251383384}, pmid = {41122527}, issn = {2474-1272}, abstract = {Purpose: To characterize real-world use of intravitreal aflibercept 8 mg across 22 US retina practices. Methods: Retrospective review of patients who received at least 1 intravitreal aflibercept 8 mg injection for treatment of neovascular age-related macular degeneration, diabetic macular edema, or diabetic retinopathy through April 1, 2024. Data from health records were collected retrospectively, including best-corrected visual acuity (BCVA), interval between treatments, and adverse events. Results: A total of 8323 eyes of 6271 patients received 20 385 intravitreal aflibercept 8 mg injections. A total of 669 eyes (8.0%) were not previously treated. Among treatment-naive eyes, mean logMAR BCVA improved from 0.57 (Snellen equivalent ~20/80) at the time of the first intravitreal aflibercept 8 mg injection, to 0.47 (Snellen equivalent ~20/60) (P < .001), 0.46 (Snellen equivalent ~20/60) (P < .001), and 0.48 (Snellen equivalent ~20/60) (P = .012) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Among previously treated eyes, mean logMAR BCVA improved from 0.46 (Snellen equivalent ~20/60) at the time of the first intravitreal aflibercept 8 mg injection, to 0.42 (Snellen equivalent ~20/50) (P < .001), 0.43 (Snellen equivalent ~20/50) (P < .001), and 0.45 (Snellen equivalent ~20/60) (P = .70) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Treatment intervals to time of second, third, and fourth intravitreal aflibercept 8 mg injections increased compared to baseline intervals, by a mean of 2.2 days (P < .001), 2.5 days (P < .001), and 13.5 days (P < .001), respectively. Intraocular inflammation was observed in 11 eyes (1 in 1853 injections). Nine eyes (1 in 2265 injections) developed suspected endophthalmitis. Conclusions: In this real-world clinical setting, intravitreal aflibercept 8 mg treatment demonstrated improvements in BCVA outcomes, with increased intervals between injections. Rates of intraocular inflammation and endophthalmitis were low.}, }
@article {pmid41123658, year = {2026}, author = {Chakravarthy, U and Foss, AJE and Panos, GD and Peto, T and Rotsos, T and Sadda, S and De Cock, E and Empeslidis, T}, title = {Management of fibrosis in neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {1}, pages = {19-34}, pmid = {41123658}, issn = {1435-702X}, mesh = {Humans ; Fibrosis/etiology/drug therapy ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; *Visual Acuity ; *Disease Management ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; *Retinal Pigment Epithelium/pathology ; }, abstract = {Subretinal fibrosis is a common end-stage sequela of neovascular age-related macular degeneration (nAMD), and it is associated with poor long-term visual outcomes. The pathogenesis of subretinal fibrosis in nAMD is largely driven by epithelial-mesenchymal and endothelial-mesenchymal transition within the retinal pigment epithelium and endothelium of the choroidal circulation. Upregulation of vascular endothelial growth factor (VEGF) expression further contributes to the observed fibrovascular content and increased vascular permeability. There is a substantial need for direct therapeutic strategies for fibrosis in nAMD, including anti-fibrotic agents. Until direct treatment strategies are developed, the management of nAMD using anti-VEGF agents must be optimized. However, fibrosis can occur in some patients otherwise successfully treated with anti-VEGF therapy, resulting in the loss of previous visual acuity (VA) gains experienced after treatment initiation. This review summarizes the current understanding of the mechanisms driving fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methods. Available evidence on how different factors relating to anti-VEGF therapy (e.g., specific agent, delays in administration, extended administration intervals, dosing or treatment regimen) and the early detection of nAMD impact the risk of fibrosis is also discussed. Lastly, insights into potential future directions for the management of fibrosis in nAMD, particularly the development of anti-fibrotic agents, are deliberated.}, }
@article {pmid41124203, year = {2026}, author = {Holz, FG and Le Mer, Y and Muqit, MMK and Hattenbach, LO and Cusumano, A and Grisanti, S and Kodjikian, L and Pileri, MA and Matonti, F and Souied, E and Stanzel, BV and Szurman, P and Weber, M and Bartz-Schmidt, KU and Eter, N and Delyfer, MN and Girmens, JF and van Overdam, KA and Wolf, A and Hornig, R and Corazzol, M and Brodie, F and Olmos de Koo, L and Palanker, D and Sahel, JA}, title = {Subretinal Photovoltaic Implant to Restore Vision in Geographic Atrophy Due to AMD.}, journal = {The New England journal of medicine}, volume = {394}, number = {3}, pages = {232-242}, pmid = {41124203}, issn = {1533-4406}, support = {NIHR203322/DH_/Department of Health/United Kingdom ; R01 EY035227/EY/NEI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Eyeglasses ; *Geographic Atrophy/etiology/pathology/surgery ; *Macular Degeneration/complications/pathology/surgery ; Prospective Studies ; Retina/pathology/surgery ; *Visual Acuity ; *Visual Prosthesis/adverse effects ; Follow-Up Studies ; Minimal Clinically Important Difference ; Treatment Outcome ; }, abstract = {BACKGROUND: Geographic atrophy due to age-related macular degeneration (AMD) is the leading cause of irreversible blindness and affects more than 5 million persons worldwide. No therapies to restore vision in such persons currently exist. The photovoltaic retina implant microarray (PRIMA) system combines a subretinal photovoltaic implant and glasses that project near-infrared light to the implant in order to restore sight to areas of central retinal atrophy.<br><br>METHODS: We conducted an open-label, multicenter, prospective, single-group, baseline-controlled clinical study in which the vision of participants with geographic atrophy and a visual acuity of at least 1.2 logMAR (logarithm of the minimum angle of resolution) was assessed with PRIMA glasses and without PRIMA glasses at 6 and 12 months. The primary end points were a clinically meaningful improvement in visual acuity (defined as &#x2265;0.2 logMAR) from baseline to month 12 after implantation and the number and severity of serious adverse events related to the procedure or device through month 12.<br><br>RESULTS: A total of 38 participants received a PRIMA implant, of whom 32 were assessed at 12 months. Of the 6 participants who were not assessed, 3 had died, 1 had withdrawn, and 2 were unavailable for testing. Among the 32 participants who completed 12 months of follow-up, the PRIMA system led to a clinically meaningful improvement in visual acuity from baseline in 26 (81%; 95% confidence interval, 64 to 93; P<0.001). Using multiple imputation to account for the 6 participants with missing data, we estimated that 80% (95% CI, 66 to 94; P<0.001) of all participants would have had a clinically meaningful improvement at 12 months. A total of 26 serious adverse events occurred in 19 participants. Twenty-one of these events (81%) occurred within 2 months after surgery, of which 20 (95%) resolved within 2 months after onset. The mean natural peripheral visual acuity after implantation was equivalent to that at baseline.<br><br>CONCLUSIONS: In this study involving 38 participants with geographic atrophy due to AMD, the PRIMA system restored central vision and led to a significant improvement in visual acuity from baseline to month 12. (Funded by Science Corporation and the Moorfields National Institute for Health and Care Research Biomedical Research Centre; PRIMAvera ClinicalTrials.gov number, NCT04676854.).}, }
@article {pmid41125297, year = {2026}, author = {Li, Z and Pan, Z and Huang, Y and Xie, H and Wu, X and Zhang, C and Wong, TY and Jonas, JB and Wang, YX}, title = {Cigarette smoking and retinal ganglion cell layer and photoreceptor outer segment thickness: The Beijing Eye Study.}, journal = {The British journal of ophthalmology}, volume = {110}, number = {4}, pages = {446-451}, doi = {10.1136/bjo-2024-326789}, pmid = {41125297}, issn = {1468-2079}, mesh = {Humans ; Male ; Female ; Middle Aged ; Tomography, Optical Coherence/methods ; *Retinal Ganglion Cells/pathology ; Aged ; Beijing/epidemiology ; *Cigarette Smoking/adverse effects/epidemiology ; *Retinal Photoreceptor Cell Outer Segment/pathology ; Cross-Sectional Studies ; China/epidemiology ; Prevalence ; Surveys and Questionnaires ; }, abstract = {PURPOSE: To examine an association of cigarette smoking on retinal layer thickness.<br><br>METHODS: The population-based Beijing Eye Study 2011 included 3468 individuals aged 50+ years. All participants underwent optical coherence tomography (OCT) of the macula. Using a multiple-surface OCT segmentation algorithm, the retina was segmented into nine layers. Information about cigarette smoking was assessed in an interview with a standardised questionnaire. The exclusion criterion was the presence of any retinal or optic nerve disease.<br><br>RESULTS: The study included 2173 participants (mean age: 61.7&#xb1;8.4 years; mean axial length: 23.1&#xb1;0.8&#x2009;mm) with 660 (30.4%) participants with a smoking history and 1513 (69.6%) non-smokers. Mean duration of the smoking period was 8.7&#xb1;14.9 years, and mean smoking quantity was 9.5&#xb1;18.2 pack-years. In multivariable analysis, higher prevalence of smoking was associated with thinner whole retina (p=0.024; B=-1.64; 95% CIs -3.07 to -0.22), thinner ganglion cell layer (GCL) (p=.044; B=-0.39; 95%&#x2009;CI -0.78 to -0.01) and thinner photoreceptor outer segment layer (POS) (p=0.024; B=-0.38; 95%&#x2009;CI -0.72 to -0.05) with adjustments of age, gender, axial length, education level and hypertension. Similar results were obtained if the retinal thickness measurements were obtained in the various macular subfields. A longer period of smoking was related to thinner whole retina (p=0.009; B=-0.06; 95%&#x2009;CI -0.10 to -0.01), thinner retinal nerve fibre layer (RNFL) (p=0.011; B=-0.01; 95%&#x2009;CI -0.02 to -0.002), thinner GCL (p=0.006; B=-0.02; 95%&#x2009;CI -0.03 to -0.01) and thinner POS (p=0.025; B=-0.01; 95%&#x2009;CI -0.02 to -0.001) with adjustments of age, gender, axial length, education level and hypertension. Higher smoking pack-years were significantly associated with thinner GCL (p=0.022; B=-0.01; 95%&#x2009;CI -0.02 to -0.002).<br><br>CONCLUSIONS: Smoking was related to thinner GCL and POS in this population-based investigation, pointing towards and agreeing with an association between smoking and optic nerve damage or age-related macular degeneration.}, }
@article {pmid41129131, year = {2025}, author = {Shor, R and Popovic, MM and Muni, RH}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs-Reply.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1077-1078}, doi = {10.1001/jamaophthalmol.2025.3723}, pmid = {41129131}, issn = {2168-6173}, }
@article {pmid41129133, year = {2025}, author = {Ahuja, AS and Paredes, AA and Young, BK}, title = {Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {999-1003}, pmid = {41129133}, issn = {2168-6173}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Glucagon-Like Peptide-1 Receptor Agonists ; Middle Aged ; Hypoglycemic Agents/therapeutic use ; *Macular Degeneration/epidemiology ; Obesity/drug therapy/complications ; Glucagon-Like Peptides/therapeutic use ; Liraglutide/therapeutic use ; Disease Progression ; Diabetes Mellitus, Type 2/drug therapy ; Risk Factors ; Glucagon-Like Peptide 1 ; Semaglutide ; }, abstract = {IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown.<br><br>OBJECTIVE: To evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs).<br><br>This retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025.<br><br>EXPOSURES: Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching.<br><br>RESULTS: A total of 91&#x202f;408 patients were included. After propensity score matching for the primary analysis, 45&#x202f;704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35&#x202f;753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35&#x202f;732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P&#x2009;<&#x2009;.001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P&#x2009;<&#x2009;.001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P&#x2009;<&#x2009;.001). No differences were observed in progression to exudative AMD.<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations.}, }
@article {pmid41129138, year = {2025}, author = {Talcott, KE and Rachitskaya, AV and Singh, RP}, title = {Glucagon-Like Peptide-1 Receptor Agonist Use and Age-Related Macular Degeneration-Where Do We Stand?.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1004-1005}, doi = {10.1001/jamaophthalmol.2025.4090}, pmid = {41129138}, issn = {2168-6173}, }
@article {pmid41129165, year = {2025}, author = {Ziemssen, F and Helbig, H}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1075}, doi = {10.1001/jamaophthalmol.2025.3711}, pmid = {41129165}, issn = {2168-6173}, }
@article {pmid41129166, year = {2025}, author = {Mammo, DA and Talcott, KE and Singh, RP}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1075-1076}, doi = {10.1001/jamaophthalmol.2025.3714}, pmid = {41129166}, issn = {2168-6173}, }
@article {pmid41129172, year = {2025}, author = {Feldman-Billard, S and Girmens, JF and Ayello-Scheer, S}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1076-1077}, doi = {10.1001/jamaophthalmol.2025.3717}, pmid = {41129172}, issn = {2168-6173}, }
@article {pmid41129178, year = {2025}, author = {Alkabbani, W and Cromer, SJ and Patorno, E}, title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.}, journal = {JAMA ophthalmology}, volume = {143}, number = {12}, pages = {1077}, doi = {10.1001/jamaophthalmol.2025.3720}, pmid = {41129178}, issn = {2168-6173}, }
@article {pmid41129903, year = {2025}, author = {Rajendran, N and Singh, A and Runyon, W and Hu, S and Kumar, R and Ratnapriya, R and Csaky, K and Sripathi, SR}, title = {Derivation of pluripotent stem cell lines (RFSCi005-A, RFSCi006-A) from siblings harboring identical high-risk complement variants with discordant age-related macular degeneration.}, journal = {Stem cell research}, volume = {89}, number = {}, pages = {103852}, doi = {10.1016/j.scr.2025.103852}, pmid = {41129903}, issn = {1876-7753}, mesh = {Humans ; *Macular Degeneration/genetics/pathology/metabolism ; Siblings ; *Induced Pluripotent Stem Cells/metabolism/cytology ; Cell Line ; Male ; Female ; Cell Differentiation ; }, abstract = {Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.}, }
@article {pmid41130334, year = {2026}, author = {Li, HY and Dong, L and Shao, L and Wei, WB}, title = {Multiomics data reveal microglia's promotion for choroidal neovascularization in endothelial cells.}, journal = {Experimental eye research}, volume = {262}, number = {}, pages = {110701}, doi = {10.1016/j.exer.2025.110701}, pmid = {41130334}, issn = {1096-0007}, mesh = {Humans ; *Microglia/metabolism/pathology ; *Choroidal Neovascularization/metabolism/genetics/pathology ; *Endothelial Cells/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Choroid/metabolism/pathology ; Male ; *Gene Expression Regulation/physiology ; Female ; Vascular Endothelial Growth Factor A/metabolism ; Aged ; Signal Transduction ; Wet Macular Degeneration/metabolism/genetics ; Cells, Cultured ; Multiomics ; }, abstract = {Choroidal neovascularization (CNV) stands as one of the leading causes of blindness worldwide, driven by the dysregulation of key signaling pathways, including vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β). This study aimed to elucidate the specific cell types within the retina and retinal pigment epithelium (RPE)/choroid complex that contribute to CNV progression, as well as to explore how the expression levels of cysteine-rich protein 2 (CSRP2), a downstream effector, are altered in the pathological mechanisms underlying CNV. By investigating these molecular and cellular dynamics, we seek to provide deeper insights into the disease's progression and identify potential therapeutic targets. Retinal tissues, RPE/choroid complexes, and blood samples from both age-related macular degeneration (AMD) caused CNV patients and healthy controls were obtained from the GEO database for differential gene expression analysis. Integrated analysis of tissue and blood samples from wet AMD patients and healthy controls identified CSRP2 as a critical biomarker gene associated with pathogenesis. To uncover potential underlying mechanisms, we conducted immune infiltration analysis and further validated our findings using single-cell RNA sequencing (scRNA-seq) data from the GEO database. Additionally, scRNA-seq data were utilized to investigate cell-cell communication networks and perform Gene Set Enrichment Analysis (GSEA). scRNA-seq analysis demonstrated that CSRP2 was significantly upregulated in microglia and endothelial cells, with concurrent activation of the VEGF and TGF-β signaling pathways. Microglia emerged as a central hub for outgoing interactions, while endothelial cells were identified as the primary target of incoming signals within these pathways. GSEA further implicated CSRP2 in CNV progression, highlighting its role in angioimmunoblastic regulated by VEGF and TGF-β signaling pathways. In the in-vitro experiments, we found that activated microglia stimulated VEGFA, TGF-β and CSRP2, which enhanced angiogenesis, migration, proliferation, permeability, and altered the phenotype of co-cultured choroidal endothelial cells. These findings underscore the pivotal involvement of CSRP2 in mediating cellular crosstalk and signaling dynamics critical to CNV development. Microglia and endothelial cells emerged as the primary cell clusters interacting under this signaling regulation, driving angiogenesis and contributing to the pathological progression of CNV. The findings provide promise alternative therapy for CNV patients casued by AMD.}, }
@article {pmid41130930, year = {2025}, author = {Ostrovsky, M and Tuli, R and Kozlov, Y and Robart, ACW and Ruparelia, S and Lebreton, L and Gou, A and Shoham-Hazon, N and Lee, TKM and Berco, E}, title = {To ac tap or not to ac tap: Multi-centre outcomes of patients receiving anti-VEGF injections.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251389427}, doi = {10.1177/11206721251389427}, pmid = {41130930}, issn = {1724-6016}, abstract = {PurposeTo compare intraocular pressure (IOP) and retinal nerve fibre layer (RNFL) thickness in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) injections with and without anterior chamber paracentesis (ACP).MethodsThis multicentre retrospective cohort study included 269 injection-naïve eyes from 210 patients with neovascular age-related macular degeneration (AMD) or diabetic macular oedema (DME). A matched subset of 140 eyes (70 with ACP, 70 without) was selected based on age, sex, diagnosis, laterality, and number of injections. RNFL thickness (overall and by quadrant) was measured at baseline and one-year follow-up. Additional outcomes included IOP, visual acuity (VA), and central retinal thickness (CRT).ResultsThe matched cohort had a mean age of 71.06 ± 11.44 years, with 61.4% female participants. ACP eyes had worse baseline VA, higher IOP, and thicker CRT (p < 0.050, for all), but showed greater VA improvement (p = 0.023) and a trend towards greater CRT reduction (p = 0.061). RNFL thinning over one year did not differ between the groups (-3.24 ± 11.82 µm vs -2.95 ± 7.81 µm, p = 0.883). No major complications were observed.ConclusionACP did not significantly reduce RNFL thinning over one year but was well tolerated. It may be considered in patients at higher risk from transient IOP elevations. Future prospective studies are warranted to clarify its role in specific patient subgroups.}, }
@article {pmid41131180, year = {2025}, author = {Graham, F}, title = {Daily briefing: People with macular degeneration can read again after retinal implant.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-025-03442-5}, pmid = {41131180}, issn = {1476-4687}, }
@article {pmid41131329, year = {2025}, author = {Peto, T and Pearce, I and Talks, J and de Salvo, G and Patel, PJ and de Silva, SR and Gale, RP and Sivaprasad, S and Varma, D and Reynolds, R and Bailey, C and Downey, L and Kiire, C and Chi, GC and Dodds, M and James, N and Downey, AK and Dayal, P}, title = {Real-world treatment patterns and visual outcomes of faricimab in patients with diabetic macular oedema in the UK at 12 months: the FARWIDE-DMO study.}, journal = {Eye (London, England)}, volume = {39}, number = {18}, pages = {3350-3358}, pmid = {41131329}, issn = {1476-5454}, mesh = {Humans ; *Visual Acuity ; *Diabetic Retinopathy/drug therapy/physiopathology/complications/diagnosis ; Female ; Male ; *Macular Edema/drug therapy/physiopathology/etiology/diagnosis ; Intravitreal Injections ; United Kingdom/epidemiology ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Middle Aged ; Treatment Outcome ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: The Faricimab Real-World Evidence (FARWIDE) studies are evaluating real-world outcomes of eyes with diabetic macular oedema (DMO)/neovascular age-related macular degeneration (nAMD) treated with faricimab in the UK. We present results from FARWIDE-DMO for eyes with 12 months of follow-up after faricimab initiation.<br><br>METHODS: FARWIDE-DMO includes patients with diagnosis of DMO who received &#x2265;1 intravitreal faricimab injection after May 2022 in the diagnosed eye(s) at 1 of 35 UK National Health Service sites. All eyes had &#x2265;12 months of follow-up after faricimab initiation as of July 2024. Treatment-na&#xef;ve (TN) eyes had no prior anti-VEGF therapy or steroid implant. Previously treated (PT) eyes switched to faricimab. Baseline characteristics, visual acuity (VA) outcomes and treatment patterns were evaluated. Intraocular inflammation (IOI) and presumed infectious endophthalmitis (PIE) incidences were pooled for all nAMD/DMO eyes with any follow-up duration. Analyses are descriptive.<br><br>RESULTS: 2147 eyes (1564 patients) were included (TN, 32.1%; PT, 67.9%). For TN eyes, mean (standard deviation [SD]) VA at baseline and 12 months were 63.9 (15.2) and 68.4 (16.3) Early Treatment Diabetic Retinopathy Study letters, respectively. VA remained stable in PT eyes. TN eyes received a mean (SD) of 4.5 (1.0) faricimab injections in months 1-6 and 1.9 (1.2) injections in months 7-12. PT eyes received 4.5 (1.2) injections in months 1-6 and 2.4 (1.3) in months 7-12. IOI and PIE rates were consistent with faricimab phase 3 trials.<br><br>CONCLUSIONS: These 1-year data support real-world effectiveness, durability and safety of faricimab in DMO.}, }
@article {pmid41132126, year = {2025}, author = {Schmidt-Erfurth, U and Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Scheibler, L and Bogunovic, H}, title = {Plain language summary of disease activity and therapeutic response to pegcetacoplan for geographic atrophy identified by deep learning-based analysis of OCT.}, journal = {Immunotherapy}, volume = {17}, number = {14}, pages = {971-981}, doi = {10.1080/1750743X.2025.2569302}, pmid = {41132126}, issn = {1750-7448}, }
@article {pmid41132628, year = {2025}, author = {Ou, S and Shi, F and Cai, M and Wu, Y}, title = {Conbercept Treatment for Heart-Shaped Vascular Intertwined Nets in Macular Neovascularization: Anti-VEGF Drug Therapy Strategy Based on Vascular Geometry Diagnosed by OCTA.}, journal = {Clinical case reports}, volume = {13}, number = {10}, pages = {e71250}, pmid = {41132628}, issn = {2050-0904}, abstract = {Macular neovascularization (MNV), a hallmark of several retinal disorders including ocular trauma and wet age-related macular degeneration, remains a major cause of vision impairment due to the proliferation of abnormal, fragile blood vessels. Anti-VEGF therapies, such as Aflibercept (Eylea), Bevacizumab (Avastin), Brolucizumab (Beovu), Conbercept (Lumitin), Faricimab (Vabysmo), Ranibizumab (Lucentis), and Pegaptanib (Macugen), have significantly transformed MNV management, targeting VEGF to curb this pathological vascular growth. In this report, we describe a 63-year-old male with a history of hypertension and diabetes who developed acute vision loss attributed to MNV secondary to hypertensive retinopathy. Optical coherence tomography angiography (OCTA) revealed unusual heart-shaped, intertwined vascular nets, informing the choice of Conbercept for intravitreal injection. This personalized therapeutic decision led to marked visual improvement over a 12-month period. The case exemplifies the importance of vascular geometry in guiding anti-VEGF selection, supported by existing literature that links specific neovascular geometries to differential drug responsiveness. Conbercept, in particular, proved effective against the complex intertwined nets observed in this patient. These findings emphasize the promise of individualized treatment strategies and the potential of OCTA-based vascular geometry classification as a tool for precision medicine.}, }
@article {pmid41134689, year = {2025}, author = {Xue, Q and Huang, J and Wang, B and Ji, J and Wang, L and Kumari, S and Lan, C and Xiao, M}, title = {FTO Fuels Aβ1-40-Induced Retinal Pigment Epithelium Cell Injury Associated With Pyroptosis by Erasing m6A Methylation of the lncRNA Neat1.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {20}, pages = {e71166}, doi = {10.1096/fj.202500272RRRR}, pmid = {41134689}, issn = {1530-6860}, support = {82101139//MOST | National Natural Science Foundation of China (NSFC)/ ; 2021J01750//| Natural Science Foundation of Fujian Province (Fujian Natural Science Foundation)/ ; 2023J01690//| Natural Science Foundation of Fujian Province (Fujian Natural Science Foundation)/ ; 2023GGA019//| Fujian Provincial Health Technology Project (Provincial Health Technology Project of Fujian Province)/ ; 2022QNA015//| Fujian Provincial Health Technology Project (Provincial Health Technology Project of Fujian Province)/ ; 2024Y9260//Fujian Provincial Department of Science and Technology ()/ ; }, mesh = {*RNA, Long Noncoding/metabolism/genetics ; *Pyroptosis ; *Retinal Pigment Epithelium/metabolism/pathology ; Humans ; Animals ; *Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Methylation ; *Adenosine/analogs &amp; derivatives/metabolism ; Macular Degeneration/metabolism/pathology/genetics ; Inflammasomes/metabolism ; Epigenesis, Genetic ; Mice, Inbred C57BL ; }, abstract = {Retinal pigment epithelium (RPE) degeneration in association with inflammation is a key feature of age-related macular degeneration (AMD) pathology. Amyloid β (Aβ) in drusenoid deposits, the hallmark of AMD, is a critical initiating component that causes RPE cell damage through the activation of the NLR family pyrin domain containing 3 (NLRP3)-mediated inflammatory response. Epigenetic mechanisms have been reported to contribute to the pathogenesis of AMD. However, the extent to which epigenetic modifications regulate Aβ-mediated RPE inflammatory damage and cell death remains unclear. N6-methyladenosine (m6A) is the most abundant RNA epigenetic regulation in eukaryotes. Herein, based on bioinformatics analysis, we identified that fat mass and obesity-associated protein (FTO) acts as an essential epigenetic regulator in Aβ1-40-mediated RPE inflammatory cell death. Activation of NLRP3 inflammasome-related RPE pyroptosis was evident through enhanced NLRP3, gasdermin D immunoreactivity, increased caspase-1 cleavage, elevated IL-1β secretion, and higher LDH activity. Deletion of FTO resulted in the inhibition of RPE pyroptosis in vitro and in vivo. Mechanistically, methylated RNA immunoprecipitation (MeRIP) combined with RNA-seq demonstrated that long noncoding RNA (lncRNA) Neat1 served as a downstream target of FTO, with FTO knockdown suppressing Neat1 expression in an m6A-dependent manner. Neat1 depletion deactivated inflammatory factors, thereby hindering Aβ1-40-induced RPE pyroptosis. Furthermore, FTO silencing attenuated Neat1-mediated pyroptosis, resulting in compromised retinal structure and function. These findings suggest that the FTO-Neat1-NLRP3 network provides potential targets to treat AMD while expanding our understanding of the role of epigenetically modified lncRNAs in Aβ-driven RPE injury.}, }
@article {pmid41135050, year = {2025}, author = {Pinhas, A and Pinhas, B and Dmitruk, E and Pinhas, S}, title = {Eye and Systemic Disease Management Changes After Teleophthalmology Screening in Primary Care: Retrospective Cross-Sectional Pilot Study of 200 Consecutive Patients.}, journal = {JMIR formative research}, volume = {9}, number = {}, pages = {e81918}, pmid = {41135050}, issn = {2561-326X}, mesh = {Humans ; Cross-Sectional Studies ; Pilot Projects ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Primary Health Care ; Aged ; Adult ; Telemedicine ; *Eye Diseases/diagnosis/therapy ; Aged, 80 and over ; Adolescent ; Young Adult ; Child ; Disease Management ; *Mass Screening/methods ; Diabetic Retinopathy/diagnosis ; Ophthalmology/methods ; }, abstract = {BACKGROUND: Undiagnosed ocular diseases and ocular complications from systemic diseases are common in primary care populations, and many can be detected through retinal imaging before symptoms develop. Asynchronous store-and-forward teleophthalmology offers a scalable way to integrate eye screening into primary care, yet its broader impact beyond diabetes and diabetic retinopathy detection remains underexplored.<br><br>OBJECTIVE: This study evaluated the outcomes of asynchronous store-and-forward teleophthalmology screening in a primary care clinic, including detection and triage of ocular conditions and subsequent changes in eye and systemic management.<br><br>METHODS: This was a retrospective cross-sectional analysis of the first 200 patients screened in a single primary care clinic in Elmhurst, New York, between January and May 2025. Each patient underwent nonmydriatic external and posterior eye imaging, which was reviewed by a remote reading eye clinician. Reports included eye findings, triage decisions (routine monitoring vs in-person referral), and management recommendations. Subsequent changes in care were extracted from primary care and in-person specialist consult notes.<br><br>RESULTS: Of 200 patients (mean age 62.1, SD 19.0, range 11-100 years), 71.5% (143/200, 95% CI 64.9-77.3) had positive eye findings, and 40% (80/200, 95% CI 33.5-46.9) were referred for in-person eye examinations. Only 8.8% (7/80, 95% CI 4.3-17.0) of referrals were for diabetic retinopathy; most were for glaucoma suspects, age-related macular degeneration, cataracts, and other eye diseases. Image quality was high, with 98.2% (390/397, 95% CI 96.4-99.1) of fundus images being at least partially adequate. Of the 32 patients with documented in-person eye follow-up, 87.5% (28/32) of evaluations confirmed the screening findings. Eye management changes were initiated in 11 patients, whereas systemic management changes occurred in 70 patients, including new prescriptions for Age-Related Eye Disease Study 2 supplements, antihypertensives, diabetes medications, and lipid-lowering agents.<br><br>CONCLUSIONS: Asynchronous teleophthalmology screening in a primary care setting effectively identified both ocular diseases and ocular complications from systemic diseases, leading to meaningful changes in eye and systemic management. The low rate of diabetic retinopathy among referrals highlights the broader diagnostic value of retinal imaging beyond diabetes management. This care model offers a scalable, high-yield strategy for proactive disease detection and interdisciplinary intervention at the primary care level.}, }
@article {pmid41135684, year = {2025}, author = {Saadane, A and von Lintig, J}, title = {The retinol-binding protein receptor STRA6 and melanin cooperatively sustain retinoid signaling and outer blood-retinal barrier integrity.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {12}, pages = {110846}, pmid = {41135684}, issn = {1083-351X}, support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY020551/EY/NEI NIH HHS/United States ; R01 EY028121/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Mice ; Mice, Knockout ; *Blood-Retinal Barrier/metabolism/pathology ; *Membrane Proteins/metabolism/genetics ; *Melanins/metabolism/genetics ; *Signal Transduction ; *Retinoids/metabolism ; Vitamin A/metabolism ; Retinal Pigment Epithelium/metabolism ; Retinol-Binding Proteins, Plasma/metabolism/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; }, abstract = {Disruption of the outer blood-retinal barrier (oBRB) is a central feature of retinal degenerative diseases, including age-related macular degeneration, yet the molecular mechanisms maintaining this barrier in the adult eye remain poorly defined. STRA6, a high-affinity receptor for retinol-binding protein (RBP4), mediates vitamin A uptake at the basolateral membrane of the retinal pigment epithelium (RPE), while melanin protects ocular retinoid stores from photooxidative stress. We previously showed that STRA6 deficiency leads to downregulation of junctional proteins in the RPE. Here, we demonstrate that STRA6 and melanin act synergistically to preserve the integrity of the oBRB. In albino Stra6 knockout mice, ocular retinoid levels were severely reduced despite normal circulating retinol levels, and dietary vitamin A delivered via chylomicrons failed to compensate for the loss of RBP4-mediated transport. This led to a functional impairment of both rod- and cone-mediated responses, even under vitamin A-sufficient conditions. Mice also showed downregulated tight junction proteins (ZO-1, Claudin-1, Claudin-3), RPE disorganization, barrier leakage, and immune cell infiltration into the subretinal space. These defects were further exacerbated under dietary vitamin A restriction. Importantly, systemic treatment with the pan-retinoic acid receptor (RAR) agonist TTNPB restored junctional gene expression and oBRB function in Stra6[-/-] mice, providing evidence that barrier failure arises from impaired retinoid signaling rather than structural loss of STRA6 and melanin. These findings define a novel role for retinoic acid in sustaining RPE barrier function and highlight the combined importance of STRA6-mediated transport and melanin-dependent photoprotection in retinal homeostasis.}, }
@article {pmid41136840, year = {2025}, author = {Jha, S and Hua, F and Dejene, R and Sarkar, S and Sharma, R and Bharti, K}, title = {Development of a Manufacturing Process for Clinical Autologous hiPSC-Derived Retinal Pigment Epithelium.}, journal = {Advances in experimental medicine and biology}, volume = {1486}, number = {}, pages = {165-178}, pmid = {41136840}, issn = {0065-2598}, mesh = {Humans ; Cell Differentiation ; *Induced Pluripotent Stem Cells/cytology/transplantation ; *Macular Degeneration/therapy/pathology ; *Retinal Pigment Epithelium/cytology/transplantation ; Tissue Engineering/methods ; Transplantation, Autologous ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. The disease progresses through early, intermediate, and advanced stages, with late forms including dry AMD (geographic atrophy) and wet AMD (choroidal neovascularization). Currently, there is no cure for dry AMD, which results from retinal pigment epithelium (RPE) cell loss. Induced pluripotent stem cell (iPSC)-based transplants offer a potential therapy by replacing atrophied RPE. This chapter outlines the manufacturing process, key parameters, and challenges of developing iPSC-derived RPE therapy. We engineered a clinical-grade iPSC-RPE patch using autologous cells from AMD patients. Starting from the patient blood, CD34+ cells were isolated, expanded, and reprogrammed using episomal plasmids. Twelve iPSC clones were generated, quality-tested, and three were selected for differentiation into mature RPE on a biodegradable scaffold. The final patch underwent QC assays for donor identity, sterility, and phenotype confirmation before transplantation. This work has led to a Phase I/IIa clinical trial to evaluate the safety and feasibility of auto-iPSC-RPE patches in AMD patients.}, }
@article {pmid41136844, year = {2025}, author = {Wang, L and Wang, YK and Li, D and Ma, J and Sun, Y and Li, X and Wang, H and Niu, S and Stacey, GN and Zhao, T and Hu, B and Zhou, Q and Wang, L and Hao, J}, title = {The Programme for Manufacture of hPSC‑Based Products for AMD and PD.}, journal = {Advances in experimental medicine and biology}, volume = {1486}, number = {}, pages = {227-236}, pmid = {41136844}, issn = {0065-2598}, mesh = {Humans ; *Macular Degeneration/therapy/pathology ; *Parkinson Disease/therapy/pathology ; *Pluripotent Stem Cells/cytology/transplantation ; Retinal Pigment Epithelium/cytology/pathology ; Cell Differentiation ; Animals ; Dopaminergic Neurons/transplantation/pathology ; *Stem Cell Transplantation/methods ; Regenerative Medicine/methods ; }, abstract = {Pluripotent stem cells (hPSCs) possess the unique ability to self-renew and differentiate into various functional cell types, positioning them as key "seed cells" in regenerative medicine. The development of PSC-based therapies offers new hope for treating complex diseases, and degenerative diseases, particularly those caused by the loss of specific cellular functions, such as macular degeneration, Parkinson's disease, spinal cord injury, diabetes, and cartilage damage. Cell replacement therapies using hPSC-committed cells can help halt disease progression or potentially cure these conditions. The Retinal Pigment Epithelium (RPE) is crucial for visual function and photoreceptor support, with its dysfunction implicated in age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Parkinson's disease (PD), a rapidly progressing neurodegenerative disorder marked by the loss of midbrain dopaminergic neurons (mDA), remains one of the most difficult neurological conditions to treat. Traditional therapies for these diseases have largely been ineffective. RPE and mDA neurons differentiated from hPSCs offer promising solutions for treating AMD and PD, their treatment methods are both cell replacement therapy, and they are the products used in the first batch of stem cell clinical research registration projects in China, so we will put these two products together. This chapter summarizes the differentiation and quality control strategies for hESC-derived RPE and mDA neurons as examples of the potential hPSC-derived cell therapies, under development at the Chinese Academy of Sciences and Beijing Institute for Stem Cell and Regenerative Medicine, for these complex, treatment-resistant diseases.}, }
@article {pmid41136910, year = {2025}, author = {Cho, Y and Yoo, WS and Kim, SJ and Chung, I}, title = {Characteristics of patients lost to follow-up after intravitreal anti-vascular endothelial growth factor therapy for exudative age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {598}, pmid = {41136910}, issn = {1471-2415}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Visual Acuity ; *Lost to Follow-Up ; Follow-Up Studies ; Tomography, Optical Coherence ; }, abstract = {BACKGROUND: This study aimed to analyze and compare the characteristics of patients with exudative age-related macular degeneration who were lost to follow-up after receiving intravitreal anti-vascular endothelial growth factor(anti-VEGF) injections versus those who maintained regular follow-up.<br><br>METHODS: This retrospective study included patients who were lost to follow-up for more than 1 year (n&#x2009;=&#x2009;79) or maintained follow-up (n&#x2009;=&#x2009;186) after treatment with intravitreal injections of ranibizumab or aflibercept for exudative age-related macular degeneration. Age, sex, place of residence, type of health insurance, distance from the hospital, laterality of involvement, and follow-up duration were analyzed.<br><br>RESULTS: There were no significant differences between the two groups in terms of age, sex, or type of health insurance. However, patients lost to follow-up resided significantly further from the hospital versus those with regular follow-up (33.1&#x2009;&#xb1;&#x2009;26.8 vs. 21.6&#x2009;&#xb1;&#x2009;8.5&#xa0;km; P&#x2009;=&#x2009;0.001). A significantly higher proportion of patients that were lost to follow-up had unilateral involvement (P&#x2009;<&#x2009;0.001) and resided in rural areas (P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Distance from the hospital, rural residency, and unilateral involvement are significantly associated with nonadherence to follow-up among patients with exudative age-related macular degeneration receiving intravitreal anti-VEGF injections.}, }
@article {pmid41138048, year = {2025}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can Gene Therapy Transform the Treatment Landscape of Posterior Segment Eye Diseases? A Comprehensive Review of Recent Advancements.}, journal = {Drugs}, volume = {85}, number = {12}, pages = {1585-1608}, pmid = {41138048}, issn = {1179-1950}, mesh = {Humans ; *Genetic Therapy/methods ; Animals ; Macular Degeneration/therapy/genetics ; *Eye Diseases/therapy/genetics ; Gene Editing ; *Retinal Diseases/therapy/genetics ; Gene Transfer Techniques ; Genetic Vectors ; *Posterior Eye Segment/pathology ; }, abstract = {Posterior segment eye diseases (PSEDs) encompass a diverse group of conditions affecting the retina, choroid, optic nerve, and vitreous humor, often leading to progressive and irreversible vision loss. Age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and inherited retinal diseases (IRDs) are among the most clinically significant PSEDs with a substantial global burden and economic impact. Conventional treatments for PSEDs have limitations that necessitate the development of novel therapies that address the underlying molecular drivers of the disease. Gene therapy has emerged as a promising approach, offering the potential for durable and curative outcomes through precise genetic manipulation. Advancements in gene therapy strategies, including gene augmentation, gene editing, RNA-based therapies, and optogenetics, have led to significant progress in preclinical studies and clinical trials across various PSED subtypes. US Food and Drug Administration (FDA) approval of voretigene neparvovec (Luxturna[®]) for RPE65-associated IRDs validated the clinical viability of ocular gene therapy, while ongoing trials for AMD, DR, and other IRDs continue to expand the therapeutic landscape. Innovations in viral and non-viral delivery systems, such as dual AAV vectors, lipid nanoparticles, and novel biomaterials, have enhanced the efficiency and specificity of gene delivery to the retina. However, challenges persist, including immune responses to viral vectors, limited transduction efficiency in certain cell types, and anatomical barriers posed by the blood-retinal barrier. Future directions in ocular gene therapy include the development of precision genome editing techniques, such as prime editing, miRNA-based regulation, and combinatorial approaches integrating gene therapy with stem cell transplantation or neuroprotective agents. As the field continues to evolve, addressing these challenges and optimizing gene therapy strategies will be crucial in translating the transformative potential of ocular gene therapy into clinical reality for patients with PSEDs.}, }
@article {pmid41138285, year = {2025}, author = {Demiot, C and De Sousa, C and Labrunie, A and Danigo, A and Authier, D and Delavaud, JM and Robert, PY and Rocher, M}, title = {Descriptive analysis of the knowledge amongst French patients about neovascular age-related macular degeneration as a function of social vulnerability, health literacy and date of diagnosis.}, journal = {Journal francais d'ophtalmologie}, volume = {48}, number = {9}, pages = {104666}, doi = {10.1016/j.jfo.2025.104666}, pmid = {41138285}, issn = {1773-0597}, mesh = {Humans ; *Health Literacy/statistics &amp; numerical data ; Female ; Male ; *Health Knowledge, Attitudes, Practice ; Aged ; France/epidemiology ; Aged, 80 and over ; *Macular Degeneration/diagnosis/epidemiology/psychology ; Patient Education as Topic ; *Vulnerable Populations/statistics &amp; numerical data/psychology ; Surveys and Questionnaires ; *Wet Macular Degeneration/diagnosis/epidemiology/psychology ; Time Factors ; Socioeconomic Factors ; Risk Factors ; Quality of Life ; }, abstract = {Patient education (PE) programs for patients with neovascular age-related macular degeneration (nAMD) are essential to reduce the disease's impact on quality of life. To establish a PE program for nAMD, a descriptive quantitative study was conducted to (i) describe the population and their knowledge concerning nAMD, (ii) classify patients according to their knowledge of disease, and (iii) their social vulnerability, health literacy and the duration since diagnosis. Socio-demographic data of 100 nAMD patients (70 women and 30 men, 80±7 years of age) were collected and compared with data on their social vulnerability (simplified EPICES score) and health knowledge (health literacy questionnaire). Patients were classified into three groups according to their knowledge, evaluated with questionnaires including the themes of pathology, information retrieval, treatment, risk factors and self-monitoring. A subgroup analysis of these knowledge profiles was assessed according to social vulnerability, health literacy and duration since diagnosis. False beliefs and lack of knowledge about nAMD were noted in almost 50% of patients. Only 15 patients were familiar with the Amsler grid. Three groups of patients were identified according to their knowledge of disease. No link was found between knowledge levels and health literacy. Patients who did not understand their disease were the most vulnerable, searched for less information, and had the most recent diagnosis. There is a significant need to improve the knowledge of nAMD patients. Social vulnerability, duration since diagnosis and heterogeneity in patient knowledge must be considered when establishing a PE program.}, }
@article {pmid41139156, year = {2025}, author = {Habot-Wilner, Z and Ostrovsky, M and Zur, D and Schwartz, S and Hagin, D and Gadoth, A and Ben-Ami, R and Paran, Y and Goldshmidt, H and Slutzkin, M and Adler, A and Levytskyi, K}, title = {Metagenomic next-generation sequencing: a game-changer in the diagnosis of unique intraocular infections.}, journal = {Eye (London, England)}, volume = {39}, number = {18}, pages = {3365-3371}, pmid = {41139156}, issn = {1476-5454}, mesh = {Humans ; *Endophthalmitis/diagnosis/microbiology ; *Eye Infections, Bacterial/diagnosis/microbiology ; *High-Throughput Nucleotide Sequencing/methods ; *Metagenomics/methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: To thoroughly describe unique intraocular infections diagnosed by metagenomic next-generation sequencing (mNGS).<br><br>METHODS: A retrospective case series of patients presenting with challenging atypical intraocular infections at Tel Aviv Sourasky Medical Center during 2024. Clinical and demographic data, as well as mNGS results were extracted from patient records. mNGS was performed on the Illumina NextSeq500 platform using a custom bioinformatics pipeline. The following parameters were examined: Reads Per Million, Reads Per Million-ratio to negative control and E-index (K-mers*coverage/reads).<br><br>RESULTS: The study included three patients with novel presentations of intraocular infections, manifesting with atypical clinical manifestations and negative routine diagnostic workups. mNGS allowed the identification of Cytomegalovirus in a 43-year-old male with a history of autosomal dominant hyper-IgE syndrome, Bartonella henselae infection manifesting with photoreceptoritis, retinal vasculitis and global retinal dysfunction in a healthy 28-year-old female, and polymicrobial endophthalmitis with Rothia mucilaginosa and Pantoea agglomerans following intravitreal faricimab injection for neovascular age-related macular degeneration in an 81-year-old male. Treatment regimens were adjusted based on mNGS results.<br><br>CONCLUSIONS: Metagenomic next-generation sequencing has an important role in the diagnosis of challenging intraocular infections. It enables comprehensive pathogen identification and enhances the precision of treatment strategies.}, }
@article {pmid41140136, year = {2025}, author = {Erbezci, M and Özen Tunay, Z and Öztürk, T}, title = {Preferred Retinal Locus in Juvenile Macular Dystrophy.}, journal = {Turkish journal of ophthalmology}, volume = {55}, number = {5}, pages = {239-244}, pmid = {41140136}, issn = {2149-8709}, mesh = {Humans ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Child ; *Macular Degeneration/physiopathology/diagnosis ; *Fovea Centralis/pathology ; Fluorescein Angiography/methods ; Follow-Up Studies ; Ophthalmoscopy ; }, abstract = {OBJECTIVES: To evaluate foveal lesion and preferred retinal locus (PRL) locations and their effects on visual acuity in juvenile macular dystrophy (JMD) patients.<br><br>MATERIALS AND METHODS: In this retrospective study, 14 JMD patients (28 eyes) with bilateral central vision loss were examined using scanning laser ophthalmoscope/optical coherence tomography. Best-corrected visual acuity (BCVA), dimensions and location of the macular lesion, PRL location, and PRL stability were evaluated.<br><br>RESULTS: Mean BCVA was 0.84&#xb1;0.17 logarithm of the minimum angle of resolution. PRL was superiorly located in 64.3% of eyes and nasally located in 35.7%. PRL location was significantly associated with patient age (r=0.541, p=0.002); nasally located PRLs were more common in younger patients (mean age 15.1&#xb1;2.8 years) while superiorly located PRLs were more common in older patients (mean age 22.4&#xb1;6.9 years). Superiorly located PRLs were significantly closer to the fovea than nasally located PRLs (p=0.014). Visual acuity worsened as lesion size increased and PRL-fovea distance increased. PRL-fovea distance was longer in younger patients and positively correlated with lesion dimensions and PRL-lesion distance.<br><br>CONCLUSION: In JMD patients, PRLs are predominantly located superiorly or nasally. In younger patients, PRLs are typically located nasally and farther from the fovea, with poorer visual acuity compared to older patients. Cortical adaptation mechanisms may play a role in changing PRL location with age. Understanding PRL characteristics in JMD is crucial for developing effective low-vision rehabilitation strategies.}, }
@article {pmid41140340, year = {2025}, author = {Christensen, CA and Gupta, N and Breazzano, MP}, title = {Novel Bilateral Geographic Atrophy Phenotype Associated With CRX Mutation.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251386364}, pmid = {41140340}, issn = {2474-1272}, abstract = {Purpose: To describe an atypical phenotype of retinal dystrophy in the setting of a heterozygous missense mutation (CRX-RD). Methods: The case is a 71-year-old woman previously diagnosed with advanced, non-neovascular, nonexudative age-related macular degeneration (AMD) who presented with longstanding blurry vision for consideration of intravitreal anti-complement factor therapy. Results: Ophthalmic examination showed geographic atrophy (GA) in both eyes, without evidence of drusen or drusenoid deposits. Genetic panel testing revealed a pathogenic, heterozygous missense mutation in CRX, the NM_000554.6(CRX) variant c.128G>A (p.Arg43His) (RCV001228802.6). Although CRX-RD is known to have phenotypic heterogeneity, cases with macular atrophy most commonly display bullseye maculopathy or benign concentric annular macular dystrophy. Conclusions: This case presenting with bilateral GA is consistent with a novel phenotype associated with a pathogenic variant of CRX and is an atypical presentation of RD simulating AMD.}, }
@article {pmid41140895, year = {2026}, author = {Xu, Z and Lin, R and Wang, X and Liu, Y and Huang, C and Wang, C and Bao, Z}, title = {Association of Physical Frailty and Genetic Predisposition with Risk of Irreversible Eye Diseases.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100910}, pmid = {41140895}, issn = {2666-9145}, abstract = {OBJECTIVE: The evidence linking frailty to overall and specific irreversible eye diseases is limited. Moreover, it is unclear whether frailty is associated with similar increased risk across individuals with different genetic risk profiles. The aim of this study was to examine the association between frailty and overall and specific irreversible eye diseases and explore the modification effect of genetic risk of glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in such associations.<br><br>DESIGN: Prospective cohort study.<br><br>PARTICIPANTS: The study included a total of 409 579 White participants in the UK Biobank study.<br><br>METHODS: Physical frailty was defined by 5 components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. Participants were classified as nonfrail, prefrail, or frail. Polygenic risk score was categorized as low (tertile 1), intermediate (tertile 2), or high (tertile 3). Cox regression was used to assess the association of physical frailty with irreversible eye diseases.<br><br>MAIN OUTCOMES AND MEASURES: Irreversible eye diseases were identified using hospital admission electronic health records and death registries.<br><br>RESULTS: Among 409 579 individuals (mean age, 56.5 years; 46.5% male) with a median follow-up of 13.1 years, 10 927, 7 095, and 919 were diagnosed with irreversible eye disease in the nonfrail, prefrail, and frail groups, respectively. Prefrail and frail individuals showed increased risks of overall irreversible eye diseases, with a 12% higher risk for prefrail individuals (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.09-1.16) and a 47% higher risk for frail individuals (HR, 1.47; 95% CI, 1.37-1.58). Increased risks were also observed for specific irreversible eye diseases, including glaucoma (HR, 1.11 [95% CI, 1.06-1.17] for prefrailty; HR, 1.43 [95% CI, 1.28-1.61] for frailty), diabetic retinopathy (HR, 1.12 [95% CI, 1.03-1.21] for prefrailty; HR, 1.53 [95% CI, 1.34-1.73] for frailty), and AMD (HR, 1.13 [95% CI, 1.08-1.19] for prefrailty; HR, 1.35 [95% CI, 1.20-1.52] for frailty). Furthermore, individuals with more severe frailty status and higher genetic risk exhibited higher risks of irreversible eye diseases than those with low genetic risk and nonfrailty.<br><br>CONCLUSIONS: Frailty was associated with an increased risk of irreversible eye diseases, particularly among individuals with higher genetic risk. These findings suggest that targeted strategies to prevent and manage frailty may contribute to reducing the risk of irreversible eye diseases.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41140896, year = {2026}, author = {Dadgar, N and Fung, K and McClintic, S and Metea, C and Llorenç, V and Saleh, M and Nakamura, YK and Jahrig, C and Kiang, L and Janowitz, C and Davin, S and Balter, A and Le Cao, KA and Karstens, L and Martin, TM and Klein, ML and Lin, P}, title = {Age-related Eye Disease Studies Supplements and Genetic Risk Score Are Crucial Determinants of Intestinal Microbial Alterations in Advanced Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100920}, pmid = {41140896}, issn = {2666-9145}, abstract = {OBJECTIVE: Determine whether an intestinal microbial signature is associated with advanced age-related macular degeneration (AMD); investigate the relationship between the microbiota and AMD genetic risk, intestinal immunoglobulin-A (IgA), and Age-Related Eye Disease Studies (AREDS) supplementation.<br><br>DESIGN: Case-control study.<br><br>METHODS: Fecal 16S rRNA sequencing, DESeq2 differential abundance, and IgA-sequencing.<br><br>SUBJECTS: Advanced AMD and age-similar non-AMD control subjects.<br><br>MAIN OUTCOME MEASURES: Differential abundance plots using DESeq2, &#x3b1; and &#x3b2; diversity, and impact of AREDS supplementation and genetic risk on AMD microbiota.<br><br>RESULTS: In 85 advanced AMD compared with 49 healthy control subjects' intestinal microbiota, exploratory partial least-squares-discriminant analysis (PLS-DA) showed that gut microbiome composition was able to predict AMD with moderate confidence (cross validation error rates, 0.28-0.36) with the potential for overfitting. A higher AMD genetic risk score was associated with lower gut microbial diversity (P = 0.0086; Spearman r = -0.3), a finding confirmed by multiple linear regression with confounding covariates, whereas AREDS supplementation was associated with increased gut bacterial diversity (coefficient, 2.64; P < 0.05). Differential abundance plots showed increased Proteobacteria and many differentially abundant genera (including Prevotella, Desulfovibrio, Oscillospira, and Ruminococcaceae) in AMD versus controls. Flow cytometry and IgA-sequencing suggested increased IgA-coating of gut bacteria in the age-related maculopathy susceptibility 2 (ARMS2) gene risk genotype, including higher IgA indices for Prevotella. These findings are hypothesis-generating and require functional validation. Predicted metabolic pathways (via piphillin) that differed between AMD and controls included lipid metabolism and xenobiotic processing by cytochrome P450; these findings are inferred and require confirmation by metabolomic studies.<br><br>CONCLUSIONS: The intestinal microbiome is able to predict advanced AMD via PLS-DA. AREDS supplementation and genetic risk are crucial determinants of the AMD microbiome, which interacts with gut immunity by increasing IgA binding to certain bacteria. Understanding how the gut microbiome and its metabolites interact with gut immunity and host genetics will allow us to further investigate the microbiome to find potentially novel therapeutic targets in AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41140906, year = {2026}, author = {Goldberg, EA and Ross, CJ and Douglas, VP and Ivanov, A and Elze, T and Miller, JW and Lorch, AC and , }, title = {Data Duplication and Errors in Large Medical Data Sets: A Case Study in the IRIS® Registry.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100933}, pmid = {41140906}, issn = {2666-9145}, abstract = {PURPOSE: To investigate entry errors and data duplication within the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) utilizing cataract surgery (CS), neodymium-doped: yttrium aluminum garnet (YAG) capsulotomy, age-related macular degeneration (AMD), and diabetic retinopathy (DR) records.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients in the IRIS Registry.<br><br>METHODS: We collected records of CS and YAG capsulotomy with specified laterality within the IRIS Registry (years 2013-2023), identifying eyes having >1 record and eyes having &#x2265;1 record on a date after the first entry (different date duplication, D d). Additionally, we identified eyes amongst records of DR and AMD with (1) a diagnosis indicating a more severe stage then reversion to the less severe stage or (2) a transition to a more severe stage before later being diagnosed with the less severe stage, defined as transition errors. We investigated potential predictors of D d and transition errors among patient and practice characteristics by evaluating the permutation feature importance (PFI) of classification models.<br><br>MAIN OUTCOME MEASURES: For CS and YAG capsulotomy, we measure the proportion of eyes having >1 procedure record, having >1 record only on the initial procedure date, and having &#x2265;1 procedure record on a date after the first entry. For DR and AMD, we measure the proportion of eyes reverting to an earlier stage after starting at a later stage and the proportion reverting to an earlier stage after transitioning to a later stage.<br><br>RESULTS: Of the 14 718 896 CS-treated eyes, 30.9% had duplicates, with 5.5% having D d . For YAG capsulotomy, out of 5 113 679 eyes, 29.1% had duplicates, with 4.1% having D d . For AMD and DR, 13.6% and 12.7% of eyes, respectively, exhibited transition errors. Models captured a relationship between the eye's first practice on record and the data errors under study, indicated by F1-loss = 0.230 (D d model), 0.062 (transition error model) on average by PFI.<br><br>CONCLUSIONS: Data duplication in large medical data sets necessitates caution when analyzing repeated procedures or relapsing conditions. Addressing problematic errors requires transparency and communication amongst stakeholders across organizations. Within the IRIS Registry, the results indicated an association between the first record's originating practice and data errors, providing an investigative entry point for upstream data stewards.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41140907, year = {2026}, author = {Nagai, N and Shinoda, H and Matsubara, H and Terasaki, H and Hirano, T and Kato, A and Miki, A and Hirai, H and Murao, F and Imaizumi, H and Gomi, F and Mitamura, Y and Ogata, N and Kusuhara, S and Yasukawa, T and Murata, T and Sakamoto, T and Kondo, M and Ozawa, Y}, title = {Associations between Progression of Retinal Pigment Epithelial and Outer Retinal Atrophy and Choroidal Thickness: A 2-Year observation.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100939}, pmid = {41140907}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the clinical course of retinal pigment epithelial and outer retinal atrophy (RORA) with best-corrected visual acuity (BCVA) and risk factors for rapid progression to explore the pathogenesis.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Data on eyes with fovea-involved RORA associated with age-related macular degeneration were collected over time from 10 hospitals in Japan.<br><br>METHODS: Data on ophthalmic examination, BCVA, and OCT images were analyzed.<br><br>MAIN OUTCOME MEASURES: Relationships between changes in BCVA and extents of RORA and outer plexiform layer (OPL) deterioration and their associations with central choroidal thickness (CCT) and pachychoroid characteristics at baseline were evaluated.<br><br>RESULTS: Of the 53 eyes of 53 patients (mean age; 74.9 &#xb1; 1.4 years), 32 eyes (60.4%) belonged to men. The progression in the mean extent of OPL deterioration was evident at year 1, whereas that of RORA, BCVA impairment, thinning of the central retinal thickness, and CCT became apparent at year 2 (P < 0.05). Changes in the extents of RORA and OPL deterioration and BCVA were correlated (P < 0.05). Baseline CCT negatively correlated with baseline RORA and the changes in extent of RORA (P < 0.05). After adjusting for age and sex, a longer extent of RORA at baseline predicted BCVA worsening &#x2265;0.04 per year (odds ratio [OR], 3.444; 95% confidence interval [CI], 1.015-11.691; P = 0.047). Greater horizontal extension of RORA &#x2265;175 &#x3bc;m/y was frequently observed in eyes with thinner CCT <180 &#x3bc;m (OR, 4.684; 95% CI, 1.288-17.036; P = 0.019), subretinal drusenoid deposits (SDDs) (OR, 6.714; 95% CI, 1.555-28.988; P = 0.011), and drusen (OR, 4.392; 95% CI, 1.176-16.410; P = 0.028) and less observed in eyes with pachychoroid characteristics (OR, 0.038; 95% CI, 0.003-0.454, P = 0.010) at baseline after adjusting for age and baseline extent of RORA; similar risks for greater vertical extension of RORA were observed.<br><br>CONCLUSIONS: The change in BCVA paralleled the changes in the extents of RORA and OPL deterioration. Rapid BCVA impairment was observed in eyes with longer RORA at baseline. A thinner choroid, SDD, and drusen were risk factors, and pachychoroid characteristics were protective factors against RORA progression. Further studies are warranted to better understand the progression of RORA and vision loss.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41141822, year = {2025}, author = {Wang, T and Zhang, Y and Xiao, W and Jin, Y and Yi, Q and Chen, Q and Xiang, J and Wang, R and Li, J and Liu, L}, title = {Tetrahedral DNA Framework Penetrating Ocular Barrier for Treatment of Retinal Oxidative Stress.}, journal = {ACS omega}, volume = {10}, number = {41}, pages = {48984-48990}, pmid = {41141822}, issn = {2470-1343}, abstract = {Excessive accumulation of reactive oxygen species in the retina is the predominant pathogenic mechanism underlying dry age-related macular degeneration (dAMD). Although antioxidant chemicals have been shown to be effective in reducing ROS levels, their bioavailability and therapeutic efficacy are restricted by ocular barriers. Herein, we developed a tetrahedral framework nucleic acid (tFNA)-based antioxidant drug for the treatment of retinal oxidative stress diseases. By exploiting their penetration capability, these tFNAs penetrated multiple ocular tissues and cellular barriers. These tFNAs protected retinal pigment epithelium cells from glyoxal-induced oxidative stress damage by exerting their intrinsic antioxidant properties through the JNK and AKT pathways upon entering the cells. The subconjunctival administration of tFNAs alleviated structural damage and reduced retinal cell apoptosis in a retinal oxidative stress rat model. These results indicated that tFNAs are a promising therapeutic drug for the treatment of retinal oxidative stress diseases, which sheds light on the development of dAMD therapy.}, }
@article {pmid41143143, year = {2025}, author = {Biswas, RK and Sheth, JU and Shrivastava, V and Kaur, J and Sinha, S and Pal, SS and Nandi, K and Das, S}, title = {Faricimab for Refractory Neovascular Age-Related Macular Degeneration: Retrospective Real-World Evidence from India.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3881-3887}, pmid = {41143143}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the anatomical and functional outcomes of faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) in a real-world Indian cohort over a six-month period.<br><br>PATIENTS AND METHODS: In this retrospective, multicenter study, 24 eyes with refractory nAMD were switched to faricimab on a pro-re-nata regimen between January 2024 and December 2024. Patients underwent monthly evaluation for three months, then per physician discretion, with measurement of best-corrected visual acuity (BCVA), central foveal thickness (CFT), and proportions of eyes with intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED).<br><br>RESULTS: The cohort's mean age was 68.1 (&#xb1;10.6) years, and prior to switching had received an average of 11.4 (&#xb1;9.1) anti-VEGF injections. During the six-month period, eyes underwent a mean of 2.63 (&#xb1; 1.34) faricimab injections (range, 1-5): 25.0% received one injection, 29.2% two, 16.7% three, 16.7% four, and 12.5% five. Mean BCVA improved from 0.66 (&#xb1;0.4) logMAR at baseline to 0.47 (&#xb1;0.34) at month 1, 0.35 (&#xb1;0.32) at month 2, and 0.27 (&#xb1;0.27) at months 3 and 6 (P&#x2264;0.0003). Mean CFT decreased from 471.1 (&#xb1;246.4) &#xb5;m to 337.3 (&#xb1;198.3) &#xb5;m (month 1), 265.1 (&#xb1;90.7) &#xb5;m (month 2), 217.7 (&#xb1;41.3) &#xb5;m (month 3), and 209.4 (&#xb1;36.0) &#xb5;m (month 6) (P<0.0001). SRF resolved in 90.9% of affected eyes (P<0.001), IRF in 87.5% (P=0.0006), and PED in 54.5% (P=0.32), with complete fluid resolution in 83.3% of eyes (P=0.00002). No ocular or systemic adverse events occurred.<br><br>CONCLUSION: In this real-world Indian cohort of refractory nAMD, faricimab delivered robust visual gains, significant CFT reduction, and high rates of fluid resolution, with over half of eyes requiring &#x2264;2 injections over six months, supporting its role as an effective switch therapy. Further prospective studies are warranted to optimize dosing intervals and long-term outcomes.}, }
@article {pmid41143474, year = {2025}, author = {Habibi, A and Ashrafkhorasani, M and Emamverdi, M and Chinasigari, PR and Goerdt, L and Gao, L and McGwin, G and Clark, ME and Abbasgholizadeh, R and Fasih-Ahmad, S and Vatanatham, C and Wang, ZC and Mishra, Z and Nittala, MG and Owsley, C and Curcio, CA and Hu, ZJ and Sadda, SR}, title = {Total Retinal Pigment Epithelium Thickness and Reflectivity, in Relation to Histology and Vision, at the Aging-AMD Transition: ALSTAR2 Baseline.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {13}, pages = {42}, pmid = {41143474}, issn = {1552-5783}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Tomography, Optical Coherence/methods ; Female ; Aged ; Male ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Visual Acuity/physiology ; *Aging/physiology ; *Macular Degeneration/physiopathology/pathology/diagnosis ; Aged, 80 and over ; Middle Aged ; Dark Adaptation/physiology ; }, abstract = {PURPOSE: The retinal pigment epithelium (RPE) is critical in age-related macular degeneration (AMD) pathophysiology. We compare total RPE thickness (TRPET) and normalized reflectivity intensity (TNRR) on optical coherence tomography (OCT) among healthy aged and early AMD (eAMD) and intermediate AMD (iAMD) eyes, and to visual function.<br><br>METHODS: Spectralis OCT volume scans from aged, eAMD, and iAMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step) of the Alabama Study on Early Age-related Macular Degeneration 2 (ALSTAR2) baseline sample were automatically segmented for vitreous, nerve fiber layer (NFL), and total RPE (measured up to the centerline of the interdigitation zone) and manually corrected. TNRR was normalized with reference to vitreous and NFL within zones of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Vision tests included rod-mediated dark adaptation (RMDA), a functional benchmark for AMD risk (reported as rod intercept time [RIT]), and other tests of rod- and cone-mediated function.<br><br>RESULTS: Of 502 eyes of 502 participants (71.8 &#xb1; 6.1 years, 59.6% female participants), 252 were healthy, 147 had eAMD, and 103 had iAMD. TRPET was significantly thinner in iAMD compared with eAMD and healthy eyes (P < 0.001) and moderately correlated with longer RIT in all eyes (r = 0.12-0.35). TNRR was lower in iAMD eyes compared to eAMD and healthy eyes (P < 0.01); correlation with RIT was weaker but significant.<br><br>CONCLUSIONS: Reduced TRPET and TNRR in AMD and their correlation with RMDA are statistically significant due to the large sample. Whether they have practical utility for AMD detection will be learned from ongoing longitudinal studies. In ALSTAR2, non-RPE layers may contribute to delayed RMDA.}, }
@article {pmid41144243, year = {2026}, author = {Perilli, R and Mastropasqua, R and Mastropasqua, L}, title = {Turning diabetic retinopathy telescreening into a multi-telescreening.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {NP12-NP13}, doi = {10.1177/11206721251389641}, pmid = {41144243}, issn = {1724-6016}, }
@article {pmid41146323, year = {2025}, author = {Lee, Y and Rahman, S and Tao, BK and Fang, T and Akil, H and Ferrara, D and Lam, S and Navajas, EV}, title = {Recognition and treatment of polypoidal choroidal vasculopathy and age-related macular degeneration in British Columbia.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {118}, pmid = {41146323}, issn = {2056-9920}, abstract = {OBJECTIVE: To assess ethnic differences in the prevalence, diagnosis, and management of polypoidal choroidal vasculopathy (PCV) compared to typical neovascular age-related macular degeneration (nAMD) among Chinese and Caucasian patients in British Columbia.<br><br>METHODS: A retrospective chart review was conducted between 2008 and 2013 based on predefined inclusion criteria. Demographic, diagnostic, and clinical outcome data&#x2014;including race, lesion type, diagnostic modality, and treatment response&#x2014;were extracted and analyzed using RStudio.<br><br>RESULTS: Of the 416 eyes reviewed, 92.07% (383/416, N&#x2009;=&#x2009;Total sample number) were from Caucasian patients and 7.93% (33/416, N&#x2009;=&#x2009;Total sample number) from Chinese patients. No statistically significant difference in median age at diagnosis was observed between ethnic groups. ICGA was used in 3.57% (2/56, N&#x2009;=&#x2009;Total number of PCV cases) of PCV cases. Anti-VEGF monotherapy was the predominant treatment modality, while combination therapy with photodynamic therapy (PDT) was employed in 5.38% (22/353&#x2009;+&#x2009;56) of cases. There were no significant differences in visual acuity (VA) gains or central retinal thickness (CRT) reductions between PCV and nAMD diagnoses, nor between ethnic groups. Under anti-VEGF monotherapy, visual acuity and central retinal thickness outcomes were similar between PCV and nAMD and across the ethnic groups evaluated, within the limitations of the study design.<br><br>CONCLUSION: PCV, though less common than typical nAMD, was identified in both Chinese and Caucasian patients, with a trend toward younger age at presentation compared to nAMD. The low utilization of ICGA may contribute to the underdiagnosis of PCV. Nevertheless, anti-VEGF monotherapy yielded comparable outcomes across diagnoses and ethnicities, underscoring the importance of equitable diagnostic and therapeutic strategies in nAMD care.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-025-00744-8.}, }
@article {pmid41146803, year = {2025}, author = {Kominami, T and Ota, J and Takeuchi, J and Yuki, K and Ushida, H}, title = {Extensive Macular Atrophy With Pseudodrusen Complicated by Macular Neovascularization in a Japanese Patient: A Case Report.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93258}, pmid = {41146803}, issn = {2168-8184}, abstract = {Recognizing the characteristic vertically oriented atrophy, pseudodrusen distribution, and retinal pigment epithelium-Bruch's membrane separation is critical for distinguishing extensive macular atrophy with a pseudodrusen-like appearance (EMAP) from age-related macular degeneration (AMD). Early identification of neovascular complications and prompt anti-vascular endothelial growth factor therapy can stabilize macular neovascularization (MNV) and help preserve residual vision in this rare retinal disorder. To the best of our knowledge, this is the first reported case of EMAP with MNV in an Asian patient. This report aims to describe the clinical presentation, imaging features, genetic findings, and therapeutic response in a Japanese woman with EMAP complicated by MNV, which is rarely reported in Asia. A 63-year-old woman presented with decades-long nyctalopia and progressive visual loss. Fundus examination and fundus autofluorescence showed vertically oriented macular atrophy, widespread pseudodrusen, and peripheral paving-stone degeneration. Optical coherence tomography (OCT) demonstrated diffuse separation of the retinal pigment epithelium from Bruch's membrane. These findings lead to the diagnosis of EMAP. Fluorescein angiography, indocyanine green angiography, and OCT angiography revealed type 1 MNV in the left eye. Whole-exome sequencing detected no pathogenic variants associated with inherited retinal disease or AMD. The neovascular lesion was treated with intravitreal aflibercept on a treat-and-extend regimen; after seven injections, the MNV became inactive.}, }
@article {pmid41147690, year = {2025}, author = {Wang, M and Gao, FJ and Tang, W and Lei, B and Hu, F and Ma, J and Sadda, SR and Kannan, R and Sreekumar, PG and Xu, G}, title = {Deficiency of 2-Oxoglutarate Carrier (Slc25a11) Drives RPE Epithelial-to-Mesenchymal Transition and Exacerbates Subretinal Fibrosis in Neovascular Age-Related Macular Degeneration.}, journal = {Aging cell}, volume = {24}, number = {12}, pages = {e70271}, pmid = {41147690}, issn = {1474-9726}, support = {R01 EY030141/EY/NEI NIH HHS/United States ; //Keck Foundation/ ; R01EY30141/EY/NEI NIH HHS/United States ; 82101124//National Natural Science Foundation of China/ ; 82101150//National Natural Science Foundation of China/ ; }, mesh = {*Epithelial-Mesenchymal Transition/genetics ; Animals ; Mice ; Fibrosis ; *Retinal Pigment Epithelium/pathology/metabolism ; Humans ; *Macular Degeneration/pathology/metabolism/genetics ; Signal Transduction ; Mitochondria/metabolism ; Mice, Inbred C57BL ; }, abstract = {Subretinal fibrosis significantly contributes to vision loss in neovascular age-related macular degeneration (nAMD). Epithelial-to-mesenchymal transition (EMT) in RPE cells is a key early step in subretinal fibrosis. While mitochondrial dysfunction in RPE is involved, the metabolic and molecular connections between EMT and mitochondria are not well understood. This study explores the role of oxoglutarate carrier (OGC; Slc25a11) on EMT and investigates the molecular mechanisms, focusing on its role in mitochondrial metabolism and GSH transport. OGC-silenced or overexpressed ARPE-19 cells were treated with TGF-β2 (10 ng/mL) for 48 h. EMT markers, cell migration, mtGSH, and mitochondrial bioenergetics and signaling pathways were assessed. In vivo, subretinal fibrosis was induced in wild-type and OGC[+/-] mice via laser photocoagulation. Fibrosis volume was measured using optical coherence tomography and immunostaining in RPE-choroid flat mounts. OGC silencing aggravated EMT, while overexpression attenuated TGF-β2-induced EMT, cell proliferation, and migration. OGC knockdown significantly enhanced RPE EMT, as evidenced by upregulated expression of α-SMA, fibronectin, collagen type I, and Slug, while E-cadherin was downregulated. OGC overexpression improved mitochondrial bioenergetics, whereas its inhibition reduced mitochondrial respiration, which was further aggravated by co-treatment with TGF-β2. Loss of OGC promoted cell proliferation and migration through Slug-mediated EMT. OGC depletion stimulated EMT via pSmad2/3 upregulation, dependent on the PI3K/AKT signaling pathway activation. In vivo studies further demonstrate that subretinal fibrosis was significantly augmented in OGC[+/-] mice via TGF-β2-dependent PI3K signaling. In conclusion, modulating OGC expression in RPE affects EMT and mitochondrial function, making OGC a potential therapeutic target for subretinal fibrosis in nAMD.}, }
@article {pmid41147841, year = {2025}, author = {Gallagher, D and Hurley, D and O'Brien, L and Petronzi, V and Connell, P and Dooley, I}, title = {VISUAL AND ANATOMICAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION IN PATIENTS WITH SUBMACULAR HEMORRHAGES SECONDARY TO WET AGE-RELATED MACULAR DEGENERATION.}, journal = {Retinal cases &amp; brief reports}, volume = {19}, number = {6}, pages = {744-748}, doi = {10.1097/ICB.0000000000001660}, pmid = {41147841}, issn = {1937-1578}, mesh = {Humans ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Vitrectomy/methods ; *Retinal Hemorrhage/etiology/therapy/diagnosis ; Male ; Female ; *Fibrinolytic Agents/administration &amp; dosage ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/complications/diagnosis ; Aged, 80 and over ; Tomography, Optical Coherence ; Retrospective Studies ; Injections, Intraocular ; Treatment Outcome ; Middle Aged ; }, abstract = {PURPOSE: Submacular hemorrhages (SMHs) are most commonly associated with wet age-related macular degeneration and their size and duration are strong prognostic factors for visual outcome. The aim of this audit was to evaluate outcomes of direct injection of submacular tissue plasminogen activator into these lesions during pars plana vitrectomy.<br><br>METHODS: All patients presenting to the Mater Misericordiae Hospital from January 2017 to December 2019 with large submacular hemorrhages secondary to wet age-related macular degeneration who underwent this treatment were included for review. All 10 patients underwent complete pars plana vitrectomy, injection of 0.2 mL (50 &#x3bc;g) of subretinal tissue plasminogen activator, and air tamponade. Preoperative and postoperative evaluations included VA testing, optical coherence tomography, and slit lamp examination.<br><br>RESULTS: Eight patients (80%) showed improvement of their VA, with four patients achieving a VA of &#x2264;0.4 LogMAR (20/50). Six patients had a total clearing of the macular hemorrhage, with a further two patients having subtotal clearance. One patient subsequently developed a retinal detachment requiring oil tamponade.<br><br>CONCLUSION: Submacular hemorrhage secondary to wet age-related macular degeneration is a sight threatening event with a varied prognosis, but in most cases, vitrectomy with subretinal tissue plasminogen activator injection results in improved anatomical and visual outcomes.}, }
@article {pmid41148250, year = {2026}, author = {Terao, R and Kitamoto, K and Aoki, S and Totani, K and Sugiyama, S and Yamanari, M and Inoue, T and Azuma, K and Obata, R}, title = {Short-term changes in retinal pigment epithelium after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration evaluated by polarization-sensitive optical coherence tomography.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {1}, pages = {129-139}, pmid = {41148250}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology/metabolism ; Prospective Studies ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Female ; Male ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Ranibizumab/administration &amp; dosage ; Follow-Up Studies ; Fluorescein Angiography ; Fundus Oculi ; Time Factors ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: To characterize changes in retinal pigment epithelium (RPE) melanin distribution after anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study enrolled treatment-na&#xef;ve nAMD eyes with macular neovascularization (MNV) type 1 and type 2. Eyes were treated with intravitreal faricimab injection every four weeks. Visual acuity and anatomical changes were assessed with multimodal imaging. Polarization-sensitive OCT (PS-OCT) was used to examine the polarimetric entropy, quantitative indicator of melanin distribution, at the RPE segment. Retinal sensitivity was assessed with microperimetry.<br><br>RESULTS: Twelve patients with MNV type 1 and seven eyes with MNV type 2 were included. Faricimab significantly improved visual acuity and central subfield thickness (p&#x2009;=&#x2009;0.0064,&#x2009;<&#x2009;0.0001, respectively). In MNV type 1, faricimab significantly increased mean entropy in the overall Early Treatment Diabetic Retinopathy Study (ETDRS) grid area (p&#x2009;=&#x2009;0.0386). In the per-grid analysis, entropy of type 1 also significantly increased, whereas type 2 showed significant reduction (p&#x2009;=&#x2009;0.0071, 0.0389, respectively). As MNV type 2 regresses, high-entropy area corresponding to MNV decreased and low-entropy area surrounding them increased (p&#x2009;=&#x2009;0.019, 0.0058, respectively), suggesting RPE migration onto MNV. RPE entropy was significantly associated with visual acuity or retinal sensitivity after the treatment (p&#x2009;=&#x2009;0.00475, 0.0307, respectively).<br><br>CONCLUSIONS: After anti-VEGF treatment for type 1 or type 2 MNV, RPE melanin distribution at the MNV and the surrounding area distinctly changed. They were associated with visual function. The present study supported deterioration of visual function in eyes with type 2 MNV after anti-VEGF treatment resulted not only from subretinal scar formation but RPE atrophy surrounding the MNV.}, }
@article {pmid41149584, year = {2025}, author = {Fang, Y and Zheng, H and Chen, Y and Ryu, B and Qian, ZJ}, title = {A Sulfated Polysaccharide from Gelidium crinale Suppresses Oxidative Stress and Epithelial-Mesenchymal Transition in Cultured Retinal Pigment Epithelial Cells.}, journal = {Marine drugs}, volume = {23}, number = {10}, pages = {}, pmid = {41149584}, issn = {1660-3397}, mesh = {*Epithelial-Mesenchymal Transition/drug effects ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Humans ; *Polysaccharides/pharmacology/isolation &amp; purification/chemistry ; Hydrogen Peroxide/pharmacology ; Cell Line ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Macular Degeneration/drug therapy ; *Rhodophyta/chemistry ; Signal Transduction/drug effects ; NF-kappa B/metabolism ; Epithelial Cells/drug effects/metabolism ; Sulfates/pharmacology/chemistry ; Edible Seaweeds ; }, abstract = {Age-related macular degeneration (AMD) progresses to vision-threatening dry and wet forms, with no effective dry AMD treatments available. The sulfated polysaccharide (GNP, 25.8 kDa) derived from Gelidium crinale exhibits diverse biological activities and represents a potential source of novel therapeutic agents. This study employed a hydrogen peroxide (H2O2)-induced oxidative stress and epithelial-mesenchymal transition (EMT) model in retinal pigment epithelial (RPE) cells to investigate GNP's protective mechanisms against both oxidative damage and EMT. The results demonstrated that GNP effectively suppressed oxidative stress, with the 600 μg/mL dose significantly inhibiting excessive reactive oxygen species (ROS) generation to levels comparable to untreated controls. Concurrently, at concentrations of 200-600 μg/mL, GNP inhibited NF-κB signaling and increased the Bax/Bcl-2 ratio, effectively counteracting H2O2-induced oxidative damage and cell apoptosis. Furthermore, in H2O2-treated ARPE-19 cells, 600 μg/mL GNP significantly reduced the secretion of N-cadherin (N-cad), Vimentin (Vim), and α-smooth muscle actin (α-SMA), while increasing E-cadherin (E-cad) expression, consequently inhibiting cell migration. Mechanistically, GNP activated the Nrf2/HO-1 pathway, thereby mitigating oxidative stress. These findings suggest that GNP may serve as a potential therapeutic agent for dry AMD.}, }
@article {pmid41149849, year = {2025}, author = {Bennie, J and Ramsey, DJ}, title = {Navigating the Decision to Discontinue Intravitreal Injection Therapy in End-Stage Neovascular Age-Related Macular Degeneration.}, journal = {Journal of personalized medicine}, volume = {15}, number = {10}, pages = {}, pmid = {41149849}, issn = {2075-4426}, abstract = {Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of anti-VEGF therapy. Results: Long-term management of nAMD with intravitreal injections of agents targeting vascular endothelial growth factor (VEGF) is crucial for slowing progression of the disease and is generally well-tolerated. However, vision often declines as the disease progresses over time, even with treatment. This article presents strategies for aligning therapeutic goals with their expected visual outcome when an eye has reached end-stage disease. It addresses considerations for how and when to stop treatment when vision becomes limited, taking into consideration the visual status of the fellow eye and incorporating input from low vision specialists who can better assess best-corrected visual acuity (BCVA) and optimize the visual function of patients. We also acknowledge the potential benefits of switching either the dose or the agent that targets VEGF to alter the long-term visual outcome of treatment. Finally, we discuss the importance of taking into consideration related manifestations of the disease, such as macular scarring, geographic atrophy, or other retinal or optic nerve diseases which may limit vision and thus the utility of continued nAMD treatment. Conclusions: Building a strong patient-physician relationship is essential for navigating the shared decision-making process of when to stop treatment for nAMD.}, }
@article {pmid41151537, year = {2026}, author = {Lee, JK and Lee, J and Park, JB and Kim, K and Yu, SY}, title = {Topographic Progression of Geographic Atrophy and Visual Acuity in Nonexudative Age-Related Macular Degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {40}, number = {1}, pages = {1-11}, pmid = {41151537}, issn = {2092-9382}, mesh = {Humans ; *Visual Acuity/physiology ; *Geographic Atrophy/diagnosis/physiopathology/etiology ; Male ; Retrospective Studies ; Female ; *Tomography, Optical Coherence/methods ; Aged ; Disease Progression ; Follow-Up Studies ; *Fluorescein Angiography/methods ; *Macular Degeneration/complications/diagnosis/physiopathology ; Fundus Oculi ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: To investigate long-term topographic progression of the geographic atrophy (GA) area based on location and analyze its correlation with visual acuity in patient with GA secondary to non-neovascular age-related macular degeneration in South Korean patient cohort.<br><br>METHODS: Medical records and imaging data of 58 eyes from 34 patients with GA were retrospectively reviewed using fundus autofluorescence (FAF). Regions of interest were defined as concentric ring-shaped zones with diameters of 1, 2, 3, and 4 mm centered on the fovea (zones 0-3), each subdivided into superior, temporal, inferior, and nasal sectors. The foveal center was determined using optical coherence tomography, and sectoral GA areas were measured on FAF with the semiautomated software (RegionFinder ver. 2.6.2.0). Correlations among GA area enlargement, GA growth rate, and changes in best-corrected visual acuity (BCVA) were evaluated.<br><br>RESULTS: The mean GA area enlarged from 4.10 to 16.57 mm2 and mean BCVA decreased from 0.34 to 1.06 logMAR at 5 years of follow-up. The mean overall GA area growth rate was 1.96 mm2/yr. During yearly follow-up from baseline to 5 years, there were significant differences in GA growth rate of zone 3 inferior (p < 0.005). The GA area changes of zone 3 inferior was significantly correlated with BCVA. In the subgroup with BCVA decreased under 1.0 logMAR during follow-up, there was a higher growth rate in zone 2 nasal sector, 2 to 3 years before.<br><br>CONCLUSIONS: The overall GA growth rate was 1.96 mm2/yr in the 5-year follow-up of our cohort. Changes in the GA growth rate in the nasal perifoveal region (zone 2) may be associated with subsequent clinically meaningful visual decline.}, }
@article {pmid41152160, year = {2025}, author = {Chen, M and Yang, W and Xu, S and Lu, Y and Yang, Z and Li, F and Gu, Z}, title = {[Research on attention-enhanced networks for subtype classification of age-related macular degeneration in optical coherence tomography].}, journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi}, volume = {42}, number = {5}, pages = {901-909}, pmid = {41152160}, issn = {1001-5515}, mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/classification/diagnostic imaging ; *Neural Networks, Computer ; }, abstract = {Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.}, }
@article {pmid41153254, year = {2025}, author = {Al-Khersan, H and Sodhi, SK and Cao, JA and Saju, SM and Pattathil, N and Zhou, AW and Choudhry, N and Russakoff, DB and Oakley, JD and Boyer, D and Wykoff, CC}, title = {Deep Learning-Based Segmentation of Geographic Atrophy: A Multi-Center, Multi-Device Validation in a Real-World Clinical Cohort.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {20}, pages = {}, pmid = {41153254}, issn = {2075-4418}, abstract = {Background: To report a deep learning-based algorithm for automated segmentation of geographic atrophy (GA) among patients with age-related macular degeneration (AMD). Methods: Validation of a deep learning algorithm was performed using optical coherence tomography (OCT) images from patients in routine clinical care diagnosed with GA, with and without concurrent nAMD. For model construction, a 3D U-Net architecture was used with the output modified to generate a 2D mask. Accuracy of the model was assessed relative to the manual labeling of GA with the Dice similarity coefficient (DSC) and correlation r[2] scores. Results: The OCT data set included 367 scans from the Spectralis (Heidelberg, Germany) from 55 eyes in 33 subjects; 267 (73%) scans had concurrent nAMD. In parallel, 348 scans were collected using the Cirrus (Zeiss), from 348 eyes in 326 subjects; 101 (29%) scans had concurrent nAMD. For Spectralis data, the mean DSC score was 0.83 and r[2] was 0.91. For Cirrus data, the mean DSC score was 0.82 and r[2] was 0.88. Conclusions: The reported deep learning algorithm demonstrated strong agreement with manual grading of GA secondary to AMD on the OCT data set from routine clinical practice. The model performed well across two OCT devices as well as amongst patients with GA with concurrent nAMD, suggesting applicability in the clinical space.}, }
@article {pmid41153266, year = {2025}, author = {Perkins, SW and Shah, N and Whitney, J and Matar, K and Yu, HJ and Wykoff, CC and Ehlers, JP}, title = {Radiomic Characterization and Automated Classification of Drusen Substructure Phenotype Associated with High-Risk Dry Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {20}, pages = {}, pmid = {41153266}, issn = {2075-4418}, support = {T32 EY024236/EY/NEI NIH HHS/United States ; T32EY024236/NH/NIH HHS/United States ; }, abstract = {Background/Objectives: Optical coherence tomography (OCT)-reflective drusen substructures (ODSs) are associated with the conversion of intermediate AMD to geographic atrophy (GA). However, ODSs must be manually identified, a laborious process introducing bias and variation. This study proposes objective radiomic metrics of drusen phenotypes and validates them for the prediction of GA development and GA growth rate. Methods: A total of 104 drusen with high-reflective cores (H-type), 105 with low-reflective cores (L-type), 129 conical drusen (C-type), and 101 normal drusen (N-type) were segmented from OCT images. Radiomic features were extracted from these drusen, and the most important features for drusen classification were extracted from the retinal pigment epithelium-Bruch's membrane compartment of 743 OCT scans of eyes with dry AMD and used to predict GA conversion and fast growth. Results: Radiomic features classified drusen phenotypes with AUC = 0.87-0.95. H-type drusen have a higher reflectivity, greater variation in reflectivity, and coarser texture (p < 0.001). L-type drusen have a lower reflectivity and greater variation in reflectivity (p < 0.0001). C-type drusen have a less spherical shape and more disordered internal reflectivity (p < 0.001). N-type drusen have a more spherical shape and more uniform internal reflectivity (p < 0.001). These radiomic features predict the conversion from intermediate AMD to GA and top-quartile GA growth rate with AUC = 0.59-0.74 at years 1-3. Conclusions: These results demonstrate the potential of clinical phenotype-grounded radiomics for objective automated drusen analysis, GA risk stratification, and clinical prediction.}, }
@article {pmid41153316, year = {2025}, author = {Romero-Oraá, R and Herrero-Tudela, M and López, MI and Hornero, R and Romero-Aroca, P and García, M}, title = {An Ensemble Model for Fundus Images to Aid in Age-Related Macular Degeneration Grading.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {20}, pages = {}, pmid = {41153316}, issn = {2075-4418}, support = {TED2021-131913B-I00//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; PID2023-148895OB-I00//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; TED2021-131913B-I00//European Regional Development Fund/ ; PID2023-148895OB-I00//European Regional Development Fund/ ; Instituto de Salud Carlos III//Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine/ ; PIF-UVa//Universidad de Valladolid/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly population. Periodic examinations through fundus image analysis are paramount for early diagnosis and adequate treatment. Automatic artificial intelligence algorithms have proven useful for AMD grading, with the ensemble strategies recently gaining special attention. Methods: This study presents an ensemble model that combines 2 individual models of a different nature. The first model was based on the ResNetRS architecture and supervised learning. The second model, known as RETFound, was based on a visual transformer architecture and self-supervised learning. Results: Our experiments were conducted using 149,819 fundus images from the Age-Related Eye Disease Study (AREDS) public dataset. An additional private dataset of 1679 images was used to validate our approach. The results on AREDS achieved a quadratic weighted kappa of 0.7364 and an accuracy of 66.03%, which outperforms the previous methods in the literature. Conclusions: The ensemble strategy presented in this study could be useful for the screening of AMD in a clinical setting. Consequently, eye care for AMD patients would be improved while clinical costs and workload would be reduced.}, }
@article {pmid41154560, year = {2025}, author = {Mimura, T and Noma, H}, title = {Title Oxidative Stress in Age-Related Macular Degeneration: From Molecular Mechanisms to Emerging Therapeutic Targets.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {41154560}, issn = {2076-3921}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, and oxidative stress, primarily mediated by reactive oxygen species (ROS), is widely recognized as a central driver of its onset and progression. The retina is highly susceptible to oxidative damage due to its elevated oxygen consumption, abundant polyunsaturated fatty acids, and continuous exposure to light. Recent studies have elucidated molecular mechanisms in which mitochondrial dysfunction, disruption of redox homeostasis, inflammation, and complement activation interact to promote degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. In addition to age-related oxidative stress, environmental factors such as motor vehicle exhaust and volatile organic compounds (VOCs) can accelerate the accumulation of lipofuscin and drusen, thereby fostering a chronic pro-inflammatory milieu. From a therapeutic perspective, beyond conventional antioxidant supplementation, emerging strategies targeting oxidative stress-related pathways have gained attention, including mitochondrial protectants, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, anti-inflammatory agents, and gene therapy. Importantly, several innovative approaches are under investigation, such as saffron supplementation with neuroprotective properties, drug repositioning of levodopa, and nanotechnology-based delivery systems to enhance retinal bioavailability of antioxidants and gene therapies. This review summarizes the pathophysiological role of oxidative stress in AMD from a molecular mechanistic perspective and discusses recent advances in research and novel therapeutic targets.}, }
@article {pmid41155071, year = {2025}, author = {Barthelemy, N and Sridhar, J and Sengillo, JD}, title = {Gene Therapy for Wet Age-Related Macular Degeneration.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {41155071}, issn = {2306-5354}, abstract = {The prevalence of wet age-related macular degeneration (AMD) in the US is expected to increase to 82 million by 2050. Addressing the specialized needs for this population will become increasingly challenging as prevalence rises. Frequent anti-vascular endothelial growth factor (anti-VEGF) injections have been the recourse for this population; however, the burden wet AMD places on patients underscores the critical need for durable therapeutic approaches. Gene therapy is a bioengineered treatment that has transformed the management of previously untreatable disorders. Ongoing advancements and refinements in its biomechanism could lead to more sustainable treatment options for wet AMD. In this article, we provide recent updates on gene therapy trials for wet AMD.}, }
@article {pmid41155120, year = {2025}, author = {Patel, MJ and Sheth, S and Mar, J and Gregori, NZ and Sengillo, JD}, title = {Surgical Approaches to Retinal Gene Therapy: 2025 Update.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {41155120}, issn = {2306-5354}, abstract = {Gene therapy offers a promising new frontier in the treatment of inherited and acquired retinal disease. This review describes the current surgical delivery approaches for gene therapy to the retina-subretinal, suprachoroidal, and intravitreal-and provides an update on the state of the art for each method in 2025.}, }
@article {pmid41155961, year = {2025}, author = {Hassan, MSA and Zhong, C and Hassan, F and Li, SK}, title = {Targeting the Eye: RNA-Based Therapies, Interferences, and Delivery Strategies.}, journal = {Pharmaceutics}, volume = {17}, number = {10}, pages = {}, pmid = {41155961}, issn = {1999-4923}, support = {R01 EY031452/EY/NEI NIH HHS/United States ; R01EY031452/EY/NEI NIH HHS/United States ; }, abstract = {Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic and molecular pathways involved in eye disorders. In addition to their potential in therapy, RNA technologies have also provided tools for mechanistic studies to improve the understanding of eye diseases, expanding the possibilities of RNA-based treatments. Despite the utility of RNA in studying eye disease mechanisms and its potential in disease treatment, only a few RNA-based therapies have been approved for posterior eye diseases. This paper reviews RNA interference and related ocular delivery and posterior eye diseases, focusing on the use of RNA aptamers, siRNA, short hairpin RNA (shRNA), and microRNA (miRNA). Approaches using RNA to advance our understanding of eye diseases and disease treatments, particularly in the posterior segment of the eye, are discussed. It is concluded that RNA therapeutics offer a novel approach to treating a variety of eye diseases by targeting their molecular causes. siRNA, shRNA, miRNA, and ASO can directly silence disease-driving genes, while RNA aptamers bind to specific targets. Although many RNA-based therapies are still in experimental stages, they hold promise for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, and inherited retinal disorders. Effective delivery methods and long-term safety are key challenges that need to be addressed for these treatments to become widely available.}, }
@article {pmid41156023, year = {2025}, author = {Yu, HS and Cho, H and Shin, YU and Hong, EH and Koh, SH}, title = {Protective Effect of Curcumin in Oxidative Stress-Induced Injury on Retinal Pigment Epithelial Cells.}, journal = {Journal of clinical medicine}, volume = {14}, number = {20}, pages = {}, pmid = {41156023}, issn = {2077-0383}, support = {2020R1A2C1010229//National Research Foundation of Korea/ ; 2021R1I1A1A01059690//National Research Foundation of Korea/ ; 202400000000843//Hanyang University/ ; }, abstract = {Background/Objectives: Oxidative stress is the major cause of retinal pigment epithelial cell death. We used oxidative stress-injured retinal pigment epithelial cells to investigate the protective effects of curcumin, a strong antioxidant, on the Nod-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: To evaluate the effect of curcumin, cell viability was measured with cell counting kit-8 and lactate dehydrogenase assays. Hydrogen peroxide (H2O2)-injured ARPE-19 cells were treated with different curcumin concentrations. We performed a wound healing assay and dichlorodihydrofluorescein diacetate staining. Western blotting and immunofluorescence staining were performed to evaluate the changes in inflammasome levels in the ARPE-19 cells. Result: H2O2 (300 μM) reduced the viability of ARPE-19 cells. However, treatment with 7.5 μM curcumin enhanced ARPE-19 cell viability and reduced cell toxicity. Curcumin also reduced reactive oxygen species (ROS) levels in the H2O2-induced damaged ARPE-19 cells and attenuated the H2O2-dependent levels of the NLRP3 inflammasome and its related signaling proteins. Conclusions: Curcumin demonstrated protective effects against oxidative stress in retinal pigment epithelial cells by attenuating the activation of the NLRP3 inflammasome pathway. These findings suggest the therapeutic potential of curcumin as an anti-inflammatory and antioxidant agent for macular degeneration.}, }
@article {pmid41156127, year = {2025}, author = {Nishiyama, T and Hirai, H and Miyata, K and Nishi, T and Ueda, T and Kase, S}, title = {A Pilot Study on Structural Changes of Choroidal Vasculature Following Intravitreal Anti-VEGF Injection in Neovascular Age-Related Macular Degeneration: Faricimab vs Ranibizumab.}, journal = {Journal of clinical medicine}, volume = {14}, number = {20}, pages = {}, pmid = {41156127}, issn = {2077-0383}, abstract = {Objectives: This paper aims to explore optical coherence tomography (OCT)-based choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents, faricimab and ranibizumab, in a pilot study. Methods: This retrospective pilot cohort study enrolled 28 treatment-naïve nAMD patients who received three consecutive intravitreal anti-VEGF injections at Nara Medical University Hospital. In total, 17 patients (61%) were Type 1 MNV and 11 patients (39%) were Type 2 MNV. Patients were divided into a faricimab group (13 eyes) and a ranibizumab group (15 eyes). The type of macular neovascularization (MNV) and the presence of polyps were recorded. The central choroidal thickness (CCT) and the ratio of luminal area to choroidal area (L/C ratio), derived from binarized OCT images, were measured at baseline after the first and third injections. Results: Type 1 MNV was observed in 61% of eyes, with polyps confirmed in 53%. There was no significant difference in best corrected visual acuity (BCVA) for both faricimab and ranibizumab during treatment (p = 0.12, 0.94, respectively). After the third injection, a dry macula was achieved in 62% of the faricimab group and 60% of the ranibizumab group. In the ranibizumab group, CCT significantly decreased after the first injection, while no significant change was observed in the faricimab group. Conversely, the L/C ratio significantly decreased in the faricimab group after the third injection (p = 0.010). Among faricimab-treated eyes, those with type 1 MNV showed a significantly greater reduction in the L/C ratio compared to type 2 MNV (p = 0.017). Conclusions: This pilot study suggests that faricimab may exert combined anti-VEGF and Ang-2 effects predominantly on type 1 MNV, potentially leading to vascular constriction. These exploratory findings warrant confirmation in larger studies.}, }
@article {pmid41156216, year = {2025}, author = {Kucharczuk, J and Kasprzak, H and Gawęcki, M}, title = {Switching from Aflibercept to Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration: Short-Term Results from Real-Life Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {20}, pages = {}, pmid = {41156216}, issn = {2077-0383}, abstract = {Purpose: To evaluate anatomical and functional outcomes after switching from aflibercept to faricimab in patients with neovascular age-related macular degeneration (nAMD) with suboptimal response. Methods: This retrospective study included 72 eyes of 66 patients with nAMD previously treated with intravitreal aflibercept using a treat-and-extend regimen. Indications for switching included persistent retinal fluid, pigment epithelial detachment (PED), lack of best-corrected visual acuity (BCVA) improvement, or inability to extend treatment intervals beyond four weeks. Patients received three monthly loading doses of faricimab followed by individualized 8- to 16-week dosing. Follow-up comprised six visits over a mean of 8.5 ± 1.4 months. Outcomes included BCVA (logMAR), retinal morphology (subretinal fluid-SRF; intraretinal fluid-IRF; pigment epithelial detachment-PED), central subfoveal thickness (CST), and treatment interval changes. Results: Switching to faricimab led to significant short-term anatomical improvement, primarily reduction in subretinal fluid (p < 0.0001), with maximal effect during the loading phase. Resolution of SRF was significant at the end of the follow up; however, IRF changes were transient and not sustained beyond three months. PED reduction reached borderline significance (p = 0.0455). CST decreased during the loading phase (p < 0.0001) but returned to baseline thereafter. BCVA improved only after loading (p = 0.0287) but not at final follow-up. Treatment intervals were extended by a mean of ~2 weeks (p < 0.0001), increasing in 80% of eyes. Eyes with fewer prior injections and better baseline BCVA achieved superior final visual outcomes. Conclusions: Switching to faricimab provides short-term anatomical benefits and treatment-interval extension without sustained visual gain. Functional improvements tended to be greater in patients with fewer injections and shorter treatment duration prior to switch.}, }
@article {pmid41156523, year = {2025}, author = {Pieńczykowska, K and Bryl, A and Mrugacz, M}, title = {The Impact of a High-Fat Diet on Eye Health.}, journal = {Nutrients}, volume = {17}, number = {20}, pages = {}, pmid = {41156523}, issn = {2072-6643}, mesh = {Humans ; *Diet, High-Fat/adverse effects ; Oxidative Stress ; Fatty Acids, Omega-3/administration &amp; dosage ; *Eye Diseases/etiology ; Lipid Metabolism ; Dietary Supplements ; Inflammation/etiology ; Retina/metabolism ; Animals ; *Eye ; Retinal Pigment Epithelium/metabolism ; }, abstract = {Background: The increasing prevalence of high-fat diets is associated with a rise in metabolic and neurodegenerative diseases. The retina and retinal pigment epithelium are metabolically active tissues exposed to oxidative stress, making them particularly vulnerable to lipid excess. Materials and Methods: A systematic literature review was conducted covering years until 2025 inclusive. Results: High-fat diets lead to cholesterol accumulation and lipid metabolism disturbances in the retina, retinal pigment epithelium, and ocular vessels. They activate inflammatory and oxidative stress pathways, resulting in structural and functional damage. Omega-3 deficiency exacerbates inflammation, while supplementation improves the tear film stability, corneal epithelial function, intraocular pressure regulation, and exerts neuroprotective effects. Conclusions: High-fat diets represent a significant risk factor for ocular diseases by disrupting lipid metabolism, enhancing inflammation, and inducing oxidative stress. Omega-3 fatty acid supplementation reduces inflammation and supports ocular functions.}, }
@article {pmid41157186, year = {2025}, author = {Chujo, S and Chung, YC and Quarta, A and Kwak, H and Soylu, C and Abbasgholizadeh, R and Alhelaly, M and Rattu, R and Corradetti, G and Nittala, MG and Sadda, SR}, title = {Improving OCTA Visualization of Macular Neovascularization via a Grayscale Inversion Method.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, pmid = {41157186}, issn = {2075-1729}, abstract = {BACKGROUND: Age-related macular degeneration is a major cause of vision loss, and improved visualization of macular neovascularization (MNV) on OCT angiography (OCTA) could enhance clinical assessment. This study aimed to establish a simple and accessible image enhancement method.<br><br>METHODS: We retrospectively analyzed 24 eyes from 22 patients with MNV at the Doheny UCLA Eye Centers. Grayscale-inverted OCTA images were generated using the basic "Invert" function in ImageJ 1.51 23. Each original and inverted image pair was assessed for seven MNV-related features: structure and area within 3 &#xd7; 3 mm, 6 &#xd7; 6 mm and 12 &#xd7; 12 mm scans, and presence of polypoidal lesions. Twenty-one ophthalmologists graded visibility using a standardized five-point scale. Paired comparisons were performed using the Wilcoxon signed-rank test.<br><br>RESULTS: Grayscale inversion significantly improved the visualization of MNV structure in 6 &#xd7; 6 mm scans (mean difference: +0.67 &#xb1; 1.02; p = 0.008), 12 &#xd7; 12 mm scans (+0.62 &#xb1; 1.07; p = 0.013), and detection of polypoidal lesions (+0.43 &#xb1; 0.98; p = 0.030). No significant differences were found for 3 &#xd7; 3 mm structure (p = 0.793) or area-related features (all p > 0.3).<br><br>CONCLUSIONS: Grayscale inversion may enhance MNV visibility and polypoidal lesion detection on OCTA. As this study relied solely on subjective assessments, future work should incorporate quantitative image analysis.}, }
@article {pmid41157282, year = {2025}, author = {Iliadis, I and Pechnikova, NA and Poimenidou, M and Almaliotis, DD and Tsinopoulos, I and Yaremenko, TV and Yaremenko, AV}, title = {Applications of Modern Cell Therapies: The Latest Data in Ophthalmology.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, pmid = {41157282}, issn = {2075-1729}, abstract = {Cell-based therapeutics are redefining interventions for vision loss by enabling tissue replacement, regeneration, and neuroprotection. This review surveys contemporary cellular strategies in ophthalmology through the lenses of therapeutic effectiveness, translational readiness, and governance. We profile principal sources-embryonic and induced pluripotent stem cells, mesenchymal stromal cells, retinal pigment epithelium, retinal progenitor and limbal stem cells-and enabling platforms including extracellular vesicles, encapsulated cell technology and biomaterial scaffolds. We synthesize clinical evidence across age-related macular degeneration, inherited retinal dystrophies, and corneal injury/limbal stem-cell deficiency, and highlight emerging applications for glaucoma and diabetic retinopathy. Delivery routes (subretinal, intravitreal, anterior segment) and graft formats (single cells, sheets/patches, organoids) are compared using standardized structural and functional endpoints. Persistent barriers include GMP-compliant derivation and release testing; differentiation fidelity, maturation, and potency; genomic stability and tumorigenicity risk; graft survival, synaptic integration, and immune rejection despite ocular immune privilege; the scarcity of validated biomarkers and harmonized outcome measures and ethical, regulatory, and health-economic constraints. Promising trajectories span off-the-shelf allogeneic products, patient-specific iPSC-derived grafts, organoid and 3D-bioprinted tissues, gene-plus-cell combinations, and cell-free extracellular-vesicle therapeutics. Overall, cell-based therapies remain investigational. With adequately powered trials, methodological harmonization, long-term surveillance, scalable xeno-free manufacturing, and equitable access frameworks, they may eventually become standards of care; at present, approvals are limited to specific products/indications and regions, and no cell therapy is the standard of care for retinal disease.}, }
@article {pmid41158172, year = {2025}, author = {Guo, YJ and Chen, ZQ and Zhao, J}, title = {Integrating plasma proteomics and genome-wide association data to identify therapeutic targets for retinal neurodegenerative diseases in Europeans.}, journal = {International journal of ophthalmology}, volume = {18}, number = {11}, pages = {2170-2182}, pmid = {41158172}, issn = {2222-3959}, abstract = {AIM: To employ proteome-wide Mendelian randomization (MR) to explore novel protein and drug targets for retinal neurodegenerative diseases (RND) in individuals of European ancestry.<br><br>METHODS: This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND, with protein data derived from two independent large-scale proteomics datasets. Potential drug targets were identified using Bayesian colocalization, followed by MR analysis, sensitivity testing, and external validation. Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.<br><br>RESULTS: The study identified six promising protein targets, each successfully replicated at least twice. The results included three proteins related to diabetic retinopathy (ICAM1, GCKR, WARS), two proteins related to age-related macular degeneration (WARS, BRD2), and two proteins related to glaucoma (SVEP1, NPTXR). Additionally, drug prediction and molecular docking indicated that five drugs (fenofibrate, trofinetide, ticagrelor, lifitegrast, acetaminophen) effectively bound to the target proteins.<br><br>CONCLUSION: This study identified six potential protein targets for RND and five existing drugs with therapeutic potential. By integrating plasma proteomics with genetic data, it provides a cost-effective framework for drug discovery.}, }
@article {pmid41158183, year = {2025}, author = {Ai, LQ and Zhu, LY and Yang, H and Ye, J}, title = {Critical role of lipid metabolism in axial myopia development.}, journal = {International journal of ophthalmology}, volume = {18}, number = {11}, pages = {2195-2204}, pmid = {41158183}, issn = {2222-3959}, abstract = {The global prevalence of myopia is becoming increasingly severe, with epidemiological models predicting that by 2050, approximately 50% of the world's population will be affected by myopia, and about 10% will suffer from high myopia. The incidence of high myopia is projected to increase fivefold, making it the leading cause of irreversible vision impairment. Myopia often leads to various complications and has been associated with other ocular diseases, including early-onset cataracts, age-related macular degeneration, and primary open angle glaucoma. As a result, the control and management of myopia have become ongoing and long-term research priorities. The pathogenesis of myopia involves complex multisystem interactions. Current mainstream theories focus primarily on choroidal hypoxia-induced scleral remodeling, with neurotransmitters such as acetylcholine and dopamine playing regulatory roles. However, recent studies have increasingly suggested that changes in nutritional intake, including proteins, fats, and cholesterol, may also be related to myopia development. The role of lipid metabolism in the onset and progression of myopia has gradually attracted growing attention. Therefore, this review aims to systematically elucidate the molecular mechanisms of lipid metabolism regulatory networks in axial myopia, integrating multidimensional factors to provide a theoretical foundation for precision intervention strategies.}, }
@article {pmid41158184, year = {2025}, author = {Kananen, F}, title = {Treatment results switching from aflibercept to bevacizumab in wet age-related macular degeneration.}, journal = {International journal of ophthalmology}, volume = {18}, number = {11}, pages = {2116-2121}, pmid = {41158184}, issn = {2222-3959}, abstract = {AIM: To examine effects of switching intravitreal aflibercept to bevacizumab in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Data from patients treated for nAMD with anti-vascular endothelial growth factor (VEGF) injections at &#xd6;rebro University Hospital between January 2014 and June 2020, were extracted from the Swedish macular register (SMR). A total of 230 eyes were included in the study: 116 in the study/bevacizumab switch group and 114 in the control/aflibercept group. Central retinal thickness (CRT) was measured at baseline and after 2y. Primary outcome was mean change in best corrected visual acuity (BCVA) between baseline and 2y. Secondary outcome variables included proportion of patients with a clinically significant change in BCVA [increase or decrease of &#x2265;15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters], mean change in CRT, number of anti-VEGF injections, number of visits assessing disease activity and number of visits with active disease.<br><br>RESULTS: The mean difference in BCVA between baseline and 2y was 1.13&#xb1;14.47 ETDRS letters in the bevacizumab switch group and 1.81&#xb1;13.01 ETDRS letters in the aflibercept group. The lower bound of the 95% confidence interval of the difference in BCVA was -4.25, indicating non-inferiority within a 5 ETDRS letter limit. No significant differences in mean change of CRT between baseline and 2y were detected (study -185.9&#xb1;167.0 versus control -149.4&#xb1;193.1 &#xb5;m, P=0.127). The distribution of clinically significant improvement (P=0.598) or worsening (P=0.508) of BCVA during follow-up did not show statistically significant differences between groups. The number of anti-VEGF injections administered (study 12.76&#xb1;2.20 versus control 13.10&#xb1;4.20, P=0.442), the number of visits assessing disease activity (P=0.301), and the number of visits with active disease (P=0.065) did not show differences between subjects receiving bevacizumab and aflibercept treatment. No significant differences were detected in baseline characteristics between the study and control groups, including age, BCVA, CRT, neovascular membrane type or location, duration of symptoms or prior cataract surgery.<br><br>CONCLUSION: Switching to off-label bevacizumab in patients responding to initial aflibercept treatment is non-inferior to continued aflibercept treatment with respect to change in visual acuity at 2y. Switching anti-VEGF from aflibercept to bevacizumab may be a viable option in clinical settings with limited resources.}, }
@article {pmid41158821, year = {2025}, author = {Sanfelippo, WA and Oley, M and Harrelson, H and Vilar, N}, title = {Artery of Percheron infarct with multiple cranial nerve palsies and Horner Syndrome.}, journal = {American journal of ophthalmology case reports}, volume = {40}, number = {}, pages = {102458}, pmid = {41158821}, issn = {2451-9936}, abstract = {PURPOSE: To report a case of a rare stroke variant involving the artery of Percheron leading to ocular motility compromise.<br><br>OBSERVATIONS: A 65-year-old man presented to the neuro-ophthalmology clinic with multiple cranial nerve palsies and Horner Syndrome. He was three weeks post-thrombolytic therapy to treat an ischemic stroke, and his pertinent medical history consisted of hyperlipidemia and macular degeneration. On physical exam, the patient experienced bilateral vertical gaze paresis, incomplete left Horner syndrome, right-sided cranial nerve VI palsy, and partial left-sided cranial nerve VII palsy. Based on the infarction patterns demonstrated on MRI, the patient was diagnosed with an artery of Percheron infarct.<br><br>CONCLUSIONS AND IMPORTANCE: The artery of Percheron is a rare variant of posterior cerebral circulation that supplies both paramedian thalamic zones in addition to variably supplying the midbrain. Overall, this case highlights the importance of considering rare anatomical variants when working up ophthalmic deficits in a stroke patient. Early diagnosis can lead to adequate therapy and prevent complications in the future.}, }
@article {pmid41159651, year = {2025}, author = {Gorski, M and Grunin, M and Herold, JM and Fröhlich, B and Behr, M and Wheeler, N and Bush, WS and Song, YE and Zhu, X and Blanton, SH and Pericak-Vance, MA and Heid, IM and Haines, JL and , }, title = {Diverse-Ancestry GWAS of Age-Related Macular Degeneration on 16,108 Examined Cases and 18,038 Controls.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {13}, pages = {51}, pmid = {41159651}, issn = {1552-5783}, support = {R01 EY012118/EY/NEI NIH HHS/United States ; R01 EY022310/EY/NEI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; Complement Factor H/genetics ; *Genetic Predisposition to Disease/ethnology ; *Genome-Wide Association Study ; *Macular Degeneration/ethnology/genetics ; *Polymorphism, Single Nucleotide ; *Population Groups/ethnology/genetics ; }, abstract = {PURPOSE: In 2016, the International Age-related Macular Degeneration Genomics Consortium analyzed data from approximately 50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD (adAMD) in individuals of European ancestry and did not include diverse ancestries, fine-mapping per ancestry, or a predictive model with/without the contributions of one lead genetic risk locus, CFH. Therefore, we analyzed full cross-ancestry IAMDGC data, utilizing the newest imputation panel, and identified genetic risk loci across and between ancestries contributing to AMD.<br><br>METHODS: In this IAMDGC 2.0 analysis, we included cross-ancestry data via custom exome chip imputed genome-wide via TOPMedv2, in 16,108 ophthalmologically confirmed adAMD cases and 18,038 examined AMD-free controls. We included both male and female subjects and four diverse ancestries. Data were analyzed from June 2021 to May 2024.<br><br>RESULTS: Utilizing diverse ancestry data (cases/controls&#xa0;=&#xa0;15,616/16,723 European, 50/357 African, 207/322 Asian, and 235/636 Other), we identified 28 loci at P&#xa0;<&#xa0;5 &#xd7; 10-8, including 2 additional AMD loci compared to IAMDGC 1.0 (SERPINA1 and CPN1). Fine-mapping supported one ancestry-shared signal around HTRA1/ARMS2 and nine signals around CFH without African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score without CFH predicted adAMD in all ancestries (area under the curve [AUC] = 0.80/0.75, 0.65/0.64, and 0.80/0.79, respectively).<br><br>CONCLUSIONS: Our results indicate that the genetic underpinning of adAMD is mostly shared between ancestries. We also identify the CFH variant as being less relevant in specific ancestries, indicating a difference in pathogenic burden between ancestries. We increased the available genomic data for AMD over 300-fold with the IAMDGC 2.0 imputation, making it a valuable resource for further AMD genetic analysis.}, }
@article {pmid41160616, year = {2025}, author = {Jia, S and Liu, Q and Liu, P and Zhao, W and Li, S}, title = {Association of perchlorate, nitrate, and thiocyanate with age-related macular degeneration in the United States.}, journal = {PloS one}, volume = {20}, number = {10}, pages = {e0334919}, pmid = {41160616}, issn = {1932-6203}, mesh = {Humans ; *Nitrates/urine/adverse effects ; *Thiocyanates/urine/adverse effects ; Female ; Male ; United States/epidemiology ; Middle Aged ; *Macular Degeneration/epidemiology/chemically induced/urine ; Aged ; *Perchlorates/urine/adverse effects ; Adult ; Nutrition Surveys ; Risk Factors ; }, abstract = {Perchlorate, nitrate, and thiocyanate are endocrine-disrupting chemicals, but their associations with AMD is unclear. This study aims to investigate this relationship. We included 4727 participants aged 40 years and older from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) were applied to investigate the single, non-linear, and combined effects on AMD risk. Nitrate exposure was positively associated with any AMD risk (OR Any AMD, 1.19; 95% CI, 1.05-1.35; P = 0.010) and early AMD risk (OR Early AMD, 1.19; 95% CI, 1.05-1.36; P = 0.010); compared to the first quartile, the highest quartile of nitrate (OR, 1.94; 95% CI, 1.18-3.19; P = 0.012) and thiocyanate (OR, 1.70; 95% CI, 1.19-2.42; P = 0.006) levels were positively associated with AMD risk. The results of RCS showed a nonlinear relationship between nitrate exposure (P for nonlinearity = 0.020), thiocyanate (P for nonlinearity = 0.041), and AMD risk. WQS analysis indicated a positive relationship between mixed exposure and AMD risk (OR, 1.24; 95% CI, 1.01 to 1.51; P = 0.037). This study indicated that high urinary nitrate and thiocyanate levels were associated with an increased AMD risk among US adults. However, the cross-sectional design precludes causal inference.}, }
@article {pmid41162371, year = {2025}, author = {Amirkavei, M and Kaikkonen, O and Turunen, T and Meller, A and Åhlgren, J and Kvanta, A and André, H and Koskelainen, A}, title = {Non-damaging laser treatment with electroretinography-based thermal dosimetry activates hormetic heat response in pig retinal pigment epithelium.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9533}, pmid = {41162371}, issn = {2041-1723}, mesh = {Animals ; *Retinal Pigment Epithelium/radiation effects/metabolism/pathology ; *Electroretinography/methods ; Swine ; Male ; *Heat-Shock Response/physiology ; *Laser Therapy/methods ; Autophagy/radiation effects ; Apoptosis/radiation effects ; Oxidative Stress ; Retina ; Lasers ; Hot Temperature ; Heat-Shock Proteins/metabolism ; }, abstract = {Enhancing protein homeostasis and antioxidant defense mechanisms in the retinal pigment epithelium (RPE) holds significant promise as a treatment option for various retinal diseases, including age-related macular degeneration. However, patient responses to laser-induced RPE hyperthermia varies substantially. To address this, we introduce a focal electroretinography (fERG)-based method for retinal temperature monitoring during laser exposure. Applying the method to anaesthetized male pigs in vivo, we study the biological effects of controlled retinal hyperthermia. Our findings reveal that temperature elevation to 44 °C with 60-second laser exposure triggers heat shock protein production and autophagy activation in RPE/choroid while avoiding oxidative stress, apoptosis, and structural damage. Importantly, our results demonstrate that visible lesions occur at temperatures above 48 °C, and that the temperature determination precision was 0.6 °C. These outcomes highlight that fERG-controlled retinal laser treatment enables reliable and safe activation of cytoprotective mechanisms in the RPE, providing a promising new therapeutic approach.}, }
@article {pmid41162502, year = {2025}, author = {Luo, M and Zhang, M and Xing, Z and Yu, W and Lv, H}, title = {Mechanistic analysis of luteolin in mitigating dry age-related macular degeneration through network pharmacology and experimental validation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {37862}, pmid = {41162502}, issn = {2045-2322}, support = {2024ZYD0114//Sichuan Provincial Department of Science and Technology/ ; S2024001//Sichuan Medical Association/ ; }, mesh = {*Luteolin/pharmacology/chemistry ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; Molecular Docking Simulation ; *Network Pharmacology ; Cell Survival/drug effects ; Protein Interaction Maps/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; Retinal Pigment Epithelium/drug effects/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Iodates ; }, abstract = {Dry age-related macular degeneration (AMD) ranks among the primary causes of irreversible vision loss in the elderly. Luteolin, with its diverse biological activities, has attracted significant attention as a promising candidate for intervening in dry AMD. Explore the protective effect of luteolin on dry AMD to address the unmet need for current therapeutic agents. Luteolin's target information and dry AMD-related genes were retrieved from public databases. Shared targets of luteolin and dry AMD were used to construct a protein‒protein interaction network, followed by Gene Ontology and pathway enrichment analyses. Finally, molecular docking between the active ingredient and core targets was validated. In vitro, sodium iodate was used to induce ARPE-19 cells, after which cell viability was analyzed via a Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential were detected via fluorescent dye staining. In the network pharmacology analysis, a total of 213 potential therapeutic targets associated with luteolin's activity against dry AMD were identified. Among these genes, TP53, TNF, IL6, AKT1, BCL2, STAT3, JUN, and CASP3 were identified as core therapeutic targets. These targets are primarily involved in pathways including lipid and atherosclerosis, cancer-related pathways, and the AGE-RAGE signaling pathway in diabetic complications. Molecular docking analyses revealed strong binding affinities between luteolin and the core targets, validating the molecular mechanisms underlying luteolin's efficacy against dry AMD. Experimental data demonstrated that luteolin not only mitigated sodium iodate-induced reductions in ARPE-19 cell viability but also decreased intracellular ROS levels and restored mitochondrial membrane potential. Luteolin effectively enhances the viability of damaged RPE cells, reduces oxidative stress levels, and protects mitochondrial function. This protective effect is likely mediated through the coordinated action of multiple targets and pathways, highlighting luteolin's promising potential in the prevention and management of dry AMD. However, this study is limited by its sole reliance on in vitro cell validation and inability to fully reflect real in vivo effects and potential side effects.}, }
@article {pmid41162529, year = {2025}, author = {Misson, GP and Anderson, SJ and Armstrong, RA and Heitmar, R}, title = {A novel computational model for human macular pigment optical density and its relationship to foveal structure.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {37865}, pmid = {41162529}, issn = {2045-2322}, mesh = {Humans ; *Macular Pigment/metabolism ; *Fovea Centralis/diagnostic imaging/metabolism ; Tomography, Optical Coherence ; Female ; Male ; Macular Degeneration/metabolism/diagnostic imaging ; Aged ; Middle Aged ; *Computer Simulation ; Xanthophylls/metabolism ; Macula Lutea/metabolism ; }, abstract = {Macular pigment optical density (MPOD) models enhance understanding of macular xanthophyll distribution, particularly relevant to age-related macular degeneration. This study investigates an existing model and introduces a novel, more accurate and biologically relevant approach. MPOD spatial profiles of 48 eyes were obtained using dual-wavelength autofluorescence imaging, with structural data from OCT and OCT-angiography. MPOD data were analyzed using (a) an existing sum of exponential and Gaussian model (MEG) and (b) a novel sum of three Gaussians model (M3G). Extracted parameters generated individualized MPOD models, from which gradients and volumes were derived. M3G-derived variables were analyzed against OCT/OCTA data using factor analysis and multiple regression. M3G demonstrated a superior fit to MPOD data (SSE = 2.60 × 10[- 3]) compared to MEG, (SSE = 35.7 × 10[- 3]) enabling automated fitting consistent over small and large datasets. M3G provided meaningful variables, including MPOD gradients, volumes and critical point eccentricities. Correlations included those between dependent variables of critical point eccentricities and central macular pigment volume with foveal avascular zone and foveal pit radii.The excellent data fit of M3G enables automated extraction of physiologically relevant parameters. Its three-component configuration is consistent with the location of macular xanthophylls. M3G is similar to models of foveal structure, suggesting a fundamental relationship.}, }
@article {pmid41162760, year = {2025}, author = {Brandl, C and Schuster, AK and Finger, RP}, title = {[Nutrition and dietary supplements in eye diseases-Part 1: age-related macular degeneration and diabetic eye diseases].}, journal = {Die Ophthalmologie}, volume = {122}, number = {11}, pages = {871-872}, doi = {10.1007/s00347-025-02326-3}, pmid = {41162760}, issn = {2731-7218}, }
@article {pmid41164518, year = {2025}, author = {Namdeo, TS and Ashok, AA}, title = {Transformative Algal Interventions in Ophthalmology, Mechanisms, and Future Potential: A Review.}, journal = {Journal of pharmacy &amp; bioallied sciences}, volume = {17}, number = {Suppl 3}, pages = {S2044-S2048}, pmid = {41164518}, issn = {0976-4879}, abstract = {Microalgae have become the focus of many studies concerning ocular health due to the varied chemical composition of algae. These organisms contain bioactive compounds especially carotenoids, polyunsaturated fatty acids (PUFAs), and antioxidants, which have proven beneficial in some diseases of the eyes. This review is focused on summarizing the potential therapeutic use of algae in treating eye diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR), and dry eye syndrome. We will also describe the pathways by which algae produce benefits, review cases of clinical studies, and explore future uses for algae in treatments.}, }
@article {pmid41165404, year = {2025}, author = {Faurite, C and Michaud, C and Cousin, E and Olivier, P and Gallice, M and Chiquet, C and Pietras, J and Attyé, A and Soler, V and Berry, I and Mermillod, M and Cottereau, BR and Peyrin, C}, title = {Neurobehavioral Changes in Macular Degeneration: Spatial Frequency Use in Scene Recognition.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {13}, pages = {54}, pmid = {41165404}, issn = {1552-5783}, mesh = {Humans ; *Macular Degeneration/physiopathology/psychology ; Male ; Female ; Magnetic Resonance Imaging ; Aged ; Middle Aged ; *Scotoma/physiopathology ; *Pattern Recognition, Visual/physiology ; Visual Acuity/physiology ; *Visual Perception/physiology ; Aged, 80 and over ; }, abstract = {PURPOSE: Central vision loss in macular diseases severely affects visual perception and cognition, particularly scene recognition. A key question is whether observed impairments result solely from reduced input or reflect functional changes in spatial frequency processing. This study investigated how macular diseases affects this processing at both behavioral and brain levels.<br><br>METHODS: We compared patients with macular diseases with age-matched controls using an artificial scotoma simulating each patient's central vision loss. Participants performed a scene categorization task with images filtered in high spatial frequencies (HSFs; fine details) or low spatial frequencies (LSFs; global shape). Patients fixated using their preferred retinal locus (PRL), whereas controls fixated on the location corresponding to the patient's fovea, within the artificial scotoma. Behavioral performance and functional magnetic resonance imaging (fMRI) responses were analyzed.<br><br>RESULTS: Patients performed worse than the healthy controls for both HSF and LSF scenes, with a more pronounced deficit for HSFs. These deficits were associated with reduced activation in occipital cortex and in the parahippocampal place area (PPA), particularly for HSF scenes. In contrast, LSF processing was relatively preserved and accompanied by increased recruitment of higher-level cognitive and oculomotor areas in patients.<br><br>CONCLUSIONS: These findings demonstrate that macular diseases leads to altered spatial frequency processing within residual vision itself, particularly affecting fine-detail analysis. This perceptual degradation is accompanied by functional brain reorganization supporting partial compensation. The results highlight the importance of considering both degraded input and adaptive mechanisms when designing rehabilitation strategies based on residual peripheral vision.}, }
@article {pmid41166891, year = {2025}, author = {Zhang, M and Shen, J and Luly, KM and Lim, Y and Shannon, SR and Jain, M and Tzeng, SY and Hackett, S and Kanan, Y and Green, JJ and Campochiaro, PA}, title = {Suppression of choroidal neovascularization by nonviral gene transfer of pigment epithelium-derived factor.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {193}, number = {}, pages = {118711}, doi = {10.1016/j.biopha.2025.118711}, pmid = {41166891}, issn = {1950-6007}, support = {R01 EY031097/EY/NEI NIH HHS/United States ; }, mesh = {*Serpins/genetics/metabolism ; Animals ; *Nerve Growth Factors/genetics/metabolism ; *Choroidal Neovascularization/therapy/genetics/pathology ; *Eye Proteins/genetics/metabolism ; *Gene Transfer Techniques ; Rats ; *Genetic Therapy/methods ; Nanoparticles/chemistry ; Mice ; Mice, Inbred C57BL ; Male ; Plasmids/administration &amp; dosage ; Retina/metabolism/pathology ; Macular Degeneration/therapy/genetics ; Rats, Sprague-Dawley ; Polymers ; Pigment Epithelium-Derived Factor ; }, abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss among individuals over 60, is characterized by progressive retinal degeneration in a critical area for vision, the macula, and neovascular complications. Pigment epithelium-derived factor (PEDF) has the potential to address both of these pathologic processes because it has both neuroprotective and anti-angiogenic activities. In this study, we used a polymeric nonviral gene transfer platform to express PEDF in the eyes of mice and rats. In mice, there was high expression of PEDF in the retina and eyecup two weeks after subretinal injection of poly(β-amino ester) (PBAE) nanoparticles (NPs) containing a plasmid encoding PEDF, and at 2 or 4 weeks after injection there was a significant reduction in the area of choroidal neovascularization (CNV) at Bruch's membrane rupture sites compared with eyes that had received subretinal injection of a control vector. As suprachoroidal injection is a route of vector delivery that can be done in an outpatient setting and may limit certain negative side effects associated with subretinal injection, this route of administration was also investigated for PEDF plasmid delivery. In rats, there was high expression of PEDF in the retina and eyecup 4 weeks after suprachoroidal injection of PEDF NPs, and a significant reduction in CNV area at Bruch's membrane rupture sites compared with those in eyes injected with control vector. These data suggest that ocular nonviral gene transfer of PEDF may provide a new treatment approach for AMD.}, }
@article {pmid41167282, year = {2026}, author = {Chen, Y and Jiang, F and Zhang, M}, title = {Response to comments on refining the translational pathway for senotherapeutics in age-related macular degeneration: Insights on biomarkers, delivery strategies, and clinical trial design.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {1012-1013}, doi = {10.1016/j.survophthal.2025.10.006}, pmid = {41167282}, issn = {1879-3304}, }
@article {pmid41167797, year = {2025}, author = {Huang, X and Chen, J and Li, J and Zhang, G and Zhu, X and Zhou, M and Bo, Q and Sun, X}, title = {Choroidal changes correlate with type 1 neovascular activity in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327839}, pmid = {41167797}, issn = {1468-2079}, abstract = {PURPOSE: To investigate the association among choroidal factors and lesion activity of polypoidal choroidal vasculopathy (PCV) and type I neovascular age-related macular degeneration (nAMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: 69 eyes with PCV or type I nAMD were retrospectively included. All eyes had either &#x2265;2 consecutive non-exudative visits without treatment or no exudation/treatment within 6-month SS-OCTA follow-up. Lesions were categorised into active and inactive based on progression, defined as exudation, branching vascular network (BVN)/macular neovascularisation enlargement or recurrence/new/growth of polypoidal lesions. Choroidal parameters, including mean choroidal thickness (MCT), choroidal vascularity index (CVI) and choroidal volume (CV), were evaluated before and after lesion progression. The association between CVI variation and lesion area growth in PCV was also analysed.<br><br>RESULTS: No baseline differences in MCT or CVI were found between PCV and nAMD. However, significant differences in CVI and MCT variation were observed between active and inactive lesions (p<0.05). In PCV, lesion activity was characterised by decreased CVI and increased MCT, while in nAMD, only MCT and CV increased. Notably, combined CVI decrease and MCT increase served as a sensitive marker for active PCV (p<0.05), but not for nAMD. CVI reduction also correlated with BVN growth in PCV (R=-0.722, p<0.01).<br><br>CONCLUSION: Choroidal parameters varied significantly during lesion progression. Combined CVI decrease and MCT increase sensitively reflected active PCV lesions and were correlated with lesion location, size and progression, highlighting the differences in the choroidal microenvironment in the activities of PCV and nAMD.}, }
@article {pmid41168499, year = {2025}, author = {Fink, DJ and Finger, RP and Terheyden, JH}, title = {[Importance of vision in old age].}, journal = {Zeitschrift fur Gerontologie und Geriatrie}, volume = {58}, number = {8}, pages = {639-644}, pmid = {41168499}, issn = {1435-1269}, mesh = {Humans ; Aged ; *Vision Disorders/diagnosis/therapy/rehabilitation/prevention &amp; control/psychology ; Aged, 80 and over ; Female ; Male ; *Quality of Life/psychology ; Germany ; }, abstract = {Vision is a significant determinant of quality of life and autonomy in older people. It declines with age due to natural processes. In the general population this is exacerbated by age-related eye diseases, such as cataract, age-related macular degeneration, glaucoma and diabetic retinopathy. The resulting impairments can lead to reduced mobility, independence and mental health and physiological ageing processes of the eye and disease-related changes in visual function are therefore associated with increased morbidity, such as an increased risk of falls and depression. Treatment, prevention and rehabilitation measures can significantly reduce the impairment of older people caused by age-related eye diseases. In order to keep pace with the increasing demand for care and to maintain vision at the highest possible level into old age, not only targeted and timely ophthalmological care are necessary but also more prevention in the field of age-related eye diseases.}, }
@article {pmid41168502, year = {2025}, author = {Jiménez-Loygorri, JI and Shang, P and Bayramoglu, I and Gómez-Sintes, R and Martín-Segura, A and Ambrosino, H and Hoang, J and Díaz, A and Geng, Z and Gavathiotis, E and Dutton, JR and Dengjel, J and Cuervo, AM and Ferrington, DA and Boya, P}, title = {Defective chaperone-mediated autophagy in the retinal pigment epithelium of age-related macular degeneration patients.}, journal = {EMBO molecular medicine}, volume = {17}, number = {12}, pages = {3472-3495}, pmid = {41168502}, issn = {1757-4684}, support = {310030_215271//SNSF/ ; R01 AG021904/AG/NIA NIH HHS/United States ; AG031782//NIH/NIA/ ; R37 AG021904/AG/NIA NIH HHS/United States ; Ram&#xf3;n Areces Postdoctoral Fellowship//Ramon Areces Foundation/ ; R01EY028554//NIH/NEI/ ; PID2021-126864NBI00//MCIN/ ; R01 EY028554/EY/NEI NIH HHS/United States ; P01 AG031782/AG/NIA NIH HHS/United States ; AG021904//NIH/NIA/ ; CRSII5_189952//SNSF/ ; 310030_212187//SNSF/ ; PRE2019-088222//MCIN/ ; }, mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *Macular Degeneration/pathology/metabolism ; *Chaperone-Mediated Autophagy ; Induced Pluripotent Stem Cells ; Oxidative Stress ; Aged ; Female ; Male ; Proteostasis ; *Autophagy ; Mitochondria/metabolism ; }, abstract = {Autophagy is one of the main intracellular recycling systems and its impairment is considered a primary hallmark of the aging process. Defective macroautophagy in the retinal pigment epithelium (RPE) has been described in age-related macular degeneration (AMD), a blindness-causing disease that affects roughly 200 million patients worldwide. The relevance of chaperone-mediated autophagy (CMA), a selective type of autophagy for proteins containing a KFERQ-like motif, in RPE cell biology and homeostasis remains to be elucidated. Here we describe decreased CMA activity in the RPE of AMD patients compared to healthy age-matched controls, along with accumulation of substrate proteins, and in donor-derived iPSC-RPE cells, which we used to further characterize AMD-associated alterations of cellular homeostasis derived from proteotoxicity. Treatment with CA77.1 (CMA activator) restores proteostasis and remodels specific subsets of the proteome in cells from healthy and AMD donors. CA77.1-treated AMD iPSC-RPE display reduced oxidative stress and improved mitochondrial function. These findings may explain the specific vulnerability of the RPE during AMD and shed light on CMA as a new druggable target for this as-of-now incurable disease.}, }
@article {pmid41169217, year = {2025}, author = {Mirshahvaladi, S and Gaire, BP and Kashani, SA and Guha, A and Koronyo, Y and Fuchs, DT and You, Y and Black, KL and Paulo, JA and Graham, SL and Gupta, V and Mirzaei, M and Koronyo-Hamaoui, M}, title = {Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00291}, pmid = {41169217}, issn = {1673-5374}, support = {R01 AG055865/AG/NIA NIH HHS/United States ; R01 AG056478/AG/NIA NIH HHS/United States ; }, abstract = {Dysregulated proteome in the retina represents a promising avenue for discovering novel therapeutic targets and noninvasive diagnostic biomarkers for neurodegenerative diseases with ocular manifestations. Advanced mass spectrometry-based proteomics techniques have shown considerable potential in investigating the retinal proteome in diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, as well as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Recent proteomics innovations are overcoming challenges such as limited sample size and protein coverage that previously hindered comprehensive retinal proteome analysis. Notably, the incorporation of artificial intelligence-driven computational pipelines, including Graphics Processing Unit-accelerated deep learning architectures, has markedly enhanced the precision and effectiveness of retinal proteomics. These advances facilitate high-resolution identification of novel protein signatures within large-scale multi-omics datasets. Furthermore, the integration of advanced artificial intelligence with state-of-the-art big data infrastructures supports the early detection of biomarkers and therapeutic targets in neurodegenerative diseases with ocular involvement, offering unprecedented disease specificity and sensitivity. In addition to these computational strides, emerging complementary and alternative technologies continue to provide valuable tools for retinal analysis, expanding the potential for identifying biomarker and therapeutic targets in both ophthalmic and neurodegenerative disorders. This review summarizes recent advancements in retinal proteomics, with a particular focus on neurodegenerative and ocular diseases.}, }
@article {pmid41169746, year = {2025}, author = {Abuleil, D and Gorbet, D and McCulloch, DL and Cohan, R and Steeves, JEK and Bang, JW and Chan, KC and Thompson, B}, title = {Anodal transcranial direct current stimulation does not alter GABA concentration or functional connectivity in the normal visual cortex.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1639838}, pmid = {41169746}, issn = {1662-4548}, abstract = {INTRODUCTION: Anodal direct current stimulation (a-tDCS) of the visual cortex is a potential rehabilitation tool for vision disorders such as amblyopia and macular degeneration. However, the underlying neural mechanisms are currently unknown. When applied to the human motor cortex, a-tDCS reduces the concentration of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that modulates neuroplasticity. Our primary aim was to assess whether the same a-tDCS paradigm alters local GABA concentration when applied to the healthy primary visual cortex. We also measured the effect of a-tDCS on visual cortex resting-state connectivity and sought to replicate reported observations of an association between visual cortex GABA concentration and the dynamics of binocular rivalry.<br><br>METHODS: Fourteen participants with normal vision completed two brain imaging sessions at least 48 hours apart. In each session, binocular rivalry dynamics, primary visual cortex GABA and glutamate-glutamine (Glx) concentrations (via magnetic resonance spectroscopy (MRS)) and resting-state functional connectivity (via task-free fMRI) were measured at baseline. Real or sham a-tDCS (20 min, 2mA) was then applied to the visual cortex in a randomized sequence followed by a second set of MRS and fMRI measurements.<br><br>RESULTS: No between-session effects of a-tDCS on GABA or Glx concentration or resting-state functional connectivity were observed. A pre-planned within-session analysis revealed a significant increase in Glx following a-tDCS that did not withstand multiple comparisons correction. No consistent relationships between binocular rivalry dynamics and GABA concentration were apparent.<br><br>DISCUSSION: Together, our results suggest that a-tDCS effects on the visual cortex may differ from the GABA-associated mechanism in motor cortex.}, }
@article {pmid41170269, year = {2025}, author = {Lloyd, A and Elbalawi, M and Kurc, M and Hussain, M and Abugreen, S}, title = {The Implementation of Faricimab in East Lancashire NHS Trust: Highlighting the Real-World Efficacy and Safety in Patients With Neovascular Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93478}, pmid = {41170269}, issn = {2168-8184}, abstract = {PURPOSE: To report the safety and efficacy of intravitreal faricimab injections (IVTF) in both treatment-naïve and treatment-resistant patients with neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This study was a retrospective real-world evidence trial where patients with nAMD were given IVTF. Group 1 (treatment-na&#xef;ve) and group 2 (switch loading dose, SLD)&#xa0;were given a course of four loading doses of IVTF four weeks apart. Group 3 (switch pro re nata, SPRN)&#xa0;was given a single IVTF and then reviewed at eight weeks. The outcome was based on visual acuity (VA) and optical coherence tomography (OCT), showing central retinal thickness (CRT), subretinal, and intraretinal fluid.<br><br>RESULTS: A total of 99 eyes from 89 patients were included. A total of 350 IVTF were given. The mean follow-up duration was 6.33 &#xb1; 1.11 months (range: 2-8 months).&#xa0;The mean change in CRT at final follow-up was&#xa0;-127.09 &#xb1; 97.39 &#xb5;m (p < 0.001) for na&#xef;ve eyes, -115.59 &#xb1; 145.02 &#xb5;m (p < 0.001) for SLD, and -57.61 &#xb1; 58.06 &#xb5;m (p < 0.001) for SPRN. The mean VA change was&#xa0;-3.47 ETDRS (Early Treatment Diabetic Retinopathy Study) (p = 0.256) for na&#xef;ve eyes, -0.79 (p = 0.45) for SLD, and +1.25 (p = 0.304) for SPRN. A total of 48 eyes (48.48%) had better VA, 22 (22.22%) had no change in VA, and 29 (29.29%) had worse VA. One patient developed bilateral sterile intraocular inflammation.<br><br>CONCLUSION: IVTF was associated with an improvement in CRT in both treatment-naive and treatment-resistant nAMD patients. There was no evidence of vasculitis or vein occlusion, highlighting the safety of faricimab in our real-world study.}, }
@article {pmid41172710, year = {2025}, author = {Singh, S and Runyon, W and Hu, S and Kennedy, PG and Singh, A and Ratnapriya, R and Kumar, R and Csaky, K and Sripathi, SR}, title = {Generation of iPSCs (RFSCi007-A, RFSCi008-A) from a patient with early-onset bilateral drusen and a healthy sibling for retinal disease modeling.}, journal = {Stem cell research}, volume = {89}, number = {}, pages = {103862}, doi = {10.1016/j.scr.2025.103862}, pmid = {41172710}, issn = {1876-7753}, mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; Siblings ; *Retinal Drusen/pathology ; Male ; Macular Degeneration/pathology ; Female ; }, abstract = {Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.}, }
@article {pmid41173219, year = {2026}, author = {Deimazar, G and Sabbaghi, H and Ahmadieh, H and Sheikhtaheri, A}, title = {Artificial intelligence for detection of age-related macular degeneration based on fundus images: A systematic review.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {980-991}, doi = {10.1016/j.survophthal.2025.10.004}, pmid = {41173219}, issn = {1879-3304}, mesh = {Humans ; *Macular Degeneration/diagnosis ; Fundus Oculi ; *Artificial Intelligence ; Neural Networks, Computer ; Deep Learning ; Algorithms ; *Diagnostic Techniques, Ophthalmological ; Machine Learning ; }, abstract = {Age-related macular degeneration (AMD) is one of the most common types of eye diseases that generally affect the elderly population over 50 years of age. The effects of AMD on the quality of vision and life are devastating. We systematically review applications and performance of machine/deep learning algorithms for AMD detection and prediction using color fundus photos. We reviewed the studies that focused on machine learning and deep learning techniques and algorithms to analyze the fundus images for AMD. The data were collected by searching Scopus, PubMed (Medline), Web of Science and IEEE Xplore databases. After screening, 42 papers were included. The findings showed that the studies used different architectures for model training and testing. Convolutional neural networks (CNN) are used mostly in the diagnosis of AMD. ResNet architecture (11 studies) was used more than other architectures. Twenty-two studies used AREDS dataset. CNN algorithm with ResNet architecture had the highest performance compared to other architectures. Studies have shown that machine learning can diagnose AMD from fundus images with high accuracy; however, calibration, fairness, explainability, external validation, generalization, prospective validation in clinical settings and regulatory requirements should be considered in the future.}, }
@article {pmid41174770, year = {2025}, author = {Trinh, M and Tee, YG and Nam, J and Chen, S and Schiller, G and Friedrich, J and Ng, D and Ly, A and Hodge, C and Nivison-Smith, L}, title = {Localising OCTA changes induced by the isometric hand-grip test to the superficial retina in neovascular age-related macular degeneration.}, journal = {Eye and vision (London, England)}, volume = {12}, number = {1}, pages = {44}, pmid = {41174770}, issn = {2326-0254}, support = {2023//Future Vision Foundation/ ; }, abstract = {PURPOSE: This study uses optical coherence tomography angiography (OCTA) topographical cluster analysis to localise where vascular changes occur during the isometric hand-grip test (IHGT) in eyes with neovascular age-related macular degeneration (AMD).<br><br>METHODS: This prospective study included single eyes from 44 participants with neovascular&#xa0;AMD. Systemic blood pressure (BP) and macular 6&#x2009;&#xd7;&#x2009;6&#xa0;mm OCTA scans were obtained before the IHGT, during the IHGT, and after the IHGT. The main outcome was the change in processed OCTA signal (%), measured within high-density (126&#x2009;&#xd7;&#x2009;126) grids and analysed by topographical clusters across the superficial retina, deep retina, and choriocapillaris. Results were compared against test-retest thresholds to differentiate true IHGT-induced changes from measurement variability.<br><br>RESULTS: The IHGT increased systolic (13.83 [3.28, 24.39] mmHg) and diastolic BP (7.04 [3.57, 10.52] mmHg; P&#x2009;<&#x2009;0.01). Adjusted for test-retest thresholds, the IHGT increased processed OCTA signal (12.84 [8.49, 26.77] %, P&#x2009;<&#x2009;0.0001) at nasal clusters in the superficial retina. These changes were moderately correlated with systolic BP increases (Spearman r&#x2009;=&#x2009;0.43, P&#x2009;<&#x2009;0.05), but not with diastolic BP. No changes were observed in the deep retina or choriocapillaris. Systemic BP and processed OCTA signal returned to baseline within 30&#xa0;s after IHGT release.<br><br>CONCLUSION: Hand-squeezing temporarily increases processed OCTA signal in the nasal superficial retina. This response may serve as a valuable marker of vascular function. Consequently, caution is warranted when interpreting OCTA following BP changes, such as those induced by physical activity or medication changes.}, }
@article {pmid41175224, year = {2026}, author = {Yang-Seeger, D and Schellstede, A and Pauleikhoff, LJB and Spitzer, MS and Birtel, J}, title = {Travel-associated emissions of intravitreal injections.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {347-353}, pmid = {41175224}, issn = {1435-702X}, mesh = {Humans ; *Intravitreal Injections ; Female ; Male ; *Travel ; Aged ; Middle Aged ; *Carbon Footprint/statistics &amp; numerical data ; Germany/epidemiology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Retrospective Studies ; Follow-Up Studies ; Aged, 80 and over ; }, abstract = {PURPOSE: Intravitreal injections (IVIs) are among the most frequently performed ophthalmic procedures and have been associated with a substantial carbon footprint. Travel-associated emissions are considered a key driver of IVIs' carbon footprint; however, no study in a country with a decentralised healthcare system has assessed IVI-related emissions. Here, the IVI-associated carbon footprint in an urban German tertiary referral centre was investigated.<br><br>METHODS: In total, 340 patients were included. The carbon footprint was assessed based on the distance travelled by patients and accompanying persons, the mode of transport, and postoperative follow-up visits. Demographic data, treatment indication, and the injected medication were collected.<br><br>RESULTS: The average travel-associated CO2 equivalent (CO2eq) for a single IVI was 11.1&#xa0;kg. Of this,&#xa0;9.1&#xa0;kg CO2eq and 2&#xa0;kg CO2eq were due to travel to the injection clinic and to follow-up visits, respectively. Anti-VEGF treatment for common diseases such as age-related macular degeneration and diabetic macular edema was associated with a lower CO2eq compared with treatment of patients suffering from&#xa0;less prevalent conditions such as uveitis (10.8&#xa0;kg vs. 15.6&#xa0;kg). The majority of patients (49%) travelled by public transport (median distance: 22.4&#xa0;km); patients travelling by car (33%) usually covered longer distances (median distance: 61.5&#xa0;km).<br><br>CONCLUSION: Travel is a meaningful contributor to the carbon footprint of IVIs. Mitigation may be achieved by various approaches, such as longer-acting therapeutic agents or bilateral injections. To implement strategies for more sustainable IVIs, ophthalmologists may be encouraged by local and national bodies to incorporate environmental criteria into their practice.}, }
@article {pmid41175863, year = {2025}, author = {Xin, Y and Jin, Y and Qian, C and Blackshaw, S and Qian, J}, title = {MetaLigand provides a prior-knowledge-guided framework for predicting non-peptide ligand mediated cell-cell communication.}, journal = {Cell reports methods}, volume = {5}, number = {11}, pages = {101217}, pmid = {41175863}, issn = {2667-2375}, mesh = {*Cell Communication ; Humans ; Ligands ; Transcriptome ; Animals ; *Computational Biology/methods ; }, abstract = {Non-peptide ligands (NPLs), including lipids, amino acids, carbohydrates, and non-peptide neurotransmitters and hormones, play a critical role in ligand-receptor-mediated cell-cell communication, driving diverse physiological and pathological processes. To facilitate the study of NPL-dependent intercellular interactions, we introduce MetaLigand, a tool designed to infer NPL availability and NPL-receptor interactions using transcriptomic data. MetaLigand compiles data for 233 NPLs, including their biosynthetic enzymes, transporter genes, and receptor genes, through a combination of automated pipelines and manual curation from comprehensive databases. The tool integrates both de novo and salvage synthesis pathways, incorporating multiple biosynthetic steps and transport mechanisms. Comparisons with existing tools demonstrate MetaLigand's ability to account for complex biogenesis pathways and model NPL availability across diverse tissues and cell types. Furthermore, analysis of single-nucleus RNA sequencing (RNA-seq) datasets from age-related macular degeneration samples revealed that distinct retinal cell types exhibit unique NPL profiles and participate in specific NPL-mediated pathological cell-cell interactions.}, }
@article {pmid41177551, year = {2025}, author = {Brunner, P and Havanur, P and Papukchieva, S and Friedrich, B and Ziemssen, F}, title = {Tracking real-world persistence and adherence to anti-VEGF intravitreal therapy with prefilled syringes: a German prescription sales analysis.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41177551}, issn = {2397-3269}, mesh = {Humans ; Germany/epidemiology ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Female ; Aged ; *Syringes ; *Drug Prescriptions/statistics &amp; numerical data ; *Bevacizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; *Ranibizumab/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration and other retinal vascular diseases. Despite proven efficacy in clinical trials, real-world data suggest suboptimal persistence and adherence. This study aimed to assess therapy continuity in routine practice using pharmacy-based dispensing data in Germany, focusing on treatment with prefilled syringes (PFS).<br><br>METHODS AND ANALYSIS: This retrospective cohort study used anonymised nationwide pharmacy sales data from Germany to evaluate patients who initiated anti-VEGF therapy with PFS between 2020 and 2023. Patient trajectories were followed from treatment initiation for up to 12 months. 46&#x2009;546 therapy beginners with 297&#x2009;454 anti-VEGF PFS purchases were included. Discontinuation of treatment was defined by not purchasing a relevant medication for >6 months.<br><br>RESULTS: Mean time on therapy for all patients was 8.1&#xb1;8.2 months (median=5.5) with 6.9&#xb1;6.1 purchases (median=5). 20.5% of patients initiating anti-VEGF treatment stopped therapy before completing the loading phase (first three injections), and more than half of all patients discontinued treatment after 6 months. 49.4% of the patients who completed the loading phase (n all=34&#x2009;895) adhered to the recommended monthly regimen. Non-adherence significantly decreased the number of injections later on (average of 7.5 vs 8.7 injections). Further, patients who stayed longer on therapy bought more PFSs within the first 6 and 12 months.<br><br>CONCLUSIONS: Real-world adherence and persistence to intravitreal anti-VEGF therapy in Germany are suboptimal, even with the use of PFS formulation. The high rate of early treatment discontinuation, especially during the loading phase, underscores the need for improved patient support, education and flexible treatment approaches to sustain long-term outcomes. A 'breaking point' or sensitive phase already seems to exist right at the beginning of therapy.}, }
@article {pmid41177553, year = {2025}, author = {Sawires, K and Nithianandan, H and Somani, S}, title = {Comparative outcomes of aflibercept biosimilars and reference aflibercept in nAMD: a systematic review and meta-analysis.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41177553}, issn = {2397-3269}, mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; *Visual Acuity ; Randomized Controlled Trials as Topic ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; }, abstract = {OBJECTIVE: To evaluate the literature-pooled functional, anatomical and safety outcomes of aflibercept biosimilars compared with reference aflibercept for neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: Systematic review and meta-analysis. Medline, Embase and CENTRAL were searched from inception to 2 June 2025. Phase 3 randomised controlled trials (RCTs) comparing aflibercept biosimilars with the reference product in patients with nAMD were included. Two independent reviewers conducted screening, data extraction, risk of bias (RoB 2) assessment and certainty of evidence assessment (Grading of Recommendations, Assessment, Development and Evaluation), with a third reviewer resolving discrepancies. Primary outcomes included mean difference (MD) change in best-corrected visual acuity (BCVA) and retinal thickness over time, risk ratio (RR) for proportion of participants gaining >15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and RR for adverse events. Meta-regression was used to evaluate the temporal stability of continuous outcomes.<br><br>RESULTS: Six RCTs involving 2044 participants (1026 biosimilar, 1018 reference) were included. Five aflibercept biosimilars were evaluated, representing more than 50% of the eight biosimilars currently approved worldwide. Meta-regression revealed no significant difference in MD change in BCVA over time between biosimilar and reference aflibercept (slope: 0.0321 letters/week; p=0.1013). For MD change in retinal thickness, an initial anatomical advantage for reference aflibercept at week 0 (intercept: 9.58&#x2009;&#xb5;m; p=0.0449) was not sustained over time (slope: -0.1685&#x2009;&#xb5;m/week; p=0.2303). The pooled RR for gaining >15 ETDRS letters from baseline was 1.19 (95% CI 0.98 to 1.45; p=0.079). No statistically significant differences were observed across 15 safety outcomes.<br><br>CONCLUSION: This systematic review and meta-analysis found no statistically significant differences in functional, anatomical or safety outcomes between aflibercept biosimilars and the reference product for nAMD, based on moderate to high certainty evidence. Functional and anatomical outcomes appeared stable across multiple timepoints. Further long-term pharmacovigilance studies and real-world data beyond 56 weeks are warranted.<br><br>PROSPERO REGISTRATION NUMBER: CRD420251048633.}, }
@article {pmid41178994, year = {2025}, author = {Li, Y and Wang, C and Deng, T and Li, X and Xu, R and Shang, Q}, title = {RARRES1 attenuates H2O2-induced RPE cell injury and inhibits choroidal neovascularization.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1641653}, pmid = {41178994}, issn = {1664-042X}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in the elderly, yet its underlying molecular mechanisms remain incompletely understood, and novel biomarkers and therapeutic targets are urgently needed. This study aimed to identify and functionally characterize potential biomarkers and therapeutic candidates for nAMD, with a focus on retinoic acid receptor responder protein 1 (RARRES1).<br><br>METHODS: Tandem mass tag (TMT)-based proteomic analysis was performed on aqueous humor samples from patients with nAMD and age-related cataracts. RARRES1 expression was examined in aqueous humor, laser-induced choroidal neovascularization (CNV) model mice, and human ARPE-19 cells exposed to H2O2. Functional studies assessed the effects of RARRES1 on oxidative stress, cell death, inflammatory and angiogenic factor expression, and signaling pathways in ARPE-19 cells. Its effects on proliferation, migration, and tube formation were tested in HUVECs. In vivo, a RARRES1-overexpressing AAV2 vector was injected intraocularly into CNV model mice, and lesion size and vascular leakage were evaluated using fundus fluorescein angiography, hematoxylin and eosin staining, and isolectin B-4 fluorescence staining.<br><br>RESULTS: RARRES1 was significantly reduced in the aqueous humor of nAMD patients, in CNV model mice, and in H2O2-treated ARPE-19 cells. Overexpression of RARRES1 in ARPE-19 cells mitigated oxidative stress-induced damage, suppressed inflammatory and angiogenic factor expression, inhibited JNK phosphorylation, and increased Sirtuin 1 and Nrf2 expression. In HUVECs, RARRES1 reduced proliferation, migration, and tube formation. In vivo, intraocular delivery of RARRES1 significantly reduced CNV lesion size and vascular leakage.<br><br>CONCLUSION: RARRES1 protects retinal pigment epithelial cells from oxidative stress, inhibits choroidal neovascularization, and modulates inflammatory and angiogenic pathways. These findings identify RARRES1 as a potential biomarker and therapeutic target for nAMD.}, }
@article {pmid41179910, year = {2026}, author = {Doshi, U and Davis, E and Al-Sheikh, M and Sahel, JA and Chhablani, J and Vupparaboina, KK and Bollepalli, SC}, title = {Generalizable Multimodal Retinal Image Registration via Label-free Vessel Segmentation.}, journal = {Biomedical signal processing and control}, volume = {113}, number = {Pt B}, pages = {}, pmid = {41179910}, issn = {1746-8094}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; }, abstract = {Multimodal retinal imaging plays a crucial role in diagnosing and managing various retinal diseases such as diabetic retinopathy and age-related macular degeneration (AMD). The majority of retinal imaging modalities including Color Fundus Photography (CF), Fluorescein Angiography (FAG), Fundus Autofluorescence (FAF), Indocyanine Green Angiography (ICG), and Optical Coherence Tomography (OCT), along with infrared imaging (IR) and B-scans, capture different aspects of the same pathology within the retina. Consequently, accurate disease quantification, monitoring, and automated diagnosis require integrating their complementary insights, which relies on accurate registration of these images. To this end, developing a robust registration algorithm applicable across all modalities assumes significance. This paper presents a generalizable, label-free approach to retinal image registration, using vessel structure, extracted using DexiNed algorithm. The proposed method was evaluated across various imaging modalities, including CF-IR, CF-FAF, CF-FAG, CF-ICG, FAF-FAG, FAF-ICG, and FAG-ICG, achieving a mean landmark error (MLE) ranging from 1.91±0.44 to 4.9±2.32 pixels. In particular, CF-IR and CF-FAF registration attained an MLE of 3.08±1.47 and 4.9±2.32 pixels respectively, performing favorably when compared to human grader annotations. Furthermore, the proposed solution eliminates the need for large labeled training datasets while effectively extracting vessel structures to enable multimodal retinal image registration, improving diagnostic precision and disease monitoring.}, }
@article {pmid41181297, year = {2025}, author = {Agius, D and Mamo, JJ and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F}, title = {Markedly Lower Rates of Age-Related Macular Degeneration in Malta Compared to European Countries: Results from The Malta Eye Study, Indicating Possible Divergent Genetic Ancestry?.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {3961-3971}, pmid = {41181297}, issn = {1177-5467}, abstract = {PURPOSE: To estimate the prevalence of age-related macular degeneration (ARMD) in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors, and compare rates with those reported in other European populations, where substantial variation has been observed.<br><br>PATIENTS AND METHODS: A population-based cross-sectional study was conducted involving 1794 participants aged 50-80 years from Malta (1% of the represented population), recruited as part of The Malta Eye Study. Standardized ophthalmic examinations were performed, including retinal imaging graded for ARMD according to Age-Related Eye Disease Study criteria and optical coherence tomography scans. Data on demographics, medical history, behavioural risk factors, and ocular characteristics were collected via structured questionnaires. Associations were assessed using multivariable logistic regression. DNA samples were also collected for future genetic analyses.<br><br>RESULTS: The overall prevalence of ARMD was 6.5% (95% CI 5.4-7.8%), with early ARMD accounting for 5.6% (95% CI 4.6-6.7%) and late ARMD for 0.4% (95% CI 0.2-0.8%). Multivariate analysis showed that ARMD prevalence increased significantly with age (OR per year 1.08; 95% CI 1.05-1.11, p<0.001) and in the male sex (OR 1.57; 95% CI 1.01-2.44, p=0.043). The other traditional ARMD risk factors did not show significant associations in this cohort. Compared to other European populations, ARMD prevalence was notably lower.<br><br>CONCLUSION: This study reports a relatively low prevalence of ARMD compared to other European settings, with age and male sex emerging as the only significant risk factors. The absence of association with other traditional risk factors may reflect underlying genetic differences or distinct gene-environment interactions. As DNA samples were collected, further investigation incorporating genetic data is warranted to better understand ARMD susceptibility in this population.}, }
@article {pmid41181732, year = {2025}, author = {Tamai, R and Nizawa, T and Kawamata, Y and Iwase, T and Baba, T}, title = {Switching From Aflibercept 2 mg to 8 mg in Vitrectomized Eyes With Neovascular Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e93645}, pmid = {41181732}, issn = {2168-8184}, abstract = {Vitrectomy may alter intravitreal pharmacokinetics through the removal of the vitreous gel, potentially accelerating the clearance of anti-vascular endothelial growth factor (VEGF) agents. Clinical trials and most real-world studies on neovascular age-related macular degeneration (nAMD) generally exclude vitrectomized eyes, and the efficacy of anti-VEGF therapy in this subgroup remains unclear. Aflibercept 8 mg, approved in Japan in 2024, delivers four times the dose of the conventional 2 mg formulation and is designed to improve durability and extend treatment intervals. We report three vitrectomized eyes from three patients with nAMD who exhibited persistent or recurrent exudation despite short-interval (≤8 weeks) aflibercept 2 mg therapy under a treat-and-extend regimen. Switching to aflibercept 8 mg led to the resolution of fluid in all cases and enabled interval extension. No ocular or systemic adverse events were observed. These findings suggest that aflibercept 8 mg can achieve improved anatomical outcomes and greater treatment durability in vitrectomized eyes with nAMD, thereby potentially reducing the treatment burden in this challenging subgroup. Larger prospective studies are required to validate these findings.}, }
@article {pmid41182355, year = {2026}, author = {Shmueli, O and Batash, T and Nitzan, I and Chowers, I and Tiosano, L}, title = {Cataract surgery in eyes with adult-onset foveomacular-vitelliform dystrophy.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {355-364}, pmid = {41182355}, issn = {1435-702X}, mesh = {Humans ; Retrospective Studies ; Male ; *Visual Acuity ; Female ; Tomography, Optical Coherence/methods ; Aged ; Middle Aged ; Follow-Up Studies ; *Cataract/complications/diagnosis ; *Vitelliform Macular Dystrophy/complications/diagnosis/physiopathology ; *Cataract Extraction/methods ; *Fovea Centralis/pathology ; Fluorescein Angiography ; Treatment Outcome ; Aged, 80 and over ; Adult ; }, abstract = {PURPOSE: To assess the outcomes and safety of cataract surgery in Adult-Onset Foveomacular-Vitelliform dystrophy (AFVD) patients.<br><br>METHODS: This retrospective study analyzed eyes with AFVD that underwent cataract surgery in a tertiary center, comparing them with eyes affected by none and neovascular age-related macular degeneration (NVAMD). Data included demographics, best-corrected visual acuity LogMAR (VA), eye examination results, and optical coherence tomography (OCT) results. The primary outcome was improvement in VA. A secondary outcome was AFVD progression such as the development of choroidal neovascularization (CNV) or retinal atrophy.<br><br>RESULTS: The cohort included 83 eyes (18 with AFVD, 27 with none-NV AMD, and 38 with NVAMD). AFVD eyes showed significant improvement in VA&#xb1;SD from pre-surgery (0.60&#x2009;&#xb1;&#x2009;0.34) to 1 month (0.23&#x2009;&#xb1;&#x2009;0.11; P&#x2009;<&#x2009;0.0001) and 12 months post-operatively (0.26&#x2009;&#xb1;&#x2009;0.12; P&#x2009;<&#x2009;0.0001). No cases of CNV or major AFVD progression changes were observed over 12 months of follow up. However, at last follow-up (62.20&#x2009;&#xb1;&#x2009;39.30 months) there was increased proportion of atrophic AFVD (44.40% compared to 5.50% at baseline; P&#x2009;=&#x2009;0.10). No difference was found comparing VA improvement one month after surgery of none-NV AMD, NVAMD and AFVD (AFVD&#x2009;=&#x2009;0.37&#x2009;&#xb1;&#x2009;0.36, none-NV AMD&#x2009;=&#x2009;0.47&#x2009;&#xb1;&#x2009;0.68, NVAMD&#x2009;=&#x2009;0.28&#x2009;&#xb1;&#x2009;0.37; P&#x2009;=&#x2009;0.29). In the none-NV AMD group, one eye developed CNV ten months post-operatively and another eye demonstrated worsening retinal atrophy one-month post-surgery. In the NVAMD group, 9 eyes developed retinal atrophy at last follow up.<br><br>CONCLUSION: Cataract surgery in&#xa0;AFVD eyes led to significant visual acuity improvement and demonstrated good safety with no&#xa0;new CNV or retinal atrophy. The similar visual improvement across the AFVD, none-NV AMD&#xa0;and NVAMD groups suggests the procedure's efficacy and safety for AFVD patients.}, }
@article {pmid41182446, year = {2025}, author = {Entezari, Z and Mahootchi, M and Eskandari, M and Ahmadieh, H}, title = {Artificial intelligence-driven diagnosis for age-related macular degeneration bridging pathology and engineering: a survey.}, journal = {International ophthalmology}, volume = {45}, number = {1}, pages = {456}, pmid = {41182446}, issn = {1573-2630}, mesh = {Humans ; *Macular Degeneration/diagnosis ; *Artificial Intelligence ; Tomography, Optical Coherence/methods ; Disease Progression ; Early Diagnosis ; Risk Factors ; }, abstract = {Age-related macular degeneration (AMD) is the primary reason for severe visual impairments, making early diagnosis critically important. This paper provides a comprehensive review of the methods used to support screening and diagnostic decisions, focusing on four categories: early, intermediate, and advanced stages of AMD, in addition to AMD across all stages. In this regard, a reference framework is initially proposed to describe research perspectives in pathology. Utilizing this framework, a literature review is conducted to identify the most reliable demographic, environmental, and comorbidity-related risk factors, clinical symptoms, and various aspects of AMD pathology, setting the necessary prerequisites for subsequent sections. The potential application of risk factors is also explained for personalized medicine. While phenotypic risk factors and genetic variants play a crucial role in predicting the progression of AMD, it is more vital to examine demographic and environmental factors at earlier stages for developing effective prevention plans. Therefore, the selection of appropriate risk factors emerges as a critical area of research. Afterward, we present a comparative analysis of different screening and diagnostic methods pertinent to AMD from an industrial engineering perspective. This analysis brings attention to the suite of artificial intelligence (AI) to describe, analyze, and evaluate diagnostic models, thereby providing a reference outline for clinical practice. AI methods can automate the interpretation of retinal images, serving as a supportive tool for clinical decision-making to improve the management of disease progression. In general, this survey highlights the necessity of developing more integrated methods to support decisions at different planning levels.}, }
@article {pmid41182913, year = {2025}, author = {Akçay, G and Kutlutürk Karagöz, I and Doğan Gökçe, G}, title = {Evaluating anxiety and depression levels in patients undergoing intravitreal injections and investigation of contributing factors.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251392036}, doi = {10.1177/11206721251392036}, pmid = {41182913}, issn = {1724-6016}, abstract = {PurposeTo evaluate anxiety and depression levels in patients receiving intravitreal injections for diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO), and their associations with visual acuity, disease type, and demographic factors.MethodsThe study included 90 patients (43 males and 47 females) mean age 73.9 ± 12.4 years; (range: 22-92 years). Anxiety levels were assessed using the state anxiety form of the State-Trait Anxiety Inventory (STAI-S), and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Best-corrected visual acuity (BCVA) was recorded, and patients were evaluated according to disease type, severity of visual impairment, and number of injections.ResultsThe mean STAI-S score was 36.2 ± 8.9, and that of HADS was 13.9 ± 12.6. There were no significant differences in STAI-S scores between the disease groups (p = 0.17). However, HADS scores were significantly lower in the RVO group than in the DME and AMD groups (p = 0.02, p = 0.04). A significant association was observed between severity of visual impairment and STAI-S scores (p = 0.016), with moderate visual impairment showing higher anxiety levels than mild and severe impairment (p = 0.07, p = 0.02). However, HADS scores were not significantly associated with visual acuity (p = 0.058). Women exhibited higher HADS scores (p = 0.036). Neither injection frequency nor waiting time significantly affected STAI-S or HADS scores (p > 0.05).ConclusionPatients receiving intravitreal injections have varying levels of anxiety and depression, considering disease type, sex, and severity of visual impairment affecting these psychological parameters. These findings provide invaluable insights into the importance of psychological support in ophthalmic care.}, }
@article {pmid41183001, year = {2025}, author = {Hu, X and Tang, Y and Zhang, H and Wang, Z and Sun, J}, title = {Alu RNA-transfected Primary Mouse Retinal Pigment Epithelium: A Pathologically Relevant In Vitro Model for Age-related Macular Degeneration.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {224}, pages = {}, doi = {10.3791/68570}, pmid = {41183001}, issn = {1940-087X}, mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/pathology/metabolism/cytology ; *Macular Degeneration/pathology/genetics ; *Disease Models, Animal ; *Alu Elements/genetics ; *Transfection/methods ; *RNA/genetics ; Mice, Inbred C57BL ; }, abstract = {Age-related macular degeneration (AMD), particularly non-exudative AMD, requires experimental models that better replicate human pathology. Current in vivo models remain technically demanding and time-intensive, whereas conventional in vitro systems fail to recapitulate disease-specific pathological triggers. Here, we present a method to establish a retinal pigment epithelial (RPE) degeneration model using primary mouse RPE cells transfected with Alu RNA, a retrotransposon directly implicated in geographic atrophy pathology. This protocol details the enzymatic isolation of primary mouse RPE cells, followed by Alu RNA transfection to induce RPE degeneration. Validation integrates morphological (hexagonal architecture), functional (polarity loss and mouse protein ZO-1 disruption), and molecular analysis (quantitative PCR). As a result, we observed multifactorial changes triggered by Alu RNA transfection: inflammatory cytokine secretion (mouse genes Ifn-β, Il-6, Tnf-α; p < 0.05) and cellular senescence (mouse genes p21 and p53 upregulation; p < 0.05). Compared to traditional acute stress models, this system recapitulates chronic inflammatory-degenerative cascades of AMD through standardized techniques, ensuring reproducibility. By combining aspects of simplified in vitro assays and complex in vivo models, this approach could serve as a preliminary platform for exploring retrotransposon-driven mechanisms and screening potential therapeutic candidates.}, }
@article {pmid41183353, year = {2025}, author = {Sabbagh, F and Zargarian, SS and Kosik-Kozioł, A and Nakielski, P and Pierini, F}, title = {Hydrogel-based ocular drug delivery systems.}, journal = {Journal of materials chemistry. B}, volume = {13}, number = {46}, pages = {14982-15006}, doi = {10.1039/d5tb01575h}, pmid = {41183353}, issn = {2050-7518}, mesh = {*Hydrogels/chemistry ; Humans ; *Drug Delivery Systems ; Animals ; *Ophthalmic Solutions/chemistry ; }, abstract = {Ocular drug delivery is challenging due to physical and physiological barriers, such as the corneal epithelium and blood-retinal barrier, resulting in limited bioavailability (<5% for eye drops) and fast degradation. For the reason of improving drug delivery to the anterior and posterior ocular segments, this review attempts to assess hydrogel-based systems as versatile systems to overcome these barriers. We thoroughly explore physicochemical and performance characterization approaches (e.g., swelling, rheology, drug release kinetics), hydrogel fabrication methods (e.g., chemical crosslinking, 3D printing), and their uses in new and commercial products. Significant advances highlight the controlled release, mucoadhesion, and biocompatibility of hydrogels, which allow prolonged drug delivery as demonstrated by commercial products such as DEXTENZA® and ReSure® Sealant for corneal sealing and post-operative inflammation control. New technologies provide greater accuracy and less invasiveness. Examples include bioengineered hydrogels for retinal regeneration, systems integrated with nanotechnology, and stimuli-responsive hydrogels (such as pH-sensitive chitosan for glaucoma). By addressing mechanical stability and regulatory criteria, characterization techniques guarantee the suitability of the hydrogel for ocular applications. Hydrogels exhibit considerable promise for personal and least invasive treatments, despite challenges like scalability and high production costs. With implications for improving clinical outcomes and patient compliance through novel biomaterials, this review highlights the important role of hydrogels in ocular drug delivery and offers an outline for future advancements in the treatment of diseases like glaucoma, age-related macular degeneration, and dry eye syndrome.}, }
@article {pmid41183696, year = {2026}, author = {Cheng, Y and Gu, S and Yu, H and Jin, J and Cheng, H and Zhang, H and Lin, J and Li, M and Zhu, H and Wang, T and Huang, Q and Liu, Y and Yue, P and Li, W and Ling, S}, title = {PYGM downregulates necroptosis signaling to attenuate sodium iodate-induced RPE cell degeneration.}, journal = {Cellular signalling}, volume = {137}, number = {}, pages = {112206}, doi = {10.1016/j.cellsig.2025.112206}, pmid = {41183696}, issn = {1873-3913}, mesh = {*Iodates/toxicity ; *Necroptosis/drug effects ; Animals ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; Mice ; *Macular Degeneration/metabolism/pathology/genetics/chemically induced ; Signal Transduction/drug effects ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Down-Regulation ; Mice, Inbred C57BL ; Disease Models, Animal ; Cell Line ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) causes incurable vision loss in elderly individuals, and there is currently only a rarely effective treatment for dry AMD. Necroptosis is attracting increasing attention in the context of AMD. This study aimed to elucidate the mechanisms underlying the induction of abnormal necroptosis in AMD.<br><br>METHODS: Sodium iodate (SI) was used to establish in vitro and in vivo retinal pigment epithelium cell (RPE) degeneration models and to simulate dry AMD-like conditions. Phenotypes and classic necroptosis markers were identified. RNA-seq was performed on the retinas of RPE-degeneration mice and combined with the GSE29801 microarray data of human AMD retinal samples to identify the key genes regulating necroptosis. Key genes were overexpressed both in vivo and in vitro to further validate their function in necroptosis and RPE degeneration.<br><br>RESULTS: Necroptosis phenotypes and the expression of the necroptosis markers RIPK1, RIPK3, and MLKL were upregulated in both SI-treated ARPE-19 cells and the RPE layer of mice. Transcriptome data from SI-treated mice and patients with AMD revealed that the reduced expression of PYGM is implicated in the regulation of necroptosis. PYGM overexpression in RPE cells and mouse retinas alleviated SI-induced RPE degeneration.<br><br>CONCLUSIONS: This study confirmed that PYGM attenuates necroptosis in cellular and animal models resembling dry AMD, providing a new perspective on exploring novel AMD treatment targets.}, }
@article {pmid41183785, year = {2025}, author = {Basilious, A and Yuan, AT and Sheidow, TG}, title = {Outcomes of 16-week extension of anti-VEGF therapy in neovascular age-related macular degeneration.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2025.10.002}, pmid = {41183785}, issn = {1715-3360}, abstract = {OBJECTIVE: To determine the outcomes of extending anti-VEGF injection intervals to 4 months in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A prospective cohort study.<br><br>PARTICIPANTS: Patients undergoing injections with standard-dose anti-VEGF (aflibercept, ranibizumab) with documented disease stability at 3-month injection intervals for &#x2265;2 years.<br><br>METHODS: The injection interval was extended to 4 months. The primary outcome of disease stability was defined as no clinical evidence of lesion growth, blood, or intraretinal or new subretinal fluid seen on ocular coherence tomography (OCT). Demographic data, visual acuity, exam findings, and OCT data were collected.<br><br>RESULTS: This study included 88 eyes (83.4 &#xb1; 7.3 years, 64.8% female) with nAMD extended to injection intervals of 4 months (56 eyes with aflibercept and 32 with ranibizumab). The recurrence rate was 10.2% (9/88). Four eyes recurred after the first 4-month extension interval, 2 eyes at the 8-month follow-up, 2 eyes at 16 months, and 1 eye at 22 months. In eyes with a recurrence (n&#x202f;=&#x202f;9), there was no significant difference (p > .05) between mean visual acuity prior to recurrence (0.18 &#xb1; 0.13 [20/30]) and at final follow-up postrecurrence (0.21 &#xb1; 0.17 [20/30]). All but 1 case returned to within 1 Snellen line of visual acuity at final follow-up. All eyes were able to regain stability at 3- or 4-month injection intervals.<br><br>CONCLUSIONS: In nAMD patients with disease stability at 3-month injection intervals for at least 2 years, the majority remained stable when extended to 4 months. Recurrences were able to achieve stability again with shorter injection intervals, without a persistent decline in visual acuity.}, }
@article {pmid41184811, year = {2025}, author = {Wang, Y and Wei, W and Pei, X and Zhan, H and Tang, Y and Li, Y and Bai, J and Li, J}, title = {PDC-DETR: a Parallel Dilated Convolutional Detection Transformer for preliminary screening of multiple macular degeneration.}, journal = {BMC medical imaging}, volume = {25}, number = {1}, pages = {439}, pmid = {41184811}, issn = {1471-2342}, support = {2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; }, abstract = {Current diagnostic approaches for macular degeneration in optical coherence tomography (OCT) images often lead to misdiagnosis due to their limited ability to capture the disease’s multiscale and irregular features. We present PDC-DETR, a Parallel Dilated Convolutional Detection Transformer, which introduces three major innovations for accurate and efficient macular degeneration analysis. First, a Parallel Feature-Optimized Attention Pyramid Network (PFOAPN) enables simultaneous modeling of global context and local details through multi-scale feature pathways. Second, a novel Wise-MPDIoU loss dynamically adjusts to variations in image quality while improving lesion localization accuracy. Third, the lightweight design ensures real-time clinical applicability, requiring only 38.2 MB parameters and 58.5 GFLOPs, while achieving 94.1% accuracy across five macular degeneration categories at 71 FPS. This study establishes a new benchmark for automated OCT-based retinal disease detection, providing both high diagnostic accuracy and practical clinical deployment potential.}, }
@article {pmid41186544, year = {2026}, author = {Lou, J and Liao, X}, title = {Re: Friedman et al: Randomized trial of biosimilar ABP 938 compared with reference aflibercept in adults with neovascular age-related macular degeneration (2025 Aug 5:S2468-6530(25)00351-3. doi: 10.1016/j.oret.2025.07.015. Online ahead of print.).}, journal = {Ophthalmology. Retina}, volume = {10}, number = {1}, pages = {e1}, doi = {10.1016/j.oret.2025.10.003}, pmid = {41186544}, issn = {2468-6530}, }
@article {pmid41187156, year = {2025}, author = {Li, Y and Wang, B and Luo, X and Zhang, M and Hu, Q and Li, X}, title = {Machine learning models for risk prediction of age-related macular degeneration in Fujian eye study.}, journal = {PloS one}, volume = {20}, number = {11}, pages = {e0335620}, pmid = {41187156}, issn = {1932-6203}, mesh = {Humans ; *Macular Degeneration/epidemiology/diagnosis ; *Machine Learning ; Female ; Male ; Aged ; Cross-Sectional Studies ; Risk Factors ; Logistic Models ; Middle Aged ; Aged, 80 and over ; Support Vector Machine ; }, abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a retinal disorder that significantly impairs vision. This study investigates various machine learning models for predicting AMD risk, laying the groundwork for further research using big data and determining the most effective predictive model.<br><br>METHODS: Utilizing data from 8211 records with 39 features from the Fujian Eye Study, a cross-sectional epidemiological investigation, several machine learning models were developed and assessed. The models included logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Data preprocessing, feature selection, and model training were all key components of the study.<br><br>RESULTS: After evaluating multiple models, the logistic regression model emerged as the most accurate, achieving a balanced accuracy of 0.6364. Among the predictive features, educational background had the highest influence on the model's predictions, with an average SHAP (SHapley Additive exPlanations) value of 0.8199. Other significant factors included outdoor time and left eye spherical equivalent (OSSE), with SHAP values of 0.6474 and 0.6377, respectively.<br><br>CONCLUSION: This study confirms that logistic regression is the most effective machine learning model for predicting AMD risk, with educational background identified as the most critical risk factor.}, }
@article {pmid41187450, year = {2025}, author = {Dashti, R and Safaei, F and Sadeghian, G and Hosseini, SA and Salimibani, M}, title = {Peptide-functionalized nanomaterials for controlled drug delivery and regenerative therapies in retinal diseases.}, journal = {Journal of biomaterials applications}, volume = {}, number = {}, pages = {8853282251395196}, doi = {10.1177/08853282251395196}, pmid = {41187450}, issn = {1530-8022}, abstract = {Degenerative retinal diseases, such as diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa, cause irreversible vision loss by destroying vital retinal cells and represent major global health concerns. Traditional therapies have limited success in fully restoring vision due to the complex retinal structure and blood-retinal barriers (BRBs), though they may help alleviate symptoms or slow disease progression in some cases. Nanochemistry and peptide-based systems represent breakthrough approaches by leveraging nanoscale precision and biological specificity. This review examines the chemical design and synthesis of nanoparticles (NPs), nanoscaffolds, and peptide conjugates used in retinal neural regeneration. It also explores their biomedical applications, especially in targeted drug delivery, tissue engineering, and cellular repair. Biodegradable polymeric NPs, liposomes, and hybrid nanostructures are designed to cross barriers, release drugs in a controlled manner, and enhance biocompatibility. PEGylation improves stability and reduces immune responses in the ocular environment, while peptide functionalization enables specific cellular targeting and minimizes inflammatory reactions. Peptide-functionalized platforms, such as RGD-modified NPs and self-assembling hydrogels, provide receptor-mediated targeting and extracellular matrix (ECM) mimicry to support retinal regeneration for improved stem cell differentiation and neuroprotection. We discuss drug/gene delivery mechanisms, cellular interactions, and immune modulation, as well as neuroprotection, stem cell therapy, and diagnostic applications. Preclinical studies have demonstrated promising efficacy in animal models; however, concerns regarding scalability, long-term safety, and non-invasive delivery persist. Next-generation technologies, such as stimuli-responsive NPs, computationally designed peptides, and patient-specific delivery systems, are on the horizon to address unmet clinical needs. By marrying nanochemistry's precision with peptides' bioactivity, these technologies have the potential to transform retinal disease treatment, enabling the restoration of vision and an improvement in quality of life for millions of people worldwide.}, }
@article {pmid41188571, year = {2026}, author = {Eilon, E and Lishinsky-Fischer, N and Levy, J}, title = {Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study.}, journal = {Eye (London, England)}, volume = {40}, number = {1}, pages = {71-76}, pmid = {41188571}, issn = {1476-5454}, mesh = {Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; *Hypertension, Pulmonary/drug therapy/complications ; *Epoprostenol/analogs &amp; derivatives/therapeutic use ; *Macular Degeneration/prevention &amp; control/epidemiology ; *Antihypertensive Agents/therapeutic use ; Risk Factors ; Incidence ; Follow-Up Studies ; *Prostaglandins, Synthetic/therapeutic use ; Proportional Hazards Models ; }, abstract = {BACKGROUND/OBJECTIVES: To assess whether systemic prostacyclin analogue (PCA) therapy in patients with pulmonary arterial hypertension (PAH) is associated with a reduced long-term risk of developing age-related macular degeneration (AMD).<br><br>SUBJECTS/METHODS: A retrospective cohort study was conducted using the TriNetX global health research network. Patients aged &#x2265;50 with a diagnosis of PAH were included and stratified by PCA treatment. Propensity score matching (1:1) was applied to balance demographics and comorbidities. Incident diagnoses of non-neovascular AMD (non-nvAMD) and neovascular AMD (nvAMD) were compared across six follow-up intervals (3-15 years) using Kaplan-Meier analysis and Cox proportional hazards models.<br><br>RESULTS: Following matching, 9862 PCA-treated and 9862 untreated PAH patients were analysed. PCA-treated patients showed a consistently lower risk of non-nvAMD across all follow-up periods (hazard ratios [HRs] 0.30-0.37; all p&#x2009;<&#x2009;0.001). A similar protective trend was observed for nvAMD, with significant associations emerging at longer follow-up (HR&#x2009;=&#x2009;0.37-0.39 at 10-15 years; p&#x2009;<&#x2009;0.05). The protective effect was robust and durable over time.<br><br>CONCLUSIONS: Systemic administration of prostacyclin analogues is associated with a significant and sustained reduction in AMD risk among patients with PAH. These findings suggest a potential preventive role for PCAs in AMD pathogenesis and merit further investigation in broader populations.}, }
@article {pmid41189030, year = {2025}, author = {Arnal, L and Mesfin, Y and Xu, C and Salvi, A and Mishra, K and Ludwig, CA}, title = {Beyond refractive error: myopia's exponential burden on retinal health with each diopter.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {121}, pmid = {41189030}, issn = {2056-9920}, support = {K23 EY035741/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; NEI P30-EY026877//P30 Vision Research Core Grant/ ; K23EY035741//National Eye Institute K23 Grant/ ; }, abstract = {BACKGROUND: As myopia reaches epidemic levels worldwide, its role in driving vision-threatening retinal complications is increasingly urgent. This study quantifies the burden of myopia by examining its association with key retinal diseases and how risk escalates with increasing severity.<br><br>METHODS: We conducted a retrospective cohort study using the STARR clinical data warehouse, including all patients with &#x2265;&#x2009;1 documented eye visit. Myopia severity was defined by spherical equivalent and axial length, classifying patients as non-myopic, myopic, highly myopic, or severely myopic. Primary outcomes included six retinal diseases associated with myopia: choroidal neovascularization (CNV), myopic macular degeneration (MMD), foveoschisis, macular hole (MH), rhegmatogenous retinal detachment (RRD), and foveal retinal detachment (FRD). Adjusted logistic regression estimated odds by myopia severity and spherical equivalent. Mean age at diagnosis was compared across groups.<br><br>RESULTS: Retinal complications occurred at younger ages with increasing myopia severity. Compared to non-myopes, myopic, highly myopic, and severely myopic patients had 2.45 (95% CI: 2.36-2.55), 2.46 (95% CI: 2.31-2.62), and 8.15 (95% CI: 7.17-9.27) times higher odds, respectively, of developing any retinal complication. Per diopter increase in myopia, the odds of each complication increased: CNV (OR 1.11; 95% CI: 1.09-1.12), MMD (OR 1.22; 95% CI: 1.18-1.25), foveoschisis (OR 1.22; 95% CI: 1.16-1.28), MH (OR 1.06; 95% CI: 1.05-1.08), FRD (OR 1.23; 95% CI: 1.16-1.32), and RRD (OR 1.10; 95% CI: 1.10-1.11). In severe myopes, odds were markedly elevated: CNV (OR 22.90), MMD (OR 60.19), foveoschisis (OR 102.98), MH (OR 6.69), FRD (OR 22.72), and RRD (OR 6.84).<br><br>CONCLUSIONS: Myopia is independently associated with higher odds of retinal diseases, and this risk increases incrementally with severity. These findings support a dose-response relationship and highlight the importance of early risk stratification, tailored monitoring, and timely referral in patients with high and severe myopia.}, }
@article {pmid41189775, year = {2025}, author = {Guzun, OV and Zadorozhnyy, OS and Konovalova, NV and Bezdetko, PA and Korol, AR and Dumbrăveanu, LG and Cușnir, VN and Cușnir, VV}, title = {Reducing the risk of age-related macular degeneration progression - five-year follow-up study in Ukraine and Moldova.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {340-349}, pmid = {41189775}, issn = {2501-2533}, mesh = {Humans ; Ukraine/epidemiology ; Disease Progression ; Follow-Up Studies ; Male ; Female ; Prospective Studies ; Aged ; *Dietary Supplements ; *Macular Degeneration/epidemiology/prevention &amp; control/diagnosis ; Moldova/epidemiology ; *Antioxidants/administration &amp; dosage/therapeutic use ; Time Factors ; *Visual Acuity ; Risk Factors ; Middle Aged ; Vitamins ; *Fatty Acids, Omega-3/administration &amp; dosage ; }, abstract = {This open prospective study aimed to evaluate the dynamics of progression of early and intermediate age-related macular degeneration (AMD) against the background of continuous use of the nutraceutical formula AREDS2, which includes omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and photobiomodulation (PBM), over a 5-year follow-up in patients from Ukraine and Moldova. Examining 126,400 patients, 163 patients (304 eyes) with early and intermediate stages of AMD were treated (5-year follow-up). Patients were divided into two groups. Patients in the 1st group (149 eyes) were prescribed a nutraceutical formula based on AREDS2 with omega-3 PUFAs, vitamin D, and resveratrol (Nutrof®Forte 1 capsule once a day continuously). The second group (155 eyes) included patients who irregularly took various vitamin-antioxidant complexes. All patients underwent PBM every 6 months. The five-year prevalence of early and intermediate AMD was estimated using data from leading ophthalmological centers in Ukraine (Odesa - 7.1%, Kharkiv - 6.6%) and Moldova (6.3%). AMD progression in the multivariate Cox regression model over five years showed a 3.24-fold reduction in relative risk (95% CI: 2.15-4.79, p=0.000) for patients with early and intermediate AMD who regularly took the recommended nutraceutical (compared to those who irregularly took various vitamin-antioxidant complexes). Patients with early and intermediate AMD are recommended to undergo courses of PBM every six months. Additionally, it is crucial to address cardiovascular issues and consistently use the AREDS2 nutraceutical formula. Adherence to these recommendations can reduce the likelihood of disease progression by at least 3.24 times over the next 5 years.}, }
@article {pmid41189785, year = {2025}, author = {Stoica, AM and Jurja, S and Dervis, N}, title = {Anti-VEGF therapy - a new hope in AMD treatment.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {322-327}, pmid = {41189785}, issn = {2501-2533}, mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Choroidal Neovascularization/drug therapy/etiology ; *Macular Degeneration/drug therapy/complications ; Ranibizumab ; *Wet Macular Degeneration/drug therapy ; Bevacizumab ; }, abstract = {Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) represents a significant global cause of visual impairment. Contemporary therapeutic approaches for neovascular AMD focus on inducing regression of CNV by inhibiting critical growth factors involved in angiogenesis. For nearly two decades, vascular endothelial growth factor (VEGF) has been the principal therapeutic target, with multiple intravitreally administered agents developed to achieve anatomical restoration and improved visual outcomes through sustained dosing.}, }
@article {pmid41189788, year = {2025}, author = {Stoica, AM and Jurja, S and Dervis, N}, title = {The Role of Vitamin D in Retinal Physiology.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {315-321}, pmid = {41189788}, issn = {2501-2533}, mesh = {Humans ; *Vitamin D/physiology ; *Retina/physiology ; *Retinal Diseases/physiopathology/metabolism/prevention &amp; control ; Oxidative Stress/physiology ; Vitamin D Deficiency/physiopathology ; Animals ; }, abstract = {Vitamin D plays a crucial role in ocular health, particularly in the function and protection of the retina. This fat-soluble vitamin is synthesized in the skin in response to UVB radiation and can also be obtained from dietary sources. Research indicates that vitamin D has neuroprotective properties, which are essential for retinal cell survival and function. The active form of vitamin D, calcitriol, has been shown to modulate inflammation and oxidative stress in retinal tissues, thus potentially preventing retinal degeneration diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Furthermore, vitamin D receptors are expressed in various retinal cells, suggesting that vitamin D directly influences retinal physiology. Deficiency in vitamin D has been associated with an increased risk of chronic eye diseases, emphasizing the importance of maintaining adequate vitamin D levels for preserving retinal health. Ongoing studies are needed to elucidate further the molecular mechanisms underlying the protective effects of vitamin D on the retina and to explore its therapeutic potential in retinal disorders.}, }
@article {pmid41189793, year = {2025}, author = {Muşat, AAM and Zamfiroiu-Avidis, N and Ştefan, C and Andreea, S and Muşat, G and Udrea, G and Popescu, IS and Muşat, O}, title = {A Case Series of Serious Adverse Events Following Anti-VEGF Intravitreal Injections.}, journal = {Romanian journal of ophthalmology}, volume = {69}, number = {3}, pages = {450-454}, pmid = {41189793}, issn = {2501-2533}, mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Bevacizumab/adverse effects/administration &amp; dosage ; *Cataract/chemically induced/diagnosis ; *Endophthalmitis/chemically induced/diagnosis ; Intravitreal Injections/adverse effects ; *Ranibizumab/adverse effects/administration &amp; dosage ; *Retinal Detachment/chemically induced/diagnosis ; Retrospective Studies ; Tomography, Optical Coherence ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; }, abstract = {PURPOSE: To highlight serious adverse effects regarding intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, which is widely used for the treatment of retinal diseases, including two cases of post-injection endophthalmitis, one of which was complicated by rhegmatogenous retinal detachment, and one case of secondary cataract following a potentially unnecessary injection.<br><br>METHODS: A retrospective analysis of three cases that developed complications after intravitreal anti-VEGF therapy.<br><br>RESULTS: All cases resulted in a decline in best corrected visual acuity (BCVA) that required additional surgical procedures.<br><br>DISCUSSION: While intravitreal anti-VEGF therapy has become the standard in the treatment of various retinal pathologies, it is not without risks. This case series presents significant adverse outcomes, emphasizing the potential for severe anatomical and functional consequences. As the global volume of anti-VEGF intravitreal injections increases, so must our commitment to patient safety, precision in diagnosis, and ethical decision making.<br><br>CONCLUSION: Although generally safe and commonly used in clinical practice, physicians must be aware of the risks of anti-VEGF therapy and must remain vigilant regarding patient selection and risk-benefit considerations.}, }
@article {pmid41191064, year = {2026}, author = {Hasan, N and Sadeghi, E and Gandhi, P and Vupparaboina, SC and Du, K and Eller, AW and Sahel, JA and Bollepalli, SC and Vupparaboina, KK and Chhablani, J}, title = {Demography, clinical profile and risk of retinal vein occlusion among patients with age-related macular degeneration - a tertiary hospital based study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {383-392}, pmid = {41191064}, issn = {1435-702X}, mesh = {Humans ; Female ; Male ; *Retinal Vein Occlusion/epidemiology/diagnosis/etiology ; Risk Factors ; Aged ; Incidence ; Prevalence ; Retrospective Studies ; *Tertiary Care Centers/statistics &amp; numerical data ; *Visual Acuity ; Aged, 80 and over ; *Macular Degeneration/complications/diagnosis/epidemiology ; Follow-Up Studies ; Risk Assessment/methods ; Tomography, Optical Coherence/methods ; Middle Aged ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) and retinal vein occlusion (RVO) share common risk factors and the risk of blindness is higher when both diseases coexist. This study aims to evaluate the risk factors of developing RVO among AMD patients and describe their clinical characteristics.<br><br>METHODS: In this single-center cohort study, 5618 Patients with AMD were divided into two groups: those who developed RVO and those who did not. Demographic, clinical and comorbidity profile were compared and multivariable logistic regression was performed to identify risk factors for RVO among patients with AMD. Additionally, baseline characteristics were compared between patients who developed central and branch retinal vein occlusion (CRVO and BRVO).<br><br>RESULTS: Among 5,618 patients with AMD, 55 developed RVO while 5563 did not. The prevalence of RVO among AMD patients was 9.79/1,000 AMD patients (95% CI:7.2-12.4) with an incidence rate of 2.04/1,000 person-years. Multivariate regression analysis revealed patients with lower BMI(OR:0.89,95%CI:0.84-0.95,p&#x2009;=&#x2009;<&#x2009;0.001), higher Charlson comorbidity index(OR:1.12,95%CI:1.02-1.22,p&#x2009;=&#x2009;0.019), African-American ethnicity(OR:4.07,95%CI:1.55-10.73,p&#x2009;=&#x2009;0.004), glaucoma(OR:2.09,95%CI:1.2-3.64,p&#x2009;=&#x2009;0.009) and neovascular AMD(OR:1.92,95%CI:1.07-3.43,p&#x2009;=&#x2009;0.028) have higher risk. On subgroup analysis, 27 patients developed CRVO, while 29 developed BRVO. The mean time to RVO development after the first visit for AMD was 4.42&#xb1;3.6 years. Patients with CRVO had significantly worse visual acuity(p&#x2009;<&#x2009;0.001), higher IOP(p&#x2009;=&#x2009;0.012), and a higher incidence of glaucoma(p&#x2009;=&#x2009;0.006) at baseline.<br><br>CONCLUSION: AMD Patients with lower BMI, higher CCI, African Americans, glaucoma, and neovascular AMD are at a higher risk of developing RVO. Identifying these risk factors is crucial to diagnose RVO promptly in patients with AMD as it has a higher prevalence compared to the general population, with a greater risk for vision loss.}, }
@article {pmid41191163, year = {2025}, author = {Zhang, J and Kamoi, K and Zong, Y and Yang, M and Zou, Y and Ohno-Matsui, K}, title = {Inflammation and Immune Pathways in Myopia: An Overview on Pathomechanisms and Treatment Prospects.}, journal = {Clinical reviews in allergy &amp; immunology}, volume = {68}, number = {1}, pages = {98}, pmid = {41191163}, issn = {1559-0267}, support = {JPMJSP2180//JST SPRING/ ; 25K02864//Japan Society for the Promotion of Science/ ; 22FC0201//Ministry of Health, Labour and Welfare/ ; 23fk0108671h0001, 23fk0108672h000//Japan Agency for Medical Research and Development/ ; FY2023//Takeda Science Foundation/ ; }, mesh = {Humans ; *Myopia/therapy/immunology/etiology/metabolism/epidemiology ; *Inflammation/immunology/metabolism ; Animals ; Cytokines/metabolism ; Anti-Inflammatory Agents/therapeutic use ; Signal Transduction ; Inflammation Mediators/metabolism ; Disease Susceptibility ; Extracellular Matrix/metabolism ; Disease Management ; }, abstract = {Myopia represents a growing global public health challenge, characterized by increasing prevalence and associated complications such as myopic macular degeneration and retinal detachment. Although genetic and environmental factors are well-recognized contributors, emerging evidence supports a pathological link between inflammation and myopia progression. Epidemiological studies indicate a higher incidence of myopia among individuals with systemic or ocular inflammatory conditions. Inflammation perturbs the ocular immune microenvironment by upregulating pro-inflammatory cytokines and matrix metalloproteinase-2, thereby accelerating extracellular matrix (ECM) degradation and scleral remodeling, which culminates in axial elongation. Conversely, excessive axial elongation in high myopia triggers choroidal microvascular dysfunction, tissue hypoxia, and disruption of the blood-retinal barrier, leading to elevated inflammatory cytokines in the aqueous humor and vitreous, thereby raising the possibility of a self-perpetuating loop. Anti-inflammatory agents, including diacerein, resveratrol, and lactoferrin, have demonstrated therapeutic potential in experimental models by modulating inflammatory pathways, reducing pro-inflammatory cytokines, and preserving ECM integrity. However, their clinical efficacy and long-term safety require further validation. Elucidating the complex interplay between inflammation and myopia is pivotal for the development of targeted interventions, moving the focus of myopia management beyond optical correction towards disease-modifying strategies.}, }
@article {pmid41191669, year = {2025}, author = {Zhou, J and He, Y and Wang, J and Cao, J and Huang, X and Chen, M and Ye, J}, title = {Malnutrition and age-related macular degeneration: mechanistic insights from UK Biobank metabolomic and imaging data.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {80}, number = {12}, pages = {}, doi = {10.1093/gerona/glaf229}, pmid = {41191669}, issn = {1758-535X}, support = {82330032//Key Program of the National Natural Science Foundation of China/ ; U20A20386//National Natural Science Foundation Regional Innovation and Development Joint Fund/ ; 2024C03204//Key Research and Development Program of Zhejiang Province/ ; 82301208//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; *Macular Degeneration/epidemiology/etiology/metabolism/diagnostic imaging ; Female ; Middle Aged ; United Kingdom/epidemiology ; *Malnutrition/complications/metabolism/epidemiology ; Metabolomics ; Biological Specimen Banks ; Aged ; Risk Factors ; Cohort Studies ; Tomography, Optical Coherence ; UK Biobank ; }, abstract = {BACKGROUND: Malnutrition, characterized by degeneration of body composition due to reduced intake or inflammation, shares some common mechanisms with age-related macular degeneration (AMD), while their associations remain unexplored.<br><br>METHODS: This cohort study utilized data from the UK Biobank. Participants without pre-existing AMD and with complete malnutrition data were included. Cox regression was employed to evaluate the longitudinal association. An ElasticNet model was used to derive a metabolomic signature of malnutrition, which was subsequently assessed for association with AMD. Malnutrition and the metabolomic signature were further tested for associations with photoreceptor thinning. Structural equation modeling was applied to delineate underlying mechanisms.<br><br>RESULTS: A total of 444&#x2009;681 participants (mean age: 56.4&#x2009;&#xb1;&#x2009;8.1 years; 45.8% male) were included, with 32&#x2009;086 (7.2%) diagnosed with malnutrition at baseline. Over a median follow-up of 13.6 years, 10 009 AMD cases were identified. Malnutrition was associated with an increased risk of AMD (hazard ratio [HR]: 1.221, 95% CI, 1.144-1.304, p&#x2009;<&#x2009;.001). The metabolomic signature of malnutrition, derived from 127 metabolites, was significantly associated with AMD risk (per SD increase: HR: 1.073, 95% CI, 1.037-1.110, p&#x2009;<&#x2009;.001) and thinner photoreceptor layer (&#x3b2;&#x2009;=&#x2009;-.214, 95% CI, -0.314 to -0.114, p&#x2009;<&#x2009;.001). Structural equation modeling revealed that malnutrition increased AMD risk partially through metabolomic changes that induced photoreceptor thinning.<br><br>CONCLUSIONS: Malnutrition in middle-aged adults was significantly associated with increased risk of AMD, which was mediated by metabolomic alterations that impaired photoreceptor health.}, }
@article {pmid41192738, year = {2026}, author = {Aphale, P and Shekhar, H and Dokania, S}, title = {Comments on "Refining the translational pathway for senotherapeutics in age-related macular degeneration: Insights on biomarkers, delivery strategies, and clinical trial design".}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {1010-1011}, doi = {10.1016/j.survophthal.2025.10.002}, pmid = {41192738}, issn = {1879-3304}, }
@article {pmid41194409, year = {2026}, author = {Zarei-Ghanavati, S and Motamed Shariati, M and Hadi, Y and Khazaei, S and Yoo, SH}, title = {Cataract surgery in the context of age-related macular degeneration: challenges and considerations.}, journal = {Journal of cataract and refractive surgery}, volume = {52}, number = {4}, pages = {398-405}, pmid = {41194409}, issn = {1873-4502}, mesh = {Humans ; *Cataract Extraction/methods ; *Macular Degeneration/complications ; *Cataract/complications ; Visual Acuity/physiology ; Lens Implantation, Intraocular ; }, abstract = {Age-related macular degeneration (AMD) and cataracts commonly coexist in the aging population, posing unique diagnostic and therapeutic challenges for ophthalmologists. Although cataract surgery can substantially improve visual function, outcomes are often influenced by the type and severity of underlying macular pathology. This narrative review explores current evidence on the impact of cataract surgery in patients with AMD, including preoperative assessment strategies, intraoperative considerations, and postoperative visual expectations. The role of multimodal imaging in detecting subclinical macular changes, advanced intraocular lenses, and the debated relationship between cataract surgery and AMD progression are discussed. Emphasis is placed on personalized patient selection and counseling to optimize outcomes. Overall, with appropriate planning and patient-centered care, cataract surgery remains a safe and beneficial intervention for most individuals with AMD.}, }
@article {pmid41194565, year = {2025}, author = {Singh, RB and Stettler, I and Romano, F and Parmar, UPS and Surico, PL and Ding, X and Kim, J and Rai, KK and Miller, JW and Miller, JB}, title = {Prevalence of Age-Related Macular Degeneration in the United States: A Medicare-Based Analysis from 2014 to 2021.}, journal = {Ophthalmic research}, volume = {68}, number = {1}, pages = {573-582}, pmid = {41194565}, issn = {1423-0259}, mesh = {Humans ; United States/epidemiology ; Aged ; Female ; Male ; Retrospective Studies ; *Medicare/statistics &amp; numerical data ; Prevalence ; Aged, 80 and over ; *Macular Degeneration/epidemiology ; Age Distribution ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of vision loss among older adults in the USA. Understanding its prevalence and demographic distribution is critical for developing targeted public health strategies. This study aimed to assess the prevalence of AMD and its clinical stages among US Medicare beneficiaries aged 65 years and older.<br><br>METHODS: We conducted a retrospective cohort study using the Vision and Eye Health Surveillance System (VEHSS) database of Medicare beneficiaries diagnosed with AMD between 2014 and 2021. Crude prevalence rates for overall AMD, early AMD, intermediate AMD, wet AMD, and geographic atrophy (GA) were calculated at national and state levels. Prevalence was stratified by age, sex, and race/ethnicity. Statistical analyses included the Mann-Whitney U test for age and sex comparisons, the Brown-Forsythe one-way ANOVA for racial/ethnic comparisons, and the Dunnett T3 test for post hoc analyses.<br><br>RESULTS: In 2021, the VEHSS-Medicare dataset included 24,129,807 individuals aged 65 and older, among whom the national prevalence of AMD was 10.40%. Prevalence rates for early AMD, intermediate AMD, wet AMD, and GA were 2.87%, 6.91%, 2.14%, and 0.73%, respectively. The number of AMD cases increased from 2.33 million in 2014 to 2.51 million in 2021. Prevalence was significantly higher in individuals aged &#x2265;85 years compared to those aged 65-84 years, and in females compared to males. Post hoc analyses demonstrated that White individuals had a significantly higher prevalence of AMD compared with all other racial/ethnic groups.<br><br>CONCLUSIONS: The prevalence of AMD among US adults aged 65 years and older was 10.4%, with higher rates observed in the oldest age groups, females, and White individuals. These findings highlight the importance of addressing disparities in AMD prevention and care, particularly in populations at greatest risk.}, }
@article {pmid41194821, year = {2025}, author = {Almpanidou, S and Gounari, E and Goulas, A and Topouzis, F and Talimtzi, P and Kouzi-Koliakou, K and Karampatakis, V and Koliakos, G}, title = {Targeting Angiogenesis and Visual Cycle in Age-Related Macular Degeneration: The Role of Stem Cells and Vinpocetine.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e93878}, pmid = {41194821}, issn = {2168-8184}, abstract = {Purpose The purpose of this study was to evaluate whether bone marrow stem cells (BMSCs), vinpocetine, or their combination can attenuate amyloid-β (Aβ)-induced alterations in angiogenesis and visual cycle gene expression in a cellular model of age-related macular degeneration (AMD). Methods Human retinal pigment epithelium (RPE) cells (ARPE-19) were exposed to Aβ 1-42 for 24h and divided into four groups: (i) co-culture with BMSCs, (ii) treated with vinpocetine, (iii) treated with BMSCs and vinpocetine, and (iv) untreated control. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the mRNA expression levels of angiogenesis-related genes, vascular endothelial growth factor (VEGF-A) and pigment epithelium-derived factor (PEDF), and RPE-associated visual cycle genes: lecithin retinol acyltransferase (LRAT), retinoid isomerohydrolase (RPE65), retinol dehydrogenase 5 (RDH5), retinol dehydrogenase 10 (RDH10), and retinaldehyde-binding protein 1 (RLPB1). Results Aβ1-42 significantly reduced ARPE-19 cell viability (p=0.002); all treatments significantly restored viability. Aβ1-42 upregulated VEGF-A expression, which was significantly downregulated by all treatments. Although Aβ1-42 slightly increased PEDF expression, all treatments significantly enhanced its upregulation, with the combination therapy showing the greatest effect (p=0.006, 0.010, and 0.002, respectively). Furthermore, Aβ 1-42 induced upregulation of most visual cycle genes was reversed by all treatments. Conclusion Aβ1-42 induces cytotoxicity, angiogenesis, and dysregulation of visual cycle genes in RPE cells in vitro. BMSCs, vinpocetine, and their combination attenuate these effects, supporting a potential role in AMD therapy pending further investigation.}, }
@article {pmid41196411, year = {2025}, author = {Furtado, J and Zapadka, TE and Park, H and Boyé, K and Demb, JB and Eichmann, A}, title = {Restoring compromised blood-retina-barrier integrity with Netrin-1 overexpression.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {389}, pmid = {41196411}, issn = {1420-9071}, support = {R01 HL125811/HL/NHLBI NIH HHS/United States ; 834161/ERC_/European Research Council/International ; 1R01HLI125811//NHLBI Division of Intramural Research/ ; 830299//American Heart Association/ ; }, mesh = {*Netrin-1/genetics/metabolism ; Animals ; *Blood-Retinal Barrier/metabolism/pathology ; Mice ; Diabetic Retinopathy/pathology/metabolism/genetics ; Choroidal Neovascularization/pathology/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Electroretinography ; Netrin Receptors/genetics ; Mice, Knockout ; Retina/metabolism/pathology ; }, abstract = {The blood-retina barrier (BRB) protects retinal neuronal function and enables vision. A compromised, leaky BRB is a hallmark of vision-threatening retinal diseases such as diabetic retinopathy (DR) and wet age-related macular degeneration (AMD) that affect millions of persons worldwide. Strategies to enhance BRB integrity hold promise as therapeutic interventions to prevent vision loss. Previous studies identified Netrin-1 (NTN1) as a key regulator of BRB stability and revealed reduced Netrin-1 signaling in DR patients, suggesting that Netrin-1 supplementation could help preserve BRB function and prevent disease progression. Herein, we used inducible genetic NTN1 overexpression to investigate effects on BRB development and maintenance. We show that global NTN1 overexpression converted leaky vessels at the P5 angiogenic front into a non-leaky state. In pathological settings, NTN1 overexpression reinforced BRB integrity in oxygen-induced retinopathy (OIR), improving electroretinogram (ERG) amplitudes and rescued vascular leak in laser-induced choroidal neovascularization (CNV). NTN1 overexpression or Ntn1 knockout minimally and transiently affected retinal angiogenesis. Global Unc5b deletion phenocopied vascular leak observed in Ntn1 deficient retinas, while angiogenesis defects differed between Ntn1 and Unc5b knockouts. These findings establish Netrin-1 as a promising therapeutic target for preventing BRB breakdown in retinal vascular diseases and suggest that reinforcing the Netrin-1/Unc5b signaling pathway may provide a strategy to selectively stabilize the BRB.}, }
@article {pmid41197713, year = {2025}, author = {Allan, KC and Cohn, EF and Bala, S and Kim, SB and Kaelber, DC and Singh, RP and Talcott, KE and Mammo, DA and Rachitskaya, AV}, title = {Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Neovascular Age-Related Macular Degeneration in a National Cohort Study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2025.10.020}, pmid = {41197713}, issn = {2468-6530}, abstract = {PURPOSE: To investigate the risk of neovascular age-related macular degeneration (AMD) in patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs).<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: This study used the TriNetX network, a large aggregated electronic health records platform from health care organizations across the United States. Adults over the age of 60 years with &#x2265;1, 2, or 3 years of ophthalmology follow-up and medication prescription documentation were included.<br><br>METHODS: Patients were grouped into those taking GLP-1RAs, alternate glucose-lowering medications, and alternate lipid-lowering medications. Cohorts were propensity matched on demographics, chronic disease prevalence, and disease severity indicators.<br><br>MAIN OUTCOME MEASURES: The primary outcomes were risk of developing nonneovascular and neovascular AMD at 1, 2, and 3 years after initial medication prescription. A secondary analysis evaluated the risk of neovascular AMD in patients with nonneovascular AMD at baseline. Significance was defined as P < 0.05 and hazard ratio (HR) threshold >1.1 or <0.9 to minimize noise in large data sets.<br><br>RESULTS: Patients prescribed GLP-1RA had greater baseline chronic disease burden and worse disease severity metrics than comparator groups. Propensity matching effectively matched chronic disease prevalence at baseline. Glucagon-like peptide-1 receptor agonist prescription was associated with a significant reduction in risk of nonneovascular AMD compared with glucose-lowering medications over 1 (HR, 0.79; 95% confidence interval [CI], 0.66-0.94), 2 (HR, 0.75; 95% CI, 0.64-0.88), and 3 (HR, 0.77; 95% CI, 0.66-0.91) years. Similar protective effects were observed when compared with lipid-lowering medications after 2 (HR, 0.84; 95% CI, 0.71-0.99) and 3 (HR, 0.8; 95% CI, 0.68-0.94) years. There was a significant reduction in risk of neovascular AMD with GLP-1RA prescription across all time points compared with both alternate glucose-lowering and lipid-lowering medications. However, there was no significant impact of GLP-1RA on the risk of conversion from nonneovascular AMD at baseline to neovascular AMD.<br><br>CONCLUSIONS: These findings suggest that GLP-1RAs may provide protective effects against nonneovascular AMD and, importantly, did not show an increased risk of neovascular AMD. Future prospective trials are needed to validate these findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41198612, year = {2025}, author = {Ortega, AJ and Daniel, S and Renwick, M and Kambhampati, P and Thompson, KN and Collier, GE and Baker, EL and Zaki, H and Hulleman, JD}, title = {Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.}, journal = {Cell death &amp; disease}, volume = {16}, number = {1}, pages = {803}, pmid = {41198612}, issn = {2041-4889}, support = {R01 EY027785/EY/NEI NIH HHS/United States ; R01-DK128031//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; R01-EY027785//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; N/A//Edward N. and Della L. Thome Memorial Foundation (Thome Memorial Foundation)/ ; R01 DK128031/DK/NIDDK NIH HHS/United States ; R01 DK125352/DK/NIDDK NIH HHS/United States ; R01-DK125352//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism/deficiency ; Mice ; Caspase 1/metabolism/genetics ; *Macular Degeneration/genetics/pathology/metabolism ; *Extracellular Matrix Proteins/genetics/metabolism ; *Aging/pathology/genetics ; Inflammasomes/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {Chronic, unresolved inflammation has long been speculated to serve as an initiating and propagating factor in numerous neurodegenerative diseases, including a leading cause of irreversible blindness in the elderly, age-related macular degeneration (AMD). Intracellular multiprotein complexes called inflammasomes in combination with activated caspases facilitate production of pro-inflammatory cytokines such as interleukin 1 beta. Specifically, the nucleotide-binding oligomerization (NOD)-like receptor protein 3 (NLRP3) has received heightened attention due to the wide range of stimuli to which it can respond and its potential involvement in AMD. In this study, we directly tested the role of Nlrp3 and its downstream effector, caspase 1 (Casp1) in mediating early AMD-like pathology (i.e., basal laminar deposits [BLamDs]) in wild-type (WT) mice and the Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) mouse model (p.R345W mutation in Efemp1). Compared to aged-matched controls, R345W[+/+] knockin mice demonstrated increased Muller cell gliosis, subretinal Iba-1[+] cells, higher Nlrp3 immunoreactivity in the retina, as well as significant transcriptional upregulation of complement component 3, Nlrp3, pro-Il1b, pro-caspase-1, and tissue inhibitor of matrix metalloproteinase 3 in the retinal pigmented epithelium (RPE)/choroid. These findings were accompanied by an age-related increase in BLamD formation in the R345W[+/+] mice. Genetic elimination of either Nlrp3 or Casp1 significantly reduced both the size and coverage of BLamDs in the R345W[+/+] background, highlighting an important and underappreciated pathway that could affect ML/DHRD onset and progression. Moreover, Nlrp3 knockout reduced spontaneous, age-related BLamDs in WT mice, suggesting translatability of our findings not only to rare inherited retinal dystrophies, but also potentially to AMD itself.}, }
@article {pmid41198978, year = {2026}, author = {Gelisken, F and Koçak, N and Wenzel, CJ and Atay Dinçer, K and Wenzel, DA}, title = {Intravitreal anti-VEGF therapy for extrafoveal macular neovascularisation secondary to age-related macular degeneration: five-year results in a tertiary centre.}, journal = {Eye (London, England)}, volume = {40}, number = {1}, pages = {83-90}, pmid = {41198978}, issn = {1476-5454}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Visual Acuity/physiology ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/therapeutic use ; Aged, 80 and over ; Tomography, Optical Coherence ; Tertiary Care Centers ; *Macular Degeneration/complications/drug therapy/physiopathology ; Bevacizumab/therapeutic use ; Follow-Up Studies ; Middle Aged ; *Wet Macular Degeneration/drug therapy/physiopathology ; Fluorescein Angiography ; Treatment Outcome ; Fovea Centralis/pathology ; }, abstract = {OBJECTIVES: To assess the long-term efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy on best-corrected visual acuity (BCVA) and foveal morphology in patients with extrafoveal macular neovascularisation (MNV) secondary to age-related macular degeneration (AMD) over five years.<br><br>METHODS: A total of 104 eyes with treatment-na&#xef;ve extrafoveal MNV treated with intravitreal anti-VEGF injections were analysed retrospectively. BCVA was assessed at baseline and annually for five years. Central foveal thickness (CFT), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED), subretinal hyperreflective material (SHRM), and foveal atrophy (incomplete/complete retinal pigment epithelium and outer retinal atrophy (iRORA/cRORA))-were documented.<br><br>RESULTS: After five years, 46% of the eyes had unchanged or improved vision by one or more lines, whereas mean BVCA declined from 0.28&#x2009;&#xb1;&#x2009;0.20 logMAR at baseline to 0.50&#x2009;&#xb1;&#x2009;0.49 logMAR after five years (p&#x2009;=&#x2009;0.016). CFT, and the prevalence of IRF and SRF decreased significantly (p&#x2009;<&#x2009;0.001), while iRORA (p&#x2009;=&#x2009;0.041), and cRORA (p&#x2009;<&#x2009;0.001) increased by year five. Presence of cRORA was associated with worse five-year BCVA (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Anti-VEGF therapy for extrafoveal MNV secondary to AMD stabilised or improved BCVA in approximately half of the patients; however, mean BCVA declined after five years. Long-term functional benefits were limited due to morphological changes in the macula, such as subfoveal atrophy.}, }
@article {pmid41198979, year = {2026}, author = {Feo, A and Boscia, G and Borrelli, E and Quarta, A and Stradiotto, E and Forte, P and Viggiano, P and Popovic, MM and Corradetti, G and Savastano, A and Boscia, F and Sarraf, D and Sadda, SR and Romano, MR}, title = {Vitelliform lesions and choroidal changes in chorioretinal disorders: pathophysiological insights and clinical implications.}, journal = {Eye (London, England)}, volume = {40}, number = {1}, pages = {12-23}, pmid = {41198979}, issn = {1476-5454}, mesh = {*Choroid Diseases/diagnostic imaging/pathology/physiopathology ; *Retinal Diseases/diagnostic imaging/pathology/physiopathology ; Humans ; *Vitelliform Macular Dystrophy/diagnostic imaging/pathology/physiopathology ; *Retinal Pigment Epithelium/diagnostic imaging/pathology/physiopathology ; *Choroid/diagnostic imaging/pathology/physiopathology ; Retinal Vessels/pathology/physiopathology ; Tomography, Optical Coherence ; Fluorescein Angiography ; }, abstract = {This narrative review aims to explore the correlation between choroidal thickness (CT), broader choroidal changes, and the development and progression of vitelliform lesions, with a focus on their potential modulatory role-whether primary or secondary- through mechanisms involving choriocapillaris (CC) and retinal pigment epithelium (RPE) dysfunction. CT was found to be significantly increased in various vitelliform maculopathies, including adult-onset foveomacular vitelliform dystrophy (AOFVD), Best disease, autosomal recessive bestrophinopathy, age-related macular degeneration (AMD), and pachychoroid disease spectrum (PDS) disorders. Notably, increased subfoveal CT was associated with the presence and progression of subretinal hyperreflective material and subretinal fluid in AOFVD and Best disease. In PDS disorders, choroidal thickening, pachyvessels, and choroidal vascular hyperpermeability were identified as key contributors to RPE dysfunction and vitelliform lesion formation. Conversely, leptovitelliform maculopathy was characterised by thinner choroid in association with reticular pseudodrusen or subretinal drusenoid deposits. An important feature is CC dysfunction, which is often associated with pachyvessels, even in the absence of a clear pachychoroid-related phenotype or choroidal thickening. These findings underscore the importance of CT evaluation in clinical practice and highlight the need for further research to elucidate the complex relationship between CT and vitelliform maculopathies.}, }
@article {pmid41199263, year = {2025}, author = {Menghini, M and Grimaldi, G and Paris, A and Bachmann, LM and Schmid, MK}, title = {One-year clinical outcomes of four-dose induction versus immediate treat-and-extend faricimab regimens in pretreated neovascular age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {624}, pmid = {41199263}, issn = {1471-2415}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Intravitreal Injections ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Aged, 80 and over ; Treatment Outcome ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Time Factors ; Antibodies, Bispecific ; }, abstract = {BACKGROUND/OBJECTIVES: This study aimed to compare one-year clinical outcomes of two faricimab treatment strategies in patients with previously treated exudative neovascular age-related macular degeneration (nAMD): (1) immediate switch to treat-and-extend dosing (T&amp;E), and (2) initiation with a four-dose induction ("loading") regimen.<br><br>SUBJECT/METHODS: Retrospective comparing two cohorts of pretreated nAMD patients with 12 months of follow-up who were either switched to Faricimab with immediate T&amp;E dosing (Lucerne protocol, "on-the-fly"), or initiated with a four-dose induction phase (Lugano protocol,"re-loading"). Both cohorts were subsequently managed according to a T&amp;E regimen. Demographic and clinical data, including prior intravitreal agents, best-corrected visual acuity (BCVA), central subfield thickness (CST) on optical coherence tomography (OCT), and length of treatment intervals were analysed. Multivariable models were adjusted for baseline differences.<br><br>RESULTS: Both cohorts (Lucerne, 183 eyes; Lugano, 33 eyes) were similar in baseline characteristics. BCVA improved by 0.81 ETDRS letters in Lucerne and by 2.42 in the Lugano cohort (p&#x2009;=&#x2009;0.250). CRT decreased by -38.3&#xa0;&#x3bc;m in Lucerne and by -57.8&#xa0;&#x3bc;m in Lugano (p&#x2009;=&#x2009;0.053). Treatment intervals increased by 2.2 weeks in Lucerne and 3.4 weeks in Lugano (p&#x2009;=&#x2009;0.092). At 12 months, 15.3% of Lucerne patients and 27.3% of Lugano patients achieved intervals&#x2009;&#x2265;&#x2009;12 weeks, with significantly higher odds of extension in Lugano (OR 3.87; p&#x2009;=&#x2009;0.013).<br><br>CONCLUSIONS: Both cohorts showed anatomical and functional improvements after switching to faricimab. The Lugano cohort, using a four-dose induction phase, showed longer treatment intervals, suggesting better disease stability.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid41199318, year = {2025}, author = {Lennikov, A and Yang, M and Elzaridi, F and Shu, DY and Hu, Z and Miller, WP and Tsonas, M and Huang, L and Yen, C and Chang, K and Chen, J and Vijikumar, A and Ashok, A and Cho, KS and Geniez, MS and Dartt, DA and Chen, DF}, title = {Non-invasive bioelectrical therapy suppresses retinal neovascularization by modulating cellular metabolism and inflammation.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {479}, pmid = {41199318}, issn = {1478-811X}, support = {HT9425-24-1-0788//U.S. Department of Defense/ ; M2021010F//BrightFocus Foundation/ ; R01EY019470/EY/NEI NIH HHS/United States ; R01 EY031696/EY/NEI NIH HHS/United States ; R01EY031696/EY/NEI NIH HHS/United States ; HT9425-23-1-1045//U.S. Department of Defense/ ; R01 EY019470/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Microglia/metabolism ; *Retinal Neovascularization/therapy/pathology/metabolism ; *Electric Stimulation Therapy ; *Inflammation/pathology/therapy/metabolism ; Mice, Inbred C57BL ; Choroidal Neovascularization/therapy/pathology ; Endothelial Cells/metabolism ; Diabetic Retinopathy/therapy/pathology/metabolism ; Adenosine Triphosphate/metabolism ; Male ; Membrane Potential, Mitochondrial ; Retina/pathology ; }, abstract = {BACKGROUND: Pathological retinal neovascularization, a major cause of blindness, occurs in conditions such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Microglial activation and chronic neuroinflammation play critical roles in disease progression by promoting vascular permeability and angiogenesis. While anti-VEGF therapies are the current standard of care, their efficacy is limited, requiring frequent intraocular injections and raising concerns about long-term retinal health. Noninvasive transpalpebral electrical stimulation (TpES) has emerged as a potential alternative therapy, but its mechanism and therapeutic impact remain poorly understood.<br><br>METHODS: To investigate the therapeutic effects of TpES, we applied daily microcurrent stimulation (300 &#xb5;A, 20&#xa0;Hz, 4&#xa0;min) in laser-induced choroidal neovascularization (CNV) and streptozotocin (STZ)-induced DR mouse models. Vascular pathology was assessed using fluorescein angiography, optical coherence tomography (OCT), and immunohistochemistry. Mechanistic studies were conducted using primary microglia and human retinal endothelial cells (HREC) to evaluate TpES-induced changes in intracellular calcium ([Ca&#xb2;&#x207a;]i) signaling, mitochondrial membrane potential, and ATP production. Additionally, human RPE/choroidal explants from healthy, AMD, and DR donors were cultured to assess TpES effects on angiogenesis in healthy and pathological human tissues.<br><br>RESULTS: TpES significantly reduced vascular leakage (by ~&#x2009;30%, p&#x2009;<&#x2009;0.001) and lesion size in the CNV model (p&#x2009;<&#x2009;0.05), while also suppressing microglial infiltration and VEGF-A expression. In the DR model, TpES attenuated microaneurysm formation, preserved endothelial tight junctions (in vitro). Mechanistic studies revealed that TpES suppressed ATP-induced microglial activation by reducing mitochondrial membrane potential and intracellular ATP levels, leading to depletion of ER calcium stores and inhibition of proinflammatory and proangiogenic signaling. TpES also directly suppressed endothelial cell migration and tube formation, as well as angiogenic sprouting in human RPE/choroidal explants.<br><br>CONCLUSIONS: These findings establish TpES as a dual-action therapy that mitigates both inflammation and pathological angiogenesis by modulating microglial and endothelial metabolism. Given its noninvasive nature and ability to target key pathways in retinal pathology, TpES represents a promising therapeutic strategy for AMD, DR, and other retinal vascular diseases.}, }
@article {pmid41200258, year = {2025}, author = {Rizwan Khan, AY and Malik, MB}, title = {Artificial Intelligence in Ophthalmology: Practical Applications, Subspecialty Evidence and Real-World Deployment.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96121}, pmid = {41200258}, issn = {2168-8184}, abstract = {Artificial Intelligence (AI) has undoubtedly emerged as a transformative technology in the field of medicine. In ophthalmology, it has been a catalyst for innovation in the methods used for the diagnosis, management, and treatment of different eye diseases. This article offers a detailed review of the literature on the application and utilization of AI technology in the field of ophthalmology. A detailed search of available literature on the use of AI in the field of ophthalmology was performed through the PubMed database and Google Scholar. Published literature on the role of AI in screening, diagnosis, and management of common ocular conditions such as diabetic retinopathy (DR), cataract, glaucoma, and age-related macular degeneration (AMD) was reviewed. Special emphasis was laid on the effectiveness and limitations of the recently developed AI systems for the detection and management of ocular conditions. We screened (n=4449) records and included (n=102) studies spanning retina, glaucoma, cornea, pediatric ophthalmology, neuro-ophthalmology, ocular oncology, surgery, emergencies, and tele-ophthalmology. Deep learning (DL) and machine learning (ML) algorithms have demonstrated significant performance in the analysis of ophthalmic data, including optical coherence tomography scans and retinal images, for accurately diagnosing and classifying diseases, predicting disease progression, and personalizing different treatment plans. In addition to the common ocular conditions, the use of AI has now spread to other domains of ophthalmology, such as pediatric ophthalmology, oculoplastics and reconstructive surgery, and triage and management of emergency ocular conditions. Various AI systems have shown accuracy similar to that of clinical experts, with the additional benefit of being less subjective and time-consuming. Despite significant progress, different challenges related to regulatory approval, standardization, data quality, and ethical considerations hamper the wide-scale implementation of AI in ophthalmology. Literature is evident on the transformative role of AI in screening, diagnosis, and management of various ocular conditions. However, currently, there are various challenges and limitations to the implementation of AI. Future research should focus on addressing these challenges while optimizing the utilization of AI algorithms for enhancing patient care in ophthalmology.}, }
@article {pmid41201702, year = {2025}, author = {Zhou, Y and Liu, J and Wang, Z and Huang, C and Wang, Q and Yu, X and Dai, C and Zhao, D and Cai, Y and Wang, T}, title = {Biological aging phenotypes mediate gut microbiota effects on age-related macular degeneration subtype progression: genetic causality by mendelian randomization and mediation analysis.}, journal = {AMB Express}, volume = {15}, number = {1}, pages = {167}, pmid = {41201702}, issn = {2191-0855}, support = {62175156//National Natural Science Foundation of China/ ; 22S31903000//Science and technology innovation project of Shanghai Science and Technology Commission/ ; 2025M771943//China Postdoctoral Science Foundation/ ; 2024409//Shanghai Post-doctoral Excellence Program/ ; 2023030716//Ningbo Top Medical and Health Research Program/ ; }, abstract = {The mechanisms driving age-related macular degeneration (AMD) progression into two major but distinct vision-threatening subtypes, geographic atrophy (GA) and choroidal neovascularization (CNV), are unclear. This study identifies causal gut microbiota (GM) taxa involved in AMD and their connections to biological aging phenotypes, including epigenetic clock acceleration, telomere length, mitochondrial DNA copy number, 731 immune cell traits, and 91 inflammatory proteins through genetic prediction. Analyzing 207 GM taxa and 205 functional pathways alongside AMD progression GWAS data, we found that class_Gammaproteobacteria significantly influences both CNV and GA, and a bidirectional gut-retina axis involving Erysipelotrichaceae was also identified. Genus_Flavonifractor, species_Ruminococcus_obeum, and species_Streptococcus_thermophilus may attenuate AMD progression. Mediation analysis revealed pathways linking Ruminococcus obeum to GA progression via SSC-A expression on CD4 + T cells, and a CNV-associated pathway mediated by CD33dim HLA-DR + CD11b- cell counts. This study provides novel genetic evidence linking GM to dynamic AMD progression, offering genetic insights for future experimental research and clinical strategies.}, }
@article {pmid41202799, year = {2025}, author = {Ryals, RC}, title = {RPE replacement therapy for dry AMD-early success in a phase 1/2 clinical trial.}, journal = {Cell stem cell}, volume = {32}, number = {11}, pages = {1637-1638}, doi = {10.1016/j.stem.2025.10.007}, pmid = {41202799}, issn = {1875-9777}, mesh = {Humans ; Clinical Trials, Phase I as Topic ; *Macular Degeneration/therapy ; *Retinal Pigment Epithelium/transplantation/cytology ; *Stem Cell Transplantation ; Clinical Trials, Phase II as Topic ; }, abstract = {The number of retinal pigment epithelium (RPE) transplantation clinical trials for dry age-related macular degeneration (AMD) is increasing quickly, with groups using different stem cell sources, delivery approaches, and immune suppression. We discuss the recent success in a phase 1/2a clinical trial[1] evaluating allogeneic RPE stem cell-derived RPE cells isolated from the RPE layer of human cadaveric eyes.}, }
@article {pmid41204997, year = {2026}, author = {Gandhi, P and Sadeghi, E and Schulman, A and Singh, SR and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Correlation of drusen burden and vascular integrity in age-related macular degeneration using three-dimensional choroidal vascular model.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {417-425}, pmid = {41204997}, issn = {1435-702X}, support = {NIH Core Grant P30 EY08098//Eye and Ear Foundation of Pittsburgh/ ; }, mesh = {Humans ; Female ; *Choroid/blood supply ; *Tomography, Optical Coherence/methods ; Male ; *Fluorescein Angiography/methods ; Aged ; *Retinal Drusen/diagnosis/etiology ; *Retinal Vessels/pathology/diagnostic imaging ; Fundus Oculi ; Visual Acuity ; *Imaging, Three-Dimensional/methods ; Aged, 80 and over ; Retrospective Studies ; Follow-Up Studies ; Middle Aged ; }, abstract = {PURPOSE: To study intricate relationship between drusen volume and evolving dynamics of retinal and choroidal vasculature in dry age-related macular degeneration (AMD).<br><br>METHODS: Patients underwent swept-source optical coherence tomography angiography (SS-OCTA) using Plex Elite 9000 device. Retinal thickness, retinal vessel perfusion, drusen volume, choroidal thickness (ChT), choroidal vascularity index (CVI), choroidal vessel diameters (MChVD), and intervessel distance (IVD) were assessed. The Advanced Research and Innovation (ARI) Network, ResUNet model, and Phansalkar thresholding were utilized for image analysis. The linear mixing model was used for the statistical analysis.<br><br>RESULTS: We assessed 53 eyes from 40 patients with dry AMD (22 eyes with early-stage, 31 eyes with intermediate-stage eyes). The mean age was 75.25 years and 62.5% were females. The mean LogMar visual acuity was 0.09&#x2009;&#xb1;&#x2009;0.17 standard deviation (SD) in early-stage and 0.19&#x2009;&#xb1;&#x2009;0.14 SD in intermediate-stage (p&#x2009;=&#x2009;0.03). Mean drusen volume was 0.075&#x2009;&#xb1;&#x2009;0.125 SD mm[3] in early-stage and 0.24&#x2009;&#xb1;&#x2009;0.26 SD mm[3] in intermediate-stage (p&#x2009;=&#x2009;0.005). Mean ChT was thicker, and mean CVI was higher in the early-stage compared to the intermediate-stage (p&#x2009;<&#x2009;0.05). A decrease of 11.48&#xa0;&#x3bc;m in MChVD for every 1&#xa0;mm&#xb3; increase in drusen volume was noted.<br><br>CONCLUSION: With increase in drusen volume, a reduction in CVI and MChVD was noted, without any significant association with changes in retinal metrics, suggesting that choroidal vessels may exhibit early changes during disease progression.}, }
@article {pmid41205411, year = {2025}, author = {Realini, G and Amato, R and Rasa, M and Ceccatelli, R and Cannavale, A and Bottoni, L and Marchini, F and Minetti, A and Giustarini, D and Canovai, A and Melecchi, A and Elia, I and Krepelova, A and Annunziata, F and Cammalleri, M and Rossi, R and Tosi, GM and Orlandini, M and Chiariello, M and Neri, F and Dal Monte, M and Galvagni, F}, title = {N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy.}, journal = {Redox biology}, volume = {88}, number = {}, pages = {103914}, pmid = {41205411}, issn = {2213-2317}, mesh = {*NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Diabetic Retinopathy/metabolism/pathology/drug therapy/genetics/prevention &amp; control ; Mice ; *Acetylcysteine/analogs &amp; derivatives/pharmacology ; Oxidative Stress/drug effects ; Humans ; Kelch-Like ECH-Associated Protein 1/metabolism/genetics ; *Retina/metabolism/drug effects/pathology ; Disease Models, Animal ; Aging/drug effects ; Retinal Pigment Epithelium/metabolism/drug effects ; Macular Degeneration/metabolism/pathology/genetics/drug therapy ; }, abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of visual impairment in older people, with oxidative stress playing a central role in the development of these diseases. In this study, we showed that N-acetylcysteine ethyl ester (NACET) not only increases intracellular cysteine and glutathione levels, but also strongly stimulates the expression and activity of the transcription factor NRF2, a master regulator of oxidative stress response, in RPE cells. Using RNA interference, mass spectrometry and mutagenesis of the NRF2 regulator KEAP1, we identified direct cysteinylation of the sensor residues Cys226 and Cys613 on KEAP1 as the molecular mechanism underlying NRF2 activation after NACET treatment. Furthermore, we demonstrated that oral administration of NACET induces NRF2 activity in the retina in vivo, attenuates retinal aging hallmarks, and prevents diabetes-induced retinal neurodegeneration in mouse models. These results position NACET as a promising therapeutic candidate for age- and oxidative stress-related retinal diseases such as AMD and DR.}, }
@article {pmid41205703, year = {2025}, author = {Yin, Q and Xie, Y and Chen, R and Lyu, Y and Yao, K and Han, H and Shentu, X}, title = {Multifunctional macrophage membrane biomimetic nanoparticles for targeted therapy of neovascular age-related macular degeneration.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {388}, number = {Pt 2}, pages = {114394}, doi = {10.1016/j.jconrel.2025.114394}, pmid = {41205703}, issn = {1873-4995}, mesh = {Animals ; *Macular Degeneration/drug therapy/pathology ; *Nanoparticles/administration &amp; dosage/chemistry ; *Choroidal Neovascularization/drug therapy/pathology ; *Biomimetic Materials/administration &amp; dosage/chemistry ; Mice, Inbred C57BL ; *Macrophages/metabolism ; Mice ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; *Curcumin/administration &amp; dosage/therapeutic use/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Humans ; Male ; *Anti-Inflammatory Agents/administration &amp; dosage/therapeutic use ; Oxidative Stress/drug effects ; Antioxidants/administration &amp; dosage ; Disease Models, Animal ; }, abstract = {Neovascular age-related macular degeneration (nAMD), characterized by choroidal neovascularization (CNV), is a major cause of blindness worldwide. Current anti-vascular endothelial growth factor (VEGF) therapy remains unsatisfactory, as this single-target treatment only alleviates the symptoms without addressing the underlying etiology. Emerging research indicates that inflammation and oxidative stress are closely related to early nAMD, where the retinal pigment epithelium (RPE) is initially impaired, leading to pathological angiogenesis. Herein, biomimetic nanoparticles (termed SHP/Cur@MNPs) are prepared by co-encapsulating SHP099, an anti-inflammatory and anti-angiogenic agent, and curcumin, an antioxidant, into poly (lactic-co-glycolic acid) (PLGA) coated with macrophage membrane. Taking advantage of the macrophage-inherited property, SHP/Cur@MNPs effectively targeted the inflamed foci, specifically the vascular endothelium. Using a laser-induced CNV mouse model, SHP/Cur@MNPs markedly inhibited neovascularization, reduced inflammation and oxidative stress, and improved retinal function. Furthermore, bioinformatics analysis explored the mechanism of the Hippo signaling pathway in the treatment of SHP/Cur@MNPs against nAMD. Collectively, our study describes a strategy using biomimetic nanoparticles to achieve the synergistic effect by targeting major risk factors associated with nAMD, which might be a novel approach for the safe and effective treatment of nAMD.}, }
@article {pmid41205855, year = {2026}, author = {Chen, Y and Jiang, F and Fu, Y and Han, N and Yang, J and Wu, X and Mao, T and Zhang, M}, title = {Transketolase regulates endoplasmic reticulum stress independent of enzymatic activity in human retinal Müller cells.}, journal = {Experimental eye research}, volume = {262}, number = {}, pages = {110732}, doi = {10.1016/j.exer.2025.110732}, pmid = {41205855}, issn = {1096-0007}, mesh = {*Transketolase/genetics/physiology/metabolism/biosynthesis ; *Endoplasmic Reticulum Stress/physiology ; Animals ; Humans ; *Ependymoglial Cells/metabolism/enzymology/pathology ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; *Macular Degeneration/pathology/metabolism/genetics/enzymology ; Cells, Cultured ; Chromatin Immunoprecipitation ; Endoribonucleases/genetics/metabolism ; Protein Serine-Threonine Kinases ; }, abstract = {Transketolase (TKT) expression in the nucleus of the retina has been reported, but its function beyond metabolism remains unclear. In this study, we investigated the role of TKT in the regulation of endoplasmic reticulum (ER) stress in the retina. Using a VEGF-overexpressing mouse model of age-related macular degeneration (AMD), we analyzed the expression and enzymatic activity of Tkt, and found that while expression levels remained unchanged, enzymatic activity was significantly reduced. Tkt localized primarily to the nucleus of the inner nuclear layer in healthy retinae but shifted outside the nuclear center in the lesion area of the AMD mouse model. ChIP-seq analysis revealed that Tkt-targeted genes were enriched in pathways related to metabolism, ER protein processing, and neurogenerative diseases. Among these targets, TKT directly bound to the promoter region of endoplasmic reticulum to nucleus signaling 1 (ERN1) and suppressed its expression, as validated by dual-luciferase reporter assays. In human Müller cells, TKT knockdown elevated ERN1 levels and exacerbated ER stress responses, while enzymatic inhibition alone had no effect on ER stress. Furthermore, TKT knockdown did not alter mitochondria respiration or glycolysis. These findings demonstrate that TKT mitigates ER stress in the human retinal Müller cells by transcriptionally regulating ERN1 in a manner that is independent of its enzymatic activity.}, }
@article {pmid41208951, year = {2025}, author = {Adrean, SD and Hill, L and Amador-Patarroyo, J}, title = {Fibrosis in Patients With Choroidal Neovascularization Based on Spectral-Domain Optical Coherence Tomography: Findings From the HARBOR Trial.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251389993}, pmid = {41208951}, issn = {2474-1272}, abstract = {Purpose: To evaluate the rate and impact of fibrosis on visual outcomes by choroidal neovascularization (CNV) type, based on spectral-domain optical coherence tomography (SD-OCT), in patients with neovascular age-related macular degeneration (nAMD). Methods: Fibrosis status and location at month 24, stratified by baseline CNV type, were evaluated using data from the HARBOR trial (NCT00891735). All patients (n = 1097) received pro re nata or monthly ranibizumab treatment. Results: Fibrosis was most common in eyes with type 2 CNV lesions (53%) compared with other types (type 1, 31%; mixed type 1 or 2, 45%; any type 3, 33%; P < .0001). The rate of fibrosis differed by less than or equal to 6% between monthly and pro re nata treatment regimens. In eyes with subretinal fibrosis, most (65% to 78%) showed subfoveal involvement at month 24. Mean visual acuity gains at month 24 were not negatively affected by the presence of fibrosis (type 1, 8.0 letters; type 2, 11.0; mixed type 1 or 2, 7.8; any type 3, 16.2), regardless of treatment regimen. Male sex and current smoking status were associated with significantly higher rates of fibrosis at month 24 (P < .0001 and P = .003, respectively). Conclusions: Many patients with nAMD develop fibrosis despite antivascular endothelial growth factor therapy, and the prevalence of fibrosis is affected by baseline CNV type.}, }
@article {pmid41211298, year = {2026}, author = {Bai, ZP and Pan, YS and Cai, YX and Chen, C and Tao, D and Zhao, XY and Shen, YF and Chen, F and Li, JH and Qu, J and Huang, XF}, title = {Investigating the Shared Genetic Architecture of 3 Age-Related Ocular Disorders.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100942}, pmid = {41211298}, issn = {2666-9145}, abstract = {PURPOSE: To explore the shared genetic architecture, causal relationships, and cell type-specific expression patterns of pleiotropic genes in age-related macular degeneration (AMD), cataract, and primary open-angle glaucoma (POAG), uncovering molecular mechanisms and informing targeted therapies.<br><br>DESIGN: A genetic association study combined with cross-trait meta-analyses, Mendelian randomization analyses, and single-cell RNA sequencing (scRNA-seq) analysis.<br><br>SUBJECTS: The data related to 3 age-related ocular diseases, including AMD, cataract, and POAG, were obtained from publicly available genome-wide association study (GWAS) databases.<br><br>METHODS: We conducted a comprehensive genetic analysis utilizing GWAS summary statistics to examine genetic correlations among AMD, cataract, and POAG. Cross-trait meta-analyses were performed to identify shared risk loci. Mendelian randomization was employed to investigate potential causal relationships between these conditions. Additionally, we analyzed scRNA-seq data to examine the expression patterns of identified pleiotropic genes across different retinal cell types.<br><br>MAIN OUTCOME MEASURES: Identification of shared risk single nucleotide polymorphisms (SNPs) and pleiotropic loci. Causal relationships between AMD, cataract, and POAG. Cell type-specific expression patterns of pleiotropic genes in retinal cells.<br><br>RESULTS: Our analysis revealed significant genetic correlations, with a negative correlation between AMD and POAG and a positive correlation between cataract and POAG. Cross-trait meta-analyses identified shared risk SNPs, with CDKN2B-AS1 emerging as a notable pleiotropic locus. Mendelian randomization analyses suggested causal relationships between AMD and cataract, as well as between POAG and AMD. Single-cell expression analysis demonstrated cell type-specific expression patterns of pleiotropic genes including ATXN2, HTRA1, SIX6, and THSD7A across retinal cells.<br><br>CONCLUSIONS: This study provides compelling evidence for shared genetic architecture and causal relationships among AMD, cataract, and POAG. The identification of specific pleiotropic genes and their expression patterns across retinal cell types offers new insights into the molecular mechanisms underlying these age-related ocular diseases, potentially informing the development of targeted therapeutic strategies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41211376, year = {2025}, author = {Kong, H and Feng, H and Wang, H}, title = {Global burden of age-related macular degeneration (1990-2021): trends, age-sex disparities, and socioeconomic dynamics from the GBD study.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1594672}, pmid = {41211376}, issn = {2296-2565}, mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Female ; Aged ; Prevalence ; *Global Burden of Disease/trends ; Middle Aged ; *Global Health/statistics &amp; numerical data ; Socioeconomic Factors ; Aged, 80 and over ; Risk Factors ; Adult ; Sex Factors ; *Health Status Disparities ; }, abstract = {OBJECTIVES: This study aimed to assess the global burden of Age-related macular degeneration (AMD) across countries, regions, and age groups by sex, sociodemographic index (SDI) level, and risk factors from 1990 to 2021, using newly updated data from the Global Burden of Disease (GBD) study. The focus was on age-related disparities in AMD burden by sex and SDI.<br><br>METHODS: This population-based study utilized AMD data from GBD 2021 (1990-2021). The burden was evaluated using the number of cases, prevalence rates per 100,000 population, and trends in years lived with disability (YLDs) and prevalence, assessed through average annual percentage changes (AAPCs) and estimated annual percentage changes (EAPCs).<br><br>RESULTS: Globally, AMD prevalence increased from 364,000 cases in 1990 to 806,000 in 2021 (+121%), while YLDs rose from 30,000 to 58,000 (+91%). However, age standardized prevalence and YLD rates (ASPRs and ASYRs) significantly declined (EAPCs: -0.26 and -0.94, respectively). Regional analyses revealed that low SDI regions (e.g., sub-Saharan Africa) bore the highest AMD burden (ASPR: 139.9 per 100,000) and exhibited a younger age distribution, with a significantly higher proportion of cases in individuals aged 55-74&#x202f;years. In contrast, high SDI regions (e.g., high-income Asia-Pacific) had a concentration of cases among those aged 70&#x202f;years or older. While medium SDI regions accounted for one-third of global cases in 2021, age-standardized rates declined most slowly in low SDI regions (EAPC: -1.03) and even trended upward in some countries. AMD cases peaked globally at ages 65-69, yet prevalence was highest among those over 85&#x202f;years (1,349.9 per 100,000), with women generally experiencing a higher burden than men. These findings highlight distinct regional patterns, with younger disease profiles in low SDI regions and aging-driven increases in high SDI regions, underscoring the need for targeted prevention and control strategies.<br><br>CONCLUSION: Although global efforts over the past 30&#x202f;years have led to a decline in AMD prevalence rates and YLDs, the absolute number of cases and YLDs continues to rise, driven by age, sex, socioeconomic status, and geographic location. These findings provide an epidemiological basis for developing global public health strategies to address these ongoing challenges.}, }
@article {pmid41212222, year = {2026}, author = {Honjo, J and Mukai, R and Itagaki, K and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sekiryu, T}, title = {A one-year study on the regression effects of aflibercept and faricimab on retinal pigment epithelial detachment.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {437-444}, pmid = {41212222}, issn = {1435-702X}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; *Retinal Detachment/drug therapy/diagnosis/etiology ; Female ; Male ; Tomography, Optical Coherence/methods ; *Visual Acuity ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology/drug effects ; Follow-Up Studies ; Fundus Oculi ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To compare long-term regressive effects on pigment epithelial detachment (PED) between aflibercept and faricimab in type 1 macular neovascularization (MNV).<br><br>METHODS: We analyzed 94 eyes from 92 patients diagnosed with type 1 MNV using multimodal imaging. Seventy-one eyes received intravitreal aflibercept injections (IVA group), and 23 received intravitreal faricimab injections (IVFa group). After three consecutive monthly injections, intervals were adjusted in 2-4 week increments within drug-specific windows (IVA, 4-12 weeks; IVFa, 8-16 weeks) through 1 year. The maximum height (MH) and horizontal maximum diameter (H-MD) of PED were measured using optical coherence tomography before treatment and at 3 months and 1year post-treatment. We also assessed associations between PED change and 1-year dry macula, and explored visual outcomes with using analysis of covariance and logistic models.<br><br>RESULTS: MH decreased in both IVA (184&#x2009;&#xb1;&#x2009;176&#x2192;126&#x2009;&#xb1;&#x2009;153&#xa0;&#x3bc;m at 3 months, P&#x2009;=&#x2009;0.0003; 124&#x2009;&#xb1;&#x2009;135&#xa0;&#x3bc;m at 1 year, P&#x2009;=&#x2009;0.0005) and IVFa (162&#x2009;&#xb1;&#x2009;124&#x2192;83&#x2009;&#xb1;&#x2009;65&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.0056; 86&#x2009;&#xb1;&#x2009;71&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.0053). The mean change in MH was not significantly different between groups (P&#x2009;=&#x2009;0.244). H-MD did not show significant regression in either group. IVFa required fewer injections (6.17&#x2009;&#xb1;&#x2009;0.39 vs. 7.90&#x2009;&#xb1;&#x2009;1.99/year; P&#x2009;<&#x2009;0.0001) and achieved a longer final intended injection interval (14.17&#x2009;&#xb1;&#x2009;2.53 vs. 8.64&#x2009;&#xb1;&#x2009;2.90 weeks; P&#x2009;<&#x2009;0.0001). In multivariable linear regression for percent MH change at 1 year, annual injection number was positively associated with percent change (&#x3b2;&#x2009;=&#x2009;7.62% points/injection, P&#x2009;=&#x2009;0.012), whereas drug type was not (P&#x2009;=&#x2009;0.633), adjusting for baseline MH (&#x3b2; = -0.078/&#xb5;m, P&#x2009;=&#x2009;0.016; all VIFs&#x2009;<&#x2009;2). At 1 year, MH was lower in dry vs. wet macula (90&#x2009;&#xb1;&#x2009;82 vs. 186&#x2009;&#xb1;&#x2009;185&#xa0;&#x3bc;m; P&#x2009;=&#x2009;0.0004). For vision, &#x2265; 0.2logMAR gain was predicted by CMT decrease (OR&#x2009;&#x2248;&#x2009;1.56 per 100&#xa0;&#x3bc;m decrease; P&#x2009;=&#x2009;0.045), while percent PED change was not significant (P&#x2009;=&#x2009;0.283).<br><br>CONCLUSION: In a treat-and-extend regimen with different label constraints, 1-year PED regression was similar for IVA and IVFa and was achieved with less treatment burden in IVFa. PED regression aligned with dry macula rather than with large visual gains, which instead tracked with retinal thickness recovery.}, }
@article {pmid41216067, year = {2025}, author = {Moafa, MA and Albahrawy, SS and Alluwimi, MS and Alrasheed, S and Elmadina, AM and Mutwaly, RF and Abdelhamid, AF and Albarnawi, EH and Alghamdi, WM and Aldebasi, YH}, title = {Assessment of Peripapillary Retinal Nerve Fibre Layer Thickness, Optic Nerve Head Rim Area, Anterior Chamber Parameters, and Axial Length in Myopic Eyes.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94271}, pmid = {41216067}, issn = {2168-8184}, abstract = {BACKGROUND: Myopic eyes commonly show structural changes, including optic nerve head (ONH) and altered anterior chamber parameters.<br><br>AIM: The study aimed to investigate the associations of peripapillary retinal nerve fibre layer (RNFL) thickness, optic disc rim area, anterior chamber parameters, and axial length in myopic eyes.<br><br>METHODS: This&#xa0;cross-sectional study was conducted at the Royal Commission Medical Centre, Yanbu, Saudi Arabia, between February and May 2025 and included 152 myopic eyes. Refraction was measured using an autorefractometer. Swept-source optical coherence tomography (SS-OCT)&#xa0;scans (optic disc cube 200&#x2009;&#xd7;&#x2009;200) were used to assess peripapillary RNFL thickness and optic disc rim area. Corneal and anterior chamber parameters, along with axial length, were measured using Pentacam AXL (OCULUS Optikger&#xe4;te GmbH, Wetzlar, Germany). Data analysis was conducted to assess the correlation between myopia severity and structural ocular changes.<br><br>RESULTS: Myopic eyes (mean spherical equivalent: -2.02 &#xb1; 1.34 D) showed a significant inverse correlation with both central corneal thickness (r = -0.193, P < 0.05) and corneal thickness at the thinnest point (r = -0.225, P < 0.05). Anterior chamber volume (r = 0.266, P < 0.001) and anterior chamber depth (r = 0.259, P < 0.001) showed significant positive correlations with myopia, while the anterior chamber angle showed no significant association (P > 0.05). Axial length was strongly correlated with myopia severity (r = 0.545, P < 0.001). Inverse correlations were observed between myopia and both peripapillary RNFL thickness (r = -0.100, P > 0.05) and ONH rim area (r = -0.134, P > 0.05). A statistically significant inverse correlation was found between peripapillary RNFL thickness and axial length (r = -0.163, P < 0.05), as well as between ONH rim area and axial length (r = -0.167, P < 0.05).<br><br>CONCLUSION: The study revealed a significant positive correlation between myopia and both anterior chamber volume and anterior chamber depth, while the anterior chamber angle remained unaffected. The increase in myopia severity was correlated with thinning of the peripapillary RNFL and a reduction in ONH rim area. These findings underscore the importance of assessing axial elongation and structural changes in myopic eyes, particularly in the context of ocular diseases such as glaucoma, myopic macular degeneration, and retinal detachment.}, }
@article {pmid41216998, year = {2025}, author = {Brouwer, NJ and Vu, THK and De Jong‐Hesse, Y and van Dijk, EHC}, title = {The prechoroidal cleft in neovascular age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70035}, pmid = {41216998}, issn = {1755-3768}, abstract = {The prechoroidal cleft is a lenticular, hypo-reflective space on optical coherence tomography imaging, located between a band of fibrovascular material underneath the retinal pigment epithelium (RPE) and Bruch's membrane. It occurs in 8%-22% of neovascular age-related macular degeneration (nAMD) eyes, most often with macular neovascularization (MNV) type 1 and 3, and less often with MNV type 2 or polypoidal choroidal vasculopathy. The presence of a prechoroidal cleft is associated with poor visual prognosis, some studies report more frequent occurrence of RPE tears and subretinal haemorrhages. Eyes with a prechoroidal cleft require more frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections to treat the nAMD and more often require a switch to other anti-VEGF medication. Clinicians should be aware of the prechoroidal cleft for diagnostic and prognostic reasons, as it may be misunderstood for other (subretinal) fluid or even a choroidal lesion.}, }
@article {pmid41217603, year = {2025}, author = {Akada, M and Hata, M and Ideyama, M and Kido, A and Miyata, M and Tamura, H and Ooto, S and Tsujikawa, A}, title = {Subtype-specific shifts in age, axial length, and clinical profile of neovascular age-related macular degeneration: a five-year study in Japan.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41217603}, issn = {1613-2246}, abstract = {PURPOSE: To evaluate 5-year temporal changes in baseline clinical characteristics-age, axial length, and best-corrected visual acuity-among treatment-naïve eyes with neovascular Age-Related Macular Degenaration (nAMD), comparing pachychoroid neovasculopathy (PNV) with drusen-driven (non-PNV) nAMD at a Japanese tertiary center.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Registry data from Kyoto University Hospital were analyzed for patients newly diagnosed with nAMD in 2013/2014 and in 2018/2019. Patients were classified as PNV or non-PNV based on findings derived from multimodal imaging-including optical coherence tomography, indocyanine-green angiography, and color fundus photography. Demographic data, axial length, best-corrected visual acuity (BCVA) at baseline and 1 year posttreatment, and the proportion of eyes achieving &#x2265;0.20 logMAR improvement were compared over time.<br><br>RESULTS: A total of 118 patients were included. In the non-PNV group, mean age rose from 74.35 &#xb1; 8.42 years to 77.39 &#xb1; 7.90 years (p = 0.021), whereas the PNV group showed a smaller, non-significant change from 68.88 &#xb1; 7.25 to 70.41 &#xb1; 9.19 years (p = 0.48). Among non-PNV cases, both mean age (p=0.021) and axial length (p=0.017) increased significantly over time. In contrast, PNV cases showed no significant changes in age or axial length. BCVA outcomes and the proportion of patients achieving &#x2265;0.20 logMAR improvement were similar across time points within each subtype. Multivariable logistic regression analysis revealed no significant associations between visual improvement and year, subtype, age, or axial length.<br><br>CONCLUSIONS: This study revealed an aging trend and axial elongation among non-PNV cases over time, underscoring a subtype-specific divergence in clinical trajectory.}, }
@article {pmid41218191, year = {2025}, author = {Călugăru, D and Călugăru, M}, title = {Ten-year follow-up of patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004728}, pmid = {41218191}, issn = {1539-2864}, }
@article {pmid41218567, year = {2025}, author = {Cai, S and Liang, X and Wu, H and Li, X and Pu, Q}, title = {Navigating the ocular barrier: Viral- and nanotechnology-based delivery systems as promising therapeutic agents for ocular diseases.}, journal = {Molecular aspects of medicine}, volume = {106}, number = {}, pages = {101421}, doi = {10.1016/j.mam.2025.101421}, pmid = {41218567}, issn = {1872-9452}, mesh = {Humans ; *Eye Diseases/therapy/drug therapy ; *Drug Delivery Systems/methods ; Animals ; *Nanotechnology/methods ; Viruses/genetics ; Gene Transfer Techniques ; }, abstract = {While the intricate and precisely specialized structure of the human eye is critical for its appropriate function, it also presents a number of anatomical and physiological barriers, such as tight junctions, enzymatic degradation, and dynamic fluid turnover, which highly restrict the intraocular bioavailability of various therapeutic compounds. This is more significant for those therapeutic compounds that are used for complications affecting the posterior segment. Accordingly, conventional therapeutic strategies for common ocular complications such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and infectious keratitis significantly demand invasive administration approaches and multiple injections, frequently resulting in various side effects and suboptimal therapeutic consequences. To address these major challenges, novel technologies, such as viral- and nanotechnology-based delivery systems, have provided emerging opportunities to bypass ocular barriers and facilitate targeted, maintained, and efficient drug and gene delivery. The present review aims to comprehensively describe the current advancements in both viral- and nanotechnology-based strategies for ocular diseases. It discusses the complex molecular structure and physiological functions of the ocular barriers, focusing on the exact mechanisms that restrict drug permeation. Moreover, this review describes the design principles, physicochemical properties, and therapeutic potential of diverse viral- and nanotechnology-based delivery systems. Their efficacy and safety profiles are thoroughly discussed across various pre-clinical and clinical studies. Furthermore, the review discusses the emergence of hybrid viral-nanotechnology delivery systems that combine the strengths of both approaches, offering enhanced targeting precision and biocompatibility. The major challenges linked to the clinical translation of these novel technologies, such as aspects of biocompatibility and immunogenicity are also addressed. This review highlights the significant transformative potential of viral vectors and nanotechnology in reforming ocular disease management and increasing patient quality of life.}, }
@article {pmid41218596, year = {2025}, author = {Debbarma, R and Dos Santos, ACF and Ramirez Gutierrez, D and Erk, KA and Koo, H and da Cunha, F and Ladisch, M}, title = {Imaging of Intra-Matrix IgG Diffusion as an Indicator of Age-Related Vitreous Changes.}, journal = {Molecular pharmaceutics}, volume = {22}, number = {12}, pages = {7445-7454}, doi = {10.1021/acs.molpharmaceut.5c00836}, pmid = {41218596}, issn = {1543-8392}, mesh = {*Immunoglobulin G/metabolism/chemistry ; *Vitreous Body/metabolism ; Hyaluronic Acid/chemistry/metabolism ; Humans ; Aged ; Viscosity ; Aged, 80 and over ; Animals ; Diffusion ; Cattle ; Macular Degeneration/drug therapy/metabolism ; Intravitreal Injections ; *Aging ; }, abstract = {Intravitreal injection of therapeutics that treat age-related macular degeneration and diabetic retinopathy requires diffusion of the protein therapeutic through hyaluronic acid (HA) in the vitreous humor. The tracking of bovine IgG movement in an in vitro HA matrix simulates protein diffusion in the vitreous humor and provides a fundamental understanding of the diffusion properties of injected IgG type biologics. Phase separation of the vitreous humor, creating pockets of liquid rich in HA, begins at about age 40 and steadily progresses, with more than 50% of the vitreous being liquid by age 80-90 years. When formulated to represent viscosity at the injection site for patients between 65 and 80 years old, the HA has a viscosity of 0.1 Pa s. The vitreous humor for patients at ages lower than 65 corresponds to a viscosity of 1 Pa s. This work shows how HA matrices may be formulated to simulate the HA environment in the vitreous humor so that IgG diffusion may be measured using label-free imaging based on tryptophan autofluorescence. A 37% increase in the mean diffusion coefficient occurred as the HA matrix viscosity decreased from 1 to 0.1 Pa s, thus indicating that protein formulations may need to be adjusted if equivalent diffusion rates are to be achieved in the vitreous humor of different ages of patients. This approach provides an in vitro preclinical screening tool that could prove useful for correlating the diffusion properties of protein therapeutics as a function of the viscoelasticity of the vitreous humor.}, }
@article {pmid41218907, year = {2025}, author = {Hong, Y and Bo, QY and Sun, XD}, title = {[Progress on predictive biomarkers for exudation in polypoidal choroidal vasculopathy].}, journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology}, volume = {61}, number = {11}, pages = {915-920}, doi = {10.3760/cma.j.cn112142-20250416-00186}, pmid = {41218907}, issn = {0412-4081}, support = {U22A20311, 82301220, 82388101//National Natural Science Foundation of China/ ; 23YF1434100//"YangFan Program"of Shanghai Municipal Committee of Science and Technology/ ; 20224Y0352//Clinical research project of Shanghai Municipal Health Commission/ ; }, mesh = {Humans ; Biomarkers ; *Choroid/blood supply ; *Choroidal Neovascularization/diagnosis ; *Choroid Diseases/diagnosis ; Macular Degeneration ; Polypoidal Choroidal Vasculopathy ; }, abstract = {Polypoidal choroidal vasculopathy (PCV) is a common subtype of neovascular age-related macular degeneration (nAMD) in Asian populations. Clinical follow-up has revealed varying degrees of activity in PCV lesions. Studies have shown that multimodal retinal imaging techniques can be used to assess the activity of PCV lesions. Abnormal branching vascular networks, polypoidal lesions, and choroidal-related features are important biological markers for predicting lesion activity. Additionally, demographic characteristics and genetic traits of patients may also serve as relevant factors for assessing the activity of PCV lesions. This review summarizes recent updates in the understanding of PCV lesion activity based on multimodal retinal imaging studies and their impact on clinical ophthalmic practice. It also explores the potential applications and prospects of lesion activity characteristics in the treatment and follow-up of PCV, aiming to provide reference for clinicians in assessing and determining the activity of PCV lesions and developing personalized treatment and follow-up plans.}, }
@article {pmid41219247, year = {2025}, author = {Chiu, CJ and Chiu, ES and Chang, ML}, title = {Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {39400}, pmid = {41219247}, issn = {2045-2322}, support = {R01 EY021826/EY/NEI NIH HHS/United States ; R21 EY028209/EY/NEI NIH HHS/United States ; RO1EY021826 and R21EY028209/GF/NIH HHS/United States ; }, mesh = {Humans ; *Porphyromonas gingivalis/immunology ; *Macular Degeneration/blood/microbiology/etiology ; Female ; Male ; *Immunoglobulin G/blood ; Middle Aged ; Case-Control Studies ; Aged ; Risk Factors ; Periodontitis/microbiology/blood ; Antibodies, Bacterial/blood ; Nutrition Surveys ; *Bacteroidaceae Infections/blood/microbiology ; }, abstract = {Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiota. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiota and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiota and AMD occurrence, we conducted a candidate microbe approach case-control study in the Third National Health and Nutrition Examination Survey (NHANES-III). Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Consistent with current evidence that host nutritional status critically modulates immune responses to the microbiota and influences human health, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 µmol/L or ≥ 20 µg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrients related to eye health and humoral response to P. gingivalis.Significance statement: While humoral response to P. gingivalis indicates an impact on age-related macular degeneration, nutritional factors may modulate the associated risk.}, }
@article {pmid41219682, year = {2026}, author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F}, title = {In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {239-249}, pmid = {41219682}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to assess the in vivo positioning, tilt, and decentration of the second-generation implantable miniature telescope (SING-IMT™; Samsara Vision, Inc., Far Hills, NJ, USA) using swept-source anterior segment optical coherence tomography (AS-OCT).<br><br>METHODS: This was a multicentric retrospective observational study conducted at two tertiary referral centers (Palagi Hospital, Florence, Italy, and Royal Victoria Infirmary Hospital, Newcastle upon Tyne, UK). Eleven eyes from 11 patients with end-stage age-related macular degeneration (AMD) underwent secondary SING IMT&#x2122; implantation at these two tertiary centers. Using high-resolution AS-OCT (CASIA2 system [Tomey, Nagoya, Japan] and Anterion system [Heidelberg Engineering, Heidelberg, Germany]), telescope alignment was assessed after 12&#xa0;months. Decentration and tilt were calculated and reported in both Cartesian and polar coordinates. Telescope configuration relative to the iris plane and corneal-telescope (C-T) distance and endothelial cell count was also evaluated.<br><br>RESULTS: The mean (&#xb1; standard deviation) follow-up was&#xa0;15.7&#x2009;&#xb1;&#x2009;2.8&#xa0;months. The mean decentration was 0.33&#x2009;&#xb1;&#x2009;0.12&#xa0;mm, with a predominant superior and nasal displacement. Mean tilt was 3.28&#x2009;&#xb1;&#x2009;1.31&#xb0;, oriented mainly in the supero-temporal direction. Three positional configurations were observed: anterior to the iris plane (36.4%), at the iris plane (36.4%), and posterior to the iris plane (27.3%). The mean C-T distance was 2.71&#x2009;&#xb1;&#x2009;0.48&#xa0;mm. Mean endothelial cell loss at 12&#xa0;months was 13.21%&#x2009;&#xb1;&#x2009;3.57%.<br><br>CONCLUSIONS: After 12&#xa0;months of follow-up, the SING IMT&#x2122; maintained stable in-the-bag fixation, with tilt and decentration values within the ranges previously reported for conventional in-the-bag intraocular lenses.}, }
@article {pmid41221122, year = {2025}, author = {Alqahtani, HB and Votruba, M and Regini, J}, title = {Do retinal implants provide long-term efficacy, safety and improve quality of life? A systematic review.}, journal = {Therapeutic advances in ophthalmology}, volume = {17}, number = {}, pages = {25158414251385884}, pmid = {41221122}, issn = {2515-8414}, abstract = {BACKGROUND: Retinal implants have emerged as interventions to partially restore functional vision such as light perception, motion detection or object localisation in patients with severe vision loss from degenerative retinal conditions, including retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD).<br><br>OBJECTIVES: To evaluate the long-term efficacy, safety and quality of life (QoL) impact of retinal implants with &#x2a7e;1&#x2009;year of follow-up.<br><br>METHODS: Following PRISMA guidelines, a systematic search was conducted (31st July to 31st August 2024) in Web of Science, PubMed, Medline, Scopus, Cochrane Library and Embase, using the terms: ('retinal implant' OR 'retinal prosthesis') AND ('long-term' OR 'follow-up') AND ('efficacy' OR 'safety' OR 'quality of life'). No publication date restrictions were applied. Eligible studies were in English, involved human subjects with retinal degenerations, and reported &#x2a7e;1&#x2009;year follow-up. Risk of bias was assessed using the Critical Appraisal Skills Programme (CASP) cohort study checklist for most studies, as they involved prospective follow-up without randomisation or control groups. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series was applied to studies with a case series design. Narrative synthesis was applied.<br><br>RESULTS: Thirteen studies met the inclusion criteria: 53.85% assessed epiretinal implants (Argus II), 30.77% subretinal (Alpha AMS and PRIMA), and 15.38% suprachoroidal (44 and 49-channel STS). Epiretinal implants improved visual function, with up to 89% better in SLT, 50%-56% in DOM, and 30%-40% reaching &#x2a7e;2.9 logMAR when activated. Subretinal implants enhanced light perception, localisation, and grating acuity (to 3.33 cycles/degree), with acuity of 20/460 and 20/550 in some cases. Suprachoroidal devices improved SLT, DOM and GVA. Adverse events were more frequent with epiretinal than other implant types. QoL outcomes improved, particularly in mobility, orientation, and daily tasks.<br><br>CONCLUSION: Retinal implants confer functional vision, but acuities remain below 20/200, and recipients continue to meet criteria for legal blindness. Given the high risk of bias, lack of controls and potential placebo effects, further high-quality evidence is needed to confirm their efficacy, safety and QoL impact.}, }
@article {pmid41222198, year = {2025}, author = {Cinque, F and de Breuk, A and Mhmud, H and De Jong, S and Vermeulen, J and Liefers, B and den Hollander, AI and Thee, E and Colijn, JM and Heesterbeek, TJ and Klaver, CC and Hoyng, CB and Lechanteur, YTE}, title = {Disease Progression in Age-Related Macular Degeneration Patients Carrying Rare Variants in the Complement Factor H or Complement Factor I Genes.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {14}, pages = {23}, pmid = {41222198}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Aged ; *Complement Factor H/genetics/metabolism ; Disease Progression ; *Complement Factor I/genetics/metabolism ; Retrospective Studies ; Visual Acuity/physiology ; Incidence ; *Macular Degeneration/genetics/epidemiology/diagnosis ; Follow-Up Studies ; Middle Aged ; Aged, 80 and over ; Prospective Studies ; Geographic Atrophy/genetics ; }, abstract = {PURPOSE: Rare variants in CFI and CFH genes are associated with AMD. This study aimed to compare the incidence of late AMD in carriers of these variants to a reference cohort using a long follow-up cohort (LF-cohort) and to examine short-term AMD progression in a short follow-up cohort (SF-cohort).<br><br>METHODS: This cohort study included two groups: the LF-cohort, observed for more than five years retrospectively and the SF-cohort, observed for one year prospectively, with patients attending in-hospital visits. One hundred twelve AMD patients with rare CFH/CFI or variants were invited from the European Genetic Database. The LF-cohort's outcome was the incidence of late AMD per 100 person-years compared to a matched reference cohort. In the SF-cohort, geographic atrophy (GA), retinal sensitivity, and visual acuity were measured.<br><br>RESULTS: The LF-cohort included 28 patients (median [interquartile range {IQR}] age, 71.3 [24.3] years; 18 females [64%]) with an incidence rate of 6.2 per 100 person-years which was higher than the reference cohort (1.8 per 100 person years (P = 0.01)). The SF-cohort consisted of 44 patients (median [IQR] age 70.5 [16.5] years; 29 (65% female). Mean annual GA growth (SD) was 0.22 mm (0.13) in 19 eyes of 12 patients. Retinal sensitivity changed for late-staged eyes (right eye: 17.2 dB to 15.7 dB, P = 0.03; left eye 17.3 dB to 16.4 dB, P = 0.06) whereas visual acuity did not.<br><br>CONCLUSIONS: Carriers of rare CFI or CFH variants show a higher incidence of late AMD. These patients may benefit from personalized gene therapy and complement inhibition in future trials.}, }
@article {pmid41222201, year = {2025}, author = {Beqiri, S and Pan, H and Kumar, BS and Berni, A and Shen, M and Hiya, FE and Cheng, Y and El-Mulki, OS and Herrera, G and Badla, O and Kastner, J and Trivizki, O and Di Nicola, M and O'Brien, RC and Waheed, NK and Wang, RK and Gregori, G and Rosenfeld, PJ}, title = {Changes in Choriocapillaris Flow Deficits Before and After the Onset of Large Choroidal Hypertransmission Defects in AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {14}, pages = {20}, pmid = {41222201}, issn = {1552-5783}, support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Aged ; Fluorescein Angiography/methods ; Regional Blood Flow/physiology ; Aged, 80 and over ; *Macular Degeneration/physiopathology/diagnosis ; Capillaries/physiopathology ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; Prospective Studies ; }, abstract = {PURPOSE: Eyes with intermediate age-related macular degeneration (iAMD) underwent swept-source optical coherence tomography angiography (SS-OCTA) imaging and were evaluated longitudinally to determine if choriocapillaris flow deficits (CCFDs) developed before or after the formation of large choroidal hypertransmission defects (hyperTDs).<br><br>METHODS: A retrospective review was performed of prospectively collected 6 &#xd7; 6-mm SS-OCTA images from eyes with iAMD that developed large hyperTDs, defined on en face images from subretinal pigment epithelium (sub-RPE) slabs positioned 64 to 400 &#xb5;m beneath Bruch's membrane (BM) as bright lesions with a greatest linear dimension (GLD) &#x2265; 250&#xa0;&#xb5;m. The onset of large hyperTDs was designated as baseline T = 0; additional visits were chosen at 1 year before and at two 1-year intervals after T = 0. A grid box strategy was implemented for the analysis of CCFDs at the site where hyperTDs formed. A change in the percentage of CCFDs greater than 5% was considered to be a true change outside the repeatability limits.<br><br>RESULTS: Twenty-seven targets from 27 eyes eligible for final analysis were followed over four visits separated by 12 &#xb1; 3 months. No targets showed a marked CCFD change above 5% prior to hyperTD onset. Only two targets showed marked increases in CCFDs after hyperTD formation. A grouped analysis of all targets showed no mean CCFD change prior to hyperTD onset, but a significant change only after the onset of hyperTD.<br><br>CONCLUSIONS: CCFD values did not increase prior to the onset of hyperTDs with increases in CCFDs detected after their onset. These results suggest that loss of choriocapillaris perfusion did not precede hyperTD formation but may play a role in hyperTD growth.}, }
@article {pmid41222493, year = {2025}, author = {Pan, SY and Chao, TF and Weng, CH and Lin, JF and Lin, CH and Lin, HJ and Wang, IJ and Chou, CC}, title = {Association between atrial fibrillation and age-related macular degeneration: A multinational cohort study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70028}, pmid = {41222493}, issn = {1755-3768}, support = {TCVGH-1136902B//Taichung Veterans General Hospital/ ; }, abstract = {PURPOSE: To assess whether atrial fibrillation (AF) is associated with an increased risk of age-related macular degeneration (AMD).<br><br>METHODS: This multinational retrospective cohort study included individuals aged 50&#x2009;years or older, with or without AF at baseline, from healthcare organisations across 21 countries during 2015-2020 in the TriNetX database. Participants were classified into those with and without AF, and followed for up to 5&#x2009;years to observe the occurrence of AMD, including both dry and wet forms, and other cerebrovascular outcomes. The AF and non-AF groups were 1:1 propensity score-matched to balance baseline characteristics and comorbidities. Outcomes were assessed using Cox regression models and Kaplan-Meier analysis.<br><br>RESULTS: A total of 113&#x2009;974 individuals were included in the final analysis. The mean follow-up (standard deviation [SD]) is 4.09 (1.30) years in the AF group and 4.53 (0.95) years in the non-AF group. During follow-up, 1169 individuals developed AMD, 527 developed dry AMD, and 242 developed wet AMD. Compared to individuals without AF, those with AF have a significantly higher risk of developing AMD (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.42-3.11), dry AMD (HR, 2.55; 95% CI, 2.12-3.07), wet AMD (HR, 2.50; 95% CI, 1.90-3.28), and ischemic stroke (HR, 1.67; 95% CI, 1.60-1.73). Across most subpopulations, AF is consistently linked to higher risks of both dry and wet AMD.<br><br>CONCLUSION: Individuals with AF experience a higher risk of developing both dry and wet forms of AMD compared to individuals without AF.}, }
@article {pmid41222660, year = {2026}, author = {Fragiotta, S and Parravano, M and Costanzo, E and De Geronimo, D and Varano, M and Borrelli, E and Barresi, C and Sacconi, R and Querques, G}, title = {Early prediction of macular neovascularization phenotypes and prognostic evolution.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {445-454}, pmid = {41222660}, issn = {1435-702X}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Tomography, Optical Coherence/methods ; Prognosis ; Aged ; *Fluorescein Angiography/methods ; Phenotype ; Follow-Up Studies ; Fundus Oculi ; *Macula Lutea/pathology ; Middle Aged ; Aged, 80 and over ; *Wet Macular Degeneration/diagnosis ; Choroid/pathology ; Time Factors ; Disease Progression ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {PURPOSE: To investigate baseline predictors of macular neovascularization (MNV) phenotypes and prognostic outcomes, including changes in visual acuity (VA) and the development of macular atrophy (MA) and fibrosis.<br><br>METHODS: A retrospective, observational, cohort study was performed on a total of 102 eyes from 97 patients with intermediate age-related macular degeneration (AMD) converting to MNV subtypes. Baseline features, including age, drusen, reticular pseudodrusen (RPD), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT), were analyzed. Predictive models that considered the baseline characteristics predicting the different MNV subtypes and prognostic outcomes were developed using Cox regression and generalized linear models.<br><br>RESULTS: Of the included eyes, 68.6% developed type 1 MNV, 15.7% type 2 MNV, and 15.7% type 3 MNV. SFCT was a significant predictor of type 2 MNV, with thicker choroid predisposing to the lesion development (HR: 1.02, CI95%: 1, 1.03, p&#x2009;=&#x2009;0.001). Age was the primary predictor for type 3 MNV (HR: 1.1, CI 95%: 1, 1.2, p&#x2009;=&#x2009;0.02). Type 2 MNV exhibited the highest rate of fibrosis at follow-up (71.4%), compared to both type 1 (43.5%) and type 3 MNV (26.7%) (p&#x2009;=&#x2009;0.04). Age at baseline and best-corrected visual acuity (BCVA) were factors associated with final vision loss (p&#x2009;<&#x2009;0.001), while the presence of drusen alone appeared protective (p&#x2009;=&#x2009;0.03). SFCT at baseline also reduced the risk of outer retinal atrophy (p&#x2009;=&#x2009;0.01).<br><br>CONCLUSIONS: SFCT served as a key indicator for type 2 MNV while aging predominantly predicted type 3 MNV. The findings may improve the early identification and tailored management of MNV phenotypes, optimizing visual outcomes and mitigating complications such as fibrosis and atrophy.}, }
@article {pmid41223116, year = {2026}, author = {Ottaiano-Poli, PA and Germano-Morrel, CS and Tomishige, KS and Macchione, RM and Kasahara, N}, title = {Comparison of balance-confidence between glaucoma and age-related macular degeneration patients who live in a developing country.}, journal = {Clinical rehabilitation}, volume = {40}, number = {3}, pages = {419-426}, doi = {10.1177/02692155251394989}, pmid = {41223116}, issn = {1477-0873}, mesh = {Humans ; Male ; Female ; *Macular Degeneration/psychology/physiopathology ; Aged ; *Postural Balance/physiology ; Brazil ; Developing Countries ; Case-Control Studies ; Middle Aged ; *Glaucoma, Open-Angle/psychology/physiopathology ; Activities of Daily Living ; *Glaucoma/psychology/physiopathology ; }, abstract = {ObjectiveTo compare balance-confidence among patients with primary open-angle glaucoma, age-related macular degeneration, and controls in Brazil.DesignCase-control study.SettingCharity hospital in São Paulo, Brazil.ParticipantsPatients with glaucoma, age-related macular degeneration, and controls without eye diseases.Main outcomes measuresActivities-specific Balance Confidence (ABC) Scale scores.ResultsThe sample consisted of 64 patients with glaucoma, 60 with age-related macular degeneration, and 60 controls. All groups were matched by age, gender, ethnic distribution, and comorbidities. The ABC Scale score was 63.1 (25.9) in the glaucoma group, 69.5 (16.4) in the age-related macular degeneration group, and 95.3 (9.1) for the controls (P < 0.001; Hedges' g -1.65 and -1.93, large effect size); glaucoma patients score did not differ from age-related macular degeneration patients (P = 0.132; Hedges' g 0.30, small effect size).ConclusionBoth glaucoma and age-related macular degeneration patients reported lower balance-confidence in performing daily activities without losing balance as compared to controls.}, }
@article {pmid41223128, year = {2026}, author = {Spooner, KL and Fraser-Bell, S and Mehta, H and Hong, T and Broadhead, G and Wong, JG and Chang, AA}, title = {Lost to Follow-Up in Neovascular Age-Related Macular Degeneration: A Systematic Review of Global Trends, Risk Factors, and Clinical Consequences.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {249}, number = {1}, pages = {79-102}, doi = {10.1159/000549177}, pmid = {41223128}, issn = {1423-0267}, mesh = {Humans ; Risk Factors ; *Wet Macular Degeneration/drug therapy/epidemiology/diagnosis ; *Lost to Follow-Up ; Global Health ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Intravitreal Injections ; }, abstract = {INTRODUCTION: Loss to follow-up (LTFU) among patients receiving anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) remains a critical challenge for maintaining visual outcomes. This systematic review and meta-analysis evaluated the prevalence, risk factors, and impact on visual prognosis of LTFU across real-world studies.<br><br>METHODS: A comprehensive literature search of PubMed, Embase, Cochrane, Scopus, and Google Scholar identified studies published between 2015 and 2025. Eligible studies included observational cohorts and registry-based analyses that reported the LTFU rates, risk factors, and visual outcomes following treatment discontinuation. Random-effects meta-analysis (DerSimonian-Laird) estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs); heterogeneity was assessed via I2 and Cochran's Q. Continuous predictors were analysed using regression-based ORs or standardized mean differences (SMDs), where appropriate.<br><br>RESULTS: We included 52 studies. Short-term LTFU was defined as 6-12 months without treatment; long-term LTFU as &#x2265;12 months. LTFU rates ranged from <5% to >75% over up to 10 years. Older age was moderately associated with LTFU (SMD = 0.47, 95% CI: 0.37-0.57; &#x2248;6-7 years older). Greater travel distance increased LTFU risk (OR = 1.35 per 10-km increase, 95% CI: 1.14-1.60). Male sex (OR = 1.20, 95% CI: 1.05-1.37) and caregiver/transport dependence (OR = 2.00, 95% CI: 1.45-2.75) were also associated with a higher likelihood of LTFU. Treat-and-extend (T&amp;E) regimens showed lower LTFU than pro re nata. Patients who were LTFU had worse visual outcomes even after resuming care.<br><br>CONCLUSION: LTFU in nAMD treatment is common and driven by demographic (age, sex, and race), socioeconomic (income and insurance), and access (distance and caregiver need) factors. Continuous treatment, early response, and structured regimens (e.g., T&amp;E) mitigate dropout risk. Interventions to improve access and personalize support are essential to reduce LTFU and preserve visual outcomes.}, }
@article {pmid41224521, year = {2025}, author = {Yeo, D and Hwang, SH and Lee, S and Jeong, J and Kong, J and Lee, H and Smith, L and Cho, J and Yim, Y and Lee, J and Kang, J and Yang, JM and Yon, DK}, title = {Global, regional and national burden of major blindness-associated ophthalmologic conditions, 1990-2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327917}, pmid = {41224521}, issn = {1468-2079}, abstract = {BACKGROUND: The global burden of blindness and vision loss continues to increase, yet comprehensive analyses of underlying causes remain limited. This study estimated the global and regional burden of blindness-related diseases from 1990 to 2021 and projected trends to 2050 to inform public health strategies.<br><br>METHODS: We analysed data from the Global Burden of Disease Study (GBD) 2021 to estimate the prevalence and disability-adjusted life years (DALYs) rates of blindness and vision loss, focusing on six major causes, including glaucoma, cataract, age-related macular degeneration, refraction disorders, near vision loss and other vision loss. We quantified the contribution of risk factors, and future trends were projected to 2050 using GBD's forecast framework.<br><br>RESULTS: In 2021, the global age-standardised prevalence and DALY rates of blindness were 15&#x2009;784.3 (95% uncertainty interval (UI), 12&#x2009;761.4-19&#x2009;502.3) and 342.8 (224.2-503.6) per 100&#x2009;000. Although global age-standardised DALY rates remained statistically stable between 1990 and 2021, regional trends varied numerically. Southern sub-Saharan Africa recorded the highest age-standardised prevalence rate in 2021 at 16&#x2009;741.4 (13&#x2009;187.8-21&#x2009;129.5), whereas the highest DALY rate was observed in South Asia at 497.1 (345.3-691.6). While the overall burden of blindness did not differ significantly by sex, glaucoma showed a higher burden in males. From 1990 to 2021, cataract DALY rates attributable to household air pollution decreased by 38.4%, with projections showing stable age-standardised rates through 2050.<br><br>CONCLUSIONS: As populations age, the global burden of vision loss is projected to grow, with particularly high impact in lower-sociodemographic index regions such as Southern Sub-Saharan Africa and South Asia.}, }
@article {pmid41226778, year = {2025}, author = {Dave, A and Tosevska, A and Morselli, M and Tom, E and Pellegrini, M and Skowronska-Krawczyk, D and Radu, RA}, title = {Dysregulated DNA Methylation in Abca4[-/-] Retinal Pigment Epithelium: Insights into Early Stage of Stargardt Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {21}, pages = {}, pmid = {41226778}, issn = {1422-0067}, support = {1R01EY025002-05/NH/NIH HHS/United States ; 1R01EY000331-10/NH/NIH HHS/United States ; na//Research to Prevent Blindness, Inc./ ; }, mesh = {*DNA Methylation/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Stargardt Disease/genetics/pathology/metabolism ; Animals ; *ATP-Binding Cassette Transporters/genetics/metabolism ; Mice ; Disease Models, Animal ; Methyl-CpG-Binding Protein 2/metabolism/genetics ; Mice, Knockout ; *Macular Degeneration/genetics/congenital ; Epigenesis, Genetic ; Humans ; }, abstract = {Stargardt disease (STGD1), the most common inherited juvenile macular degeneration, is caused by biallelic mutations in the ABCA4 gene. Currently, there is no approved treatment. In this study, we investigated early-stage epigenomic changes in the retinal pigment epithelium (RPE) of Abca4[-/-] mice, a well-established model of STGD1. Reduced representation bisulfite sequencing (RRBS) revealed hypermethylation of gene regions associated with disease-related pathways, implicating methyl-CpG-binding protein 2 (MeCP2) and RE1-silencing transcription factor (REST) as potential regulators. Notably, DNA methylation of a subset of genes preceded their transcriptional change and disease phenotypes in Abca4[-/-] RPE. Together with the detected age-dependent increase in MeCP2 levels in Abca4[-/-] RPE, these findings suggest that early DNA methylation changes may contribute to RPE dysfunction and eventual cell loss in STGD1.}, }
@article {pmid41229226, year = {2025}, author = {Rakic, N and Van Cauwenberge, F and Georges, A and Rakic, JM}, title = {[Early management of vitreous hemorrhage : clinical experience of the University Hospital of Liege].}, journal = {Revue medicale de Liege}, volume = {80}, number = {11}, pages = {703-707}, pmid = {41229226}, issn = {0370-629X}, mesh = {Humans ; *Vitreous Hemorrhage/surgery/therapy/diagnosis/etiology ; Retrospective Studies ; Male ; Female ; Aged ; Hospitals, University ; Middle Aged ; Vitrectomy ; Adult ; Aged, 80 and over ; Visual Acuity ; Young Adult ; }, abstract = {Hemorrhages occurring in the vitreous body have multiple etiologies. They cause an immediate and severe loss of visual acuity and sometimes require urgent surgical management by vitrectomy. We report in a retrospective series the clinical data of 76 patients treated at the University Hospital of Liège, highlighting the high incidence of retinal tears caused by posterior detachment of the vitreous body, the predominance of proliferative diabetic retinopathy in young patients, and that of age-related macular degeneration in older patients. Surgical intervention allows a very significant and fast improvement in visual acuity while avoiding the natural history of retinal tears which, in a hemorrhagic context, lead to retinal detachment with a very bad prognosis.}, }
@article {pmid41229552, year = {2025}, author = {Schuster, AK and Leisle, L and Picker, N and Vorwerk, H and Hahn, P and Wasem, J and Lewis, P}, title = {Economic and Medical Burden of Non-Exudative Age-Related Macular Degeneration in Germany: A Retrospective Observational Claims Data Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4129-4144}, pmid = {41229552}, issn = {1177-5467}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in higher-income countries. This study aimed to explore the medical and economic burden of non-exudative AMD patients living in Germany.<br><br>METHODS: German claims data (AOK PLUS) were utilized in this retrospective analysis. Prevalent non-exudative AMD only patients were compared to (i) non-exudative AMD patients with a concomitant exudative AMD diagnosis and (ii) propensity score matched non-AMD controls in terms of patient characteristics and eye-related diagnostic/monitoring patterns during baseline (in 2020) as well as in terms of the healthcare resource use and associated costs during the follow-up (in 2021).<br><br>RESULTS: The sample comprised 25,439 patients diagnosed with non-exudative AMD only and 7,153 diagnosed with both types of AMD (mean age: 79/81 years | female: 64.3%/64.5%). The total health insurance costs for non-exudative AMD only patients were estimated to be 6,500 &#x20ac; per person-year (pPY), which was about 500 &#x20ac; pPY higher than in matched non-AMD controls. The total costs further increased by about 3,500 &#x20ac; pPY in the presence of concomitant exudative AMD. Also, the healthcare resources (especially related to ophthalmological care) were utilized more frequently by non-exudative AMD patients compared to non-AMD controls, and even more so by patients with concomitant exudative AMD.<br><br>CONCLUSION: Non-exudative AMD patients were associated with an increased medical and economic burden compared to non-AMD individuals living in Germany.}, }
@article {pmid41230053, year = {2025}, author = {Ambiya, V and Kapoor, G and Sharma, VK}, title = {Large subfoveal pigment epithelial detachment causing macular hole formation: Surgical approach.}, journal = {Oman journal of ophthalmology}, volume = {18}, number = {3}, pages = {382-384}, pmid = {41230053}, issn = {0974-620X}, abstract = {Subfoveal pigment epithelial detachments (PEDs) have been reported to develop full-thickness macular hole (FTMH). The response to treatment has been varied in different reports, with most cases having persistent PED even after successful surgical closure of the macular hole. Here, we report an unusual case of nonneovascular age-related macular degeneration, having a large subfoveal serous PED, leading to the formation of a large FTMH, which showed complete flattening of the PED with a successful closure of the macular hole with the surgical approach.}, }
@article {pmid41230077, year = {2025}, author = {Sriram, R and Manayath, GJ}, title = {Subretinal injection of tissue plasminogen activator for submacular hemorrhage - When and how to do.}, journal = {Oman journal of ophthalmology}, volume = {18}, number = {3}, pages = {284-290}, pmid = {41230077}, issn = {0974-620X}, abstract = {Submacular hemorrhage (SMH) causes irreversible loss of vision as it causes permanent anatomical and functional damage to photoreceptors. The various causes include polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, retinal artery macroaneurysm, high myopia, and trauma. The current treatment modalities include antivascular endothelial growth factor (anti-VEGF) monotherapy, anti-VEGF ± gas pneumatic displacement ± intravitreal recombinant tissue plasminogen activator injection (rtPA), and triple therapy (intravitreal anti-VEGF + intravitreal rtPA + perfluoropropane gas injection). The surgical displacement of the SMH by vitrectomy with subretinal tissue plasminogen activator injection + intravitreal anti-VEGF + gas tamponade has been a valuable addition to our armamentarium. Evidence suggests that this novel technique provides better anatomical and functional outcomes in terms of visual acuity when the surgical displacement is performed within the prompt time frame in comparison to other available modalities of treatment. The current lacuna in the literature is the absence of level 1 evidence to support the surgical displacement as the first-line therapy. Hence, we review the current evidence and provide recommendations regarding this ever-promising therapy that can be vision-saving.}, }
@article {pmid41230290, year = {2025}, author = {Shloush, M and Eleff, A and Eleff, E}, title = {Ophthalmology Considerations in End-of-Life Care.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94396}, pmid = {41230290}, issn = {2168-8184}, abstract = {Ophthalmologic interventions can significantly impact quality of life, even in the context of end-of-life care. This paper explores the ethical and clinical considerations for ophthalmologic treatments in hospice care, with a focus on cataract surgery, age-related macular degeneration (ARMD) therapy, retinal detachment (RD) repair, glaucoma, painful blind eye (PBE) management, benign and surface ocular tumors, and corneal or anterior segment diseases. A review of published literature and clinical precedent was conducted to assess the benefits, risks, and practical limitations of ophthalmologic procedures in hospice patients, with an emphasis on quality of life. Cataract surgery has been shown to be cost-effective in hospice settings, offering significant improvements in vision and overall quality of life. Treatment for ARMD, though requiring ongoing injections, can provide benefits within weeks and help sustain visual function. RD repair, while more complex, can substantially restore vision when appropriately managed. Palliative glaucoma interventions, including individualized target intraocular pressures and laser therapy, can minimize treatment burden while maintaining comfort. PBEs may be managed with retrobulbar chlorpromazine or alcohol injections, and enucleation or evisceration may be considered when pain persists. Benign or surface ocular tumors and corneal or anterior segment diseases can often be addressed with conservative, comfort-focused measures to reduce symptoms and preserve quality of life. Ophthalmologic procedures should be considered viable options in end-of-life care when clinically indicated, with careful ethical review. Restoration of vision contributes meaningfully to the quality of life and deserves thoughtful inclusion in care planning.}, }
@article {pmid41230723, year = {2026}, author = {Usmani, E and Bahrami, B and Ebneter, A and Chan, WO}, title = {Cessation of Anti-VEGF Treatment Therapy in Age-Related Macular Degeneration: A Narrative Review.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {2}, pages = {275-283}, doi = {10.1111/ceo.70034}, pmid = {41230723}, issn = {1442-9071}, mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity ; *Withholding Treatment ; Quality of Life ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; }, abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD), significantly improving visual outcomes and enhancing the quality of life for affected patients. However, the decision to discontinue anti-VEGF therapy in nAMD management remains complex and lacks consensus, with various criteria being applied. This narrative review examines the available evidence on the cessation of anti-VEGF treatment in nAMD in detail.}, }
@article {pmid41231253, year = {2026}, author = {Yu, Y and Sun, Y and Zhao, T}, title = {The roles of glycerophospholipids in the aging retina and age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {309-323}, pmid = {41231253}, issn = {1435-702X}, support = {No. 2023SK2032//Key Research and Development Program of Hunan Province of China/ ; No. kq2502054//the Changsha Municipal Natural Science Foundation/ ; No. 2025JGB161//Project Program of central south university graduate education teaching reform/ ; }, mesh = {Humans ; *Macular Degeneration/metabolism ; *Aging/physiology/metabolism ; *Glycerophospholipids/metabolism ; *Retina/metabolism/pathology ; Animals ; }, abstract = {Glycerophospholipids (GPs) are integral constituents of cellular membranes, and play a crucial role in the regulation of lipid metabolism homeostasis and physiological conditions. However, pathological alterations associated with aging, such as variations in plasma GP concentrations, disruptions in intercellular GP transport, and local accumulation of excessive GPs, have been observed. These changes induce irreversible cellular degeneration, ultimately leading to tissue damage in organs such as the brain and retina. A growing body of evidences has demonstrated that GPs play significant roles in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Similarly, GPs have been implicated in the pathogenesis and progression of age-related macular degeneration (AMD), a degenerative condition affecting the choroid and retinal layers of the eye. Understanding the homeostasis of GP metabolism in the aging retina and in AMD is essential for elucidating the pathogenic processes involved in AMD. In this review, we present a comprehensive overview of the mechanisms of GPs in the aging retina and their correlation with degenerative processes associated with AMD. KEY MESSAGES: What is known Metabolic dysregulation of glycerophospholipids (GPs) plays vital roles in age-related macular degeneration (AMD) and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Patients with age-related neurological disorders exhibit a significantly higher risk of developing AMD compared to healthy individuals, potentially due to shared pathological mechanisms, including mitochondrial metabolic disturbance, chronic inflammation and autophagy dysfunction. What is new The interconnection between multiple GP species and their metabolites has been established to delineate complex pathogenic mechanisms underlying the aging retina and AMD, including cell senescence, autophagy and apoptosis, oxidative stress, inflammation, vascular abnormalities. GPs may serve as potential therapeutic targets to prevent or delay the progression of AMD.}, }
@article {pmid41232598, year = {2026}, author = {Yang, Z and Zhang, W and Gu, X and Zhao, X and Sadda, SR and Cheung, G and Koh, A and Loewenstein, A and Li, B and Wang, C and Zhang, J and Yang, J and Jin, K and Meng, L and Chen, L and He, M and Yuan, M and Luo, M and Li, N and Ruamviboonsuk, P and Yu, Q and Zhao, Q and Cheng, S and Peng, W and Zhang, X and Zhang, X and Liu, X and Wang, Y and Xu, Z and Xie, Z and Xu, Z and Ma, Z and Zhao, C and Chen, Y}, title = {Polypoidal choroidal vasculopathy: In-depth insights and promising future directions.}, journal = {Progress in retinal and eye research}, volume = {110}, number = {}, pages = {101414}, doi = {10.1016/j.preteyeres.2025.101414}, pmid = {41232598}, issn = {1873-1635}, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnosis/therapy ; *Choroid/blood supply ; Fluorescein Angiography/methods ; *Polyps/diagnosis/therapy ; Animals ; Angiogenesis Inhibitors/therapeutic use ; *Choroid Diseases/diagnosis ; Polypoidal Choroidal Vasculopathy ; }, abstract = {Polypoidal choroidal vasculopathy (PCV) is an ocular condition predominantly affecting elderly individuals of Asian descent, characterized by the presence of polypoidal lesions and branching neovascular networks in the sub-retinal pigment epithelium (RPE) space. It has garnered increased attention for its potential differences from neovascular age-related macular degeneration. Genetic studies have identified specific genetic markers associated with PCV. Advances in imaging techniques, particularly optical coherence tomography (OCT) and OCT angiography, have significantly enhanced the diagnosis of PCV and our insight into its unique pathogenesis. Treatment strategies for PCV have evolved, with anti-vascular endothelial growth factor (VEGF) monotherapy becoming the primary treatment, and combination therapies including photodynamic therapy showing promising results. Consideration of targets beyond VEGF and the incorporation of artificial intelligence (AI) based analysis strategies may open the door to more personalized, precise, and effective treatments for patients. This review comprehensively discusses the current knowledge and recent advancements in PCV, including its epidemiology, genetics, biomarkers, pathogenesis, diagnosis, and management. It also highlights the need to explore mechanism underlying the higher prevalence of PCV in pigmented races, clarify the roles of pachychoroid and pachydrusen in PCV pathogenesis, and develop animal models that can better recapitulate the disease's pathological features.}, }
@article {pmid41232694, year = {2026}, author = {Rashid, M and Azeem, S and Shahid, IF and Ali, MKB and Shahid, F and Fatima, A and Rashid, A and Azeem, E}, title = {Efficacy and safety of aflibercept biosimilars compared to reference aflibercept for retinal diseases: A systematic review and meta-analysis.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {780-792}, doi = {10.1016/j.survophthal.2025.11.007}, pmid = {41232694}, issn = {1879-3304}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use ; *Biosimilar Pharmaceuticals/therapeutic use ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use ; Visual Acuity ; *Diabetic Retinopathy/drug therapy ; Treatment Outcome ; *Macular Edema/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Randomized Controlled Trials as Topic ; }, abstract = {Aflibercept biosimilars offer cost-effective alternatives to reference aflibercept for retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). By inhibiting vascular endothelial growth factor-mediated vascular damage, they aim to improve visual outcomes with comparable safety and efficacy, increasing treatment access while reducing cost burden. We evaluate their performance against the reference drug. A comprehensive search was done across Cochrane, Embase, PubMed, Scopus and ClinicalTrials.gov. Randomized controlled trials were included, and quality was assessed via RoB 2.0 tool. A random-effects model estimated standardized mean differences (SMD) and risk ratios. 11 studies (4064 participants) were analyzed, 8 focused on nAMD and 2 on DME. No significant differences in best-corrected visual acuity changes were observed between biosimilars and reference aflibercept in studies on nAMD (SMD = -0.04, 95 % confidence inerval [CI]: -0.15-0.06) or DME (SMD = 0.11, 95 % CI: -0.12-0.33). Central subfield thickness change at week 4 and the endpoint also showed no significant differences. Similarly, no significant differences were seen in choroidal neovacularization size, vision maintenance, anti-drug antibody development, treatment-emergent adverse events, or ocular adverse effects. Biosimilar aflibercept show similar efficacy and safety to the original for nAMD and DME, with no significant differences in key outcomes. They offer a cost-effective alternative that offers similar clinical benefits while improving treatment accessibility.}, }
@article {pmid41235547, year = {2025}, author = {}, title = {Correction to "Peptide-Bound Aflibercept Eye Drops for Treatment of Neovascular Age-Related Macular Degeneration in Nonhuman Primates".}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {48}, pages = {e19902}, doi = {10.1002/advs.202519902}, pmid = {41235547}, issn = {2198-3844}, }
@article {pmid41235805, year = {2026}, author = {Hashimoto, Y and Reddie, I and Louw, Z and Gillies, M}, title = {Macular Atrophy in the Better-Seeing Eye of Australian Patients Treated for Neovascular Age-Related Macular Degeneration.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {2}, pages = {295-297}, doi = {10.1111/ceo.70032}, pmid = {41235805}, issn = {1442-9071}, support = {//Roche/ ; //Bayer/ ; 1195021//National Health and Medical Research Council/ ; //Astellas/ ; //Apellis/ ; }, }
@article {pmid41236117, year = {2025}, author = {Singerman, L and Gugiu, C and Tschosik, E and Doll, H and Singerman, B and Gentile, B}, title = {DERIVATION OF A SHORT FORM OF THE NATIONAL EYE INSTITUTE VISUAL FUNCTION QUESTIONNAIRE-25 IN SUBJECTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.}, journal = {Retina (Philadelphia, Pa.)}, volume = {45}, number = {12}, pages = {2319-2328}, pmid = {41236117}, issn = {1539-2864}, mesh = {Humans ; *Visual Acuity/physiology ; Psychometrics ; Female ; Male ; Surveys and Questionnaires ; Aged ; *Wet Macular Degeneration/physiopathology/drug therapy ; *National Eye Institute (U.S.) ; Angiogenesis Inhibitors/therapeutic use ; Reproducibility of Results ; United States ; Ranibizumab/therapeutic use ; *Sickness Impact Profile ; Aged, 80 and over ; *Quality of Life ; Middle Aged ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {PURPOSE: Develop a short form of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) using Rasch methodology in patients with neovascular age-related macular degeneration.<br><br>METHODS: Data on 32 items of the NEI VFQ-25 were analyzed from 1,294 patients in 3 studies of ranibizumab in neovascular age-related macular degeneration. Items were first grouped by visual function type; iterative multiple-group rating scale Rasch analyses were used to derive the Visual Function Questionnaire-Short Form (VFQ-SF). Item and scale-level VFQ-SF psychometric properties were assessed with estimation of meaningful within-patient change.<br><br>RESULTS: Fourteen of 32 items were eliminated initially; the final optimal subset included 7 items measuring 5 domains. The seven-item VFQ-SF had strong internal consistency (average item-total correlation 0.67, Cronbach alpha 0.88), test-retest reliability (intraclass correlation coefficient 0.79-0.91), and high NEI VFQ-25 composite score correlation (r = 0.93). Convergent (mean r = 0.76) and divergent (mean r = 0.24) validity were demonstrated. Known-groups validity was shown by mean VFQ-SF scores monotonically increasing with best-corrected visual acuity severity categories with large between group effect sizes (>2.8). Responsiveness was confirmed with VFQ-SF change linearly related to best-corrected visual acuity change. A meaningful within-patient change estimate of seven points was derived.<br><br>CONCLUSION: The seven-item VFQ-SF measures composite vision-related functioning, met all psychometric benchmarks, and is fit-for-purpose in neovascular age-related macular degeneration patients.}, }
@article {pmid41237838, year = {2026}, author = {Wei, Y and Hu, X and Liu, Y and Zhang, J and Zhao, L and Yang, J and Xie, Z and Shi, D and Ma, L}, title = {ALKBH5-mediated m6A modification of ID2 mRNA promotes choroidal neovascularization and subretinal fibrosis.}, journal = {Cellular signalling}, volume = {138}, number = {}, pages = {112237}, doi = {10.1016/j.cellsig.2025.112237}, pmid = {41237838}, issn = {1873-3913}, mesh = {*Choroidal Neovascularization/genetics/metabolism/pathology ; Animals ; Humans ; *AlkB Homolog 5, RNA Demethylase/metabolism/genetics ; *RNA, Messenger/metabolism/genetics ; Mice ; Fibrosis ; *Adenosine/analogs &amp; derivatives/metabolism ; Mice, Inbred C57BL ; Retina/pathology/metabolism ; RNA-Binding Proteins/metabolism ; Macular Degeneration/genetics/pathology/metabolism ; Disease Models, Animal ; Cell Movement ; Male ; }, abstract = {Choroidal neovascularization (CNV) and subretinal fibrosis are pivotal in the pathogenesis of wet age-related macular degeneration (wAMD) and contribute significantly to blindness. The role of N6-methyladenosine (m6A) modifications in the progression of wAMD remains unclear. This study identifies a significant upregulation of the RNA demethylase A-ketoglutarate dioxygenase ALKB homolog 5 (ALKBH5) in macular samples of wAMD donors. Mechanistically, ALKBH5 enhances retinal microvascular endothelial cell (RMEC) migration, angiogenesis, and endothelial-mesenchymal transition (EndMT) by upregulating DNA binding/differentiation protein 2 (ID2). Further analysis reveals that ALKBH5 interacts with the YTHDF2 binding domain of the m6A reader, which recognizes the m6A sequence on ID2 mRNA. This interaction stabilizes ID2 mRNA and modulates its m6A methylation, thereby influencing the epigenetic network in wAMD. In laser-induced CNV mouse models, ALKBH5 knockdown significantly inhibits CNV and subretinal fibrosis while protecting the retinal photoreceptor layer, thus preserving visual function. This study highlights the ALKBH5-YTHDF2-ID2 axis as a critical regulator in wAMD and suggests it as a novel therapeutic target for subretinal fibrosis in wAMD.}, }
@article {pmid41237938, year = {2026}, author = {Wang, Y and Xia, Z and Jia, L and Zhang, K and Wei, P and Han, G}, title = {Metabolomic biomarkers across plasma, serum, and ocular fluids in age-related macular degeneration: narrative review and evidence synthesis.}, journal = {Experimental eye research}, volume = {262}, number = {}, pages = {110749}, doi = {10.1016/j.exer.2025.110749}, pmid = {41237938}, issn = {1096-0007}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Macular Degeneration/metabolism/blood/diagnosis ; *Metabolomics/methods ; *Aqueous Humor/metabolism ; Disease Progression ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss globally. It is a degenerative disorder characterized by progressive macular damage and systemic metabolic dysregulation. Metabolomics elucidates relationships between metabolic alterations and disease phenotypes, providing scientific foundation for biomarker-driven predictive diagnostics. Current AMD staging predominantly relies on a linear classification based on clinical symptoms and imaging phenotypes. But metabolic alterations often precede morphological changes, providing a crucial window for early screening and intervention. Recent multi-biofluid metabolomic studies have identified key metabolic biomarkers, including glycerophospholipid pathway metabolites, acylcarnitines, branched-chain amino acids, and adenosine. They are predictive of transition from non-advanced to advanced stages. This review summarizes stage-specific metabolic biomarkers across AMD progression, such as 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (18:0-20:4 PC), sphingosylphosphorylcholine (LysoSM[d18:1]), lysophosphatidylcholine (LysoPC[18:4]), short-chain acylcarnitines (e.g., acetylcarnitine [C2]), long-chain acylcarnitines (e.g., linoleoylcarnitine [C18:2]), and valerylcarnitine (C5). These biomarkers may allow for timely intervention before irreversible visual impairment and underscore the importance of differential metabolic signatures between stable and progressive stages for early disease management. By unveiling the dynamic changes of these critical metabolites, and providing evidence for their prognostic value in stage transition, this review proposes an evidence-based foundation for early risk stratification and precision intervention in AMD.}, }
@article {pmid41242720, year = {2025}, author = {Zheng, X and Mi, Y and Cao, Y and Tong, L and Wan, M}, title = {Plasma caffeine level as a protective factor against age-related eye diseases: a two-sample Mendelian randomisation study.}, journal = {The British journal of nutrition}, volume = {}, number = {}, pages = {1-7}, doi = {10.1017/S0007114525105291}, pmid = {41242720}, issn = {1475-2662}, abstract = {Traditional studies examining caffeine intake and age-related eye diseases (ARED) have shown inconsistent results, potentially related to variations in caffeine assessment methods. This two-sample Mendelian randomisation study investigated associations between plasma caffeine and four ARED: senile cataract, diabetic retinopathy (DR) and glaucoma and age-related macular degeneration (AMD). Summary data on genetically predicted plasma caffeine came from a genome-wide association study of 9876 European-ancestry participants across six population-based studies. ARED data were extracted from FinnGen Consortium clinical records. We further examined causal effects on glaucoma subtypes: primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) and assessed intraocular pressure (IOP) as a potential mediator. Higher genetically predicted plasma caffeine levels were associated with reduced risk of senile cataract (OR 0·84, 95 % CI 0·78, 0·90, P < 0·001), DR (OR 0·81, 95 % CI 0·74, 0·88, P < 0·001), glaucoma (OR 0·83, 95 % CI 0·73, 0·95, P = 0·008) and PACG (OR 0·74, 95 % CI 0·54, 0·99, P = 0·046). No associations were observed with AMD or POAG. Mediation analysis suggested that 41 % (95 % CI −0·14, −0·01) of caffeine’s effect on glaucoma was mediated by IOP. Our findings indicate that elevated plasma caffeine may protect against senile cataract, DR and glaucoma, but not AMD. Effects differed by glaucoma subtype, with IOP partially explaining the overall association. This study provides genetic evidence supporting caffeine’s role in mitigating ARED risk, highlighting its potential therapeutic implications.}, }
@article {pmid41243864, year = {2025}, author = {Cui, Y and Li, H and Fan, W and Wu, H and Wang, J and Qu, C and Pu, N and Tao, Y}, title = {Dialogue Between the Clock Gene Bmal1 and Retinopathy: What Is the Exact Relationship?.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {11}, pages = {e70490}, pmid = {41243864}, issn = {1755-5949}, support = {221100310200//the Science and Technology Major Project of Henan Province/ ; 224200510013//the Zhongyuan Science and Technology Leading Talent Project/ ; }, mesh = {Humans ; *ARNTL Transcription Factors/genetics/metabolism ; Animals ; Circadian Rhythm/physiology/genetics ; *Retinal Diseases/genetics/metabolism ; Circadian Clocks/genetics/physiology ; Retina/metabolism ; CLOCK Proteins/genetics ; Diabetic Retinopathy/genetics ; }, abstract = {BACKGROUND: Circadian clock coordinates the physiologic and behavioral activities with a 24-hour solar rhythm to maintain the temporal homeostasis of the body. In the mammalian retina, the circadian system regulates the physiological function of this organ. The realm of ocular circadian rhythm has earned kinds of research interest as the circadian rhythms dysfunction will disrupt the retinal homeostasis. Bmal1 functions as a major transcriptional regulator of the circadian clock.<br><br>RESULTS: In the retina, Bmal1 mediates the processing of light information, sustains photoreceptor viability and governs neurotransmitter release. Moreover, Bmal1 gene is believed to be a pathologic cofactor of the diabetic retinopathy (DR), age-related macular degeneration (AMD), premature aging and refractive myopia. To date, the precise mechanisms underlying the pathological effects mediated by Bmal1 remain incompletely elucidated.<br><br>CONCLUSIONS: This review presents recent findings and evidence regarding the contributory role of Bmal1 in retinal degeneration and its deficits, while exploring its therapeutic potential. And th review provides a comprehensive analysis of the underlying mechanisms of the clock gene Bmal1 in other diseases, with the aim of offering insights into innovative therapeutic strategies for retinopathy.}, }
@article {pmid41244030, year = {2025}, author = {Momenaei, B and Wakabayashi, T and Adams, OE and Wang, K and Regillo, CD and Spirn, M and Ho, AC and Hsu, J and Kaiser, R and Yonekawa, Y and Orlin, A and Garg, SJ}, title = {Short-Term Changes in Intraocular Pressure Following Intravitreal Injection of Pegcetacoplan.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251390791}, pmid = {41244030}, issn = {2474-1272}, abstract = {Purpose. To determine short-term changes in intraocular pressure (IOP) after intravitreal injection of 0.1 mL pegcetacoplan (Syfovre; Apellis Pharmaceuticals) for the treatment of geographic atrophy (GA). Methods. This prospective, interventional study evaluated a case series of patients with GA without corneal pathology or a history of vitreoretinal surgery who received pegcetacoplan injections. IOP was measured with a handheld applanation tonometer immediately prior to injection, immediately after injection, and at 5, 10, 20, and 30 minutes postinjection. Results. Fifty-one patients (total 73 eyes) were enrolled. The mean (±SD) preinjection IOP was 15.3 ± 3.3 mm Hg, which significantly increased to 40.2 ± 13.7 mm Hg (P < .001) immediately after injection. Subsequent IOP measurements showed a gradual decrease to 31.3 ± 11.6 mm Hg at 5 minutes (P < .001), 23.2 ± 9.7 mm Hg at 10 minutes (P < .001), 19.6 ± 8.6 mm Hg at 20 minutes (P < .001), and 16.4 ± 4.9 mm Hg at 30 minutes (P = .05) postinjection. No further treatment was required, except that the left eye of 1 patient with a history of primary open-angle glaucoma and persistent IOP elevation underwent anterior chamber tap 20 minutes after injection. Multivariate linear regression analysis revealed that a higher IOP at 30 minutes postinjection was significantly associated with the preinjection IOP (P = .004) and with a history of glaucoma (P = .019). Conclusions. Following pegcetacoplan injections, immediate IOP elevation was observed, which gradually declined within the first 30 minutes. Eyes with higher baseline IOP or a history of glaucoma exhibited higher postinjection IOP.}, }
@article {pmid41244346, year = {2025}, author = {Wang, Y and Jiang, D and Wang, Q and Cao, Y and Guo, H and Lu, Y and Tian, F}, title = {Three-dimensional tissue engineering and organoid technologies for retinal regeneration and therapy.}, journal = {Bioengineering &amp; translational medicine}, volume = {10}, number = {6}, pages = {e70051}, pmid = {41244346}, issn = {2380-6761}, abstract = {The human eye, a masterpiece of evolution, orchestrates the intricate process of vision. The retina is a tissue with a layered structure that plays a critical role in converting light signals into neural impulses interpretable by the brain. Various eye conditions such as glaucoma, retinitis pigmentosa, age-related macular degeneration, and other retinopathies are characterized by damage or degeneration in the retina. Recent strides in organoid cultivation and advanced three-dimensional (3D) bioengineering technologies offer promising avenues for potential therapeutic interventions. Compared to traditional two-dimensional cell culture models, which are non-natural and limited in accuracy, 3D models, including organoids, electrospinning constructs, microfabrication-based scaffolds, and hydrogel systems, are more delicate, especially in recapitulating tissue architecture, offering spatial patterning, and enabling vascularization. Retinal organoids are 3D multicellular structures derived from stem cells that can mimic the retina's layered architecture and functionality. However, their inherent complexity, including the presence of multiple differentiated cell types, may not be necessary for all disease modeling applications. In contrast, engineered 3D technologies can be tailored to specific retinal diseases by incorporating only the most relevant cell types, matrix stiffness, and spatial arrangements, offering greater experimental control and reproducibility in targeted therapeutic testing. In the following paper, we will discuss organoid generation in detail. Besides retinal organoids, bioprinting is another promising avenue for regenerative medicines. We further review a suite of 3D fabrication strategies, including inkjet and laser-assisted bioprinting, electrospun scaffolds, and hydrogel systems, and evaluate their current and potential applications in modeling retinal diseases and developing translational therapies. We will also delve into the contemporary advancements in retinal therapies, particularly emphasizing the roles and prospects of organoid and engineered 3D technologies.}, }
@article {pmid41244990, year = {2026}, author = {Tan, JCK and Montesano, G and Behning, C and Dunbar, HMP and Finger, RP and Tufail, A and Terheyden, JH and Holz, FG and Luhmann, UFO and Crabb, DP and , }, title = {Using the Rate of Global and Pointwise Microperimetry Change to Predict Structural Conversion in Intermediate Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100950}, pmid = {41244990}, issn = {2666-9145}, abstract = {PURPOSE: Studies evaluating functional change in age-related macular degeneration (AMD) using microperimetry often measure the difference in global mean sensitivity at interval time points versus baseline. We evaluate the rate of global and pointwise microperimetry change in intermediate AMD (iAMD) in the multicenter MACUSTAR (Registration NCT03349801) study and assess their prognostic value in structural conversion to late-stage AMD.<br><br>DESIGN: Prospective study.<br><br>SUBJECTS: Four hundred forty-seven subjects with iAMD (Beckman classification) from 20 European sites.<br><br>METHODS: Subjects that underwent mesopic microperimetry on &#x2265;3 follow-up visits were included. Two methods of assessing functional progression were evaluated: (1) global mean sensitivity regression and (2) pointwise sensitivity regression at fastest progressing N number of locations (N from 1 to 10). Rates of microperimetry progression were then evaluated in an initial series of visits prior to structural conversion to late-stage AMD.<br><br>MAIN OUTCOME MEASURES: Area under the receiving operating characteristic (AUC) curves and Cox proportional hazard models were used to assess risk of structural conversion based on rate of functional progression.<br><br>RESULTS: The mean age of subjects was 72 (standard deviation 7) years. The median number of visits and duration of follow-up was 6 visits and 3 years, respectively. Structural conversion to late-stage AMD was observed in 80 (17.9%) eyes. In the visits prior to conversion, there was a greater rate of global mean sensitivity loss in eyes that eventually developed late-stage AMD compared with those that did not (-1.05 vs. -0.30 decibels/year, P < 0.001). The AUC for classifying structural conversion versus no conversion was 0.72 for global sensitivity progression and 0.75-0.76 for between 1 and 10 fastest progressing N pointwise locations. The rate of global (hazard ratio 1.7, confidence interval [CI] 1.4-2.0) and pointwise (hazard ratio 1.2, CI 1.2-1.3) microperimetry progression in the initial series of visits was significantly associated with structural conversion (P < 0.0001).<br><br>CONCLUSIONS: In the analysis of longitudinal microperimetry data from the MACUSTAR study, the rate of global and pointwise sensitivity change was significantly greater and strongly prognostic of eyes that developed structural conversion. Our findings support use of these trend-based pointwise analysis methods in assessing functional progression in iAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41244992, year = {2026}, author = {Kleinman, DM and Wykoff, CC and Borkar, DS and Guymer, RH and Kocab, AJ and Puscas, L and Wietholter, SC and Kesteloot, LL and Zacks, DN}, title = {ONL1204 for the Treatment of Geographic Atrophy: Phase Ib Study Evaluating Safety, Tolerability, and Efficacy.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100954}, pmid = {41244992}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the safety and tolerability of ONL1204, a novel, small peptide inhibitor of the fragment apoptosis stimulator receptor, for the treatment of patients with geographic atrophy (GA).<br><br>DESIGN: A phase Ib multicenter study involving a dose-escalation/open-label (DE/OL) component and a randomized, double-masked, sham-controlled natural history/treatment (NHS/T) component.<br><br>PARTICIPANTS: Patients aged &#x2265;55 years with GA secondary to age-related macular degeneration.<br><br>METHODS: Dose-escalation/OL patients received a single intravitreal injection of either 50 &#x3bc;g, 100 &#x3bc;g, or 200 &#x3bc;g of ONL1204 and were followed for 24 weeks. Participants in the NHS/T component were randomized (1:1:1) to either 50 &#x3bc;g or 200 &#x3bc;g of ONL1204 or sham injection, after a 24-week NHS phase. Two injections were administered 12 weeks apart, and patients were observed for an additional 12 weeks.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was safety, assessed by monitoring adverse events (AEs), ophthalmic examination, electrophysiology, fundus photography, fundus autofluorescence, and OCT. Additional endpoints included measurement of GA lesion area and best-corrected visual acuity.<br><br>RESULTS: Six patients were enrolled in the DE/OL component and 22 patients in the NHS/T component. All patients in the DE/OL component completed the study with no major safety findings or dose-limiting toxicities. Seventeen patients were randomized in the NHS/T component, with 15 patients completing the study. All ophthalmic AEs were mild or moderate in severity. ONL1204 demonstrated a favorable effect on GA lesion growth, with numerically favorable slower lesion growth compared with the fellow eye in the DE/OL component at 6 months and a numerically slower growth rate (mean difference [standard error of the mean] of -0.524 mm[2] [0.39]; P = 0.202) in the 200 &#x3bc;g ONL1204 group compared with the sham group in the treatment phase of the NHS/T component. There were no changes in the treatment group with respect to visual acuity suggestive of any safety issues.<br><br>CONCLUSIONS: ONL1204 was safe and well tolerated at all evaluated doses, with the potential to reduce GA lesion growth and improve vision. These results support further evaluation of ONL1204 in patients with GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41245253, year = {2025}, author = {Cen, S and Xie, S and Ibrahim, KS and Baran, MR and Li, X and Reilly, J and Tan, Z and He, Z and Shu, X}, title = {Modified Zhujing pill regulates RPE cholesterol metabolism and gut microbiota in an age-related macular degeneration mouse model.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1691360}, pmid = {41245253}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Macular Degeneration/drug therapy/metabolism ; Mice ; Disease Models, Animal ; *Drugs, Chinese Herbal/pharmacology/administration &amp; dosage ; *Cholesterol/metabolism ; *Retinal Pigment Epithelium/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Male ; Cytokines/metabolism ; Cecum/microbiology ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common retinal disorder, causing blindness in aged individuals. One of the traditional Chinese medicines, modified Zhujing pill (MZP), has been widely used to treat various ocular disorders, including AMD; however, its protective mechanisms remain elusive. In this study, we explored the functional role of MZP in high-fat-diet-fed mice, a commonly used model for AMD.<br><br>METHODS: Compounds of MZP water extract were identified by high-performance liquid chromatography (HPLC)/mass spectrometry (MS)/MS. The mice were divided into three groups: group 1 mice fed with control diet (CD), group 2 mice fed with high-fat diet (HFD), and group 3 mice fed with HFD for 12 weeks; groups 1 and 2 were then treated with physiological saline, while group 3 was treated with MZP for 4 weeks. The cholesterol level and expression of cholesterol homeostasis-associated genes, antioxidant genes, and proinflammatory cytokines in mouse tissues were measured using biochemical approaches. Mouse cecum microbiota compositions and metabolic functions were analyzed using 16rRNA sequencing and bioinformatics approach.<br><br>RESULTS: HFD-fed mice had high levels of cholesterol in the retinal pigment epithelial (RPE) cells, liver, and serum, a decreased expression of cholesterol homeostasis-associated genes and antioxidant genes in the RPE and liver, and an increased expression of proinflammatory cytokines. MZP treatment counteracted HFD-induced pathologic effects. Additionally, HFD altered cecum bacterial compositions and diversities associated with individual metabolic pathways. These metabolic pathways are involved in the biosynthesis of bacterial metabolites, mitochondrial function, oxidative stress, and inflammation. MZP reversed most of the changes back to control characteristics.<br><br>CONCLUSION: We postulate that the beneficial effects of MZP against AMD are possibly related to lowering the cholesterol level, suppressing oxidative stress and inflammation, and modulating gut microbiota and associated functions.}, }
@article {pmid41247474, year = {2026}, author = {Vahldiek, A and Heine, L and Vahldiek, B and Schröter, J and Wolf, JN and Swora, M and Reissberg, L and Pauleikhoff, L and Kleesiek, J and Pauleikhoff, D}, title = {Automated measurement of macular neovascularization lesion size in nAMD using AI segmentation.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {455-463}, pmid = {41247474}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; *Artificial Intelligence ; *Fluorescein Angiography/methods ; Follow-Up Studies ; *Macula Lutea/pathology ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Fundus Oculi ; Intravitreal Injections ; Aged, 80 and over ; }, abstract = {PURPOSE: To compare artificial intelligence (AI)-based annotations of hyperreflective material (HRM) and manual demarcation of macular neovascularization (MNV) on optical coherence tomography (OCT) volume scans in neovascular age-related macular degeneration (nAMD), and to assess the suitability of AI-driven OCT segmentation for longitudinal lesion monitoring.<br><br>METHODS: In this retrospective study, 42 eyes from 36 patients (21 f, 15&#xa0;m; mean age baseline 76.6 y) with exudative nAMD were analyzed using longitudinal spectral-domain OCT data. Manual MNV demarcations on en-face OCT projections served as ground truth and were compared to AI-predicted HRM segmentations generated by a 3D nU-Net model on OCT scans. HRM and MNV lesion areas were quantified at multiple time points, and agreement between manual and AI-based measurements was evaluated using Pearson correlation, ordinary least squares regression and robust regression.<br><br>RESULTS: A highly similar mean lesion growth was observed when comparing HRM/MNV lesion sizes in longitudinal measurements. Point-by-point comparison revealed a strong overall correlation (r&#x2009;=&#x2009;0.78) between AI-predicted and manually annotated HRM areas with increasing significance with longer follow-up. However, two aspects were responsible for some AI measurements being larger than manual measurements: At baseline, AI measurements included hyperreflective subretinal fluid as HRM, which was resorbed after three anti-VEGF injections, and during longer-term follow-up, manually annotated MNV areas were occasionally smaller than those derived from AI-based HRM segmentation due to the manual underestimation of very thin HRM.<br><br>CONCLUSIONS: AI-based segmentation of HRM on OCT scans demonstrates strong overall agreement with manual MNV measurements, particularly on longitudinal assessments. Despite some AI-based overestimations occurring at baseline and some manual MNV underestimations during follow-up, measurements between both methods were highly comparable over time.}, }
@article {pmid41247476, year = {2026}, author = {Rosso, WC and Chakravarthy, U and Girado, SEM and Rosenstiehl, S and Peto, T and Rodriguez, FJ}, title = {Characterization of subretinal hyperreflective material and short-term visual acuity in patients with neovascular age related macular degeneration after loading dose with antiangiogenics.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {2}, pages = {465-471}, pmid = {41247476}, issn = {1435-702X}, mesh = {Humans ; *Visual Acuity ; Female ; Aged ; Tomography, Optical Coherence/methods ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; Fluorescein Angiography/methods ; Follow-Up Studies ; Retrospective Studies ; Fundus Oculi ; *Ranibizumab/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Time Factors ; Dose-Response Relationship, Drug ; Treatment Outcome ; Bevacizumab/administration &amp; dosage ; *Retina/pathology ; Recombinant Fusion Proteins/administration &amp; dosage ; }, abstract = {PURPOSE: This study analyzes the morphological characteristics of subretinal hyperreflective material (SHRM) and its relationship with short-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial grown factor (anti-VEGF) at the Fundación Oftalmológica Nacional between 2011 and 2017.<br><br>METHODOLOGY: An analytical observational study was conducted on 65 treatment-na&#xef;ve nAMD patients who initiated treatment between January 2011 and December 2017. Spectral-Domain Optical Coherence Tomography (SD-OCT) was graded to determine quantitative and qualitative SHRM characteristics. SHRM features and best corrected visual acuity (BCVA) were correlated before and after treatment, and associations between SHRM characteristics and BCVA improvement after the loading phase were analyzed.<br><br>RESULTS: The median age was 75.5 years (range 68-84), and 56.9% were women. Aflibercept was the most widely used anti-VEGF (40%). Median BCVA improved from 0.8 logMAR (range 0.5-1.2) to 0.7 logMAR (range 0.4-1) after treatment. At baseline, a significant correlation was found between worse BCVA and SHRM horizontal extension (r=0.7, p=0.001), low reflectivity (p=0.017), and undefined margins (p=0.037). SHRM characteristics associated with BCVA improvement after treatment included low reflectivity (p=0.048), non-homogeneity (p=0.048), smaller width (p=0.043), and the presence of the external limiting membrane (ELM) (p=0.002) and ellipsoid zone (EZ) (p=0.017).<br><br>CONCLUSION: SHRM features such as low reflectivity, non-homogeneity, reduced width, and the presence of ELM/EZ were associated with improved short-term visual outcomes. These findings provide insight into favorable short-term SHRM characteristics, which may help establish early treatment criteria and support its role as a prognostic biomarker.<br><br>KEY MESSAGES: WHAT IS KNOWN : Neovascular age-related macular degeneration (nAMD) is a progressive disease that severely impacts vision if untreated. Subretinal hyperreflective material (SHRM) is a recognized biomarker on spectral-domain optical coherence tomography (SD-OCT) and has been studied as a predictor of long-term visual outcomes in patients treated with anti-VEGF therapy.<br><br>WHAT IS NEW: This study evaluates SHRM characteristics and their relationship with short-term visual outcomes after the loading dose of anti-VEGF treatment.SHRM features such as low reflectivity, undefined borders, smaller horizontal extent, and the presence of external limiting membrane (ELM) and ellipsoid zone (EZ) are associated with early visual improvement. SHRM features such as low reflectivity, undefined borders, smaller horizontal extent, and the presence of external limiting membrane (ELM) and ellipsoid zone (EZ) are associated with early visual improvement. These findings suggest that SHRM morphology could serve as an early prognostic biomarker, potentially guiding treatment decisions for better visual outcomes.}, }
@article {pmid41248230, year = {2026}, author = {Fragiotta, S and Sacconi, R and Beretta, F and Querques, G}, title = {Basal Laminar Deposits and Pseudodrusen: Rethinking Their Role in Age-Related Macular Degeneration Progression.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {3}, pages = {399-409}, doi = {10.1097/IAE.0000000000004683}, pmid = {41248230}, issn = {1539-2864}, mesh = {Humans ; *Retinal Drusen/diagnosis ; Disease Progression ; *Macular Degeneration/diagnosis ; *Retinal Pigment Epithelium/pathology ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Fundus Oculi ; Eye Diseases, Hereditary ; Bruch Membrane/pathology ; }, abstract = {PURPOSE: To explore the association between basal laminar deposits (BLamD) and pseudodrusen and its clinico-prognostic significance in the context of age-related macular degeneration (AMD).<br><br>METHODS: A comprehensive narrative review of the literature was conducted, focusing on histopathological, clinical, and imaging studies that examine BLamD and subretinal drusenoid deposits (SDD) in AMD. Histopathological and clinical studies were analyzed to understand the composition, distribution, and clinical significance of these deposits.<br><br>RESULTS: Imaging and histologic studies suggest that BLamD may serve as an indicator of AMD severity. BLamD is consistently observed in eyes with pseudodrusen and is characterized by a thin double-layer sign in vivo with a hyporeflective interior. On fundus autofluorescence, BLamD retain an intrinsic autofluorescence, leading to a dark grey appearance of the nascent atrophic lesions. The association with SDD, also known as reticular pseudodrusen, can synergically affect the outer retina and retinal pigment epithelium, leading to a rapidly progressive atrophy.<br><br>CONCLUSION: BLamD is a key pathologic feature in AMD, particularly in eyes with pseudodrusen. Their presence may contribute to disease progression, highlighting the need for further research into their prognostic significance and potential as therapeutic targets. A critical consideration is the need to improve multimodal imaging recognition, facilitating their identification in future clinical studies.}, }
@article {pmid41248269, year = {2025}, author = {Starr, MR and Bakri, SJ}, title = {Response to Letter to the Editor regarding: "10-year Follow-Up of Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Anti-VEGF Injections".}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004729}, pmid = {41248269}, issn = {1539-2864}, }
@article {pmid41248379, year = {2025}, author = {Shumye, AF and Desalegn, GK and Tegegn, MT and Worku, EM and Lorato, MM and Bogale, ZM and Tegegne, MM and Alimaw, YA and Mengistu, HG and Bekele, MM and Bayabil, AZ and Birhan, GS and Eticha, BL}, title = {Burden and predictors of age-related macular degeneration among old age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia: a multicentre cross-sectional prospective study.}, journal = {BMJ open}, volume = {15}, number = {11}, pages = {e105305}, pmid = {41248379}, issn = {2044-6055}, mesh = {Humans ; Ethiopia/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology/etiology ; Aged ; Middle Aged ; Prospective Studies ; Risk Factors ; Hospitals, Special/statistics &amp; numerical data ; *Diabetes Mellitus/epidemiology ; Prevalence ; Aged, 80 and over ; Adult ; Age Factors ; }, abstract = {OBJECTIVE: This study aims to assess the burden and predictors of age-related macular degeneration (AMD) among older age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia.<br><br>DESIGN: A multicentre cross-sectional study was conducted among older patients with diabetes using a systematic random sampling technique.<br><br>SETTING: The study was conducted at five comprehensive specialised hospitals in Northwest Ethiopia from 8 May to 8 June 2023.<br><br>PARTICIPANTS: The study included 832 diabetic individuals aged 40 years and above.<br><br>MAIN OUTCOME MEASURES: Data were collected using a pretested structured questionnaire and physical examinations.<br><br>RESULT: In this study, a total of 832 participants were involved, with a response rate of 96.85%. The burden of AMD was 15.4% (95% CI 13.0% to 18.0%). Male sex (adjusted OR (AOR) 2.04, 95%&#x2009;CI 1.17 to 3.56), older age (AOR 6.91, 95%&#x2009;CI 3.17 to 15.08), diabetes duration of 10 and more years (AOR 3.00, 95%&#x2009;CI 1.91 to 4.69), higher body mass index (AOR 2.56, 95%&#x2009;CI 1.15 to 5.71), presence of hypertension (AOR 2.45, 95%&#x2009;CI 1.56 to 3.85) and family history of diabetes mellitus (DM) (AOR 2.29, 95%&#x2009;CI 1.40 to 3.76) were positively associated with AMD.<br><br>CONCLUSIONS: This study found that the prevalence of AMD among patients with diabetes was 15.4%. Older age, male sex, longer DM duration, higher body mass index, presence of hypertension and family history of DM were significantly associated with AMD. Targeted screening of at-risk individuals for AMD, public health awareness campaigns focusing on these factors and further research to understand the burden and underlying mechanisms of these associations with AMD are recommended.}, }
@article {pmid41251528, year = {2025}, author = {Singh, SR and Sadeghi, E and Schulman, A and Du, K and Gandhi, P and Narayan, SA and Arora, S and Ibrahim, MN and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J}, title = {Comparison of Three-Dimensional Choroidal Contour in Patients With Neovascular Age-Related Macular Degeneration and Their Fellow Eyes.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {11}, pages = {26}, pmid = {41251528}, issn = {2164-2591}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Cross-Sectional Studies ; *Choroid/diagnostic imaging/pathology ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnostic imaging ; *Imaging, Three-Dimensional/methods ; Aged, 80 and over ; *Choroidal Neovascularization ; Middle Aged ; Macular Degeneration ; }, abstract = {PURPOSE: To compare the three-dimensional choroidal contour map of patients with neovascular age-related macular degeneration (nAMD) and their fellow eyes.<br><br>METHODS: This cross-sectional study included 30 patients with nAMD in one eye and early/intermediate AMD in the fellow eye. Wide-field (12 &#xd7; 12 mm) swept source optical coherence tomography volumetric scans were obtained. Choroidal inner boundaries (CIBs) and choroidal outer boundaries (COBs) were delineated based on our previously reported deep learning model. Best-fit spherical radius (R, mm) was calculated for CIB and COB and compared in both groups using paired t tests. The regional variation of RCIB and RCOB in different sectors (superior, inferior, nasal, temporal, and central) was compared. P values of &#x2264;0.05 were considered statistically significant.<br><br>RESULTS: The mean RCIB was 32.8 &#xb1; 8.6 mm and 32.5 &#xb1; 9.4 mm in nAMD group and their fellow eyes, respectively (P = 0.80). Similarly, the mean RCOB was 31.3 &#xb1; 7.0 mm in the nAMD group with no statistically significant variation in their fellow eyes (early/intermediate AMD, 31.5 &#xb1; 9.0 mm; P = 0.88). Comparison of RCIB (nAMD, 15.0 &#xb1; 9.1 mm; fellow eye, 15.2 &#xb1; 10.4 mm; P = 0.91) and RCOB (nAMD, 13.6 &#xb1; 8.1 mm; fellow eye, 12.2 &#xb1; 9.0 mm; P = 0.48) in the central sector where AMD lesions were located was not significant. Intragroup sectoral comparisons of RCIB and RCOB in both groups were statistically significant (all P values < .01).<br><br>CONCLUSIONS: RCIB and RCOB exhibited significant regional variations across different sectors in both eyes, including nAMD and fellow eyes. However, the comparison of RCIB and RCOB between the two groups was not significantly different.<br><br>TRANSLATIONAL RELEVANCE: The study of choroidal contour may help to understand the pathological changes in age-related macular degeneration.}, }
@article {pmid41254090, year = {2025}, author = {Wolfram, L and Schwämmle, M and Gimpel, C and Merle, DA and Tang, J and Clark, SJ and Böhringer, D and Schlunck, G}, title = {Extracellular matrix stiffness modulates angiogenic properties of the retinal pigment epithelium.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {40349}, pmid = {41254090}, issn = {2045-2322}, mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; *Extracellular Matrix/metabolism ; Humans ; *Neovascularization, Physiologic ; Cell Line ; Vascular Endothelial Growth Factor A/metabolism ; Culture Media, Conditioned/pharmacology ; Thrombospondin 1/metabolism ; Bruch Membrane/metabolism ; Macular Degeneration/metabolism/pathology ; }, abstract = {Physiological and pathological processes, such as aging and basal deposit aggregation in degenerative retinal diseases like age-related macular degeneration (AMD), alter the mechanical properties of Bruch's membrane (BrM). These mechanical changes in the extracellular matrix (ECM) significantly affect retinal pigment epithelial (RPE) cells, influencing their morphology, transcriptome and angiogenic behavior. ARPE-19 cells were cultured on hydrogels of physiological stiffness (30 and 80 kPa) and on conventional tissue culture plastic (TCP) for comparison. Gene expression was analyzed by droplet digital PCR (ddPCR), while protein-level changes were examined using immunofluorescence (IF), Western blotting (WB) and enzyme-linked immunosorbent assays (ELISA). Stiffness-dependent modulation of endothelial cells by RPE-conditioned media was investigated using in vitro angiogenesis assays. RPE cells cultured on softer substrates exhibited enhanced angiogenic properties, including increased expression of CD44 and vascular endothelial growth factor (VEGF). In contrast, stiffer substrates promoted antiangiogenic responses, associated with altered distribution of thrombospondin 1 (THBS1). These findings underscore the importance of ECM mechanics in modulating angiogenic signaling and highlight their potential relevance in retinal pathologies such as AMD. Local disruptions in adhesion or mechanical cues, potentially caused by basal deposits, may contribute to proangiogenic behavior even in the context of globally increased tissue stiffness with age.}, }
@article {pmid41258038, year = {2025}, author = {Barbosa, M and Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Barry, MP and Ambresin, A}, title = {Intravitreal faricimab in patients with aflibercept-refractory neovascular age-related macular degeneration: short and long-term outcomes and assessment of volume dynamics using an artificial intelligence-based tool.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {126}, pmid = {41258038}, issn = {2056-9920}, abstract = {PURPOSE: This study assessed the short- and long-term outcomes of intravitreal (IVT) faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. The main aim was to investigate whether faricimab might enable longer treatment intervals versus aflibercept through improved fluid control, evaluated through use of an artificial intelligence-based quantification tool to evaluate retinal fluid dynamics.<br><br>METHODS: This observational cohort study involved patients with refractory nAMD who received at least three consecutive IVT aflibercept 2.0&#xa0;mg injections before switching to IVT faricimab (with a four-month loading phase followed by a treat-and-extend regimen) due to persistent or recurrent disease despite 4-8-week treatment intervals. Functional and anatomical outcome measures were recorded, and fluid volume dynamics were quantified, at baseline, monthly to Month 4, and at Months 6, 9, and 12.<br><br>RESULTS: Seventy-four eyes from 60 patients were included, with a mean&#x2009;&#xb1;&#x2009;standard deviation duration of prior aflibercept therapy of 24&#x2009;&#xb1;&#x2009;17 months. Fifty-two eyes completed 12-month follow-up. At Month 12, mean best-corrected visual acuity showed no significant change from baseline (+&#x2009;0.01 Early Treatment of Diabetic Retinopathy Study letters, p&#x2009;=&#x2009;0.64). Significant reductions in mean central retinal thickness (-&#x2009;80.8&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.0001) and maximal pigment epithelium detachment (PED) height (-&#x2009;28.2&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.011), were observed at Month 4 and maintained to Month 12. Mean fluid volumes (intraretinal fluid [IRF], subretinal fluid [SRF]), and PED decreased significantly at Month 4 (-&#x2009;26.3 nL, p&#x2009;=&#x2009;0.007; -41.5 nL, p&#x2009;=&#x2009;0.0001; and -&#x2009;175.4 nL, p&#x2009;=&#x2009;0.0001, respectively). At Month 12, reductions in IRF and PED volumes were sustained. The maximal fluid-free interval increased from 4.4 weeks, prior to switching to faricimab, to 6.5 weeks (p&#x2009;=&#x2009;0.001) after switching, while mean last treatment interval improved from 5.0&#x2009;&#xb1;&#x2009;1.4 weeks at baseline to 7.3&#x2009;&#xb1;&#x2009;2.6 weeks at month 12 (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: Faricimab may offer a valuable alternative for patients with refractory nAMD. The use of four loading injections administered monthly, followed by a treat-and-extend regimen can result in maintenance of visual acuity and improve anatomical parameters and retinal fluid activity, allowing for longer treatment intervals.}, }
@article {pmid41258608, year = {2025}, author = {Sun, Y and Zhang, WY and Song, CL and Pan, ZQ and Du, GJ and Song, ZQ and Ren, J and Bo, LY and An, JJ and Wang, M}, title = {Effects of Plastein Reaction Mediated Corn Glutelin Hydrolysate on the Structure and Its Anti-Inflammatory Activity of ARPE-19 Cells in Vitro.}, journal = {Journal of food science}, volume = {90}, number = {11}, pages = {e70650}, doi = {10.1111/1750-3841.70650}, pmid = {41258608}, issn = {1750-3841}, support = {TSBICIP-KJGG-022//Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project/ ; 22HHSWSS00001//"Major Project" of Haihe Laboratory of Synthetic Biology/ ; 130212124135//Heilongjiang Education Department of Basic Business Project of China/ ; 145309403//Heilongjiang Education Department of Basic Business Project of China/ ; }, mesh = {*Anti-Inflammatory Agents/pharmacology/chemistry ; Humans ; *Protein Hydrolysates/chemistry/pharmacology ; Cell Line ; *Glutens/chemistry/pharmacology ; Antioxidants/pharmacology/chemistry ; *Zea mays/chemistry ; Amino Acids/chemistry ; Tumor Necrosis Factor-alpha/metabolism ; Retinal Pigment Epithelium/drug effects/cytology ; Interleukin-6/metabolism/immunology ; Interleukin-1beta/metabolism ; }, abstract = {Corn glutelin hydrolysate (CGH) has demonstrated potential diverse biological activities; however, its application in the food industry is often limited by physicochemical properties (e.g., peptide instability, solubility, or essential amino acid deficiency). The Plastein reaction, a very safe chemical reaction, involving exogenous amino acids (AAs), shows promise in altering the functionality of CGH. In this study, CGH was modified via the Plastein reaction using histidine, cysteine, or tryptophan to generate CGH-His, CGH-Cys, and CGH-Trp. These modified products with superior antioxidant activity and functional characteristics were screened out, and their anti-inflammatory activity was evaluated via an LPS-induced retinal inflammation ARPE-19 cell model. The results indicated that the free amino group contents of all three AA-modified CGHs were significantly lower than those of their corresponding mixtures (P < 0.05). Among the modifiers, CGH-Trp exhibited a significantly enhanced DPPH radical scavenging rate (78.66%), hydroxyl radical scavenging rate (58.35%), ABTS radical scavenging rate (83.29%), and average particle size (381.67 nm) (P < 0.05), compared to unmodified CGH. Structural characterization analysis revealed that the incorporation of tryptophan led to peptide condensation and improved thermal stability. Furthermore, pre-treatment with 10 µg/mL of CGH-Trp significantly reduced the secretion of TNF-α, IL-6, and IL-1β by 33.46%, 32.17%, and 44.49%, respectively, in ARPE-19 cells, compared to the LPS-induced group. This study confirms that the Plastein reaction promotes peptide condensation in CGH in the presence of exogenous amino acids and improves the characteristic, antioxidant, and anti-inflammatory activities, highlighting its potential as a preventive strategy for age-related macular degeneration (AMD).}, }
@article {pmid41262233, year = {2025}, author = {Abbas, A and Singaravelu, J and Fein, JG}, title = {Real-World Clinical Usage and Safety Profile of Intravitreal Pegcetacoplan in Age-Related Macular Degeneration-Associated Geographic Atrophy.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251387554}, pmid = {41262233}, issn = {2474-1272}, abstract = {Purpose: To examine the clinical usage and safety profile in real-world patients with age-related macular degeneration (AMD) receiving intravitreal pegcetacoplan (Syfovre) for the treatment of geographic atrophy, and to explore the effect of intravitreal pegcetacoplan on neovascular AMD (nAMD) disease activity. Methods: Information on patient demographics, AMD classification, treatment history, visual acuity, and ocular adverse events were extracted from the electronic medical records. Results: A total of 1069 patients (1451 eyes) initiated intravitreal pegcetacoplan treatment between February 2023 and October 2023 and were followed up until March 2024. Patients received a mean (±SD) 3.3 ± 2.1 injections, and the mean (±SD) follow-up after pegcetacoplan administration was 7.5 ± 2.3 months. The majority of this cohort displayed stable visual acuity throughout treatment, with logMAR values in 821 patients remaining within 0.20 of the initial value. Ocular hypertension occurred in 36 patients (2.5% of eyes). Seventy-six patients (5.2% of eyes) with non-neovascular AMD at treatment initiation subsequently developed nAMD. Five patients (0.34% of eyes) had intraocular inflammation, including 3 with anterior uveitis, 1 with nonocclusive retinal vasculitis, and 1 with hemorrhagic occlusive retinal vasculitis with subsequent poor outcomes. A rate of retinal vasculitis of 0.03% per injection and a rate of overall intraocular inflammation of 0.1% per injection were observed. In total, 460 patients with nAMD received intravitreal pegcetacoplan. Stability of the anti-vascular endothelial growth factor (anti-VEGF) treatment interval was observed in 289 of 396 patients (73%). Preserved or improved visual acuity while undergoing anti-VEGF therapy was noted in 384 of 396 patients (97%). Conclusions: Real-world data on intravitreal pegcetacoplan treatment identifies clinician practice patterns and demonstrates an acceptable safety profile, with complications leading to long-term vision loss following pegcetacoplan administration being rare in this cohort.}, }
@article {pmid41262993, year = {2025}, author = {Geetha, J and Govindhan, S and Kalifa, MRHM and Gaur, A and Varatharajan, S}, title = {Association of Visual Impairment and Falls in Elderly Individuals-A Cross-Sectional Study.}, journal = {Current health sciences journal}, volume = {51}, number = {2}, pages = {185-190}, pmid = {41262993}, issn = {2067-0656}, abstract = {BACKGROUND: Falls are considered to be the most frequent and significant cause of unintentional harm and mortality among the elderly. Impaired vision is a significant risk factor for falls.<br><br>AIM: To analyse the relationship between visual impairment and falls in the elderly.<br><br>METHODOLOGY: This hospital-based cross-sectional study included 270 participants after obtaining informed consent. Details of demographic profile, lifestyle, gait and balance deficits, ophthalmic and systemic condition were collected. The identification of independent risk variables for falls in the elderly was performed by logistic regression analysis.<br><br>RESULTS: Among 270 participants, 115 participants had falls. The mean age of fallers was 72.97 years. Females had significant falls. 87.8% of participants had visual impairment. Visual risk factors like cataract (80.9%), uncorrected refractive error (59.1%), glaucoma (24.3%), age-related macular degeneration (20.2%), and corneal opacity (13%) were very strongly associated with fall (P<0.001). On multivariate logistic regression analysis visual risk variables like Cataract, uncorrected refractive error and glaucoma had a significant association with falls (P<0.05) with an adjusted odds ratio (aOR) of less than 1. Diabetic retinopathy had strong association of fall (P<0.001) with aOR of 41.8 (95% CI 4.27-409.2).<br><br>CONCLUSION: Falls and visual impairment are public health concerns that require attention. Since many causes of visual impairment in the elderly are reversible, lowering the risk of falls in this population may be a controllable goal.}, }
@article {pmid41263219, year = {2026}, author = {Dang, TM and Invernizzi, A and Nguyen, V and Hashimoto, Y and Romano, F and Cozzi, M and Arnold, J and Wong, J and Mehta, H and Fraser-Bell, S and Barry, R and Barthelmes, D and Gillies, M and Luckie, A}, title = {Twelve-Month Outcomes of Brolucizumab in Routine Clinical Practice: Fight Retinal Blindness! Registry.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {2}, pages = {233-240}, doi = {10.1111/ceo.70033}, pmid = {41263219}, issn = {1442-9071}, support = {//Novartis/ ; }, mesh = {Humans ; Retrospective Studies ; Visual Acuity/physiology ; *Registries ; Male ; Female ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Aged, 80 and over ; *Blindness/prevention &amp; control ; Tomography, Optical Coherence ; Fluorescein Angiography ; Middle Aged ; Australia ; Drug Substitution ; }, abstract = {BACKGROUND: We analysed 12-month real-world outcomes of treatment of eyes with neovascular age-related macular degeneration switched to brolucizumab from a first-generation VEGF inhibitor to determine whether switching chronically active eyes that required frequent treatment improved control of the disease safely with fewer injections.<br><br>METHODS: Retrospective analysis of Australian and Italian data from the prospectively designed observational Fight Retinal Blindness! registry. We studied eyes that switched to brolucizumab and received at least two injections with 12&#x2009;months of follow-up.<br><br>RESULTS: Of the 81 eligible eyes, the proportion of inactive lesions increased from 5% at baseline to 37% 12&#x2009;months after switching to brolucizumab (p&#x2009;<&#x2009;0.001). Mean (95% CI) visual acuity (VA) was stable (0.6 [-1.5, 2.8] letters, p&#x2009;=&#x2009;0.55), while median treatment intervals increased from 44 to 63&#x2009;days (p&#x2009;<&#x2009;0.001). Nearly a third (30%) of eyes switched back to another VEGF inhibitor within 12&#x2009;months. Eyes that stayed on brolucizumab had a significantly longer mean treatment interval at 12&#x2009;months than eyes that switched off it (66.1 [Q1, Q3: 56, 91] vs. 49 [28, 63.2] days, p&#x2009;&#x2264;&#x2009;0.001) while VA change and inactivation rates were similar. Intraocular inflammation (IOI) was recorded in 7 (9%) eyes receiving at least one injection of brolucizumab.<br><br>CONCLUSIONS: Eyes that switched from a first generation VEGF inhibitor to brolucizumab in routine clinical practice achieved a clinically significant extension of their treatment interval, with more than a third becoming inactive but with a relatively high rate of IOI.}, }
@article {pmid41264299, year = {2026}, author = {Yee, H and Wong, CMJ and Gupta, P and Thakur, S and Fenwick, E and Lamoureux, EL and Man, REK}, title = {Prevalence, Risk Determinants, and Burden of Undiagnosed Age-Related Eye Diseases Among Older Asian Adults.}, journal = {JAMA ophthalmology}, volume = {144}, number = {1}, pages = {23-32}, pmid = {41264299}, issn = {2168-6173}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Asian People/ethnology ; *Cataract/epidemiology/diagnosis/ethnology ; *Cost of Illness ; Cross-Sectional Studies ; *Diabetic Retinopathy/epidemiology/diagnosis/ethnology ; *Glaucoma/epidemiology/diagnosis/ethnology ; *Macular Degeneration/diagnosis/epidemiology/ethnology ; Prevalence ; Risk Factors ; Singapore/epidemiology ; *Undiagnosed Diseases/epidemiology ; }, abstract = {IMPORTANCE: While population-based surveys have identified a high prevalence of undiagnosed eye diseases among Asian adults, these studies were conducted more than a decade ago, and there is a paucity of contemporary data.<br><br>OBJECTIVES: To determine the contemporary prevalence of undiagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and glaucoma and their shared risk determinants and to evaluate these conditions' patient-centered and economic burden in a large multiethnic cohort of older Asian adults.<br><br>This cross-sectional cohort study was conducted among individuals from the Population Health and Eye Disease Profile in Elderly Singaporeans study (PIONEER-1, conducted from December 2017 to November 2022), a population-based cohort of community-dwelling individuals of Chinese, Malay, and Indian ethnicity aged 60 years or older living in Singapore. Data analysis was performed from April 2024 to December 2024.<br><br>EXPOSURES: The 4 eye diseases were diagnosed clinically by a study ophthalmologist; participants were considered undiagnosed if no prior physician diagnosis or related interventions were reported.<br><br>MAIN OUTCOMES AND MEASURES: One primary outcome, visual impairment (VI), was assessed clinically using the logMAR chart at 4 m by certified optometrists, while key patient-centered and economic outcomes were assessed using validated questionnaires.<br><br>RESULTS: This study was conducted among 1878 individuals from the PIONEER-1 study, among whom mean (SD) age was 72.7 (8.3) years and 1013 participants (53.9%) were female. A total of 742 participants (weighted prevalence: 35.8%) had at least 1 type of undiagnosed eye disease, with 650 participants (87.6%), 87 participants (11.7%), and 5 participants (0.7%) having 1, 2, and 3 conditions, respectively. Among individuals with AMD, DR, cataracts, or glaucoma, the weighted prevalences of undiagnosed disease were 89.8%, 89.8%, 40.8%, and 48.1%, respectively. Younger age (odds ratio [OR], 1.08 per year decrease; 95% CI, 1.06-1.10; P&#x2009;<&#x2009;.001), wearing multifocal glasses (OR, 1.75; 95% CI, 1.19-2.59; P&#x2009;=&#x2009;.005), and Malay (OR, 1.71; 95% CI, 1.21-2.43; P&#x2009;=&#x2009;.003) and Indian (OR, 1.43; 95% CI, 1.00-2.04; P&#x2009;=&#x2009;.05) ethnicities compared with Chinese individuals were associated with greater odds of having undiagnosed eye disease. Individuals with undiagnosed eye diseases reported -1.97% to -4.57% lower scores in health- and vision-related quality of life, as well as a greater likelihood of having VI (OR, 2.46; 95% CI, 1.68-3.61; P&#x2009;<&#x2009;.001). Additionally, undiagnosed individuals incurred 1.73-fold higher health care expenditures compared with those who were diagnosed (diagnosed: reference; undiagnosed: OR, 1.73; 95% CI, 1.06-2.84; P&#x2009;=&#x2009;.03).<br><br>CONCLUSIONS AND RELEVANCE: In this cross-sectional cohort study, the rates of undiagnosed age-related eye diseases were relatively high, and these conditions were associated with poorer patient-centered outcomes and greater health care expenditure. These results support the use of community eye screening services and health awareness campaigns targeted toward individuals at the lower end of the older than 60 years spectrum and those of Malay and Indian ethnicities to mitigate the detrimental effects of undiagnosed eye diseases in these individuals.}, }
@article {pmid41265309, year = {2026}, author = {Parra-Sánchez, &#xc1; and Román-Vallina, A and Fernández, E and Martínez-Navarrete, G}, title = {Computational modeling of anti-VEGFA drug interactions with VEGF-A: Insights into therapeutic strategies for neovascular AMD.}, journal = {Computational biology and chemistry}, volume = {120}, number = {Pt 1}, pages = {108788}, doi = {10.1016/j.compbiolchem.2025.108788}, pmid = {41265309}, issn = {1476-928X}, mesh = {*Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Humans ; *Macular Degeneration/drug therapy/metabolism ; Molecular Docking Simulation ; Ranibizumab/chemistry/pharmacology ; *Angiogenesis Inhibitors/chemistry/pharmacology ; Bevacizumab/chemistry/pharmacology ; Recombinant Fusion Proteins ; Receptors, Vascular Endothelial Growth Factor ; Antibodies, Monoclonal, Humanized ; }, abstract = {Vascular endothelial growth factor A (VEGF-A) is the main driver of pathological angiogenesis and represents the primary therapeutic target in neovascular age-related macular degeneration (nAMD). Several anti-VEGF agents are currently available, but systematic comparisons of their molecular interactions with VEGF-A remain limited. In this study, we performed the first integrated in silico evaluation of six clinically relevant anti-VEGF drugs: abicipar, aflibercept, bevacizumab, brolucizumab, faricimab, and ranibizumab. Structural modeling, residue conservation analysis, molecular docking (HADDOCK), and binding affinity prediction (PRODIGY) were employed to assess drug-VEGF-A interactions in terms of stability, energetic contributions, and key conserved residues. Our results showed that bevacizumab exhibited the most stable interaction profile, dominated by van der Waals forces and supported by highly conserved residues. Aflibercept displayed strong electrostatic stabilization, while ranibizumab and brolucizumab achieved robust interactions through mixed forces. Faricimab presented weaker binding stability but its dual-target mechanism, involving VEGF-A and angiopoietin-2, may extend its therapeutic efficacy beyond VEGF-A inhibition. Abicipar demonstrated favorable stability despite structural differences from conventional antibodies. Notably, hydrophobic interactions were consistently identified as a central determinant of complex stability across all drugs, whereas an excess of charged residues correlated with reduced affinity. This systematic analysis highlights the coexistence of evolutionary conservation and rational molecular engineering as complementary strategies shaping anti-VEGF drug performance. Overall, our findings demonstrate that computational modeling offers a cost-effective and predictive tool to guide the optimization of current therapies and the rational design of next-generation anti-VEGF agents for nAMD and other retinal vascular disorders.}, }
@article {pmid41267136, year = {2025}, author = {Choy, S and Chun, JM and Seok, JW and Park, SR and Kim, JD}, title = {Effectiveness of photobiomodulation therapy for ophthalmic diseases: protocol for a systematic review and meta-analysis of disease-specific and shared physiological outcomes.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {231}, pmid = {41267136}, issn = {2046-4053}, support = {KSN2511012//Korea Institute of Oriental Medicine/ ; }, mesh = {Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; *Low-Level Light Therapy/methods ; *Eye Diseases/therapy/radiotherapy ; Research Design ; Treatment Outcome ; }, abstract = {BACKGROUND: Photobiomodulation therapy (PBMT)-a noninvasive therapeutic strategy-employs low-level red or near-infrared light to regulate cellular bioenergetics, reduce oxidative stress, and modulate inflammation. It has demonstrated therapeutic potential for several ophthalmic diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa, and dry eye disease. However, the clinical evidence remains fragmented due to heterogeneity in study designs, treatment parameters, and outcome measures. Moreover, existing reviews are largely confined to single diseases. Robust, prespecified assessments that standardize disease-specific endpoints and only explore shared physiological measures across conditions remain scarce.<br><br>METHODS: The protocol is registered in the PROSPERO database. This review will follow the PRISMA guidelines; randomized controlled trials and comparative nonrandomized clinical studies involving PBMT interventions for any clinically diagnosed ophthalmic disease will be included. Eligible comparators will include sham treatment, no treatment, or standard care, and outcomes will be primarily analyzed at the disease-specific level, with endpoints including best-corrected visual acuity, drusen volume, intraocular pressure, and diabetic retinopathy severity. Selected shared physiological or functional outcomes (e.g., electroretinogram amplitude, tear cytokine concentrations, and optical coherence tomography measurements of retinal structure) will be examined in a secondary exploratory framework to provide hypothesis-generating insights across conditions. Databases-including PubMed, Embase, Cochrane Library, Web of Science, and Scopus-will be searched for articles published up to July 31, 2025. Two reviewers will independently select studies, extract data, and assess risk of bias. Random-effects models will be used for the meta-analysis, and heterogeneity will be explored through prespecified subgroup (disease type, wavelength, irradiance, fluence, session duration, treatment frequency) and exploratory meta-regression analyses.<br><br>DISCUSSION: This review will provide pooled effect estimates for PBMT based on clinical outcomes across ophthalmic diseases. These will be stratified by intervention parameters and outcome types (disease-specific and shared physiological/biomarker-based). Rather than aiming to determine optimal treatment strategies, the findings are intended to provide exploratory insights and generate hypotheses for future clinical research. The study will synthesize clinical evidence regarding the effect of PBMT on ophthalmic diseases, highlighting methodological considerations to guide the design of future trials and serve as an exploratory framework for understanding potential multidisease and multioutcome perspectives.<br><br>PROSPERO CRD420251033569.}, }
@article {pmid41268217, year = {2025}, author = {Amer, M and Sonne, S and Piri, N}, title = {Hyperreflective Choroidal Foci: A Comprehensive Review.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {20}, number = {}, pages = {}, pmid = {41268217}, issn = {2008-2010}, abstract = {Hyperreflective choroidal foci (HCF) are a finding on optical coherence tomography that may serve as a biomarker in various retinal and choroidal pathologies. These discrete hyperreflective spots, identified in various layers of the choroid, have been linked to inflammatory, vascular, and degenerative conditions. This review examines the clinical significance, histopathological correlation, and implications of HCF in various diseases, including diabetic retinopathy, age-related macular degeneration, Stargardt disease, choroideremia, Vogt-Koyanagi-Harada disease (VKH), idiopathic posterior uveitis, retinitis pigmentosa, and central serous chorioretinopathy (CSR), as well as non-pathological states. Although further studies are required to validate the findings in each pathology described herein, HCF may be used as a background prognostic marker of disease progression and therapeutic response, albeit with caution.}, }
@article {pmid41268988, year = {2025}, author = {Kozak, I and Sinclair, SH and Zhang, E and Murati, F and Lee, E and Stepura, A and Dey, A and Ribaric, N}, title = {Application of Deep Learning for Advanced Detection and Quantification of Drusen in Nonexudative AMD From Retinal Multispectral Imaging.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {11}, pages = {35}, pmid = {41268988}, issn = {2164-2591}, mesh = {*Deep Learning ; Humans ; *Retinal Drusen/diagnosis/diagnostic imaging ; *Macular Degeneration/diagnosis ; *Retina/diagnostic imaging/pathology ; Neural Networks, Computer ; Aged ; *Geographic Atrophy/diagnosis ; }, abstract = {PURPOSE: To propose a novel deep learning-based methodology for drusen detection and quantification in early age-related macular degeneration (AMD) using retinal multispectral images. The retinal multispectral images highlight features in several nonoverlapping spectral bands that the deep learning models leverage for automatic drusen detection and quantification in dry AMD.<br><br>METHODS: The proposed novel methodology comprises quality assessment of retinal images, region of interest extraction, drusen segmentation, and drusen quantification stages. Different deep learning models (such as UNet++ convolutional neural network with EfficientNetV2 encoder) have been implemented for these stages. A total of 170 drusen and 150 nondrusen retinal images (single eye) were split into four training and validation data sets to analyze the performance of a deep learning model for drusen segmentation.<br><br>RESULTS: The proposed methodology achieved an average score, recall, and precision of 0.691, 0.668, and 0.776, respectively, across all four validation sets. This work also analyzed the performance of the proposed deep learning model for discriminating drusen and drusen-like lesions, achieving a pixel-wise segmentation accuracy of 99.998%. The number and the diameter of the detected drusen were also computed. A Dice score distribution for drusen segmentation with different numbers and sizes of drusen per eye is also shown.<br><br>CONCLUSIONS: This work demonstrates that deep learning models applied to retinal multispectral images can provide accurate and clinically significant drusen segmentation and quantification, thereby facilitating early detection, longitudinal monitoring, and reduction of the risk of vision loss from AMD.<br><br>TRANSLATIONAL RELEVANCE: Deep learning-assisted detection of drusen from multispectral retinal images will refine and improve clinical diagnosis of early nonexudative age-related macular degeneration.}, }
@article {pmid41269403, year = {2025}, author = {Jin, J and Hand, R and Meltzer, M and Abate, C and Geva, M and Hayden, MR and Ross, CA}, title = {Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {121}, pmid = {41269403}, issn = {1559-1182}, mesh = {*Receptors, sigma/antagonists &amp; inhibitors/agonists/metabolism ; *Huntington Disease/drug therapy/pathology/metabolism ; Animals ; *Neuroprotective Agents/pharmacology/therapeutic use ; Sigma-1 Receptor ; *Piperidines/pharmacology/therapeutic use ; Mice ; Humans ; Neurons/drug effects/metabolism/pathology ; Huntingtin Protein/metabolism ; }, abstract = {Pridopidine is a selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Activation of the S1R by pridopidine is neuroprotective in multiple preclinical models of neurodegenerative disease. The sigma-2 receptor (S2R) is evolutionarily and structurally unique from the S1R. Nevertheless, the S1R and S2R share an overlapping yet distinct ligand binding profile. Inhibition of the S2R is neuroprotective and S2R antagonists are in clinical development for Alzheimer's Disease (AD), ⍺-synucleinopathies, and dry age-related macular degeneration. In this study, we hypothesized that simultaneous activation of the S1R by pridopidine and inhibition of the S2R by the selective S2R antagonist FA10 might provide enhanced protection against mutant huntingtin (mHTT) expression in an in vitro model of neurodegeneration. Consistent with previous studies, pridopidine reduced neuronal cell death in a mouse primary neuron mHTT model. Similarly, we found that inhibition of the S2R by FA10 was also sufficient to protect against mHTT induced neurodegeneration in this model. The combination treatment of pridopidine and FA10 achieved greater efficacy than either compound alone, even at lower concentrations. The combination of these compounds may allow for lower efficacious doses leading to improved safety profiles and reduced off-target effects. This novel combinatorial approach, in which the S1R is activated while simultaneously inhibiting the S2R may prove to be a highly effective therapeutic strategy for HD and other neurodegenerative diseases.}, }
@article {pmid41269906, year = {2026}, author = {Korobelnik, JF and Chaudhary, V and Mitchell, P and Kang, SW and Allmeier, H and Lee, J and Zhang, X and Machewitz, T and Bailey, C}, title = {Aflibercept 2 mg for Neovascular Age-Related Macular Degeneration: XTEND at 3 Years.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {249}, number = {1}, pages = {17-29}, pmid = {41269906}, issn = {1423-0267}, mesh = {Humans ; Female ; Intravitreal Injections ; Aged ; Prospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Time Factors ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Aged, 80 and over ; Fundus Oculi ; *Macula Lutea/pathology ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {UNLABELLED: <p>Introduction: Long-term, global data evaluating intravitreal aflibercept (IVT-AFL) 2 mg for treatment of neovascular age-related macular degeneration (nAMD) in real-world practice are needed. This study investigated the long-term, real-world effectiveness and safety of IVT-AFL 2 mg in patients with nAMD.<br><br>METHODS: XTEND was a multicenter, observational, prospective study. Enrollment was conducted between May 2019 and May 2020; the patient follow-up period was 36 months. Treatment-na&#xef;ve patients were treated with IVT-AFL 2 mg (fixed dosing or treat-and-extend [T&amp;E]) according to the local label; for the T&amp;E regimen, treatment intervals could be extended according to the national label (either European Medicines Agency [EMA]-aligned or non-EMA-aligned).<br><br>RESULTS: Overall, 1,483 patients across 17 countries were treated with IVT-AFL 2 mg; mean &#xb1; standard deviation (SD) age was 78.8 &#xb1; 8.5 years; 60.4% were female. Overall, 62.6% of patients completed the 36-month follow-up visit. The mean (95% confidence interval [CI]) changes in best-corrected visual acuity from baseline were +4.6 (3.7, 5.4), +2.3 (1.3, 3.3), and +0.9 (-0.2, 1.9) at months 12, 24, and 36, respectively. The mean (95% CI) changes in central subfield thickness from baseline were -106 (-114, -99) &#x3bc;m, -109 (-117, -102) &#x3bc;m, and -110 (-118, -103) &#x3bc;m at months 12, 24, and 36, respectively. The mean &#xb1; SD numbers of injections from baseline to months 12, 24, and 36 were 7.7 &#xb1; 2.7, 11.3 &#xb1; 5.3, and 13.7 &#xb1; 7.5, respectively. No new safety concerns were identified.<br><br>CONCLUSION: This study demonstrates that improvements with IVT-AFL 2 mg were maintained through month 36, suggesting that long-term durability of vision is achievable in patients with treatment-na&#xef;ve nAMD in real-world practice. </p>.}, }
@article {pmid41270236, year = {2025}, author = {Shi, N and Li, J and Shang, M and Zhang, W and Xu, K and Li, Y and Liang, L}, title = {Detection and Management of Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Noninvasive Retinal Images and Artificial Intelligence: Systematic Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e81328}, pmid = {41270236}, issn = {1438-8871}, mesh = {Humans ; *Artificial Intelligence ; Deep Learning ; *Geographic Atrophy/diagnostic imaging/etiology/diagnosis/therapy ; *Macular Degeneration/complications/diagnostic imaging ; *Retina/diagnostic imaging ; Tomography, Optical Coherence ; }, abstract = {BACKGROUND: Geographic atrophy (GA), the endpoint of dry age-related macular degeneration (AMD), is irreversible. The recent approval by the Food and Drug Administration of a complement component 3 inhibitor marks a significant breakthrough, highlighting the critical importance of early detection and management of GA. Consequently, there is an urgent and unmet need for efficient, accurate, and accessible methods to identify and monitor GA. Artificial intelligence (AI), particularly deep learning (DL), applied to noninvasive retinal imaging, offers a promising solution for automating and enhancing GA management.<br><br>OBJECTIVE: This systematic review aimed to assess the performance of AI using noninvasive imaging modalities and compare it with clinical expert assessment as the ground truth.<br><br>METHODS: Two consecutive searches were conducted on PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CINAHL. The last search was performed on October 5, 2025. Studies using AI for GA secondary to dry AMD via noninvasive retinal imaging were included. Two authors worked in pairs to extract the study characteristics independently. A third author adjudicated disagreements. Quality Assessment of Diagnostic Accuracy Studies-AI and Prediction Model Risk of Bias Assessment Tool (PROBAST) were applied to evaluate the risk of bias and application.<br><br>RESULTS: Of the 803 records initially identified, 176 were found through an updated search. Subsequently, 200 papers were assessed in full text, of which 41 were included in the final analysis, 10 for GA detection, 20 for GA assessment and progression, and 11 for GA lesion prediction. The reviewed studies collectively involved at least 24,592 participants (detection: n=7132, assessment and progression: n=14,064, and prediction: n=6706), with a wide age range of 50 to 94 years. The studies spanned a diverse array of countries, including the United States, the United Kingdom, China, Austria, Australia, France, Israel, Italy, Switzerland, and Germany, as well as a multicenter study encompassing 7 European nations. The studies used a variety of imaging modalities to assess GA, including color fundus photography, fundus autofluorescence, near-infrared reflectance, spectral domain-optical coherence tomography (OCT), swept-source (SS)-OCT, and 3D-OCT. DL algorithms (eg, U-Net, ResNet50, EfficientNetB4, Xception, Inception v3, and PSC-UNet) consistently showed remarkable performance in GA detection and management tasks, with several studies achieving performance comparable to clinical experts.<br><br>CONCLUSIONS: AI, particularly DL-based algorithms, holds considerable promise for the detection and management of GA secondary to dry AMD with performance comparable to ophthalmologists. This review innovatively consolidates evidence across GA management-from initial detection to progression prediction-using diverse noninvasive imaging. It has strong potential to augment clinical decision-making. However, to realize this potential in real-world settings, future research is needed to robustly enhance reporting specifications, ensure data diversity across populations and devices, and implement rigorous external validation in prospective, multicenter studies.}, }
@article {pmid41270813, year = {2026}, author = {Jiang, L and Xu, Z and Ma, J and Cai, W and Lin, R and Hu, C and Luo, Y and Liang, F and Wu, Y and Yu, J}, title = {siRASA1 in vascular endothelial cells alleviates subretinal fibrosis through inhibiting macrophage-myofibroblast transdifferentiation via SHH signaling pathway.}, journal = {Cellular signalling}, volume = {138}, number = {}, pages = {112261}, doi = {10.1016/j.cellsig.2025.112261}, pmid = {41270813}, issn = {1873-3913}, mesh = {*Hedgehog Proteins/metabolism ; Humans ; *Cell Transdifferentiation/drug effects ; Signal Transduction/drug effects ; Fibrosis ; *Macrophages/metabolism/drug effects ; Animals ; *Myofibroblasts/metabolism/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Mice ; Vascular Endothelial Growth Factor A ; *Retina/pathology/metabolism ; }, abstract = {Subretinal fibrosis (SRF) is a vision-threatening complication of neovascular age-related macular degeneration (nAMD) driven by angiogenesis, inflammation, and collagen deposition，which is refractory to current anti-VEGF treatments. This study investigates the role of RASA1 in promoting SRF through Sonic Hedgehog (SHH) signaling. We found that VEGF stimulation upregulates RASA1 in human umbilical vein endothelial cells (HUVECs), potentiating the secretion of SHH. Secreted SHH then activates the SHH-SMO/PTCH1-GLI1 axis in macrophages, driving their transdifferentiation into myofibroblasts and promoting fibrogenesis. Furthermore, a positive feedback loop was identified: macrophage-derived EFNB2 activated EphB4-RASA1 in HUVECs, exacerbating fibrosis. To therapeutically disrupt this circuit, we engineered a multifunctional nanoparticle system, MGPDA@Eylea/siRASA1, for the co-delivery of siRASA1 and the anti-VEGF drug Eylea. This nanotherapeutic demonstrated excellent biocompatibility and effectively attenuated the fibrotic cascade by suppressing RASA1 expression, inhibiting SHH signaling, and mitigating macrophage-to-myofibroblast transition (MMT), thereby delaying SRF progression. Our work unveils a previously unrecognized intercellular circuit driving fibrosis and presents a promising nanomedicine-based strategy for managing fibrotic complications in nAMD.}, }
@article {pmid41271910, year = {2025}, author = {Tabuchi, H and Nagasato, D and Tanabe, M and Murata, K and Ishitobi, N and Kato, D and Kazunori, A}, title = {Evaluation of deep learning-based retinal pigment epithelium segmentation for a widely used optical coherence tomography device.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {41310}, pmid = {41271910}, issn = {2045-2322}, mesh = {Humans ; *Tomography, Optical Coherence/methods/instrumentation ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; *Deep Learning ; Algorithms ; Aged ; Macular Degeneration/diagnostic imaging ; Male ; Female ; Diabetic Retinopathy/diagnostic imaging ; Middle Aged ; *Image Processing, Computer-Assisted/methods ; }, abstract = {To develop our proposed technology method to improve retinal pigment epithelium (RPE) detection in optical coherence tomography (OCT) images and compare its efficacy with Topcon's automated segmentation algorithm across multiple retinal diseases and healthy eyes. OCT images from 88 patients with age-related macular degeneration (AMD) were used for our proposed technology model training and validation. For testing with separate images were obtained from patients with AMD (100), diabetic retinopathy (DR; 50), epiretinal membrane (ERM; 50), branch retinal vein occlusion (BRVO; 50), and healthy eyes (50). The proposed technology was used to identify RPE in OCT images using the Pyramid Scene Parsing Network on top of ResNet-50. The accuracy of the proposed technology method in RPE detection was measured using the mean absolute error (MAE) and compared with Topcon's automated segmentation algorithm for each retinal condition. As compared with Topcon's automated segmentation algorithm, the proposed technology showed significantly better MAEs across all conditions: AMD (2.18 vs. 4.79), DR (1.69 vs. 3.17), ERM (1.50 vs. 2.67), BRVO (1.86 vs. 2.98), and healthy eyes (1.59 vs. 2.28). Notably, the proposed technology's superiority was most evident in the AMD group. The proposed technology method outperformed Topcon's automated segmentation algorithm in accurately visualizing RPE in OCT images across all tested conditions, especially in AMD. Our results indicate the proposed technology's potential to elevate the RPE segmentation which can lead to enhancing ophthalmology care by providing more accurate OCT imaging analyses.}, }
@article {pmid41272236, year = {2025}, author = {Pidishetty, D and Damera, SK and Murugavel, M and Susaimanickam, PJ and Chittajallu, SNSH and Kushawah, G and Sarkar, P and Bharadwaj, SR and Mishra, R and Mariappan, I}, title = {Loss of retinal stem cell reserve and lipofuscin accumulation accelerates cone-rod degeneration and replicates Stargardt disease in abca4b null zebrafish.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44988}, pmid = {41272236}, issn = {2045-2322}, mesh = {Animals ; Zebrafish/genetics ; *Lipofuscin/metabolism ; *Stargardt Disease/genetics/pathology/metabolism ; *ATP-Binding Cassette Transporters/genetics ; Disease Models, Animal ; *Stem Cells/metabolism/pathology ; *Zebrafish Proteins/genetics/metabolism ; *Retina/pathology/metabolism ; Retinal Cone Photoreceptor Cells/metabolism/pathology ; Retinal Rod Photoreceptor Cells/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Gene Knockout Techniques ; *Cone-Rod Dystrophies/pathology/metabolism/genetics ; CRISPR-Cas Systems ; Mutation ; *Macular Degeneration/genetics/pathology/metabolism ; }, abstract = {Mutations in ABCA4 gene causes Stargardt macular degeneration, which manifests with toxic lipofuscin deposits in the outer retina, gradual atrophy of RPE cells, followed by photoreceptor cell loss. The cone-enriched retina, with macula-like 'area-temporalis' of zebrafish are better models than rodents for studying human macular dystrophies. Here, we generated abca4b knockout zebrafish model using CRISPR/Cas9 editing and evaluated the early and late-stage retinal changes. In adult abca4b[-/-] mutants, the RPE cells exhibited hyperpigmentation, altered retinomotor behaviour and lipofuscin accumulation, but they remained viable. However, the photoreceptors underwent progressive degeneration, with a sequential loss of blue and UV cones, followed by red and green cones and finally the rod cells. This triggered the chronic activation and early depletion of retinal stem cells at the ciliary marginal zone of mutants and resulted in accelerated outer-retinal degeneration and severe visual defects, despite them retaining the Müller glia-dependant retinal repair potential.}, }
@article {pmid41273407, year = {2026}, author = {Ferreira, AM and Vilares-Morgado, R and Martins, L and Marques-Couto, P and Rocha-Sousa, A and Carneiro, &#xc2; and Falcão, M}, title = {Non-exudative macular neovascularization: a 3-year follow-up study assessing the progression for exudative or atrophic stages.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {689-699}, pmid = {41273407}, issn = {1435-702X}, mesh = {Humans ; Male ; Female ; Follow-Up Studies ; Disease Progression ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Aged ; Fundus Oculi ; *Visual Acuity ; *Macula Lutea/pathology ; *Geographic Atrophy/diagnosis ; Aged, 80 and over ; Time Factors ; *Wet Macular Degeneration/diagnosis ; Retrospective Studies ; *Retinal Pigment Epithelium/pathology ; Middle Aged ; }, abstract = {INTRODUCTION: Non-exudative macular neovascularization (NE-MNV) has been linked to smaller areas of geographic atrophy (GA), suggesting it may slow the progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA). This study aims to determine whether NE-MNV affects the prevalence and progression to later stages of age-related macular degeneration (AMD) over 3 years in the fellow eyes of patients with unilateral exudative AMD.<br><br>METHODS: Observational study including 61 patients with unilateral exudative AMD assessing 3-year cRORA progression and exudative conversion in the fellow eye. Patients were grouped based on the presence (NE-MNV) or absence of NE-MNV (no NE-MNV). The prevalence and progression of tomographic cRORA, GA on fundus autofluorescence (FAF) and exudative conversion rates were compared.<br><br>RESULTS: Sixty-one patients were included in our cohort. The prevalence of NE-MNV was 24.6%. We identified a 36.3% bilateral exudative conversion rate (n&#x2009;=&#x2009;4) in the NE-MNV group and a 15.2% conversion rate in the eyes without NE-MNV (n&#x2009;=&#x2009;7) at 3 years (p&#x2009;=&#x2009;0.036). There were no significant differences in cRORA or FAF GA prevalence between groups (2/15 (13.3%) with NE-MNV vs. 11/35 (31.4%) without NE-MNV, p&#x2009;=&#x2009;0.410). Eyes with NE-MNV presented a significantly smaller cRORA greatest linear diameter (GLD) than eyes without NE-MNV (1342.3&#x2009;&#xb1;&#x2009;1260 vs. 2897&#x2009;&#xb1;&#x2009;1925.3, p&#x2009;=&#x2009;0.023), and a smaller FAF GA area (4.5&#x2009;&#xb1;&#x2009;3.7 vs. 11.9&#x2009;&#xb1;&#x2009;10.6 mm2, p&#x2009;=&#x2009;0.042). The presence of reticular pseudodrusen and hypertransmission defects were significantly associated with the GA phenotype (p&#x2009;=&#x2009;0.002 and p&#x2009;<&#x2009;0.001, respectively) while the identification of concurrent large drusen was significantly associated with the presence of MNV, both exudative and non-exudative (p&#x2009;=&#x2009;0.023). The increase in OCTA NE-MNV area and the presence of anastomosis and loops pattern were associated with exudative conversion (p&#x2009;=&#x2009;0.046 and p&#x2009;=&#x2009;0.032, respectively).<br><br>CONCLUSION: The presence of NE-MNV was associated with smaller cRORA GLD and FAF GA area, corroborating that NE-MNV may prevent the progression of cRORA. One third of the eyes with NE-MNV converted to exudative AMD over 3-years. Reticular pseudodrusen, hypertransmission defects and concurrent large drusen were significant OCT biomarkers for late stages AMD. Extended monitoring is required to confirm these results at long term.}, }
@article {pmid41275318, year = {2025}, author = {Lim, J and Cho, H and Ramkumar, H and Adrean, SD}, title = {Neovascular age-related macular degeneration complicated by large submacular hemorrhage managed with faricimab monotherapy.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {142}, pmid = {41275318}, issn = {2056-9920}, abstract = {PURPOSE: To retrospectively evaluate the visual and anatomic outcomes of intravitreal faricimab monotherapy in treatment naïve neovascular age-related macular degeneration (nAMD) patients presenting with large submacular hemorrhage (SMH).<br><br>METHODS: Patients with neovascular age-related macular degeneration (nAMD) presenting with at least 50% subretinal hemorrhage (SRH) involving the fovea between March 2023 and June 2025 were identified. Patients with greater than 750 microns of total thickness of subfoveal hemorrhage were excluded. Patients were treated with faricimab as first line therapy utilizing a treat-extend-stop protocol for one year. Spectral domain optical coherence tomography (SD-OCT) and fluorescein angiogram (FA)/ indocyanine green angiography (ICG) were used to determine total CNV lesion size, SRH area size, and macular thickness. Visual acuity and SD-OCT were also obtained at each visit.<br><br>RESULTS: Six patients were identified that met the inclusion criteria. There were two males and four females. The average age of was 83.0 years. Prior to treatment, the average total CNV lesion size was 19.7mm[2] and the average hemorrhage area was 14.5 mm[2] for an average SRH percentage of 73.8%. The average central macular thickness (CMT) prior to treatment was 478.3 &#x3bc;m and the average CMT 6 months after beginning treatment was 306.8 &#x3bc;m (p = 0.0031). The average CMT 1 year after treatment was 259.0 &#x3bc;m (p = 0.0017). Average ETDRS letters before treatment was 48.8 letters {Snellen equivalent 20/138} with a range of 23&#x2013;70 letters. Average ETDRS letters after 6 months of treatment was 60.3 letters {Snellen equivalent 20/63} with a range of 42 to 76 letters (p = 0.017). Average ETDRS letters after 1 year of treatment was 64.7 letters {Snellen equivalent 20/50} with a range from 26 to 80 letters (p < 0.014). The average number of injections was 9.3 at 1 year.<br><br>CONCLUSION: In patients with nAMD complicated by at least 50% SRH, there was improved vision and decreased CMT. On average, vision improved by 16.4 ETDRS letters and improved on average from 20/138 to 20/50 on Snellen after 1 year of faricimab monotherapy. These patients may be successfully managed with faricimab monotherapy. While visual acuity overall improved, some patients had more improvement than others likely due to the location of the CNV.}, }
@article {pmid41276957, year = {2026}, author = {Yang, CC and Weng, CC and Chou, YB and Huang, YM and Lin, TC and Chen, SJ and Hwang, DK}, title = {Early anatomical outcomes of faricimab vs aflibercept 2 mg in treatment-naïve neovascular age-related macular degeneration and polypoidal choroidal vasculopathy: A head-to-head comparative study in Taiwan.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {89}, number = {1}, pages = {54-60}, pmid = {41276957}, issn = {1728-7731}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Visual Acuity ; Aged, 80 and over ; Middle Aged ; *Choroidal Neovascularization/drug therapy ; Polypoidal Choroidal Vasculopathy ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: While clinical trials have established the non-inferiority of faricimab compared to aflibercept regarding 1-year visual acuity, real-world evidence directly comparing their early effects on anatomical changes remains limited. This study aimed to compare the early effects of these treatments in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This retrospective study included treatment-na&#xef;ve nAMD patients who received three monthly intravitreal injections of 6.0&#x2009;mg/0.05&#x2009;ml faricimab or 2.0&#x2009;mg/0.05&#x2009;ml aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), and subretinal hyperreflective material (SHRM) were assessed monthly for 4 months.<br><br>RESULTS: A total of 76 eyes of 76 patients (38 per group) were enrolled in this study. Baseline characteristics were comparable between the two groups, and there were no significant differences in BCVA, CMT, SFCT, SRF, and IRF at 4 months (p > 0.05). However, the faricimab group had significant improvements in BCVA at months 2, 3, and 4 (p < 0.05), while this was not seen in the aflibercept group. The decrease in mean logarithm of the minimum angle of resolution (logMAR) was from 0.78&#x2009;&#xb1;&#x2009;0.47 to 0.66&#x2009;&#xb1;&#x2009;0.65 in the faricimab group compared to 0.78&#x2009;&#xb1;&#x2009;0.41 to 0.72&#x2009;&#xb1;&#x2009;0.60 in the aflibercept group (p = 0.348) at 4 months. Moreover, significantly fewer faricimab-treated patients had PED (67.6% vs 91.9%, p = 0.016), SHRM (32.4% vs 59.5%, p = 0.022), and HRF (52.9% vs 89.2%, p = 0.001) at 4 months.<br><br>CONCLUSION: Faricimab and aflibercept demonstrated comparable effects on BCVA, CMT, and SFCT. However, faricimab was associated with better early control of PED, SHRM, and HRF. Further prospective trials are needed to validate our findings.}, }
@article {pmid41277047, year = {2026}, author = {Choe, S and Ye, J and Zhang, T and Gao, J}, title = {Advanced Drug Delivery Systems for Age-Related Macular Degeneration Treatment: Latest Trends and Future Prospects.}, journal = {Advanced healthcare materials}, volume = {15}, number = {9}, pages = {e03757}, doi = {10.1002/adhm.202503757}, pmid = {41277047}, issn = {2192-2659}, support = {W2442037//National Natural Science Foundation of China/ ; 2023GSP006851//Chinese Government Scholarship/ ; }, mesh = {Humans ; *Drug Delivery Systems/methods ; *Macular Degeneration/drug therapy ; Animals ; Hydrogels/chemistry ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. While wet AMD is primarily characterized by choroidal neovascularization, dry AMD is characterized by dysfunction of the retinal pigment epithelium. One of the key challenges in AMD treatment is achieving efficient drug delivery to the posterior segment, a task complicated by the anatomical and physiological barriers, such as rapid clearance from the vitreous. Current therapeutic approaches, mainly constituted by frequent intravitreal injections of anti-vascular endothelial growth factor agents for wet AMD, place a heavy burden on patients, leading to complications such as retinal detachment and endophthalmitis. This review highlights recently developed drug delivery systems designed to overcome these challenges and the potential of these systems to transform AMD management. These systems include hydrogels, nanocarriers, and biologically derived vesicles, which enable sustained, localized drug release and improved targeting. Additionally, device-based delivery systems such as microneedles, ultrasound-mediated systems, magnetically guided systems, 3D bioprinting, and implantable sustained-release devices are explored for their potential to reduce injection frequency and improve therapeutic outcomes. Lastly, it outlines future efforts needed to accelerate the clinical adoption of these innovative therapies, with a focus on patient safety, efficacy, and quality of life in AMD treatment.}, }
@article {pmid41278702, year = {2025}, author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE}, title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41278702}, issn = {2692-8205}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and C. elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for non-canonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.}, }
@article {pmid41278837, year = {2025}, author = {Oshima, Y and Hussey, KA and Hagen, J and Smit-McBride, Z and Moorthy, M and Matsubara, JA and Flajnik, M and Johnston, RJ and Vogel, BE}, title = {Complement Factor H and its C. elegans homolog regulate IFT52/OSM-6 and CNG channel localization in sensory neurons.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41278837}, issn = {2692-8205}, support = {P30 EY012576/EY/NEI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Current disease models propose AMD pathogenesis is a consequence of cytolytic damage and tissue inflammation that result from defective repression of alternative complement pathway activity by complement factor H (CFH). However, recent studies demonstrate functions for CFH that are outside of its established role in the alternative complement pathway, suggesting that novel CFH-mediated mechanisms may influence AMD initiation and progression. Our previous demonstration that CFH and its nematode homolog, CFH-1, modulate inversin/NPHP-2 accumulation in vertebrate photoreceptor and C. elegans sensory neuron cilia during aging suggests that AMD patients with CFH loss-of-function mutations have cilia defects that may contribute to photoreceptor dysfunction. Here, we investigate the consequences of CFH and CFH-1 loss-of-function mutations on the dynamics and localization of intraflagellar transport (IFT) train and visual cycle components in these cells. In C. elegans sensory neurons, IFTB1 components IFT52/OSM-6 and IFT88/OSM-5 are transported at similar rates in WT animals but IFT52/OSM-6 transport slows significantly in cfh-1 mutant animals while IFT88/OSM-5 is unaffected. Defective localization of IFT52/OSM-6 in photoreceptors of CFH knockout mice and in human photoreceptors from AMD high-risk CFH Y402H homozygotes, suggest an evolutionarily conserved role for CFH in promoting IFT52/OSM-6 transport and localization in sensory neuron cilia. In addition, distribution of CNG channel subunits in C. elegans cfh-1 mutant sensory neurons and CFH Y402H high-risk human photoreceptors are distinct from their WT and Y402 low-risk counterparts. Together, the data indicate previously unappreciated functions for CFH in IFT train organization and cilia protein localization and suggest a novel mechanism for photoreceptor segment thinning, an early AMD biomarker that has been linked to CFH high-risk variants.}, }
@article {pmid41279129, year = {2025}, author = {Zhang, PW and Liu, S and Li, W and Fan, L and Li, S and Wan, ZH and Berlinicke, CA and Merbs, SL and Zack, DJ}, title = {Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41279129}, issn = {2692-8205}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: Large-scale genome-wide association studies (GWAS) have identified the human 10q26 locus as a major genetic risk factor for age-related macular degeneration (AMD). The AMD-associated interval has been refined to a 5,196 bp segment flanking the ARMS2-HTRA1 region, excluding HTRA1 and the ARMS2 3' indel (443del54ins) variant by risk haplotype analysis. Although the missense SNP rs10490924 has been proposed as a functional variant, its role in AMD remains controversial, and the causative variants and underlying mechanisms within this region remain unresolved.<br><br>METHODS: An unbiased bioinformatic screen identified a 5-SNP block within the 5,196 bp interval that potentially alters c-ABL protein binding. Protein-DNA interactions were validated using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Genetic association with AMD (dry and wet subtypes) was assessed in patient cohorts using blood genomic DNA. The regulatory effect of the 5-SNP block was further examined using luciferase reporter assays.<br><br>FINDINGS: We identified a 5-SNP block located ~556 bp upstream of the ARMS2 start codon, representing a cluster of predicted c-ABL tyrosine kinase binding sites. This block, in complete linkage disequilibrium with rs10490924 (A69S), showed a strong association with both wet and dry AMD (136 controls, 179 dry AMD, 251 wet AMD). EMSA and ChIP confirmed direct c-ABL binding, while luciferase reporter assays demonstrated reduced transcriptional activity mediated by the 5-SNP block in the presence of c-ABL.<br><br>INTERPRETATION: Our results suggest that the c-ABL-responsive 5-SNP regulatory streak in the ARMS2 promoter region act as functional non-coding elements that may contribute to AMD pathogenesis through altered transcriptional regulation.}, }
@article {pmid41279388, year = {2025}, author = {Maniglia, M and Vice, J and Maxwell, E and Visscher, KM and Seitz, AR}, title = {Examining oculomotor behavior in central vision loss with a gaze-contingent display.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41279388}, issn = {2692-8205}, support = {R21 EY033623/EY/NEI NIH HHS/United States ; }, abstract = {Patients with central vision loss due to macular degeneration (MD) must rely on their peripheral vision for tasks normally performed by the fovea. Many patients develop a preferred retinal locus (PRL), an eccentric retinal location used as a substitute for the damaged fovea in tasks such as face recognition, navigation, and reading. However, the mechanisms underlying PRL development remain elusive, and no single hypothesis fully explains its characteristics. Investigations into PRL development are hindered by oculomotor assessments, which often focus on fixation ability while neglecting other eye movement characteristics and potentially conflating different behaviors over time. In previous work, we introduced a series of oculomotor metrics in cases of simulated central vision loss, demonstrating that complex profiles of eye movement behavior can be extracted from a simple visual task. Here we present longitudinal data from 10 patients with MD as evidence of the feasibility of using these metrics to characterize different profiles of eye movements following central vision loss. Consistent with findings in healthy individuals using artificial scotoma, the metrics reveal substantial individual differences in behavior, both at baseline and after visual training. Overall, patients exhibit significantly higher saccadic re-referencing than controls, despite larger inter-individual differences. These metrics provide a detailed evaluation of oculomotor behavior in patients with central vision loss and offer a valuable tool for assessing progress in training protocols.}, }
@article {pmid41280070, year = {2025}, author = {Shin, K and Brown, W and Tian, Y and Gopinath, T and Bobkov, AA and Marinelli, F and Marassi, FM}, title = {Structural basis for lipid binding by the blood protein vitronectin, a component of HDL.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41280070}, issn = {2692-8205}, support = {P01 AG081167/AG/NIA NIH HHS/United States ; P30 CA030199/CA/NCI NIH HHS/United States ; R35 GM118186/GM/NIGMS NIH HHS/United States ; }, abstract = {Vitronectin (Vn) is a multifunctional blood glycoprotein involved in cell adhesion and migration, blood coagulation, and inflammation. It is a component of the high-density lipoprotein (HDL) proteome, and often found associated with the calcified, lipid-rich, protein deposits that are a hallmark of age-related macular degeneration, Alzheimer's disease, atherosclerosis and other aging-related diseases. Here we explored the molecular basis for lipid binding by Vn using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and all-atom molecular dynamics (MD) simulations. The data reveal a hydrophobic groove on the surface of the hemopexin-like (HX) domain of Vn, that is capable of binding phosphatidylcholine (PC). Conformational landscape analyses of multiple, independent MD simulations identify key structural motifs and intermolecular contacts mediating the association of Vn with PC, and show that lipid binding is guided by interactions with positively charged and hydrophobic residues that organize the lipids in a tail-to-tail bilayer-like arrangement within the groove. Collectively, the data establish a comprehensive structural model for Vn association with HDL and provide mechanistic insight into its accumulation within lipid-rich deposits characteristic of age-related pathologies.}, }
@article {pmid41281747, year = {2025}, author = {Yang, B and Yang, K and Chen, Y and Xi, R and Han, J and Li, S and Chen, J and Wu, Y}, title = {Activation of GSDME by all-trans-retinal increases sensitivity to photoreceptor ferroptosis.}, journal = {International journal of biological sciences}, volume = {21}, number = {15}, pages = {7029-7042}, pmid = {41281747}, issn = {1449-2288}, mesh = {Animals ; *Ferroptosis/physiology/drug effects/genetics ; Mice ; Mice, Knockout ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism ; *Retinaldehyde/metabolism/pharmacology ; Mice, Inbred C57BL ; Lipid Peroxidation ; Mitochondria/metabolism ; Retinal Degeneration/metabolism ; Macular Degeneration/metabolism ; ATP-Binding Cassette Transporters ; }, abstract = {Impaired clearance of all-trans-retinal (atRAL) due to visual cycle dysfunction contributes to photoreceptor atrophy, a key pathological hallmark of Stargardt disease type 1 (STGD1) and dry age-related macular degeneration (AMD). Prior studies have shown that light-induced atRAL accumulation promotes ferroptosis and activates gasdermin E (GSDME) in retinal photoreceptors of Abca4[-/-]Rdh8[-/-] mice, a model for STGD1 and dry AMD that exhibits visual cycle disorders. However, the role of GSDME in photoreceptor ferroptosis remains unclear. In this study, we revealed that GSDME activation by atRAL triggered photoreceptor ferroptosis and retinal atrophy via mitochondrial damage and oxidative stress. Knocking out GSDME significantly attenuated light-induced photoreceptor ferroptosis and retinal degeneration in Abca4[-/-]Rdh8[-/-] mice. Moreover, deleting the Gsdme gene in photoreceptor cells prevented atRAL-induced ferroptosis by inhibiting mitochondrial reactive oxygen species (mitoROS) production, iron overload, and lipid peroxidation. Notably, treatment with the mitoROS scavenger MitoTEMPO mitigated ferroptosis in atRAL-loaded photoreceptor cells and dramatically relieved photoreceptor ferroptosis and retinal degeneration in light-exposed Abca4[-/-]Rdh8[-/-] mice. We found that both GSDME elimination and MitoTEMPO treatment repressed atRAL-induced photoreceptor ferroptosis and retinal atrophy by inactivating the mitoROS-induced oxidative stress. In conclusion, GSDME-mediated photoreceptor ferroptosis is crucial for inducing structural and functional damage of the retina in retinopathies caused by atRAL accumulation, thereby providing new therapeutic insights for the prevention and treatment of STGD1 and dry AMD.}, }
@article {pmid41282061, year = {2025}, author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ}, title = {APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41282061}, issn = {2693-5015}, support = {R01 AG067478/AG/NIA NIH HHS/United States ; RF1 AG088226/AG/NIA NIH HHS/United States ; }, abstract = {APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer's disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2, ε3/ε3, and ε4/ε4 APOE-TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε4 22L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε2 22L mice performed significantly better than ε4/ε4 22L mice but significantly worse than ε3/ε3 22L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP[Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε2 22L and ε3/ε3 22L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε4 22L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε4 22L mice. ε4/ε4 22L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε2 22L, with ε3/ε3 22L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4-affected mechanisms: increased conversion and accumulation of PrP[Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4, the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.}, }
@article {pmid41282676, year = {2025}, author = {Banijamali, SMA and Versek, C and Lashkari, K and Bex, P and Sridhar, S}, title = {Mobile Objective Diagnostics of Macular Degeneration using Dark-Adapted Visual Evoked Potentials.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {41282676}, support = {R44 AG057250/AG/NIA NIH HHS/United States ; }, abstract = {PURPOSE: Delayed Dark-Adapted vision Recovery (DAR) is a known biomarker for Age-related Macular Degeneration (AMD); however, its measurement is often cumbersome for both patients and examiners. In this study, we developed NeuroVEP, a portable, wireless, and user-friendly system designed to objectively assess Dark-Adapted Visual Evoked Potentials (DAVEP).<br><br>METHODS: NeuroVEP consists of a headset with a smartphone that delivers controlled photo-bleach and monocular pattern reversal stimuli while utilizing custom electroencephalography (EEG) electrodes and electronics to measure DAVEP. The system allows for separate analysis of the near peripheral and macular visual field of each eye, completing the test in a comfortable, single-session format (<25 minutes) without requiring subjective patient feedback.The NeuroVEP test protocol included: (i) Mesopic luminance pattern reversal VEP for macular and peripheral regions (5 mins), (ii) Full-field photopic pattern reversal VEP (2.5 mins), (iii) Scotopic luminance DAVEP recovery post photo-bleach (up to 15 mins), measured simultaneously from both eyes.The data were analyzed for 66 participants, divided into four cohorts: (A) Age-matched healthy controls with no ophthalmic pathologies (n=10), (B) Early-stage AMD (AREDS1) (n=19), (C) Intermediate-stage AMD (AREDS3) (n=18), (D) Advanced-stage AMD (AREDS4/5) (n=19).Advanced signal processing and machine learning methodologies were applied to filter and process the VEP responses from the DAR segment of the experiment. 13 discriminating features were extracted from the processed signals and classified for each participant using a Bayesian statistical framework and Gaussian Mixture Model (GMM).<br><br>RESULTS: The algorithm demonstrated: 86% accuracy in early-stage AMD detection (Healthy vs. Early AMD) (Sensitivity: 97%, Specificity: 65%, AUC-ROC: 0.81 and AUC-PR: 0.92) and 93% accuracy in overall AMD detection (Healthy vs. All AMD stages) (Sensitivity: 98%, Specificity: 65%, AUC-ROC: 0.82 and AUC-PR: 0.97).<br><br>CONCLUSIONS: We successfully developed a portable, objective user-friendly VEP system and an advanced Bayesian-GMM statistical analysis framework capable of identifying DAR deficits in AMD patients. This novel technology shows high potential for early AMD detection and could serve as a non-invasive, objective diagnostic tool for AMD screening in clinical and remote settings.}, }
@article {pmid41282784, year = {2025}, author = {Zhang, PW and Wan, ZH and Liu, S and Wang, J and Sripathi, S and Li, W and Ahn, J and Li, S and Fan, L and Berlinicke, CA and Qian, J and Merbs, SL and Zack, DJ}, title = {HTRA1-AS1, an ARMS2-region long non-coding RNA, is downregulated in retinas of age-related macular degeneration patients.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {41282784}, support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY020406/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: The human 10q26 locus is a major genetic risk factor for age-related macular degeneration (AMD). Fine mapping by linkage and large-scale genome-wide association studies (GWAS) has narrowed this region to a 30-kb interval encompassing the ARMS2 and HTRA1 genes. However, the causative gene(s), risk variants, and underlying pathogenic mechanisms remain unresolved.<br><br>METHODS: Long non-coding RNA (lncRNA) candidates within the ARMS2-HTRA1 region were identified using human postmortem retinal RNA-seq data and public databases (NCBI, Ensembl). Candidate transcripts were validated by RT-PCR and Sanger sequencing. Published single-cell RNA-seq datasets were analysed to define cell type-specific expression, and RNA levels were compared between AMD and non-AMD donor retinas. Additionally, expression changes were assessed in human iPSC-derived retinal pigment epithelium (RPE) cells exposed to cigarette smoke extract (CSE) and paraquat (PQT).<br><br>RESULTS: We identified and validated a lncRNA, HTRA1-AS1, and its transcript variants (ENST00000647969.1) within the ARMS2 locus. HTRA1-AS1 overlaps ARMS2 and is transcribed in the antisense orientation. It is predominantly expressed in rod photoreceptors, M&#xfc;ller glia and Choroid/RPE, and its retinal expression was significantly reduced in AMD compared with controls (43 AMD donors vs. 44 controls, p = 0.007). By contrast, HTRA1 mRNA showed no significant difference (p = 0.121). Furthermore, ENST00000647969.1, HTRA1-AS1 and ARMS2 expression increased dramatically, up to 101-fold, 8-fold and 75-fold, respectively, in induced pluripotent stem cells (iPSC)-derived RPE cells following cigarette smoke extract (CSE)-induced oxidative stress but showed no significant change after paraquat treatment.<br><br>CONCLUSION: These findings suggest that HTRA1-AS1, a dysregulated lncRNA within the ARMS2 locus, may act as a non-coding element contributing to transcriptional mis-regulation underlying AMD pathogenesis.}, }
@article {pmid41283408, year = {2025}, author = {Barranco Garcia, J and Ferrazzini, T and Coito, A and Brügger, D and Abegg, M}, title = {Recovery of the Pupillary Response After Light Adaptation Is Slowed in Patients with Age-Related Macular Degeneration.}, journal = {Journal of eye movement research}, volume = {18}, number = {6}, pages = {}, pmid = {41283408}, issn = {1995-8692}, abstract = {Purpose: This study evaluates a novel, non-invasive method using a virtual reality (VR) headset with integrated eye trackers to assess retinal function by measuring the recovery of the pupillary response after light adaptation in patients with age-related macular degeneration (AMD). Methods: In this pilot study, fourteen patients with clinically confirmed AMD and 14 age-matched healthy controls were exposed to alternating bright and dark stimuli using a VR headset. The dark stimulus duration increased incrementally by 100 milliseconds per trial, repeated over 50 cycles. The pupillary response to the re-onset of brightness was recorded. Data were analyzed using a linear mixed-effects model to compare recovery patterns between groups and a convolutional neural network to evaluate diagnostic accuracy. Results: The pupillary response amplitude increased with longer dark stimuli, i.e., the longer the eye was exposed to darkness the bigger was the subsequent pupillary amplitude. This pupillary recovery was significantly slowed by age and by the presence of macular degeneration. Test diagnostic accuracy for AMD was approximately 92%, with a sensitivity of 90% and a specificity of 70%. Conclusions: This proof-of-concept study demonstrates that consumer-grade VR headsets with integrated eye tracking can detect retinal dysfunction associated with AMD. The method offers a fast, accessible, and potentially scalable approach for retinal disease screening and monitoring. Further optimization and validation in larger cohorts are needed to confirm its clinical utility.}, }
@article {pmid41283579, year = {2025}, author = {Cao, JA and Zhou, AW and Teagle, GM and Baumann, LM and Sahraravand, RA and Wong, CW and De Zanet, S and Jovic, N and Steiner, P and Patel, SB and Minaker, SA and MacCumber, MW and Brown, DM and Al-Khersan, H and Wykoff, CC}, title = {Geographic Atrophy Progression in Clinical Practice Before and After Pegcetacoplan Treatment.}, journal = {Vision (Basel, Switzerland)}, volume = {9}, number = {4}, pages = {}, pmid = {41283579}, issn = {2411-5150}, support = {N/A//Texas Retina Research Foundation (TRRF), Houston, Texas/ ; }, abstract = {This retrospective study evaluated changes in ocular characteristics and retinal pigment epithelium (RPE) and photoreceptor ellipsoid zone (EZ) depletion rates before and after intravitreal pegcetacoplan initiation in clinical practice. A total of 168 eyes from 110 patients with GA secondary to age-related macular degeneration (AMD) who received at least 3 pegcetacoplan injections were included. Data was collected from 5 years before to 9 months after pegcetacoplan initiation. RPE and EZ depletion areas were measured using an automated artificial intelligence (AI) algorithm on optical coherence tomography (OCT) images. At baseline, 76 eyes (45.2%) had concurrent neovascular AMD (nAMD), with mean RPE and EZ depletion areas of 3.3 mm[2] and 4.9 mm[2], respectively. By pegcetacoplan initiation, these increased to 8.6 mm[2] and 11.2 mm[2], respectively, with 151 eyes (89.9%) having concurrent nAMD and 155 eyes (92.3%) having subfoveal GA. Pre-treatment to post-treatment RPE and EZ square root depletion rates decreased from 0.25 mm/year to 0.096 mm/year, and 0.26 mm/year to 0.049 mm/year, respectively. Mean best-recorded visual acuity (BRVA) worsened by 0.05 logMAR annually before and after treatment. These real-world findings align with data from the pegcetacoplan phase 3 trials, showing reduced RPE and EZ depletion rates without changes in rates of BRVA loss. Additional studies are warranted.}, }
@article {pmid41284475, year = {2025}, author = {Cui, Y and Song, Z and Wang, X}, title = {Bisphosphonate-related ocular adverse events: a pharmacovigilance study based on the FAERS database.}, journal = {Endocrine connections}, volume = {14}, number = {12}, pages = {}, pmid = {41284475}, issn = {2049-3614}, abstract = {This retrospective study aimed to identify and characterize signals of ocular adverse events (AEs) related to bisphosphonates (BPs) using FDA adverse event reporting system (FAERS) data (Q1 2004 to Q3 2024) to inform future safety investigations. Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods to identify BP-related ocular AE signals. In addition, a modified ROR method was utilized to examine differences across gender and age. Among 6,965 ocular AE reports for five BPs (alendronate, zoledronate, pamidronate, risedronate, and ibandronate), 136 positive signals were identified, predominantly unlisted in drug labels. Notable risks included ocular inflammatory AEs (especially zoledronate) and novel risk signals such as cataract, glaucoma, and macular degeneration. Standardized MedDRA queries (SMQ) linked BPs to 11 eye disorders, with scleral disorders common to all five BPs and pamidronate involving the broadest SMQ categories. Ocular AEs for alendronate, zoledronate, and pamidronate exhibited age-related differences, while those for alendronate and zoledronate showed gender differences. This study identifies high-risk and novel ocular AEs related to BPs. These findings warrant further validation in future studies.}, }
@article {pmid41292308, year = {2026}, author = {Kim, TR and Kim, TG and Choi, J and Yu, SY and Kim, K}, title = {Quantitative Analysis of Drusen in South Korean Patients: A 36-Month Follow-Up Study.}, journal = {Korean journal of ophthalmology : KJO}, volume = {40}, number = {1}, pages = {87-98}, pmid = {41292308}, issn = {2092-9382}, mesh = {Humans ; Retrospective Studies ; Female ; Male ; Follow-Up Studies ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/epidemiology ; Republic of Korea/epidemiology ; Aged ; Middle Aged ; Disease Progression ; Time Factors ; Fundus Oculi ; *Macular Degeneration/diagnosis/epidemiology ; Fluorescein Angiography/methods ; Aged, 80 and over ; Incidence ; *Retinal Pigment Epithelium/pathology ; }, abstract = {PURPOSE: This study aimed to quantitatively evaluate longitudinal changes in drusen area and volume over 36 months in South Korean patients and to identify the factors associated with these changes and the development of advanced age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective study, 38 eyes from 38 patients diagnosed with drusen were analyzed. The drusen area and volume were measured using spectral-domain optical coherence tomography (SD-OCT; Cirrus 5000, Carl Zeiss Meditec) with an automated retinal pigment epithelium elevation map algorithm. To minimize bias from variable follow-up intervals, an annualized classification framework was adopted. Based on percentage change in drusen area within the 5-mm circle, eyes were categorized as progressed (increase >20%), stable (change within &#xb1;20%), or regressing (decrease >20%).<br><br>RESULTS: Both drusen area and volume increased significantly up to 24 months (area, p = 0.003; volume, p = 0.028) and then showed a modest decline at 36 months, remaining above baseline levels. No significant difference in the proportions of progressed, stable, or regressing eyes was observed across 12-month intervals or compared with baseline (all p > 0.05). A larger baseline 5-mm drusen area was significantly associated with the development of advanced AMD (adjusted odds ratio, 2.818; 95% confidence interval, 1.022-7.767; p = 0.045). Eyes that exhibited at least one episode of drusen regression showed a higher incidence of advanced AMD (36.8% vs. 5.3%, p = 0.042).<br><br>CONCLUSIONS: Drusen in South Korean patients demonstrated dynamic morphological remodeling over time. Drusen regression was not a benign phenomenon but rather a potential high-risk marker for progression to advanced AMD. These findings highlight the importance of population-specific, quantitative SD-OCT monitoring for early risk stratification in East Asian eyes.}, }
@article {pmid41293061, year = {2025}, author = {Lorenzi, M and Ebohon, S and Kissner, J and Comiskey, J and Paap, M and Bouchet, C and Garnham, A and Wissinger, E}, title = {Network Meta-Analysis of Bevacizumab Gamma Versus Competing Interventions for Treating Neovascular Age-Related Macular Degeneration in the United Kingdom.}, journal = {Journal of market access &amp; health policy}, volume = {13}, number = {4}, pages = {58}, pmid = {41293061}, issn = {2001-6689}, abstract = {This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments.}, }
@article {pmid41293704, year = {2025}, author = {Guo, Y and Hormel, TT and Wu, AL and Gao, M and Hwang, TS and Bailey, ST and Jia, Y}, title = {AI-aided segmentation of four types of drusen in volumetric OCT.}, journal = {Biomedical optics express}, volume = {16}, number = {11}, pages = {4380-4391}, pmid = {41293704}, issn = {2156-7085}, support = {P30 EY010572/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; R01 EY036429/EY/NEI NIH HHS/United States ; R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY031394/EY/NEI NIH HHS/United States ; R01 EY027833/EY/NEI NIH HHS/United States ; T32 EY023211/EY/NEI NIH HHS/United States ; R01 EY035410/EY/NEI NIH HHS/United States ; R43 EY036781/EY/NEI NIH HHS/United States ; }, abstract = {Drusen are a hallmark biomarker of age-related macular degeneration (AMD), with their size, number, and morphology (type) closely linked to disease severity and progression. Accurate segmentation and classification of drusen from optical coherence tomography (OCT) images are essential for objective AMD assessment and monitoring. In this work, we present a deep learning framework that combines a convolutional neural network for automated drusen segmentation with a dedicated classification module to distinguish four clinically relevant, distinct drusen types based on segmentation output. We evaluated our approach on a comprehensive dataset and achieved a mean Dice score of 0.74 ± 0.21 for voxel-wise segmentation accuracy and a critical success index of 0.69 ± 0.24 for drusen count accuracy. This method demonstrates substantial improvements in the quantitative drusen analysis and offers a promising tool for enhanced AMD diagnosis and tracking of disease progression.}, }
@article {pmid41293996, year = {2025}, author = {Xin, X and Zhao, X and Han, X and Pu, W}, title = {ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression.}, journal = {BioFactors (Oxford, England)}, volume = {51}, number = {6}, pages = {e70057}, pmid = {41293996}, issn = {1872-8081}, support = {2023GLLH0239//Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of InnerMongolia Academyof Medical Sciences/ ; 2023YK17//Scientific Research Program of Aerospace Medical and Healthcare Technology Group Co./ ; }, mesh = {Oxidative Stress/drug effects ; Humans ; Hydrogen Peroxide/pharmacology ; *Glucose/metabolism ; Cellular Senescence/drug effects ; Animals ; Cell Line ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Macular Degeneration/genetics/metabolism/pathology ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; }, abstract = {Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H2O2-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.}, }
@article {pmid41294302, year = {2025}, author = {Quarta, A and Corradetti, G and Romano, F and Trinco, A and Feo, A and Corvi, F and Nardi, C and Alhelaly, M and Abbasgholizadeh, R and Chujo, S and Popovic, M and Soylu, C and Chung, YC and Kwak, HD and Rattu, R and Nittala, MG and Staurenghi, G and Sadda, SR}, title = {Distinct Profiles of Choriocapillaris Involvement in Extensive Macular Atrophy With Pseudodrusen-Like Appearance and Geographic Atrophy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {14}, pages = {64}, pmid = {41294302}, issn = {1552-5783}, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/etiology ; Retrospective Studies ; Female ; *Choroid/blood supply ; Cross-Sectional Studies ; Male ; Tomography, Optical Coherence/methods ; Aged ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Drusen/diagnosis/physiopathology ; Capillaries/pathology/physiopathology ; *Macular Degeneration/complications/diagnosis/physiopathology ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Regional Blood Flow/physiology ; }, abstract = {PURPOSE: To quantitatively compare choriocapillaris flow deficit percentages (CCFD%) between eyes with extensive macular atrophy with pseudodrusen-like appearance (EMAP) and geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and to identify predictive factors for CCFD% at the atrophy margin.<br><br>METHODS: This retrospective cross-sectional study included 53 eyes (27 with GA and 26 with EMAP). CCFD% were computed within a 500-&#xb5;m-wide marginal zone (CCFD%_M) and beyond the margin (CCFD%_BM) using compensated en face optical coherence tomography angiography (OCTA) images. Atrophy-to-fovea distance (AFD) was quantified by pixel-wise Euclidean analysis.<br><br>RESULTS: Eyes with EMAP demonstrated significantly higher CCFD% compared to GA both at the atrophy margin (CCFD%_M, P < 0.05) and beyond (CCFD%_BM, P < 0.01). In univariable analysis, belonging to the GA group was associated with a 5.9-unit reduction in CCFD%_M, reflecting a substantial preservation of choriocapillaris (CC) perfusion in GA relative to EMAP. AFD was greater in EMAP (2.35 &#xb1; 0.56 mm) than GA (1.74 &#xb1; 0.55 mm; P = 0.014) suggesting more eccentric positioning of the lesions in the former. A multivariable mixed-effects model confirmed disease subtype (EMAP vs. GA) as an independent determinant of CC impairment with EMAP associated with a significantly higher CCFD%_M (P < 0.01).<br><br>CONCLUSIONS: CC impairment is more pronounced in EMAP than in GA, with EMAP exhibiting more extensive and diffuse CCFD, particularly at the atrophy margins. This pattern may reflect a more aggressive vascular compromise in EMAP. These findings underscore a distinct CC pathoanatomy between the two conditions, with implications for disease progression and therapeutic targeting.}, }
@article {pmid41294847, year = {2025}, author = {Alam, J and Ponnam, A and Souvangini, A and Gopi, S and Ildefonso, CJ and Biswal, MR}, title = {EPO-R76E Enhances Retinal Pigment Epithelium Viability Under Mitochondrial Oxidative Stress Induced by Paraquat.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, pmid = {41294847}, issn = {2073-4409}, support = {R01 EY033415/EY/NEI NIH HHS/United States ; R01EY033415/EY/NEI NIH HHS/United States ; }, mesh = {*Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; *Mitochondria/metabolism/drug effects ; *Paraquat/toxicity/pharmacology ; *Erythropoietin/genetics/metabolism ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; NF-E2-Related Factor 2/metabolism ; Apoptosis/drug effects ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, primarily driven by oxidative stress-induced degeneration of retinal pigment epithelium (RPE). Erythropoietin (EPO), a hematopoietic cytokine with neuroprotective properties, has been shown to reduce apoptosis and retinal degeneration. In this study, we examined the cytoprotective role of a non-erythropoietic EPO variant, EPO-R76E, in suppressing oxidative stress and mitochondrial dysfunction related to oxidative stress in RPE cells. Stable ARPE-19 cell lines expressing EPO-R76E were generated via lentiviral transduction and exposed to paraquat to induce oxidative stress. Oxidative stress was induced using paraquat. EPO-R76E expression conferred increased cell viability and resistance to mitochondrial damage, as assessed by cytotoxicity assays. Western blot analysis revealed reduced expression of ferritin and p62/SQSTM1, diminished activation of p-AMPK and NRF2, and restoration of GPX4 levels, indicating enhanced antioxidant defenses. Moreover, intracellular iron accumulation and reactive oxygen species were significantly reduced in EPO-R76E-expressing cells exposed to paraquat. These findings suggest that EPO-R76E promotes mitochondrial homeostasis and modulates oxidative stress pathways. Our study positions EPO-R76E as a promising therapeutic candidate for halting RPE degeneration in AMD.}, }
@article {pmid41297424, year = {2025}, author = {Zhou, L and Ma, Y and Li, X and Cao, G}, title = {Gut-eye axis in ophthalmic diseases: Focus on ocular neurodegeneration.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {193}, number = {}, pages = {118800}, doi = {10.1016/j.biopha.2025.118800}, pmid = {41297424}, issn = {1950-6007}, mesh = {*Gastrointestinal Microbiome ; Humans ; Animals ; *Eye Diseases/microbiology ; Brain-Gut Axis ; *Neurodegenerative Diseases/microbiology ; Eye/metabolism ; }, abstract = {Ocular neurodegeneration comprises a group of complex processes that severely affect visual function and is recognized as a key pathogenetic process in a variety of blinding ocular diseases, including glaucoma, diabetic retinopathy, age-related macular degeneration and retinitis pigmentosa. Although these diseases have different etiologies and mechanisms, apoptosis, metabolic disorders and oxidative damage are common features shared by all of them. Increasing evidence indicates that gut microbiota regulates distant organs by engaging in the host's neural, endocrine, immune regulation and even intercellular information. However，in ocular degenerative diseases, specific gut microbiota and their metabolites play an important role in ocular degenerative diseases. Therefore, in this review, we summarize the pathways through which the "gut-eye axis" functions and the mechanisms by which it interacts with ocular degenerative diseases, as well as the alterations in gut microbiota profiles observed in several common ocular degenerative diseases. Additionally, we provide an outlook on the clinical application of the "gut-eye axis", including its potential diagnostic, therapeutic, and adjunctive therapies.}, }
@article {pmid41297526, year = {2025}, author = {Paneerselvam, GS and Wai, NJ and Sheng, LJ and Kenneth, LKC}, title = {Cost-Effectiveness of Vascular Endothelial Growth Factor Inhibitors in the Management of Wet Age-Related Macular Degeneration: A Systematic Review.}, journal = {Value in health regional issues}, volume = {53}, number = {}, pages = {101542}, doi = {10.1016/j.vhri.2025.101542}, pmid = {41297526}, issn = {2212-1102}, abstract = {OBJECTIVES: To evaluate the cost-effectiveness of VEGF inhibitors, ranibizumab, aflibercept, bevacizumab, brolucizumab, pegaptanib, and conbercept for wAMD treatment.<br><br>METHODS: A systematic search was conducted in PubMed, Cochrane, and SpringerLink databases to identify cost-effectiveness analyses and cost-utility analyses related to wAMD treatment. Eligible studies were assessed using Drummond's 10-point checklist to evaluate methodological quality. The extracted data included intervention costs, quality-adjusted life-years, and incremental cost-effectiveness ratios.<br><br>RESULTS: Twenty-two studies met the inclusion criteria. Bevacizumab and brolucizumab were frequently reported as cost-effective alternatives, offering comparable or superior visual outcomes at lower costs than ranibizumab or aflibercept. Pegaptanib was consistently less cost-effective. Findings for ranibizumab versus aflibercept varied by treatment regimen and analytic assumptions. Across studies, cost-effectiveness estimates were influenced by model perspective, time horizon, exclusion of adverse events, and single-eye modeling. A further limitation is that in contexts of non-inferior efficacy, small incremental quality-adjusted life-years differences may artificially inflate incremental cost-effectiveness ratios, potentially overstating the costs relative to benefits.<br><br>CONCLUSIONS: Decision making in wAMD treatment requires more thorough economic evaluations that incorporate standardized methodologies and lengthy cost assessments.}, }
@article {pmid41300254, year = {2025}, author = {Shi, C and Lee, J and Shi, D and Wang, G and Yuan, F and Lai, TYY and Liu, J and Lu, Y and Liu, D and Qin, B and Zee, BC}, title = {AI-Based Retinal Image Analysis for the Detection of Choroidal Neovascular Age-Related Macular Degeneration (AMD) and Its Association with Brain Health.}, journal = {Brain sciences}, volume = {15}, number = {11}, pages = {}, pmid = {41300254}, issn = {2076-3425}, abstract = {Purpose: This study aims to develop a method for detecting referable (intermediate and advanced) age-related macular degeneration (AMD) and neovascular AMD, as well as providing an automatic segmentation of choroidal neovascularisation (CNV) on colour fundus retinal images. We also demonstrated that brain health risk scores estimated by AI-based Retinal Image Analysis (ARIA), such as white matter hyperintensities and depression, are significantly associated with AMD and neovascular AMD. Methods: A primary dataset of 1480 retinal images was collected from Zhongshan Hospital of Fudan University for training and 10-fold cross-validation. Additionally, two validation subdataset comprising 238 images (retinal images and wide-field images) were used. Using fluorescein angiography-based labels, we applied the InceptionResNetV2 deep network with the ARIA method to detect AMD, and a transfer ResNet50_Unet was used to segment CNV. The risks of cerebral white matter hyperintensities and depression were estimated using an AI-based Retinal Image Analysis approach. Results: In a 10-fold cross-validation, we achieved sensitivities of 97.4% and 98.1%, specificities of 96.8% and 96.1%, and accuracies of 97.0% and 96.4% in detecting referable AMD and neovascular AMD, respectively. In the external validation, we achieved accuracies of 92.9% and 93.7% and AUCs of 0.967 and 0.967, respectively. The performances on two validation sub-datasets show no statistically significant difference in detecting referable AMD (p = 0.704) and neovascular AMD (p = 0.213). In the segmentation of CNV, we achieved a global accuracy of 93.03%, a mean accuracy of 91.83%, a mean intersection over union (IoU) of 68.7%, a weighted IoU of 89.63%, and a mean boundary F1 (BF) of 67.77%. Conclusions: The proposed method shows promising results as a highly efficient and cost-effective screening tool for detecting neovascular and referable AMD on both retinal and wide-field images, and providing critical insights into CNV. Its implementation could be particularly valuable in resource-limited settings, enabling timely referrals, enhancing patient care, and supporting decision-making across AMD classifications. In addition, we demonstrated that AMD and neovascular AMD are significantly associated with increased risks of WMH and depression.}, }
@article {pmid41300437, year = {2025}, author = {Hong, SJ and Lee, DH and Choi, JW and Lee, H and Sung, Y and Kim, GJ}, title = {Nrf2 Activated by PD-MSCs Attenuates Oxidative Stress in a Hydrogen Peroxide-Injured Retinal Pigment Epithelial Cell Line.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {41300437}, issn = {2076-3921}, support = {RS - 2025 - 431 02313877//Industry - Academia - Research Institute (IAR) Collabo R&amp;D Fund Grant funded by the Korean Government/ ; }, abstract = {Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H2O2) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H2O2 treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H2O2 treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H2O2-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.}, }
@article {pmid41301489, year = {2025}, author = {Intonti, S and Olivieri, C and Reibaldi, M and Borrelli, E and Curcio, C and Conedera, FM}, title = {Translational Molecular and Fluid Biomarkers for Age-Related Macular Degeneration: Practical Insights from Animal Models and Humans.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, pmid = {41301489}, issn = {2218-273X}, support = {PZ00P3_223803/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Macular Degeneration/metabolism/diagnosis/pathology/genetics ; Disease Models, Animal ; Oxidative Stress ; Mice ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management.}, }
@article {pmid41301509, year = {2025}, author = {Nardella, M and Pellegrini, M and Yu, AC and Adamo, GG and Mura, M and Busin, M}, title = {Nanotechnology-Based Delivery Systems and Retinal Pigment Epithelium: Advances, Targeting Approaches, and Translational Challenges.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, pmid = {41301509}, issn = {2218-273X}, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Drug Delivery Systems/methods ; Animals ; *Nanotechnology/methods ; Translational Research, Biomedical ; Nanomedicine/methods ; Macular Degeneration/drug therapy ; Retinal Diseases/drug therapy ; Nanoparticles/chemistry ; }, abstract = {The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application.}, }
@article {pmid41301918, year = {2025}, author = {Lee, Y and Seo, JH}, title = {Potential Causal Effects of Cystatin C on Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.}, journal = {Biomedicines}, volume = {13}, number = {11}, pages = {}, pmid = {41301918}, issn = {2227-9059}, support = {VHSMC24002//Veterans Health Service Medical Center Research Grant/ ; }, abstract = {Background/Objectives: Previous studies have shown an association between kidney function and age-related macular degeneration (AMD). This study aims to assess whether the kidney function-related parameters of serum cystatin C and creatinine levels are associated with increased risk of AMD and its subtypes. Methods: Genetic instruments for variants associated with serum cystatin C and creatinine levels as exposure at genome-wide significance (p < 5.0 × 10[-8]) were obtained from the UK Biobank. Genetic data for AMD and its subtypes were obtained from the FinnGen project. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of serum cystatin C and creatinine levels on AMD and its subtypes. Results: Using an inverse-variance weighted approach, higher cystatin C levels are associated with an increased risk of AMD [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04 to 1.22, p = 0.004 for overall AMD; OR = 1.14, 95% CI: 1.04 to 1.25, p = 0.007 for dry AMD; OR = 1.14, 95% CI: 1.03 to 1.26, p = 0.011 for wet AMD]. However, serum creatinine levels did not significantly impact the risk of AMD or its subtypes. Conclusions: This study provides genetic evidence that higher cystatin C levels may be a causal risk factor for AMD and its subtypes, whereas serum creatinine was not. This result implies the need to investigate the effect of cystatin C on AMD potentially independent of kidney function.}, }
@article {pmid41302082, year = {2025}, author = {Liesenhoff, C and Meyrl, C and Krause, D and Eckardt, F and Lorger, A and Deiters, V and Schiefelbein, J and Klaas, JE and Schworm, B and Priglinger, SG and Siedlecki, J}, title = {High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent?.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, pmid = {41302082}, issn = {2075-1729}, abstract = {Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept.}, }
@article {pmid41302976, year = {2025}, author = {Molin, C and Midena, E and Convento, E and Midena, G and Pilotto, E}, title = {Fixation Stability as a Surrogate for Reading Abilities in Age-Related Macular Degeneration: A Perspective.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41302976}, issn = {2077-0383}, abstract = {Age-related macular degeneration (AMD) significantly impacts central vision, fixation site and stability and reading abilities. This work aims to analyze the relationship between retinal fixation parameters measured using microperimetry and reading performance in patients with AMD. We identified the role of fixation stability measurement in the evaluation of reading abilities and discussed its implications both in clinical practice and in clinical trials. Our analysis highlights the importance of retinal fixation assessment as a precise surrogate for evaluating reading ability outcomes in AMD patients and as new clinical endpoint to demonstrate the functional effects of present and emerging target therapies.}, }
@article {pmid41303214, year = {2025}, author = {Wu, KY and Qian, SY and Camiré, A and Kim, DT and Giunta, M}, title = {Aflibercept for Wet Age-Related Macular Degeneration: A Prospective, Randomized Trial Comparing Treat-And-Extend and Fixed Bimonthly Dosing.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41303214}, issn = {2077-0383}, support = {Unknown//Bayer (Canada)/ ; }, abstract = {Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study's goal is to propose new treatment protocols by comparing the efficacy of bimonthly fixed dosing aflibercept injections versus the treat-and-extend (T&amp;E) approach for wet AMD. Secondary objectives included categorical best-corrected visual acuity (BCVA) changes, anatomical outcomes, treatment intervals, and adverse events. Methods: This study is a 1-year randomized, open-label, prospective trial that included 44 eyes from 44 patients, 32 in the T&amp;E arm and 12 in the bimonthly arm. Treatment-naïve AMD patients with neovascularization were randomized to a bimonthly fixed dosing group or a T&amp;E group after receiving 3 consecutive monthly aflibercept injections. Following the induction doses, retreatment intervals for patients in the T&amp;E arm were adjusted based on a predetermined algorithm. Results: Over 12 months, mean BCVA improvements were 5.0 letters in the bimonthly group and 4.1 in the T&amp;E group (p = 0.096 for non-inferiority test). On average, T&amp;E patients received 9.6 injections compared to 7.7 for those in the fixed dosing group (p < 0.001). Anatomical outcomes were comparable in both treatment arms. Conclusions: In our trial, the T&amp;E approach provided significant visual improvements, but did not meet the threshold for non-inferiority when compared to fixed bimonthly dosing. It was also unable to minimize treatment burden over the course of the first year of injections. Further research is required to optimize the T&amp;E algorithm with aflibercept.}, }
@article {pmid41303260, year = {2025}, author = {Lee, SY and Hwang, DD}, title = {Short-Term Effects of Intravitreal Ranibizumab Biosimilar Injections in Patients with Neovascular Age-Related Macular Degeneration on Retinal Nerve Fiber Layer Thickness.}, journal = {Journal of clinical medicine}, volume = {14}, number = {22}, pages = {}, pmid = {41303260}, issn = {2077-0383}, abstract = {Background/Objectives: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD), but concerns remain regarding its potential effects on optic nerve structure. Evidence on the structural safety of ranibizumab biosimilars, including LucenBS[®], is still limited. This study aimed to investigate the short-term effects of intravitreal LucenBS[®] injections on peripapillary retinal nerve fiber layer (RNFL) thickness in previously treated nAMD patients using optical coherence tomography (OCT). Methods: This retrospective, observational case series included 24 eyes from 24 nAMD patients who had previously received anti-VEGF agents other than ranibizumab biosimilar. In bilateral cases, the eye that developed nAMD earlier was selected. Patients received between one and three LucenBS[®] injections, and the mean follow-up period after the final injection was 11.92 ± 4.81 weeks. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and peripapillary RNFL thickness were assessed before and after each injection using spectral-domain OCT. Sectoral and global RNFL values were compared using the Wilcoxon signed-rank test. Results: The mean age of participants was 74.6 ± 9.0 years, and baseline BCVA and IOP were 0.83 ± 0.66 logMAR and 14.88 ± 2.80 mmHg, respectively. RNFL thickness showed no significant changes in either global or sectoral regions after any injection (all p > 0.05). CMT significantly decreased after the first injection (p = 0.007), but remained stable with subsequent treatments. BCVA remained stable after the first and second injections, but slightly worsened after the third injection (p = 0.012). IOP showed no significant changes at any time point. Conclusions: Short-term intravitreal LucenBS[®] injections did not induce structural alterations in the peripapillary RNFL, supporting their short-term ocular safety in previously treated nAMD patients. Although CMT improved after the first injection, functional and anatomical responses varied with repeated dosing. Larger, long-term studies are required to further validate the structural and functional safety of ranibizumab biosimilars in nAMD management.}, }
@article {pmid41303405, year = {2025}, author = {Noreen, S and Lim, SS and Lee, D}, title = {Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303405}, issn = {1422-0067}, support = {RS-2021-NR060133//NRF/ ; }, mesh = {Humans ; *NAD/metabolism ; Animals ; *Aging/metabolism/drug effects ; *Retinal Diseases/metabolism/prevention &amp; control/drug therapy ; Niacinamide/analogs &amp; derivatives/pharmacology/therapeutic use ; Diabetic Retinopathy/metabolism/drug therapy/prevention &amp; control ; Macular Degeneration/metabolism/drug therapy ; Mitochondria/metabolism/drug effects ; Retina/metabolism/drug effects ; Oxidative Stress/drug effects ; *Protective Agents/pharmacology ; Nicotinamide Mononucleotide/pharmacology/therapeutic use ; Pyridinium Compounds ; }, abstract = {Nicotinamide adenine dinucleotide (NAD[+]) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD[+] is linked to the development of pathological retinal conditions, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction, oxidative stress, and inflammation occur in these diseases. This review summarizes substantial evidence of therapeutic NAD[+] boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside. They help improve mitochondrial function and lessen neurovascular injury. We also emphasize the importance of natural products and sirtuins in facilitating cytoprotective effects through the regulation of mitochondrial balance and inflammation. Developments in drug delivery methods, such as nanoparticle encapsulation and targeted eye treatments, are promising for enhancing the bioavailability and effectiveness of NAD[+] boosters. The novelty of this work is its combination of mechanistic insights regarding NAD[+] metabolism with efficacy data from preclinical studies. Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD[+] metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes.}, }
@article {pmid41303406, year = {2025}, author = {Chao, WW and Chao, HW and Peng, PH and Lee, YT and Chao, HM}, title = {Retinal Ischemia: Therapeutic Effects and Mechanisms of Paeoniflorin.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303406}, issn = {1422-0067}, mesh = {Animals ; *Glucosides/pharmacology/therapeutic use ; *Monoterpenes/pharmacology/therapeutic use ; Rats ; Rats, Wistar ; Male ; Vascular Endothelial Growth Factor A/metabolism ; *Ischemia/drug therapy/metabolism/pathology ; Disease Models, Animal ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Retinal Diseases/drug therapy/metabolism/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Cell Survival/drug effects ; Reperfusion Injury/drug therapy/metabolism/pathology ; Apoptosis/drug effects ; Neuroprotective Agents/pharmacology ; Glycosides ; }, abstract = {Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H2O2) or by subjecting retinal neuronal cells to 8 h of oxygen-glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties.}, }
@article {pmid41303411, year = {2025}, author = {Gyenes, A and István, L and Papp, A and Resch, M and Récsán, Z and Ecsedy, M and Szepessy, Z and Szabó, A and Lesch, B and Barcsay, G and Borbándy, &#xc1; and Sándor, GL and Nagy, ZZ and Kovács, I}, title = {Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303411}, issn = {1422-0067}, mesh = {Humans ; *Visual Acuity/drug effects ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Male ; Female ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy/physiopathology ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; }, abstract = {The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate 'time in range' (TIR). TIR is defined as 'time spent with best-corrected visual acuity (BCVA) better than 20/40' and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05-1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action.}, }
@article {pmid41303866, year = {2025}, author = {Kang, SG and Singh, M and Lee, G and Lee, KE and Vinayagam, R}, title = {Formulation of α-Linolenic Acid-Based Microemulsions for Age-Related Macular Degeneration: Physicochemical Tests and HET-CAM Assays for Anti-Angiogenic Activities.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {11}, pages = {}, pmid = {41303866}, issn = {1648-9144}, support = {1345370673, LINC3.0-2023-54//Ministry of Education and National Research Foundation of Korea/ ; }, mesh = {Emulsions/therapeutic use ; *alpha-Linolenic Acid/therapeutic use/pharmacology ; Animals ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy ; Chorioallantoic Membrane/drug effects ; Humans ; Chick Embryo ; Drug Delivery Systems/methods ; Chickens ; Mice ; Intravitreal Injections/methods ; }, abstract = {Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood-retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (Smix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a Smix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94-56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen's egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections.}, }
@article {pmid41304869, year = {2025}, author = {Alali, NM and Aljahdali, A and AlBalawi, HB and Al Jarallah, OJ and Al Zaid, SM and Abuallut, I and ALMarek, F and Shajry, I and Alotaibi, YA and Hazzazi, MA and Magliyah, MS}, title = {Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {11}, pages = {}, pmid = {41304869}, issn = {1424-8247}, abstract = {Background/Objectives: Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of approximately 26 kilodaltons (scFv, ~26 kDa) targeting all VEGF-A isoforms. Intravitreal brolucizumab (6 mg) is FDA-approved for neovascular age-related macular degeneration (nAMD) (2019) and diabetic macular edema (DME) (2022). We systematically review the literature on brolucizumab for nAMD and DME, focusing on efficacy, safety, pharmacokinetics, real-world outcomes, and cost-effectiveness in adult and pediatric patients. Methods: Our method involves a comprehensive literature search of PubMed, Embase, Scopus, Cochrane, and related databases (through late 2024) using terms including "brolucizumab," "Beovu," "neovascular AMD," "diabetic macular edema," "safety," "pharmacokinetics," and "pediatric." High-quality clinical trials, meta-analyses, regulatory documents, and real-world studies were prioritized. Results: In pivotal Phase III trials (HAWK/HARRIER for nAMD), brolucizumab 6 mg demonstrated non-inferior visual acuity (VA) gains to aflibercept, with >50% of eyes maintained on 12-week dosing and greater retinal fluid reduction. In DME trials (KESTREL/KITE), brolucizumab was similarly non-inferior to aflibercept for VA and showed superior anatomic drying, with 33-48% of eyes maintained on ≥12-week intervals. However, brolucizumab use has been associated with intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion: clinical trials and post hoc analyses reported higher rates of these events than comparator agents. Real-world cohorts found IOI in ~4-10% of treated eyes, often occurring early (within 3 months) after initiation. Conclusions: In conclusion, Brolucizumab is an effective anti-VEGF option for nAMD and DME, providing durable anatomic control with fewer injections. Non-inferior vision outcomes and superior fluid resolution have been demonstrated. However, it carries a distinct risk of IOI and occlusive vasculitis, necessitating careful patient selection, dosing, and monitoring.}, }
@article {pmid41305085, year = {2025}, author = {Wang, MH}, title = {Explainable Artificial Intelligence Framework for Predicting Treatment Outcomes in Age-Related Macular Degeneration.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {22}, pages = {}, pmid = {41305085}, issn = {1424-8220}, support = {82501368//National Natural Science Foundation of China/ ; }, mesh = {Treatment Outcome ; *Macular Degeneration/diagnosis/therapy ; Humans ; Male ; Female ; Middle Aged ; Aged ; Prognosis ; *Large Language Models ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, yet current tools for forecasting treatment outcomes remain limited by either the opacity of deep learning or the rigidity of rule-based systems. To address this gap, we propose a hybrid neuro-symbolic and large language model (LLM) framework that combines mechanistic disease knowledge with multimodal ophthalmic data for explainable AMD treatment prognosis. In a pilot cohort of ten surgically managed AMD patients (six men, four women; mean age 67.8 ± 6.3 years), we collected 30 structured clinical documents and 100 paired imaging series (optical coherence tomography, fundus fluorescein angiography, scanning laser ophthalmoscopy, and ocular/superficial B-scan ultrasonography). Texts were semantically annotated and mapped to standardized ontologies, while images underwent rigorous DICOM-based quality control, lesion segmentation, and quantitative biomarker extraction. A domain-specific ophthalmic knowledge graph encoded causal disease and treatment relationships, enabling neuro-symbolic reasoning to constrain and guide neural feature learning. An LLM fine-tuned on ophthalmology literature and electronic health records ingested structured biomarkers and longitudinal clinical narratives through multimodal clinical-profile prompts, producing natural-language risk explanations with explicit evidence citations. On an independent test set, the hybrid model achieved AUROC 0.94 ± 0.03, AUPRC 0.92 ± 0.04, and a Brier score of 0.07, significantly outperforming purely neural and classical Cox regression baselines (p ≤ 0.01). Explainability metrics showed that >85% of predictions were supported by high-confidence knowledge-graph rules, and >90% of generated narratives accurately cited key biomarkers. A detailed case study demonstrated real-time, individualized risk stratification-for example, predicting an >70% probability of requiring three or more anti-VEGF injections within 12 months and a ~45% risk of chronic macular edema if therapy lapsed-with predictions matching the observed clinical course. These results highlight the framework's ability to integrate multimodal evidence, provide transparent causal reasoning, and support personalized treatment planning. While limited by single-center scope and short-term follow-up, this work establishes a scalable, privacy-aware, and regulator-ready template for explainable, next-generation decision support in AMD management, with potential for expansion to larger, device-diverse cohorts and other complex retinal diseases.}, }
@article {pmid41307029, year = {2024}, author = {Araki, T and Shimazawa, M and Nakamura, S and Otsu, W and Numata, Y and Sakata, M and Kabayama, K and Tsusaki, H and Hara, H}, title = {Macular white dot lesions with hyperreflective optical coherence tomography findings in cynomolgus and rhesus monkeys.}, journal = {Molecular vision}, volume = {30}, number = {}, pages = {219-233}, pmid = {41307029}, issn = {1090-0535}, mesh = {Animals ; *Tomography, Optical Coherence ; Macaca mulatta ; Female ; Macaca fascicularis ; Electroretinography ; *Macula Lutea/pathology/ultrastructure/physiopathology ; Retinal Pigment Epithelium/pathology/ultrastructure ; *Macular Degeneration/pathology/physiopathology ; }, abstract = {PURPOSE: We screened 28 female cynomolgus monkeys (CMs) and 25 female rhesus monkeys (RMs) for white dots (WDs) in the macula and detected several animals with WDs in colonies at the Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories (SNBL) facility. To determine the functional and morphological characteristics of WDs, we conducted ophthalmological and pathological examinations on these animals.<br><br>METHODS: Fundus examination, optical coherence tomography (OCT), and focal electroretinogram (f-ERG) were conducted for all animals. Histopathology and transmission electron microscopy were conducted for one representative adult CM with WDs.<br><br>RESULTS: In both CMs and RMs, individual differences were observed in the number of WDs in the macula (ranging from approximately 10 to 500 per eye). Hyperreflective granules were observed between the ellipsoid zone (EZ) and the retinal pigment epithelium (RPE) in OCT. Both CMs and RMs exhibited a significant increase in the thicknesses of the RPE and choroid in WD animals compared to their normal counterparts. In the f-ERG, significant decreases and/or tendencies toward decreases in amplitudes and increases in implicit times of both a- and b-waves were observed in animals with WDs. In pathology, diffuse vacuolization of the RPE cells with tiny granules was observed in the macula.<br><br>CONCLUSIONS: Based on the results of OCT and pathological examinations, it was suggested that animals with WDs can develop macular degeneration in the future. To assess their suitability as a model for precursor lesions of age-related macular degeneration, it is imperative to continue monitoring the animals used in the present study until they reach a more advanced age of approximately another 5-10 years.}, }
@article {pmid41307906, year = {2025}, author = {Liem, Y and Vemula, V and Lim, CC and Chong, CCY and Choo, JCJ and Cheng, CY and Sabanayagam, C}, title = {Impact of chronic kidney disease on the incidence of visual impairment and age-related eye diseases in a multi-ethnic Asian population.}, journal = {Journal of global health}, volume = {15}, number = {}, pages = {04316}, pmid = {41307906}, issn = {2047-2986}, mesh = {Humans ; Middle Aged ; Aged ; Male ; Female ; *Renal Insufficiency, Chronic/complications/ethnology/epidemiology ; Singapore/epidemiology ; Incidence ; Adult ; Aged, 80 and over ; *Vision Disorders/epidemiology/ethnology ; *Eye Diseases/epidemiology/ethnology ; *Asian People/statistics &amp; numerical data ; Risk Factors ; Cataract/epidemiology ; }, abstract = {BACKGROUND: The kidney and eye share common metabolic and vascular risk factors, and chronic kidney disease (CKD) has been associated with the prevalence of visual impairment (VI). In this study, we examined the association of CKD with incident VI and major age-related eye diseases, including cataract, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, in a multi-ethnic Asian population.<br><br>METHODS: We analysed data from 6486 Chinese, Malay, and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases study at baseline (2004-11) and six-year follow-up visit (2011-17) and were free of VI and the respective eye diseases at baseline. We defined CKD (n&#x2009;=&#x2009;564; 8.7%) as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m[2], and categorised the severity of CKD into stages G1-G5. Eye examinations included refraction, slit-lamp examinations, and retinal imaging. We defined incident VI as best-corrected visual acuity <20/40 in the better eye. Eye diseases examined included cataract, AMD, retinopathy, including DR in those with diabetes and glaucoma. We examined associations between CKD, VI, and eye diseases using multivariable logistic regression models adjusted for age, gender, ethnicity, diabetes, and hypertension status, presenting the results as odds ratios (ORs) and 95% confidence intervals (CIs).<br><br>RESULTS: CKD participants had a higher incidence of any VI (14.3% vs. 3.3%; P&#x2009;<&#x2009;0.001), any AMD (8.0% vs. 5.4%; P&#x2009;<&#x2009;0.001), and cataracts (65.1% vs. 40.8%; P&#x2009;<&#x2009;0.001) than non-CKD participants. VI incidence increased with CKD severity in G1-G2 (3.3%), G3a (13.5%), and G3b-G5 (16.3%) (P&#x2009;<&#x2009;0.001). In multivariable models, CKD was associated with incident VI (OR&#x2009;=&#x2009;1.47; 95% CI&#x2009;=&#x2009;1.03-2.10) and moderate/worse DR (OR&#x2009;=&#x2009;2.62; 95% CI&#x2009;=&#x2009;1.35-5.10).<br><br>CONCLUSIONS: Our results suggest that the presence of CKD increases the risk and severity of VI and eye diseases in Asian adults. Our findings highlight the importance of regular eye exams for CKD patients to reduce the risk of VI.}, }
@article {pmid41308839, year = {2026}, author = {Wang, W and Wazny, VK and Mahadzir, MDA and Maier, AB}, title = {Multivitamin and mineral use: A rapid review of meta-analyses on health outcomes.}, journal = {Ageing research reviews}, volume = {114}, number = {}, pages = {102965}, doi = {10.1016/j.arr.2025.102965}, pmid = {41308839}, issn = {1872-9649}, mesh = {Female ; Humans ; Pregnancy ; Cognition/drug effects ; COVID-19 ; *Dietary Supplements ; *Minerals/administration &amp; dosage/therapeutic use ; *Vitamins/administration &amp; dosage/therapeutic use ; Meta-Analysis as Topic ; }, abstract = {Multivitamin and mineral (MVM) supplements are among the most widely used dietary supplements globally, however, their role in promoting healthspan and longevity remains unclear. This review evaluated comprehensive findings from meta-analyses to clarify their health effects. A rapid review of MEDLINE and EMBASE identified 19 eligible meta-analyses published from 2000 to 2025, encompassing 5535,426 participants, including over 333,943 pregnancies and 904,947 children exposed to maternal MVM supplementation. Randomized controlled trials indicated that MVM use improved global cognition, episodic memory, and immediate recall in older or cognitively intact adults, reduced psychological symptoms in healthy individuals, and lowered systolic blood pressure in at-risk populations. However, no benefits were found for all-cause mortality, COVID-19 outcomes, visual acuity, or multiple cognitive domains, and a higher risk of age-related macular degeneration progression was reported. Observational studies found associations between MVM use and a reduced risk of colorectal cancer, coronary heart disease, cataracts, and fragility hip fractures, but not breast or prostate cancer, stroke, or overall mortality. During pregnancy, MVM supplementation was linked to reduced risks of small-for-gestational-age births and pediatric cancers, but not to preterm birth, stillbirth, or low birth weight. Overall, the findings revealed a lack of consistency in the definition of MVM supplementation, and substantial variability in MVM effectiveness depending on population, age, and health status. These results highlighted the importance of shifting from generalized supplementation approaches to more targeted, personalized nutritional strategies to support healthspan and longevity.}, }
@article {pmid41308856, year = {2026}, author = {Chuang, CC and Chen, YS and Lu, WY and Su, SC and Liao, TY and Yang, SF and Hsieh, YH}, title = {Protective role of Oxyresveratrol against NaIO3-induced oxidative stress in RPE cells via targeting NRF2-mediated ferroptosis in vitro and in vivo.}, journal = {European journal of pharmacology}, volume = {1010}, number = {}, pages = {178402}, doi = {10.1016/j.ejphar.2025.178402}, pmid = {41308856}, issn = {1879-0712}, mesh = {*Oxidative Stress/drug effects ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; Humans ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism/cytology ; *Ferroptosis/drug effects ; *Iodates/toxicity ; Mice ; Cell Line ; *Stilbenes/pharmacology/therapeutic use ; *Macular Degeneration/pathology/chemically induced/metabolism/drug therapy ; Mice, Inbred C57BL ; *Plant Extracts/pharmacology ; Male ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Disease Models, Animal ; Kelch-Like ECH-Associated Protein 1/metabolism ; Apoptosis/drug effects ; }, abstract = {Age-related macular degeneration (AMD) is a chronic retinal disorder that occurs when oxidative damages are gradually accumulated to the center of retina. Oxyresveratrol (OxyR), a naturally occurring stilbene found in many plants, has been reported to exhibit anti-inflammatory and anti-oxidative activities. To fill this gap, we explored the effect of OxyR on retinal pigment epithelial cells in response to oxidative stress and on a mouse model of AMD and further dissected the molecular mechanism underlying OxyR's actions. In this study, we demonstrated that OxyR efficiently impeded both apoptosis and ferroptosis of a human ARPE-19 cells induced by sodium iodate (NaIO3). Such protective effect of OxyR on NaIO3-induced ARPE-19 cells was accompanied with altered expression levels of NRF2, KEAP1, and several ferroptosis-related proteins. Moreover, OxyR treatment, coupled with silencing of NRF2, ferroptosis inhibitor (ferrostatin-1) or depletion of ROS, enhanced the protection of ARPE-19 cells from NaIO3-induced damages. Consistently, oral gavage of OxyR restored the reduction of retinal thickness and attenuated the upregulation of NRF2 in retinal pigment epithelium layers of NaIO3-treated mice. These results demonstrated that OxyR mitigates NaIO3-induced ARPE19 cell death via targeting NRF2-ferroptosis signaling. Our findings provided potential avenues for the use of OxyR in controlling AMD.}, }
@article {pmid41308857, year = {2026}, author = {Cen, S and Liu, S and Zhao, M and Tang, L}, title = {Comparative efficacy and safety of faricimab, aflibercept, conbercept, and ranibizumab for neovascular age-related macular degeneration: A systematic review and network meta-analysis.}, journal = {European journal of pharmacology}, volume = {1010}, number = {}, pages = {178406}, doi = {10.1016/j.ejphar.2025.178406}, pmid = {41308857}, issn = {1879-0712}, mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Macular Degeneration/drug therapy ; Randomized Controlled Trials as Topic ; *Ranibizumab/therapeutic use/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/adverse effects ; Treatment Outcome ; Visual Acuity/drug effects ; Antibodies, Bispecific ; }, abstract = {BACKGROUND: Existing meta-analyses of anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration focus mainly on ranibizumab and aflibercept, with limited data on newer agents (faricimab, conbercept). This network meta-analysis (NMA) comprehensively compares all four key agents.<br><br>METHODS: We systematically searched multiple databases for randomized controlled trials. Bayesian random-effects network meta-analysis was conducted, with evidence certainty assessed using CINeMA (Confidence in Network Meta-Analysis).<br><br>RESULTS: Thirty-nine randomized controlled trials involving 11,548 participants were included. For best-corrected visual acuity, agents showed comparable efficacy (high to moderate evidence); differences were neither statistically nor clinically significant. Choroidal neovascularization regression showed no important differences (mostly low certainty evidence). For retinal thickness, superior reductions versus ranibizumab 0.5&#xa0;mg were observed with aflibercept 2&#xa0;mg (MD: -14.27, 95&#xa0;% CrI: -27.25, -1.75; high certainty), aflibercept 8&#xa0;mg (MD: -32.43, 95&#xa0;% CrI: -57.40, -7.75; high certainty), and conbercept 0.5&#xa0;mg (MD: -10.26, 95&#xa0;% CrI: -19.43, -0.98; moderate certainty). Faricimab required significantly fewer injections (high certainty evidence). Aflibercept 2&#xa0;mg showed better ocular safety than faricimab 6&#xa0;mg (OR: 0.58, 95&#xa0;% CrI: 0.37, 0.90) and ranibizumab 0.5&#xa0;mg (OR: 0.72, 95&#xa0;% CrI: 0.53, 0.97; high certainty).<br><br>CONCLUSION: Aflibercept and conbercept may be preferred when anatomical outcomes are prioritized, whereas faricimab's extended dosing interval could benefit treatment-adherent populations. The superior safety profile of aflibercept 2&#xa0;mg warrants consideration in risk averse patients. These differential effects support personalized therapeutic decision-making.}, }
@article {pmid41308944, year = {2026}, author = {Wang, L and Wang, Z}, title = {Therapeutic targeting of lncRNAs in age-related ocular disease.}, journal = {Experimental eye research}, volume = {263}, number = {}, pages = {110771}, doi = {10.1016/j.exer.2025.110771}, pmid = {41308944}, issn = {1096-0007}, mesh = {Humans ; *RNA, Long Noncoding/genetics ; *Aging/genetics ; *Eye Diseases/genetics/therapy ; *Macular Degeneration/genetics ; *Gene Expression Regulation/physiology ; Animals ; Oxidative Stress ; *Glaucoma/genetics ; *Cataract/genetics ; }, abstract = {Age-related ocular diseases, including age-related macular degeneration, cataract, and glaucoma, are significant causes of visual loss and blindness worldwide. Long non-coding RNAs (lncRNAs) participate in gene regulation, epigenetic control, and cellular homeostasis, and increasing evidence implicates them in age-related ocular disorders by modulating oxidative stress, inflammation, angiogenesis, apoptosis, and extracellular matrix remodeling within ocular tissues. LncRNAs are linked to retinal degeneration, lens opacity, and optic nerve damage, supporting their promise as biomarkers and targets for treatment approaches. This review summarizes current understanding of lncRNA-related processes in age-related ocular disease and emphasizes their potential roles in diagnosis, prognosis, and treatment. An integrated view of lncRNA function in aging ocular tissues may guide precision medicine strategies to prevent or slow vision loss in older individuals.}, }
@article {pmid41310732, year = {2025}, author = {Yoo, HS and Chakravarthy, H and Xi, J and Cui, J and Ai, Z and Hosseini, A and Song, J and Tan, N and Ma, N and Zhou, C and Li, B and Bell, R and Haegert, A and Le Bihan, S and Ju, MJ and Granville, DJ and Matsubara, JA}, title = {Granzyme B contributes to subretinal fibrosis in neovascular age-related macular degeneration by modulating inflammation and epithelial-mesenchymal transition.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {1}, pmid = {41310732}, issn = {1742-2094}, abstract = {BACKGROUND: More than half of patients with neovascular age-related macular degeneration (nAMD) develop subretinal fibrosis, regardless of anti-vascular endothelial growth factor (VEGF) therapy. No treatment exists for subretinal fibrosis, as its pathophysiology remains elusive. Granzyme B (GzmB) is a serine protease elevated in human eyes with nAMD and contributes to choroidal neovascularization (CNV). Although GzmB is involved in dermal and cardiac fibrosis, its role in subretinal fibrosis has yet to be elucidated.<br><br>METHODS: Using the two-stage laser-induced mouse model of subretinal fibrosis, fibrotic lesions were induced in younger (3&#x2013;6 months old) and older (7&#x2013;14 months old) C57BL/6J and GzmB deficient mice. Seven days after the second laser, in vivo imaging of fibrotic lesions was performed using custom-built polarization diversity-optical coherence tomography (PD-OCT) system. Eyes were collected and used for either retina wholemounts or cross-sections. Wholemounts were immunostained to assess pathological features of fibrosis and determine the size of fibrotic lesions and mast cell counts within fibrotic lesions. Cross-sections were processed to quantify the levels of GzmB substrates within fibrotic lesions, namely pro-fibrotic thrombospondin-1 (TSP-1) and anti-fibrotic decorin (DCN), the extent of macrophage-to-myofibroblast transition (MMT), activation of astrocytes/M&#xfc;ller cells and finally photoreceptor cell death. ARPE-19 wound healing assay was performed to study the direct role of GzmB in RPE wound healing in vitro. GzmB-mediated transcriptional changes in ARPE-19 were determined by performing bulk RNA sequencing. Immunocytochemistry was performed to assess epithelial-mesenchymal transition (EMT).<br><br>RESULTS: GzmB deficiency resulted in smaller fibrotic lesions in older mice and was associated with decreased levels of TSP-1 and increased levels of DCN within fibrotic lesions. It also led to increased MMT but reduced mast cell counts within fibrotic lesions, which was correlated with reduced photoreceptor cell death. In ARPE-19, exogenous application of GzmB impaired wound closure and promoted partial EMT by selectively modulating genes involved in transforming growth factor-&#x3b2; signaling, EMT, inflammation, angiogenesis and cell-cell interaction.<br><br>CONCLUSIONS: Our study reveals that extracellular GzmB is a key contributor to subretinal fibrosis in nAMD, modulating inflammation, EMT and photoreceptor degeneration. These findings suggest GzmB as a promising therapeutic target for mitigating the development of subretinal fibrosis in nAMD.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-025-03619-9.}, }
@article {pmid41311657, year = {2025}, author = {Hanson, J and Yamamoto, M and Tsui, E and Tsui, I}, title = {Efficacy of faricimab for recalcitrant multifactorial cystoid macular edema.}, journal = {American journal of ophthalmology case reports}, volume = {40}, number = {}, pages = {102475}, pmid = {41311657}, issn = {2451-9936}, abstract = {PURPOSE: More information is emerging on faricimab-svoa (faricimab) used for etiologies beyond wet age-related macular degeneration (AMD) and diabetic macular edema (DME), including ongoing trials for use in macular edema following retinal vein occlusion (RVO). This manuscript describes a case of recalcitrant postoperative cystoid macular edema (CME), confounded by a history of branch retinal vein occlusion (BRVO), in which faricimab resulted in resolution of CME after incomplete response to topical anti-inflammation drops, intravitreal aflibercept and bevacizumab, a corticosteroid intravitreal implant, grid laser therapy, and suprachoroidal triamcinolone acetonide (SCS-TA).<br><br>OBSERVATIONS: An 83-year-old pseudophakic male with history of steroid-induced ocular hypertension and BRVO with mild preoperative CME and visual acuity (VA) of 20/160 presented with significant worsening CME following a pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peel for an epiretinal membrane (ERM) in the right eye. CME persisted for eight years despite treatment with topical anti-inflammatories, anti-VEGF injections, a dexamethasone intravitreal implant, grid laser therapy, and a SCS-TA injection. However, after 3 faricimab injections, CME resolved with a CST change from 748 &#x3bc;m to 339 &#x3bc;m and VA improved from 20/50 to 20/40.<br><br>CONCLUSIONS AND IMPORTANCE: This case demonstrates the effectiveness of faricimab in treatment of CME resistant to other therapies and the importance of continued attempts at using new agents for chronic, recurrent CME. The unique benefits of new agents like faricimab, with both VEGF and Ang-2 inhibition, may be particularly helpful in mixed or inflammatory CME when other proven therapies have failed.}, }
@article {pmid41312453, year = {2025}, author = {Wei, L and Yan, W and Zhang, K and Gao, F and Li, Z and Pan, R and Zhang, Z and Wang, X}, title = {Allogeneic whole-eye transplantation: advancements, challenges, and future directions in vision restoration.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1691259}, pmid = {41312453}, issn = {2296-858X}, abstract = {Vision loss remains a significant global health burden, primarily driven by irreversible ocular conditions such as age-related macular degeneration (AMD), glaucoma, severe ocular trauma, and intraocular malignancies. Despite advances in retinal prosthetics and stem cell-based therapies, current treatment options are still limited in their ability to fully restore visual function. Allogeneic whole-eye transplantation (WET) has recently gained attention as a novel and potentially transformative strategy for vision restoration. This review synthesizes recent progress in the field, including advancements in microsurgical techniques, immunosuppressive protocols, and neural integration strategies, drawing on evidence from both preclinical animal models and emerging human studies. Key components, including optic nerve (ON) regeneration, vascular anastomosis, immune tolerance, and donor-recipient matching, are critically examined. Furthermore, we address ongoing barriers, including graft viability, chronic rejection, central visual pathway rewiring, and ethical considerations surrounding the procurement of donor eyes. While substantial milestones have been achieved, particularly in experimental settings, clinical translation remains in its early stages. This review highlights current limitations and proposes future directions for multidisciplinary research aimed at overcoming these challenges and advancing WET toward clinical reality.}, }
@article {pmid41312773, year = {2025}, author = {Ju, X and Ramke, J and Turnbull, PR}, title = {Emerging research on non-neovascular age-related macular degeneration treatments.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/08164622.2025.2579872}, pmid = {41312773}, issn = {1444-0938}, abstract = {Age-related macular degeneration (AMD) is a common condition that causes vision impairment in the elderly, significantly impacting their physical and psychosocial well-being. Historically, treatment options to slow or prevent atrophic AMD progression have been limited but are recently increasing in number. This scoping review aims to provide an overview of the research (both preclinical and clinical) on non-neovascular AMD (including early, intermediate, and geographic atrophy) treatments published in the past decade. Our study protocol was prospectively registered on the Open Science Framework.Searches were conducted on MEDLINE, Embase, ProQuest, and CINAHL for studies investigating treatments for atrophic AMD (including early, intermediate, and geographic atrophy stages) published between 1 January 2014 and 14 July 2024, the search date. Data screening, full-text review, and extraction were independently performed by two researchers. Study characteristics and outcomes were summarised, and the results were synthesised narratively. The search identified 1,211 studies, of which 132 were included in this review. Studies were most often conducted in the United States (n = 92, 68.7%) or Europe (n = 25, 18.5%) and most frequently investigated antioxidant or anti-inflammatory treatments (n = 30, 22.7%) or complement pathway inhibitors (n = 25, 18.9%) as potential therapies. Over three quarters (n = 101, 76.5%) of the included studies reported positive outcomes. Across the decade, the number of studies published increased at an annual rate of 24.0%.This review highlights the growing body of research on atrophic AMD treatments over the past decade, with antioxidant and anti-inflammatory treatments emerging as prominent, promising avenues. However, more phase III human clinical trials are needed to ensure that future therapies effectively serve the global AMD population.}, }
@article {pmid41313467, year = {2025}, author = {Cheng, X and Lohmann, T and Johnen, S and Walter, P and Baumgarten, S}, title = {Relationship between monocyte-to-lymphocyte ratio and age-related macular degeneration: Findings from a national cross-sectional study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251402991}, doi = {10.1177/11206721251402991}, pmid = {41313467}, issn = {1724-6016}, abstract = {BackgroundRecent advances have revealed the important role of the immune system in the progression of age-related macular degeneration (AMD). Monocyte-to-lymphocyte ratio (MLR) is a combined marker reflecting inflammation status. However, research on the correlation between MLR and AMD is limited.MethodsIn this cross-sectional analysis, weighted multivariable logistic regression, multinomial logistic regression, subgroup analysis, smoothed curve fitting and threshold effect analysis were used to investigate the relationship between MLR and AMD based on data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).ResultsThis study included data of 4,655 participants. The proportions of no AMD, early AMD and late AMD were 92.27%, 6.79% and 0.95%, respectively. After adjusting for covariates, weighted multivariable logistic regression analysis revealed that MLR was positively associated with AMD (OR = 3.22, 95%CI 1.32-7.82). Threshold effect analysis revealed that higher MLR associated with prevalence of AMD after MLR was greater than 0.37 (OR = 8.93, 95%CI 2.53-31.60). The diagnostic performance of MLR > 0.37 for AMD was assessed using ROC curve analysis. In addition, MLR was proven to have a significant positive correlation with early AMD (OR = 1.20, 95%CI 1.19-1.21) and late AMD (OR = 9.21, 95%CI 9.10-9.31) through weighted multinomial logistic regression.ConclusionsOur study demonstrates that an elevated MLR is independently associated with the prevalence of AMD.}, }
@article {pmid41314477, year = {2026}, author = {Poirot, M and Buñay, J and Ayadi, S and Silvente-Poirot, S and de Medina, P}, title = {Liver X receptors and the hallmarks of aging: From molecular mechanisms to therapeutic opportunities.}, journal = {Ageing research reviews}, volume = {114}, number = {}, pages = {102967}, doi = {10.1016/j.arr.2025.102967}, pmid = {41314477}, issn = {1872-9649}, mesh = {Humans ; *Liver X Receptors/metabolism/agonists ; *Aging/metabolism ; Animals ; Signal Transduction ; }, abstract = {Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy, mitochondrial function, epigenetics, senescence, stem cell dynamics, and intercellular communication. This positions LXRs at the crossroads of multiple hallmarks of aging. This review synthesizes current knowledge on endogenous and synthetic LXR ligands, their transcriptional mechanisms, and their effects on the aforementioned hallmarks and age-related pathophysiology. The clinical development of pan-LXR agonists for atherosclerosis has been hindered by side effects, notably hepatic steatosis. Emerging strategies, including LXRβ-selective ligands, selective LXR modulators (SLiMs), and biased agonists such as dendrogenin A, offer ways to separate the protective vascular, metabolic, and neuroprotective effects from adverse outcomes. Additionally, we explore how LXR signaling intersects with the hallmarks of aging and how it can be leveraged to intervene in atherosclerosis, diabetes, cancer, osteoporosis, age-related macular degeneration, and neurodegenerative diseases. Positioning LXRs within the geroscience framework suggests that LXRs may serve as pharmacological hubs to delay aging and its comorbidities. Future work should prioritize isoform- and tissue-selective approaches, metabolite-inspired ligand design, and integration with the hallmarks of aging to unlock the full therapeutic potential of LXRs.}, }
@article {pmid41316066, year = {2025}, author = {Pei, Y and Meng, J and He, W and Zhang, K and Guo, D and Lu, Y and Zhu, X}, title = {Unique liver function in high myopia: associations with myopic macular degeneration.}, journal = {BMC ophthalmology}, volume = {25}, number = {1}, pages = {677}, pmid = {41316066}, issn = {1471-2415}, support = {82301188//National Natural Science Foundation of China/ ; 82122017//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; Middle Aged ; *Myopia, Degenerative/physiopathology/blood/complications ; *Macular Degeneration/blood/physiopathology/etiology ; Adult ; Liver Function Tests ; *Liver/physiopathology ; ROC Curve ; gamma-Glutamyltransferase/blood ; Lipids/blood ; }, abstract = {PURPOSE: To investigate liver function and lipid indexes in patients with high myopia and their association with myopic macular degeneration (MMD).<br><br>METHODS: This cross-sectional comparative study included 995 emmetropic patients and 805 highly myopic patients. Serum levels of liver function and lipid indexes were measured using a Roche C702 biochemical analyzer. Ultra-widefield fundus photographs of eyes were classified according to the International META-PM Classification: Category 0: No myopic retinal degeneration, Category 1: tessellated fundus, Category 2: diffuse choroidal retinal atrophy, Category 3: patchy choroidal retinal atrophy, Category 4: macular atrophy. A machine learning model based on liver function indexes was employed to predict the presence of MMD in patients with high myopia.<br><br>RESULTS: Serum levels of albumin (Alb), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and triglyceride (TG) were significantly lower, whereas high-density lipoprotein cholesterol (HDL) and apolipoprotein-A (Apo-A) were higher in patients with high myopia than those in emmetropic patients (all P&#x2009;<&#x2009;0.05). Significant differences in serum ALT and GGT were found among MMD categories (both P&#x2009;<&#x2009;0.05). Multivariate logistic regression showed that MMD4 was associated with lower serum GGT than MMD1 (P&#x2009;<&#x2009;0.05). The decision tree model to predict MMD achieved an area under the curve (AUC) of 0.735 using serum GGT (sensitivity&#x2009;=&#x2009;53.12%; specificity&#x2009;=&#x2009;82.09%; P&#x2009;<&#x2009;0.001). When using multiple liver function indexes, the AUC of the model reached 0.803 (sensitivity&#x2009;=&#x2009;73.4%; specificity&#x2009;=&#x2009;76.1%; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: We identified close associations between liver function and MMD, suggesting serum GGT serve as a potential diagnostic indicator for MMD among highly myopic patients.}, }
@article {pmid41316395, year = {2025}, author = {Dundar, A and Cetik Yildiz, S}, title = {Kynurenine pathway metabolites as potential biomarkers in age-related macular degeneration: an ELISA-based prospective study.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {131}, pmid = {41316395}, issn = {2056-9920}, abstract = {OBJECTIVES: Age-related macular degeneration (AMD), in which oxidative stress, inflammation and metabolic imbalances play a role in its pathogenesis, is one of the leading causes of irreversible vision loss. The kynurenine (KYN) pathway, one of the principal routes of tryptophan (TRP) metabolism, constitutes an important mechanism in retinal neurodegeneration. Based on this information, our study aimed to compare the serum TRP, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA) and, quinolinic acid (QA) levels of AMD patients and to investigate the diagnostic values of these biomarkers.<br><br>METHODS: Serum samples were collected from AMD patients and control groups. TRP, KYN, KYNA, 3HK, 3HAA, and QA levels were measured using a commercial ELISA method. KYN pathway activity, KYN/TRP and, KYNA/3HK ratios were also assessed. Mann-Whitney U test, ROC analysis, Spearman correlation were applied for statistical comparisons.<br><br>RESULTS: According to our results, 3HK was significantly higher in the AMD group, while TRP, KYN, QA, and KYNA/3HK ratio were higher in the control. ROC analysis revealed 3HK to be the strongest discriminatory marker. The KYNA/3HK ratio also provided significant diagnostic value. Correlation analysis revealed strong negative correlations between 3HK and KYN, QA, and especially KYNA/3HK. Conversely, strong positive correlations were found between KYN and KYNA/3HK, and between TRP, KYN, QA, and KYNA.<br><br>CONCLUSION: KYN pathway metabolites exhibit significant alterations in patients with AMD. 3HK levels and the reduction of the KYNA/3HK ratio suggest a disruption of the neurotoxic-neuroprotective balance and imply that KYN pathway dysfunction may play a role in the pathogenesis of AMD. Among the biomarkers examined, 3HK displayed the highest diagnostic performance, while the KYNA/3HK ratio emerged as an additional biological indicator. These findings indicate that 3HK and the KYNA/3HK ratio may serve as potential biomarker candidates for the early diagnosis and monitoring of AMD.}, }
@article {pmid41316464, year = {2025}, author = {Zhang, Z and Yang, H and Tan, L and Li, Y and Ren, X and Li, X}, title = {Associations between the monocyte‑lymphocyte ratio and age‑related macular degeneration among US adults: evidence from NHANES 2005-2008.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {2}, pmid = {41316464}, issn = {2056-9920}, support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; }, abstract = {BACKGROUND: Previous studies have established an association between age-related macular degeneration (AMD) and chronic systemic inflammation. However, the relationship between AMD and the monocyte-to-lymphocyte ratio (MLR), a novel inflammatory biomarker, remains unclear. In this study, we aimed to investigate the association between MLR and AMD using data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).<br><br>METHODS: Data from three NHANES cycles (2005-2008) were analyzed to preliminarily assess the association between MLR and AMD, excluding participants with incomplete data. We utilized weighted logistic regression models, restricted cubic spline functions (RCS) and constructed receiver operating characteristic (ROC) curves to evaluate the association between MLR and AMD.<br><br>RESULTS: A total of 4,894 participants were deemed eligible for our analysis, with 379 individuals diagnosed with AMD. The Monocyte to Lymphocyte Ratio (MLR) was significantly elevated in the AMD group compared to the non-AMD group. After adjusting for potential confounding factors, we found that elevated MLR levels were significantly associated with an increased risk of AMD, with an OR of 2.56, 95% CI: (1.17,5.58), P&#x2009;=&#x2009;0.022. The restricted cubic spline (RCS) analysis revealed a significant nonlinear relationship between MLR and AMD, with an inflection point at 0.26 (nonlinear P&#x2009;<&#x2009;0.05). Furthermore, the receiver operating characteristic (ROC) curve analysis demonstrated that MLR exhibited acceptable discrimination for AMD.<br><br>CONCLUSIONS: Elevated MLR is associated with an increased risk of AMD, suggesting that MLR may serve as a simple and effective clinical biomarker of AMD.}, }
@article {pmid41317302, year = {2026}, author = {Hashimoto, Y and Arai, Y and Takahashi, H and Tampo, H and Kondo, R and Takahashi, H and Yoshida, H and Takahashi, R and Inoda, S and Kaburaki, T and Yanagi, Y}, title = {Increased aqueous flare after intravitreal brolucizumab injections compared to aflibercept in neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {701-709}, pmid = {41317302}, issn = {1435-702X}, support = {21K09751//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Aqueous Humor/diagnostic imaging/metabolism ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Recombinant Fusion Proteins/administration &amp; dosage ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Tomography, Optical Coherence ; *Visual Acuity ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Fluorescein Angiography ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {PURPOSE: To evaluate aqueous flare values in patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor (VEGF) therapy, including brolucizumab.<br><br>METHODS: This retrospective study included 101 patients treated with intravitreal anti-VEGF injections at Jichi Medical University Hospital from March to July 2021. Aqueous flare values were measured in both affected and fellow eyes. The number of treated eyes was 28 for aflibercept and 73 for brolucizumab. Flare values were compared between affected and fellow eyes, and associations with age, gender, drug type, number of injections, disease duration, and time since last injection were analyzed. We also measured flare values from pre-filled syringes.<br><br>RESULTS: In unilateral treatment cases, brolucizumab-treated eyes had significantly higher aqueous flare values than fellow eyes (6.7 vs. 6.2 photon counts/ms, P&#x2009;=&#x2009;0.0032), while no significant difference was observed with aflibercept (6.9 vs. 6.7 pc/ms, P&#x2009;=&#x2009;0.55). Flare values increased significantly with age in the brolucizumab group (P&#x2009;=&#x2009;0.0076) but not in the aflibercept group (P&#x2009;=&#x2009;0.56). The number of brolucizumab injections did not alter flare values. Multivariate analysis identified age as the only significant factor associated with increased aqueous flare. The mean (standard deviation) flare values measured from pre-filled syringes were 430 (15.6) pc/ms for Beovu[&#xae;] (brolucizumab) and 161.8 (31) pc/ms for Eylea[&#xae;] (aflibercept).<br><br>CONCLUSION: In nAMD, aqueous flare values were higher in brolucizumab-treated eyes and increased with age but were unaffected by the number of injections. Different flare values of each drug might affect the aqueous flare values within hours after injection.}, }
@article {pmid41317829, year = {2026}, author = {Kerwin, AF and Perlman, EM and Browning, DJ}, title = {Atrophy Advisor: A Clinical Tool for Dry Macular Degeneration With Geographic Atrophy.}, journal = {American journal of ophthalmology}, volume = {283}, number = {}, pages = {81-90}, doi = {10.1016/j.ajo.2025.11.037}, pmid = {41317829}, issn = {1879-1891}, mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy/physiopathology ; Female ; Retrospective Studies ; Male ; Aged ; Visual Acuity/physiology ; Aged, 80 and over ; Disease Progression ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/drug therapy ; Follow-Up Studies ; Intravitreal Injections ; }, abstract = {OBJECTIVE: To develop and evaluate Atrophy Advisor, a clinical decision tool integrating geographic atrophy (GA) progression and personalized lifespan estimates to help clinicians considering complement factor inhibitor injections for dry macular degeneration with GA.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: Fifty consecutive patients with GA secondary to nonexudative age-related macular degeneration, seen at Wake Forest-affiliated retina clinics from May 2013 to June 2025.<br><br>METHODS: Fundus images at two or more time points were analyzed using ImageJ to measure the distance from the fovea to the nearest GA edge. Pixel-to-micron conversion was made using an assumed vertical disk diameter of 1800 microns. Demographics, comorbidities, and corrected visual acuities were extracted from records. Lifespan estimates were calculated using University of Connecticut and Social Security Administration algorithms and compared to observed outcomes.<br><br>MAIN OUTCOME MEASURES: GA edge-to-fovea distance, GA progression rate, corrected visual acuity, and predicted vs observed lifespan.<br><br>RESULTS: Median age was 78 years (IQR: 74-82); 64% were female. Baseline median GA-to-fovea distance was 792 &#xb5;m (IQR: 508-1213 &#xb5;m), declining to 395 &#xb5;m (IQR: 194-702 &#xb5;m) at last follow-up. Median GA progression was 122 &#xb5;m/y (range 2-626 &#xb5;m/y), with a direct relationship between initial distance and progression rate (P = .006, R&#xb2; = 0.146). Lifespan calculators (University of Connecticut and Atrophy Advisor) yielded median estimates of 11.9 and 11.0 years, respectively, influencing treatment guidance in 4% of cases.<br><br>CONCLUSIONS: Atrophy Advisor is feasible for combining GA progression kinetics and lifespan estimates to inform treatment decisions. Variability in progression rates and lifespan predictions highlights the need for personalized approaches. Limitations include measurement variability and retrospective design; future studies should validate the tool in larger, prospective cohorts.}, }
@article {pmid41318054, year = {2026}, author = {Zhang, Z and Shan, X and Liang, F and Fang, L}, title = {Integrative single-cell transcriptomic and experimental analyses unveil Qihuang granule's protection against retinal photodamage via PI3K/AKT/mTOR-mediated autophagy.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {190}, number = {}, pages = {106881}, doi = {10.1016/j.biocel.2025.106881}, pmid = {41318054}, issn = {1878-5875}, mesh = {Animals ; *TOR Serine-Threonine Kinases/metabolism/genetics ; *Autophagy/drug effects/radiation effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Rats ; *Phosphatidylinositol 3-Kinases/metabolism/genetics ; Humans ; Signal Transduction/drug effects ; Rats, Sprague-Dawley ; *Retina/drug effects/metabolism/pathology/radiation effects ; Single-Cell Analysis ; Light/adverse effects ; Male ; *Transcriptome/drug effects ; }, abstract = {Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.}, }
@article {pmid41321555, year = {2025}, author = {Gregori, G and Mangoni, L and Muzi, A and Mariotti, C and Lupidi, M}, title = {Neovascular Maculopathy after Laser Retinal Rejuvenation Therapy in a Young Myopic Patient: A Case Report.}, journal = {Case reports in ophthalmology}, volume = {16}, number = {1}, pages = {841-846}, pmid = {41321555}, issn = {1663-2699}, abstract = {INTRODUCTION: Laser photobiomodulation, including retinal rejuvenation therapy (2RT), is a system which selectively targets the retinal pigment epithelium by a concise 3 ns pulse duration. The advantage of this laser system over the traditional thermal laser is that the pulsed, very short duration laser effects can be titrated as spatially confined photodisruptors without resultant conductive thermal spread and therefore collateral damage. It has been investigated primarily in age-related macular degeneration (AMD), particularly in decreasing drusen and slowing the rate of AMD progression. In this case, we have described a case of neovascular maculopathy occurring shortly after 2RT in a young myopic patient.<br><br>CASE PRESENTATION: We report the case of a 28-year-old male who presented with unilateral visual impairment following laser 2RT. Two months before, he was subjected to photorefractive keratectomy for moderate myopia (-3.00 D). The baseline optical coherence tomography (OCT) imaging revealed "sharp-peaked" pigment epithelium detachment (PED) in the subfoveal area. Fluorescein angiography indicated a focal area of irregular foveal hyperfluorescence. Observation was advised, and laser 2RT was performed. However, 1 month later, the patient developed a neovascular lesion in the same eye, confirmed by OCT-angiography, requiring urgent intravitreal anti-VEGF therapy.<br><br>CONCLUSIONS: In summary, this case illustrates a progressive maculopathy culminating in choroidal neovascularization triggered by laser 2RT in a young myopic patient.}, }
@article {pmid41323371, year = {2025}, author = {Iwama, Y and Masuda, T and Maeyama, A and Eade, KT and Friedlander, M and Nishida, K and Mandai, M}, title = {Cell-based regenerative therapy for retinal diseases: challenges and emerging bioengineering strategies.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {1101-1112}, pmid = {41323371}, issn = {2352-3204}, abstract = {Cell-based regenerative therapy holds promise for a broad spectrum of retinal diseases characterized by irreversible photoreceptor cell (PRC) loss, including retinitis pigmentosa (RP) and age-related macular degeneration. While gene therapy has delivered landmark successes for selected indications, it does not directly replace lost PRCs and is not well suited for advanced-stages of diseases. In this context, cell-based regenerative approaches-either PRC suspensions or retinal sheets-aim to rebuild the outer retinal circuitry and restore light responses across different retinal diseases. In addition to its relatively high prevalence (1 in 3000-5000 individuals), the PRC-specific degeneration pattern in RP has motivated numerous preclinical studies aimed at clinical application. In this review, we first outline the two major graft modalities-cell suspensions and retinal sheet transplantation-from the perspective of their respective advantages and limitations. Here, we summarize preclinical and clinical evidence for both modalities, highlighting the first-in-human trial of transplantation of human iPSC-derived retinal organoid sheets in late-stage RP, which demonstrated a favorable safety profile and two-year graft survival. We then analyze the challenges that emerged from this first-in-human trial and discuss potential bioengineering and biological solutions. Finally, we consider the prospects of extending these transplantation strategies beyond RP to macular diseases, where PRC replacement may also provide therapeutic benefit. Collectively, the field is transitioning from proof-of-concept to diversified clinical exploration; converging advances in developmental biology, genome engineering, and high-throughput cell analytics are poised to accelerate functional vision restoration in retinal diseases.}, }
@article {pmid41324896, year = {2026}, author = {Kojima, H and Yamashita, A and Nakano, Y and Booka, A and Tatara, Y and Yamada, T and Akimitsu, J and Miyoshi, Y and Osaka, R and Suzuma, K}, title = {Significant Correlation Between Choroidal Thickness and Decrease in Choroidal Blood Flow After Switching to Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {393-402}, pmid = {41324896}, issn = {2193-8245}, abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) therapy suppresses neovascularization in neovascular age-related macular degeneration (nAMD) but may reduce ocular blood flow. However, its relationship with choroidal thickness remains unclear. This study evaluated 1-month outcomes after switching from intravitreal aflibercept or ranibizumab to intravitreal brolucizumab (IVBr) in patients with refractory nAMD.<br><br>METHODS: This prospective, single-center study included 50 eyes of 50 patients with nAMD. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), choroidal stromal area (SA), choroidal luminal area (LA), optic nerve head (ONH) mean blur rate (MBR), and choroidal (CHOR) MBR were evaluated before and 1&#xa0;month after switching to IVBr, with blood flow measured using laser speckle flowgraphy. Univariate analyses were performed to identify potential predictors of changes in CHOR-MBR, and variables with P&#x2009;<&#x2009;0.1 were entered into a multiple regression model.<br><br>RESULTS: BCVA was maintained. CRT decreased from 371.6&#x2009;&#xb1;&#x2009;118.7 to 288.8&#x2009;&#xb1;&#x2009;89.7&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.001). SFCT decreased from 231.9&#x2009;&#xb1;&#x2009;118.7 to 196.0&#x2009;&#xb1;&#x2009;117.4&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.001). CVI showed no significant changes, while SA and LA exhibited significant reductions. ONH-MBR and CHOR-MBR decreased (P&#x2009;=&#x2009;0.004 and P&#x2009;<&#x2009;0.001, respectively). The baseline SFCT was the only significant predictor of change in CHOR-MBR. Older age correlated with thinner baseline SFCT and a greater decrease in CHOR-MBR.<br><br>CONCLUSIONS: IVBr is associated with significant reductions in CRT and SFCT and may decrease choroidal blood flow, particularly in older patients and those with thinner SFCTs.<br><br>TRIAL REGISTRATION: UMIN-CTR Registration ID, UMIN000041382.}, }
@article {pmid41325920, year = {2026}, author = {Wang, Z and Zhang, Q and Li, B and Chen, J and Yoshida, S and Sun, B and Zhou, Y}, title = {tRNA-derived small RNAs-Biogenesis, functions, and potential applications in ocular diseases: A review.}, journal = {International journal of biological macromolecules}, volume = {337}, number = {Pt 2}, pages = {149334}, doi = {10.1016/j.ijbiomac.2025.149334}, pmid = {41325920}, issn = {1879-0003}, mesh = {Humans ; *Eye Diseases/genetics/metabolism ; *RNA, Transfer/genetics/metabolism ; Animals ; *RNA, Small Untranslated/genetics ; Gene Expression Regulation ; }, abstract = {tRNA-derived small RNAs (tsRNAs), a burgeoning class of small non-coding RNAs, are emerging as pivotal regulators in gene expression and cellular signaling networks. Derived from specific cleavage of precursor or mature tRNAs, these molecules exhibit diverse functionalities, including epigenetic remodeling, transcriptional regulation, and translational modulation. Growing evidence underscores their significant roles in the pathogenesis of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, myopia, and cataract, where they influence critical processes like angiogenesis, inflammation, and neuronal homeostasis. Their dynamic expression profiles in ocular tissues and biofluids position tsRNAs as promising diagnostic biomarkers and therapeutic targets. This review systematically delineates the biogenesis and classification of tsRNAs, elaborates their multifaceted molecular mechanisms, and comprehensively examines their implications in ocular diseases. We further discuss the translational potential of tsRNAs in early detection and precision treatment of ocular diseases, while highlighting current challenges and future directions in this rapidly evolving field.}, }
@article {pmid41326361, year = {2025}, author = {Sarkar, S and Kannan, R and Panigrahi, T and Veeramani, K and Mb, T and Shanker Bhattacharya, S and Ghosh, A}, title = {Comparative transcriptomic analysis of retinal response to diverse cellular stresses reveals relative contributions of different cell death processes and signalling networks.}, journal = {Cell death &amp; disease}, volume = {16}, number = {1}, pages = {876}, pmid = {41326361}, issn = {2041-4889}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/TSG/20/1/600029//DBT India Alliance (Wellcome Trust/DBT India Alliance)/ ; }, mesh = {Animals ; Oxidative Stress/genetics ; *Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Cell Death/genetics ; *Signal Transduction/genetics ; Endoplasmic Reticulum Stress/genetics ; *Retina/metabolism/pathology ; *Transcriptome ; Retinal Pigment Epithelium/metabolism/pathology ; Apoptosis/genetics ; *Retinal Degeneration/genetics/pathology/metabolism ; }, abstract = {Retinal degeneration comprises a diverse group of progressive disorders leading to visual impairment and ultimately blindness. These include inherited retinal dystrophies (IRDs), diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, affecting millions worldwide. The underlying pathology involves dysfunction and death of photoreceptor cells and the retinal pigment epithelium (RPE), driven by various stress-induced cell death mechanisms. Although multiple pathways have been reported, the relative contribution of each remains incompletely understood, highlighting the need for further investigation. Therefore, we studied how different stress types that induce retinal degeneration alter the global gene expression profile in vivo (C57BL/6 mice), aiming to identify predominant cell death mechanisms as well as key genes and networks. Retinal toxicity was induced using established models of oxidative stress, hypoxia, endoplasmic reticulum (ER) stress, and chronic inflammation. Transcriptomic profiling revealed both unique and convergent gene expression changes associated with each stressor. In total, 170, 328, 146, and 151 genes were significantly altered under oxidative stress, inflammation, ER stress, and hypoxia, respectively (Log2 fold change >2 or <-2; p < 0.05). Genes such as Arhgap26, Ccdc9, Ube2e2, and Fndc3b were commonly dysregulated across ER stress, inflammation, and oxidative stress, whereas Nfix, Elp6, Naca, and Plcd3 were selectively altered in oxidative stress, inflammation, ER stress, and hypoxia, respectively. Analysis of cell death-related gene subsets revealed that pyroptosis was commonly activated across different stress types. Additionally, autophagy-mediated cell death, ferroptosis, and extrinsic apoptosis were preferentially associated with oxidative stress, chronic inflammation, and hypoxia, respectively. Both ER and oxidative stress models showed strong activation of autophagy-associated cell death. Together, these findings delineate distinct molecular signatures and predominant cell death mechanisms triggered by specific stressors, providing important insights that could aid in developing targeted therapies to prevent or slow retinal degeneration.}, }
@article {pmid41327637, year = {2025}, author = {Jian, L and Huang, Z and Qi, J and Meng, J and Zhang, K and Zhu, X}, title = {Associations between estimated glucose disposal rate and age-related ocular diseases in cardiovascular-kidney-metabolic syndrome stages 0-3: a large prospective cohort study.}, journal = {BMJ open ophthalmology}, volume = {10}, number = {1}, pages = {}, pmid = {41327637}, issn = {2397-3269}, mesh = {Humans ; Prospective Studies ; Female ; Male ; *Metabolic Syndrome/complications/metabolism ; Middle Aged ; *Eye Diseases/epidemiology/etiology/metabolism ; Aged ; Risk Factors ; *Blood Glucose/metabolism ; *Cardiovascular Diseases/complications/metabolism ; Incidence ; United Kingdom/epidemiology ; Follow-Up Studies ; }, abstract = {OBJECTIVE: This study investigated the relationship between estimated glucose disposal rate (eGDR) and the risk of age-related ocular diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR) and retinal detachment (RD), in individuals with stages 0-3 of cardiovascular-kidney-metabolic (CKM) syndrome.<br><br>METHODS AND ANALYSIS: This prospective cohort study included 223&#x2009;120 participants from the UK Biobank. The CKM stages were defined based on adiposity, metabolic risk factors and subclinical cardiovascular disease. Lower eGDR values indicate greater insulin resistance. Outcomes were incidences of macular degeneration, glaucoma, cataract, DR and RD. HRs and 95% CIs were estimated using Cox proportional hazards models. Non-linear relationships were explored using restricted cubic splines.<br><br>RESULTS: The study showed that macular degeneration (HR 0.92, 95%&#x2009;CI 0.87 to 0.97, p=0.001) and glaucoma (HR 0.91, 95%&#x2009;CI 0.87 to 0.95, p<0.001) were linearly associated with eGDR. Cataracts exhibited a U-shaped association with eGDR (P non-linear=0.001) and DR exhibited an L-shaped association (P non-linear=0.018). Quartile stratification of eGDR significantly differentiated risk in DR (Q4 vs Q1: HR 0.15, 95%&#x2009;CI 0.04 to 0.52, p=0.003) and RD (Q4 vs Q1: HR 0.65, 95%&#x2009;CI 0.47 to 0.89, p=0.007). Stratified effects analysis revealed that these associations were more significant in advanced CKM syndrome stages.<br><br>CONCLUSIONS: eGDR is associated with ocular diseases risk in CKM syndrome, especially in advanced stages. This finding suggests the potential use of eGDR for guiding ophthalmic screening in CKM management.}, }
@article {pmid41328469, year = {2025}, author = {Ermilov, VV and Nesterova, AA}, title = {[Amyloidogenesis and neurotrophic dysfunction in age-related macular degeneration in correlation with Alzheimer's disease].}, journal = {Arkhiv patologii}, volume = {87}, number = {6}, pages = {61-68}, doi = {10.17116/patol20258706161}, pmid = {41328469}, issn = {0004-1955}, mesh = {Humans ; *Alzheimer Disease/pathology/metabolism/genetics/complications ; *Macular Degeneration/pathology/metabolism/genetics/complications ; *Amyloidosis/pathology/metabolism/genetics ; *Amyloid/metabolism/genetics ; Aged ; Glaucoma, Open-Angle/pathology/metabolism/genetics ; }, abstract = {The pathogenesis of diseases associated with amyloid deposition in various organs and tissues has been a concern for researchers and clinicians since their discovery. Particular attention is paid to the relationship between amyloidogenesis and neurotrophic disorders in age-related neurodegenerative pathology. In this context, the amyloid cascade theory and the neurotrophic dysfunction theory remain relevant, as evidenced by the results of numerous studies conducted in recent years. Meanwhile, it has been shown that amyloidosis, being a systemic pathological process, affects ocular tissues and extraocular structures in various forms with diverse clinical and morphological manifestations. This highlights the need for improved diagnostics of ocular amyloidosis and the study of its association with geriatric ophthalmic diseases such as age-related macular degeneration (AMD), senile cataract, primary open-angle glaucoma, and pseudoexfoliation syndrome. Accumulating evidence suggests that both amyloidogenesis and neurotrophic disturbances share common triggers and mutually contribute to the development of neurodegenerative pathology in both AMD and Alzheimer's disease (AD). Therapeutic strategies aimed not only at suppressing amyloidogenesis and correcting neurotrophic dysfunction but also at the overall regulation of these two pathogenic mechanisms may have a positive effect on geriatric ophthalmic diseases and AD, significantly improving the quality of life of elderly patients. This article summarizes current concepts on the role of neurotrophic dysfunction and amyloidogenic processes in the development of AMD.}, }
@article {pmid41328785, year = {2025}, author = {Jonas, JB and Panda-Jonas, S and Wang, YX and Jonas, RA}, title = {Associations of macular drusen in an East Asian population. The Beijing Eye Study.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70043}, pmid = {41328785}, issn = {1755-3768}, support = {82271086//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: To assess associations of macular drusen in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease.<br><br>METHODS: Participants of the population-based cross-sectional Beijing Eye Study underwent optical coherence tomography. Macular volume scans were assessed for macular drusen.<br><br>RESULTS: The study included 870 eyes (870 participants) (age: 64.7&#x2009;&#xb1;&#x2009;9.9&#x2009;years; range: 50-91&#x2009;years), randomly selected within the groups of early AMD (n&#x2009;=&#x2009;356 (40.9%) eyes), intermediate AMD (n&#x2009;=&#x2009;201; 23.1%), late AMD (n&#x2009;=&#x2009;6; 0.7%) and within eyes without AMD (n&#x2009;=&#x2009;307; 35.3%). In multivariable analysis, higher drusen count was associated (r[2]&#x2009;=&#x2009;25) with older age (beta: 0.08; p&#x2009;=&#x2009;0.048), higher serum concentration of cholesterol (beta: 0.10; p&#x2009;=&#x2009;0.008), shorter axial length (beta: -0.09; p&#x2009;=&#x2009;0.03), thicker subfoveal choroidal thickness (beta: 0.08; p&#x2009;=&#x2009;0.04), higher prevalences of macular hyperpigmentations (beta: 0.13; p&#x2009;<&#x2009;0.001), hyperreflective foci (HRFs) (beta: 0.12; p&#x2009;=&#x2009;0.004) and reticular pseudodrusen (beta: 0.27; p&#x2009;<&#x2009;0.001), and a lower prevalence of a visible Henle's layer (beta: -0.15; p&#x2009;<&#x2009;0.001). Larger drusen size was associated with shorter axial length (beta: -0.08; p&#x2009;=&#x2009;0.03), thicker subfoveal choroidal thickness (beta: 0.18; p&#x2009;<&#x2009;0.001), higher prevalences of macular hypopigmentations (beta: 0.14; p&#x2009;<&#x2009;0.001) and HRFs (beta: 0.31; p&#x2009;<&#x2009;0.001), and lower prevalences of a visible Henle's layer (beta: -0.19; p&#x2009;<&#x2009;0.001) and of reticular pseudodrusen (beta: -0.09; p&#x2009;=&#x2009;0.02).<br><br>CONCLUSIONS: In this population-based study on Chinese, higher macular drusen count was associated with shorter axial length, thicker subfoveal choroidal thickness, higher prevalences of macular hyperpigmentations, HRFs and reticular pseudodrusen and lower prevalence of a visible Henle's layer. These findings may be clinically helpful and etiologically interesting.}, }
@article {pmid41329005, year = {2025}, author = {Trinh, M and Duong, A and Cheung, R and Chen, S and Ng, D and Friedrich, J and Hodge, C and Nivison-Smith, L and Ly, A}, title = {Determinants of Intergrader Agreement for Key Retinal Photography and OCT Biomarkers in AMD.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {4}, pmid = {41329005}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Biomarkers ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Photography/methods ; Middle Aged ; Aged, 80 and over ; Retinal Drusen ; *Retina/pathology/diagnostic imaging ; Retinal Pigment Epithelium/pathology ; }, abstract = {PURPOSE: To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol.<br><br>METHODS: Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (&#x2265;90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors.<br><br>RESULTS: Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01).<br><br>CONCLUSIONS: Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (&#x2265;90%), may improve consistency.<br><br>TRANSLATIONAL RELEVANCE: Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.}, }
@article {pmid41331277, year = {2025}, author = {Moon, S and Park, S and Kim, CG and Kim, J and Yoon, YS and Kim, JH}, title = {Predicting visual acuity using optical coherence tomography in patients with neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {90}, pmid = {41331277}, issn = {2045-2322}, support = {25ZK1100//Electronics and Telecommunications Research Institute/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Visual Acuity ; Retrospective Studies ; Aged, 80 and over ; *Macular Degeneration/diagnostic imaging/physiopathology/drug therapy ; Middle Aged ; Artificial Intelligence ; }, abstract = {This study aimed to assess the feasibility of an artificial intelligence(AI) model to predict visual acuity(VA) using optical coherence tomography(OCT) in treatment-naïve patients with neovascular age-related macular degeneration (AMD). This retrospective study enrolled 240 patients(240 eyes) with pseudophakic neovascular AMD who received antivascular endothelial growth factor therapy. Each patient underwent 10 visits where they underwent best-corrected visual acuity(BCVA) testing and horizontal OCT scans, yielding 2,400 images. The images were cropped, resized to 224 × 224 pixels, and partitioned at the patient level to avoid data leakage. A pretrained VGG16 CNN was modified for five-class VA classification (< 0.1, 0.1-0.3, 0.3-0.5, 0.5-0.8, ≥ 0.8). The performance was assessed by five-fold cross-validation using the macro-averaged AUC, accuracy, Top-2 accuracy, and binary accuracy (threshold VA = 0.5). The average performance showed a macro-averaged AUC of 0.772, accuracy of 50.3%, Top-2 accuracy of 71.0%, and binary accuracy of 79.6%. For high-confidence predictions (29.2% of the samples), the accuracy improved to 74.1%, with a binary accuracy of 94.2%. ROC analyses demonstrated AUCs of 0.73-0.83 across VA categories, with the strongest discrimination for VA < 0.1 (AUC 0.83). The confusion matrix showed that the VA 0.5-0.8 and ≥ 0.8 categories achieved relatively higher accuracies; however, misclassifications mainly occurred between these adjacent ranges, with frequent bidirectional errors observed. Our pretrained VGG16 showed moderate ability at predicting VA from OCT images in patients with neovascular AMD. While the overall classification was limited, high binary accuracy highlights the potential clinical value of distinguishing good from poor vision.}, }
@article {pmid41332270, year = {2025}, author = {Li, KV and Pan, A and Liu, YV and Antonio-Aguirre, B and Wang, J and Adams, M and McNerney, C and Tun, SBB and Jimenez, K and Lu, Y and Li, Z and McNally, M and Barathi, VA and Johnston, RJ and Singh, MS}, title = {Application of Machine Learning to Discriminate Photoreceptor Cell Species in Xenotransplanted Chimeric Retinas.}, journal = {Clinical and translational science}, volume = {18}, number = {12}, pages = {e70420}, pmid = {41332270}, issn = {1752-8062}, support = {EY001765//Johns Hopkins University/ ; R01 EY030872/EY/NEI NIH HHS/United States ; //Juliette RP Vision Foundation/ ; //Maryland Technology Development Corporation/ ; /FFB/Foundation Fighting Blindness/United States ; //Joseph Albert Hekimian Fund/ ; R01EY033103/EY/NEI NIH HHS/United States ; R01EY030872/EY/NEI NIH HHS/United States ; //Shulsky Foundation/ ; F31EY033187/EY/NEI NIH HHS/United States ; G2019300//BrightFocus Foundation/ ; //Wilmer Pooled Professor Fund (PPF) Lutty Grant/ ; 147042//Knights Templar Eye Foundation/ ; }, mesh = {*Machine Learning ; Animals ; Humans ; Mice ; Swine ; *Transplantation, Heterologous/methods ; *Retina/cytology/transplantation ; *Retinal Degeneration/pathology/therapy ; *Photoreceptor Cells, Vertebrate/transplantation ; Disease Models, Animal ; Species Specificity ; Organoids/transplantation/cytology ; Heterografts ; Human Embryonic Stem Cells/transplantation/cytology ; }, abstract = {Photoreceptor transplantation is being studied to restore visual function in retinal diseases causing blindness, including age-related macular degeneration, hereditary eye diseases, and traumatic retinopathy. Preclinical studies often involve delivering exogenous human photoreceptor cells into animal models' retinas. A key readout in such experiments is distinguishing donor cell integration from artificial labeling secondary to material transfer of cytosolic or nuclear labels. Recognizing donor (human) versus animal photoreceptor nuclei is key, but purely immunohistology discrimination is challenging due to antigenic species overlap or intercellular antigen transfer. To address this, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. We aim to evaluate the feasibility of computer-assisted nuclear detection combined with random forest classification to automate species differentiation in DAPI-stained photoreceptors after xenotransplantation into mouse and pig retinas. Our models were trained on single-species samples and validated with mixed-species samples. We then transplanted human embryonic stem cell-derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post-xenotransplantation, validated by histological assessment using an antihuman nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semiautomated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.}, }
@article {pmid41334300, year = {2025}, author = {Sarkar, AD and Kannan, NB and Thakur, S and Balakrishnan, TN and Ramasamy, K}, title = {Long-Term Outcome of Intravitreal Expansile Gas and Bevacizumab Injection for Macular Neovascularization-Induced Subfoveal Hemorrhage: A Retrospective Study.}, journal = {Journal of current ophthalmology}, volume = {37}, number = {1}, pages = {86-92}, pmid = {41334300}, issn = {2452-2325}, abstract = {PURPOSE: To analyze the results of the long-term outcome of pneumatic displacement (PD) with intravitreal bevacizumab (IVB) for subfoveal hemorrhage (SFH) secondary to polypoidal choroidal vasculopathy (PCV)/macular neovascularization secondary to neovascular age-related macular degeneration (n-AMD).<br><br>METHODS: This is a retrospective and interventional study executed in the population of southern part of India who attended a tertiary care ophthalmic hospital over a decade. Patients who presented with a complaint of diminution of vision following SFH secondary to PCV or n-AMD who were treated with PD using sulphur hexafluoride (SF6) along with IVB were included in the study. The patients were followed up for at least 24 months posttreatment. Finally, a dataset of 54 patients was chosen who fulfilled all the criteria and a thorough analysis on their long-term outcome was done.<br><br>RESULTS: The mean age at baseline was 57.55 &#xb1; 13.02 years. Average treatment delay was measured 9.43 &#xb1; 5.22 days. Best-corrected visual acuity (BCVA) on presentation was 1.07 &#xb1; 0.46 in logMAR. The average size of the SFH was measured 4.46 &#xb1; 1.17-disc diameter area. The average long-term follow-up was measured 29.33 &#xb1; 4.53 months. Final BCVA improved to 0.74 &#xb1; 0.62 in logMAR (P < 0.001). Overall improvement in BCVA was significantly better, although only a minority of patients (n = 24, 44.44%) improved BCVA &#x2265; 0.3 in logMAR. Subgroup analysis reveals smaller SFH (&#x2264;2 disc diameter) and presentation earlier than 1 week shows comparatively better visual outcome.<br><br>CONCLUSIONS: The study shows encouraging results on the long-term follow-up with respect to anatomical and visual acuity outcome. This serves as the second largest dataset on PD with IVB for SFH secondary to PCV/n-AMD in ophthalmic literature.}, }
@article {pmid41334307, year = {2025}, author = {Sadeghi, E and Mahmoudinezhad, G and Valsecchi, N and Vupparaboina, SC and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Long-Term Follow-Up of Dry Age-Related Macular Degeneration Patients.}, journal = {Journal of current ophthalmology}, volume = {37}, number = {1}, pages = {78-85}, pmid = {41334307}, issn = {2452-2325}, abstract = {PURPOSE: To assess the progression rate from dry age-related macular degeneration (dAMD) to advanced AMD and possible risk factors.<br><br>METHODS: Demographics, medical and ocular conditions, baseline eye examinations, optical coherence tomography features, and progression rates to advanced AMD were collected.<br><br>RESULTS: We included 74 eyes from 47 dAMD patients, with a mean age of 74.58 &#xb1; 8.29 years and 38.30% males. During a follow-up period of 8.9 &#xb1; 0.4 years, 40 eyes (54.05%) progressed to advanced AMD, with 25 eyes (33.78%) developing neovascular AMD (nAMD) and 22 eyes (29.72%) progressing to geographic atrophy (GA). Patients progressing to advanced AMD were older (77.8 &#xb1; 6.5 vs. 73.8 &#xb1; 9.5, P = 0.03). A higher incidence of open-angle glaucoma (OAG) was noted in progressing eyes (32.5% vs. 8.8%, P = 0.01), along with thinner baseline central macular thickness (CMT) (247.93 &#xb1; 32.55 vs. 268.67 &#xb1; 16.75, P = 0.007). Smokers with OAG had a higher tendency to develop nAMD (P < 0.05). Females with lower best-corrected visual acuity (BCVA) were more likely to develop GA (P < 0.001).<br><br>CONCLUSIONS: The progression rate to advanced AMD was 54.05% over 8.9 &#xb1; 0.4 years. Advanced age, reduced baseline CMT, and lower BCVA were linked to progression. OAG and smoking were associated with higher nAMD, while females had a higher risk of GA.}, }
@article {pmid41335183, year = {2026}, author = {Borrelli, E and Coco, G and Scorcia, V and Carnevali, A and Reibaldi, M and Giannaccare, G}, title = {A Response to: Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {499-501}, pmid = {41335183}, issn = {2193-8245}, }
@article {pmid41335184, year = {2026}, author = {Augustin, AJ and Koss, M}, title = {Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {495-497}, pmid = {41335184}, issn = {2193-8245}, }
@article {pmid41335185, year = {2026}, author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F}, title = {Correction: In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {251-252}, doi = {10.1007/s40123-025-01294-w}, pmid = {41335185}, issn = {2193-8245}, }
@article {pmid41335372, year = {2026}, author = {Shirley, M}, title = {Elamipretide: First Approval.}, journal = {Drugs}, volume = {86}, number = {3}, pages = {377-383}, pmid = {41335372}, issn = {1179-1950}, mesh = {Humans ; Drug Approval ; *Oligopeptides/therapeutic use/pharmacology/adverse effects ; *Barth Syndrome/drug therapy ; United States ; United States Food and Drug Administration ; }, abstract = {Elamipretide (Forzinity™) is a mitochondrial cardiolipin binder being developed by Stealth BioTherapeutics for the treatment of a range of disorders featuring mitochondrial dysfunction. In September 2025, elamipretide was granted accelerated approval in the USA for use to improve muscle strength in adult and pediatric patients with Barth syndrome weighing ≥ 30 kg. With this accelerated approval, elamipretide became the first disease-specific treatment approved for Barth syndrome, an ultra-rare X-linked recessive genetic disorder. Elamipretide is also under phase III clinical development for use in the treatment of dry age-related macular degeneration and mitochondrial myopathies. This article summarizes the milestones in the development of elamipretide leading to this first approval for Barth syndrome.}, }
@article {pmid41335529, year = {2025}, author = {Machna, B and Jastrzebska-Miazga, I and Pacwa, A and Liu, X and Oseka, M and Smedowski, A}, title = {Experimental models of myopia development: A review of literature.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {76}, number = {4}, pages = {335-367}, doi = {10.26402/jpp.2025.4.01}, pmid = {41335529}, issn = {1899-1505}, mesh = {*Myopia/physiopathology/etiology/epidemiology/pathology ; Humans ; Animals ; *Disease Models, Animal ; Refraction, Ocular ; }, abstract = {Myopia is one of the most prevalent refractive errors and one of the leading causes of visual impairment and blindness worldwide. It results from a mismatch between the axial length and optical power of the eye, resulting in a focal plane that lies in front of the retina. In children and young adults, myopia is most commonly caused by excessive elongation of the eyeball during development - a hallmark of school-age and some early-onset genetic forms of myopia. However, myopic refractive error can also result from other mechanisms, such as increased lens power in age-related nuclear cataracts or corneal steepening in keratoconus, which are not associated with axial elongation. The prevalence of myopia in young Asian adults has increased from 20-30% to 80-85% over the last 50 years. In contrast, recent meta-analytic data for European young adults, emphasizing studies with cycloplegic refraction essential for accuracy, indicate myopia prevalence rates of approximately 19-24%. The prevalence of high myopia (greater than or equal to-6.0 diopters) has increased disproportionately to myopia in the last 50 years, from 1-5% to 10-20% and became a global problem. The reason for this state of affairs is believed to be lifestyle and prolonged near vision activities. Although refractive error can be corrected, sight-threatening pathologies such as retinal detachment, macular degeneration, glaucoma, and cataracts are more challenging to control. Owing to years of research, the biological mechanisms of eye growth and refractive development are increasingly elucidated. The signaling cascade mechanisms that link the retinal image processing and alterations in choroidal thickness and scleral development have also been studied. While the retina can detect defocus and changes in defocus, decades of research have led to a growing understanding of the fundamental pathways in visually guided eye growth, yet the precise initial mechanisms by which the retina senses and transduces these optical signals continue to be an active and important area of investigation. Animal studies have demonstrated that the retina can locally regulate visually guided eye growth through intrinsic mechanisms, even in the absence of direct input from the brain. The precise molecular mechanisms underlying common forms of myopia, particularly those involving axial elongation, are yet to be fully elucidated. This reflects the complexity and multifactorial influences inherent even in these prevalent forms, alongside the challenges posed by experimental models in completely recapitulating all aspects of the human condition.}, }
@article {pmid41335743, year = {2025}, author = {Herrero-Tudela, M and Romero-Oraa, R and Hornero, R and Gutierrez-Tobal, GC and Lopez, MI and Romero-Aroca, P and Garcia, M}, title = {Explainable Artificial Intelligence for Early Detection and Diagnosis of Age-Related Macular Degeneration.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2025}, number = {}, pages = {1-4}, doi = {10.1109/EMBC58623.2025.11254905}, pmid = {41335743}, issn = {2694-0604}, mesh = {*Artificial Intelligence ; *Macular Degeneration/diagnosis ; Early Diagnosis ; Humans ; Datasets as Topic ; Neural Networks, Computer ; Deep Learning ; *Diagnosis, Computer-Assisted/methods ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Early identification of individuals at risk of progressing from an asymptomatic stage to advanced AMD is critical for preventing severe vision loss. Automated image assessment systems for AMD can enhance screening efficiency by reducing time, cost, and effort. Despite the success of convolutional neural networks in AMD detection, their limited interpretability restricts their use in clinical practice. To address this issue, we present an explainable deep-learning approach based on ResNetRS-200, incorporating Kernel SHAP for model interpretability. Our approach achieved a quadratic kappa of 0.6927 and an accuracy of 60.95% on the publicly available Age-Related Eye Disease Study dataset, while achieving a quadratic kappa of 0.7784 and an accuracy of 77.95% on a private dataset. Kernel SHAP analysis highlighted specific retinal regions close to the macula influencing the predictions of the model, providing a clinically interpretable framework, and enhancing diagnostic confidence. Our findings demonstrate the effectiveness of the proposed framework for automated AMD grading. Therefore, the proposed method could be an explainable diagnostic aid for the early detection and grading of AMD.Clinical relevanceThis research establishes the useful- ness of an eXplainable Artificial Intelligence approach using ResNetRS-200 architecture and Kernel SHAP for automated AMD grading.}, }
@article {pmid41337039, year = {2025}, author = {Abay, SG and Asmare, MH and Geurts, L}, title = {An Affordable Smartphone-based Fundus Imaging Device for Retinal Examination.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2025}, number = {}, pages = {1-6}, doi = {10.1109/EMBC58623.2025.11254224}, pmid = {41337039}, issn = {2694-0604}, mesh = {*Smartphone ; Humans ; *Fundus Oculi ; *Retina/pathology/diagnostic imaging ; Glaucoma/diagnosis ; Equipment Design ; Optic Disk/pathology ; }, abstract = {Fundus imaging is widely used for diagnosing and monitoring ocular diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. However, the high cost and limited availability of conventional fundus cameras pose significant barriers, particularly in resource-constrained settings. This study introduces the Glaucoma Screening on Phone (GSoP), an affordable and portable smartphone-based fundus imaging adapter designed to address these challenges. The adapter is developed using accessible and cost-effective components. We recorded retinal videos from dilated pupil with a focus on the optic disc region, which provides critical information on the degeneration of the optic nerve. While field testing revealed artifacts such as glare that reduced overall image quality, the GSoP demonstrated its ability to capture diagnostically relevant images of the optic disc region. A subjective qualitative comparison with the commercially available ophthalmoscope called oDocs-nun showed that although the GSoP's field of view is smaller, it effectively highlights the optic nerve head, a critical area for glaucoma screening. Our approach is well-suited for mydriatic video-based screening due to its limited field of view. With a production cost of under C10, the GSoP offers a practical and accessible solution for primary healthcare and educational purposes. Future improvements, including glare reduction mechanisms, AI-driven automation, and modular design options, have the potential to enhance its diagnostic capabilities and broaden its impact.}, }
@article {pmid41340913, year = {2025}, author = {Sun, M and Wang, J and Fan, W and Wang, K and Wang, Y and Zhang, J and Ding, S and Zhang, C and Feng, Z and Wang, YG and Song, Z and Tao, Y}, title = {From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics.}, journal = {Materials today. Bio}, volume = {35}, number = {}, pages = {102537}, pmid = {41340913}, issn = {2590-0064}, abstract = {Delivering medications to targeted lesions poses significant challenges due to the unique anatomical structure and physical barriers of the eyeball. Polymer nanomicelles are spontaneously assembled from surfactants and amphiphilic polymers, encapsulating insoluble drugs within their cores to augment their hydrosolubility. Nanomicelles have demonstrated potential to surmount these biological hurdles and convey encapsulated therapeutic agents to intended sites. Nanomicelle can prolong the drug half-life and promote molecule permeation through ocular epithelium. Notably, they can be formulated at concentrations marginally exceeding the critical micelle concentration while maintaining a stable conformation, thereby boosting therapeutic effectiveness. Moreover, the physicochemical attributes of polymeric micelles can be precisely adjusted by integrating diverse hydrophilic or hydrophobic moieties. Surface modifications can further impart specific charges or facilitate targeted organ delivery enhancing adhesion to ocular tissues and mitigating systemic toxicity. This review delves into the utilization of polymer nanomicelles in ophthalmological practice, encompassing block copolymer design, the pharmacokinetics of encapsulated drugs within nanomicelles, and the molecule pathways governing nanomedicines. This review also explores their applications in treating ocular disorders including infectious keratitis, DED, glaucoma, corneal graft rejection, neovascular age-related macular degeneration (nAMD), and DR, while introducing progress in clinical deployment and potentials in ocular diagnosis. We also discuss the key challenges in clinical translation and scalable manufacturing. With continued optimization, polymer nanomicelles are poised to become a versatile, non-invasive platform for personalized ophthalmologic therapies.}, }
@article {pmid41341962, year = {2025}, author = {Ly, A and Harnick, E and Jowsey, T and Bannatyne, AJ}, title = {Qualitative Factors Impacting Patients and Clinicians Regarding Intravitreal Injections for Retinal Disorders: A Scoping Review.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4349-4365}, pmid = {41341962}, issn = {1177-5467}, abstract = {BACKGROUND: Intravitreal injections are among the most frequently performed eye procedures worldwide. They are vital in managing vision-related retinal conditions such as neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion. This review scopes qualitative research concerning people's beliefs, perspectives, experiences and behaviors towards intravitreal injections.<br><br>METHODS: Academic databases (PubMed, Embase, CINAHL and Web of Science) were searched for studies focused on qualitative research of intravitreal injections in adult patients, published between January 2000 and May 2024. We extracted data regarding publication and participants' characteristics, main study objectives, and methodological approaches.<br><br>RESULTS: Of the 795 identified citations, 28 met the inclusion criteria. Most studies reported on patients' emotional experiences of undergoing intravitreal injections, with the fear of vision loss compounded with ongoing injections prompting significant anxiety and uncertainty for patients. Other studies also reported on the physical component as the invasiveness of the procedure caused pain and discomfort, which varied with the clinician's delivery of the injection. One study reported on clinician experiences of performing intravitreal injections, stating that the treatment decisions are dependent on patient-related factors such as their adherence to regular injections. Overall, qualitative research in ophthalmology is increasing, with most studies employing semi-structured interviews with thematic analysis.<br><br>CONCLUSION: Qualitative research offers valuable insights into both patient and clinician experiences of intravitreal injections, which can shape person-centered and sustainable models of intravitreal treatment. Understanding qualitative factors such as personal experiences and barriers to treatment can refine the delivery of intravitreal injections and ultimately improve patient adherence.}, }
@article {pmid41342587, year = {2025}, author = {Zhao, S and Voegele, F and Tang, J and Clark, SJ and Tschulakow, AV and Julien, S}, title = {Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {23}, pages = {e71307}, pmid = {41342587}, issn = {1530-6860}, support = {//Dr. Werner Jackstaedt Stiftung, Germany/ ; //Guangzhou Elites Scholarship Council, China/ ; //Open access Publishing Fund of University of Tuebingen/ ; }, mesh = {Animals ; *Geographic Atrophy/chemically induced/pathology/metabolism ; *Iodates/toxicity ; Rats ; Disease Models, Animal ; Rats, Long-Evans ; Retinal Pigment Epithelium/pathology/metabolism ; *Inflammation/pathology/metabolism/chemically induced ; Tomography, Optical Coherence ; Electroretinography ; Male ; }, abstract = {Geographic atrophy (GA) is characterized by the loss of choriocapillaris, retinal pigment epithelium (RPE) and photoreceptors and is an advanced form of age-related macular degeneration (AMD)-a leading cause of central vision loss in the elderly. The development of effective treatments has been hindered by the lack of reliable animal models that recapitulate the structural, functional, and molecular hallmarks of GA. In this study, we established and extensively characterized a sodium iodate (NaIO3)-induced model of GA in pigmented Long Evans rats using a comprehensive set of in vivo and histological techniques. NaIO3 was administered intraperitoneally at 80 mg/kg to induce bilateral retinal degeneration. Morphological, functional, and ultrastructural changes were evaluated using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG), light and electron microscopy, and immunohistochemistry at pre-dose and 3, 7, and 14 days post-injection. The model exhibited typical GA features including choriocapillaris loss, RPE degeneration, photoreceptor death, Bruch's membrane remodeling, and mitochondrial damage. Complement activation (C3, C5b-9) and immune cell infiltration (Iba1, CD68) were observed, along with gliosis and RPE65 loss. ERG analysis revealed profound and persistent functional deficits. These findings demonstrate that the NaIO3 rat model robustly mimics the key pathological events in GA, particularly at 7 days post-injection, making it a suitable model for preclinical evaluation of therapeutic interventions targeting choriocapillaris and RPE protection.}, }
@article {pmid41342623, year = {2025}, author = {Peter, VG and Hayoz, M and Scandella, D and Sznitman, R and Escher, P and Zinkernagel, MS}, title = {AI-Assisted Optical Coherence Tomography Segmentation for Enhanced Diagnosis of Inherited Retinal Diseases.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {8}, pmid = {41342623}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis/diagnostic imaging/genetics ; *Artificial Intelligence ; Male ; Female ; Middle Aged ; Aged ; Algorithms ; Adult ; Macular Degeneration/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Retina/diagnostic imaging ; }, abstract = {PURPOSE: Inherited retinal diseases (IRDs) are rare and diverse, posing a diagnostic challenge in ophthalmology. This study aimed to determine whether artificial intelligence (AI)-assisted image processing can improve IRD diagnosis and provide insights into disease characteristics. We used an optical coherence tomography (OCT) segmentation algorithm to characterize retinal features in IRDs. Two control groups were included to enhance the contextual understanding of these features: healthy eyes and eyes with age-related macular degeneration (AMD). An AI-driven classification model was then used to classify the data into disease and control groups.<br><br>METHODS: We analyzed 327 images from 181 patients with IRD and 146 control individuals, including healthy subjects and patients with AMD. IRD cases were stratified into macular and retinal dystrophies. Automated segmentation of six retinal layers and detection of nine biomarkers were performed on retinal OCT images using the AI-based RetinAI Discovery tool. A random forest classifier differentiated macular IRD, retinal IRD, and controls.<br><br>RESULTS: The model detected IRD with 91% accuracy and achieved 91% accuracy in differentiating macular from retinal IRD. Key OCT features for differentiation included reduced perifoveal photoreceptor and outer nuclear layer thicknesses and increased retinal nerve fiber layer thickness in retinal IRD. Macular IRD featured significant foveal photoreceptor and outer nuclear layer thinning.<br><br>CONCLUSIONS: This study shows that standardized OCT image analysis combined with AI-based classification can accurately detect and stratify IRDs. The model's high accuracy highlights its potential as a reliable diagnostic tool in ophthalmology.<br><br>TRANSLATIONAL RELEVANCE: This AI-assisted OCT evaluation approach enhances ophthalmic diagnostics by improving IRD detection and classification.}, }
@article {pmid41342744, year = {2025}, author = {Cakici, O and Yilmaz, OF and Karaca, S and Sarmis, A and Mutlu, MA and Sahin, ZB and Borucu, B and Oguz, H}, title = {Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251393397}, doi = {10.1177/11206721251393397}, pmid = {41342744}, issn = {1724-6016}, abstract = {PurposeThis study aimed to investigate the conjunctival microbiota of patients requiring intravitreal injections due to diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO).MethodsA total of 182 participants (46 DR, 71 AMD, 16 RVO, and 49 controls) were enrolled between August and November 2024. Conjunctival swabs were collected from both eyes under sterile conditions prior to injection and cultured on 5% sheep blood and chocolate agar. Microorganisms were identified using Vitek MS.ResultsNo significant differences were observed among the groups in overall microbial growth frequency (all p > 0.05). Gram-negative bacteria, fungi, and polymicrobial growth were more frequently detected in DR and AMD patients, suggesting a trend toward greater microbial diversity, although these differences were not statistically significant.ConclusionDR and AMD patients exhibited higher prevalence of gram-negative, fungal, and polymicrobial colonization. These findings underscore the importance of strict aseptic preparation, povidone-iodine disinfection, and targeted prophylactic strategies to minimize post-injection infection risk in high-risk populations.}, }
@article {pmid41343426, year = {2025}, author = {DeLucia, PR and Oberfeld, D and Kearney, JK and Cloutier, M and Jilla, AM and Zhou, A and Corona, ST and Cormier, J and Taylor, A and Wykoff, CC and Baurès, R}, title = {Visual, auditory, and audiovisual time-to-collision estimation among participants with age-related macular degeneration compared to a normal-vision group: The TTC-AMD study.}, journal = {PloS one}, volume = {20}, number = {12}, pages = {e0337549}, pmid = {41343426}, issn = {1932-6203}, mesh = {Humans ; *Macular Degeneration/physiopathology ; Male ; Female ; Aged ; *Visual Perception/physiology ; *Auditory Perception/physiology ; Aged, 80 and over ; Middle Aged ; Cues ; *Vision, Ocular ; }, abstract = {Little is known about whether and to what degree people with different amounts of visual impairment rely on hearing instead of vision for mobility, particularly in judgments of collision. We measured how much importance was assigned to visual and auditory cues during time-to-collision judgments made by people with age-related macular degeneration (Impaired Vision Group; IV) compared to a control group without age-related macular degeneration (Normal Vision Group; NV). A virtual reality system simulated a roadway with an approaching vehicle viewed from the perspective of a pedestrian. Participants pressed a button to indicate the time the vehicle would reach them. The vehicle was presented visually only, aurally only, or both simultaneously. Standardized regression coefficients and general dominance weights indicated that time-to-collision (TTC) judgments were determined by both auditory and visual cues in both groups. In the vision-only modality condition, the relative importance of distance and optical size compared to TTC was higher in the IV group compared to the NV group, but with a relatively small effect size. In all modality conditions, the mean absolute error of TTC estimates was comparable between groups, and a multimodal advantage was not observed. Intraindividual variability was greater in the IV group only in the AV condition. The implication is that similar performance can be achieved through the use of different sources of information. Importantly, people with and without IV achieved similar performance but showed differences in the relative importance of different sensory sources of information. A comparison of two IV subgroups differing in severity suggested that simply having IV in both eyes is not sufficient to predict TTC estimation differences between people with IV and people without IV who have normal vision. Rather it appears to be the degree of bilateral visual impairment of the IV that matters.}, }
@article {pmid41344859, year = {2026}, author = {Schmidt, I and Volkmer, P and Müskens, RPHM and van der Waaij, AM and van Dam, GM and Huiskamp, EA and Nagengast, WB}, title = {Targeted Fluorescence Imaging of Bevacizumab-800CW in Patients with Neovascular Age-Related Macular Degeneration.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {67}, number = {1}, pages = {119-125}, pmid = {41344859}, issn = {1535-5667}, mesh = {Humans ; *Bevacizumab/administration &amp; dosage/pharmacokinetics/adverse effects ; Male ; Female ; Aged ; *Macular Degeneration/diagnostic imaging/drug therapy/metabolism ; Middle Aged ; *Optical Imaging/methods ; Aged, 80 and over ; Angiogenesis Inhibitors ; }, abstract = {The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.}, }
@article {pmid41345313, year = {2026}, author = {Niknahad, A and Zielińska, A and Auffarth, GU and Son, HS and Lee, H and Khoramnia, R and Łabuz, G}, title = {[Emerging technology for retinal function testing: two-photon microperimetry].}, journal = {Die Ophthalmologie}, volume = {123}, number = {1}, pages = {12-21}, pmid = {41345313}, issn = {2731-7218}, mesh = {Humans ; *Visual Field Tests/methods/trends/instrumentation ; *Retina/physiopathology ; *Retinal Diseases/diagnosis/physiopathology ; Photons ; }, abstract = {The technique of 2‑photon microperimetry is an emerging procedure that combines measurement of retinal sensitivity with retinal imaging and offers substantial improvements compared to conventional microperimetry. Conventional microperimetry relies on 1‑photon linear absorption while 2‑photon microperimetry relies on the simultaneous absorption of two photons, leading to enough energy for photoisomerization of visual pigments and perception of colors, such as green. This 2‑photon absorption process has shown a lower spread of measurements at one retinal location, leading to more reproducible data compared to conventional microperimetry. The current literature also suggests that 2‑photon microperimetry provides more reliable measurements in the presence of lens opacities, a common issue in an aging eye. Furthermore, it has been successfully utilized to assess retinal function in patients with diabetic retinopathy, age-related macular degeneration and glaucomatous neuropathy. These advantages highlight the very promising application in clinical settings. Future adjustments focusing on implementing this technology in the clinical practice could improve outcomes in the early detection and monitoring of retinal diseases.}, }
@article {pmid41346473, year = {2025}, author = {Buscaglia, M and Gouriou, B and Asquoët, Y and Le Goïc, N and Le Grand, F and Hachem, M and Soudant, P}, title = {Production of [13]C-labeled docosahexaenoic acid from heterotrophic marine microorganisms Aurantiochytrium mangrovei and Crypthecodinium cohnii enabling fluxomic applications.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {13}, number = {}, pages = {1690863}, pmid = {41346473}, issn = {2296-4185}, abstract = {Docosahexaenoic acid (DHA, 22:6n-3) is the predominant polyunsaturated fatty acid in the human brain and eyes, playing a crucial role in vision and cognitive development. DHA deficiency has been associated with ocular diseases, such as macular degeneration and glaucoma, as well as neurodegenerative disorders. Since the human body has a limited ability to synthesize DHA from its precursor, alpha-linolenic acid (ALA, 18:3n-3), targeted DHA supplementation is essential for these patients. To investigate DHA metabolism and integration, researchers commonly use stable ([2]H,[13]C) or radioactive ([3]H,[14]C) isotopes, which are expensive and not widely accessible, restricting the scope and duration of studies. This study aimed to develop a sustainable method for biosynthesizing uniformly labeled [13]C-DHA by culturing the heterotrophic protists Aurantiochytrium mangrovei and Crypthecodinium cohnii with [13]C-glucose. The major fatty acids (FA) of A. mangrovei included 16:0, 22:5n-6 (DPA), and DHA, with DHA accounting for 50.5% ± 4.9% of the total FA. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed a[13]C-enrichment of DHA at 96.7% ± 0.4% after the effective High Performance Liquid Chromatography (HPLC) purification. The predominant FA of C. cohnii were 12:0, 14:0, 16:0, and DHA, with DHA representing around 27% of the total FA and exhibiting a[13]C-enrichment of 86.3% ± 1.6%. Based on FA content, A. mangrovei showed a balanced distribution of neutral and polar lipids, with DHA predominantly in the polar fraction (57.8% ± 3.1%), whereas C. cohnii exhibited a predominance of neutral lipids (82.4% ± 0.3%), which contained the majority of its DHA (57.5% ± 1.0%).}, }
@article {pmid41347874, year = {2025}, author = {Trivizki, O and Wykoff, CC and Smoor, MA and Rabinovitch, D and Zhou, A and Cao, JA and Lechanteur, YTE and van den Heuvel, L and van Gool, AJ and Gloerich, J and Vergroesen, JE and Klaver, CCW}, title = {Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {24}, pmid = {41347874}, issn = {1552-5783}, mesh = {Humans ; *Aqueous Humor/metabolism ; *Geographic Atrophy/drug therapy/metabolism ; Prospective Studies ; Male ; Aged ; Female ; *Proteome/metabolism/drug effects ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Complement C3/antagonists &amp; inhibitors ; Proteomics/methods ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: Pegcetacoplan, a complement component 3 (C3) inhibitor, has recently received U.S. Food and Drug Administration approval for treating geographic atrophy (GA), an advanced stage of age-related macular degeneration (AMD). However, the limited treatment response prompts further investigations into its molecular effects.<br><br>METHODS: We prospectively collected aqueous humor (AH) samples from 11 patients with GA before and at 2 months during pegcetacoplan treatment. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome, and global normalization was applied to account for differences in protein concentration. To assess global proteomic shifts over time, principal component analysis (PCA) was performed. The Friedman test was used to assess differences in protein intensities across time points while adjusting for multiple testing using Benjamini-Hochberg false discovery rate (FDR) correction.<br><br>RESULTS: A total of 283 proteins were analyzed. PCA revealed temporal changes in global protein expression profiles, with a significant shift between baseline and month 2 (P = 0.01). The levels of complement components C3 (P = 0.12) and C5 (P = 0.27) remained stable after initiation of treatment, but the levels of C1qB, C1RL, C2, C6, C7, C8, C9, factor D, factor H, and factor I increased significantly (all P < 0.05). Most non-complement proteins showed no significant changes; however, beta-2-glycoprotein 1 (FDR = 0.09), kininogen 1 (FDR < 0.05), and prothrombin (FDR < 0.05) increased significantly, and kallistatin (FDR < 0.05) and plasma serine protease inhibitor (FDR < 0.05) decreased.<br><br>CONCLUSIONS: This exploratory study suggests that pegcetacoplan modulates the AH proteome in GA. Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts.}, }
@article {pmid41348248, year = {2025}, author = {Bartol-Puyal, FA and Sánchez Monroy, J and Puzo Bayod, M and Mallén, V and Méndez-Martínez, S and Calvo, P and Pablo, L}, title = {Choroidal changes after antiVEGF in neovascular age-related macular degeneration with type 1 and 3 macular neovascularization.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {8}, pmid = {41348248}, issn = {1573-2630}, mesh = {*Wet Macular Degeneration/drug therapy/pathology ; *Choroid/diagnostic imaging/drug effects/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage ; Retrospective Studies ; Intravitreal Injections ; Follow-Up Studies ; *Ranibizumab/administration &amp; dosage ; Tomography, Optical Coherence ; *Choroidal Neovascularization/drug therapy/pathology ; Humans ; Male ; Female ; Aged ; Aged, 80 and over ; }, abstract = {PURPOSE: To analyze choroidal thickness (CT) in patients with neovascular age-related macular degeneration (nAMD) with type 1 macular neovascularization (MNV) and type 3 (or retinal angiomatous proliferation) after antiVEGF treatment for two years.<br><br>METHODS: Retrospective study enrolling Caucasian na&#xef;ve patients with nAMD (type 1 MNV), and patients with type 3 MNV with no other ophthalmological disorders, and without switching treatment. Nine manual CT measurements were performed on optical coherence tomography (OCT) Spectralis (Heidelberg Engineering). Demographic data, smoking, disease activity, and number of injections, among others were recorded. Three visits were analyzed: pretreatment baseline visit, first and last visits with no disease activity.<br><br>RESULTS: 53 eyes of 53 patients with type 1 MNV, and 41 eyes of 41patients with type 3 MNV were analyzed. Both groups received the same number of injections (p&#x2009;=&#x2009;0.282). Type 3 MNV patients showed lower CT (between 143.29 and 174.17&#x3bc;m) than type 1 MNV patients (between 169.91 and 220.17&#x3bc;m) in the baseline visit, but differences disappeared in first and last visits. Choroidal thinning was only observed in type 1 MNV patients between baseline and first visit (p&#x2009;<&#x2009;0.05). In the las visit, they had a CT between 87 and 96% of baseline measurement. No other influencing factor was detected.<br><br>CONCLUSIONS: Patients with nAMD (type 1 MNV) have higher CT than patients with type 3. However, patients with type 1 MNV experience significant choroidal thinning, and CT is similar in both groups after antiVEGF treatment. Smoking, type of drusen or other OCT features have no influence in this reduction.}, }
@article {pmid41348378, year = {2025}, author = {Wang, S and Hong, Y and Qu, Y and Zheng, K and Luo, H and Chen, R and Jia, H and Liu, X and Sun, X}, title = {Association between low handgrip strength and the increased risk of age-related macular degeneration: results from UK biobank cohort study.}, journal = {Aging clinical and experimental research}, volume = {38}, number = {1}, pages = {16}, pmid = {41348378}, issn = {1720-8319}, mesh = {Humans ; *Hand Strength/physiology ; Male ; Female ; *Macular Degeneration/epidemiology/physiopathology ; Middle Aged ; Aged ; United Kingdom/epidemiology ; Prospective Studies ; Risk Factors ; Adult ; Incidence ; Biological Specimen Banks ; Biomarkers/blood ; Cohort Studies ; Proportional Hazards Models ; UK Biobank ; }, abstract = {OBJECTIVES: To determine whether handgrip strength is associated with the incidence of age-related macular degeneration.<br><br>METHODS: A prospective cohort study of over 500 thousand UK Biobank participants aged 40-69 years. Individuals&#x2009;&#x2265;&#x2009;50 years and without age-related macular degeneration at baseline were included. Exposure was the handgrip strength measured by dynamometer. Primary outcome was the incidence of age-related macular degeneration during 13 years of follow-up. Cox proportional-hazard models were fitted to estimate the risk effect for handgrip strength on age-related macular degeneration, and stratified for sociodemographic and lifestyle factors. Mediation models were regressed to explore underlying mechanisms driven by inflammatory and erythrocyte-related biomarkers.<br><br>RESULTS: 382174 eligible participants in the UK Biobank were included. After 4680431 person-year, 7987 individuals (2.09%) developed age-related macular degeneration. Individuals in the lowest quintile of handgrip strength had higher risk of age-related macular degeneration incidence (Hazard Ratio, 1.25; 95% CI, 1.16-1.35) compared with those in the highest quintile. Per 5&#xa0;kg decrement in handgrip strength was associated with increased risk of age-related macular degeneration incidence (Hazard Ratio, 1.06; 95% CI, 1.04-1.08) with similar trend among all subgroups except for sex. Specific inflammatory and erythrocyte-related biomarkers partially (37.5%) mediated the incidence of age-related macular degeneration as substantial biological mechanisms following handgrip strength decrease.<br><br>CONCLUSIONS: Our findings suggest that handgrip strength is associated with the incidence of age-related macular degeneration under the mediation of systemic proinflammatory factors. The current study holds an outlook for improved visual health over the evaluation and intervention of muscle strength in old-age population.}, }
@article {pmid41348407, year = {2025}, author = {Hang, Z and Li, Y and Ren, W and Du, H}, title = {The blood-retinal barrier in ocular pathologies: an updated narrative review.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {10}, pmid = {41348407}, issn = {1573-2630}, mesh = {Humans ; *Blood-Retinal Barrier/physiopathology/pathology ; *Retinal Diseases/physiopathology ; *Eye Diseases/physiopathology ; }, abstract = {PURPOSE: To provide a comprehensive overview of the structural and functional characteristics of the blood-retinal barrier (BRB), examine its critical role in the pathogenesis of major ocular diseases, and summarize current and emerging therapeutic strategies aimed at restoring BRB integrity.<br><br>METHODS: A literature search was conducted in PubMed, Scopus, and Web of Science databases, focusing primarily on publications from the past 10 years supplemented by seminal earlier works. This narrative review synthesizes evidence on BRB molecular anatomy, pathological mechanisms, disease-specific roles, and therapeutic interventions.<br><br>RESULTS: The BRB comprises inner (iBRB) and outer (oBRB) compartments with distinct cellular and molecular architectures. BRB dysfunction is driven by convergent mechanisms including aging, hyperglycemia, oxidative stress, inflammation, and hypoxia, which disrupt tight junction proteins and promote aberrant angiogenesis. This barrier breakdown constitutes a pivotal pathogenic driver in major blinding diseases: age-related macular degeneration, diabetic retinopathy and retinal vein occlusion, glaucoma, and uveitis. Current standard treatments include anti-VEGF agents and corticosteroids. Emerging strategies target Wnt/&#x3b2;-catenin signaling, employ senolytic therapies, utilize biomaterial-based drug delivery, and develop organ-on-a-chip models for personalized medicine.<br><br>CONCLUSIONS: BRB disruption represents a critical inflection point in ocular disease progression, triggering self-perpetuating cycles of neuroinflammation and degeneration. Effective restoration requires multi-faceted approaches combining anti-angiogenic, antiinflammatory, and barrier-strengthening mechanisms. Future research should focus on dynamic functional assessment, single-cell multi-omics integration, and adaptive therapeutic strategies to prevent irreversible vision loss.}, }
@article {pmid41349782, year = {2026}, author = {Horrigan, WF and Caron, Q and Rodriguez, A and Singh, R and Anand-Apte, B}, title = {The effect of age on wound healing in the laser induced choroidal neovascularization model.}, journal = {Experimental eye research}, volume = {263}, number = {}, pages = {110790}, pmid = {41349782}, issn = {1096-0007}, support = {R01 EY027083/EY/NEI NIH HHS/United States ; R01 EY020861/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; T32 GM137868/GM/NIGMS NIH HHS/United States ; R01 EY016490/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/physiopathology/metabolism/etiology/pathology ; Mice, Inbred C57BL ; *Disease Models, Animal ; Mice ; *Wound Healing/physiology ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Aging/physiology ; Tomography, X-Ray Computed ; Laser Coagulation ; Epithelial-Mesenchymal Transition ; Indocyanine Green ; Choroid/pathology ; Gliosis ; Fibrosis ; }, abstract = {The laser induced model of choroidal neovascularization (LiCNV) is a commonly used in vivo rodent model to study neovascular age-related macular degeneration (nAMD), although progression of this model is not well understood. In this study we characterize and compare the longitudinal progression of wound healing of laser induced choroidal neovascular (CNV) lesions in young and old mice. Using 2-month and 12-month-old C57BL/6J mice and ocular computerized tomography (OCT), fluorescein and indocyanine green angiography we performed a longitudinal imaging analysis at 3-, 7-, 14- and 28-days following laser injury. This was compared with immunohistochemical analysis of the lesions at similar timepoints for markers of angiogenesis, fibrosis, epithelial-to-mesenchymal transition (EMT), and gliosis. OCT analysis determined an increased lesion volume in older mice. In contrast younger mice demonstrated earlier vascularization and fibrosis with no difference in neovascularization or leakage. Reactive gliosis occurs directly above the laser-induced CNV lesion in both ages. The RPE in this model encloses the lesion area by day 14 in both young and old mice. This study concludes that age is an important variable in some but not all aspects of laser-induced CNV.}, }
@article {pmid41350718, year = {2025}, author = {Ruiz-Medrano, J and Pana, I and García-Zamora, M and Flores-Moreno, I and Puertas, M and Ruiz-Moreno, JM}, title = {Faricimab treat-and-extend approach for neovascular age-related macular degeneration: insights from real-world clinical practice.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {5}, pmid = {41350718}, issn = {2056-9920}, abstract = {PURPOSE: To evaluate the clinical outcomes of the switch to faricimab in a treat-and-extend (T&amp;E) regimen patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective cohort study included consecutive patients with nAMD who had previously been treated with anti-VEGF agents in a T&amp;E regimen, with treatment intervals (TI) that could not be extended beyond 12 weeks, and a minimum follow-up of 24 weeks. These patients were switched to faricimab therapy in a T&amp;E regimen for at least 6 months. The primary endpoint was the TI between intravitreal injections (IVIs), and the secondary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to the last follow-up visit (LFUV).<br><br>RESULTS: A total of 225 eyes from 188 patients were included, with a mean age of 79.6&#x2009;&#xb1;&#x2009;7.4 years. Previous anti-VEGF treatments included ranibizumab (n&#x2009;=&#x2009;34), aflibercept (n&#x2009;=&#x2009;144), brolucizumab (n&#x2009;=&#x2009;6), and bevacizumab (n&#x2009;=&#x2009;41). TI1 (5.9&#x2009;&#xb1;&#x2009;2.0 weeks) matched the prior treatment interval. Significant increases in treatment intervals were observed at subsequent time points (TI2: 8.2&#x2009;&#xb1;&#x2009;3.2 weeks, TI3: 10.1&#x2009;&#xb1;&#x2009;3.9 weeks, TI4: 10.7&#x2009;&#xb1;&#x2009;4.3 weeks, TI5: 9.9&#x2009;&#xb1;&#x2009;4.0 weeks, and TI6: 8.5&#x2009;&#xb1;&#x2009;4.4 weeks; p&#x2009;<&#x2009;0.001). BCVA remained stable, going from 0.41&#x2009;&#xb1;&#x2009;0.23 to 0.43&#x2009;&#xb1;&#x2009;0.24 (p&#x2009;=&#x2009;0.0112). The mean number of injections was 5.9&#x2009;&#xb1;&#x2009;1.9, with a mean follow-up duration of 51.4&#x2009;&#xb1;&#x2009;11.8 weeks.<br><br>CONCLUSIONS: The switch to faricimab in a T&amp;E regimen significantly increased treatment intervals maintaining BCVA in patients with nAMD under other anti-VEGF treatments. No serious adverse events were reported. Longer follow-up is needed to confirm these results.}, }
@article {pmid41350762, year = {2025}, author = {Ma, Y and Zan, H and Li, L and Li, S and Yu, X and Li, J and Cai, J and Zhang, H and Yang, J and Zhang, R and Salvi, R and Li, W and Wang, H and Yin, S}, title = {Global burden and geospatial drivers of sensory impairment with sense organ disease projections to 2050.}, journal = {Communications medicine}, volume = {6}, number = {1}, pages = {8}, pmid = {41350762}, issn = {2730-664X}, support = {82271161//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82330034//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {BACKGROUND: Sense organ diseases represent the leading causes of years lived with disability. Despite its major impact, a comprehensive understanding of sense organ diseases burden remains limited.<br><br>METHODS: Based on the data from the Global Burden of Disease Study 2021 and nighttime light exposure data from remote-sensing satellites, we did secondary analysis and described the epidemiological characteristics of sense organ diseases globally and nationally. The relationship between the specific causes of blindness and vision loss and nighttime light exposure was further explored. We assessed the trends, causes and cross-country inequalities related to sense organ diseases and forecasted the burden of disease until 2050.<br><br>RESULTS: Here we show that in 2021, there are more than 2 billion prevalent cases and more than 77 million years lived with disability cases of sense organ diseases globally. Both age-related macular degeneration and near vision loss show positive correlations with nighttime light exposure. The global burden of sense organ diseases continues to rise from 1990 to 2021, primarily driven by population growth and ageing. Health inequalities exist between different countries and increase over time. Projections of years lived with disability for sense organ diseases from 2022 to 2050 show that although the age-standardized rate remains stable, the number increases significantly.<br><br>CONCLUSIONS: Over the past 32 years, the global burden of sense organ diseases has increased, and cross-country inequalities have intensified due to the trends of population growth and aging. Therefore, it is urgently necessary to formulate more targeted and effective prevention and management strategies.}, }
@article {pmid41352547, year = {2026}, author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Zhang, S}, title = {Multimodal and 3D imaging presentation of the evolution of pressure-related CNV.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105305}, doi = {10.1016/j.pdpdt.2025.105305}, pmid = {41352547}, issn = {1873-1597}, mesh = {Humans ; Female ; Aged ; *Choroidal Neovascularization/diagnostic imaging/etiology/drug therapy ; *Multimodal Imaging/methods ; *Imaging, Three-Dimensional/methods ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Macular Degeneration/drug therapy ; Indocyanine Green ; }, abstract = {This study reports a unique case that visually demonstrates the six-year evolution of a pressure-related choroidal neovascularization (CNV) using multimodal image registration and three-dimensional (3D) reconstruction. A 65-year-old female with neovascular age-related macular degeneration received 33 anti-VEGF injections over six years but experienced continued vision decline. Through precise registration of indocyanine green angiography, and optical coherence tomography angiography images, combined with 3D modeling of swept-source OCTA volume data. We found that the main trunk of this large, tree-like type II CNV originated from an abnormally dilated great vein, which exhibited an anastomosis with an accompanying great vein. Furthermore, the 3D reconstruction viewed from the scleral side revealed that this vein was closely opposed to and shared a shunt branch with an underlying choroidal great artery. The CNV appeared to function as a "pressure-relief valve," sprouting from the venous trunk to alleviate pressure. This case underscores the critical role of deep multimodal imaging integration in tracing CNV origins and reveals that some anti-VEGF-resistant CNVs may represent hemodynamic compensatory disorders secondary to pre-existing large vessel structural abnormalities, rather than purely neovascular diseases.}, }
@article {pmid41352549, year = {2026}, author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Wang, X}, title = {SS-OCTA versus ICGA: a comparison of detection efficiency for large choroidal vein patterns in AMD patients.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105303}, doi = {10.1016/j.pdpdt.2025.105303}, pmid = {41352549}, issn = {1873-1597}, mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Retrospective Studies ; Aged ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; *Indocyanine Green ; Aged, 80 and over ; *Macular Degeneration/diagnostic imaging ; *Choroidal Neovascularization/diagnostic imaging ; Middle Aged ; *Wet Macular Degeneration/diagnostic imaging ; }, abstract = {PURPOSE: To compare the efficacy of swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in visualizing and classifying large choroidal vein topography, and to evaluate the association between specific venous patterns and pachychoroid spectrum disease (PSD)-associated macular neovascularization (MNV).<br><br>METHODS: This retrospective cross-sectional study included 222 eyes from 160 patients with neovascular age-related macular degeneration (nAMD). All participants underwent both SS-OCTA and ICGA imaging. Choroidal venous patterns were classified into four types based on ICGA venous phase images: watershed, anastomotic, upper thicker, and lower thicker. SS-OCTA images were processed and analyzed using Fiji software. Diagnostic agreement between modalities was assessed using Cohen's Kappa. Logistic regression was used to evaluate the association between venous patterns and disease subtypes.<br><br>RESULTS: SS-OCTA and ICGA showed almost perfect agreement in classifying choroidal venous patterns in discernible cases (unweighted Kappa = 0.978). Among 77 eyes where ICGA failed to provide a clear classification, SS-OCTA achieved a definitive diagnosis in 87.0 % (P < 0.001), with the anastomotic type being the most common. Furthermore, the watershed pattern was significantly more prevalent in non-PCV nAMD compared to PCV (29.8 % vs. 12.1 %, p = 0.002), suggesting distinct choroidal venous backgrounds between these subtypes.<br><br>CONCLUSION: SS-OCTA provides a reliable, non-invasive alternative to ICGA for visualizing and classifying large choroidal veins, with superior performance in cases obscured by hemorrhage or leakage. The distinct distribution of venous patterns across nAMD subtypes highlights the potential role of choroidal venous architecture in disease phenotyping and pathogenesis.}, }
@article {pmid41352581, year = {2026}, author = {Dinah, C and Esmaeelpour, M and Rachitskaya, AV and De Salvo, G and Munk, MR}, title = {Functional endpoints in patients with geographic atrophy: What to consider when designing a clinical trial.}, journal = {Progress in retinal and eye research}, volume = {110}, number = {}, pages = {101421}, doi = {10.1016/j.preteyeres.2025.101421}, pmid = {41352581}, issn = {1873-1635}, mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/therapy ; *Clinical Trials as Topic/methods ; *Visual Acuity/physiology ; Quality of Life ; *Research Design ; Endpoint Determination ; }, abstract = {There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure-function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.}, }
@article {pmid41353311, year = {2025}, author = {Willmington, C and Kirby, A and Murphy, A}, title = {The economic impact of retinal diseases for which gene therapy is emerging: a systematic literature review.}, journal = {Health economics review}, volume = {16}, number = {1}, pages = {21}, pmid = {41353311}, issn = {2191-1991}, support = {101073316//European Union's Horizon Europe/ ; }, abstract = {BACKGROUND: Retinal disease is one of the leading causes of blindness and vision impairment worldwide, including Europe. With the advent of gene therapy, the treatment landscape for retinal disease is changing and clinical trials are underway investigating the therapeutic potential of gene therapy in both acquired and inherited retinal diseases. Given the high price of innovative medicines, it is essential to consider the current costs associated with retinal diseases to inform economic evaluations early in the life cycle of these forthcoming treatments. These could inform future reimbursement decisions, health budgets and service delivery plans.<br><br>AIM: This systematic literature review sought to examine the economic burden of retinal diseases, for which gene therapy is emerging for patients in Europe.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline, a systematic search was performed using the Medline, CINAHL, EconLit and Embase databases. The searches were restricted to English language articles published after 1st January 2000. Following article selection, data were extracted in a tabular form and a narrative synthesis was performed.<br><br>RESULTS: A total of 28 research studies were identified and included in the review that varied in terms of disease of interest, size, country setting, methodology, as well as how costs were reported and valued. While many retinal diseases were considered, almost half of the articles related to the costs of neovascular age-related macular degeneration (nAMD). Significant cost variations were observed across the studies as costs ranged from 45 USD to almost 30,000 USD per patient per annum, across all conditions combined.<br><br>CONCLUSION: This systematic literature review evidences the heterogeneity among studies analysing the economics of retinal diseases underlying vision impairment. The paucity in the literature, signals the need for further research investigating the costs associated with retinal diseases, for which innovative therapies are expected to enter the market and will be subject to evaluation by decision-makers, whose decisions will have a significant impact on the delivery of these technologies to patients.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13561-025-00707-7.}, }
@article {pmid41353467, year = {2025}, author = {E de Carlo Forest, T and Marin, AI and Gill, Z and Gnanaraj, R and Patnaik, JL and Poppelaars, F and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Frazer-Abel, AA and Holers, VM and Mandava, N}, title = {Association between systemic complement levels and choroidal thickness in advanced non-neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1442}, pmid = {41353467}, issn = {2045-2322}, support = {R01 EY032456/EY/NEI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; R01EY032456//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, mesh = {Humans ; Female ; Male ; *Macular Degeneration/pathology/blood/diagnostic imaging/immunology ; *Choroid/pathology/diagnostic imaging ; Aged, 80 and over ; Aged ; Cross-Sectional Studies ; Tomography, Optical Coherence ; *Complement System Proteins/metabolism ; Complement Activation ; }, abstract = {To investigate associations between systemic complement activation and choroidal thickness (CT) in advanced non-neovascular age-related macular degeneration (nnAMD). Cross-sectional study of 96 patients (187 eyes) with advanced nnAMD enrolled in the University of Colorado AMD Registry (August 2014-June 2021). Medical histories, multimodal imaging, and plasma samples were collected. Plasma was analyzed via enzyme-linked immunosorbent assay and multiplex Luminex assays for complement factors C1q, monoclonal B-cell lymphocytosis, C2, C4, C4b, C3, C3a, Factor B, Bb, Factor D, Factor H, Factor I, C5 and soluble C5b-9. CT was measured subfoveally and at 1000 μm intervals superiorly, inferiorly, nasally, and temporally using Spectralis OCT. Linear modeling with generalized estimating equations assessed log-transformed OCT and complement factors. The mean age was 82.2 years (± 7.1 SD); 54.2% were female. Average CT was negatively associated with Bb (β=-0.47, SE: 0.12, p = 0.0001) and the Bb/Factor B ratio (β=-0.28, SE: 0.12, p = 0.02), but not other complement markers. Bb levels correlated with alternative pathway components but not with classical or lectin pathway markers. We found a key association between systemic complement activation of Factor B and choroidal thickness in patients with advanced nnAMD, implying the potential involvement of the systemic alternative pathway in nnAMD patients.}, }
@article {pmid41353670, year = {2026}, author = {Poteet, J and Koetting, C and Vakharia, PS}, title = {Role of B Vitamins in Preventing the Development and Progression of Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {1}, pages = {1-19}, pmid = {41353670}, issn = {2193-8245}, support = {Editorial/writing assistance//Bausch + Lomb/ ; Funding for rapid service fee//Bausch + Lomb/ ; }, abstract = {No current treatments are curative for age-related macular degeneration (AMD), and preventing disease progression is challenging. Dietary factors play a role in the course of macular degeneration, and management of AMD commonly includes nutraceuticals (e.g., supplementation with a combination of antioxidant vitamins and minerals). This commentary summarizes the existing literature, emerging evidence, and upcoming research on the role of B vitamins in both preventing the development of AMD and slowing its progression.}, }
@article {pmid41354182, year = {2026}, author = {Xu, L and Chen, ZA and Wu, CH and Chen, YP and Wu, SH and Mou, CY and Tseng, CL and Chien, Y and Chan, HW and Yang, TC and Chiou, SH}, title = {Dual-functionalized mesoporous silica nanoparticles for topical axitinib delivery to the posterior eye segment.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {217}, number = {}, pages = {107398}, doi = {10.1016/j.ejps.2025.107398}, pmid = {41354182}, issn = {1879-0720}, mesh = {Animals ; *Silicon Dioxide/chemistry/administration &amp; dosage ; *Axitinib/administration &amp; dosage/pharmacokinetics/chemistry ; *Nanoparticles/chemistry/administration &amp; dosage ; Choroidal Neovascularization/drug therapy/metabolism ; Mice ; Porosity ; Mice, Inbred C57BL ; *Posterior Eye Segment/metabolism/drug effects ; Ophthalmic Solutions/administration &amp; dosage ; Administration, Topical ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacokinetics/chemistry ; Drug Delivery Systems ; Male ; Drug Carriers/chemistry ; }, abstract = {Topical drug delivery to the posterior eye segment remains a significant challenge due to ocular anatomical barriers, particularly in diseases such as wet age-related macular degeneration (AMD), where treatment typically relies on frequent intravitreal (IVT) injections of anti-angiogenic agents. In this study, we present a non-invasive eye drop formulation of axitinib (AXT), a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, encapsulated within 25-nm dual-functionalized mesoporous silica nanoparticles (AXT@dual-MSNs) engineered for efficient retinal delivery. The nanoparticles feature sulfonate-functionalized mesopores that enhanced AXT loading and solubilization, along with a PEGylated/quaternary ammonium-modified surface that improved colloidal stability and favored intramesopore drug confinement. Following topical administration, AXT@dual-MSNs achieved retinal accumulation via the conjunctiva-sclera-choroid pathway, effectively bypassing the corneal route. A pharmacokinetic analysis confirmed rapid, transscleral delivery of AXT with therapeutically relevant concentrations in the retina. In a laser-induced choroidal neovascularization (CNV) mouse model, a well-established surrogate for wet AMD, AXT@dual-MSN eyedrops significantly suppressed neovascular lesion formation, outperforming free-drug eyedrops and IVT AXT injection. Notably, the formulation exhibited excellent ocular tolerance, with no evidence of local toxicity or contralateral eye exposure. This work introduces a novel nanocarrier system capable of overcoming the longstanding delivery barrier to the posterior eye segment via eyedrops, offering a safe, effective, and clinically translatable alternative to IVT injections. The modular design of AXT@dual-MSNs also holds promise for expanding topical access to other hydrophobic or labile therapeutics targeting retinal diseases.}, }
@article {pmid41354398, year = {2026}, author = {Fernández, Y and Subirada, PV and Vaglienti, MV and Tovo, A and Paz, MC and Barcelona, PF and Sánchez, MC}, title = {Glial fibrillary acidic protein, an early and sustained indicator of retinopathy progression.}, journal = {Experimental eye research}, volume = {263}, number = {}, pages = {110796}, doi = {10.1016/j.exer.2025.110796}, pmid = {41354398}, issn = {1096-0007}, mesh = {*Glial Fibrillary Acidic Protein/metabolism ; Humans ; Disease Progression ; Biomarkers/metabolism ; *Retinal Diseases/metabolism/diagnosis ; Astrocytes/metabolism ; Ependymoglial Cells/metabolism ; Gliosis/metabolism ; Animals ; Retina/metabolism ; Neuroglia/metabolism ; }, abstract = {Macroglial cells, particularly astrocytes and Müller glial cells (MGCs), are crucial for maintaining retinal health and function. Both cell types express glial fibrillary acidic protein (GFAP), although their expression levels and patterns differ. In a healthy retina, astrocytes constitutively express GFAP, whereas MGCs typically show low or undetectable levels. In response to retinal insults, macroglial cells are activated through a process known as gliosis to preserve retinal homeostasis. The gliotic response includes cellular hypertrophy and the upregulation of intermediate filaments -primarily GFAP- as a protective mechanism. However, when harmful stimuli persist, both astrocytes and MGCs may contribute to pathology, becoming associated with ongoing damage and loss of retinal function. Changes in GFAP expression have been described in conditions like diabetic retinopathy, sickle-cell retinopathy, and age-related macular degeneration, indicating retinal stress and dysfunction. A deeper understanding of GFAP's dual role in retinal diseases is critical for developing effective treatments for these conditions and for identifying its potential as a biofluid-based biomarker.}, }
@article {pmid41354925, year = {2025}, author = {Nafar, H and Mahdavi Sharif, P and Rezaei, N}, title = {Advances in nanomedicine-based retinal drug delivery: mechanisms and translational applications.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {33}, pmid = {41354925}, issn = {1477-3155}, mesh = {Humans ; *Nanomedicine/methods ; Animals ; *Drug Delivery Systems/methods ; *Retinal Diseases/drug therapy ; Nanoparticles/chemistry ; *Retina/drug effects/metabolism ; Blood-Retinal Barrier ; Intravitreal Injections ; Translational Research, Biomedical ; Biological Availability ; }, abstract = {Retinal diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), alongside optic neuropathies such as glaucoma, are primary contributors to irreversible visual impairment and blindness, and not only impact the quality of life but also place considerable socioeconomic pressures on healthcare systems worldwide. Despite the availability of several therapeutic modalities, the clinical management of these conditions remains challenging due to the unique anatomical and physiological barriers of the eye (i.e., tear film, cornea, blood-aqueous barrier, and the blood-retinal barrier), which impede achieving therapeutic drug concentrations in the posterior segment. Topical administration exhibits low bioavailability, while systemic delivery is generally inefficient and associated with adverse effects. Intravitreal injections (IVIs) deliver drugs directly to the vitreous but necessitate frequent administration, hence increasing risks of endophthalmitis, retinal detachment, and patient non-compliance. Nanomedicine has revolutionized drug delivery science across various medical fields, offering significant advantages for therapeutic interventions. Nanoparticle (NP)-based systems enhance drug solubility and stability, improve pharmacokinetic profiles, facilitate passage across biological barriers, and enable targeted delivery to specific cells or tissues with surface modifications, thereby potentially increasing bioavailability while minimizing systemic toxicity. This review aims to illustrate recent advancements in the design principles, preclinical applications, and translational potential of NP-based drug delivery systems aimed at addressing the challenges inherent in treating posterior segment eye diseases. NPs (ranging from polymeric and lipid-based systems to inorganic and hybrid forms) have been able to effectively carry various formulations of antiangiogenic, anti-inflammatory, anti-neoplastic, and antioxidant compounds, as well as genetic materials, to counteract such disorders. NP's size, surface charge, and composition can be modulated to optimize interaction with ocular tissues and overcome barriers. With their controlled and sustained drug release, NPs decrease the required frequency of IVIs. In addition, NPs can encapsulate a wide range of therapeutic agents (including hydrophobic molecules, proteins, and nucleic acids) and are amenable to the functionalization of their surfaces with ligands for specific receptors on retinal cells, thereby enhancing therapeutic efficacy and minimizing local toxicities. The findings of this review will establish a research agenda for translating NP-based interventions into clinical practice.}, }
@article {pmid41356440, year = {2025}, author = {Mimura, T and Noma, H}, title = {Metabolites of traffic-related volatile organic compounds in age-related macular degeneration.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e20405}, pmid = {41356440}, issn = {2167-8359}, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Macular Degeneration/urine/metabolism ; Aged ; *Volatile Organic Compounds/urine/metabolism ; *Vehicle Emissions/analysis/toxicity ; Middle Aged ; *Air Pollutants/adverse effects ; Gas Chromatography-Mass Spectrometry ; Aged, 80 and over ; Case-Control Studies ; }, abstract = {BACKGROUND: Volatile organic compounds (VOCs), commonly emitted from vehicle exhaust and industrial activities, are prevalent air pollutants in urban environments. These compounds have been reported to cause various health effects through mechanisms such as oxidative stress and neurotoxicity. Recently, air pollution has attracted attention as a potential risk factor for age-related macular degeneration (AMD); however, the association between VOC exposure and AMD remains unclear.<br><br>OBJECTIVE: This study aimed to assess VOC exposure levels among urban-dwelling AMD patients by quantifying urinary metabolites and investigating the association between VOCs and AMD.<br><br>METHODS: This cross-sectional study included 40 untreated AMD patients (AMD group), 10 cataract patients (Cataract group), and 10 healthy controls (Healthy group). Representative urinary metabolites of VOCs-2-methylhippuric acid, 3-methylhippuric acid, mandelic acid, phenylglyoxylic acid, and trans,trans-muconic acid-were measured using gas chromatography-mass spectrometry (GC/MS), with concentrations corrected for urinary creatinine. Group comparisons were performed based on creatinine-adjusted metabolite levels.<br><br>RESULTS: The AMD group exhibited elevated urinary VOC metabolite levels compared to both control groups. The ratios of mean concentrations in the AMD group versus the Healthy and Cataract groups, respectively, were: 2-methylhippuric acid (201% and 181%), 3-methylhippuric acid (190% and 139%), mandelic acid (304% and 198%), phenylglyoxylic acid (118% and 90%), and trans,trans-muconic acid (214% and 92%). Among these, 2-methylhippuric acid and mandelic acid were significantly higher in the AMD group than in both controls (p&#xa0;<&#xa0;0.001 and p&#xa0;=&#xa0;0.042; p&#xa0;<&#xa0;0.001, respectively). Trans,trans-muconic acid also showed a significant increase compared to the Healthy group (p&#xa0;<&#xa0;0.001). Correlation analysis within the AMD group revealed moderate but significant associations for 2-methylhippuric acid (r&#xa0;=&#xa0;0.29, p&#xa0;=&#xa0;0.011), mandelic acid (r&#xa0;=&#xa0;0.47, p&#xa0;<&#xa0;0.001), and trans,trans-muconic acid (r&#xa0;=&#xa0;0.27, p&#xa0;=&#xa0;0.020). Multivariate logistic regression identified mandelic acid as an independent factor significantly associated with AMD (odds ratio = 17.20, p&#xa0;<&#xa0;0.001). Subgroup analysis categorized the AMD group into drusenoid AMD, typical AMD (t-AMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). No significant differences in urinary VOC metabolite levels were observed among the four subtypes after multiple comparison adjustment.<br><br>CONCLUSIONS: These findings indicate that AMD patients are exposed to higher levels of traffic-related VOCs. While mandelic acid-a styrene metabolite-was independently associated with AMD, its role should be interpreted as a potential exposure marker rather than a definitive disease biomarker. Further longitudinal studies are warranted to clarify causal relationships between VOC exposure and AMD development.}, }
@article {pmid41356765, year = {2025}, author = {Warner, JD and Tuli, A and Zhang, DD and Singireddy, R and Ebrahimiadib, N and Chen, J}, title = {Full-Spectrum Pachychoroid Manifestation in One Eye: A Case Report.}, journal = {Case reports in ophthalmology}, volume = {16}, number = {1}, pages = {896-902}, pmid = {41356765}, issn = {1663-2699}, abstract = {INTRODUCTION: The pachychoroid spectrum refers to a group of chorioretinal disorders including pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). These conditions are thought to represent progressive stages, beginning with subclinical retinal pigment epithelium (RPE) changes in PPE, advancing to serous retinal detachment in CSC, followed by choroidal neovascularization in PNV, and culminating in aneurysmal dilation of vessels in PCV. We present a rare case of the pachychoroid spectrum in which lesions in all four stages were simultaneously observed in a single, fovea-sparing eye.<br><br>CASE PRESENTATION: An 85-year-old man presented with a 1-month history of a visual disturbance in his left eye. Examination revealed all four stages of pachychoroid disease in the same eye: choroidal neovascular membrane (CNV) with subretinal hemorrhage (pachychoroid neovascularization, PNV), multiple RPE defects (PPE), and findings consistent with CSC and PCV. He was treated with a combination of anti-VEGF injections and focal laser therapy with the lesions stabilizing after 2 years.<br><br>CONCLUSION: Although it has features similar to age-related macular degeneration, pachychoroid spectrum is a distinct disease entity, with a slower onset and greater response to initial therapy. It may necessitate therapies otherwise not used for other causes of neovascularization like focal laser treatment and verteporforin photodynamic therapy. It is a unique pathologic process presenting with varying stages/lesions that have distinct morphological features but are thought to be a part of the same spectrum.}, }
@article {pmid41358132, year = {2025}, author = {Pashandi, Z and Liu, M and Azam, M and Das, S and Sheves, M and Jastrzebska, B}, title = {Therapeutic Potential of Partial Retinoid Agonists against Vertebrate Rhodopsin Misfolding Disorders.}, journal = {ACS omega}, volume = {10}, number = {47}, pages = {57487-57502}, pmid = {41358132}, issn = {2470-1343}, support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY032874/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; T32 GM158814/GM/NIGMS NIH HHS/United States ; }, abstract = {Mutations in rod opsin are a leading cause of inherited retinal degenerative diseases such as retinitis pigmentosa (RP). Pharmacological compounds that stabilize rhodopsin (Rho) and mitigate cellular stress pathways hold promise for therapeutic intervention. Among these, retinoid analogs have shown efficacy in models of autosomal dominant RP (adRP) and age-related macular degeneration (AMD). In this study, we evaluated the pharmacological potential of two partial retinoid agonists, acyclic-retinal and 9-cis-9-demethyl-retinal, as well as newly synthesized retinol and amine derivatives of 9-cis-9-demethyl-retinal. A photoreceptor-derived 661W cell line stably expressing two RP-linked misfolding rod opsin mutants, P23H and T289P, was used to assess the compound activity. We investigated the effects on opsin folding, glycosylation, membrane localization, and pigment regeneration. Both acyclic-retinal and 9-cis-9-demethyl-retinal promoted mature glycosylation and enhanced cell surface trafficking of P23H and T289P rod opsins. Spectroscopic analysis confirmed that these compounds regenerated functional, photosensitive pigments and stabilized the receptor in the Meta-I conformation upon light exposure. Notably, 9-cis-9-demethyl-retinal exhibited higher binding affinity than 9-cis-retinal, without impairing visual signaling postphotoisomerization. Among the derivatives, the amine form of 9-cis-9-demethyl-retinal was most effective in promoting proper folding and localization of misfolded rod opsin, outperforming the corresponding retinol analog. These findings support the therapeutic potential of acyclic-retinal, 9-cis-9-demethyl-retinal, and its derivatives for rescuing misfolded rod opsin and delaying photoreceptor degeneration in RP.}, }
@article {pmid41361163, year = {2025}, author = {Farashi, S and Abbott, CJ and Ansell, BRE and Wu, Z and Altay, L and Arnon, E and Arnould, L and Bagdasarova, Y and Balaskas, K and Chen, FK and Chew, E and Chowers, I and Clarke, S and Cukras, C and Delcourt, C and Delyfer, MN and den Hollander, AI and Fauser, S and Finger, RP and Gabrielle, PH and Han, J and Hodgson, LAB and Hogg, R and Holz, FG and Hoyng, C and Kumar, H and Lad, EM and Lee, A and Luhmann, UFO and Mauschitz, MM and McKnight, AJ and McLenachan, S and Mishra, A and Moghul, I and Orozco, LD and Sampson, DM and Scott, LW and Sitnilska, V and Song, S and Stockwell, A and Swaroop, A and Terheyden, JH and Tiosano, L and Tufail, A and Yaspan, BL and ,  and ,  and Pébay, A and Fletcher, EL and Guymer, RH and Bahlo, M and , }, title = {HTRA1/lncRNA HTRA1-AS1 dominates in age-related macular degeneration reticular pseudodrusen genetic risk with no complement involvement.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {10854}, pmid = {41361163}, issn = {2041-1723}, support = {K23 EY026988/EY/NEI NIH HHS/United States ; GNT1195236//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1157776//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Independent Research Institute Infrastructure Support Scheme//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT2008382//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1154389//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1194667//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Z01EY000546//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; Operational Infrastructure Support//Department of Health, State Government of Victoria (Victorian Department of Health)/ ; }, mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/genetics ; *Macular Degeneration/genetics/pathology ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Aged ; Male ; Female ; *RNA, Long Noncoding/genetics ; Polymorphism, Single Nucleotide ; Retina/pathology/metabolism ; *Retinal Drusen/genetics ; Chromosomes, Human, Pair 10/genetics ; Chromosomes, Human, Pair 1/genetics ; Quantitative Trait Loci ; Middle Aged ; Aged, 80 and over ; Proteins/genetics ; }, abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2165 AMD+/RPD+ and 4181 AMD+/RPD- compared to 7639 control participants, both chromosomes 1 (CFH) and 10 (ARMS2/HTRA1) major AMD risk loci are reidentified. However association is only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD- cases. The chromosome 1 locus is notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA HTRA1-AS1 (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. HTRA1-AS1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identifies even stronger enrichment for the chromosome 10 risk genotype.}, }
@article {pmid41361469, year = {2025}, author = {Wang, X and Gui, S and Liu, X and Tao, Y and Gao, J and Liu, H}, title = {Eriocitrin inhibits sodium iodate-induced cuproptosis and barrier function impairment in retinal pigment epithelium via SIRT7/YAP/ATP7A pathway.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {86}, pmid = {41361469}, issn = {1479-5876}, support = {2023zhyx-C72//the Research Fund Project of Anhui Institute of Translational Medicine/ ; }, mesh = {*Retinal Pigment Epithelium/drug effects/pathology/metabolism ; *Iodates ; Animals ; Humans ; *Signal Transduction/drug effects ; Cell Line ; Mice, Inbred C57BL ; Mice ; Macular Degeneration/pathology/drug therapy ; YAP-Signaling Proteins ; Oxidative Stress/drug effects ; Cell Survival/drug effects ; Apoptosis/drug effects ; *Adaptor Proteins, Signal Transducing/metabolism ; *Flavones/pharmacology ; Reactive Oxygen Species/metabolism ; }, abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is characterized by retinal pigment epithelium (RPE) barrier dysfunction, and currently lacks effective treatment options. Eriocitrin is a natural flavonoid with antioxidant and anti-inflammatory properties, and its potential role in inhibiting cuproptosis and improving RPE barrier function remains unclear.<br><br>METHODS: ARPE-19 cells treated with sodium iodate (NaIO&#x2083;) were used to establish an in vitro AMD model. The effects of eriocitrin at various concentrations (0-100 &#xb5;M) and treatment durations on cell viability were assessed using the CCK-8 assay. ELISA and ROS fluorescence were used to assess inflammation and oxidative stress levels. Western blotting and qPCR analysis were employed to evaluate the expression of copper-dependent programmed cell death (cuproptosis)-related markers. RPE barrier function was analyzed by transepithelial electrical resistance (TEER), FITC-dextran permeability assays, and the expression of tight junction proteins. We further utilized siRNA to knockdown SIRT7 and ATP7A gene, and pharmacological inhibition of YAP using verteporfin. In vivo, a NaIO&#x2083;-induced AMD model was established in both C57BL/6J and SIRT7 silencing mice, followed by administration of eriocitrin (25 or 50&#xa0;mg/kg). Retinal histology and protein expression were subsequently analyzed.<br><br>RESULTS: Eriocitrin significantly ameliorated NaIO&#x2083;-induced reductions in cell viability, decreased ROS levels, and suppressed inflammatory cytokine expression. It also restored RPE barrier function in a dose-dependent manner. Mechanistically, eriocitrin modulated SIRT7 expression, inhibited YAP activity, and enhanced ATP7A expression. Genetic silencing or knockdown of SIRT7 markedly weakened the protective effects of eriocitrin, including its antioxidant and barrier-restoring functions. YAP inhibition by verteporfin partially mimicked the actions of eriocitrin, while ATP7A silencing completely abrogated its effects, indicating that the SIRT7/YAP/ATP7A axis plays a crucial role in the therapeutic mechanism of eriocitrin against AMD.<br><br>CONCLUSION: This study demonstrated that eriocitrin alleviates NaIO&#x2083;-induced oxidative stress and RPE barrier dysfunction by modulating the SIRT7/YAP/ATP7A signaling pathway and inhibiting cuproptosis. Our findings indicated eriocitrin as a promising natural therapeutic candidate for dry AMD and lay the foundation for developing flavonoid-based anti-cuproptosis strategies.}, }
@article {pmid41362358, year = {2026}, author = {Hinterhuber, L and Birner, K and Schrittwieser, J and Coulibaly, LM and Fuchs, P and Schürer-Waldheim, S and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Reiter, GS}, title = {Biomarker-Specific Test-Retest Repeatabilities of Microperimetry in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100978}, pmid = {41362358}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the biomarker-specific intradevice and interdevice repeatability of microperimetry (MP) examinations in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Cross-sectional study.<br><br>SUBJECTS: Twenty eyes of 20 individuals with nAMD.<br><br>METHODS: Patients underwent 2 consecutive MP assessments on the MP-3 (photopic) and Macular Integrity Assessment ([MAIA], mesopic), each in a randomized sequence. The pointwise sensitivity values were obtained using a 45-stimuli grid and were coregistered with the OCT volumes. Intraretinal fluid (IRF), subretinal fluid, and pigment epithelium detachment (PED) were quantified with deep learning, whereas subretinal hyperreflective material (SHRM) and ellipsoid zone (EZ) loss were manually annotated. Intradevice repeatability was assessed using Bland-Altman plots, coefficient of repeatability (CoR) and intraclass correlation coefficient. Differences in fixation stability and examination time were calculated using mixed-effect models.<br><br>MAIN OUTCOME MEASURES: Intradevice and interdevice repeatability and impact of OCT biomarkers on repeatability.<br><br>RESULTS: Analysis of a total of 3600 stimuli points revealed a CoR of &#xb1;6.37 decibel and &#xb1;5.68 for MP-3 and MAIA, respectively. Presence of OCT biomarkers had a significant impact on repeatability in the MP-3 for IRF (P < 0.0001), SHRM (P = 0.015), and EZ loss (P < 0.0001). Statistically significant results were obtained in the MAIA for IRF (P < 0.0001), PED (P < 0.0001), SHRM (P = 0.0005), and EZ loss (P < 0.0001). Intraclass correlation coefficients revealed excellent intradevice repeatability and good interdevice repeatability, ranging from 0.83 [95% confidence interval [CI]: 0.60-0.91] to 0.94 [95% CI: 0.93-0.94].<br><br>CONCLUSIONS: OCT biomarkers IRF, SHRM, and EZ loss significantly impacted repeatability under photopic and mesopic testing conditions with the MAIA also revealing a statistically significant association for PED. These findings demonstrate the viability of the MP devices to detect functional variability associated with nAMD biomarkers. Repeatability between consecutive MP tests in 2 commonly used MP devices showed good-to-excellent metrics in nAMD, which further supports the use of MP as a viable outcome measure in clinical trials and practice.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41366440, year = {2025}, author = {Soni, T and Gupta, S and Bharany, S and Rehman, AU and Ghoniem, RM and Taye, BM}, title = {Retinal vessel segmentation using multi scale feature attention with MobileNetV2 encoder.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {43369}, pmid = {41366440}, issn = {2045-2322}, mesh = {Humans ; *Retinal Vessels/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Diabetic Retinopathy/diagnostic imaging ; Algorithms ; Macular Degeneration/diagnostic imaging ; Glaucoma/diagnostic imaging ; *Retinal Diseases/diagnostic imaging ; }, abstract = {This work introduces the MSFAUMobileNet model, a complex U-Net structure tailored for retinal blood vessel segmentation, which is a critical process for detecting and monitoring retinal diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD). The model uses Multi-Scale Feature Aggregation (MSFA), Residual Connections, and Attention Mechanisms to enhance its segmentation accuracy. Utilizing MobileNetV2 as the encoder, the model is capable of effectively generating 13 bottleneck layers' worth of hierarchical features. Although residual connections and attention mechanisms are useful in improving the segmentation process and guaranteeing the precise outlining of intricate vascular networks, MSFA extracts spatial information at various resolutions. The model was tested on the DRIVE dataset and produced exceptionally high scores with accuracy at 99.99%, Dice coefficient at 99.95%, and Intersection over Union (IoU) at 99.94%. These scores show how efficiently the model separates the complex retinal network, enabling early treatment and detection of retinal disease. MSFAUMobileNet is a good medical image analysis software for real clinical practice owing to its computational speed and precision, particularly in the management of retinal disease.}, }
@article {pmid41369339, year = {2025}, author = {Boey, E and Zaidi, H and Tang, T and Yazdanyar, A}, title = {Role of Angiogenesis in Retinal Diseases and New Advances in Drug Development.}, journal = {Cells}, volume = {14}, number = {23}, pages = {}, pmid = {41369339}, issn = {2073-4409}, mesh = {Humans ; Animals ; *Drug Development/methods ; *Neovascularization, Pathologic/drug therapy ; *Angiogenesis Inhibitors/therapeutic use ; *Retinal Diseases/drug therapy/etiology/pathology ; Macular Degeneration/complications ; Diabetes Complications ; }, abstract = {Dysregulation of angiogenesis can cause a disruption in oxygen and nutrient delivery, resulting in impaired neural retinal function. Understanding the underlying components involved in its pathophysiology is essential to develop new treatments for preserving and restoring vision. The aim of this review is to describe the role of angiogenesis in different retinal and choroidal pathologies and evaluate current and emerging anti-angiogenic therapies for retinopathies. Current research articles, focusing on the latest clinical trials from the last two decades, were used to write this review. We discuss normal angiogenesis, in contrast to pathological angiogenesis, in four diseases: retinal vein occlusion (RVO), age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinopathy of prematurity (ROP). Alongside these diseases, this review discusses relevant anti-angiogenic therapies that have been approved for use and are under active investigation through clinical trials for their safety and efficacy.}, }
@article {pmid41371587, year = {2025}, author = {Chan, KS and Congivaram, HTS and Cuamatzi-Castelan, AS and Lavine, JA and , }, title = {Levodopa and Dopamine Agonists in Neovascular Age-Related Macular Degeneration in the Sight Outcomes Research Collaborative Database.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, pmid = {41371587}, issn = {2468-6530}, support = {K08 EY030923/EY/NEI NIH HHS/United States ; R01 EY034486/EY/NEI NIH HHS/United States ; R01 EY036341/EY/NEI NIH HHS/United States ; R01 EY036826/EY/NEI NIH HHS/United States ; }, abstract = {OBJECTIVE: There is a need for therapies that delay neovascular age-related macular degeneration (AMD) progression. Levodopa (L-DOPA) and dopamine receptor D2 (DRD2) agonists have been proposed as potential agents. We investigated the association between dopamine agonist (DA) exposure and conversion to neovascular AMD using the Sight Outcomes Research Collaborative (SOURCE) database.<br><br>DESIGN: Retrospective cohort analysis from SOURCE.<br><br>PARTICIPANTS: Eyes with nonneovascular AMD at the early or intermediate stage.<br><br>METHODS: We included eyes with a diagnosis of early- or intermediate-stage AMD in 1 eye. We excluded eyes with new exposure to L-DOPA or DRD2 agonist after the time of nonneovascular AMD diagnosis or when a variable of interest was unknown. Propensity score matching was performed, and survival analysis with Cox proportional hazard models was conducted in 3 separate analyses: (1) eyes with no DA exposure versus eyes exposed to any DA; (2) eyes with no DA exposure versus eyes with exposure to DRD2 agonist; and (3) eyes with no DA exposure versus eyes with exposure to L-DOPA.<br><br>MAIN OUTCOME MEASURES: Adjusted hazard ratios of any (1) DA exposure, (2) DRD2 agonist exposure, and (3) L-DOPA exposure in association with conversion to new-onset neovascular AMD.<br><br>RESULTS: There was a 47% reduced likelihood of conversion to neovascular AMD in eyes exposed to L-DOPA compared with those without DA exposure over 5 years (P = 0.028). There was no association between exposure to any DA or exposure to DRD2 agonist and conversion to neovascular AMD.<br><br>CONCLUSIONS: Levodopa exposure was associated with reduced conversion from nonneovascular AMD to new-onset neovascular AMD. A randomized clinical trial to study whether L-DOPA decreases the development of neovascular AMD should be considered.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41372725, year = {2025}, author = {Chang, CP and Hwang, YS and Chou, HD and Yeung, L and Kang, EY and Wu, WC and Lai, CC and Liu, L and Wu, JS and Chen, KJ and Chao, AN and Lin, JY and Chen, YT and Tsai, TH and Ho, MC and Chen, YH}, title = {Use of brolucizumab in refractory neovascular age-related macular degeneration: characteristics and biomarkers of intraocular inflammation from an Asian real-world study.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41372725}, issn = {1613-2246}, abstract = {PURPOSE: To investigate the clinical features and biomarkers associated with intraocular inflammation (IOI) following brolucizumab treatment in Asian switched neovascular age-related macular degeneration (nAMD) patients.<br><br>STUDY DESIGN: Multi-center, retrospective cohort study.<br><br>METHODS: This study included 109 eyes from 93 nAMD patients switched from other anti-vascular endothelial growth factor (VEGF) agents to brolucizumab (Beovu) without loading. Baseline characteristics, IOI timing, initial symptoms, and risk factors were assessed.<br><br>RESULTS: IOI was observed in 17 eyes from 14 patients, including anterior uveitis (AU, n = 7), intermediate uveitis (IU, n = 5), and panuveitis with or without retinal vasculitis (RV, n = 5). Two eyes were asymptomatic. The median duration for IOI onset was 26 days, with 11 of 17 eyes (82.4%) developing IOI before the third brolucizumab injection. Firth-penalized multivariate Cox regression analysis depicted that the total number of anti-VEGF injections within one year prior to brolucizumab initiation (HR = 1.4, p = 0.009) and retinal angiomatous proliferation (RAP) (HR = 10.9, p = 0.009), may be associated with IOI development. In contrast, baseline macular neovascularization (MNV) size and the presence of retinal pigment epithelial and outer retinal atrophy were not associated with IOI occurrence.<br><br>CONCLUSION: Vigilant examination after the initial brolucizumab injections is critical. Patients with identified risk factors may need meticulous monitor following brolucizumab injections.}, }
@article {pmid41373306, year = {2025}, author = {Virk, A and Qin, H and Shahid, MM and Liu, H and Feng, C and Allison, K}, title = {The Impact of Social Determinants of Health on Ocular Diseases in Western New York: A Comparative Ecological Study of Two U.S. Counties.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {23}, pages = {}, pmid = {41373306}, issn = {2227-9032}, abstract = {Background/Objectives: As the world becomes more connected, it is becoming critical for clinicians to understand other cultures, races, and ethnicities to provide the most effective therapy. A comprehensive understanding of all communities necessitates an examination of the social determinants of health (SDH). Eye diseases and many other conditions are influenced by SDH. To elucidate the impact of SDH on eye health, a comparative ecological analysis of Monroe and Erie Counties in New York State was conducted to identify any differences in SDH and glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy prevalence. Methods: The CDC Vision and Eye Health Surveillance System (VEHSS) was utilized to collect glaucoma, AMD, and diabetic retinopathy data in Monroe and Erie Counties, New York State, and the USA for 2019. The American Community Survey, County Health Rankings, and Neighborhood Atlas data portals were used to collect the county socioeconomic demographics, along with other health statistics. Results: Overall, Erie County had a higher prevalence of AMD (9.56% vs. 6.61%, p < 0.0001) and glaucoma (13.05% vs. 11.71%, p < 0.0001) compared to Monroe County. Erie County also had a higher prevalence of AMD and glaucoma across all races, aside from North American Natives. Erie County also had a greater primary care shortage, with only 1 primary care physician for every 1230 individuals. Although income inequality and poverty were similar between Erie and Monroe Counties, Erie County also has more racial segregation regarding the residential layout (ranked 74 on a scale of 0 to 100, with 100 being the most segregated). Conclusions: The results indicate that Erie County had an increased prevalence of AMD and glaucoma compared to Monroe County in 2019, along with a greater primary care shortage. Although this analysis targeted Western New York, disparities such as lack of primary care access and segregation are prevalent across the US, necessitating widespread action to address these problems.}, }
@article {pmid41373488, year = {2025}, author = {Yang, JY and Kim, Y and An, S and Han, JW and Choi, JS and Park, TK}, title = {Retinal Organoid-Derived Exosomes Reduce CNV Lesion and Restore RPE Integrity in Mouse Laser-Induced Choroidal Neovascularization (CNV) Model.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373488}, issn = {1422-0067}, support = {RS-2025-02217948//National Research Foundation of Korea (NRF)/ ; RS-2024-00452984//National Research Foundation of Korea (NRF)/ ; Soonchunhyang University Research fund//Soonchunhyang University Research fund/ ; }, mesh = {Animals ; *Choroidal Neovascularization/therapy/metabolism/pathology/etiology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Exosomes/metabolism/transplantation ; Mice ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; *Organoids/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Retina/metabolism ; Induced Pluripotent Stem Cells/metabolism/cytology ; Lasers/adverse effects ; }, abstract = {To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal Organoid-derived exosome (RO-Exo) distribution after intravitreal (IVT) injection, calcein-labeled RO-Exo was observed using confocal microscopy. CNV was induced in C57BL/6 J mice by laser photocoagulation. RO-Exo was isolated from retinal organoids (differentiation days 55-65) and injected 5 days post-laser. Therapeutic efficacy was evaluated on day 12. Vascular leakage and CNV size were assessed by angiography and CD31 immunostaining. We also examined HIF-1α/VEGF-A expression (Western blotting), Retinal Pigment Epithelium (RPE) integrity markers (immunofluorescence staining for α-SMA, fibronectin, and ZO-1), and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway (phospho-ERK, -p38, -JNK) in CNV lesions. After IVT injection, RO-Exo migrated to the RPE layer, showing high retinotropic distribution. In the CNV model, RO-Exo significantly reduced vascular leakage and CNV size, with greater suppression of HIF-1α and VEGFA expression than aflibercept, the standard-of-care anti-VEGF drug. CD31-positive vasculature was decreased, accompanied by downregulation of fibronectin (a fibrotic marker) and restoration of RPE hexagonality and integrity. Furthermore, RO-Exo inhibited the activation of ERK, P38, and JNK in CNV lesions. Our study results demonstrate that RO-Exo exhibits multi-target therapeutic effects-including anti-angiogenic, anti-fibrotic, and neuroprotective actions-offering a promising alternative to conventional anti-VEGF therapy for nAMD.}, }
@article {pmid41373629, year = {2025}, author = {Mahmud, NM and Paraoan, L and Kamalden, TA}, title = {Thymoquinone Attenuates NF-κβ Signalling Activation in Retinal Pigment Epithelium Cells Under AMD-Mimicking Conditions.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373629}, issn = {1422-0067}, support = {RP033-14HTM//University of Malaya/ ; H-20001-00-E000059//Ministry of Higher Education/ ; }, mesh = {*Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Benzoquinones/pharmacology ; Humans ; *Signal Transduction/drug effects ; *NF-kappa B/metabolism ; *Macular Degeneration/metabolism/pathology/drug therapy ; Tumor Necrosis Factor-alpha/pharmacology ; Oxidative Stress/drug effects ; Cell Line ; Antioxidants/pharmacology ; }, abstract = {Oxidative stress in retinal pigment epithelium (RPE) cells plays a key role in the development of age-related macular degeneration (AMD), a leading cause of vision loss in the elderly. Thymoquinone, a bioactive antioxidant from Nigella sativa, has shown promise in reducing cellular oxidative stress. In AMD, prolonged exposure to oxidative stress may activate the NF-κβ signalling pathway in RPE cells, contributing to chronic inflammation, and its regulation by thymoquinone remains understudied. This study investigates the effects of thymoquinone in TNFα-induced RPE cells exposed to AGEs to mimic ageing conditions relevant for AMD. Gene and protein expression levels of NF-κβ pathway markers (P65, pP65 and Iκβα) were measured using qPCR and Western blotting, and statistical analysis was performed using Student's t-test and one-way ANOVA. Thymoquinone pretreatment at 0.1 µM and 10 µM significantly reduced the expression of these markers in TNFα-stimulated RPE cells. Notably, AGE-exposed cells demonstrated a heightened response to thymoquinone compared to non-AGE-exposed controls. These findings suggest that thymoquinone modulates NF-κβ signalling and may serve as a potential adjuvant therapeutic agent for AMD.}, }
@article {pmid41373691, year = {2025}, author = {Huo, W and Yin, J and Ghose, P and Schafer, JC and Chaum, E and Bhattacharya, S}, title = {Prominin-1 Regulates Retinal Pigment Epithelium Homeostasis: Transcriptomic Insights into Degenerative Mechanisms.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373691}, issn = {1422-0067}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; S10 OD021630/OD/NIH HHS/United States ; Unrestricted Departmental Research Grant//Research to Prevent Blindness/ ; Gift//Potocsnak Family/ ; P30 EY008126/EY/NEI NIH HHS/United States ; GF02527//International Retinal Research Foundation/ ; P30 CA068485/CA/NCI NIH HHS/United States ; P30EY08126/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; *Homeostasis ; *Transcriptome ; *AC133 Antigen/genetics/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; *Retinal Degeneration/genetics/metabolism/pathology ; Signal Transduction ; Glycoproteins ; }, abstract = {Inherited retinal degenerations (IRDs), driven by pathogenic mutations, often involve primary dysfunction of the retinal pigment epithelium (RPE)-a pathogenic feature shared with atrophic age-related macular degeneration (aAMD), despite aAMD's multifactorial etiology. Prominin-1 (Prom1), traditionally linked to photoreceptor pathology, has an unclear role in RPE homeostasis. We assessed Prom1 expression in C57BL/6J mouse retina sections and RPE flat mounts using immunohistochemistry and generated Prom1-knockout (KO) mouse RPE cells via CRISPR/Cas9. Bulk RNA sequencing with DESeq2 and gene set enrichment analysis (GSEA) revealed Prom1-regulated pathways. Prom1-KO cells exhibited upregulation of Grem1, Slc7a11, Serpine2, Il1r1, and IL33 and downregulation of Ablim1, Cldn2, IGFBP-2, BMP3, and OGN. Hallmark pathway interrogation identified reduced expression of PINK1 (mitophagy) and MerTK (phagocytosis), implicating defects in mitochondrial quality control and outer segment clearance. Enrichment analysis revealed activation of E2F/MYC targets, mTORC1 signaling, oxidative phosphorylation, and TNFα/NF-κB signaling, alongside suppression of apical junctions, bile acid metabolism, and Epithelial-Mesenchymal Transition (EMT) pathways. These findings suggest Prom1 safeguards RPE integrity by modulating stress responses, mitochondrial turnover, phagocytosis, metabolism, and junctional stability. Our study uncovers Prom1-dependent signaling networks, providing mechanistic insights into RPE degeneration relevant to both IRD and aAMD, and highlights potential therapeutic targets for preserving retinal health.}, }
@article {pmid41374087, year = {2025}, author = {Bogdănici, CG and Bogdănici, CM and Pavel, IA and Ganea, CV and Donica, VC and Cărăușu, EM}, title = {Associations Between Nutritional Factors, Obesity and Ocular Diseases: A Narrative Literature Review.}, journal = {Nutrients}, volume = {17}, number = {23}, pages = {}, pmid = {41374087}, issn = {2072-6643}, mesh = {Humans ; *Obesity/complications ; *Eye Diseases/etiology/epidemiology ; *Nutritional Status ; Micronutrients/deficiency ; Risk Factors ; Oxidative Stress ; Macular Degeneration/etiology ; Diet ; }, abstract = {Background: Nutritional imbalances significantly affect ocular physiology, contributing to dry eye disease, cataracts, age-related macular degeneration (AMD), and optic neuropathies. This review summarizes recent evidence on how micronutrient deficiencies and obesity influence eye health. Methods: A narrative search was performed in PubMed, Scopus, and ScienceDirect (last 10 years). Human studies evaluating associations between micronutrients, dietary patterns, obesity, and ocular diseases were included. Out of 843 records, 50 studies met the eligibility criteria. Results: Deficiencies in vitamins A, D, E, C, and B-complex were consistently linked to ocular surface inflammation, retinal oxidative stress, cataracts, AMD, and nutritional optic neuropathies. Altered levels of zinc, copper, selenium, and magnesium were associated with impaired photoreceptor function, glaucoma risk, and retinal degeneration. Obesity emerged as an independent risk factor for AMD, diabetic retinopathy, and glaucoma through mechanisms involving oxidative stress and vascular dysfunction. Evidence from AREDS/AREDS2 supports targeted antioxidant supplementation in intermediate AMD. Conclusions: Adequate nutritional status and metabolic balance play a critical role in preserving ocular health. Early detection and correction of deficiencies may prevent or slow the progression of several eye diseases. Further high-quality trials are needed to define optimal nutritional recommendations.}, }
@article {pmid41374757, year = {2025}, author = {Takahashi, H and Tsuge, T and Kondo, Y and Yanagi, Y and Inoda, S and Morikawa, S and Senoo, Y and Kaburaki, T and Oshika, T and Yamasaki, T}, title = {Intraocular Cytokine Level Prediction from Fundus Images and Optical Coherence Tomography.}, journal = {Sensors (Basel, Switzerland)}, volume = {25}, number = {23}, pages = {}, pmid = {41374757}, issn = {1424-8220}, support = {21K09751//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Aged ; Female ; *Cytokines/metabolism ; Fundus Oculi ; Deep Learning ; Middle Aged ; Retina/diagnostic imaging/metabolism ; Aged, 80 and over ; Aqueous Humor/metabolism ; Neural Networks, Computer ; Macular Degeneration/diagnostic imaging ; Image Processing, Computer-Assisted ; }, abstract = {The relationship between retinal images and intraocular cytokine profiles remains largely unexplored, and no prior work has systematically compared fundus- and OCT-based deep learning models for cytokine prediction. We aimed to predict intraocular cytokine concentrations using color fundus photographs (CFP) and retinal optical coherence tomography (OCT) with deep learning. Our pipeline consisted of image preprocessing, convolutional neural network-based feature extraction, and regression modeling for each cytokine. Deep learning was implemented using AutoGluon, which automatically explored multiple architectures and converged on ResNet18, reflecting the small dataset size. Four approaches were tested: (1) CFP alone, (2) CFP plus demographic/clinical features, (3) OCT alone, and (4) OCT plus these features. Prediction performance was defined as the mean coefficient of determination (R[2]) across 34 cytokines, and differences were evaluated using paired two-tailed t-tests. We used data from 139 patients (152 eyes) and 176 aqueous humor samples. The cohort consisted of 85 males (61%) with a mean age of 73 (SD 9.8). Diseases included 64 exudative age-related macular degeneration, 29 brolucizumab-associated endophthalmitis, 19 cataract surgeries, 15 retinal vein occlusion, and 8 diabetic macular edema. Prediction performance was generally poor, with mean R[2] values below zero across all approaches. The CFP-only model (-0.19) outperformed CFP plus demographics (-24.1; p = 0.0373), and the OCT-only model (-0.18) outperformed OCT plus demographics (-14.7; p = 0.0080). No significant difference was observed between CFP and OCT (p = 0.9281). Notably, VEGF showed low predictability (31st with CFP, 12th with OCT).}, }
@article {pmid41375896, year = {2025}, author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S}, title = {Clinical Characteristics of Patients with Neovascular Age-Related Macular Degeneration and Responses to Anti-VEGF Therapy: Four-Group Stratification Based on Drusen and Punctate Hyperfluorescence.}, journal = {Journal of clinical medicine}, volume = {14}, number = {23}, pages = {}, pmid = {41375896}, issn = {2077-0383}, abstract = {Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen-/PH-, Drusen+/PH-, Drusen-/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan-Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH- group had a higher retreatment rate and required more injections than the Drusen-/PH+ and Drusen+/PH+ groups. The Drusen+/PH- group was older than the Drusen-/PH+ and Drusen-/PH- groups. The Drusen-/PH+ group had a thicker choroid than the Drusen+/PH- group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH- group and the thicker choroid of the Drusen-/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies.}, }
@article {pmid41377064, year = {2026}, author = {Rathi, S and Didangelos, A and Pisarenka, S and Green, R and Zafeiri, S and Emery-Billcliff, P and Patel, N and Whalley, P and Zamiri, P and Tilakaratna, V and Szula, E and Hasan, R and Munye, MM and Unwin, RD and Bishop, PN and Keefe, D and Clark, SJ}, title = {CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1).}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100980}, pmid = {41377064}, issn = {2666-9145}, abstract = {PURPOSE: Preclinical evaluation of a novel gene therapy called CTx001 for treating geographic atrophy (GA). CTx001 encodes a protein called mini-CR1, which is a soluble fragment of complement receptor 1.<br><br>DESIGN: CTx001 was used in vitro and in vivo to analyze expression and complement-modulating activity. Mini-CR1 was used in vitro to analyze complement-modulating activity, and its ability to cross human Bruch's membrane was evaluated ex vivo.<br><br>PARTICIPANTS: CTx001, which is a self-complementary rAAV2 gene therapy vector expressing mini-CR1. Recombinant mini-CR1 protein, retinal pigment epithelium (RPE) cell lines, serum, human donor Bruch's membrane, and a rat model.<br><br>METHODS: Recombinant mini-CR1 protein was produced in mammalian cells and purified. C3b and C4b breakdown assays were performed. Wieslab assays measured complement regulatory activity in serum. Mini-CR1 binding to C3b was measured using biolayer interferometry. The diffusion of mini-CR1 across human Bruch's membrane was assessed using an Ussing chamber. Retinal pigment epithelium cell lines were transduced with CTx001 to assess expression, including directionality and complement modulatory activity. In vivo efficacy of CTx001 was tested using a rat laser-induced choroidal neovascularization (CNV) model.<br><br>MAIN OUTCOME MEASURES: C3b/iC3b/C4b degradation, inhibition of membrane attack complex (MAC) formation in human serum, mini-CR1 binding to C3b, vector transduction efficiency, protein secretion and localization, and complement inhibition in vivo.<br><br>RESULTS: Mini-CR1 demonstrated potent cofactor activity for factor I-mediated cleavage of C3b, iC3b, and C4b; therefore, it inhibits both the alternative and classical complement pathways. It inhibited complement activation with an IC50 of 125 nM in human serum. Mini-CR1 demonstrated high-affinity binding to C3b. The mini-CR1 protein diffused across human Bruch's membrane and retained activity postdiffusion. CTx001-transduced RPE cells secreted mini-CR1 apically and basolaterally, leading to reduced C3 activation and MAC deposition. In rats, subretinal administration of CTx001 resulted in a 75.4% reduction in MAC deposition in CNV lesions (P < 0.01).<br><br>CONCLUSIONS: CTx001 is a potent inhibitor of complement. It efficiently transduces RPE cells, resulting in apical and basolateral secretion and crosses Bruch's membrane, so it is expected to deliver mini-CR1 to the retina and choroid. These findings support its further development as a 1-time gene therapy for addressing complement overactivation in GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41377065, year = {2026}, author = {Fragiotta, S and Querques, G and Polito, MS and Costanzo, E and Rossi, T and Varano, M and Pannarale, FM and Sakurada, Y and Parravano, M}, title = {Structural Biomarkers Influencing Drusenoid Pigment Epithelial Detachment Lifecycle and the Development of Late Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {1}, pages = {100977}, pmid = {41377065}, issn = {2666-9145}, abstract = {PURPOSE: Drusenoid pigment epithelial detachment (dPED) is a notable phenotype in age-related macular degeneration (AMD), often evolving into macular complications such as macular neovascularization (MNV) and geographic atrophy (GA). The aim of this study was to identify potential prognostic biomarkers associated with the development of both MNV and GA.<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: Patients with dPED in the setting of AMD.<br><br>METHODS: This observational study analyzed OCT biomarkers to assess the dPED lifecycle and identify features predictive of macular complications. Seventy-one eyes with dPED from 51 patients were reviewed over an average follow-up of 37.5 &#xb1; 17.6 months (range: 24-104), examining structural alterations via multimodal imaging, which included color fundus photography, fundus autofluorescence, and OCT, while fluorescein angiography, indocyanine green angiography, or both were performed as needed. Associations between baseline biomarkers and macular complications were assessed using Cox proportional hazard models with a frailty term to account for intereye correlation. The Fine-Gray model was used to account for competing risk analysis.<br><br>MAIN OUTCOME MEASURES: Incidence and time to development of macular complications (MNV and GA) and their associations with baseline OCT biomarkers (cuticular drusen, hyperreflective foci, external limiting membrane/ellipsoid zone integrity, and retinal pigment epithelium [RPE] hypertransmission), modeled with frailty-adjusted Cox proportional hazards and Fine-Gray competing risks; secondary measures included dPED lifecycle features (collapse, timing) and morphometrics (height, width, volume).<br><br>RESULTS: Key findings included a 39.4% incidence of dPED collapse, with 60.7% of cases progressing to complications postcollapse. In the multivariable Cox proportional model, cuticular drusen (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.62-9.2, P = 0.002) and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95% CI: 1.97-22, P = 0.02) represented the main prognostic indicators of macular complications. In the Fine-Gray competing risks analysis, cuticular drusen remained a significant independent predictor (subdistribution hazard ratio [sHR] = 18.1, 95% CI: 1.89-174, P = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98-22.61, P = 0.002) and external limiting membrane disruption at baseline (sHR = 3.69, 95% CI: 1.03-13.14, P = 0.044) were factors significantly associated with increased GA risk.<br><br>CONCLUSIONS: These results underscore the prognostic relevance of specific imaging biomarkers in dPED. Recognizing these features early may support timely treatment and help prevent irreversible photoreceptor and RPE damage.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41377141, year = {2025}, author = {Zhang, LL and Yu, JM and Fan, ZX and Xie, WQ and Zou, L and Sheng, F}, title = {Regulated cell death in age-related macular degeneration: Regulatory mechanisms and therapeutic potential.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {11}, pages = {101285}, pmid = {41377141}, issn = {2214-0883}, abstract = {Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.}, }
@article {pmid41378371, year = {2025}, author = {Meng, N and Xia, L and Gong, Y and Shi, C and Lu, P}, title = {A Bibliometric Analysis of Research Progress on Age-Related Macular Degeneration and Autophagy From 2010 to 2024.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {6670966}, pmid = {41378371}, issn = {2090-004X}, abstract = {BACKGROUND: Autophagy regulates intracellular metabolism and is crucial in the development of age-related macular degeneration (AMD). Despite the growing number of studies on AMD and autophagy in recent years, bibliometric analyses in this field remain scarce. Therefore, a bibliometric analysis was applied to explore the research trends and hot spots of this field in this study.<br><br>METHODS: We collected publications on autophagy in AMD from the MEDLINE database, covering the period from January 2010 to October 2024. The "bibliometrix" R package (Version R 4.2.3) was utilized for bibliometric analysis, and WPS Excel, PowerPoint, and Word (12.1.0.18276) were used to manage data and create related tables.<br><br>RESULTS: A total of 349 articles were included. The amount of literature was on the rise from 2010 to 2024. China leads in article quantity, whereas the United States holds the most influence. Although Finland ranks the third position in publication volume, followed by China and the United States, Finland led research in this field, with the University of Eastern Finland being the most active and prolific institution and Kaarniranta Kai as the most productive and influential author. International Journal of Molecular Sciences and Autophagy is the journal with the most volume. The three most referenced studies primarily examine the interplay between inflammation, oxidative stress, and autophagy in retinal pigment epithelial cells. The analysis for keywords found that mitophagy has also received increasing attention in this field.<br><br>CONCLUSIONS: This bibliometric analysis identifies current research hotspots in autophagy related to AMD and informs future research directions. Future trends in this field may involve identifying and developing novel autophagy-targeted therapies for the prevention and treatment of AMD.}, }
@article {pmid41381091, year = {2025}, author = {Shi, Q and Zhan, D and Wang, W and Wu, X and Sheng, S and Wang, Y}, title = {Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study.}, journal = {The Journal of international medical research}, volume = {53}, number = {12}, pages = {3000605251404265}, pmid = {41381091}, issn = {1473-2300}, mesh = {Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Retinal Diseases/genetics/complications ; *Alzheimer Disease/genetics ; *Cognitive Dysfunction/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Macular Degeneration/genetics ; Dementia, Vascular/genetics ; *Lewy Body Disease/genetics ; }, abstract = {ObjectiveThis study employed a bidirectional two-sample Mendelian randomization approach to investigate the causal links between Alzheimer's disease, Lewy body dementia, vascular dementia, and various retinal diseases.MethodsSummary data from large-scale genome-wide association studies of European ancestry were used to select genetic variants as instrumental variables. Causal estimates were derived using the inverse variance-weighted method, complemented by Mendelian randomization-Egger, weighted median, and weighted mode analyses to ensure robustness.ResultsGenetically predicted Alzheimer's disease was associated with a reduced risk of disorders of the choroid and retina (odds ratio = 0.93, 95% confidence interval: 0.88-0.98), retinal detachments and breaks (odds ratio = 0.90, 95% confidence interval: 0.84-0.97), and retinal detachment with retinal break (odds ratio = 0.84, 95% confidence interval: 0.74-0.95). Lewy body dementia was negatively associated with age-related macular degeneration (odds ratio = 0.88, 95% confidence interval: 0.79-0.98), disorders of the choroid and retina (odds ratio = 0.96, 95% confidence interval: 0.93-0.99), and degeneration of the macula (odds ratio = 0.93, 95% confidence interval: 0.88-0.98). Vascular dementia showed negative associations with age-related macular degeneration (odds ratio = 0.93, 95% confidence interval: 0.87-0.99) and degeneration of the macula (odds ratio = 0.96, 95% confidence interval: 0.93-0.99). Conversely, reverse Mendelian randomization indicated that genetic liability to macular degeneration and choroidal/retinal disorders was causally associated with cognitive performance and a reduced risk of Alzheimer's disease.ConclusionsFindings support inverse causal relationships in which specific dementias may reduce retinal disease risk and vice versa, suggesting complex shared biological mechanisms.}, }
@article {pmid41383281, year = {2025}, author = {Cheng, S and Ma, Y and Huang, F and Luo, R and Han, L and He, L and Yuan, ZX}, title = {Mesenchymal Stem Cell-Derived Exosomes for Ocular Diseases: Therapeutic Mechanisms and Clinical Perspectives.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {14521-14550}, pmid = {41383281}, issn = {1178-2013}, mesh = {*Exosomes/chemistry/transplantation ; Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; *Eye Diseases/therapy ; Animals ; Drug Delivery Systems/methods ; }, abstract = {Ocular diseases represent a major and increasing public health concern. Although current treatment options are available, the management of complex cases, such as corneal diseases, diabetic retinopathy, glaucoma, age-related macular degeneration, and uveitis, remains inadequate. Recent studies have demonstrated that mesenchymal stem cell-derived exosomes (MSC-Exos), obtained from bone marrow, adipose tissue, and umbilical cord, have emerged as a promising cell-free therapeutic platform for various ocular diseases. These nanovesicles can be delivered via systems such as topical eye drops and intravitreal injection, targeting ocular tissues to exert anti-inflammatory, anti-apoptotic, and tissue-repairing effects. This review systematically synthesizes recent advances and the molecular mechanisms underlying the use of MSC-Exos in treating ocular diseases. Moreover, it provides an in-depth discussion of the challenges in the clinical application of MSC-Exos in ophthalmology, including standardized production, dosage optimization, delivery system improvement, and targeting enhancement, and proposes engineered targeting strategies based on surface modification and carrier optimization. Overall, this work establishes a rigorous framework for advancing MSC-Exos from experimental models to clinical implementation, offering novel therapeutic strategies through these innovative biopharmaceuticals for previously untreatable ocular conditions.}, }
@article {pmid41383834, year = {2025}, author = {Li, MM and Zhang, H and Cen, ZM and Su, DW}, title = {Management of submacular hemorrhage secondary to age-related macular degeneration with vitrectomy and subretinal tissue plasminogen activator injection: Outcomes and prognostic factors.}, journal = {SAGE open medicine}, volume = {13}, number = {}, pages = {20503121251403361}, pmid = {41383834}, issn = {2050-3121}, abstract = {PURPOSE: To evaluate the efficacy of pars plana vitrectomy combined with subretinal tissue plasminogen activator injection, pneumatic displacement, and intraoperative intravitreal antivascular endothelial growth factor therapy for treating submacular hemorrhage secondary to polypoidal choroidal vasculopathy or neovascular age-related macular degeneration.<br><br>METHODS: This retrospective study enrolled 28 patients who were diagnosed with submacular hemorrhage secondary to polypoidal choroidal vasculopathy or neovascular age-related macular degeneration, all of whom received a minimum follow-up period of 6&#x2009;months. Key preoperative parameters, such as submacular hemorrhage height and diameter, tissue plasminogen activator dosage, and hemorrhage duration, were documented. Postoperative outcomes evaluated included the degree of submacular hemorrhage displacement, visual acuity changes, incidence of complications, and the requirement for additional intravitreal antivascular endothelial growth factor injections during the follow-up period.<br><br>RESULTS: The mean patient age was 66.71&#x2009;&#xb1;&#x2009;10.62&#x2009;years. The mean visual acuity progressively improved from a preoperative logMAR of 1.57&#x2009;&#xb1;&#x2009;0.64 to 1.26&#x2009;&#xb1;&#x2009;0.67, 1.15&#x2009;&#xb1;&#x2009;0.59, 1.14&#x2009;&#xb1;&#x2009;0.55, and 1.12&#x2009;&#xb1;&#x2009;0.56 at postoperative months 1, 3, and 6, respectively. Complete hemorrhage displacement was achieved in 85.71% (24/28) of cases. Preoperative hemorrhage duration was significantly negatively correlated with postoperative best-corrected visual acuity at 1&#x2009;month (r&#x2009;=&#x2009;0.46; p&#x2009;=&#x2009;0.013), 3&#x2009;months (r&#x2009;=&#x2009;0.42; p&#x2009;=&#x2009;0.028), 6&#x2009;months (r&#x2009;=&#x2009;0.41; p&#x2009;=&#x2009;0.032), and final follow-up (r&#x2009;=&#x2009;0.38; p&#x2009;=&#x2009;0.047).<br><br>CONCLUSIONS: Pars plana vitrectomy with tissue plasminogen activator subretinal injection, pneumatic displacement, and intraoperative vitreous antivascular endothelial growth factor injection represents a safe and effective approach for managing submacular hemorrhage secondary to polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. The duration of submacular hemorrhage emerges as the most critical prognostic factor for final visual outcomes. Patients with hemorrhage duration exceeding 14&#x2009;days demonstrate a significantly reduced likelihood of achieving favorable visual outcomes.}, }
@article {pmid41384795, year = {2025}, author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX}, title = {Changes of the Optic Nerve Head and Macula in High Myopia in a 10-Year Follow-Up: The Beijing Eye Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {39}, pmid = {41384795}, issn = {1552-5783}, mesh = {Humans ; *Optic Disk/pathology ; Male ; Female ; Follow-Up Studies ; Aged ; Tomography, Optical Coherence/methods ; *Macula Lutea/pathology ; Middle Aged ; *Myopia, Degenerative/epidemiology/diagnosis ; Beijing/epidemiology ; Incidence ; Disease Progression ; China/epidemiology ; *Myopia ; }, abstract = {PURPOSE: To assess the incidence of myopic changes of the optic nerve head and macula in highly myopic eyes.<br><br>METHODS: All highly myopic eyes (axial length >26.0 mm or refractive error &#x2264;-6.0 diopters) examined in the longitudinal population-based Beijing Eye Study 2001/2011 underwent fundus photography (2001/2011) and optic coherence tomography (2011).<br><br>RESULTS: The study included 89 highly myopic eyes (patient age, 65.0 &#xb1; 9.8 years). Progressive macula changes were detected in 63 of 89 eyes (71%), including increases in fundus tessellation (n = 61 [69%]), diffuse chorioretinal atrophy (n = 15 [17%]), lacquer cracks (n = 12 [14%]), patchy atrophies (n = 8 [9%]), macular atrophy (n = 6 [7%]), and overall myopic macular degeneration stage (n = 23 [26%]). Without considering fundus tessellation changes, any macular change was detected in 31 of 80 eyes (35%). Progressive optic nerve head changes were found in 69 of 89 eyes (78%), including optic disc diminution (n = 28 [32%]), disc enlargement (n = 13 [15%]), change in disc shape (n = 36 [40%]), enlargement in beta/gamma zone (n = 68 [76%]) or delta zone (n = 22 [25%]), and lengthening of parapapillary retinal vessels (n = 47 [53%]). Any type of progression of the macula and/or optic nerve head was detected in 74 of 89 eyes (83%), and without considering fundus tessellation changes in 70 of 89 eyes (79%). Higher incidence of any macular change (fundus tessellation change not considered) and of optic nerve head changes correlated with longer axial length (odds ratio [OR], 2.15 [P < 0.001] and OR, 2.20 [P = 0.02], respectively) and older age (OR, 1.11 [P = 0.001] and OR, 1.08 [P = 0.02], respectively). Optic disc diminution correlated with disc shape change from a more circular to an elliptical shape (OR, 37.9; 95% confidence interval, 9.7-148.0; P < 0.001) and in all eyes with beta/gamma zone enlargement.<br><br>CONCLUSIONS: Over the 10-year follow-up, >75% of highly myopic eyes showed progressive myopic changes of the optic nerve head and macula.}, }
@article {pmid41385093, year = {2026}, author = {Lingardo, S and Sacconi, R and Balduzzi, E and Beretta, F and Menean, M and Querques, G}, title = {The spectrum of pachychoroid neovasculopathy.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {617-632}, pmid = {41385093}, issn = {1435-702X}, mesh = {Humans ; *Choroidal Neovascularization/diagnosis ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroid/blood supply/pathology ; *Central Serous Chorioretinopathy/diagnosis ; Fundus Oculi ; Multimodal Imaging/methods ; *Retinal Pigment Epithelium/pathology ; }, abstract = {PURPOSE: To provide a comprehensive overview of pachychoroid neovasculopathy (PNV), focusing on its current understanding in terms of clinical behavior, multimodal retinal imaging characteristics, and treatment.<br><br>METHODS: A narrative review of the literature on PNV was conducted using the following keywords: pachychoroid neovasculopathy, pachychoroid, pachychoroid disease spectrum, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, polypoidal choroidal vasculopathy.<br><br>RESULTS: PNV is a clinical entity within the pachychoroid disease spectrum, typically presenting as type 1 choroidal neovascularization (CNV). It may arise either directly from pachychoroid pigment epitheliopathy (PPE) without prior central serous chorioretinopathy (CSC) or from chronic CSC. PNV is frequently misdiagnosed as neovascular age-related macular degeneration (nAMD), particularly in patients older than 50 years, making multimodal retinal imaging essential for distinguishing its characteristic features from CNV secondary to AMD. The therapeutic management of PNV depends on its underlying initial condition and differs from the treatment strategy for CNV secondary to AMD.<br><br>CONCLUSIONS: Recognizing PNV as a distinct entity is crucial for optimizing diagnosis and treatment. Multimodal retinal imaging is essential to ensure appropriate therapeutic management.<br><br>KEY MESSAGES: What is known? Pachychoroid neovasculopathy (PNV) is a distinct clinical entity within the pachychoroid disease spectrum, frequently misdiagnosed as neovascular age-related macular degeneration (nAMD). What is new? PNV includes subtypes arising from pachychoroid pigment epitheliopathy or chronic central serous chorioretinopathy, which differ in treatment responses and strategies. Multimodal retinal imaging plays an essential role in differentiating PNV from nAMD. The lack of standardized diagnostic criteria for PNV highlights the need for shared definitions to improve PNV classification, patient stratification, and treatment selection.}, }
@article {pmid41385282, year = {2025}, author = {Sagiv, RG and Rosenblatt, HN and Zamir, E and Altarescu, A and Ben-Zaken, SG and Rotfogel, Z}, title = {Efficiency of anti-vascular endothelial growth factor drug switch in patients who did not respond to a series of bevacizumab injections.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_1740_25}, pmid = {41385282}, issn = {1998-3689}, abstract = {PURPOSE: To assess the effectiveness of switching anti-vascular endothelial growth factor (VEGF) agents in eyes with retinal pathologies that poorly respond to intravitreal bevacizumab injections.<br><br>METHODS: We compared central macular thickness (CMT) and VA between eyes with suboptimal responses to at least three bevacizumab injections that either continued with bevacizumab or switched to aflibercept or ranibizumab. Eyes were categorized into group D (DME), group N (neovascular age-related macular degeneration [nAMD]), and group A - all eyes (D and N plus eyes with retinal vein occlusion (RVO) or pseudophakic central macular edema [PCME]). Each group was further divided into those continuing bevacizumab (D1, N1, A1) or switching to aflibercept or ranibizumab (D2, N2, A2).<br><br>RESULTS: A total of 21 eyes were included in group D (8 in D1 and 13 in D2), 28 in group N (14 in N1 and 14 in N2), and 59 eyes in group A (25 in A1 and 34 in A2). In all eyes with treatment shift, CMT decreased: 38.5 (SD: 46.2), 92.6 (SD: 106.8), and 82.1 (SD: 115.6) microns in D2, N2, and A2, respectively. CMT difference was statistically significant between N1 versus N2 and between A1 versus A2 (P = 0.025 and 0.004, respectively). No significant difference in VA was observed.<br><br>CONCLUSION: Switching anti-VEGF agents appears anatomically beneficial in nonresponding eyes. Notably, the inclusion of a control group continuing bevacizumab despite poor response allows for a more reliable evaluation of treatment efficacy, addressing a key limitation of prior studies and contributing to the evidence-based rationale for agent switching.}, }
@article {pmid41388185, year = {2026}, author = {Rinaldi, M and Cennamo, G and Concilio, M and Corvino, G and Riccardo, A and Nubi, R and Costagliola, C}, title = {Aflibercept 8 mg in Neovascular AMD-A Fast-Drying Anti-VEGF Drug: A Prospective Morpho-Functional Pilot Study.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {677-687}, pmid = {41388185}, issn = {2193-8245}, abstract = {INTRODUCTION: This study investigated early anatomical and functional outcomes in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) treated with 8 mg aflibercept compared to patients treated with the standard dose of 2 mg aflibercept using spectral domain optical coherence tomography (SD-OCT), microperimetry, and macular pigment optical density (MPOD) after loading phase administration.<br><br>METHODS: This prospective, observational study included 30 eyes of 30 patients (mean age 70&#x2009;&#xb1;&#x2009;5&#xa0;years; 15 male, 15 female) recruited between January and June 2025 at the Eye Clinic of the University of Naples "Federico II". Patients were assigned to one of two age- and gender-matched groups receiving intravitreal injections of aflibercept at the dose of 2&#xa0;mg (group&#xa0;A) or 8&#xa0;mg (group&#xa0;B). All patients underwent complete ophthalmological examination, SD-OCT, OCT angiography, microperimetry, fixation stability, and measurement of MPOD at baseline, month&#xa0;2, and month&#xa0;4.<br><br>RESULTS: Group&#xa0;B showed an improvement in all parameters, compared to group&#xa0;A, in particular: a greater reduction in central macular thickness (CMT) (p&#x2009;=&#x2009;0.008), an improvement in best-corrected visual acuity (BCVA) (p&#x2009;=&#x2009;0.012), increased retinal sensitivity (p&#x2009;=&#x2009;0.015), increased MPOD (p&#x2009;=&#x2009;0.027), and reduced bivariate contour ellipse area (BCEA) (p&#x2009;=&#x2009;0.039). Group&#xa0;B showed a faster drying rate during the first 2&#xa0;months (70 vs. 40&#xa0;&#x3bc;m/month) and overall at month&#xa0;4.<br><br>CONCLUSIONS: Intravitreal injections of aflibercept 8&#xa0;mg resulted in significant short-term anatomical and functional improvement compared to standard dose and thus appear to be an effective option to achieve faster results in nAMD. MPOD can be considered as a potential new biomarker of macular health to study retinal functional response.<br><br>TRIAL REGISTRATION: The research protocol was registered on ClinicalTrials.gov (NCT07074054).}, }
@article {pmid41388211, year = {2025}, author = {Srivastava, V and Yadav, P and Yadav, A and Parashar, P}, title = {Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon.}, journal = {AAPS PharmSciTech}, volume = {27}, number = {1}, pages = {55}, pmid = {41388211}, issn = {1530-9932}, mesh = {Humans ; *Artificial Intelligence/trends ; *Drug Delivery Systems/methods ; *Eye Diseases/drug therapy ; Precision Medicine/methods ; Administration, Ophthalmic ; Animals ; Machine Learning ; Eye/drug effects/metabolism ; }, abstract = {BACKGROUND: Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.<br><br>AREA COVERED: This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.<br><br>EXPERT OPINION: AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.}, }
@article {pmid41389973, year = {2026}, author = {Xiong, X and Li, Q and Zhang, Y and Liu, P and Pan, Y and Song, Q}, title = {Exploring copper metabolism and cuproptosis, and their implications in ocular diseases.}, journal = {European journal of pharmacology}, volume = {1011}, number = {}, pages = {178472}, doi = {10.1016/j.ejphar.2025.178472}, pmid = {41389973}, issn = {1879-0712}, mesh = {Humans ; *Copper/metabolism ; Animals ; *Eye Diseases/metabolism/pathology ; Mitochondria/metabolism/pathology/drug effects ; Oxidative Stress ; }, abstract = {Copper is a vital trace element for all living organisms and plays an important role in numerous physiological functions, including the formation of mitochondrial respiratory chain complexes, antioxidant defense, and signal transduction. However, excess copper can cause cellular toxicity and initiate a form of cell death that is characterized by the aggregation of lipoylated proteins and a reduction in Fe-S cluster proteins. This series of events can culminate in mitochondrial process of respiratory dysfunction known as cuproptosis. Excessive copper can also inhibit the ubiquitin-proteasome system, which results in the accumulation of harmful proteins and a vicious cycle of Fenton and Haber-Weiss reactions that trigger oxidative stress and cellular damage. The eye, particularly the retina, is one of the most energy-dependent tissues in the body and has an extraordinary dependence on mitochondrial function. Dysregulated copper-ion levels can lead to mitochondrial dysfunction, which can cause various ocular diseases, including uveal melanoma, age-related macular degeneration, and diabetic retinopathy. Therefore, the relationship between copper and ocular diseases provides promising research opportunities. This review summarizes recent research findings on copper metabolism, cuproptosis, and their implications in ocular diseases. It also introduces potential therapeutic approaches for related diseases, including copper chelation therapy, copper ionophores and nanomedicine, and genetic treatment strategies.}, }
@article {pmid41390041, year = {2026}, author = {Lin, Z and Deng, H and Wang, S and Wang, Z and Yang, G and Huang, K}, title = {Apoferritin-conjugated melanin nanoparticles rescue photoreceptor degeneration via dual iron chelation and ROS scavenging in dry AMD therapy.}, journal = {International journal of biological macromolecules}, volume = {337}, number = {Pt 2}, pages = {149586}, doi = {10.1016/j.ijbiomac.2025.149586}, pmid = {41390041}, issn = {1879-0003}, mesh = {Animals ; *Nanoparticles/chemistry ; Mice ; *Reactive Oxygen Species/metabolism ; *Apoferritins/chemistry/pharmacology ; *Iron Chelating Agents/pharmacology/chemistry ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Melanins/chemistry/pharmacology ; Oxidative Stress/drug effects ; Disease Models, Animal ; Humans ; Ferroptosis/drug effects ; Antioxidants/pharmacology ; Iron/metabolism ; Iodates ; *Free Radical Scavengers/pharmacology/chemistry ; Mice, Inbred C57BL ; }, abstract = {Oxidative stress in the retina and dysregulation of iron homeostasis are established as central pathogenic mechanisms in dry age-related macular degeneration (dAMD). Nonetheless, effective clinical treatments to counteract retinal degeneration in this condition are still absent. Our research began with developing a single-cell transcriptome profile of retinal tissue subjected to sodium iodate (NaIO3)-induced oxidative injury. This analysis identified ferroptosis in photoreceptor cells as a key driver of disease progression. Apoferritin (AFn) is a hollow, spherical protein nanocage formed by 24 self-assembled subunits, enabling supramolecular iron storage through ferroxidase-mediated mineralization while providing dynamic iron buffering and antioxidant protection in biological systems. We then engineered a biomimetic nanoparticle, AFn-MNP, by combining Afn with melanin nanoparticles (MNP). AFn-MNP displayed significant ferrous ion-chelating ability and antioxidant activity, effectively mitigating NaIO3-triggered photoreceptor ferroptosis in vitro and in vivo. Significantly, a single intravitreal injection of 10 μg AFn-MNP effectively counteracted visual impairment in NaIO3-induced dAMD model mice, reversed damage to photoreceptor synaptic terminals, and significantly alleviated photoreceptor degeneration and retinal oxidative injury. In summary, our results indicate that AFn-MNP holds significant promise as a novel therapy for dAMD and other retinal degenerative diseases linked to oxidative damage and impaired iron metabolism.}, }
@article {pmid41390091, year = {2026}, author = {Tao, L and He, D and Chen, Y and Cai, P and Yang, K and Wu, J and Liao, C and Chen, J and Wu, Y}, title = {Gene editing of JNK alleviates sodium iodate-induced retinal degeneration in mice.}, journal = {Life sciences}, volume = {385}, number = {}, pages = {124145}, doi = {10.1016/j.lfs.2025.124145}, pmid = {41390091}, issn = {1879-0631}, mesh = {Animals ; *Iodates/toxicity ; Mice ; *Retinal Degeneration/chemically induced/genetics/therapy ; Mice, Inbred C57BL ; *Gene Editing/methods ; Electroretinography ; Disease Models, Animal ; Retinal Pigment Epithelium/pathology/metabolism ; Tomography, Optical Coherence ; Mice, Knockout ; Male ; Retina/pathology ; Macular Degeneration/genetics/chemically induced ; *Mitogen-Activated Protein Kinase 9/genetics ; }, abstract = {PURPOSE: Dry age-related macular degeneration (dry AMD) still lacks effective treatment strategies due to its complex mechanisms. Although c-Jun N-terminal kinase (JNK) signaling has been reported to be associated with retinal degeneration in dry AMD, the efficacy of JNK gene editing in treating dry AMD remains unclear. This study aims to investigate the protective potential of JNK genetic inhibition in a sodium iodate (SI)-induced retinal degeneration model that recapitulates the key features of human dry AMD.<br><br>METHODS: A retinal degeneration model was constructed from a single intraperitoneal injection of 50&#xa0;mg/kg body weight SI into C57BL/6&#xa0;J mice. The retina was examined by electroretinography (ERG), fundus imaging, optical coherence tomography (OCT), hematoxylin and eosin (H&amp;E) staining, and whole-mount ZO-1 immunofluorescence staining. Protein levels were determined using Western blotting. Jnk1[+/-]Jnk2[-/-] mice were obtained by crossbreeding Jnk2[-/-] mice with Jnk1[+/-] mice.<br><br>RESULTS: In C57BL/6&#xa0;J mice, SI robustly activated JNK signaling in the retinal pigment epithelium (RPE)/choroid, triggering a parallel loss of retinal function and structural integrity. By contrast, Jnk1[+/-]Jnk2[-/-] mice were largely protected: both the SI-evoked JNK response in the RPE/choroid and the ensuing retinal degeneration were markedly attenuated.<br><br>CONCLUSIONS: Gene editing of JNK is effective in ameliorating SI-driven retinal injury and may serve as a promising therapeutic avenue for dry AMD.}, }
@article {pmid41390463, year = {2025}, author = {Dastgheib, KA}, title = {Histopathologic evidence of VEGF in early neovascular AMD: from a 1992 hypothesis to a 1994 discovery - a historical perspective.}, journal = {International journal of retina and vitreous}, volume = {11}, number = {1}, pages = {137}, pmid = {41390463}, issn = {2056-9920}, abstract = {BACKGROUND: In the early1990s, neovascular age-related macular degeneration (nAMD) was the leading cause of irreversible vision loss in older adults, yet its molecular basis remained unknown. In 1992, a hypothesis was proposed in which localized hypoxia could trigger vascular endothelial growth factor (VEGF)-mediated choroidal neovascularization in nAMD. Although hypoxia was recognized in ischemic retinopathies, nAMD was not considered a hypoxia-mediated retinal vascular disease.<br><br>MAIN BODY: In 1994, this hypothesis was tested using antigen retrieval immunohistochemistry on paraffin-embedded whole human eye sections with early nAMD. The study demonstrated strong VEGF immunoreactivity in the retinal pigment epithelium in the macular area but not in normal control eyes, providing the first direct histopathologic evidence of VEGF expression at the site of disease in intact human eyes with early nAMD. Until that point, the role of VEGF in ischemic retinopathies was being uncovered, but its involvement in early-stage nAMD had not yet been demonstrated.<br><br>CONCLUSION: The 1992-1994 work established both the hypothesis and the first direct tissue evidence linking VEGF to early nAMD. This discovery, made just over a decade before the advent of anti-VEGF therapy, anticipated one of ophthalmology's most transformative achievements, preserving vision for millions worldwide.}, }
@article {pmid41392555, year = {2026}, author = {Andreev, V and Yakovleva, M and Kostyukov, A and Sokolova, V and Shcheslavskiy, V and Goltsman, G and Feldman, T and Kuzmin, V and Ostrovsky, M and Morozov, P}, title = {Interrogation of Retinal Lipofuscin by Fluorescence Lifetime Imaging Microscopy.}, journal = {Journal of biophotonics}, volume = {19}, number = {3}, pages = {e202500418}, doi = {10.1002/jbio.202500418}, pmid = {41392555}, issn = {1864-0648}, support = {23-65-10005//Russian Science Foundation/ ; 122041400102-9//Ministry of Science and Higher Education of the Russian Federation/ ; 23-SCH06-20//Moscow State University Program of Development/ ; }, mesh = {*Lipofuscin/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Microscopy, Fluorescence/methods ; Humans ; *Retina/metabolism ; Animals ; Macular Degeneration/metabolism/pathology ; Time Factors ; }, abstract = {Age-related macular degeneration is a disease that affects the middle part of the vision and involves pathological alterations in the retinal pigment epithelium. Accurate and timely evaluation of the retinal pigment epithelium is a cornerstone of effective treatment planning. In this study, we present the development of a preclinical method for early diagnostics of age-related macular degeneration using time and spectral characteristics of fluorescence of lipofuscin granules from the retinal pigment epithelium. Using the unique system based on a superconducting single-photon detector and time-correlated single-photon counting electronics integrated in the confocal laser scanning microscope we determined the parameters of fluorescence (distribution long and short fluorescence lifetime components and their contribution to the total fluorescence signal as well as fluorescence spectral shift) that have a diagnostic value for differentiation of the normal and pathological states in the degenerative diseases of the retina and retinal pigment epithelium.}, }
@article {pmid41393074, year = {2025}, author = {Nagaoka, K and Makino, S and Inoda, S and Kaburaki, T}, title = {Secondary Angle Closure Glaucoma due to Massive Subretinal and Suprachoroidal Hemorrhage in Neovascular Age-Related Macular Degeneration: Clinical Case and Literature Review.}, journal = {Case reports in ophthalmological medicine}, volume = {2025}, number = {}, pages = {2230622}, pmid = {41393074}, issn = {2090-6722}, abstract = {Massive subretinal hemorrhage secondary to neovascular age-related macular degeneration (nAMD) is relatively uncommon, and reports of secondary angle closure glaucoma associated with such hemorrhage are even rarer. We report a case of a 93-year-old woman with a history of nAMD who developed this condition, along with a review of the relevant literature.}, }
@article {pmid41393127, year = {2025}, author = {Lin, TH and Lin, YY and Huang, YT and Huang, YC and Tien, PT and Wan, L and Lin, HJ}, title = {Chronic kidney disease increases the risks of age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1635766}, pmid = {41393127}, issn = {2296-858X}, abstract = {IMPORTANCE: Age-related macular degeneration (AMD) and chronic kidney disease (CKD) are common causes of morbidity, with systemic risk factors shared. Clarifying the association between the two is crucial to guiding comprehensive management.<br><br>OBJECTIVE: This study aimed to systematically review current and latest evidence on the influence of CKD on AMD prevalence. An investigation was performed into various AMD stages and how different CKD severities exert their effects.<br><br>DATA SOURCES: Databases of PubMed and Embase were searched from their inception to 11 November 2024. Reference lists of studies were reviewed, and relevant researchers were contacted. The study was accepted and registered with PROSPERO (CRD420250612669).<br><br>STUDY SELECTION: Eligible studies of the current review are observational, peer-reviewed, and include quantitative comparisons of AMD prevalence between populations with and without CKD. Studies with overlapping data or investigating AMD incidence were excluded. Twenty studies met the inclusion criteria from the 3,218 initially identified.<br><br>DATA EXTRACTION AND SYNTHESIS: We extracted data and assessed study quality using the Appraisal tool for Cross-Sectional Studies (AXIS) tool for cross-sectional studies. Our meta-analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and were conducted with Review Manager 5.4.1. Risk of bias was evaluated using the AXIS quality appraisal tool, and the overall certainty of evidence was qualitatively assessed following the GRADE approach.<br><br>MAIN OUTCOMES AND MEASURES: Primary outcomes are the prevalence of all-stage, early-stage, and late-stage AMD among CKD and non-CKD patients. Secondary outcomes investigated AMD prevalence among patients with different CKD stages. We reported in our analyses the risk ratios (RRs) with 95% confidence intervals (CIs).<br><br>RESULTS: All-stage AMD prevalence was found to be higher among CKD patients (RR: 1.65; 95% CI: 1.49-1.83). Similarly, early-stage AMD was more prevalent among CKD patients (RR: 1.47; 95% CI: 1.26-1.71). In late-stage AMD, an even stronger association was shown (RR: 3.72; 95% CI: 2.14-6.45). Meanwhile, there was no significant difference in AMD prevalence between moderate and advanced CKD stages (RR: 1.08; 95% CI: 0.48-2.46).<br><br>CONCLUSION AND RELEVANCE: Our findings indicate that CKD is significantly associated with higher AMD prevalence. These findings suggest the effects of shared systemic mechanisms and underscore the need for ophthalmic screening in CKD patients. Further studies are needed to strengthen causality and expand generalizability beyond the Asian population.<br><br>The systematic review was registered in PROSPERO (CRD420250612669).}, }
@article {pmid41394258, year = {2025}, author = {Blehm, C and Hall, B}, title = {Comparison of Visual Field Assessments Between the Humphrey Field Analyzer, Tempo, and Virtual Eye Elite Perimeters.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4535-4542}, pmid = {41394258}, issn = {1177-5467}, abstract = {PURPOSE: To compare test duration and the agreement of summary metrics between the TEMPO, Virtual Eye ELITE (VEE), and Humphrey Field Analyzer (HFA) perimeters.<br><br>METHODS: This was a prospective, randomized, comparative study. Subjects were excluded if they were unable to tolerate ophthalmic imaging or had any ocular or systemic conditions that could affect visual field test results, such as age-related macular degeneration, peripheral retinal disease, or severe glaucoma. Eligible subjects were assessed at 1 visit with all perimeters for total bilateral acquisition time, mean deviation (MD), pattern standard deviation (PSD), foveal threshold (FT), visual field index (VFI), false positives and false negatives, and administered a questionnaire.<br><br>RESULTS: A total of 54 subjects completed the study. Mean bilateral visual field acquisition time differences were significant between TEMPO and HFA (p < 0.001) and TEMPO and VEE (p < 0.001), and not significant between HFA and VEE (p = 0.34). Mean MD differences were not significant between TEMPO and HFA (p = 0.96) and were significant for TEMPO and VEE (p = 0.01) and HFA and VEE (p = 0.02). Mean PSD differences were not significant between TEMPO and HFA (p = 0.27), TEMPO and VEE (p = 0.72), or HFA and VEE (p = 0.72). Mean foveal threshold differences were significant between TEMPO and HFA (p < 0.001), TEMPO and VEE (p < 0.001), and HFA and VEE (p < 0.001). A significantly higher percentage of subjects reported agreement that the testing was "Easy" to perform with the TEMPO compared to HFA (p < 0.001), TEMPO compared to VEE (p = 0.006), and with VEE compared to HFA (p = 0.002).<br><br>CONCLUSION: The results suggest similar summary metrics between the HFA, TEMPO, and VEE perimeters. There was faster acquisition time with the TEMPO. These results also indicate the potential for streamlined clinical workflow.}, }
@article {pmid41394857, year = {2025}, author = {Fan, Q and Li, Z}, title = {Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1703382}, pmid = {41394857}, issn = {1664-3224}, mesh = {Humans ; *Blood-Retinal Barrier/immunology ; *Autoimmunity ; *Immunity, Innate ; Animals ; *Immune Privilege/immunology ; *Adaptive Immunity ; *Retina/immunology/pathology ; *Retinal Diseases/immunology ; Uveitis/immunology ; }, abstract = {The retina preserves vision by tightly regulating inflammation ("immune privilege") via blood-retinal barriers, neuroglial checkpoints, and tolerogenic cues. This actively maintained-and potentially restorable-state is breached in major retinal diseases through three recurrent archetypes. We synthesize 2015-2025 advances into a framework of barrier failure, innate dysregulation, and adaptive autoimmunity. Across age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and non-infectious uveitis (NIU): AMD exhibits complement-microglia para-inflammation with later outer-barrier compromise; DR exemplifies inner-BRB failure with inflammatory amplification; RP begins with degeneration-triggered innate activation and progresses to combined innate-adaptive injury; NIU represents T-cell-driven breach of the blood-retinal barrier. Interventional human evidence supports immunity as a therapeutic target: complement inhibition slows geographic atrophy; anti-VEGF reduces leak; intravitreal corticosteroids suppress inflammatory edema; and anti-TNF/IL-6R improve refractory NIU. Emerging strategies aim at privilege restoration-reinforcing myeloid checkpoints, tempering inflammasomes, and exploring tolerance-oriented approaches to re-educate adaptive immunity. Evidence from preclinical and early translational studies indicates that ocular tissues can imprint regulatory/anergic programs on pathogenic T cells, supporting mechanism-aligned, patient-tailored immunotherapy as a testable route to restore regulation, mitigate inflammation, and slow degeneration.}, }
@article {pmid41394869, year = {2025}, author = {Wei, Y and Lin, Y and Li, Y and Liu, J and Yang, Y and Chen, H and Han, Z and Wang, K and Qian, T and Ju, Y and Zheng, W}, title = {Redefining cell death: ferroptosis as a game-changer in ophthalmology.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1709354}, pmid = {41394869}, issn = {1664-3224}, mesh = {*Ferroptosis ; Humans ; Animals ; *Eye Diseases/metabolism/pathology/etiology ; Reactive Oxygen Species/metabolism ; *Ophthalmology ; Cell Death ; }, abstract = {Ferroptosis, recently proposed as a novel type of cell death, is characterized by unique characteristics and recognition functions. It is involved in diverse physiological processes and in the onset and progression of various diseases and is characterized by reactions between reactive oxygen species (ROS) and iron-dependent lipid peroxidation. This process is finely regulated by a variety of metabolic pathways. Ferroptosis fundamentally differs from conventional cell death mechanisms such as apoptosis, necrosis, and autophagy. In recent years, research on ferroptosis in the field of ophthalmology has gradually emerged, and a large amount of evidence has shown that it is closely related to the occurrence and development of ophthalmic diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal ischemia-reperfusion injury (RIRI), retinitis pigmentosa, dry eye disease, cataracts, and glaucoma. This paper provides a comprehensive review of the latest advancements in ferroptosis within ophthalmological research and systematically describes the molecular mechanisms and pathophysiological significance of ferroptosis in the pathogenesis and progression of ophthalmic diseases. Exploring the mechanisms of ferroptosis holds promise for the delivery of novel molecular targets and therapeutic approaches to prevent and treat ophthalmic diseases. Additionally, its clinical translational and application are anticipated to surmount current therapeutic limitations and emerge as a significant direction for breakthroughs in the precision medicine era.}, }
@article {pmid41395976, year = {2025}, author = {Shekho, N and Vergmann, AS and Pedersen, FN and Stokholm, L and Thinggaard, BS}, title = {Characterizing and assessing vision-related quality of life among patients discontinued treatment for neovascular age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70044}, pmid = {41395976}, issn = {1755-3768}, support = {//The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark/ ; 167-A6477//The Chief Physicians' Council Research Foundation (Overl&#xe6;ger&#xe5;dets Forskningsfond), Odense University Hospital/ ; }, abstract = {PURPOSE: This study characterized and assessed vision-related quality of life (VRQoL) in patients with neovascular age-related macular degeneration (nAMD) who discontinued treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF), comparing them to those undergoing treatment. Secondarily, it explored reasons for treatment discontinuation against medical advice.<br><br>METHODS: This survey-based cross-sectional study used data collected for the Danish study, "Identification of Patient-Reported Barriers in Treatment for nAMD" (I-OPTA) at Odense University Hospital, Denmark. I-OPTA included a self-developed questionnaire and the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Main outcomes were demographics, treatment details, NEI-VFQ-25 scores, and reasons for treatment discontinuation against medical advice. Linear regression models investigated the impact of variables on the composite NEI-VFQ-25 score.<br><br>RESULTS: The study included 172 (32.6%) patients who had discontinued treatment and 356 (67.4%) patients who were undergoing treatment; 10 (5.8%) discontinued against medical advice. Discontinued patients were older (median 81.0&#x2009;years, p-value&#x2009;=&#x2009;0.004), had lower best-corrected visual acuity (BCVA) in the worse-seeing eye (p-value<0.001), had a shorter treatment duration (p-value&#x2009;=&#x2009;0.001) and lived alone (p-value&#x2009;=&#x2009;0.044). Discontinued patients showed lower scores in all NEI-VFQ-25 domains except ocular pain. Higher BCVA correlated with a higher composite score of NEI-VFQ-25. Reasons for discontinuation against medical advice included treatment burden and perceived inefficacy.<br><br>CONCLUSION: Patients who discontinued treatment for nAMD report lower VRQoL, with lower BCVA in the worse-seeing eye, older age, living alone, and unilateral treatment possibly contributing to treatment discontinuation. Future studies on visual acuity and retinal fluid in this group could guide decisions on treatment discontinuation, emphasizing patients' quality of life.}, }
@article {pmid41396384, year = {2025}, author = {Li, Z and Jin, S and Xu, W and Zhang, M and Liu, X}, title = {Advances in the treatment of blinding retinal diseases.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {21}, pmid = {41396384}, issn = {1573-2630}, support = {No. 82371043//National Natural Science Foundation of China/ ; No.20240601014RC//the Project of Outstanding Talents in Scientific and Technological Innovation and Entrepreneurship for Middle-aged and Young Scientists of Jilin Provincial Science and Technology Department/ ; }, mesh = {Humans ; *Genetic Therapy/methods ; *Retinal Diseases/therapy/complications ; *Blindness/etiology/therapy ; *Retinal Pigment Epithelium/transplantation ; *Stem Cell Transplantation/methods ; }, abstract = {Blinding retinal diseases, including inherited and degenerative conditions, rank globally among the primary causes of permanent vision loss. While certain degenerative retinal diseases like age-related macular degeneration and diabetic retinopathy can be partially managed through intravitreal anti-VEGF injections or the use of complement inhibitors, most patients still lack effective treatment options. Recently, several promising therapeutic avenues have surfaced, such as stem cell-derived retinal pigment epithelium cell transplantation, gene therapy, and the implantation of retinal prostheses. This review summarizes recent clinical trials and advances in gene therapy for inherited retinal diseases, outlines techniques for retinal pigment epithelium cell transplantation, and discusses methods to improve graft survival. It also examines strategies for enhancing the resolution of retinal prostheses and explores their future clinical potential, providing new perspectives on the management of degenerative retinal conditions.}, }
@article {pmid41396449, year = {2025}, author = {Karaca, I and Wei, Y and Nelson, R and Sassen, SH and Daynes, K and Clark, F and Brown, T and Messina, A and Pfau, M and Zhang, Y and Schmitz-Valckenberg, S and Fleckenstein, M}, title = {Association of Mesopic and Dark-Adapted Retinal Sensitivity With Type 1 Macular Neovascularization in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {45}, pmid = {41396449}, issn = {1552-5783}, support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Aged ; *Dark Adaptation/physiology ; Visual Field Tests ; *Mesopic Vision/physiology ; Visual Fields/physiology ; Aged, 80 and over ; Visual Acuity/physiology ; Tomography, Optical Coherence ; *Retina/physiopathology ; *Macular Degeneration/physiopathology/complications ; }, abstract = {PURPOSE: To assess the impact of type 1 macular neovascularization (MNV) on mesopic and dark-adapted (DA) cyan retinal sensitivity using fundus-controlled perimetry (FCP [microperimetry]) in patients with age-related macular degeneration (AMD).<br><br>METHODS: This index study includes baseline data from AMD patients with type 1 MNV without complete retinal pigment epithelium and outer retinal atrophy (cRORA). Mesopic and DA-cyan sensitivity were measured using FCP with standardized and MNV-lesion-tailored test grids. We applied linear mixed-effects models to compare retinal sensitivity in regions with versus without co-localized type 1 MNV. Age-specific hill-of-vision data that served as reference were estimated using Bayesian quantile regressions.<br><br>RESULTS: Of the 55 eyes with baseline data, 27 eyes without cRORA (27 patients; mean age, 76.8 &#xb1; 6.7 years; 74.1% female) were included in this detailed analysis. In regions co-localizing with type 1 MNV, unadjusted mesopic sensitivity was significantly increased by a mean of 2.10 dB (95% confidence interval [CI], 1.58-2.63; P < 0.001), whereas unadjusted DA-cyan sensitivity was significantly reduced by 3.12 dB (95% CI, 2.38-3.86; P < 0.001) compared to regions without evidence of MNV. When adjusting for age-specific hill-of-vision reference data, mesopic sensitivity remained significantly higher by 0.78 dB (95% CI, 0.29-1.28; P = 0.002) and DA-cyan sensitivity remained significantly lower by 2.07 dB (95% CI, 1.33-2.80; P < 0.001) in regions co-localizing with type 1 MNV versus those without MNV.<br><br>CONCLUSIONS: In AMD, areas overlying type 1 MNV showed higher mesopic but reduced DA-cyan sensitivity, suggesting localized preservation yet subtype-specific vulnerability. These findings will be further examined through structural analyses and prospective validation in our ongoing study.}, }
@article {pmid41396593, year = {2025}, author = {Zhong, Y and Qin, Y}, title = {Frailty-Driven Risk Stratification in Age-Related Ophthalmic Diseases: Thresholds, Precision Screening, and Mendelian Randomization Insights.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {17}, pmid = {41396593}, issn = {2164-2591}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Male ; Aged ; *Frailty/diagnosis ; Middle Aged ; Female ; *Eye Diseases/diagnosis/epidemiology ; Macular Degeneration/epidemiology ; Risk Assessment/methods ; Adult ; Nutrition Surveys ; Cataract ; Risk Factors ; Aged, 80 and over ; Glaucoma ; Disease Progression ; }, abstract = {PURPOSE: To define frailty thresholds for accelerated progression of age-related ophthalmic diseases and inform precision intervention.<br><br>METHODS: Using NHANES 2005-2008 (n = 7081 adults &#x2265; 40 years), we constructed a 49-item frailty index (FI) via the deficit accumulation model. Missing data were addressed with complete-case analysis (n = 4120) and multiple imputation. Two analytic cohorts were defined: (1) objective diagnosis group and (2) composite diagnosis group. Multivariable logistic regression with restricted cubic splines (RCS) assessed associations between the FI and age-related macular degeneration (AMD), cataract, glaucoma, and diabetic retinopathy (DR). Bidirectional Mendelian randomization (MR) tested causality.<br><br>RESULTS: Findings were consistent across complete-case and imputed datasets. In continuous analyses, the FI was associated with AMD (composite odds ratio [OR] = 1.17; objective OR = 1.16), cataract (OR = 1.30), DR (OR = 1.33), and glaucoma (OR = 1.12). In categorical analyses, extreme frailty (FI > 0.45) conferred the highest risks: cataract (OR = 2.51), DR (OR = 2.04), AMD (OR = 1.77), and glaucoma (OR = 1.45). RCS analyses identified nonlinear thresholds at FI = 0.20 (AMD) and FI = 0.19 (cataract), whereas DR and glaucoma showed linear trends. MR supported a causal effect of frailty on four diseases, with no evidence for reverse causation.<br><br>CONCLUSIONS: Frailty was shown to accelerate ophthalmic disease progression. Three clinical implications are proposed here: (1) prioritized screening for individuals with FI > 0.45, (2) recognizing FI thresholds around 0.19 to 0.20 as potential early warning signals for accelerated AMD and cataract, and (3) integrating geriatric and ophthalmic care.<br><br>TRANSLATIONAL RELEVANCE: This study provides actionable FI thresholds to identify high-risk aging populations and reinforces frailty as a modifiable upstream driver of ocular aging.}, }
@article {pmid41397442, year = {2026}, author = {Li, N and Hong, R and You, H and Xu, F and Zhang, Q and Lin, Y and Su, Y and Lan, D and Jin, L and She, J}, title = {DELP Treatment on Vision and Retinal Microcirculation in Patients With Acute Ischemic Stroke: Report of Five Cases and Literature Review.}, journal = {Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy}, volume = {30}, number = {2}, pages = {168-175}, pmid = {41397442}, issn = {1744-9987}, support = {2023YFC3604500//National Key Research and Development Program of China/ ; 2023YFC3604505//National Key Research and Development Program of China/ ; 22Y31900200//Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; 22Y31900203//Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; Z155080000004//National Clinical Key Specialty Project Foundation/ ; SHDC22023304//Shanghai Municipal Hospital Development Center/ ; 82230084//National Natural Science Foundation of China/ ; 82172545//National Natural Science Foundation of China/ ; 82201404//National Natural Science Foundation of China/ ; //Shanghai Blue Cross Hospital Co., Ltd. and Shanghai Tongji University Educationg Development Foundation/ ; 2024QN05//Shanghai Jing'an District Science and Technology Commission and Jing'an District Health Commission/ ; }, mesh = {Humans ; Microcirculation ; Aged ; Male ; Female ; *Ischemic Stroke/therapy/complications/physiopathology ; Visual Acuity ; Middle Aged ; Retinal Vessels/diagnostic imaging ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; }, abstract = {BACKGROUND: The delipid extracorporeal lipoprotein filter from plasma (DELP) treatment can effectively reduce blood lipid, increase blood flow, and improve neurological deficits in patients with acute ischemic stroke (AIS). However, its effect on vision and retinal microcirculation in stroke patients has never been reported.<br><br>METHODS: Between November 2023 and June 2024, five patients underwent DELP treatment as a routine adjuvant therapy for AIS. Detailed ophthalmological examinations, including best corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA), were performed on them one day prior to and 1-3&#x2009;days following the DELP treatment.<br><br>RESULTS: Among the ten eyes examined, six had diabetic retinopathy (DR), two had dry age-related macular degeneration (dAMD), one had idiopathic epiretinal membrane (iERM), and one was normal. Surprisingly, after DELP treatment, the BCVA improved by 0.2LogMAR in six eyes, 0.1LogMAR in three eyes, and remained unchanged in one eye. The vessel density (VD) in the fovea increased in six eyes, remained unchanged in three eyes, and decreased in one eye. The non-perfusion area (NPA) in the superficial capillary plexus (SCP) decreased in six eyes, remained unchanged in two eyes, and increased in two eyes. The NPA in the deep capillary plexus (DCP) decreased in eight eyes and remained unchanged in two eyes. A small amount of bleeding occurred in Patient 3's right eye, and no other adverse events were observed post-treatment.<br><br>CONCLUSIONS: In this case series, the DELP treatment showed a potentially significant therapeutic effect on the BCVA and retinal microcirculation in AIS patients with good safety and provided a rationale for further investigation. At the same time, this treatment may provide an effective option for the treatment of eye diseases such as DR, iERM, and AMD.}, }
@article {pmid41397462, year = {2026}, author = {Liesenhoff, C and Krause, D and Eckardt, F and Lorger, A and Meyrl, C and Deiters, V and Hafner, M and Schiefelbein, J and Klaas, J and Schworm, B and Priglinger, SG and Siedlecki, J}, title = {Efficacy of 2 mg vs. High-Dose 8 mg Aflibercept in Neovascular Age Related Macular Degeneration.}, journal = {Klinische Monatsblatter fur Augenheilkunde}, volume = {243}, number = {2}, pages = {103-109}, doi = {10.1055/a-2760-5850}, pmid = {41397462}, issn = {1439-3999}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Female ; Male ; Aged ; Treatment Outcome ; Dose-Response Relationship, Drug ; Visual Acuity/drug effects ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged, 80 and over ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; }, abstract = {PURPOSE: To investigate the efficacy of switching treatment from 2 mg aflibercept to high-dose 8 mg aflibercept in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: The database was screened for eyes with nAMD switched from 2&#x2009;mg to 8&#x2009;mg aflibercept. Demographic data, multimodal imaging, treatment parameters and outcomes were recorded. Efficacy of 2&#x2009;mg vs. 8&#x2009;mg aflibercept was compared four injections prior to, and four injections after switching by analysing central subfield thickness (CST), subretinal fluid (SRF) and intraretinal fluid (IRF) as well as visual acuity (VA).<br><br>RESULTS: Sixteen consecutive eyes of 16 patients (mean age 78.5&#x2009;&#xb1;&#x2009;5.5 years) were identified. There were 13 women (81.3%) and 3 men (18.7%). Prior to switching, mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 8.1&#x2009;&#xb1;&#x2009;2.1 years and pretreatment amounted to a mean of 27.8&#x2009;&#xb1;&#x2009;23.6 injections. Mean injection intervals were similar prior to and after switching (5.05 vs. 5.13 weeks; p&#x2009;=&#x2009;0.76). CST remained stable before and after switching (p&#x2009;=&#x2009;0.25). After switching, the percentage of eyes with a dry macula increased from 0% to 37.5% (p&#x2009;=&#x2009;0.02) and the percentage of eyes with SRF decreased from 93.8% to 56.3% (p&#x2009;=&#x2009;0.037). There was a trend, but no significant effect towards a reduction of IRF (18.8% to 6.3%, p&#x2009;=&#x2009;0.60). Visual acuity remained stable irrespective of treatment (p&#x2009;=&#x2009;0.78).<br><br>CONCLUSIONS: Concerning CST on OCT, no clear advantage of high-dose 8&#x2009;mg aflibercept over conventional 2&#x2009;mg aflibercept was seen in this study. However, with high-dose 8&#x2009;mg aflibercept the number of eyes with a dry macula increased, and the amount of eyes with SRF decreased significantly. In pretreated eyes, the analysis of macular fluid compartments (as compared to CST) might be more sensitive for comparing treatment effects between 2&#x2009;mg and 8&#x2009;mg aflibercept.}, }
@article {pmid41398283, year = {2025}, author = {Antonietti, M and Mercado, C and Smiddy, WE and Schwartz, SG}, title = {Central retinal vein occlusion following intravitreal injections: a case series highlighting multifactorial risk.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {12}, pmid = {41398283}, issn = {2056-9920}, support = {GR004596-1//Research to Prevent Blindness Unrestricted Grant/ ; }, abstract = {INTRODUCTION: Intravitreal injections are standard treatment for various manifestations of age-related macular degeneration (AMD) but are associated with rare complications, including central retinal vein occlusion (CRVO). This report describes three cases of CRVO following intravitreal injections in patients with AMD.<br><br>METHODS: Retrospective case series describing three patients with AMD who developed CRVO after intravitreal injections.<br><br>RESULTS: CRVO occurred after ranibizumab (Lucentis, South San Francisco, CA), brolucizumab (Beovu, Novartis, Basel, Switzerland), and pegcetacoplan (Syfovre, Apellis, Waltham, MA) injections. All patients had multiple systemic vasculopathic risk factors. No intraocular inflammation or vasculitis was observed on examination, and fluorescein angiography was not performed. Visual outcomes were poor despite anti-VEGF treatment. None of the three patients developed neovascular glaucoma under our observation. The timing relationship between injection and CRVO varied, and causality could not be established.<br><br>CONCLUSION: CRVO may occur after intravitreal injections across different drug classes, even with agents that have low inflammatory potential. These cases highlight the multifactorial nature of this event and the importance of considering systemic vasculopathy when evaluating post-injection complications.}, }
@article {pmid41398318, year = {2026}, author = {Keshet, Y and Ngo, WK and Salcedo-Ledesma, A and Walia, JJ and Spaide, RF}, title = {Quantitative assessment of hyperreflective dots in the outer nuclear layer over neovascular lesion components.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {363-368}, pmid = {41398318}, issn = {1476-5454}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Aged ; Male ; Female ; *Wet Macular Degeneration/diagnosis/diagnostic imaging ; Aged, 80 and over ; Subretinal Fluid/diagnostic imaging ; *Choroidal Neovascularization/diagnosis ; Middle Aged ; Microglia/pathology ; }, abstract = {OBJECTIVES: To evaluate the outer nuclear layer for hyperreflective dots (HRD), a proposed imaging correlate of retinal microglia, in eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: High-resolution optical coherence tomography (OCT) of eyes with nAMD was evaluated with the aid of a custom ImageJ plugin that automatically identified HRD and plotted them on the corresponding near infrared (IR) fundus image. Areas of subretinal fluid (SRF), double layer sign (DLS), and the area of neovascularisation as imaged by OCT angiography (A) were mapped to the near-IR image. The number of HRD overlying these regions was tabulated.<br><br>RESULTS: There were 38 eyes of 38 patients. SRF was present in 23 eyes, there was a median 8.5 HRD /mm[2] over this area. DLS was present in all eyes and with a median of 6.5 HRD/mm[2] over this area. Neovascularisation was detectable using OCTA with a median of 6.8 HRD/mm[2]. The density of HRD/mm[2] was not significantly different over areas of DLS with fluid compared to areas of DLS without SRF (P&#x2009;=&#x2009;0.22). The median HRD/mm[2] for uninvolved areas of the retina was 0.7, a difference that was significantly less than over areas of SRF, DLS, and OCTA detected neovascularisation (P&#x2009;<&#x2009;0.001 for all comparisons).<br><br>CONCLUSIONS: There is an aggregation of HRD in the outer retina over lesion components of nAMD. These HRD may be present in response to SRF, but their existence over regions of the neovascular lesion without SRF suggests that additional factors are involved in their recruitment.}, }
@article {pmid41398938, year = {2025}, author = {Kose, H and Ozkan, B and Kanli, A and Karabas, LV and Akpinar, G and Kasap, M and Sumer, F}, title = {Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.}, journal = {BMC geriatrics}, volume = {25}, number = {1}, pages = {1019}, pmid = {41398938}, issn = {1471-2318}, mesh = {Humans ; *Proteomics/methods ; Female ; Male ; Aged ; Prospective Studies ; *Macular Degeneration/metabolism/diagnosis ; *Vitreous Body/metabolism/chemistry ; Case-Control Studies ; *Eye Proteins/metabolism ; Aged, 80 and over ; Middle Aged ; Biomarkers/metabolism ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) represents one of the most common causes of permanent vision impairment in individuals over 50 years of age.<br><br>METHODS: This study aims to characterize AMD using proteomic analysis to enhance diagnosis and treatment strategies. In a prospective case-control clinical trial, vitreous fluids (VF) from thirteen AMD patients were collected during surgery and analyzed by 2DE-based MALDI TOF-TOF MS/MS. PANTHER and STRING analyses were performed to investigate the biological relationships between the identified proteins and to determine relevant cellular pathways.<br><br>RESULTS: A total of 11 proteins were differentially regulated between AMD patients and healthy controls. Among them, Apolipoprotein E was significantly up-regulated (&#x2191;3-fold), while ten proteins, including alpha-crystallin A chain (&#x2193;779-fold), beta-crystallin B2 (&#x2193;232-fold), and haptoglobin (&#x2193;15-fold), were markedly down-regulated. These quantitative differences underscore the critical role of lipid metabolism, oxidative stress response, and inflammation in AMD pathogenesis.<br><br>CONCLUSION: The identified proteins are related to biological regulation, retinal protection, and regulation of inflammation and angiogenesis processes. The up-regulation of Apolipoprotein E highlights its involvement in lipid metabolism and inflammatory modulation, while the sharp down-regulation of crystallin family proteins suggests compromised retinal protection against oxidative stress and apoptosis. These protein alterations provide new insights into AMD pathogenesis and may serve as potential biomarkers for early diagnosis and novel therapeutic targets in managing the disease.}, }
@article {pmid41399598, year = {2025}, author = {Flindris, K and Gorgoli, K and Koumpoulis, I}, title = {A Case Series of Bacillary Layer Detachment (BALAD) in Neovascular Age-Related Macular Degeneration (nAMD): A Novel Optical Coherence Tomography (OCT) Biomarker.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96819}, pmid = {41399598}, issn = {2168-8184}, abstract = {Bacillary layer detachment (BALAD) is a newly recognized optical coherence tomography (OCT) finding, defined as a split at the photoreceptor inner segment (myoid zone) resulting in a dome-shaped intraretinal fluid cavity. BALAD has been reported in various chorioretinal diseases and may serve as a novel structural OCT biomarker of severe exudation. We present a case series of BALAD in neovascular age-related macular degeneration (nAMD) to characterize its multimodal imaging features and discuss its diagnostic and prognostic significance. Three patients with active nAMD exhibited BALAD on spectral-domain OCT. In each instance, OCT cross-sections showed a sharply demarcated hyporeflective intraretinal cavity beneath an intact external limiting membrane (ELM) and above the ellipsoid zone (EZ). OCT angiography (OCTA) revealed an underlying high-flow choroidal neovascular network corresponding to the BALAD in all cases. All three patients initially had significant visual impairment. Two patients were treated with serial intravitreal anti-vascular endothelial growth factor (VEGF) injections, resulting in rapid resolution of the BALAD cavity, reabsorption of subretinal and intraretinal fluid, and marked improvement in best-corrected visual acuity (e.g., from 20/400 to 20/40). The third patient, who declined treatment, developed persistent BALAD with progressive subfoveal fibrosis and no visual recovery. BALAD in nAMD indicates an aggressive disease phenotype with intense outer retinal fluid accumulation and photoreceptor layer schisis. Prompt anti-VEGF therapy was associated with anatomical recovery and vision improvement in the treated cases. Recognizing BALAD on OCT and OCTA is clinically important, as it differentiates intraretinal from subretinal pathology and underscores the need for early, aggressive treatment to mitigate irreversible retinal damage in nAMD.}, }
@article {pmid41399815, year = {2025}, author = {Leozappa, M and Mavilio, A and Durante, G and Piccinni, L and Miggiano, A}, title = {SING IMT telescopic intraocular lens implantation in a patient with inverse retinitis pigmentosa: A case report.}, journal = {American journal of ophthalmology case reports}, volume = {40}, number = {}, pages = {102479}, pmid = {41399815}, issn = {2451-9936}, abstract = {PURPOSE: To report the off-label use of the SING IMT telescopic intraocular lens (IOL) (Samsara Vision) in a patient with inverse retinitis pigmentosa (RP) and cataracts, evaluating its impact on visual acuity and functional outcomes.<br><br>OBSERVATIONS: A 77-year-old female with inverse RP, bilateral cataracts, hypertension, and hypercholesterolemia presented with hand motion visual acuity (&#x2265;2.3 LogMAR) bilaterally, assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 2 meters. An external telescopic simulator improved visual acuity to 6 letters (1.58 LogMAR) in the left eye. Preoperative assessments, including optical coherence tomography, fundus autofluorescence, and electrophysiological testing, confirmed central macular degeneration and supported left-eye SING IMT implantation. Phacoemulsification with SING IMT implantation was performed, followed by a visual rehabilitation program. By 6 months, visual acuity reached 6 ETDRS letters (1.58 LogMAR) at 3 meters. Functional improvements included reading, writing, sewing, and television viewing, with enhanced autonomy and mood. Mild corneal edema resolved within 1 week, and no posterior capsular opacification or cystoid macular edema occurred during 8 months of follow-up.<br><br>CONCLUSION AND IMPORTANCE: This case reporting use of the SING IMT in inverse RP demonstrates its potential to improve vision and quality of life in patients with central vision loss from retinal dystrophies, surpassing typical cataract surgery outcomes. The 2.5x magnification and structured rehabilitation were key to functional gains. Larger studies are needed to validate efficacy and refine patient selection.}, }
@article {pmid41400582, year = {2025}, author = {Ma, H and Li, S and Le, Y and Stanford, D and Freeman, WM and Ding, XQ}, title = {Single Cell RNAseq Analysis of Thyroid Hormone Effects on Retinal Glial Cells.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.1221}, pmid = {41400582}, issn = {2152-5250}, abstract = {Thyroid hormone (TH) signaling regulates cellular metabolism and stress response in the retina. Increased TH levels in circulation are associated with a higher incidence of age-related macular degeneration. Furthermore, stimulation of TH signaling induces retinal degeneration in mice, which is accompanied by the activation of retinal glial cells. Here, we investigated the transcriptional changes induced by triiodothyronine (T3) in retinal glial cells using single-cell RNA sequencing (scRNAseq) and bioinformatic analyses. One-month-old C57BL/6 mice were given T3 (20 μg/ml in drinking water) for four weeks, after which their retinal cells were collected to assess viability and undergo scRNAseq. The resulting data were analyzed using the Seurat package, visualized by the Loupe Browser, and Ingenuity Pathway Analysis. Analyses of differentially expressed genes (DEGs) in Müller cells, astrocytes, and microglia revealed significant enrichment in pathways associated with stress, immune response, and degeneration. Müller cells exhibited upregulation of mitochondrial dysfunction, acute-phase response, and sirtuin signaling pathways. Astrocytes displayed downregulation of synaptogenesis, neurovascular coupling, cAMP response elements, and calcium signaling. Microglia showed upregulation of coordinated lysosomal expression and regulation signaling, systemic lupus erythematosus in T cells, and multiple sclerosis signaling, and downregulation of actin-binding Rho activating signaling, retinoic acid receptor activation signaling, and IL-17 signaling. The distinct and overlapping transcriptional responses suggest that each retinal glial cell type plays a specific and coordinated role in adapting to stress. This study offers new insights into TH-induced retinal stress and degeneration at the transcriptional and pathway-level responses of retinal glial cells.}, }
@article {pmid41402599, year = {2026}, author = {Zhou, WD and Dong, L and Yang, YH and Zhao, HQ and Zhang, RH and Li, YT and Yu, CY and Li, HY and Wu, HT and Shi, XH and Shao, L and Wei, WB}, title = {Retinal single-cell blood velocity in eyes with varied axial length using adaptive optics scanning laser ophthalmoscopy.}, journal = {Eye (London, England)}, volume = {40}, number = {2}, pages = {268-274}, pmid = {41402599}, issn = {1476-5454}, mesh = {Humans ; Adult ; Male ; *Ophthalmoscopy/methods ; Female ; Middle Aged ; *Axial Length, Eye/pathology ; Young Adult ; *Myopia/physiopathology ; Blood Flow Velocity/physiology ; *Retinal Vessels/physiology/physiopathology ; *Retinal Artery/physiology ; }, abstract = {BACKGROUND: To investigate the hemodynamic changes in the retinal vasculature of the macular region in eyes with axial myopia.<br><br>METHODS: Individuals with varying axial lengths were included in this study. Inclusion criteria was the absence of any ocular or systemic diseases. A commercial adaptive optics scanning laser ophthalmoscopy was used to capture images of retinal vessels within the 5&#xb0;-10&#xb0; areas above and below the foveal centre. This system provided noninvasive imaging of single blood cells and automatically calculated blood velocity while detecting the flow direction. Vessels were classified based on their diameter.<br><br>RESULTS: The study included 90 patients (180 eyes; 35 (38.9%) men) with a mean age of 34.3&#x2009;&#xb1;&#x2009;12.2 years (range: 19-62 years) and a mean axial length of 25.8&#x2009;&#xb1;&#x2009;1.9&#x2009;mm (range: 21.4-30.6&#x2009;mm). The mean blood velocity in retinal arteries and veins was 35.2&#x2009;&#xb1;&#x2009;11.4&#x2009;mm/s and 34.9&#x2009;&#xb1;&#x2009;13.2&#x2009;mm/s, respectively. Single-cell blood velocity was significantly increased with longer axial length in large retinal arteries (diamater&#x2265;100&#x3bc;m) (B&#x2009;=&#x2009;2.73; &#x3b2;&#x2009;=&#x2009;0.32; P&#x2009;=&#x2009;0.01); and medium retinal arteries (diameter<100&#x3bc;m) (B&#x2009;=&#x2009;1.83; &#x3b2;&#x2009;=&#x2009;0.27; P&#x2009;=&#x2009;0.003). Correspondingly, the blood velocity of medium retinal arteries in the myopic group was significantly higher than that in the non-myopic group (t&#x2009;=&#x2009;3.37; P&#x2009;=&#x2009;0.001). Single-cell blood velocity was significantly increased with longer axial length in medium retinal veins (diameter <110 &#x3bc;m) (B&#x2009;=&#x2009;2.0; &#x3b2;&#x2009;=&#x2009;0.3; P&#x2009;=&#x2009;0.016). Correspondingly, the blood velocity of medium retinal veins in the myopic group was significantly higher than that in the non-myopic group (t&#x2009;=&#x2009;2.25; P&#x2009;=&#x2009;0.03).<br><br>CONCLUSIONS: Single-cell retinal blood velocity was significantly increased with longer axial length. These findings suggest that the hemodynamic changes observed in axial myopia, including higher arterial and venous blood velocities, may provide a potential explanation for the lower prevalence of diabetic retinopathy, age-related macular degeneration, and branch retinal vein occlusion reported in previous epidemiological studies.}, }
@article {pmid41402601, year = {2026}, author = {Sadeghi, E and Chhablani, J}, title = {Response to: 'Comment on 'Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration".}, journal = {Eye (London, England)}, volume = {40}, number = {2}, pages = {281}, pmid = {41402601}, issn = {1476-5454}, }
@article {pmid41404347, year = {2025}, author = {Attia, M and Pavlovic, T and Muliawan, A and Tuya, F and Mihalatos, M and Iwanicki, M and Kang-Mieler, J}, title = {Therapeutic potential of taurine in a pigmented rat model of age-related macular degeneration.}, journal = {Frontiers in ophthalmology}, volume = {5}, number = {}, pages = {1701761}, pmid = {41404347}, issn = {2674-0826}, abstract = {PURPOSE: To investigate the potential protective effects of taurine supplementation against retinal degeneration in an animal model of mild dry age-related macular degeneration (AMD).<br><br>METHODS: To test the effects of a taurine supplement in mild dry AMD, sodium iodate (NaIO3)-induced retinal degeneration model was used. Two administration methods, intraperitoneal (IP) and intravenous (IV), were used to deliver NaIO3 in pigmented Long Evans rats to generate mild and severe dry AMD, respectively. Structural abnormalities were evaluated in vivo using near-infrared (IR) reflectance fundus imaging and optical coherence tomography (OCT). Using the slow progressive mild AMD model, we investigated the neuroprotective effects of oral taurine supplementation (1.5% w/v in drinking water) against NaIO3-induced retinal degeneration over 20 weeks. In addition, a human Retinal Pigment Epithelium (RPE, hTERT-RPE1) cell culture model was used to directly assess taurine's ability to protect against NaIO3-related oxidative stress.<br><br>RESULTS: The high-dose IV model (80 mg/kg) exhibited extensive and severe retinal damage, with ONL thinning by 64.2% and total retinal thickness (TRT) by 47.6%, predominantly in the peripapillary region. In contrast, the lower-dose IP model (50 mg/kg) displayed milder, more gradual deterioration (outer nuclear layer (ONL) thinning by 19.4% and TRT by 11.5%). Oral taurine supplementation significantly preserved ONL and TRT in vivo and supported RPE-1 cell survival, proliferation, and motility, under NaIO3 conditions.<br><br>CONCLUSION: Taurine supplementation provided significant structural protection against NaIO3-induced damage both in vivo and in cell culture, demonstrating its potential as a therapeutic candidate for mitigating mild dry AMD progression.}, }
@article {pmid41404584, year = {2025}, author = {Che, S and Ma, Y and Cao, J}, title = {Association between serum carotenoid concentrations and risk of major age-related eye diseases among middle-aged and older adults.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1596799}, pmid = {41404584}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related eye diseases are the main causes of progressive and irreversible vision loss in aging populations worldwide. Carotenoids, as a group of common natural antioxidants, can suppress free radicals produced by complex physiological reactions, thereby protecting the eyes from the effects of oxidative stress, cell apoptosis, and mitochondrial dysfunction. The present study aims to explore the association between serum carotenoid concentrations and risk of major age-related eye diseases among middle-aged and older adults in the United States.<br><br>METHODS: This study involved 1,478 participants aged &#x2265;50&#x202f;years from the 2005-2006&#x202f;cycles of the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of prevalence of cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in relation to serum carotenoid concentrations.<br><br>RESULTS: Compared to participants in the first quartile, those in highest quartile of serum &#x3b1;-carotene (OR: 0.37; 95% CI: 0.21-0.64), &#x3b2;-carotene (OR: 0.57; 95% CI: 0.33-0.95), lutein/zeaxanthin (OR: 0.45; 95% CI: 0.27-0.76), and total carotenoid (OR: 0.58; 95% CI: 0.35-0.97) were negatively associated with risk of cataract; those in highest quartile of serum &#x3b2;-carotene (OR: 0.30; 95% CI: 0.11-0.77) and &#x3b2;-cryptoxanthin (OR: 0.28; 95% CI: 0.12-0.68) were negatively associated with risk of diabetic retinopathy; and those in highest quartile of lycopene (OR: 0.37; 95% CI: 0.18-0.78) was negatively associated with risk of AMD. In addition, subgroup analysis results indicated that participants in highest quartile of serum &#x3b1;-carotene (OR: 0.16; 95% CI: 0.08-0.32), &#x3b2;-carotene (OR: 0.40; 95% CI: 0.21-0.75), lycopene (OR: 0.46; 95% CI: 0.24-0.87), lutein/zeaxanthin (OR: 0.45; 95% CI: 0.25-0.84), and total carotenoid (OR: 0.41; 95% CI: 0.22-0.77) concentrations were negatively associated with risk of any ocular disease among female participants. By contrast, no associations were observed among male participants.<br><br>CONCLUSION: Our study demonstrated that higher serum concentrations of carotenoids were negatively associated with the risk of age-related eye diseases, particularly among middle-aged and older female participants.}, }
@article {pmid41405093, year = {2025}, author = {Suzuki, T and Terao, R and Nagahara, M and Hayashi, K and Azuma, K and Shinzawa, K and Moriwaki, K and Shiraya, T and Honjo, M and Ueta, T}, title = {iPLA2β Protects Retinal Pigment Epithelium From Ferroptosis in a Sodium Iodate-Induced Model of Dry AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {55}, pmid = {41405093}, issn = {1552-5783}, mesh = {Animals ; *Ferroptosis/physiology/drug effects ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Iodates/toxicity ; Disease Models, Animal ; Mice ; Mice, Knockout ; Electroretinography ; *Group VI Phospholipases A2/physiology ; Mice, Inbred C57BL ; Oxidative Stress ; *Macular Degeneration/chemically induced/metabolism ; Blotting, Western ; Real-Time Polymerase Chain Reaction ; Lipid Peroxidation ; }, abstract = {PURPOSE: Ferroptosis, characterized by lipid peroxidation, has been implicated in retinal pigment epithelium (RPE) degeneration in dry age-related macular degeneration (AMD). This study aimed to investigate the role of calcium-independent phospholipase A2 group VI (iPLA2β) in protecting RPE cells from oxidative stress using a sodium iodate (NaIO3)-induced dry AMD model.<br><br>METHODS: The iPLA2&#x3b2; knockout (KO) and wild-type (WT) mice were subjected to NaIO3 administration. Retinal structure and function were evaluated by histology and electroretinography. The involvement of ferroptosis was assessed by quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Pharmacological intervention experiments used ferrostatin-1, &#x3b1;-tocopherol, and necrostatin-1s to evaluate protective effects. Western blotting was performed for RIP3 phosphorylation, and RIP3 KO mice were used to further assess necroptosis involvement.<br><br>RESULTS: The iPLA2&#x3b2; KO mice exhibited normal retinal morphology and function under baseline conditions. NaIO3 exposure caused pronounced RPE and photoreceptor degeneration, a characteristic downregulation of genes responsive to ferroptotic stress, elevated lipid peroxidation, and impaired visual function, which were markedly rescued by ferrostatin-1 and &#x3b1;-tocopherol, and partially by necrostatin-1s. NaIO3 did not induce RIP3 phosphorylation, and necrostatin-1s appeared to exert antioxidative effects. RIP3 KO mice developed severe RPE degeneration after NaIO3 exposure, significantly attenuated by necrostatin-1s. These findings indicate that lipid peroxidation-mediated ferroptosis, rather than necroptosis, is the primary mechanism of NaIO3-induced retinal degeneration, particularly at low doses of NaIO3.<br><br>CONCLUSIONS: The iPLA2&#x3b2; functions as a key suppressor of lipid peroxidation-mediated RPE degeneration in the NaIO3 model. Targeting ferroptosis-particularly via iPLA2&#x3b2;-may represent a potential therapeutic approach for protecting the RPE from oxidative stress-induced injury in dry AMD, although further validation in human tissues will be necessary.}, }
@article {pmid41405094, year = {2025}, author = {Enzendorfer, ML and Mai, J and Riedl, S and Bogunovic, H and Menten, MJ and Rueckert, D and Fritsche, LG and Prevost, AT and Sivaprasad, S and Pfau, M and Scholl, HPN and Lotery, AJ and Sacu, S and Schmidt-Erfurth, U}, title = {Functional Outcomes Across High-Risk OCT-Based Phenotypes in Intermediate Age-Related Macular Degeneration-PINNACLE Study Report 11.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {54}, pmid = {41405094}, issn = {1552-5783}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/physiopathology/diagnosis ; Phenotype ; *Retina/physiopathology/pathology ; Retinal Drusen/physiopathology ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Visual Field Tests ; Visual Fields/physiology ; }, abstract = {PURPOSE: To evaluate the association between structural optical coherence tomography (OCT) biomarkers and functional outcomes in intermediate age-related macular degeneration (iAMD) and to investigate whether stratifying eyes by OCT-based biomarkers identifies phenotypes of iAMD with impaired visual function.<br><br>METHODS: The baseline cohort of the PINNACLE trial underwent OCT imaging, microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA) testing. OCT volumes were assessed for the presence of different morphologic features. Drusen volume and outer nuclear layer (ONL) and ellipsoid zone (EZ) thickness were quantified. Linear mixed-effect models evaluated associations between each feature and functional outcomes, including a stratification into phenotypes based on significant OCT morphology with each eye assigned to a single group.<br><br>RESULTS: This analysis included 247 eyes of 190 patients (mean age, 74.2 &#xb1; 7.4 years). The presence of subretinal drusenoid deposits (SDDs) and markers of retinal atrophy were significant contributors to lower mean retinal sensitivity (P < 0.05). Also, higher drusen volume and lower ONL and EZ thickness were associated with lower sensitivity. Significant changes in BCVA, LLVA, and low-luminance deficits (LLDs) were associated with increasing drusen volume and the presence of hyperreflective foci (HRF). Significant functional differences were found between individual phenotypic groups, especially highlighting functional deficit in eyes with signs of early atrophy.<br><br>CONCLUSIONS: Integrating comprehensive analyses of structural OCT biomarkers with functional assessments revealed distinct phenotypic subtypes of iAMD that are associated with significant functional deficits. Particularly, early atrophy markers should be considered for patient selection and risk assessment in clinical trials and routine practice.}, }
@article {pmid41406245, year = {2026}, author = {Borrelli, E and Reibaldi, M}, title = {The importance of imaging biomarkers for predicting outcomes in neovascular AMD.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {185-186}, doi = {10.1177/11206721251407415}, pmid = {41406245}, issn = {1724-6016}, }
@article {pmid41406248, year = {2026}, author = {Bartolomeo, N and Barbosa, M and Pannatier Schuetz, Y and Castro, DG and Nascimbeni, AC and Barry, MP and Ambresin, A}, title = {Pigment epithelial detachment as a biomarker for faricimab treatment outcomes in naïve neovascular age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {36}, number = {2}, pages = {296-303}, doi = {10.1177/11206721251400508}, pmid = {41406248}, issn = {1724-6016}, mesh = {Humans ; Retrospective Studies ; *Retinal Detachment/diagnosis/drug therapy/etiology ; Male ; Female ; Tomography, Optical Coherence ; Visual Acuity/physiology ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; *Retinal Pigment Epithelium/pathology ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography ; Biomarkers ; Aged, 80 and over ; Treatment Outcome ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {ObjectiveTo assess baseline pigment epithelial detachment (PED) and other OCT biomarkers for predicting response to faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).DesignThis was an observational, retrospective, single-arm, monocentric cohort study.Subjects and methodsFifty-seven eyes of 51 patients with naive nAMD-associated PED and treated with faricimab were included in the study. Best-corrected visual acuity (BCVA) and OCT were performed at baseline, monthly until Month 4, and at Months 6, 9, and 12. Fluid volume dynamics and other OCT biomarkers were quantified using an AI-based tool.ResultsAt Month 12, mean BCVA increased by 4 letters (P < 0.01), mean CRT decreased by 66.2 µm (P < 0.0001), and mean maximum PED height decreased by 70.4 µm (P < 0.001). AI-based PED dynamics showed rapid and sustained reductions from 488.2 nL at baseline to 166.6 nL at Month 12 (P < 0.0001), with more profound reductions in serous versus fibrous PED volume. All AI-quantified OCT biomarkers were significantly (P < 0.0001) changed from baseline after the loading phase. OCT biomarkers, PED, and fluid dynamics during the loading phase were correlated with functional and anatomic outcomes at Month 4 and Month 12.ConclusionsFaricimab had a rapid, profound and sustained drying effect on the retinas of eyes with nAMD and PED, with marked reductions in OCT biomarkers after loading and sustained to Month 12. These improvements coincided with significant improvements in BCVA. PED height, type, and volume at baseline correlated with short- and long-term treatment outcomes.}, }
@article {pmid41407269, year = {2026}, author = {Khanani, AM and Danzig, CJ and Heier, JS and Jaffe, GJ and Kaiser, PK and Lally, DR and Patel, SS and Vajzovic, L and Weng, CY and Patel, H and Clark, J and Desai, D and Luo, D and Henry, E and Holz, FG and , }, title = {Avacincaptad Pegol for Geographic Atrophy Secondary to Age-Related Macular Degeneration: Two-Year Efficacy and Safety Results from the GATHER2 Phase 3 Trial.}, journal = {Ophthalmology}, volume = {133}, number = {4}, pages = {451-465}, doi = {10.1016/j.ophtha.2025.12.011}, pmid = {41407269}, issn = {1549-4713}, mesh = {Humans ; Male ; Female ; *Geographic Atrophy/drug therapy/etiology/diagnosis ; Aged ; *Aptamers, Nucleotide/therapeutic use/adverse effects/administration &amp; dosage ; *Visual Acuity/physiology ; Treatment Outcome ; Double-Blind Method ; Aged, 80 and over ; Follow-Up Studies ; *Polyethylene Glycols/therapeutic use/administration &amp; dosage/adverse effects ; Tomography, Optical Coherence ; *Macular Degeneration/complications/drug therapy/diagnosis ; Intravitreal Injections ; Middle Aged ; Fluorescein Angiography ; Complement Inactivating Agents/therapeutic use/adverse effects ; }, abstract = {PURPOSE: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2 mg was investigated in GATHER2, with positive year 1 results published. Herein, 2-year results are reported.<br><br>DESIGN: Phase 3, randomized, sham-controlled study (ClinicalTrials.gov identifier, NCT04435366).<br><br>PARTICIPANTS: Patients with non-center point-involving geographic atrophy (GA).<br><br>METHODS: Eligible patients were randomized 1:1 to receive monthly ACP 2 mg (n = 225) or sham (n = 222) for 1 year. At month 12, patients who received ACP 2 mg were randomized again 1:1 to dosing every month (EM; n = 96) or every other month (EOM; n = 93) with ACP 2 mg. Patients who had received monthly sham continued with sham (n = 203).<br><br>MAIN OUTCOME MEASURES: The safety and efficacy of ACP versus sham administration over 2 years and the effect of ACP EM or EOM dosing in year 2.<br><br>RESULTS: Overall, 175 and 184 patients in the ACP and sham group completed the study at year 2, respectively. At 2 years, treatment with ACP demonstrated a continued reduction in GA growth (slope) with both ACP EM and EOM versus sham. From baseline to year 2, the mean rate of GA area growth was 4.46 mm[2] (standard error [SE], 0.25 mm[2]) with ACP EM and 5.18 mm[2] (SE, 0.17 mm[2]) with sham, a difference in growth of 0.724 mm[2] (95% confidence interval [CI], 0.133-1.315 mm[2]; P = 0.0165), representing a 14% difference. From baseline to year 2, the mean rate of GA area growth was 4.20 mm[2] (SE, 0.25 mm[2]) with ACP EOM, a difference in growth of 0.976 mm[2] (95% CI, 0.377-1.575 mm[2]; nominal P = 0.0015) versus sham, representing a 19% difference. The incidence of choroidal neovascularization (study eye) was 11.6% with ACP (all treated) versus 9.0% with sham over 2 years. No events of retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred over 2 years.<br><br>CONCLUSIONS: Dosing of ACP 2 mg, either EM or EOM, continued to reduce GA growth versus sham therapy over 2 years with no new safety signals compared with year 1.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41407273, year = {2026}, author = {Poudel, S and Cui, Y and Meng, T and Liang, W and Zhou, K and Cheng, R and Zhao, L and Yuan, T and Kaffash, E and Halquist, MS and Ma, JX and Xu, Q}, title = {Long-acting fenofibrate-loaded microparticles for treating retinal disorders.}, journal = {International journal of pharmaceutics}, volume = {689}, number = {}, pages = {126503}, pmid = {41407273}, issn = {1873-3476}, support = {R01 EY033477/EY/NEI NIH HHS/United States ; R01 EY034510/EY/NEI NIH HHS/United States ; R01 EY033330/EY/NEI NIH HHS/United States ; R01 EY034742/EY/NEI NIH HHS/United States ; R01 EY019309/EY/NEI NIH HHS/United States ; UG3 EY036558/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Fenofibrate/administration &amp; dosage/pharmacokinetics/pharmacology/chemistry ; Delayed-Action Preparations/administration &amp; dosage ; Male ; PPAR alpha/agonists ; Diabetes Mellitus, Experimental/drug therapy ; Rabbits ; *Diabetic Retinopathy/drug therapy ; Rats ; Mice ; Rats, Sprague-Dawley ; Intravitreal Injections ; Particle Size ; Hypolipidemic Agents/administration &amp; dosage ; Mice, Inbred C57BL ; Retina/drug effects/metabolism ; Mice, Knockout ; Receptors, LDL/genetics ; }, abstract = {Age-related macular degeneration (AMD) and Diabetic retinopathy (DR) are the most common forms of retinal disorders and are the leading causes of vision loss. Traditional treatments such as anti-VEGF therapies often require repeated intravitreal injections. Up to 40 % DR/AMD patients do not adequately respond to the anti-VEGF therapies. Therefore, non-VEGF therapies with alternative mechanisms are needed to address these unmet clinical needs. Fenofibrate (an FDA-approved low-cost oral drug) is a peroxisome proliferator-activated receptor-α (PPARα) agonist. We developed large-sized fenofibrate-loaded biodegradable microparticles capable of achieving high drug loading (up to 25 wt%) and sustained in vitro release exceeding six months (larger particles that load more drug and last longer). These long-acting Feno-MP exhibited desired particle size suitable for intravitreal injection (IVT) through fine gauge needles. The lead Feno-MP-F6 maintained sustained drug levels in the retina for at least 6 months following a single intravitreal injection without obvious toxic issues in rats and rabbits. This study investigated a 6-month-long therapeutic effects of a single dose of fenofibrate-loaded microparticles (Feno-MP) via a non-VEGF, PPARα-dependent mechanism in streptozotocin (STZ)-induced diabetic rats (a DR model), Vldlr[-/-] mice (a wet-AMD model), and Abca4[-/-]/Rdh8[-/-] mice (a dry-AMD model). Comprehensive analyses revealed broad therapeutic benefits across all the three disease models. In the STZ-induced DR model, one single IVT dose of Feno-MP restored both photopic and scotopic electroretinogram (ERG) responses, decreased leukostasis, and enhanced blood-retinal barrier function over a period of 6 months. In Vldlr[-/-] mice, a wet-AMD model, Feno-MP effectively reduced both subretinal and intraretinal neovascularization and decreased retinal vascular leakage for at least 6 months. In Abca4[-/-]/Rdh8[-/-] mice, single Feno-MP treatment preserved photoreceptors, increased cone photoreceptors survival and improved mitochondrial function up to 6 months. Our study showed that Feno-MP may become a promising therapy for DR, wet-AMD and even dry-AMD with only 1-2 IVT injections/year. This work represents the approach to repurpose the oral drug fenofibrate for long-lasting intraocular delivery through a sustained release system.}, }
@article {pmid41408005, year = {2026}, author = {Kayembe-Mulumba, B and Leffondré, K and Larsen, PP and Hucteau, &#xc9; and Korobelnik, JF and Delcourt, C and Delyfer, MN}, title = {Association of current Statin use with incident age-related macular degeneration: using time-varying propensity scores.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {731-741}, pmid = {41408005}, issn = {1435-702X}, support = {Fondation Bordeaux Universit&#xe9;//Fondation Bordeaux Universit&#xe9;/ ; Mutuelles AXA//Mutuelles AXA/ ; Th&#xe9;a Pharma//Th&#xe9;a Pharma/ ; Macu-Life Project//Macu-Life Project/ ; }, mesh = {Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Aged ; Female ; Male ; Incidence ; *Propensity Score ; Prospective Studies ; *Macular Degeneration/epidemiology/diagnosis ; Follow-Up Studies ; France/epidemiology ; Aged, 80 and over ; Time Factors ; Risk Factors ; Disease Progression ; *Population Surveillance ; }, abstract = {PURPOSE: Statins exhibit pleiotropic properties that may influence age-related macular degeneration (AMD) progression. However, since their prescription is predominant in older populations at high cardiovascular risk, a lack of robust approach to control for confounding by indication could partly explain controversial results in previous studies. We therefore analyzed the association of current statin use with incident AMD using time-varying propensity score-based inverse probability of treatment weighting (IPTW).<br><br>METHODS: Analysis of data from the ALIENOR study, a 14-year French prospective population-based cohort of 963 adults aged 73 years and older in Bordeaux, followed every 2-3 years (2006-2020), with repeated assessments of statin use through a face-to-face questionnaire. AMD status was assessed using retinal multimodal imaging every 2-3 years (2006-2020). Incident intermediate and advanced AMD were analyzed separately. Combining time-varying IPTW balancing and covariates adjustment, we fitted time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (aHRs [95% confidence intervals]) for incident AMD associated with current statin use (defined as using statin within the last three years prior to the current visit).<br><br>RESULTS: Over a median follow-up of 7 years, cumulative incidence was 36% and 10% among the participants analyzed for intermediate (n&#x2009;=&#x2009;475) and advanced (n&#x2009;=&#x2009;692) AMD, respectively. After accounting for confounding by indication, current statin use was not associated with increased hazards of intermediate (aHR: 1.02 [0.72-1.45]) and advanced (aHR: 1.08 [0.61-1.91]) AMD. Analyses of statin subtypes (lipophilic and hydrophilic) and all lipid-lowering agents consistently yielded non-significant association with the hazards of AMD. Findings were consistent across sensitivity analyses.<br><br>CONCLUSION: These findings suggest that, after controlling for confounding by indication, statins may not substantially influence the risk of developing intermediate or advanced AMD in older adults, despite the biological plausibility.}, }
@article {pmid41408289, year = {2025}, author = {Kantor, AB and Rickert, M and Cheng, H and Flanagan, K and Salgotra, V and Suppahia, A and Ryu, JK and Widboom, PF and Warfield, JR and Akassoglou, K and Stavenhagen, JB}, title = {Development of a humanized anti-fibrin monoclonal antibody for the treatment of neuroinflammatory and retinal diseases.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {19}, pmid = {41408289}, issn = {1742-2094}, abstract = {UNLABELLED: Vascular dysfunction and subsequent innate immune activation are key players of neurodegenerative, retinal, and inflammatory diseases, including Alzheimer's disease (AD), multiple sclerosis (MS), diabetic retinopathy (DR), and age-related macular degeneration (AMD). At sites of vascular damage, conversion of the blood coagulation protein fibrinogen to fibrin exposes a cryptic inflammatory epitope, γ377–395, which can bind CD11b/CD18 and CD11c/CD18 complement receptors on microglia, macrophages, and dendritic cells. Genetic targeting of the fibrin γ377–395 epitope or its pharmacologic inhibition with the mouse monoclonal antibody 5B8 protects from inflammation and neurodegeneration in AD and MS mouse models. Here, we present the development of THN391, a first-in-class humanized antibody, to neutralize fibrin toxicity without adverse anticoagulant effects for the treatment of neurodegenerative, retinal, and inflammatory diseases. THN391 was affinity matured with 100-fold greater affinity than 5B8, engineered to lack Fc effector function, and have improved developability properties for clinical use. THN391 blocks the interaction of fibrin with CD11b/c and does not bind fibrinogen nor interfere with coagulation, consistent with the crystal structure of its binding interface to the γ377–395 epitope. THN391 and its Fc wild-type counterpart THN313 showed preclinical efficacy in experimental autoimmune encephalomyelitis (EAE) mouse models of MS and in a rodent model of retinal disease. Both THN391 and THN313 reduced demyelination, inflammatory foci, and clinical scores in EAE, demonstrating that anti-fibrin γ377-395 antibodies function as pure antagonists, blocking fibrin from activating CD11b/c complement receptors. THN391 was as effective as the standard of care vascular endothelial growth factor (VEGF) antagonists in reducing laser-induced neovascular lesions in a rat model of neovascular macular degeneration. Taken together, these results support the clinical development of THN391 for neurological diseases and ophthalmic indications.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-025-03650-w.}, }
@article {pmid41408394, year = {2026}, author = {Giraldo-Suarez, WY and Bonilla-Escobar, FJ and Lozano-Cruz, E}, title = {Comment on: 'Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results'.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {431}, pmid = {41408394}, issn = {1476-5454}, }
@article {pmid41411005, year = {2026}, author = {Lee, WK and Wong, TY and Chen, SJ and Sun, X and Cheung, CMG and Silva, R and Ricci, F and Zhang, X and Machewitz, T and Schulze, A and Schmidt-Ott, UM and Zhao, M and Hasanbasic, Z and Leal, S and Iida, T and , }, title = {Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: Post Hoc Analysis of the PULSAR Randomized Clinical Trial.}, journal = {JAMA ophthalmology}, volume = {144}, number = {2}, pages = {129-137}, pmid = {41411005}, issn = {2168-6173}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Choroid/blood supply ; *Choroidal Neovascularization/drug therapy/diagnosis/physiopathology ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Fundus Oculi ; Intravitreal Injections ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis/physiopathology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; }, abstract = {IMPORTANCE: In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD). This post hoc subgroup analysis evaluated clinical outcomes in participants with polypoidal choroidal vasculopathy (PCV).<br><br>OBJECTIVE: To compare the efficacy and safety of aflibercept, 8 mg vs 2 mg, monotherapy among participants with PCV in the PULSAR trial.<br><br>This was a post hoc subgroup analysis of the PULSAR randomized clinical trial. The setting included hospitals and clinics in 12 countries where indocyanine green angiography (ICGA) was performed to identify PCV. Included were a subgroup of adults with nAMD enrolled in the PULSAR trial with ICGA-confirmed PCV. Study data were analyzed from August 2020 to July 2022.<br><br>INTERVENTIONS: Participants were randomly assigned 1:1:1 to aflibercept, 8 mg, every 12 weeks or 16 weeks, or aflibercept, 2 mg, every 8 weeks, each after 3 initial monthly doses. From week 16, dosing intervals in the treatment arms receiving 8 mg every 12 weeks and every 16 weeks were shortened if predefined disease activity criteria were met at prespecified visits.<br><br>MAIN OUTCOMES AND MEASURES: Least-squares (LS) mean change in BCVA from baseline at week 48.<br><br>RESULTS: A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, -4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; -0.7; 95% CI, -4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48.<br><br>CONCLUSIONS AND RELEVANCE: Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04423718.}, }
@article {pmid41412300, year = {2026}, author = {Holt, CA and Niedert, C and Gedtal, M and Virgili, G and Hogg, RE and Qureshi, R}, title = {Prognostic factors for age-related macular degeneration progression: An overview of systematic reviews.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {759-773}, doi = {10.1016/j.survophthal.2025.12.003}, pmid = {41412300}, issn = {1879-3304}, mesh = {Humans ; Disease Progression ; *Macular Degeneration/diagnosis ; Prognosis ; *Systematic Reviews as Topic ; Tomography, Optical Coherence/methods ; Risk Factors ; }, abstract = {Age-related macular degeneration (AMD) is a progressive and irreversible degenerative disease of the retina. Slowing progression to late AMD is the only way to prevent vision loss. Given that AMD treatments are noncurative, understanding the personal characteristics associated with progression is of critical importance for people with increased AMD risk. We conducted an overview of systematic reviews and meta-analyses (SRMAs) to assess the scope of the existing literature on prognostic factors (PFs) for AMD progression. We included all systematic reviews of PFs for the progression of AMD from early or intermediate to late. We used the Cochrane Eyes and Vision Database of Systematic Reviews (current to September, 2024). We identified 64 potentially relevant studies in the database and included 17 SRMAs, which most commonly studied functional or structural ocular (10/17), lifestyle (7/17), and intervention-related factors (7/17). Across all reviews, 218 PFs were reported. We extracted 79 and grouped these into 20 distinct types of PFs across 8 categories. The modifiable PFs with most evidence for slowing progression were increased dietary supplementation with antioxidants and multivitamins and reduced smoking. Most PFs were non modifiable. Although most PFs may not be targetable, by integrating high-risk optical coherence tomography findings, monitoring relevant comorbidities, and considering individual lesion characteristics, clinicians may better predict disease trajectories and support patients in slowing progression and preserving vision. Notably, no reviews studied social determinants as potential PFs for AMD progression, representing a critical gap in the evidence base. Future reviews should investigate social, systemic, and AI-identified biomarkers to provide a more comprehensive understanding of AMD progression.}, }
@article {pmid41412389, year = {2026}, author = {Hasbolat, H and Christensen, UC and Lund-Andersen, C}, title = {Vitreous Hemorrhage Due to Posterior Vitreous Detachment: Incidence of Retinal Detachment and Spontaneous Clearance during Observation.}, journal = {Ophthalmology}, volume = {133}, number = {4}, pages = {487-494}, doi = {10.1016/j.ophtha.2025.11.014}, pmid = {41412389}, issn = {1549-4713}, mesh = {Humans ; Male ; Female ; *Vitreous Hemorrhage/etiology/epidemiology/diagnosis ; *Retinal Detachment/epidemiology/etiology/diagnosis ; Retrospective Studies ; *Vitreous Detachment/complications/diagnosis ; Aged ; Incidence ; Middle Aged ; Remission, Spontaneous ; Vitrectomy ; Follow-Up Studies ; Aged, 80 and over ; Visual Acuity ; Risk Factors ; }, abstract = {PURPOSE: To investigate the natural course of vitreous hemorrhage (VH) due to posterior vitreous detachment (PVD).<br><br>DESIGN: Retrospective chart review.<br><br>PARTICIPANTS: Consecutive patients with VH due to presumed PVD between January 1, 2017, and December 31, 2021. Patients were followed conservatively.<br><br>METHODS: Patients with a first episode of VH at a large eye hospital were included retrospectively through review of medical charts. Patients with a history of proliferative diabetic retinopathy, retinal venous occlusion, or wet age-related macular degeneration were excluded.<br><br>MAIN OUTCOME MEASURES: Patients were followed for a minimum of 2 years until one of the following outcomes occurred: spontaneous VH clearing, rhegmatogenous retinal detachment (RRD), vitrectomy for persistent VH, or referral to a medical retinal service.<br><br>RESULTS: We included 366 patients (366 eyes); mean age was 65.2 years (standard deviation, 10.8), and 42.9% were women. Vitreous hemorrhage obscured the fundus in 295 eyes (80.6%). Vitreous hemorrhage cleared spontaneously in 227 eyes (62%), whereas RRD occurred in 61 eyes (17%). Rhegmatogenous retinal detachment plateaued at 20 days, indicating a time-dependent pattern. The risk of retinal detachment was significantly higher in men (hazard ratio [HR], 2.90 [1.64-5.12], P < 0.001) compared with women. Older patients exhibited a lower risk of RRD (HR, 0.27; 95% confidence interval [CI], 0.13-0.59, P < 0.001 in the 65- to 73-year age group and HR, 0.25; 95% CI, 0.10-0.63, P = 0.003 in the 73- to 94-year age group). Spontaneous clearing was associated with the density of VH. After 60 days, only 48% of the eyes cleared spontaneously. Thirty-six eyes did not clear, requiring vitrectomy after a median duration of 98 days (62.75-140.75).<br><br>CONCLUSIONS: This study demonstrates that VH presumed secondary to PVD showed great variability but generally took several months to clear, with 62% resolving spontaneously. However, 17% developed RRD, the majority during the first 3 weeks. Male gender and young age increased RRD risk. These findings highlight the importance of vigilant monitoring during the early phase and indicate that individual patient characteristics may guide management strategy. Further prospective studies are warranted to refine risk stratification and optimize management protocols in this patient population.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41413355, year = {2026}, author = {Regillo, C and Kaiser, PK and Kertes, PJ and Gillies, M and Maio-Twofoot, T and Lawrence, D and Holz, FG}, title = {TALON phase IIIb study: 64 week results of brolucizumab versus aflibercept using treat-and-extend for neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {369-375}, pmid = {41413355}, issn = {1476-5454}, mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Male ; Female ; Aged ; Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Aged, 80 and over ; Tomography, Optical Coherence ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage/adverse effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Double-Blind Method ; }, abstract = {OBJECTIVE: To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg in patients with neovascular age-related macular degeneration (nAMD) using an identical 4-week adjustment Treat-and-Extend regimen.<br><br>METHODS: Patients received brolucizumab (n&#x2009;=&#x2009;366) or aflibercept (n&#x2009;=&#x2009;368) at Weeks 0, 4, 8 and 16, followed by 4-week interval adjustments depending on disease activity (DA) up to a maximum treatment interval of 16 weeks (q16w). After introduction of the urgent safety measure (USM), patients in either arm requiring a 4-week interval were discontinued from study treatment and moved to standard of care (SoC).<br><br>RESULTS: At Week 64, more brolucizumab patients had a last treatment interval of q16w with no DA vs aflibercept (28.4% vs 12.2%). In the brolucizumab arm, 22.4%, 26.0% and 23.2% of patients were on treatment intervals of 12, 8 and 4 weeks (on SoC after USM), respectively, compared with 23.9%, 22.0% and 41.8% in the aflibercept arm. The average change in best-corrected visual acuity (letters) from baseline at Weeks 60 and 64 was comparable (brolucizumab: +4.7; aflibercept: +4.9). Average change in central subfield thickness (&#xb5;m) at Weeks 60 and 64 was -182.9&#x2009;&#xb5;m in the brolucizumab arm vs -167.5&#x2009;&#xb5;m with aflibercept. Incidence of ocular adverse events (AEs), serious ocular AEs and AEs of special interest in the brolucizumab vs aflibercept arms were 31.1% vs 27.7%, 2.7% vs 0.8%, 6.0% vs 1.6%, respectively.<br><br>CONCLUSIONS: The Week 64 results in TALON reaffirmed those reported at Week 32, demonstrating extended treatment intervals and an overall favourable benefit/risk profile for brolucizumab in patients with nAMD.}, }
@article {pmid41415014, year = {2025}, author = {Selya, A}, title = {Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251405729}, pmid = {41415014}, issn = {2474-1272}, }
@article {pmid41417677, year = {2026}, author = {Berco, E and Kozlov, Y and Ostrovsky, M and Tuli, R and Kin Man Lee, T and Samocha, K and Shcolnik, E and Goldfeather Ben Zaken, S and Shoham-Hazon, N}, title = {Comparative Real-World Efficacy of Anti-Vascular Endothelial Growth Factor Agents in Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Study.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {249}, number = {1}, pages = {50-60}, pmid = {41417677}, issn = {1423-0267}, mesh = {Humans ; Retrospective Studies ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; Female ; *Visual Acuity ; Intravitreal Injections ; Male ; *Bevacizumab/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Treatment Outcome ; Aged ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Aged, 80 and over ; Fundus Oculi ; Dose-Response Relationship, Drug ; }, abstract = {UNLABELLED: <p>Introduction: This study directly compared the real-world effectiveness of bevacizumab, aflibercept 2 mg, and ranibizumab as first-line treatments for neovascular age-related macular degeneration (nvAMD).<br><br>METHODS: A multicenter retrospective cohort of treatment-na&#xef;ve nvAMD eyes managed with a treat-and-extend regimen in Israel and Canada. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcomes included treatment burden (total injections and final maintained interval), non-response (persistent/worsening exudation or functional decline despite adequate treatment), non-extension (final interval of 4 weeks), and absence of active exudation.<br><br>RESULTS: A total of 322 eyes received bevacizumab (n = 174), aflibercept (n = 110), or ranibizumab (n = 38) over a mean follow-up of 16.75 &#xb1; 12.66 months. Mean VA improved from 0.77 &#xb1; 0.47-0.60 &#xb1; 0.45 logarithm of the minimum angle of resolution following an average of 10.5 &#xb1; 6.3 injections. Aflibercept produced greater CRT reduction (-51.94 &#x3bc;m; p < 0.001), fewer injections (-2.35; p = 0.001), longer final intervals (+2.14 weeks; p < 0.001), and lower odds of non-response (adjusted odds ratio [aOR] 0.016; p < 0.001) and non-extension (aOR 0.128, p < 0.001) versus bevacizumab. It showed the largest mean VA gain, just short of significance on multivariable analysis (p = 0.059). Ranibizumab showed greater CRT reduction (-44.53 &#x3bc;m; p = 0.012) and lower non-extension odds (aOR 0.079; p = 0.001) than bevacizumab but did not significantly reduce treatment burden or improve VA.<br><br>CONCLUSION: In this first real-world, head-to-head comparison, aflibercept and ranibizumab outperformed bevacizumab in key anatomic and treatment-efficiency outcomes, with aflibercept showing the most consistent advantages. These findings highlight clinically relevant differences among anti-vascular endothelial growth factor agents and underscore the importance of real-world data to guide nvAMD management. </p>.}, }
@article {pmid41418433, year = {2026}, author = {Song, SY and Lee, SH and Park, JW and Lim, HK and Seo, JW and Park, DH and Cho, SS}, title = {Protective effects of a 1:1 mixture of 7,17-dihydroxy-DHA and 10,17-dihydroxy-DHA (SF) against blue light-induced retinal damages in A2E-laden ARPE-19 Cells.}, journal = {Tissue &amp; cell}, volume = {99}, number = {}, pages = {103287}, doi = {10.1016/j.tice.2025.103287}, pmid = {41418433}, issn = {1532-3072}, mesh = {Humans ; *Light/adverse effects ; *Retinal Pigment Epithelium/drug effects/pathology/radiation effects/metabolism ; *Docosahexaenoic Acids/pharmacology ; Apoptosis/drug effects/radiation effects ; Cell Line ; Cell Survival/drug effects/radiation effects ; Lutein/pharmacology ; *Protective Agents/pharmacology ; Oxidative Stress/drug effects ; *Retina/pathology/drug effects/radiation effects ; Blue Light ; Retinoids ; }, abstract = {In this study, we investigated the anti-age-related macular degeneration (AMD) effects of SF, a 1:1 mixture of 7,17-dihydroxy-docosahexaenoic acid (DHA) and 10,7-dihydroxy-DHA, in human retinal pigmented epithelial (RPE) cells. Cytotoxicity in RPE cells was first confirmed, while non-toxicity was confirmed at concentrations below 2 μg/mL. Irradiation of RPE cells with bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) and blue light resulted in a cell viability of less than 80 %, whereas SF treatment increased cell viability in a concentration-dependent manner. In addition, apoptosis induced by A2E and blue light was found to be regulated by lutein and SF. Lutein and SF treatments regulated the Bcl family, with SF showing stronger efficacy in regulating Bax and Bad expression than lutein. Furthermore, SF affected MAPKs, particularly by regulating the expression of JNK and p-38. SF may have similar effects on the expression of inflammatory proteins and pro-inflammatory cytokines at 5 μg/mL and 2 μg/mL concentrations of lutein and SF. Lastly, SF appeared to regulate the expression of Nrf2, OH-1, SOD1, and 4-HNE, which are biomarkers of oxidative and carbonyl stress. In conclusion, SF may exert its protective effects by regulating various signaling pathways in response to A2E and blue light stimulation at the cellular level.}, }
@article {pmid41420177, year = {2025}, author = {Wang, K and Tian, T and Chen, Z and He, X and Xiang, Y and Zuo, G and Cheng, S}, title = {Therapeutic potential of curcumin in ophthalmic diseases: mechanisms and clinical applications.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1408}, pmid = {41420177}, issn = {1479-5876}, mesh = {*Curcumin/therapeutic use/pharmacology ; Humans ; *Eye Diseases/drug therapy ; Animals ; Antioxidants/therapeutic use ; Clinical Trials as Topic ; }, abstract = {Ocular diseases impacting both the front and back segments of the eye are major contributors to worldwide vision loss. Curcumin, extracted from the rhizome of Curcuma longa, is a lipophilic polyphenol whose broad pharmacologic profile, including antioxidant, anti-inflammatory, antimutagenic, antimicrobial, and antineoplastic, renders it an attractive prospect for ocular therapeutics. However, much of the existing research primarily focuses on the general mechanisms of curcumin in the human body, with a lack of comprehensive reviews specifically addressing its mechanisms in ophthalmic diseases. Therefore, this review aims to explore curcumin's therapeutic potential in ophthalmic disorders and examine its mechanisms of action in terms of its anti-inflammatory, antioxidant, anti-angiogenic, neuroprotective roles, and antibacterial effects. The influence of curcumin on a range of ocular diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, dry eye disease, pterygium, and uveitis, was also discussed. An analysis of preclinical and clinical studies conducted over the past 5 years suggested that curcumin holds promise as a therapeutic agent for various eye disorders. Furthermore, the review addressed the challenges faced in the clinical translation of curcumin in ophthalmology, such as issues related to dosage, formulation, and long-term safety. Despite curcumin's promising efficacy in preclinical models, several hurdles remain in its clinical application, highlighting the need for further research to facilitate its broader use in ophthalmic treatment.}, }
@article {pmid41420782, year = {2026}, author = {Lopez, J and de Carlo Forest, TE and Azargui, S and Gill, ZS and Lisker-Cervantes, A and Gnanaraj, R and Lynch, AM and Palestine, AG and Mandava, N and Mathias, MT and Manoharan, N and Grove, N and Bradley, C and Patnaik, JL}, title = {Visual functioning and geographic atrophy imaging characteristics in age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {927-934}, pmid = {41420782}, issn = {1435-702X}, support = {Research to Prevent Blindness//Research to Prevent Blindness/ ; Frederic C. Hamilton Macular Degeneration Foundation//Frederic C. Hamilton Macular Degeneration Foundation/ ; Helene and Marshall Abrahams AMD Research Fund//Helene and Marshall Abrahams AMD Research Fund/ ; UM1 TR004399/TR/NCATS NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Geographic Atrophy/diagnosis/physiopathology/etiology ; *Visual Acuity/physiology ; Male ; Cross-Sectional Studies ; Female ; Aged ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Macular Degeneration/physiopathology/diagnosis/complications ; *Fovea Centralis/pathology ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Surveys and Questionnaires ; Middle Aged ; *Registries ; }, abstract = {PURPOSE: To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and geographic atrophy (GA) imaging characteristics including foveal involvement, multifocal lesions, and GA size.<br><br>METHODS: This cross-sectional cohort study included patients from the University of Colorado Age-related macular degeneration (AMD) registry, enrolled between July 2014 and May 2023, who had GA in at least one eye and completed the VFQ-25 at time of study enrollment. GA size was averaged between the two eyes for each patient. General linear modeling was used to assess the association between GA imaging characteristics with the outcome of Rasch-transformed VFQ-25 scores.<br><br>RESULTS: A total of 140 AMD patients with GA and VFQ-25 scores were included in the study. LogMAR visual acuity for the better-seeing eye of each patient was negatively associated with Rasch-transformed VFQ scores (-3.03, standard error (SE): 0.46, p&#x2009;<&#x2009;0.0001). Foveal involvement in both eyes was significantly associated with worse Rasch-transformed scores when compared to those without foveal involvement in either eye (-1.33, SE: 0.38, p&#x2009;=&#x2009;0.0006). Multifocal lesions in both eyes compared with unifocal lesions in both eyes had no significant difference in score (p&#x2009;=&#x2009;0.179). GA size was significantly associated with worse VFQ-25 scores (-0.09, SE: 0.02), p&#x2009;<&#x2009;0.0001), which did not remain significant after adjustment for LogMAR of both eyes (p&#x2009;=&#x2009;0.137).<br><br>CONCLUSIONS: We found bilateral foveal involvement and averaged GA size were significantly associated with worse Rasch-transformed VFQ-25 scores, but these associations did not remain significant after adjustment for visual acuity. Unilateral GA was significantly associated with better scores. This study highlights the impact GA imaging characteristics and bilateral involvement have on visual functioning.<br><br>KEY MESSAGES: WHAT IS KNOWN: Geographic atrophy (GA) in age-related macular degeneration negatively impacts visual functioning, and prior studies suggest that both lesion characteristics and visual acuity contribute to patient-reported outcomes.The gold-standard for Telangiectatic capillaries (TelCaps) detection is indocyanine green angiography, which is invasive and may not be readily available in all settings.<br><br>WHAT IS KNEW: Bilateral foveal involvement and larger GA size were significantly associated with worse visual functioning as measured by Rasch-transformed VFQ-25 scores.Infrared reflectance imaging complemented by optical coherence tomography B-scans are effective in the detection and measurement of TelCaps, which appeared to be dynamic lesions that remodel over time. Patients with unilateral GA reported better visual functioning, underscoring the importance of preserving vision in the better-seeing eye.Eyes with DME and TelCaps with at least one year of follow-up ended up with persistent edema and stable or worse vision after injection therapy.}, }
@article {pmid41421557, year = {2026}, author = {Lai, A and Issa, M and Pereira, A and Ghafri, MA and Dollin, M and Hurley, B and Chhablani, J and Yan, P}, title = {Age-related choroidal atrophy: A systematic review of multimodal imaging, clinical features, and differentiation from other forms of macular degeneration.}, journal = {Survey of ophthalmology}, volume = {71}, number = {3}, pages = {774-779}, doi = {10.1016/j.survophthal.2025.12.005}, pmid = {41421557}, issn = {1879-3304}, mesh = {Humans ; *Choroid/pathology/diagnostic imaging ; *Multimodal Imaging/methods ; *Macular Degeneration/diagnosis ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Geographic Atrophy/diagnosis ; Atrophy ; Diagnosis, Differential ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; }, abstract = {We conducted a systematic review on the clinical and imaging characteristics of age-related choroidal atrophy (ARCA) that distinguish ARCA from age-related macular degeneration (AMD) and geographic atrophy (GA). Studies were included if they reported on ARCA using clinical or multimodal imaging criteria and differentiated it from AMD and GA. Extracted data included subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), inner retinal layer thicknesses, and fundus findings. Risk of bias was assessed using the Joanna Briggs Institute checklists. Narrative synthesis and descriptive statistics were performed (PROSPERO (ID: CRD420251041101)). Seven studies (n = 329 patients) met inclusion criteria. ARCA was characterized by choroidal thinning (mean SFCT: 69.8-96.45 µm), preserved retinal pigment epithelium (RPE) on fundus autofluorescence, scleral visibility, and fundus features including peripapillary atrophy (83.3 %), tessellated fundus, and pseudodrusen. Compared to control, patients with ARCA had significantly thinner peripapillary nerve fiber layer (mean: 84.2 µm vs. 90.2 µm; p = 0.047) and reduced mean ganglion cell layer, macular internal plexiform layer and CVI. ARCA contrasts with AMD and GA by its distinct imaging features, less severe visual impairment, higher glaucoma prevalence (35.3 %), and more favorable response to anti-vascular endothelial growth factor agents when choroidal neovascularization is present. ARCA is a distinct clinical entity characterized by specific choroidal and retinal findings on multimodal imaging including lower CVI, thin SFCT, preserved RPE with scleral visibility, peripapillary atrophy, and inner retinal thinning. Further studies are warranted to standardize diagnostic criteria and understand long-term outcomes of ARCA.}, }
@article {pmid41422350, year = {2026}, author = {Zhang, C and Gilead, N and Jiang, Z and Fenner, BJ and Tan, AC and Chan, HH and Teo, KYC and Cheung, CMG}, title = {Cuticular drusen in Asian neovascular age-related macular degeneration: Clinical features and polypoidal choroidal vasculopathy association.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {3}, pages = {743-751}, pmid = {41422350}, issn = {1435-702X}, support = {OFLCG23 may-0032//National Medical Research Council Open Fund Large Collaborative Grant/ ; }, }
@article {pmid41422988, year = {2026}, author = {Ghosh, S and Parua, P and Jana, K and Ghosh, SK and Ghosh, A and Debnath, B and Halder, J and Sahoo, RK and Rai, VK and Dash, P and Das, C and Kar, B and Ghosh, G and Rath, G}, title = {Recent advances of novel nanoformulations combatting blue light hazards in the retina.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110806}, doi = {10.1016/j.exer.2025.110806}, pmid = {41422988}, issn = {1096-0007}, mesh = {Humans ; *Light/adverse effects ; *Retina/radiation effects ; *Retinal Diseases/etiology/drug therapy/prevention &amp; control ; *Drug Delivery Systems/methods ; *Nanoparticles ; Animals ; Oxidative Stress/drug effects ; *Antioxidants/administration &amp; dosage ; Blue Light ; }, abstract = {Exposure to blue light significantly threatens retinal health, affecting approximately 73 % of the global population. It impairs vision, lowers the quality of life, and adds to public health challenges. Its treatment is getting difficult due to chronicity, limited drug efficacy, side effects, and ocular barriers that hinder conventional drug delivery. Nanoformulations (NFs) have gained attention as adaptable drug delivery systems (DDSs), offering controlled release and customizable physicochemical characteristics. Their application in ocular therapy has shown promise for targeting both anterior and posterior segments of the eye. By accommodating a broad spectrum of therapeutic agents, these nanocarriers help address the limitations of traditional retinal drug delivery methods and offer potential in mitigating blue light-induced retinal damage. Several NFs have shown significant promise in addressing blue light hazards and the retina-related diseases through various mechanisms. Nano-based formulations offer promising strategies for protecting the retina and treating retinal diseases caused by blue light exposure. Antioxidant-loaded liposomes and hydrogels, such as those containing lutein and zeaxanthin, help reduce oxidative stress. In contrast, curcumin-loaded nanoparticles (Cur-NPs) mitigate inflammation in conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR). Polymeric NPs enable gene-specific silencing of pathogenic targets, and metallic NPs enhance photothermal therapy by selectively destroying abnormal retinal cells. These advanced delivery systems, including protective nanofilms, offer improved bioavailability, targeted delivery, and minimal side effects, making them effective tools in combating retinal damage. This review emphasizes the potential of NFs for advanced drug delivery against blue light-induced retinal hazards, highlighting pharmaceutical and pharmacological findings, recent insights, key challenges, and proposed solutions for a better future.}, }
@article {pmid41423015, year = {2026}, author = {Chen, X and Zhuang, X and He, G and Li, M and Zhang, X and Pu, J and Ji, Y and Zhang, Y and Hao, X and Wen, F}, title = {Increased choroidal stromal volume and altered choriocapillaris perfusion in neovascular AMD: An SS-OCTA association study.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105327}, doi = {10.1016/j.pdpdt.2025.105327}, pmid = {41423015}, issn = {1873-1597}, mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Choroid/blood supply/diagnostic imaging/pathology ; Aged ; *Tomography, Optical Coherence/methods ; Middle Aged ; *Wet Macular Degeneration/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Choroidal Neovascularization/diagnostic imaging ; }, abstract = {PURPOSE: This study aimed to characterize quantitative choroidal metrics using swept-source optical coherence tomography angiography (SS-OCTA) across different stages associated with neovascular age-related macular degeneration (nAMD) and to identify structural and vascular associations.<br><br>METHODS: This cross-sectional study utilized SS-OCTA to quantify 6.0 &#xd7; 6.0 mm&#xb2; macular choriocapillaris flow density (CCFD), choroidal volume (CV), choroidal stromal volume (CSV), and choroidal vascular volume (CVV), choroidal stromal index (CSI), choroidal vascularity index (CVI) and CSV/CVV ratio. Comparisons were conducted between each pair of three groups: control eyes from healthy participants, fellow eyes and nAMD affected eyes from the same unilateral nAMD patients (fellow eyes representing a potential preclinical stage).<br><br>RESULTS: The study included 230 healthy control eyes from 116 age- and sex- matched participants, 110 unaffected fellow eyes and 104 nAMD affected eyes from 110 unilateral nAMD patients. Median CCFD was 45.33% (IQR: 4.82%) in controls, 46.50% (IQR: 2.35%) in fellow eyes and 44.41% (IQR: 6.68%) in nAMD eyes. Significant differences were found between controls and fellow eyes (Adjusted P = 0.003) and between fellow eyes and nAMD eyes (Adjusted P < 0.001). Median CSV was significantly higher in both unaffected fellow eyes (5.92 mm&#xb3;, IQR: 2.67 mm&#xb3;; Adjusted P = 0.006) and nAMD affected eyes (6.12 mm&#xb3;, IQR: 2.71 mm&#xb3;; Adjusted P = 0.012) compared to controls (5.49 mm&#xb3;, IQR: 2.00 mm&#xb3;). Other absolute volumes also showed significant intergroup differences: CV differed between control and fellow eyes (Adjusted P = 0.033), while CVV differed significantly only between affected and fellow eyes (Adjusted P = 0.015). In contrast, normalized compositional metrics (CSI, CVI and CSV/CVV ratio) showed no significant intergroup differences (all Adjusted P > 0.05). Multivariate regression analysis in nAMD affected eyes revealed an overall inverse correlation between CSV and CCFD, with this relationship reaching statistical significance the superior nasal, nasal, inferior temporal, inferior and inferior nasal quadrants (P < 0.05).<br><br>CONCLUSION: This cross-sectional study demonstrated an association between increased CSV and the presence of nAMD, including in high-risk fellow eyes. The inverse correlation between CSV and CCFD in nAMD eyes suggested a potential interplay between stromal expansion and microvascular compromise. These findings highlighted increased CSV as a candidate biomarker that warranted investigation in future longitudinal studies to determine its prognostic value for nAMD development.}, }
@article {pmid41424614, year = {2025}, author = {Song, X and Gao, G and Ye, K and Xu, P and Wang, Y and Zhang, S and Zheng, D and Ge, J and Zhong, X}, title = {Subretinal suspensions of hiPSC-derived retinal pigment epithelium cells form functional monolayers in NOD-SCID mice facilitating treatment of advanced retinal diseases.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {503-514}, pmid = {41424614}, issn = {2352-3204}, abstract = {INTRODUCTION: Transplantation of human induced pluripotent stem cells derived retinal pigment epithelium (hiPSC-RPE) is regarded as one of the most promising strategies for advanced retinal degenerative diseases leading to blindness, such as age-related macular degeneration. Despite its therapeutic potential, this approach is encumbered by critical challenges, notably the survival of donor RPE cells post-transplantation and the successful reconstruction of a functional RPE layer.<br><br>METHODS: With our previously reported strategy, abundant hiPSC-RPEs were generated from human induced pluripotent stem cells. These cells were characterized in vitro by morphology, marker expression and function. Further, hiPSC-RPE cell suspensions were injected into the eyes of NOD-SCID mice. Animals were monitored by optical coherence tomography screening and color fundus imaging to evaluate the survival of hiPSC-RPEs. Polarity, maturity, integration and phagocytosis of hiPSC-RPEs were analyzed histologically.<br><br>RESULTS: hiPSC-RPE cells exhibited a cobblestone morphology with abundant microvilli and tight junctions, expressed RPE specific molecular markers, and possessed ability to phagocytize photoreceptor outer segments (POS), thereby resembling the characteristics of the native human RPE cells. Following transplantation into NOD-SCID mice, the cells survived for the 8-week testing period and formed a highly organized monolayer in regions with an intact Bruch's membrane (BM) in the host retina. The reconstructed RPE layer expressed both human-specific and RPE-specific markers with POS phagocytic function. No severe adverse effects, such as malignant tumors or infections, were observed.<br><br>CONCLUSIONS: These findings demonstrate that hiPSC-RPE suspensions can survive and form RPE monolayers with morphological and functional features analogous to those of native human RPE cells in the host retina with a healthy BM. Our study may facilitate the development of cell-based therapies for treatment of advanced retinal degenerations.}, }
@article {pmid41425305, year = {2025}, author = {Jensen, EG and Jakobsen, TS and Schnabolk, G and Wilson, K and Rask-Pedersen, M and Jensen, N and Andersen, GR and Thiel, S and Aagaard, L and Rohrer, B and Askou, AL and Corydon, TJ}, title = {Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.}, journal = {Molecular therapy. Methods &amp; clinical development}, volume = {33}, number = {4}, pages = {101620}, pmid = {41425305}, issn = {2329-0501}, abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of vision loss and is characterized by choroidal neovascularization (CNV). Current CNV management requires multiple treatments and lacks long-term efficiency, creating a need for better therapeutics. wAMD pathogenesis is associated with excessive activation of the complement system, contributing to retinal damage. Therefore, we generated a vector expressing the small alternative pathway-targeting nanobody, hC3Nb1, to treat wAMD. We demonstrate that hC3Nb1 is efficiently expressed and secreted by mammalian cells and shows full alternative pathway and partial classical pathway inhibition in vitro. A dual-promoter approach was used to generate a lentiviral-based vector for co-expression of hC3Nb1 and marker protein eGFP. Profound and safe hC3Nb1-expression, along with its secretion from the retinal pigment epithelium (RPE), was confirmed following subretinal injection of nanobody expressing-vector in mice. The therapeutic potential of vector-encoded hC3Nb1 was demonstrated in vitro by protecting RPE from complement-mediated stress, and in vivo by reducing laser-induced CNV sizes in a mouse model consistent with complement inhibition. For the first time, nanobodies expressed in the eye are used therapeutically, and our findings suggest that hC3Nb1-based gene therapy may be a safe and long-acting treatment for wAMD and other chorioretinal diseases with dysregulated complement activation.}, }
@article {pmid41425574, year = {2025}, author = {Li, P and Wang, Q and Yang, Y and Ding, Z}, title = {Autoimmune thyroid disease and human health: a systematic review of Mendelian randomization studies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1689498}, pmid = {41425574}, issn = {1664-3224}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Thyroiditis, Autoimmune/genetics/epidemiology ; Genetic Predisposition to Disease ; *Autoimmune Diseases/genetics ; }, abstract = {UNLABELLED: We systematically summarized current Mendelian randomization (MR) evidence on the causal relationships between autoimmune thyroid disease (AITD) and a wide range of human health outcomes. Original MR studies related to AITD published up to March 1, 2025, were retrieved from PubMed and Embase. For studies investigating the same exposure-outcome associations, meta-analyses were performed to synthesize the evidence after excluding overlapping samples where applicable. The methodological quality of the included studies was assessed using the STROBE-MR checklist. A total of 123 MR publications met the inclusion criteria. MR analyses indicated that AITD significantly increased the risk of coronary atherosclerosis, deep venous thrombosis, chronic obstructive pulmonary disease, major depression, diabetic neuropathy, carpal tunnel syndrome, neuromyelitis optica spectrum disorder, diabetic retinopathy, childhood absence epilepsy, rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, inflammatory bowel disease, crohn's disease, vitiligo, myasthenia gravis, alopecia areata, type 1 and type 2 diabetes, sarcoidosis, frozen shoulder, drug eruptions, cataract, early age-related macular degeneration, pernicious anemia, Helicobacter pylori infection, temporomandibular disorders, migraine, frailty, primary biliary cholangitis, knee osteoarthritis, gout, and osteoporosis, while decreasing the risk of lung cancer, polyneuropathies, allergic rhinitis, telomere length, and serum vitamin A levels. The included MR studies were of high methodological quality and provided robust evidence supporting the bidirectional relationships between AITD and various health outcomes. These findings emphasize the importance and necessity of preventing and managing AITD while offering new perspectives and directions for future research on its prevention and treatment.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42023469038.}, }
@article {pmid41425744, year = {2025}, author = {Johari Moghadam, MM and Montazeri, F and Feldman, S and Lee, SC and Yiu, G and Moshiri, A and Emami-Naeini, P and Moussa, K and Park, SS}, title = {Longitudinal Choriocapillaris and Retinal Vascular Flow Changes on OCTA with Progression to Advanced AMD.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4651-4662}, pmid = {41425744}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate retinal and choriocapillaris (CC) vascular flow changes on optical coherence tomography angiography (OCTA) associated with progression of intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) or neovascular AMD (nAMD).<br><br>PATIENTS AND METHODS: This retrospective, longitudinal cohort study included 68 eyes from 50 patients with iAMD at baseline who underwent OCTA and clinical examination at baseline and at 24 months. Quantitative analysis of CC flow deficits (FDs) and superficial capillary plexus vessel density (VD) was performed at baseline and after 24 months by comparing eyes that progressed to GA or nAMD to eyes that remained stable.<br><br>RESULTS: Over 24 months, 7 eyes (10.3%) developed GA and 9 eyes (13.2%) developed nAMD, including 2 that progressed to both. Eyes that developed GA had significantly greater CC FD total area at baseline when compared with stable iAMD eyes (p=0.013) and developed significant decrease in parafoveal VD (p=0.026) and full macular VD (p=0.019) after GA onset. In contrast, eyes that developed nAMD showed no significant OCTA differences at baseline when compared to stable iAMD eyes but developed a new significant increase in CC FD total area (p=0.044) and FAZ perimeter (p=0.036) after nAMD onset (p=0.044).<br><br>CONCLUSION: In iAMD eyes progressing to GA, CC ischemia was detectable before GA onset, with subsequent retinal VD loss after GA development. In iAMD eyes progressing to nAMD, CC ischemia developed concurrent with neovascularization. OCTA-derived CC and retinal flow metrics may serve as non-invasive biomarkers to stratify iAMD eyes at risk for progression.}, }
@article {pmid41425747, year = {2025}, author = {Helland-Hansen, BA and Sverstad, A and Petrovski, G and Larsen, SE}, title = {Dynamic Pupillary Responses in Age-Related Macular Degeneration: A Controlled Clinical Study Using High-Frequency Video-Oculography.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {19}, number = {}, pages = {4689-4707}, pmid = {41425747}, issn = {1177-5467}, abstract = {PURPOSE: To investigate whether dynamic pupillary responses differ between patients with age-related macular degeneration (AMD) and healthy controls (HC), and to evaluate their potential as functional biomarkers using high-frequency, VR-based video-oculography.<br><br>METHODS: A controlled clinical study included 17 AMD patients and 17 age-matched HCs; four AMD participants were excluded for low recording quality. Dynamic pupillary responses were recorded with the BulbiCam video-oculography system (400 Hz), which presented independent monocular light stimuli through multiple permutations of bright (300 cd/m&#xb2;) and dark (5 cd/m&#xb2;) conditions. Measured variables included pupil diameter, latency, peak velocity, and pupil diameter-time integral (PDTI). Each eye was tested separately, and repeated sessions were analysed for reliability (intraclass correlation coefficient, ICC), repeatability (agreement index, AI), and stability (stability index, SI). Group differences were assessed using analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis.<br><br>RESULTS: AMD eyes showed larger steady-state pupil diameter and higher PDTI than controls (p < 0.05). First peak velocity was reduced in the worst eye only, while latencies were unchanged. PDTI and diameter demonstrated high reliability and stability across repetitions, and ROC analysis confirmed effective group discrimination.<br><br>CONCLUSION: High-frequency VR pupillometry detected reproducible functional alterations in AMD, consistent with impaired macular photoreceptor input but preserved reflex transmission. PDTI and diameter serve as diagnostic (population-level) and monitoring (patient-level) biomarkers, offering a non-invasive and objective method for AMD detection and follow-up in clinical and research settings.}, }
@article {pmid41426719, year = {2025}, author = {Agius, D and Mamo, J and Calleja, N and Smith, AF and Carbonaro, F}, title = {Estimating the costs and quality of life impact of vision loss in the population aged 50-80 years in Malta: evidence from The Malta Eye Study.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1706208}, pmid = {41426719}, issn = {2296-2565}, mesh = {Humans ; Aged ; *Quality of Life ; Aged, 80 and over ; Male ; Middle Aged ; Female ; Malta/epidemiology ; *Vision Disorders/economics/epidemiology ; *Cost of Illness ; *Health Care Costs/statistics &amp; numerical data ; Prevalence ; }, abstract = {BACKGROUND: Visual impairment and related ocular conditions impose substantial direct, indirect, and intangible costs, encompassing healthcare expenses, productivity losses, and reduced quality of life. Despite the global relevance of visual impairment, no comprehensive cost analysis has yet been conducted in an older adult Maltese population aged 50-80 years.<br><br>METHODS: Prevalence estimates from the population-based Malta Eye Study were used to calculate indirect costs via the gross national income per capita method with disability weight assumptions. Direct medical costs for key ocular conditions, including refractive error, cataract, age-related macular degeneration, diabetic retinopathy, and glaucoma, were estimated using prevalence, hospital, and private data performance indices and relevant cost data, enabling estimation of service coverage and unmet care needs. Intangible costs were derived from quality-of-life measures using the National Eye Institute Visual Function Questionnaire-39 to calculate disability weights and years lived with disability (YLD).<br><br>RESULTS: The productivity losses from blindness and moderate-severe visual impairment among individuals aged 50-80 were estimated at &#x20ac;16.0 million per annum (95% CI &#x20ac;6.0-&#x20ac;43.0 million). The estimated annual direct medical costs from the main ocular causes were estimated to sum up to &#x20ac;53.4 million (95% CI &#x20ac;44.6-&#x20ac;67.0 million), with unmet needs amounting to &#x20ac;20.8 million (95% CI &#x20ac;15.5-&#x20ac;28.5 million). Cataract (56.9%) and refractive error (24.5%) accounted for the highest shares of such costs. Vision-related quality of life correlated with the severity and laterality of visual impairment. Mild unilateral visual impairment carried the highest YLD rate 2264.4 YLDs per 100,000 while uncorrected refractive error carried the highest YLD rate among the visually impairing causes (2452.7 YLDs per 100,000).<br><br>DISCUSSION: Visual impairment imposes a considerable economic and quality-of-life burden on an older adult population in Malta, driven largely by cataracts, refractive error, and productivity losses. These results emphasize the need for preventive and treatment strategies and underscore the importance of future cost-benefit and cost-effectiveness analyses to help guide eye health policy in Malta.}, }
@article {pmid41427444, year = {2025}, author = {Yi, C and Luo, C and Zhao, J and Roubeix, C and Lechner, J and Penalva, R and Yang, N and Liu, J and Wang, Q and Chakravarthy, U and Sennlaub, F and Chen, M and Xu, H}, title = {Long-term low-dose aspirin promotes laser-induced choroidal neovascularization through suppressing TSP-1 expression.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1716229}, pmid = {41427444}, issn = {1662-5102}, abstract = {PURPOSE: To investigate the impact of low-dose, long-term aspirin use on neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Adult C57BL/6J or Thbs-1[-/-] mice were treated with daily aspirin (1.25 mg/kg) for 8 weeks before being subjected to laser-induced choroidal neovascularization (CNV). The animals were left for 7-10 days with continued aspirin use before the eyes were collected for further investigations. Bone marrow-derived macrophages (BMDMs) and primary retinal pigment epithelial (RPE) cells were treated with different concentrations of aspirin (1, 10, 100 &#x3bc;M) for two days before being subjected to LPS+IFN&#x3b3; for 16 h. The expression of cytokine genes was evaluated by qRT-PCR. The concentrations of thrombospondin-1 (TSP-1) were measured by ELISA.<br><br>RESULTS: Aspirin treatment did not affect circulating immune cell profiles in normal mice but significantly increased CD11b[+] cells in laser-induced CNV mice. The treatment significantly increased the severity of laser-induced CNV and reduced serum levels of TSP-1. In vitro aspirin treatment upregulated Tnfa and Ccl22, down-regulated Thbs-1 mRNA expression, and reduced TSP-1 production in LPS+IFN&#x3b3;-treated M1 BMDMs but not RPE cells. Thbs-1[-/-] mice developed severe laser-induced CNV, which was not affected by aspirin intervention. nAMD patients had significantly lower serum levels of TSP-1 than healthy controls, although no significant difference was found between nAMD patients with and without aspirin use.<br><br>CONCLUSION: Low-dose long-term aspirin use promoted the severity of laser-induced CNV by down-regulating TSP-1. Lower serum levels of TSP-1 may be a risk factor for nAMD. The long-term ocular safety of aspirin should be validated in prospective cohorts.}, }
@article {pmid41428610, year = {2025}, author = {Muzi, A and Gregori, G and Mangoni, L and Mogetta, V and Chhablani, J and Fruttini, D and Fiore, T and Rizzo, C and Mariotti, C and Lupidi, M}, title = {Functional and Structural Impact of Switching to Bevacizumab in neovascular-AMD Patients Treated with Aflibercept or Ranibizumab.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251409237}, doi = {10.1177/11206721251409237}, pmid = {41428610}, issn = {1724-6016}, abstract = {PurposeTo evaluate the functional and structural outcomes in patients with neovascular age-related macular degeneration (nAMD) switched from ranibizumab or aflibercept to bevacizumab.MethodsThis retrospective study included 197 eyes of 192 patients (mean age 83 ± 6 years; 38% male). Patients previously treated with ranibizumab (n = 79) or aflibercept (n = 118) were transitioned to bevacizumab. Best-corrected visual acuity (BCVA) was recorded with ETDRS charts and converted to logMAR. Spectralis SD-OCT was used to evaluate intraretinal and subretinal fluid, presence of retinal pigment epithelium detachment (PED), PED height and central retinal thickness (CRT) at baseline and after 6 months.ResultsMean BCVA decreased from 0.4 ± 0.3 to 0.5 ± 0.4 logMAR (p = 0.048). The proportion of eyes with intraretinal or subretinal fluid rose from 27% to 69% (p = 0.017). Subgroup analysis indicated greater functional and structural worsening in younger patients and in those switched from aflibercept. Mean PED height showed a non-significant increase from 163 ± 94 to 166 ± 95 µm (p = 0.091), mean PED height showed a non-significant increase from 163 ± 94 to 166 ± 95 µm (p = 0.091). In contrast, mean CRT increased substantially from 294 ± 30 µm at baseline to 310 ± 26 at 6 months (p (p < 1 × 10[-7]).ConclusionsSwitching from ranibizumab or aflibercept to bevacizumab may lead to reduced visual function and an increase in structural-OCT markers of disease activity, including greater intraretinal/subretinal fluid, CRT and worsening PED features, particularly in younger individuals and in eyes previously treated with aflibercept.}, }
@article {pmid41429246, year = {2026}, author = {Murray, M and Schifano, F and Chiappini, S and Corkery, JM and Guirguis, A}, title = {Potential Eye Disorders in People With and Without Type 2 Diabetes Mellitus Exposed to GLP-1 Receptor Agonists: An Examination of the FAERS (FDA Adverse Event Reporting System) Database.}, journal = {American journal of ophthalmology}, volume = {283}, number = {}, pages = {279-290}, doi = {10.1016/j.ajo.2025.12.015}, pmid = {41429246}, issn = {1879-1891}, mesh = {Humans ; *Diabetes Mellitus, Type 2/drug therapy ; Retrospective Studies ; *Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; *Glucagon-Like Peptide-1 Receptor Agonists ; United States/epidemiology ; United States Food and Drug Administration/statistics &amp; numerical data ; *Hypoglycemic Agents/adverse effects/therapeutic use ; Female ; Male ; Databases, Factual ; Middle Aged ; Aged ; *Eye Diseases/chemically induced/epidemiology ; Glucagon-Like Peptides/adverse effects ; }, abstract = {PURPOSE: As use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for Type 2 diabetes (T2DM) and weight management increases, emerging research identifies various adverse drug reactions. This study aimed to expand this research base, focusing on eye disorders in people with and without T2DM, a novel consideration.<br><br>DESIGN: A retrospective clinical cohort disproportionality analysis of reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS).<br><br>METHODS: FAERS was queried regarding selected GLP-1RAs. Python 3.11 was adopted to develop a program, quantifying reported cases between January 2017 - September 2025 (January 2022-September 2025 for tirzepatide) meeting the criteria for cases with and without T2DM. Main outcome measures Reporting Odds Ratios (RORs) >4.000 and 95% confidence intervals were calculated, with metformin and orlistat as controls.<br><br>RESULTS: Compared to metformin, semaglutide showed increased reporting of optic ischemic neuropathy (ROR: 12.269 [0.915-1.967]), cataract (ROR: 31.879 [2.463-4.461]) and retinopathy (ROR: 5.185 [0.556-2.736]) in T2DM patients, and retinopathy (ROR: 9.424 [1.081-3.406]) and retinal hemorrhage (ROR: 10.253 [0.319-4.336]) in non-T2DM patients. Tirzepatide showed increased reporting of optic ischemic neuropathy (ROR: 4.619 [0.726-2.335]) and macular degeneration (ROR: 15.579 [0.554-4.938]) in T2DM patients and eye swelling (ROR: 6.475 [0.407-3.329]) in non-T2DM patients. Liraglutide showed increased reporting of cataract (ROR: 53.866 [2.945-5.028]), diabetic retinopathy (ROR: 18.162 [1.753-4.045]) and macular degeneration (ROR: 26.261 [1.076-5.460]) in T2DM patients and cataract (ROR: 9.628 [1.387-3.142]) and macular degeneration (ROR: 9.557 [0.110-4.405]) in non-T2DM patients.<br><br>CONCLUSIONS: These results provide a signal of increased reporting of various eye disorders with GLP-1RA use compared to metformin across T2DM and non-T2DM patient cases. Further research is required to support these findings and confirm a biological causation.}, }
@article {pmid41429947, year = {2025}, author = {Gelir, F and Akan, T and Carmichael, OT and Bhuiyan, MS and Conrad, SA and Vanchiere, JA and Kevil, CG and Bhuiyan, MAN}, title = {Topological Feature Extraction from Multi-color Channels for Pattern Recognition: An Application to Fundus Image Analysis.}, journal = {Journal of imaging informatics in medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10278-025-01791-1}, pmid = {41429947}, issn = {2948-2933}, support = {R01HL145753//Foundation for the National Institutes of Health/ ; P20 GM121307/GM/NIGMS NIH HHS/United States ; R01HL145753-01S1//Foundation for the National Institutes of Health/ ; R01HL172970//Foundation for the National Institutes of Health/ ; R01HL149264//Foundation for the National Institutes of Health/ ; R01HL145753-03S1//Foundation for the National Institutes of Health/ ; P20GM121307//Foundation for the National Institutes of Health/ ; }, abstract = {The automated analysis of medical images is crucial for early disease detection. In recent years, deep learning has become popular for medical image analysis. In this study, we employed color-based topological features with deep learning for pattern recognition. The data topology provides information about the image's shape and global features such as connectivity and holes. We used different color channels to identify changes in topological footprints by altering the image's color. We extracted topological, local binary pattern (LBP), and Gabor features and used machine learning and deep learning models for disease classification. The model's performance was tested using three open-source fundus image databases: the Asia Pacific Tele-ophthalmology Society (APTOS 2019) data, the Optic Retinal Image Database for Glaucoma Analysis (ORIGA), and the Automatic Detection Challenge on Age-Related Macular Degeneration (ICHALLENGE-AMD). We have found that topological features from different color models provide important information for disease diagnosis.}, }
@article {pmid41430144, year = {2025}, author = {Hengerer, FH and Stanzel, B and Hoyos-Chacon, J and Suarez, M and Beckers, S and Busatto, P and Badalà, F}, title = {Safety and efficacy of an extended macular vision intraocular lens (IOL) for age-related macular degeneration (AMD) in real-world settings.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {47}, pmid = {41430144}, issn = {1471-2415}, mesh = {Humans ; Retrospective Studies ; *Visual Acuity/physiology ; Female ; Male ; Aged ; *Lenses, Intraocular ; Aged, 80 and over ; *Macular Degeneration/surgery/physiopathology/complications ; *Lens Implantation, Intraocular ; Prosthesis Design ; Middle Aged ; Postoperative Complications ; Treatment Outcome ; }, abstract = {PURPOSE: To assess the safety and efficacy of the EyeMax Mono (SharpView Ophthalmology) extended macular vision intraocular lens (IOL), in patients with age-related macular degeneration (AMD) undergoing cataract surgery.<br><br>METHODS: This retrospective multicentre study analyzed real-world data from 196 AMD eyes (146 patients) across 15 medical centres in Europe. All eyes received the single-piece, hydrophobic acrylic, EyeMax Mono IOL. AMD severity was classified by the centre. Outcomes included intraoperative and postoperative complications and changes in corrected distance and near visual acuity (CDVA and CNVA, respectively).<br><br>RESULTS: The postoperative spherical equivalent was +&#x2009;1.25&#x2009;&#xb1;&#x2009;1.32 D. Postoperative LogMAR CDVA improved significantly from a baseline of 0.57&#x2009;&#xb1;&#x2009;0.38 to 0.38&#x2009;&#xb1;&#x2009;0.34 (n&#x2009;=&#x2009;191, p&#x2009;<&#x2009;0.001), while CNVA improved from 0.49&#x2009;&#xb1;&#x2009;0.32 at baseline to 0.35&#x2009;&#xb1;&#x2009;0.27 postoperatively (n&#x2009;=&#x2009;141, p&#x2009;<&#x2009;0.001). 63% gained&#x2009;>&#x2009;1 line of CDVA and 27.5% gained&#x2009;&#x2265;&#x2009;3 lines. For CNVA, 41.5% gained&#x2009;>&#x2009;1 line, and 21.8% gained&#x2009;&#x2265;&#x2009;3 lines. The greatest gains occurred in intermediate AMD eyes: CDVA&#x2009;+&#x2009;0.21 logMAR, CNVA&#x2009;+&#x2009;0.12 logMAR. Only 2.1% of eyes lost&#x2009;>&#x2009;1 line of CDVA or CNVA.<br><br>CONCLUSIONS: The EyeMax Mono intraocular lens (IOL) safely enhances both distant (CDVA) and near (CNVA) visual acuity in patients with age-related macular degeneration, particularly in eyes with intermediate AMD. These findings are consistent with those in the published scientific literature.}, }
@article {pmid41430718, year = {2025}, author = {Martins, B and Boia, R and Correia, D and Ribeiro-Rodrigues, T and Ramalho, J and Ambrósio, AF and Girão, H and Fernandes, R}, title = {Retinal pigment epithelium-derived extracellular vesicles mediate outer blood retinal barrier disruption in response to AMD-related stress.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {542}, pmid = {41430718}, issn = {1478-811X}, support = {Doctoral research fellowship 2020.04811//Foundation for Science and Technology (FCT, Portugal)/ ; CIBB (Center for Innovative Biomedicine and Biotechnology) research unit (UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020)//Foundation for Science and Technology (FCT, Portugal)/ ; }, mesh = {*Extracellular Vesicles/metabolism ; Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/pathology/metabolism ; Swine ; *Blood-Retinal Barrier/metabolism/pathology ; Mice ; Lipopolysaccharides/pharmacology ; Mice, Inbred BALB C ; Humans ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly, primarily affecting the central vision. This progressive degenerative disease is characterized by the dysregulation and degeneration of the retinal pigment epithelium (RPE), a crucial cell layer beneath the photoreceptors that maintains outer retinal homeostasis. Emerging evidence suggests that during AMD, stressed RPE cells release extracellular vesicles (EVs) carrying bioactive cargo, which may compromise the outer blood-retinal barrier (oBRB) and accelerate disease progression. This study explores the role of EVs released by RPE cells under pro-inflammatory conditions in disrupting retinal integrity.<br><br>METHODS: Highly polarized primary cultures of porcine RPE (pRPE) and porcine eyecups with the RPE exposed were treated with tumor necrosis factor (TNF), lipopolysaccharide (LPS), or EVs derived from inflamed RPE cells. Additionally, Balb/c mice were intravitreally injected with RPE-derived EVs.<br><br>RESULTS: We show that EVs secreted by the apical membrane domain of porcine RPE cells exposed to LPS or TNF impair the RPE monolayer in polarized cultures, disrupt the oBRB in ex vivo porcine eyecups, and induce retinal structural damage detected in vivo in Balb/c mice. Intravitreal injection of LPS-derived EVs triggers photoreceptor and RPE layers thinning, increases reactivity in astrocytes and M&#xfc;ller cells, promotes pro-inflammatory microglial activation and recruitment, particularly into the outer retina, and elevates retinal apoptosis. Mechanistically, matrix metalloproteinases (MMPs) activity mediates EV-induced RPE monolayer disruption, whereas MMPs activity inhibition mitigates these effects.<br><br>CONCLUSION: Our findings reveal a novel EV-driven mechanism contributing to retinal degeneration progression, highlighting inflammation-derived apical EVs as key players in diseases involving oBRB dysfunction. Targeting EV-mediated signaling and MMPs activity may offer therapeutic strategies for preserving retinal structure and function in inflammatory retinal diseases such as age-related macular degeneration.}, }
@article {pmid41432505, year = {2025}, author = {Yusef, Y and Avetisov, KS and Khalatyan, AS and Shishparenok, AN and Blinova, VG and Gladilina, YA and Zhdanov, DD}, title = {[Monocyte telomere length as a novel biomarker of macular atrophy and response to anti-VEGF therapy in age-related macular degeneration].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {6}, pages = {52-61}, doi = {10.17116/oftalma202514106152}, pmid = {41432505}, issn = {0042-465X}, mesh = {Humans ; Male ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Monocytes/metabolism/pathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Degeneration/diagnosis/drug therapy ; Visual Acuity ; *Telomere/genetics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Biomarkers ; *Macula Lutea/pathology/diagnostic imaging ; Treatment Outcome ; *Geographic Atrophy/diagnosis/drug therapy ; }, abstract = {UNLABELLED: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. Monocyte telomere length is proposed as a marker of cellular senescence in this condition.<br><br>PURPOSE: This study investigated the association between monocyte telomere length and retinal parameters in different forms of AMD, as well as in patients receiving antiangiogenic therapy.<br><br>MATERIAL AND METHODS: Monocyte telomere length was measured in 84 patients (mean age 79&#xb1;9 years) divided into four groups: non-exudative AMD with geographic atrophy (neAMD-GA), neovascular AMD (nAMD) with macular atrophy (nAMD-MA), nAMD without MA, and controls. Monocytes were isolated using immunomagnetic separation, and telomere length was determined by quantitative PCR (qPCR). Retinal parameters were assessed via optical coherence tomography (OCT) of the macular region.<br><br>RESULTS: Significant telomere shortening was observed in AMD compared to the controls (p<0.05). In the nAMD-MA group, telomere length correlated positively with best-corrected visual acuity (BCVA) after treatment (rs=0.661; p=0.0014) and the type of atrophy (p<0.0001); shorter telomeres were associated with greater BCVA decline after therapy (rs=-0.452; p=0.0419). In nAMD without MA, telomere length correlated with reduced height of neuroepithelial detachment (NED) under anti-VEGF treatment (rs=0.50; p=0.0252). No significant associations were found in the neAMD-GA and control groups.<br><br>CONCLUSION: These findings highlight monocyte telomere length as a potential biomarker for predicting macular atrophy progression and treatment outcomes in AMD. Further research is needed to confirm these associations and to explore sex/ethnic disparities in telomere length in this disease.}, }
@article {pmid41432509, year = {2025}, author = {Neroeva, NV and Fursova, AZ and Faizrakhmanov, RR and Plyukhova, AA and Bobykin, EV and Gordeeva, MV and Karlova, EV and Bosov, ED and Nikiforova, AA}, title = {[Use of faricimab in neovascular age-related macular degeneration and diabetic macular edema in Russia. Results of the FARWATER retrospective study].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {6}, pages = {82-91}, doi = {10.17116/oftalma202514106182}, pmid = {41432509}, issn = {0042-465X}, mesh = {Humans ; Male ; Female ; Russia/epidemiology ; Retrospective Studies ; *Macular Edema/drug therapy/diagnosis/etiology/physiopathology ; Visual Acuity/drug effects ; *Diabetic Retinopathy/drug therapy/diagnosis/complications/physiopathology ; Aged ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Middle Aged ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; Antibodies, Bispecific ; }, abstract = {UNLABELLED: Despite the positive outcomes of anti-VEGF therapy, neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) remain major medical and social challenges, and optimization of their treatment is an urgent need.<br><br>PURPOSE: This study evaluated the effectiveness of Vabysmo (faricimab) in the treatment of patients with nAMD and DME in real-world clinical practice in Russia.<br><br>MATERIAL AND METHODS: A multicenter retrospective analysis was conducted based on the medical records of 328 patients (370 eyes) with nAMD and 87 patients (112 eyes) with DME (both treatment-na&#xef;ve and previously treated with anti-VEGF agents) who received faricimab from July 2023 to February 2025. The following primary effectiveness indicators were assessed: changes in visual acuity (VA) and central retinal thickness (CRT) after the first four faricimab injections. Secondary outcome indicators included changes in VA, CRT, and selected disease biomarkers at 6, 12, and 18 months of treatment, as well as injection intervals during the maintenance phase.<br><br>RESULTS: After the first four consecutive faricimab injections, VA improved by 8.1 ETDRS letters (p<0.05) in the nAMD group and by 12.8 ETDRS letters (p<0.05) in the DME group. CRT decreased by 103.3 &#x3bc;m (p<0.05) and 177.4 &#x3bc;m (p<0.05), respectively. These improvements remained stable during further follow-up (8.78&#xb1;4.51 months in the nAMD group and 10.48&#xb1;5.24 months in the DME group, up to a maximum of 19 months in both groups). The proportion of patients who achieved injection intervals of &#x2265;12 weeks was 27.9% in the nAMD group and 38.5% in the DME group.<br><br>CONCLUSION: Faricimab demonstrated high clinical effectiveness in real-world settings in patients with nAMD and DME, with the potential to reduce the treatment burden for patients and the healthcare system.}, }
@article {pmid41432510, year = {2025}, author = {Fursova, AZ and Strunina, YV}, title = {[Analysis the frequency of using Aflibercept (8 mg) in the treatment of neovascular age-related macular degeneration and diabetic macular edema compared with other anti-VEGF agents].}, journal = {Vestnik oftalmologii}, volume = {141}, number = {6}, pages = {92-100}, doi = {10.17116/oftalma202514106192}, pmid = {41432510}, issn = {0042-465X}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Macular Edema/drug therapy/diagnosis/etiology ; Intravitreal Injections/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/administration &amp; dosage ; Visual Acuity ; *Macular Degeneration/drug therapy/diagnosis ; }, abstract = {PURPOSE: This study aimed to evaluate the frequency of use of the drug aflibercept in the form of a 114.3 mg/mL, 0.263 mL solution for injection (hereinafter aflibercept 8 mg), compared with alternative anti-VEGF agents in adult patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) over a long-term period (2 years).<br><br>MATERIAL AND METHODS: A review of the literature was conducted to assess the frequency of administration of anti-VEGF drugs included in the Vital and Essential Drugs (VED) list as of 01.10.2025. Based on the results of published studies, an indirect comparison was performed evaluating the frequency of administration of aflibercept (114.3 mg/mL, 0.263 mL) with ophthalmic drugs used in clinical practice (aflibercept 40 mg/mL, 0.278 mL; brolucizumab 120 mg/mL, 0.23 mL; ranibizumab 10 mg/mL, 0.23 mL) in patients with nAMD and DME over 2 years of therapy. The difference in the number of injections should be interpreted as follows: a negative value indicates fewer injections of aflibercept 8 mg compared with brolucizumab 6 mg and ranibizumab 0.5 mg, while a positive value corresponds to fewer injections when compared with aflibercept 2 mg (as accepted in the original publication).<br><br>UNLABELLED: If the difference in frequency of drug administration was statistically significant, additional assessments were performed: the potential number of avoided injections when using a less frequent dosing regimen, and the potential number of additional patients who could receive such treatment.<br><br>RESULTS: Aflibercept 8 mg administered in dosing intervals extended up to 24 weeks for patients with nAMD was associated with a statistically significant reduction in the number of injections compared with aflibercept 2 mg: 2.37 (95% CI: 1.88 to 2.86) and 2.6 (95% CI: 2.11 to 3.09); with brolucizumab 6 mg: -1.82 (95% CI: -2.8 to -0.8) and -1.7 (95% CI: -3.0 to -0.4); with ranibizumab 0.5 mg: -7.17 (95% CI: -8.5 to -5.9) and -3.15 (95% CI: -3.7 to -2.6) in the first and second year, respectively.<br><br>UNLABELLED: Aflibercept 8 mg administered in dosing intervals extended up to 24 weeks for patients with DME was associated with a statistically significant reduction in the number of injections compared with aflibercept 2 mg: 3.57 (95% CI: 3.1 to 4.0) and 2.7 (95% CI: 2.1 tot 3.3); with brolucizumab 6 mg: -1.97 (95% CI: -2.5 to -1.4) and -1.56 (95% CI: -2.2 to -1.0) in the first and second year, respectively. In a similar comparison between aflibercept 8 mg and ranibizumab 0.5 mg (extended-interval regimen) in DME patients, the difference in the number of injections was 5.7 injections in both the first and second year; however, the value was calculated without determining the confidence interval (CI), which is a limitation of this study.<br><br>CONCLUSIONS: The use of aflibercept 8 mg in the treatment of nAMD and DME demonstrates a reduction in the number of intravitreal injections, accompanied by a significant reduction in the socioeconomic burden.}, }
@article {pmid41432839, year = {2025}, author = {Galindo, AM and Ohayon, A and Hod, K and Levin, MF and Geffen, N and Shulman, S}, title = {Real-world evidence of long-term durability and efficacy of faricimab as an advanced treatment line for NVAMD and DME.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {47}, pmid = {41432839}, issn = {1573-2630}, mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; Aged ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Edema/drug therapy/diagnosis ; Follow-Up Studies ; Treatment Outcome ; Tomography, Optical Coherence/methods ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Aged, 80 and over ; Time Factors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate the efficacy and durability of intravitreal Faricimab (Vabysmo) in patients with neovascular age-related macular degeneration (NVAMD) and diabetic macular edema (DME).<br><br>METHODS: A retrospective study was conducted at a tertiary ophthalmology center. Eyes with NVAMD or DME which had received previous Anti-vascular endothelial growth factor (A-VEGF) treatment before switching to Faricimab were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection intervals were recorded at baseline and follow-up visits of up to 2.5 years.<br><br>RESULTS: A total of 192 eyes (160 with NVAMD and 32 with DME) from 155 patients were included. The mean patient age was 79.5&#x2009;&#xb1;&#x2009;9.6 years, with an average follow-up duration of 468.1&#x2009;&#xb1;&#x2009;120.4 days from baseline. In the NVAMD cohort, BCVA improved from 0.43&#x2009;&#xb1;&#x2009;0.33 logMAR at baseline to 0.34&#x2009;&#xb1;&#x2009;0.30 at 1.5 years (p&#x2009;<&#x2009;0.05). CST decreased significantly from a mean of 308.3&#x2009;&#xb1;&#x2009;65.3 Micrometers to 242.4&#x2009;&#xb1;&#x2009;44.8 Micrometers at two years (p&#x2009;<&#x2009;0.001). The mean interval between injections increased from a mean of 33.9&#x2009;&#xb1;&#x2009;9.6 days at baseline to 77.6&#x2009;&#xb1;&#x2009;42.6 days at two years, reflecting a significant extension throughout the observation period (p&#x2009;<&#x2009;0.001). In eyes with DME, CST declined from 403.6&#x2009;&#xb1;&#x2009;121.9 Micrometers at baseline to 303.2&#x2009;&#xb1;&#x2009;105.2 Micrometers at one year (p&#x2009;<&#x2009;0.001), while BCVA remained stable. Injection intervals extended from 34.4&#x2009;&#xb1;&#x2009;10.3 to 60.9&#x2009;&#xb1;&#x2009;20.5 days at one year (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: In this study of previously treated eyes with NVAMD and DME, Faricimab demonstrated sustained anatomical and functional benefits alongside meaningful injection interval extension.}, }
@article {pmid41432997, year = {2025}, author = {Liang, L and Song, Z and Li, Y and Li, H}, title = {The global disease burden and associated risk factors of age-related macular degeneration: a comprehensive analysis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {50}, pmid = {41432997}, issn = {1573-2630}, mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Female ; Risk Factors ; Prevalence ; Aged ; Global Burden of Disease/trends ; Middle Aged ; Global Health ; Disability-Adjusted Life Years ; Aged, 80 and over ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness among middle-aged and older adults, bringing a heavy health burden. Understanding the patterns of AMD disease burden and the risk factors associated with early AMD development is crucial for formulating targeted public health policies.<br><br>METHODS: We estimated the prevalence of AMD and disability-adjusted life year (DALY) using data from the 2021 Global Burden of Disease (GBD). Our analysis examined trends in prevalence and DALY by age, sex, and sociodemographic index (SDI) at global, regional, and national levels from 1990 to 2021. We performed data analysis using two Mendelian randomization (MR) samples to explore the causal relationship between lipid metabolism, nutrients, and early AMD risk. The primary analysis was conducted using the inverse variance weighting method, along with a range of sensitivity analyses.<br><br>RESULTS: In 2021, AMD's DALY was 570,000, the age-standardized prevalence rate (ASPR) was 94.00/100,000 (95% UI, 78.32-114.42), and the age-standardized disability rate (ASDR) was 6.78/100,000 (95% UI, 4.70-9.32). The burden of AMD showed a downward trend during the study period. The disease burden is closely related to socioeconomic development and is unevenly distributed, with a heavier burden in low sociodemographic index (SDI) regions, especially in southern and central sub-Saharan Africa. Age-specific DALYs showed a gradual increasing trend, with female DALYs higher than male DALYs in all age groups. Decomposition analysis showed that population growth led to an increase in AMD DALYs. Projections from the Bayesian Age-Period Cohort (BAPC) model indicate that global AMD DALYs may continue to rise by 2045. Additionally, multivariate Mendelian randomization (MVMR) evaluation results showed that triglycerides (TG) (OR, 0.82; 95% CI, 0.73-0.92; p&#x2009;=&#x2009;0.001) and high-density lipoprotein (HDL) (OR, 1.15; 95% CI, 1.04-1.28; p&#x2009;=&#x2009;0.009) were significantly associated with early AMD. For every one standard deviation increase in TG levels, the risk of AMD decreases by an average of 18%. Higher TG levels are a protective factor for early AMD. However, the effect of HDL on AMD is the opposite of that of TG. For every one standard deviation increase in HDL levels, the risk of AMD increases by an average of 15%. Higher HDL levels are a risk factor for AMD.<br><br>CONCLUSIONS: AMD remains a major health problem worldwide, especially in low SDI regions. Population growth and aging have the most significant impact on AMD DALYs. HDL was identified as a risk factor, while TG was identified as a protective factor. These findings highlight the need for targeted interventions in low SDI regions, including dietary control, early screening, and addressing socioeconomic factors through balanced dietary plans.}, }
@article {pmid41433217, year = {2026}, author = {Li, Y and Mou, B and Song, X}, title = {Long-Term Trends in the Global Burden of Age-Related Macular Degeneration: Sex Differences, Aging Effects, and Future Projections in Middle-Aged and Older Adults.}, journal = {Ophthalmic research}, volume = {69}, number = {1}, pages = {8-23}, pmid = {41433217}, issn = {1423-0259}, mesh = {Humans ; Female ; Male ; Aged ; *Macular Degeneration/epidemiology ; Middle Aged ; Prevalence ; Global Health ; Aged, 80 and over ; Global Burden of Disease/trends ; Disability-Adjusted Life Years/trends ; Sex Factors ; *Aging ; Risk Factors ; Sex Distribution ; Age Distribution ; Quality-Adjusted Life Years ; }, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in middle-aged and older populations worldwide. Understanding its long-term epidemiological trends is essential for anticipating future healthcare needs and guiding preventive strategies. This study characterizes the global, regional, and national burden of AMD in adults aged ≥45 years, with a focus on sex disparities, aging effects, and projected trends.<br><br>METHODS: Using data from the Global Burden of Disease Study 2021, we analyzed the prevalence and disability-adjusted life years (DALYs) of AMD across age, sex, region, country, and Socio-Demographic Index (SDI) groups. We applied an age-period-cohort model to disentangle the effects of aging, temporal changes, and birth cohort on AMD risk. Frontier analysis was conducted to identify best-practice benchmarks in disease burden reduction. The association between SDI and AMD burden was assessed to evaluate health inequities. An autoregressive integrated moving average (ARIMA) model was used to project age-standardized DALY rate (ASDR) and prevalence rate from 2022 to 2036.<br><br>RESULTS: Between 1990 and 2021, the absolute number of AMD cases and DALYs nearly doubled. In 2021, both prevalence and DALY rates increased exponentially with age, with females exhibiting consistently higher rates across all age groups. The age-period-cohort model indicated a declining trend in AMD risk over successive birth cohorts, suggesting potential improvements in early-life or cumulative risk factors. Notably, the highest age-standardized rates were observed in low-SDI regions, highlighting significant global inequities in disease burden. ARIMA projections suggest a modest but concerning increase in the global ASDR, rising to 6.80 (95% CI: 5.82-7.78) by 2036, with female ASDR reaching 7.46 (95% CI: 6.29-8.63).<br><br>CONCLUSION: The burden of AMD remains substantial and is projected to grow, particularly among aging populations and in low-resource settings. The persistent sex disparity, especially the elevated burden in elderly women, calls for targeted screening and intervention programs. These findings emphasize the need for equitable, age- and sex-sensitive public health strategies to mitigate the rising impact of AMD in the coming decades.}, }
@article {pmid41435998, year = {2026}, author = {Li, Y and Yuan, S and Zhang, C and Hu, P and Huang, X and Zhou, J and Liu, D and Zhou, X}, title = {Engineered nanoparticles for subconjunctival delivery to the retinal pigment epithelium: A multi-target therapy for dry AMD.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {390}, number = {}, pages = {114563}, doi = {10.1016/j.jconrel.2025.114563}, pmid = {41435998}, issn = {1873-4995}, mesh = {*Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Animals ; Chitosan/chemistry/administration &amp; dosage ; *Nanoparticles/administration &amp; dosage/chemistry ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Lactoferrin/administration &amp; dosage/chemistry ; *Resveratrol/administration &amp; dosage ; Conjunctiva/metabolism ; Male ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism ; Drug Delivery Systems ; Oxidative Stress/drug effects ; }, abstract = {Dry age-related macular degeneration (dAMD) is a leading cause of irreversible blindness, driven by oxidative stress-induced retinal pigment epithelial (RPE) cell degeneration. Existing therapies suffer from poor bioavailability and insufficient multi-pathway modulation. To address this, we developed P(R)/T-Lf nanoparticles, a subconjunctivally administered nanotherapy co-loaded with resveratrol (Res) and dual-functionalized with trimethyl chitosan (TMC) and lactoferrin (Lf). The P(R)/T-Lf NPs exhibited: (1) prolonged ocular retention via TMC-mediated mucoadhesion and enhanced RPE targeting through Lf receptor binding; (2) sustained Res release over 35 days, effectively scavenging reactive oxygen species and inhibiting ferroptosis by downregulating NOX2, ACSL4, and COX2 while restoring GPX4; (3) superior therapeutic outcomes in NaIO3-induced dAMD models, preserving retinal morphology and function. Comparative studies demonstrated that P(R)/T-Lf NPs outperformed non-targeted controls. This nanoplatform provides a translation-ready strategy to concurrently tackle oxidative stress, inflammation, and ferroptosis via sustained, targeted delivery, representing a transformative approach for dAMD therapy.}, }
@article {pmid41437494, year = {2026}, author = {Jianjun, Y}, title = {Bilateral hypertensive retinopathy (grade 4): Case report and review of the literature on intravitreal injection anti-VEGF therapy.}, journal = {Clinical and experimental hypertension (New York, N.Y. : 1993)}, volume = {48}, number = {1}, pages = {2604831}, doi = {10.1080/10641963.2025.2604831}, pmid = {41437494}, issn = {1525-6006}, mesh = {Humans ; Intravitreal Injections ; *Hypertensive Retinopathy/drug therapy/complications ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Female ; Middle Aged ; Macular Edema/drug therapy/etiology ; Aged ; Visual Acuity ; Ranibizumab ; Choroidal Neovascularization/etiology/drug therapy ; Treatment Outcome ; Bevacizumab ; }, abstract = {OBJECTIVE: To introduce bilateral hypertensive retinopathy (HR) (grade 4) complicated with macular edema (ME) patients with binocular intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) treatment.<br><br>METHODS: Three cases of hypertensive retinopathy were observed. The fundus examination was consistent with HR (grade 4). The patients received anti-VEGF intraocular injection.<br><br>RESULTS: The patient's ME and optic nerve edema were significantly reduced, visual acuity was significantly improved, and a case of secondary choroidal neovascularization (CNV) in the fundus of HR (grade 4) was also noted.<br><br>CONCLUSIONS: The use of intravitreal anti-VEGF agents in stage IV hypertensive retinopathy appears satisfactory but not perfect. In severe cases with vitreous hemorrhage, early injection avoids vitrectomy.}, }
@article {pmid41438708, year = {2025}, author = {Liu, X and Wang, Y and Huang, J and Chen, L and Cai, T and Wang, Q and Li, S and Yu, G and Chen, Y and Luo, D and Ding, X}, title = {Sustained suppression of choroidal neovascularization by intraocularly stable tetrahedral network encapsulated miR-22-3p.}, journal = {Materials today. Bio}, volume = {35}, number = {}, pages = {102578}, pmid = {41438708}, issn = {2590-0064}, abstract = {Choroidal neovascularization (CNV), characterized by abnormal vessel growth and vascular leakage, is the hallmark of wet age-related macular degeneration (wAMD) and a leading cause of irreversible vision loss. Although anti-vascular endothelial growth factor (VEGF) therapies remain the current standard, their frequent administration and limited long-term efficacy highlight the need for novel treatments. Here, we developed a miR-22-3p-loaded tetrahedral framework nucleic acids (tFNAs-miR22) nanostructure and evaluated its efficacy in CNV suppression. The nanocomplex was structurally validated, exhibiting high assembly fidelity and superior intraocular stability compared to serum conditions. In a laser-induced CNV mouse model, a single intravitreal injection of tFNAs-miR22 significantly reduced lesion size and leakage by day 10, with efficacy comparable to aflibercept. In a rat model of stable and long-lasting CNV, tFNAs-miR22 demonstrated durable inhibition of vascular leakage by Day 21, showing greater persistence compared to aflibercept. This effect was dose-dependent, with the high-dose group outperforming aflibercept in suppressing leakage. Transcriptomic profiling of hypoxia-challenged HUVECs further revealed that tFNAs-miR22 modulates angiogenic pathways, including suppression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) axis. These findings demonstrate the potent and long-lasting therapeutic effects of tFNAs-miR22, supporting its promise as a next-generation, gene-regulatory nanotherapy for sustained inhibition of CNV.}, }
@article {pmid41439215, year = {2026}, author = {Ueda-Arakawa, N and Sato, Y and Miyake, M and Takahashi, A and Mori, Y and Miyara, Y and Hara, C and Kitajima, Y and Maruko, R and Kawai, M and Ohnaka, M and Koizumi, H and Maruyama-Inoue, M and Yanagi, Y and Iida, T and Kondo, M and Sakamoto, T and Tsujikawa, A}, title = {Impact of Reticular Pseudodrusen on Clinical and Ocular Characteristics and Progression Rate of Geographic Atrophy in Japanese Patients.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100984}, pmid = {41439215}, issn = {2666-9145}, abstract = {PURPOSE: To elucidate the impact of reticular pseudodrusen (RPD) on the clinical and ocular characteristics and progression rate of geographic atrophy (GA) in Japanese patients.<br><br>DESIGN: A multicenter, retrospective, observational cohort study.<br><br>PARTICIPANTS: A total of 173 eyes from 173 Japanese patients (135 with conventional GA and 35 with pachychoroid GA) were included; 79 eyes with conventional GA were included in the follow-up group.<br><br>METHODS: Reticular pseudodrusen status, GA type (conventional/pachychoroid), GA location (central/noncentral), GA pattern (unifocal/multifocal), subfoveal choroidal thickness (SFCT), and fellow-eye status were assessed using multimodal imaging. The GA progression rate was calculated in both mm[2]/year and mm/year (square root transformation [SQRT]) after semiautomatic measurement of the GA area on fundus autofluorescence images.<br><br>MAIN OUTCOME MEASURES: Clinical and ocular characteristics and progression rate of GA according to RPD status.<br><br>RESULTS: Reticular pseudodrusen were observed in 42.4% (73 eyes) of the 173 study eyes, 54.1% of the eyes with conventional GA, and none of the eyes with pachychoroid GA. Among patients with conventional GA, those with RPD were significantly more female (56.2 vs. 30.6%, P = 0.003), had better visual acuity (0.31 vs. 0.50 in logarithm of the minimum angle of resolution, P = 0.03), a smaller SFCT (141.7 vs. 185.0 &#x3bc;m, P = 0.02), higher prevalence of noncentral (56.2 vs. 32.3%, P = 0.005) and multifocal GA (68.5 vs. 29.0%, P < 0.001), and bilateral late age-related macular degeneration (AMD) (93.1 vs. 65.0%, P < 0.0001) than those without RPD. The GA progression rate was significantly higher in eyes with RPD than in eyes without RPD (0.34 vs. 0.18 mm/year [SQRT], P < 0.001).<br><br>CONCLUSIONS: Reticular pseudodrusen are frequently observed in Japanese patients with conventional GA. Clinical and ocular characteristics differ according to the RPD status, similarly in White patients. Geographic atrophy in the presence of RPD progresses rapidly, at a rate comparable to that in White patients, and most patients with RPD exhibit bilateral late AMD. Given that RPD in eyes with GA constitutes a strong risk factor for both fast GA progression and bilateral late AMD, GA with RPD should be treated at an early stage prior to foveal involvement, even though GA in Asians has been reported to progress slowly.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41439218, year = {2026}, author = {Vo, A and Shen, LL and Pak, I and Taha, AT and Diaz, AZ and Stewart, JM}, title = {Association between Baseline Subfoveal Choroidal Thickness and Anatomical and Functional Outcomes in Geographic Atrophy.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100986}, pmid = {41439218}, issn = {2666-9145}, abstract = {OBJECTIVE: To investigate the relationship between baseline subfoveal choroidal thickness (SFChT) and both visual outcomes and geographic atrophy (GA) growth rate, and to assess whether SFChT mediates the treatment effect of oral metformin on GA progression.<br><br>DESIGN: Secondary analysis of a randomized controlled trial.<br><br>PARTICIPANTS: Seventy eyes (34 metformin; 36 observation) from 44 participants (21 metformin; 23 observation) with GA and &#x2265;6 months of follow-up in the METformin for the MINimization of Geographic Atrophy Progression study.<br><br>METHODS: Subfoveal choroidal thickness was measured from baseline OCT. We calculated GA area growth rate by subtracting the GA area at the first visit from the GA area at the last visit and dividing the result by the time interval. Geographic atrophy perimeter-adjusted growth rate was calculated by dividing GA area growth rate by the mean GA perimeter between the first and last visit.<br><br>MAIN OUTCOME MEASURES: Longitudinal changes in GA area and visual acuity.<br><br>RESULTS: Baseline SFChT was not significantly associated with baseline GA area (P = 0.51), baseline best-corrected visual acuity (BCVA) (P = 0.49), baseline low-luminance visual acuity (LLVA) (P = 0.85), or rim area focal hyperautofluorescence signals (P = 0.29). Baseline SFChT was not significantly associated with GA perimeter-adjusted growth rate (P = 0.74), the decline rate of BCVA (P = 0.14), and the decline rate of LLVA (P = 0.71). However, sensitivity analyses in GA subgroups found that baseline SFChT was associated with decreased rate of BCVA decline in patients with foveal-involving GA (Spearman &#x3c1; = 0.03, P = 0.03). Baseline SFChT did not significantly influence the effect of oral metformin on GA perimeter-adjusted growth rate (P = 0.78).<br><br>CONCLUSIONS: Greater baseline SFChT was significantly associated with slower BCVA decline in eyes with foveal-involving GA, suggesting a possible localized role of choroidal thickness in preserving central vision. However, SFChT was not associated with GA growth rate, LLVA decline, or baseline anatomical and functional measures. It also did not mediate the effect of oral metformin. While SFChT lacks prognostic value for GA progression overall, it may hold limited relevance for central vision outcomes in foveal-involving GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41441525, year = {2025}, author = {Cohen, R and Kerman, T and Trivizki, O}, title = {Bilateral Sterile Intraocular Inflammation Following Intravitreal Aflibercept 8 mg Injections: A Case Report.}, journal = {Reports (MDPI)}, volume = {8}, number = {4}, pages = {}, pmid = {41441525}, issn = {2571-841X}, abstract = {Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet's folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management.}, }
@article {pmid41443408, year = {2025}, author = {Joo, JH and Zhao, AH and Chalasani, M and Allan, KC and Rachitskaya, AV}, title = {Impact of Glucagon-Like Peptide-1 Receptor Agonists on Age-Related Macular Degeneration at a Tertiary Ophthalmology Center.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2025.12.014}, pmid = {41443408}, issn = {2468-6530}, abstract = {OBJECTIVE: There is ongoing debate in the literature on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on age-related macular degeneration (AMD). This study examines the effect of GLP-1RA on the risk of AMD development compared with other glucose-lowering medications at a single ophthalmology center.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: A total of 30 515 GLP-1RA users, 48 906 sodium-glucose transport protein 2 inhibitor (SGLT-2i) users, 286 066 metformin users, and 164 361 insulin users aged &#x2265;50 years had a 1-year minimum drug duration between 2016 and 2025. After propensity score matching (PSM), each cohort included 7561 patients. Patients with diabetic macular edema, severe or proliferative diabetic retinopathy, and with history of prior retinal surgeries were excluded.<br><br>METHODS: The relative risk (RR) of developing nonexudative AMD was measured at yearly drug duration intervals up to 3 years using logistic regression models controlling for age, sex, race, smoking status, and hemoglobin A1C percentage. Manual review was performed on a random sampling of AMD cases to optimize accuracy. Cox proportional hazards (CPHs) validation analyses in PSM cohorts were performed, matching additionally for body mass index, history of hypertension, chronic kidney disease, and diabetes duration.<br><br>MAIN OUTCOME MEASURES: The primary outcome was the RR of nonexudative AMD up to 3 years on GLP-1RAs compared with alternative antihyperglycemic agents.<br><br>RESULTS: Glucagon-like peptide-1 receptor agonist was associated with decreased risk of nonexudative AMD compared with metformin and insulin at all 3 years and compared with SGLT-2i only after 3 years of use (3 years: metformin relative risk [RR] = 0.25; 95% confidence interval [CI], 0.14-0.41; insulin RR = 0.28; 95% CI, 0.15-0.46; SGLT-2i RR = 0.42; 95% CI, 0.22-0.74). In PSM cohorts, CPH analyses showed a reduced risk only compared with insulin (hazards ratio = 0.45; 95% CI, 0.27-0.76).<br><br>CONCLUSIONS: Glucagon-like peptide-1 receptor agonist use was associated with a lower risk of nonexudative AMD compared with metformin, insulin, and SGLT-2i in logistic regression models. The risk reduction persisted for insulin in CPH analyses in smaller PSM cohorts.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41443587, year = {2026}, author = {Kwan, WC and Brunton, EK and Goris, T and Begeng, JM and Kameneva, T and Stoddart, PR and Ibbotson, MR and Richardson, RT and Tong, W}, title = {Hybrid optogenetic and electrical stimulation of retinal ganglion cells for artificial vision.}, journal = {Brain stimulation}, volume = {19}, number = {1}, pages = {103012}, doi = {10.1016/j.brs.2025.103012}, pmid = {41443587}, issn = {1876-4754}, mesh = {Animals ; *Retinal Ganglion Cells/physiology ; *Optogenetics/methods ; Mice, Transgenic ; Rats ; *Electric Stimulation/methods ; *Visual Prosthesis ; Mice ; Action Potentials/physiology ; }, abstract = {INTRODUCTION: Millions of adults worldwide experience severe visual impairment due to photoreceptor loss from retinal diseases such as retinitis pigmentosa and macular degeneration. Retinal prostheses that provide artificial vision by stimulating the surviving retinal ganglion cells (RGCs) have emerged as a promising therapy. However, all clinically approved retinal prostheses that use electrical stimulation face the issue of electrical spread. As such, the quality of restored vision provided by existing devices has been limited. Optogenetic approaches provide greater spatial precision, however, they have poor temporal properties compared to electrical stimulation.<br><br>MATERIALS AND METHODS: We developed an opto-electrical hybrid approach and surveyed this stimulation strategy in the retina of two animal models: normal-sighted transgenic mice that express ChR2-H134R in a sub-population of RGCs and the degenerated retina of Royal College of Surgeons rats with residual RGCs transduced with ChrimsonR. We conducted whole-cell patch clamp recordings and measured calcium transients with the biosensor GCaMP7s to determine single-cell and population responses to hybrid stimulation, respectively.<br><br>RESULTS: Hybrid stimulation reduced both electrical and optogenetic activation thresholds. Optical thresholds could be halved with electrical supplementation and synergistically, the opto-electrical coupling reduced the electrical intensity requirements to elicit action potentials by &#x223c;50&#xa0;% (p&#xa0;<&#xa0;0.0001). Additionally, hybrid stimulation evoked significantly higher firing frequencies, by an order of up to 2&#xd7;, when compared to electrical or optical-only methods (p&#xa0;<&#xa0;0.0001). These properties of hybrid stimulation were replicated in the diseased retina, where the reduced activation thresholds contributed to significantly reduced spread of activation compared to electrical stimulation alone (p&#xa0;<&#xa0;0.05), a challenge that persists in devices that utilize extracellular electrical stimulation. Hybrid stimulation improved the spatial resolution of RGC activation when applied at retina-electrode spacing reflective of current epiretinal and suprachoroidal devices.<br><br>CONCLUSION: Combining the optogenetic and electrical modes of activation enabled significant reductions of each component in the stimulus, leading to more localised stimulation when compared to electrical-only stimulation, while also reducing the optical intensity required for optogenetic activation.&#xa0;Together with improvements in response reliability, hybrid stimulation may not only improve the resolution and refresh rate of future visual prostheses but may also provide greater control in neuromodulation for any bionic device that interfaces with neural tissue.}, }
@article {pmid41443801, year = {2025}, author = {Ouchi, C and Hosokawa, MM and Kimura, S and Shiode, Y and Matoba, R and Morita, T and Morizane, Y}, title = {Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older.}, journal = {Acta medica Okayama}, volume = {79}, number = {6}, pages = {405-412}, doi = {10.18926/AMO/69842}, pmid = {41443801}, issn = {0386-300X}, mesh = {Humans ; Aged, 80 and over ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Visual Acuity ; Ranibizumab/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Choroidal Neovascularization/drug therapy ; Retrospective Studies ; }, abstract = {We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes.}, }
@article {pmid41444944, year = {2025}, author = {Khathami, AA and Baklola, M and Alalyani, MA and Aljuaid, AT and Alsaeed, R and Ghramah, AA and Aljuaid, OT and AlGarni, RH and Alshahrani, RS and Aldreweash, RS and Alshehri, RS and Albishi, SA and Almutairi, GM and Al-Bawah, N and Ghaith, KAA}, title = {Multimodal artificial intelligence in retinal vascular and neovascular macular diseases: a systematic review of diagnostic and prognostic applications.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {46}, doi = {10.1186/s12886-025-04561-3}, pmid = {41444944}, issn = {1471-2415}, mesh = {Humans ; *Artificial Intelligence ; Prognosis ; *Multimodal Imaging ; *Retinal Vein Occlusion/diagnosis ; *Wet Macular Degeneration/diagnosis ; Tomography, Optical Coherence ; *Diabetic Retinopathy/diagnosis ; }, abstract = {BACKGROUND: Retinal vascular diseases, including diabetic retinopathy (DR) and retinal vein occlusion (RVO), and neovascular macular diseases such as neovascular age-related macular degeneration (nAMD) are leading causes of vision loss worldwide. With the rapid growth of artificial intelligence (AI), multimodal approaches that integrate diverse imaging modalities and clinical data have emerged as powerful tools for improving diagnosis, prognosis, and risk stratification.<br><br>METHODS: This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence on the diagnostic and prognostic applications of multimodal AI in retinal vascular diseases. Six databases (PubMed, Embase, Scopus, Web of Science, IEEE Xplore, and Cochrane Library) were searched for English-language studies published between 1 January 2019 and 1 November 2025. Eligible studies applied AI or machine learning models integrating two or more data modalities for diagnosis, prognosis, or prediction in DR, RVO, or AMD. Data extraction, quality appraisal, and narrative synthesis were performed.<br><br>RESULTS: From 11,659 identified records, 12 studies met the eligibility criteria. Multimodal AI systems consistently outperformed unimodal models and, in several cases, exceeded expert ophthalmologist performance. Diagnostic accuracy for AMD and polypoidal choroidal vasculopathy (PCV) ranged from 87% to 96%, with fusion-based approaches achieving area under the curve (AUC) values up to 0.989. Prognostic models predicting treatment response or recurrence in nAMD and RVO achieved AUCs between 0.972 and 0.980, surpassing both clinician and single-modality baselines. Hybrid and foundation models integrating imaging, clinical, and textual data demonstrated promising results but variable robustness. Most studies were retrospective, single-center, and exhibited moderate-to-high risk of bias, emphasizing the need for larger, prospective, multicenter validation to establish clinical applicability and generalizability.<br><br>CONCLUSION: Multimodal AI demonstrates superior diagnostic and prognostic performance compared to unimodal models and, in some cases, outperforms expert clinicians in managing retinal vascular diseases. Integrating complementary data sources, such as OCT, fundus imaging, and clinical information, enhances model accuracy and generalizability.}, }
@article {pmid41446234, year = {2025}, author = {Lewis, TR and Castillo, CM and Phan, S and Shores, CR and Hayase, KK and Kim, KY and Ellisman, MH and Alekseev, O and Burns, ME and Arshavsky, VY}, title = {RPE pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion in Adam9 knockout mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41446234}, issn = {2692-8205}, support = {P30 EY005722/EY/NEI NIH HHS/United States ; S10 OD034447/OD/NIH HHS/United States ; K08 EY033857/EY/NEI NIH HHS/United States ; R01 EY030451/EY/NEI NIH HHS/United States ; U24 NS120055/NS/NINDS NIH HHS/United States ; R01 EY024320/EY/NEI NIH HHS/United States ; R00 EY033763/EY/NEI NIH HHS/United States ; K99 EY033763/EY/NEI NIH HHS/United States ; }, abstract = {Vision begins in the outer segment compartment of photoreceptor cells, which is constantly renewed through the addition of membrane material at its base and ingestion of mature membranes at its tip by the retinal pigment epithelium (RPE). The close apposition of outer segments to the RPE is believed to be critical for maintaining this renewal process. Yet, in several retinal diseases, expansion of the subretinal space separating photoreceptors from the RPE does not immediately impact photoreceptor functionality. Here, we analyzed outer segment function and renewal in the Adam9 knockout mouse characterized by a major expansion of the subretinal space. Surprisingly, photoreceptor-RPE separation affected neither the sensitivity of photoreceptor light-responses nor the normal rate of outer segment renewal in this mouse prior to the onset of photoreceptor degeneration. The latter is achieved through the formation of elongated RPE "pseudopods" extending across the enlarged subretinal space to ingest outer segment tips. This work suggests that pseudopod formation may underlie the persistence of photoreceptor function in human diseases accompanied by photoreceptor-RPE separation, such as vitelliform macular dystrophy or age-related macular degeneration associated with subretinal drusenoid deposits.}, }
@article {pmid41448386, year = {2026}, author = {Wang, X and Delle, C and Nedergaard, M and Wostyn, P}, title = {Glymphatic transport and ocular diseases.}, journal = {Progress in retinal and eye research}, volume = {110}, number = {}, pages = {101433}, doi = {10.1016/j.preteyeres.2025.101433}, pmid = {41448386}, issn = {1873-1635}, mesh = {Humans ; *Glymphatic System/metabolism/physiology ; Animals ; *Eye Diseases/physiopathology/metabolism ; }, abstract = {The high metabolic demand of retinal neurons requires tightly regulated mechanisms to maintain homeostasis and ensure the efficient clearance of metabolic waste and excess water. Recent studies have identified a glymphatic-like system in the rodent eye, and growing evidence supports the existence of a similar pathway in the human eye, facilitating fluid exchange and waste removal. The ocular glymphatic system supports bidirectional flow along the optic nerve - anterograde from the retina and retrograde from the brain. In this review, we integrate findings from preclinical models and clinically grounded hypotheses to identify key contributors to glymphatic dysfunction in ocular diseases. These include impaired laminar barrier integrity, pathological perivascular space expansion, aquaporin-4 abnormalities, immature vasculature, and pathological immune activation. Glymphatic impairment has been implicated in murine models of glaucoma, diabetic retinopathy, and ocular manifestations of Alzheimer's disease. Additionally, disrupted glymphatic flow is suspected in papilledema, spaceflight associated neuro-ocular syndrome, and Terson syndrome. We further explore novel associations between glymphatic dysfunction and other blinding disorders such as myopic optic neuropathy, age-related macular degeneration, neuromyelitis optica spectrum disorders, and retinal vasculitis. In delineating these mechanistic links, this review provides a conceptual framework to guide future research in glymphatic contributions to ocular diseases.}, }
@article {pmid41448679, year = {2025}, author = {Oldham, E and Hall, RH and Jones, G and Modi, J and Ward, S and Magee, T and Fitzgerald, K and Magana, K and Hughes, G and Ford, AI and Vassar, M}, title = {Assessing uptake of the macular degeneration core outcome set in clinical trials: a cross-sectional study.}, journal = {BMJ open}, volume = {15}, number = {12}, pages = {e104705}, pmid = {41448679}, issn = {2044-6055}, mesh = {Humans ; *Clinical Trials as Topic/standards ; Cross-Sectional Studies ; *Macular Degeneration/therapy ; *Outcome Assessment, Health Care/standards ; }, abstract = {PURPOSE: Establishing comparability between measured outcomes in clinical trials poses a significant obstacle for systematic reviewers. Core outcome sets (COSs) were developed to address this issue. The macular degeneration (MD) COS is designed to standardise outcome measurement across clinical trials for MD. This study investigates the uptake of the MD COS in standardising outcome measurement across clinical trials.<br><br>DESIGN: Cross-sectional analysis METHODS: We conducted a search on ClinicalTrials.gov to locate MD clinical trials that were registered 5 years prior to COS publication through the search date of 26 June 2023 and obtained a pool of 2152 registered studies. After applying various inclusion and exclusion criteria, we analysed 159 trials. We then analysed the COS uptake using an interrupted time series analysis (ITSA) and performed performed analyses of variance (ANOVAs) and Pearson correlations to evaluate associations between trial characteristics and outcome measurement.<br><br>RESULTS: ITSA showed no significant change in uptake following the MD COS (2016): mean percentage of completion of the COS increased by 0.24% per month before publication (p=0.27) and by 0.07% per month after publication (p=0.62), indicating no meaningful post-publication slope change in COS use. For context, visual acuity was most commonly measured, while several patient-reported and disutility domains were infrequently captured.<br><br>CONCLUSION: No discernible patterns in COS usage for MD trials were observed. We recommend further collaboration between regulators and COS developers to help with COS uptake. Additionally, we suggest that further studies analyse adherence to COSs in respect to regulatory recommendations.}, }
@article {pmid41449919, year = {2026}, author = {Tang, J and Chen, J and Li, Z and Zhang, G and Zhu, L and Li, H and Su, W and Qin, S}, title = {Genetic Correlation and Mendelian Randomization Analyses Reveal Causal Links Between Metabolic-Associated Diseases or Risk Factors and Major Eye Diseases.}, journal = {Current eye research}, volume = {51}, number = {3}, pages = {320-331}, doi = {10.1080/02713683.2025.2585338}, pmid = {41449919}, issn = {1460-2202}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; Risk Factors ; *Eye Diseases/genetics ; *Polymorphism, Single Nucleotide ; Male ; Genetic Predisposition to Disease ; Female ; Cataract/genetics ; *Metabolic Diseases/genetics ; Macular Degeneration/genetics ; }, abstract = {PURPOSE: This study aims to elucidate the causal relationships and shared genetic architecture between metabolic-associated diseases and risk factors-including hypertension, type 1 diabetes (T1D), type 2 diabetes (T2D), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body mass index (BMI)-and primary vision-threatening eye disorders, involving glaucoma, cataracts, refractive disorders, and age-related macular degeneration (AMD).<br><br>METHODS: We analyzed genome-wide association study (GWAS) summary statistics from > 500&#xa0;000 individuals of European ancestry in the FinnGen, UK Biobank, and MRC-IEU databases to ensure adequate sample size. Linkage disequilibrium score regression (LDSC) was applied to estimate genetic correlations, while two-sample Mendelian randomization (MR) was performed to assess causal effects. Furthermore, a bidirectional Mendelian Randomization was further conducted to examine the directionality of associations between hypertension and cataracts.<br><br>RESULTS: This study was the first to reveal genetic correlations and causal effects of hypertension on cataracts, particularly senile cataracts. MR analysis provided evidence that hypertension is causally associated with an increased risk of cataracts, particularly senile cataract, whereas the reverse association was not supported. Additionally, LDL cholesterol was suggested as a protective factor for AMD, while HDL cholesterol was associated with an increased risk. The LDSC analysis also indicated a suggestive genetic correlation between T2D and both cataracts and glaucoma, but not for T1D.<br><br>CONCLUSION: This study provides comprehensive evidence of genetic correlations and potential causal relationships between metabolic-associated conditions and major eye diseases contributing to vision loss.}, }
@article {pmid41450867, year = {2026}, author = {Mukherjee, S and Nagarkar, A and Prasad, M and Agron, E and Weber, C and Chew, EY and De Silva, T}, title = {A Datasheet for Age-Related Eye Disease Study 2 on the Database of Genotypes and Phenotypes.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100953}, pmid = {41450867}, issn = {2666-9145}, abstract = {OBJECTIVE: To provide a comprehensive summary of the controlled-access Age-Related Eye Disease Study 2 (AREDS2) data elements, encompassing phenotypic, imaging, dietary, genetic, and ancillary data.<br><br>DESIGN: Dataset description of a multicenter, phase III, randomized clinical trial evaluating lutein + zeaxanthin, &#x3c9;-3, or both long-chain polyunsaturated fatty acid supplementation in intermediate age-related macular degeneration (AMD). Secondary randomization was offered to all AREDS2 participants to evaluate varying levels of zinc and the potential for elimination of &#x3b2;-carotene, which increases the risk of lung cancer in smokers.<br><br>PARTICIPANTS: A total of 4203 participants aged 50-85 years with bilateral intermediate AMD (bilateral large drusen &#x2265;125 &#x3bc;m) or intermediate AMD in one eye and advanced AMD in the other eye were enrolled at 82 clinical centers between 2006 and 2008.<br><br>METHODS: Participants attended annual clinic visits, including eye examinations, visual acuity, slit lamp, intraocular pressure, and imaging that included stereoscopic 30&#xb0; color fundus (fields 1-3) and fundus reflex images in all participants, while fundus autofluorescence images and spectral-domain OCT images were acquired in selected clinics. Telephone contacts at 3 and 6 months and annually thereafter collected adverse events and reinforced visit compliance.<br><br>MAIN OUTCOME MEASURES: Progression to advanced AMD (central geographic atrophy or neovascular AMD), incidence of cataract surgery, and loss of &#x2265;15 letters (&#x2265;3 lines) of visual acuity from baseline.<br><br>RESULTS: Controlled-access data are archived under the database of Genotypes and Phenotypes (dbGaP) website with the accession number phs002015.v2.p1. The data elements include main-study phenotype tables plus multiple ancillary-study tables with cardiovascular, cognitive, nutritional biochemistry, and genetic data. Additional data include dietary assessments, image gradings, visual acuity testing, and cataract surgery documentation. Blood or saliva from >2000 participants was collected; exome-chip data from >1800 and whole-genome sequencing from 1363 participants, including 488 who also participated in the original AREDS, are available under the International AMD Genomics Consortium and dbGaP.<br><br>CONCLUSIONS: The AREDS2 dataset's rigorous interventional design, standardized longitudinal ophthalmic imaging gradings, comprehensive dietary and genetic information, and ancillary cardiovascular and cognitive assessments constitute an invaluable resource for elucidating AMD progression, informing nutritional strategies, and artificial intelligence-driven diagnostics.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41451083, year = {2025}, author = {Chen, X and Li, H and Jiao, Z and Liu, Y and Wu, Y and Qiu, X and Zou, Y and Liu, G}, title = {Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and age-related macular degeneration: insights from two observational studies.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1724938}, pmid = {41451083}, issn = {2296-858X}, abstract = {OBJECTIVES: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is an innovative measure for assessing cardiovascular disease risk, primarily associated with lipid profiles. Lipid metabolism disorders have been reported to be associated with age-related macular degeneration (AMD), yet the relationship between NHHR and AMD has not been previously explored. This study primarily aims to investigate the potential association between NHHR and the prevalence of AMD.<br><br>METHODS: A comprehensive cross-sectional stratified survey using the National Health and Nutrition Examination Survey (NHANES) dataset of the US was conducted, including 4,017 participants aged 40&#x202f;years and older, from 2005 to 2008. The NHHR was calculated as [Total Cholesterol (TC)&#x202f;-&#x202f;High-Density Lipoprotein Cholesterol (HDL-C)]/HDL-C. Data on AMD were derived from retinal photography. Logistic regression, stratified analysis, RCS curve, ROC/AUC, and subgroup interaction analysis were used to explore the relationship between NHHR and AMD. Meanwhile, patients who visited the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine (PHFT, China) between November 2021 and September 2025 were recruited retrospectively. All participants who met the study inclusion criteria were screened from the hospital-wide integrated informatics platform for clinical research. Finally, the clinical data of 96 eligible participants of PHFT were included in this study for conducting external validation analysis.<br><br>RESULTS: The cross-sectional study from NHANES included 4,017 participants, of whom 3,678 (91.56%) had no AMD and 339 (8.44%) exhibited AMD. The external validation study from PHFT consisted of 48 patients with AMD and 48 non-AMD participants. Both studies indicated that compared with the non-AMD group, the AMD group had a significantly lower NHHR (p&#x202f;<&#x202f;0.01). In the fully adjusted Model, when NHHR was stratified into tertiles, the results showed that for each one-unit increase in NHHR, the risk of AMD in individuals in the highest tertile was reduced by 33.1 and 76.8%, respectively. The results of the RCS curve and threshold effect analyses from the two studies confirmed a negative correlation trend between the two variables (p&#x202f;<&#x202f;0.05). The subgroup and interaction analysis, based on data from the NHANES, shows consistent associations between NHHR and AMD across various subgroups.<br><br>CONCLUSION: Our preliminary research indicates that NHHR might be a reliable independent indicator of the risk of developing AMD. In the future, large-scale sample studies and more prospective research are still needed to confirm our findings.}, }
@article {pmid41452565, year = {2026}, author = {Koizumi, H and Honda, S and Yasukawa, T and Kishino, G and Sekiryu, T and Schulze, A and Yamashita, T and Schmidt-Ott, U and Zhao, M and Zhang, X and Berliner, AJ and Chu, KW and Reed, K and Cheng, Y and Bhore, R and Vitti, R and Fujita, I and Leal, S and Iida, T and , }, title = {Intravitreal aflibercept 8 mg in patients from Japan with neovascular age-related macular degeneration: 48-week subgroup analysis of the PULSAR trial.}, journal = {Japanese journal of ophthalmology}, volume = {70}, number = {1}, pages = {139-149}, pmid = {41452565}, issn = {1613-2246}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Visual Acuity ; Double-Blind Method ; Male ; Female ; Japan/epidemiology ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; Tomography, Optical Coherence ; Treatment Outcome ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Follow-Up Studies ; Time Factors ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Middle Aged ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macula Lutea/pathology ; }, abstract = {PURPOSE: To evaluate the 1-year efficacy and safety of aflibercept 8 mg compared with aflibercept 2 mg in a pre-specified analysis of patients from Japan with neovascular age-related macular degeneration (nAMD) included in PULSAR.<br><br>STUDY DESIGN: PULSAR (NCT04423718) was a global, phase 3, randomized, double-masked, non-inferiority study of adults with nAMD. Patients were randomized 1:1:1 to receive aflibercept 8 mg every 12 weeks (8q12), or every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups.<br><br>METHODS: This subgroup analysis of Japan and non-Japan cohorts from PULSAR evaluated changes from baseline in best-corrected visual acuity (BCVA), central subfield retinal thickness, durability and safety outcomes.<br><br>RESULTS: In the Japan subgroup, least squares (LS) mean (95% CI) changes from baseline in BCVA at week 48 were +6.5 (+0.7, +12.3), +7.9 (+5.1, +10.6), and +4.7 (-0.5, +9.9) letters for patients in the 8q12 (n = 31), 8q16 (n = 33), and 2q8 (n = 33) groups, respectively. The majority of patients in the 8q12 (82.1%) and 8q16 (93.8%) groups maintained their randomized dosing intervals through Week 48. Ocular treatment-emergent adverse events were reported in 35.5%, 30.3%, and 39.4% of patients in the Japan subgroup in 8q12, 8q16, and 2q8 groups, respectively. Similar efficacy and safety results were observed in the non-Japan subgroup.<br><br>CONCLUSION: Aflibercept 8 mg has similar efficacy and safety to aflibercept 2 mg when administered at extended dosing intervals in both the Japan and non-Japan subgroups, consistent with the overall PULSAR results.}, }
@article {pmid41453515, year = {2025}, author = {Myers, WK and Heath, G and Rohrer, B}, title = {Rate of Age-Related Macular Degeneration in Patients Prescribed Glucagon-Like Peptide-1 Receptor Agonists or Other Weight Loss Therapies.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, pmid = {41453515}, issn = {2468-6530}, support = {I01 BX003050/BX/BLRD VA/United States ; T32 GM132055/GM/NIGMS NIH HHS/United States ; I01 RX000444/RX/RRD VA/United States ; R01 EY030072/EY/NEI NIH HHS/United States ; IK6 BX004858/BX/BLRD VA/United States ; }, abstract = {PURPOSE: To compare the hazard of age-related macular degeneration (AMD) among nondiabetic, weight loss-eligible adults prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide or liraglutide) versus other weight loss (OWL) pharmacotherapies (phentermine, orlistat, setmelanotide, phentermine-topiramate, or bupropion-naltrexone).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Adults aged &#x2265;50 years without diabetes who met the criteria for weight loss pharmacotherapy and were prescribed GLP-1 RAs or OWL medications were included. Before matching, 60&#x2009;336 patients were included in the GLP-1 RA group and 21 609 in the OWL cohort; after matching, 20&#x2009;959 patients remained in each cohort.<br><br>METHODS: Cohorts were constructed using de-identified data from the TriNetX Research Network (June 2021-October 2025). Nondiabetic status was defined as the absence of a diabetes mellitus diagnosis, hemoglobin A1c &#x2265;6.5%, or metformin or insulin use. Patients met criteria for weight loss pharmacotherapy with documentation of an obesity diagnosis, body mass index (BMI) &#x2265;30 kg/m[2], or BMI &#x2265;27 kg/m[2] with dyslipidemia or hypertension, recorded within 1 year before initiation. Inclusion required &#x2265;2 prescriptions for a single study medication &#x2265;6 months apart. Patients with recorded medication cross-exposure or outcome diagnoses before index were excluded. Cohorts were matched for demographics, established AMD risk factors, covariates influencing treatment allocation, access to ophthalmic care, and proxies for social determinants of health using 1:1 propensity score matching. Outcomes were assessed using Cox proportional hazards models.<br><br>MAIN OUTCOME MEASURES: Hazard ratios (HRs) of nonexudative AMD, exudative AMD, and any AMD (exudative, nonexudative, or unspecified). Changes in BMI and hemoglobin A1c were analyzed to contextualize findings.<br><br>RESULTS: Compared with OWL pharmacotherapies, GLP-1 RAs were associated with a lower hazard of nonexudative AMD (HR, 0.47; 95% confidence interval [CI], 0.28-0.78) and any AMD (HR, 0.61; 95% CI, 0.43-0.85), with no difference for exudative AMD (HR, 0.63; 95% CI, 0.30-1.32). Body mass index and hemoglobin A1c were similar over follow-up.<br><br>CONCLUSIONS: Among nondiabetic adults aged &#x2265;50 years eligible for weight loss pharmacotherapy, prescriptions for GLP-1 RAs were associated with a lower incidence of nonexudative and any (nonexudative, exudative, or unspecified) AMD diagnoses compared with OWL medications. The difference in new exudative AMD diagnoses was not statistically significant.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41453674, year = {2026}, author = {Palakkan, AA and Kumar, GS}, title = {Retinal organoids in age-related macular degeneration: Promise, pitfalls, and progress.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110831}, doi = {10.1016/j.exer.2025.110831}, pmid = {41453674}, issn = {1096-0007}, mesh = {Humans ; *Organoids/pathology ; *Macular Degeneration/pathology ; *Retina/pathology ; Animals ; }, abstract = {Recent advancements in organoid technology have revolutionized our understanding of organ development and disease modelling. However, despite significant progress, retinal organoids continue to face several limitations, including imperfect architecture, incomplete maturation, limited functional integration, and lack of vascularization. These challenges hinder their potential as accurate models of human retinal biology and disease. In this review, we examine the currently available models of age-related macular degeneration, evaluate the potential of retinal organoids, and discuss their respective advantages and limitations. We also explore strategies to overcome the existing challenges in retinal organoid systems, drawing parallels from progress made in other organoid fields, where similar limitations have been addressed. Implementing these strategies may enhance the structural and functional fidelity of retinal organoids, thereby improving their utility in modelling retinal disorders and advancing regenerative medicine.}, }
@article {pmid41454061, year = {2026}, author = {Guo, S and Liu, R and Liu, Y and Liu, F}, title = {Comment on "Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration".}, journal = {Eye (London, England)}, volume = {40}, number = {2}, pages = {280}, pmid = {41454061}, issn = {1476-5454}, }
@article {pmid41455312, year = {2026}, author = {Zhang, M and Bi, H and Guo, D}, title = {Advances in study of endoplasmic reticulum stress in ophthalmic diseases: an overview.}, journal = {Biochemical and biophysical research communications}, volume = {797}, number = {}, pages = {153182}, doi = {10.1016/j.bbrc.2025.153182}, pmid = {41455312}, issn = {1090-2104}, mesh = {*Endoplasmic Reticulum Stress ; Humans ; *Eye Diseases/pathology/metabolism ; Animals ; Endoplasmic Reticulum/metabolism/pathology ; Diabetic Retinopathy/pathology/metabolism ; }, abstract = {The endoplasmic reticulum (ER) is a vital intracellular organelle in protein synthesis, folding, and modification. When cells experience excessive protein synthesis, glucose metabolism disorders, or calcium imbalance, the ER can become damaged or overburdened, triggering ER stress. Dysregulated ER stress can lead to various pathophysiological processes, including apoptosis, inflammation, protein aggregation, and lipid metabolism abnormalities. These processes are closely associated with the onset and progression of numerous diseases. Notably, many ophthalmic conditions, such as age-related macular degeneration, glaucoma, and diabetic retinopathy, are intricately linked to ER stress. This review provides a concise overview of the role of ER stress in the development and progression of ophthalmic diseases. It also explores the potential of targeting ER stress as a therapeutic approach for these conditions. By modulating ER stress and its associated pathways, new therapeutic strategies may be developed to improve patient outcomes. Future research should aim to elucidate the specific molecular mechanisms linking ER stress to ophthalmic diseases and to validate the efficacy and safety of interventions targeting ER stress, offering new perspectives and methods for the prevention and treatment of ophthalmic diseases.}, }
@article {pmid41455821, year = {2025}, author = {Haghighi, T and Gholami, S and Sokol, JT and Biswas, A and Lim, JI and Leng, T and Thompson, AC and Tabkhi, H and Alam, MN}, title = {Compact vision language models enable efficient and interpretable optical coherence tomography through layer-specific multimodal learning.}, journal = {Communications medicine}, volume = {6}, number = {1}, pages = {32}, pmid = {41455821}, issn = {2730-664X}, support = {R15EY035804//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; AI4Health seed garnt//UNC | University of North Carolina at Charlotte (UNC Charlotte)/ ; R21 EY035271/EY/NEI NIH HHS/United States ; R21EY035271//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R15 EY035804/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: Translating the intricate anatomical signatures of retinal disease from optical coherence tomography (OCT) B-scans into clear, accurate clinical narratives demands algorithms that seamlessly fuse visual features with domain expertise.<br><br>METHODS: We curated a multimodal dataset of 40,000 OCT B-scans from public repositories and private clinical cohorts, each paired with expert-validated summaries spanning six conditions: diabetic macular edema, diabetic retinopathy, geographic atrophy, drusen, choroidal neovascularization, and healthy retina. We introduce LO-VLM, a compact (247M parameter) vision-language model (VLM) that infuses anatomical guidance into both encoder and decoder for free-form summary generation and multiclass disease classification. Benchmarking against state-of-the-art RetinaVLM, LLaVA-Med, and a ViT vision only model demonstrates superior performance.<br><br>RESULTS: In a blinded evaluation by three board certified retina specialists, LO-VLM narratives achieves a mean = 8.5 (standard deviation = 1.15) out of 10, compared to a mean = 5.5 (standard 32 deviation = 1.13) for RetinaVLM (p < 0.0001). In quantitative evaluations, LO-VLM achieves an SBERT similarity of 80.3% and a BERTScore F1 of 71.5%, representing improvements of 8.2% and 28.8% over specialized VLM baselines. For disease classification, LO-VLM reaches 96% accuracy (F1 = 96%), outperforming ViT by 13% and exceeding medical VLM benchmarks by over 62% (p < 0.05).<br><br>CONCLUSIONS: By reconciling interpretability with computational efficiency, LO-VLM establishes a paradigm for efficient AI models in OCT interpretation.}, }
@article {pmid41457155, year = {2025}, author = {Yang, S and Mu, D and Li, X}, title = {Luteolin alleviates angiogenesis in HUVECs by inhibiting VEGFA expression: integrating network pharmacology and experimental validation.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {3706}, pmid = {41457155}, issn = {2045-2322}, mesh = {Humans ; *Luteolin/pharmacology ; *Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Network Pharmacology ; Cell Movement/drug effects ; Signal Transduction/drug effects ; *Neovascularization, Pathologic/drug therapy/metabolism ; Macular Degeneration/drug therapy/metabolism/pathology ; Protein Interaction Maps/drug effects ; *Neovascularization, Physiologic/drug effects ; Cell Proliferation/drug effects ; Angiogenesis ; }, abstract = {To analyze the potential therapeutic value and mechanism of luteolin in age-related macular degeneration (AMD) using network pharmacology and cellular experiments. SHD-compound targets were retrieved from the TCMSP database, while AMD-related targets were extracted from OMIM and DisGeNET databases. Overlapping targets were identified via Venny 2.1. A PPI network was constructed using the STRING database, followed by functional enrichment analysis of overlapping targets via Metascape. Pharmacological networks were mapped using Cytoscape. For cellular experiments, the optimal concentration of luteolin was determined by CCK-8 assay. Human umbilical vein endothelial cells (HUVECs) were divided into: Control group (Without any intervention), Model group (VEGF165-induced model), and Treatment group (VEGF165-induced + luteolin). Angiogenesis was evaluated via scratch, transwell migration, invasion, and tube formation assays. VEGFA protein expression was assessed by Western blot. We identified 157 SHD-compound targets and 87 AMD-related targets, yielding 6 overlapping targets (ESR1, PON1, SOD1, APOB, VEGFA, IL6). PPI networks and enrichment analysis revealed that luteolin in SHD may inhibit AMD neovascularization via VEGFA signaling pathways. The concentration of luteolin (25 µmol/L) used in the experiments was selected based on the dose-response results. In vitro assays showed the Treatment group exhibited: significantly reduced horizontal migration (scratch assay, p < 0.05), decreased vertical migration (transwell assay, p < 0.05), suppressed invasion (p < 0.05), and inhibited tube formation (p < 0.05). Western blot confirmed reduced VEGFA expression in the treatment group (p < 0.05). Luteolin alleviates angiogenesis in HUVECs by inhibiting VEGFA expression, highlighting its potential as a therapeutic candidate for neovascular AMD.}, }
@article {pmid41457739, year = {2025}, author = {Kanthar, T and Vatcharavongvan, P and Prasert, V}, title = {Retrospective Analysis of Intervention Effectiveness in Preventing Glaucoma Blindness in a Tertiary Care Setting.}, journal = {Journal of evaluation in clinical practice}, volume = {31}, number = {8}, pages = {e70341}, doi = {10.1111/jep.70341}, pmid = {41457739}, issn = {1365-2753}, mesh = {Humans ; Male ; Retrospective Studies ; *Blindness/prevention &amp; control/etiology/epidemiology ; Female ; Thailand/epidemiology ; Middle Aged ; Cross-Sectional Studies ; Aged ; *Glaucoma/complications/therapy ; Tertiary Care Centers ; Risk Factors ; Trabeculectomy ; }, abstract = {RATIONALE: The global prevalence rate of glaucoma blindness is extremely high and is a leading cause of irreversible blindness. Despite many advancements in treatment, evaluating glaucoma blindness remains challenging due to the long time required for its development and the combined use of treatment modalities.<br><br>AIMS AND OBJECTIVES: To evaluate the effectiveness of various treatment modalities in preventing glaucoma-related blindness using a 5-year retrospective study from a tertiary care hospital in Thailand.<br><br>METHODS: A retrospective, cross-sectional study was conducted on 1031 glaucoma patients diagnosed between October 2017 and September 2022. Patients with advanced pterygium, corneal opacity, or macular degeneration were excluded. Data on demographics, clinical characteristics, and treatment modalities (medications, phacoemulsification with intraocular lens implantation [PE with IOL], laser iridotomy [LI], and trabeculectomy) were analyzed. Blindness was defined according to WHO criteria. Multivariate logistic regression assessed associations between blindness and risk factors.<br><br>RESULTS: Of the 1031 patients, 21.0% experienced blindness. Secondary glaucoma (SG) had the highest blindness rate (33.5%) compared to primary open-angle glaucoma (POAG, 19.0%) and primary angle-closure glaucoma (PACG, 19.9%). Multimodal interventions significantly reduced blindness in POAG (adjusted OR: 0.57; 95% CI: 0.38-0.87; p&#x2009;=&#x2009;0.027), but no significant benefit was observed in PACG or SG. PE with IOL showed the lowest blindness rate (14.9%), while trabeculectomy had the highest (47.2%). Treatment initiation within 5 years of diagnosis did not significantly affect blindness rates.<br><br>CONCLUSION: Multimodal interventions effectively reduce blindness in POAG but not in PACG or SG. Future studies should explore the impact of adherence, IOP fluctuation, and secondary glaucoma etiology on outcomes to optimize treatment strategies.}, }
@article {pmid41458157, year = {2025}, author = {Duan, MM and Qi, H and Tu, X}, title = {Knowledge-enhanced AI drives diagnosis of multiple retinal diseases in fundus fluorescein angiography.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1703606}, pmid = {41458157}, issn = {2296-634X}, abstract = {PURPOSE: This study aimed to develop and validate a deep learning model for the accurate multi-class classification of six retinal diseases using fundus fluorescein angiography (FFA) images.<br><br>METHODS: We applied a knowledge-enhanced pre-training strategy (KeepFIT) using a ResNet-50 image encoder on two large FFA corpora: a curated atlas and a clinical report dataset. The resulting visual encoder was fine-tuned to classify six conditions, including diabetic retinopathy and macular degeneration. The model's performance and generalizability were assessed on two independent test sets, one of which was sourced from an external institution.<br><br>RESULTS: Our proposed deep learning model, leveraging a knowledge-enhanced pre-training strategy, demonstrated robust performance in classifying six distinct retinal diseases using fundus fluorescein angiography images. The model achieved a strong and consistent micro-average area under the curve (AUC) of 0.92 across two independent test sets. Notably, it showed excellent classification performance for critical conditions such as venous occlusion (VO) and neovascular age-related macular degeneration (nAMD), with AUC values reaching 0.95 and 0.96, respectively.<br><br>CONCLUSION: The knowledge-enhanced pre-training strategy significantly improves the diagnostic accuracy and generalizability of deep learning models for FFA analysis. This approach provides a scalable and effective framework for automated retinal disease screening, holding significant potential for clinical decision support, especially in resource-limited settings.}, }
@article {pmid41458191, year = {2026}, author = {Li, N and Dang, Y}, title = {Atypical Retinitis Pigmentosa With Macular Sparing in a Patient With Compound Heterozygous ABCA4 Variants: A Case Report and Diagnostic Challenge.}, journal = {Clinical case reports}, volume = {14}, number = {1}, pages = {e71545}, pmid = {41458191}, issn = {2050-0904}, abstract = {Inherited retinal dystrophies are a complex group of disorders causing progressive vision loss. The ABCA4 gene is associated with a wide spectrum of retinopathies, most commonly Stargardt disease, which is characterized by central macular degeneration. Retinitis Pigmentosa (RP) is a less common but recognized ABCA4-associated phenotype, typically involving severe, pan-retinal degeneration. A 25-year-old male presented with a 5-year history of nyctalopia and progressive peripheral visual field loss. Best-corrected visual acuity was 1/20 in the right eye and 20/20 in the left eye. Fundus examination revealed pale optic discs, attenuated retinal arteries, and peripheral bone spicule-like pigment deposits, with notable sparing of the macula. Genetic analysis identified compound heterozygous variants in the ABCA4 gene: a known pathogenic variant, c.4793C>A (p.Ala1598Asp), inherited from his father, and a novel variant, c.1769A>G (p.Asp590Gly), inherited from his mother. The novel variant was re-evaluated according to ACMG/AMP guidelines and classified as likely pathogenic based on its absence in population databases, co-segregation with disease, and high in silico prediction scores. This case presents a diagnostic challenge, with a clinical phenotype of macular sparing RP and strong genetic evidence implicating ABCA4. These findings expand the potential phenotypic spectrum of ABCA4-retinopathy and underscore the critical role of genetic testing in diagnosing patients with atypical presentations of inherited retinal disease. Further investigation is needed to fully elucidate the pathogenic mechanism of the novel variant and its contribution to this unusual clinical picture.}, }
@article {pmid41458648, year = {2025}, author = {Kayabaşı, M and Karataş, E and Ayhan, Z and Kartı, &#xd6; and Saatci, AO}, title = {Evolution of the Onion Ring Sign in Radiation Retinopathy.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97758}, pmid = {41458648}, issn = {2168-8184}, abstract = {A 53-year-old male with a history of radiation therapy for thyroid ophthalmopathy was followed up for chronic bilateral vision loss and macular edema refractory to multiple intravitreal treatments for over 19 years. His clinical course included multiple intravitreal injections including triamcinolone acetonide, bevacizumab, pegaptanib, ranibizumab, aflibercept 2 and 8 mg, and dexamethasone implant. At the 17th year of follow-up, spectral-domain optical coherence tomography (OCT) revealed intensely hyperreflective, horizontally layered deposits within intraretinal cystic spaces without posterior shadowing, consistent with the onion ring sign. Fundoscopic examination showed highly refractile, golden-yellow lipid exudates corresponding to these OCT findings. Unlike previously reported cases of age-related macular degeneration and diabetic retinopathy, where these deposits were located primarily beneath or above the retinal pigment epithelium, the deposits in this patient were located within the inner retinal layers. The present case demonstrates that the onion ring sign may develop in long-standing radiation retinopathy, likely reflecting the cumulative effects of chronic vascular injury and persistent macular edema. The recognition of this OCT feature may aid in understanding the natural history, chronicity, and metabolic burden of retinal vascular disorders.}, }
@article {pmid41458867, year = {2025}, author = {Matsuo, T and Matsuo, N}, title = {Long-Term Outcome of Xenon-Arc Photocoagulation for Retinopathy of Prematurity in the 1970s in Japan: Eleven Patients With 32- to 49-Year Follow-Up.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97797}, pmid = {41458867}, issn = {2168-8184}, abstract = {OBJECTIVES: Photocoagulation or cryocautery, or their combinations, are the standard of care for retinopathy of prematurity at the recommended timing, which is based on the International Classification of Retinopathy of Prematurity. In Japan, the effectiveness of xenon-arc photocoagulation and cryocautery in retinopathy of prematurity was reported on an empirical basis first in 1968, and became the standard of care in retinopathy of prematurity in the 1970s, 10 years earlier compared with the other countries. In this study, we reported the up to 49 years visual outcome of 11 patients with retinopathy of prematurity who underwent xenon-arc photocoagulation and cryocautery in the 1970s.<br><br>METHODS: A retrospective review was made on the medical records of 11 consecutive patients who underwent xenon-arc photocoagulation for retinopathy of prematurity in the years 1974 to 1980, and were followed up until the period from 2009 to 2025. The birthweight ranged from 865 g to 2300 g at a median of 1350 g, and the gestational age at birth ranged from 27 weeks to 36 weeks at a median of 30 weeks. The corrected gestational age at the time of photocoagulation ranged from 32 weeks to 53 weeks, with a median of 37 weeks. Oxygen was given to all 11 patients, except for one who was born in the earliest year 1974. The retinopathy of prematurity was at stage 3 in both eyes of seven patients, with plus disease signs in four patients, at stage 2 with and without plus disease in two patients, at stage 2 and stage 3 in each eye of one patient, and at stage 1 with plus disease in both eyes of one patient. The entire 360-degree photocoagulation was given in seven patients, while partial photocoagulation was applied in four patients. Additional cryocautery was applied in six patients.<br><br>RESULTS: The age at the last visit ranged from 32 to 49 years with a median of 46 years. At the last visit, seven patients showed the best-corrected visual acuity in decimals of 0.8 or better in both eyes. One dizygotic twin showed no light perception in the phthisic right eye and 0.1 in the left eye with macular degeneration and nystagmus after he underwent cataract surgery at the age of 34 years. The other twin had the best-corrected visual acuity of 0.5 in the right eye and 0.02 in the left eye due to macular degeneration after he underwent cataract surgeries in both eyes at the age of 36 years. Two patients developed rhegmatogenous retinal detachment in one eye at the age of 44 and 41 years, respectively, and underwent vitrectomy with silicone oil tamponade, resulting in visual acuity of 0.1 and 0.3, respectively. Two patients experienced vitreous hemorrhage in one eye, which was absorbed spontaneously at the ages of 37 years and 42 years, respectively. One patient underwent partial scleral buckling for localized rhegmatogenous retinal detachment. No patient used intraocular pressure-lowering eyedrops.<br><br>CONCLUSION: Most patients with xenon-arc photocoagulation for retinopathy of prematurity in the 1970s maintained standard levels of visual acuity up to 49 years in the follow-up. Cataract, retinal detachment, and vitreous hemorrhage were noted as late complications and were coped with on an individual basis. The conclusion would have a meaning, even though not novel, that the patients with retinopathy of prematurity would have benefited from the xenon-arc photocoagulation and cryocautery.}, }
@article {pmid41460325, year = {2026}, author = {Sadda, SR and Wykoff, CC and Chowers, I and Korobelnik, JF and Narayana, R and Pappuru, RR and Holz, FG and Guymer, R and Cheung, CMG and Boyer, DS and Ip, M and Niessen, HG and Holenkamp, N and Durbin, M and Magazzeni, S and Cairns, AM and Ciller, C and Jovic, N and Blair, J and De Zanet, S and Lee, AY}, title = {Initiation of a global consortium to study the progression of age-related macular degeneration: RIMR AMD consortium report # 1.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {935-943}, pmid = {41460325}, issn = {1435-702X}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Disease Progression ; *Macular Degeneration/diagnosis ; *Macula Lutea/pathology/diagnostic imaging ; }, abstract = {PURPOSE: To describe the design and organizational structure of a global collaborative consortium aimed at aggregating longitudinal multimodal imaging data to better understand the progression of age-related macular degeneration (AMD) and facilitate therapeutic development.<br><br>METHODS: The Ryan Initiative for Macular Research (RIMR) AMD Consortium was established as a nonprofit organization, bringing together academic institutions, biopharmaceutical companies, and imaging technology providers. The consortium collects, de-identifies, and harmonizes longitudinal optical coherence tomography (OCT) data, as well as associated clinical metadata, from multiple international clinical centers using a cloud-based infrastructure. Imaging data is converted and stored in DICOM format, and associated clinical data is mapped to the OMOP Common Data Model. All analyses are conducted within a secure cloud environment, supporting both built-in and member-contributed artificial intelligence (AI) tools.<br><br>RESULTS: As of the time of reporting, the Consortium has ingested over 100,000 OCT volumes from more than 5,000 subjects across 7 global cohorts spanning 4 continents and 3 major OCT platforms. Based on information provided by the data providers, the dataset encompasses a wide range of AMD stages, from normal aging to late-stage neovascular or atrophic AMD, with longitudinal follow-up extending beyond 15 years for some subjects. A data harmonization pipeline has been established to convert all ingested OCT data to the DICOM standard and is thus ready for automated analysis to gain disease-related insights.<br><br>CONCLUSIONS: The RIMR AMD Consortium represents a novel model for global collaboration in AMD research, enabling the pooling and analysis of heterogeneous imaging data while addressing privacy, regulatory, and interoperability challenges. This framework may serve as a model for similar initiatives in other ocular diseases.}, }
@article {pmid41460363, year = {2025}, author = {Wang, C and Li, H and Wang, T and Li, X and Liu, J and Deng, A and Jiao, X}, title = {The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {57}, pmid = {41460363}, issn = {1573-2630}, support = {2024BSQD05//the Doctoral Startup Fund of the Affiliated Hospital of Shandong Second Medical University/ ; ZR2025QC815//the Shandong Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Probiotics/therapeutic use ; Dysbiosis ; *Immunomodulation ; *Eye Diseases/therapy/microbiology/immunology ; }, abstract = {PURPOSE: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.<br><br>METHODS: PubMed and Web of Science were searched (January 2020-October 2025) using the terms "gut microbiota", "ocular diseases", and "immunomodulatory therapies". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.<br><br>RESULTS: Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.<br><br>CONCLUSIONS: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.}, }
@article {pmid41462510, year = {2025}, author = {Inoda, S and Takahashi, H and Hashimoto, Y and Yoshida, H and Takahashi, H and Takayama, T and Tsuchiya, S and Matsumoto, D and Kawashima, H and Kaburaki, T and Yanagi, Y}, title = {One year outcomes of intravitreal faricimab for treatment Naïve neovascular AMD and associations with baseline aqueous humor cytokines.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44717}, pmid = {41462510}, issn = {2045-2322}, abstract = {UNLABELLED: This study investigated the one-year real-world clinical outcomes of intravitreal faricimab (IVF) in treatment-naïve neovascular age-related macular degeneration (nAMD) and its association with aqueous humor cytokine profiles. Thirty-four eyes of 32 nAMD patients, who received initial IVF at Jichi Medical University were included. These eyes showed significant improvements in central retinal subfield thickness (CST), central choroidal thickness (CCT), and best-corrected visual acuity (BCVA) one year post-IVF (all P < 0.01). Among 24 measurable cytokines, only VEGF-A was significantly higher in eyes with a dry macula at week 16 (P = 0.0030). Three cytokines were significantly higher in eyes with longer injection interval. Higher levels of galectin-1 and VCAM-1, and lower levels of P-selectin, were correlated with greater CST reduction (P = 0.020, 0.0061, and 0.012, respectively). Conversely, five cytokines including Ang-1 were correlated with greater BCVA improvement (all P < 0.05). In conclusion, an anatomical perspective faricimab demonstrated anatomical efficacy for VEGF-driven nAMD in the loading phase, while multiple cytokines associated with vascular instability or fibrosis appear to contribute to its durability. Notably, Ang-1 may be linked to visual improvement, suggesting that the neurotrophic effects of Ang-1 could be enhanced by Ang-2 inhibition.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-28911-9.}, }
@article {pmid41462634, year = {2025}, author = {Lin, HD and Tsai, RK and Wen, YT and Liu, PK}, title = {HDGF Protects Retinal Pigment Epithelium from Glyoxal-Induced Ferroptosis via SIRT1/PGC-1α/Nrf2 Pathway.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41462634}, issn = {2076-3921}, support = {MOST 109-2314-B-037-039//National Science and Technology Council, Taiwan/ ; MOST 110-2314-B-037-115//National Science and Technology Council, Taiwan/ ; KMUH109-9R50//Kaohsiung Medical University Hospital, Taiwan/ ; KMUH110-0R50//Kaohsiung Medical University Hospital, Taiwan/ ; }, abstract = {Age-related macular degeneration (AMD) is driven in part by the accumulation of reactive metabolites like glyoxal (GO), which induces retinal pigment epithelium (RPE) degeneration. Here, we demonstrate that GO triggers ferroptosis in human ARPE-19 cells, as characterized by iron-dependent lipid peroxidation, glutathione depletion, and reactive oxygen species (ROS) accumulation. This ferroptotic cell death is coupled with profound mitochondrial dysfunction, featuring network fragmentation and the downregulation of the key regulators MFN2, PGC-1α, and SIRT1. We identify hepatoma-derived growth factor (HDGF) as a potent protector against GO-induced damage. HDGF operates through a dual mechanism: it activates the p38 MAPK/AKT and SIRT1/PGC-1α axes to restore mitochondrial biogenesis and homeostasis, while concurrently enhancing the glutathione/GPX4 antioxidant system to suppress ferroptosis. This cytoprotective action is mediated via the PGC-1α/Nrf2 pathway, which integrates the enhancement of antioxidant defenses with the preservation of mitochondrial integrity. Our findings establish HDGF as a novel therapeutic agent for AMD, uniquely capable of concurrently targeting the interconnected pathways of ferroptosis and mitochondrial dysfunction, thereby addressing a critical unmet need in retinal disease treatment.}, }
@article {pmid41462675, year = {2025}, author = {Tundo, GR and Zingale, GA and Pandino, I and Peroni, E and Sbardella, D and Bocedi, A}, title = {The Interplay Between the Ubiquitin-Proteasome System and Oxidative Stress: A Future Perspective in Eye Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41462675}, issn = {2076-3921}, abstract = {Redox unbalance, a molecular trait common to neurodegenerative conditions and para-physiological processes like aging, is a critical factor in disease development and in exacerbating progression. The mechanism by which redox imbalance perturbs cellular homeostasis is strongly linked to the activity and function of the ubiquitin-proteasome system (UPS). The UPS, along with autophagy, is the primary intracellular proteolytic system, regulating targeted proteolysis and removing damaged proteins. Consequently, the UPS serves also as the first line of defense for cellular recovery following exposure to redox stressors. Paradoxically, the composition and function of the UPS can also be negatively targeted by redox unbalance through a vicious cycle. The alterations in redox balance and UPS biological mechanisms are involved in the etiopathogenesis of chronic eye disorders. These disorders encompass a diverse repertoire of pathologies affecting the retinal layers (e.g., age-related macular degeneration, diabetic retinopathy) and the optic nerve (e.g., glaucoma). Nowadays, the comprehension of the interplay between proteostasis and oxidative redox status remains pivotal for identifying new therapeutic approaches. Encouragingly, a number of anti-oxidant compounds have been reported to modulate proteasome activity against redox insults in vitro and in vivo. Furthermore, these compounds provide cytoprotective roles in both in vitro and animal models of eye diseases. Therefore, this review highlights recent research on the interplay of the UPS with oxidative stress in physio-pathological conditions, focusing on the onset and progression of ocular diseases, thereby providing new insights into UPS-oxidative stress interaction.}, }
@article {pmid41462709, year = {2025}, author = {Szewczyk-Roszczenko, OK and Pietruszyńska, M and Iwańska, IA and Roszczenko, P and Bielawski, K and Gornowicz, A and Bielawska, A}, title = {Plant-Based Care and Therapy in Ophthalmology.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {41462709}, issn = {2076-3921}, abstract = {Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects on eye health. This work provides an overview of selected bioactive substances, such as carotenoids (β-carotene), flavonoids, vitamins C and E, and phytochemicals derived from plants. These agents exhibit antioxidative, anti-inflammatory, antimicrobial, and regenerative properties that may support ocular surface integrity, reduce oxidative damage, and improve visual performance. The integration of such natural remedies into ocular health strategies may offer complementary benefits to conventional therapies.}, }
@article {pmid41462921, year = {2025}, author = {Machida, A and Kurihara, J and Hirata, Y and Machida, E and Murakami, R and Oka, A and Yoneda, A and Tsuiki, E and Oishi, A}, title = {Flexible Loading Phase Treat-and-Extend Regimen with Faricimab for Neovascular Age-Related Macular Degeneration: A Real-World Study.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, pmid = {41462921}, issn = {2227-9059}, support = {Nos. 22K09793 and 25K20183//Japan Society for the Promotion of Science/ ; }, abstract = {Background/Objectives: We aimed to evaluate the efficacy of a flexible loading-phase treat-and-extend regimen using faricimab, in which the number of loading-phase intravitreal injections was tailored to individual disease activity. Methods: This observational cohort study included 50 treatment-naïve eyes with neovascular age-related macular degeneration, treated with faricimab in Japan; approximately half of the eyes had polypoidal choroidal vasculopathy (PCV). Disease activity after one injection was assessed at the second visit (4 weeks later) to determine the treatment interval for subsequent injections. The primary outcome measure was the injection interval and visual/anatomical outcomes at 1 year after treatment initiation. Results: Of the 50 eyes, 43 completed a 1-year follow-up, including 27 eyes with PCV. The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.35 ± 0.32 to 0.19 ± 0.3 over 1 year. Overall, 60.5% achieved 16-week intervals, and 74.4% reached intervals of ≥12 weeks. A shorter loading phase (two or three injections) was associated with fewer total injections and higher rates of fluid resolution, without compromising visual outcomes. The presence of PCV and ellipsoid zone disruption were identified as risk factors for failure to extend treatment intervals beyond 16 weeks. Conclusions: A flexible loading-phase treat-and-extend regimen using faricimab yields outcomes comparable to those of the TENAYA protocol, with fewer injections, despite the high proportion of eyes with PCV. This simple approach is straightforward in design and may reduce treatment burden while maintaining efficacy.}, }
@article {pmid41463016, year = {2025}, author = {Giorgianni, F and Beranova-Giorgianni, S}, title = {Proteasome and Ribosome Ubiquitination in Retinal Pigment Epithelial (RPE) Cells in Response to Oxidized Low-Density Lipoprotein (OxLDL).}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, pmid = {41463016}, issn = {2227-9059}, support = {N/A//Retina Research Foundation/ ; }, abstract = {Background/Objectives: Oxidative stress plays a significant role in the development and progression of age-related macular degeneration (AMD). Retinal pigment epithelium (RPE) cells are specialized multifunctional cells indispensable for the maintenance of vision. The dysfunction and death of RPE cells in the macula characterize the onset and development of AMD. Of the various toxic agents that impact the health of the RPE, particular focus has been given to various forms of lipoproteins and their cytotoxic derivatives normally present in the retina. Oxidized low-density lipoprotein (OxLDL), derived from LDL in a pro-oxidative environment, is found adjacent to RPE cells as part of drusen, extracellular deposits that are a hallmark feature of AMD. OxLDL is a potent inflammatory agent and it has been implicated in cardiovascular and neurodegenerative conditions. The cellular molecular mechanisms triggered by OxLDL are only partially understood. The focus of this study was to characterize changes in the proteome of RPE cells after exposure to OxLDL, with a focus on the characterization and quantification of ubiquitinated proteins. Methods: Identification and quantification were performed with a high-resolution LC-MS/MS-based proteomics workflow after immune-enrichment for ubiquitinated peptides. Results: In total, out of the more than 1000 RPE ubiquitinated peptides quantified, OxLDL treatment caused a significant increase in ubiquitinated peptides compared to LDL and untreated cells. Principal component analysis (PCA) of the differentially ubiquitinated proteins (265) reduced the data complexity in two main groups of variables (proteins). Conclusions: Gene ontology enrichment analysis of the grouped proteins with the highest loading contribution to principal component 1 (PC1) and principal component 2 (PC2) revealed significant ubiquitination changes upon OxLDL treatment in proteins of the ubiquitin-proteasome system (UPS) responsible for proteasome-mediated catabolic processes and in protein members of the cellular translation machinery.}, }
@article {pmid41463332, year = {2025}, author = {Yu, X and Fan, H and Zhang, H and Li, X}, title = {Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, pmid = {41463332}, issn = {2218-273X}, support = {82371044, 82171042, 82171085//National Natural Science Foundation of China/ ; TJWJ2023XK009//Tianjin Health Commission Key Discipline Special Project/ ; }, mesh = {Humans ; Animals ; *Retinal Diseases/therapy/metabolism/pathology ; *Retinaldehyde/metabolism ; cis-trans-Isomerases/metabolism/genetics ; Genetic Therapy ; Retinal Pigment Epithelium/metabolism ; Regeneration ; Retinoid Isomerohydrolase ; }, abstract = {11-cis-retinal, the indispensable chromophore of photoreceptor opsins, is fundamental for light detection and the initiation of visual signal transduction. Its synthesis and regeneration through the visual cycle are critical not only for phototransduction but also for maintaining retinal homeostasis. Disruption of key enzymes, such as retinal pigment epithelium (RPE)65 and retinol dehydrogenases, results in toxic retinoid accumulation, oxidative stress, and progressive photoreceptor degeneration. These pathological mechanisms contribute to inherited and acquired retinal diseases, including Stargardt disease type 1, age-related macular degeneration, Leber congenital amaurosis, retinitis pigmentosa, and fundus albipunctatus. Recent therapeutic advances, ranging from gene replacement therapy with RPE65 (voretigene neparvovec, Luxturna[®]) to small-molecule modulators and antioxidant strategies, underscore the translational potential of targeting chromophore metabolism. This review outlines molecular processes underlying chromophore synthesis and regeneration, elucidates how disruptions in these processes contribute to inherited and acquired retinal pathologies, and evaluates existing and emerging therapeutic strategies that target chromophore metabolism. We highlight ongoing challenges and critical knowledge gaps to guide future investigations on basic science, translational research, and clinical practice. This review provides a comprehensive overview of the molecular mechanisms, current therapeutic approaches, and outstanding challenges, with a focus on future intervention directions.}, }
@article {pmid41464830, year = {2025}, author = {Bellucci, C and Virgili, M and Romano, A and Tedesco, SA and Mora, P}, title = {Laser Speckle Flowgraphy (LSFG) in Age-Related Macular Degeneration and Diabetic Retinopathy: A Systematic Review of Recent Literature.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, pmid = {41464830}, issn = {2077-0383}, abstract = {Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010-2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders.}, }
@article {pmid41465162, year = {2025}, author = {Lee, Y and Kim, S and Seo, JH}, title = {Causal Association Between Psoriasis and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.}, journal = {Genes}, volume = {16}, number = {12}, pages = {}, pmid = {41465162}, issn = {2073-4425}, support = {VHSMC25017//research grant from the Veterans Health Service Medical Centre/ ; }, mesh = {Humans ; *Macular Degeneration/genetics/epidemiology ; *Psoriasis/genetics/complications ; Mendelian Randomization Analysis/methods ; Polymorphism, Single Nucleotide/genetics ; Genome-Wide Association Study ; *Genetic Predisposition to Disease ; }, abstract = {BACKGROUND/OBJECTIVES: Psoriasis and age-related macular degeneration (AMD) may share immune-related pathophysiologic characteristics. However, few studies have investigated the relationship between psoriasis and AMD. We assessed the possible causal link between psoriasis and AMD in European populations.<br><br>METHODS: Single-nucleotide polymorphisms associated with psoriasis exposure were employed as instrumental variables (IVs) based on genome-wide significance (p < 5.0 &#xd7; 10-8) in the FinnGen genome-wide association study (GWAS). The GWAS data for AMD were obtained from 11 studies performed by the International AMD Genomics Consortium. We performed a two-sample Mendelian randomisation (MR) study to estimate causal effects using the inverse-variance weighted, weighted median, and MR-Egger methods, as well as the MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) test.<br><br>RESULTS: We observed significant causal associations of psoriasis with AMD. Using the weighted median method, the odds ratio (OR) was 1.09 (95% CI = [1.03-1.16] and p = 0.005), and using the MR-PRESSO test, the OR was 1.04 (95% CI = [1.00-1.09] and p = 0.043).<br><br>CONCLUSIONS: A potential causal association between psoriasis and AMD underscores the need to investigate inflammation as a risk factor for AMD.}, }
@article {pmid41466299, year = {2025}, author = {Hanson, RLW and Airody, A and Saad, A and Gale, RP}, title = {Early Detection Of neovascular age-Related mAcular Degeneration in the cOmmunity assessing persistence, adherence and acceptability: study protocol for the DORADO randomized controlled trial.}, journal = {Trials}, volume = {27}, number = {1}, pages = {78}, pmid = {41466299}, issn = {1745-6215}, support = {RE23_016_331617//Roche Products/ ; }, mesh = {Humans ; Early Diagnosis ; Quality of Life ; Tomography, Optical Coherence ; Randomized Controlled Trials as Topic ; Visual Acuity ; Time Factors ; United Kingdom ; *Patient Compliance ; *Patient Acceptance of Health Care ; *Wet Macular Degeneration/diagnosis ; Predictive Value of Tests ; *Community Health Services ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the Western world, with an estimated 40,000 newly diagnosed cases in the UK every year. Early detection and treatment of nAMD are important to achieve good visual acuity and quality-of-life (QoL) outcomes. Whilst early treatment of the second eye, following detection using optical coherence tomography (OCT) imaging, has shown maintenance of visual acuity and health-related QoL and reduced health and social care costs, there is a paucity of information about the benefits of early detection of nAMD in the first eye. In particular, although it is reasonable to consider a form of targeted screening of those most likely to develop nAMD, it is unclear if those invited would adhere to such a programme.<br><br>METHODS: In this randomized controlled trial, 130 participants will be recruited from community-based eye healthcare practices within the UK whilst attending their routine appointment. Participants will be randomized to either a standard care arm to attend a further follow-up appointment at 12&#xa0;months, or an intervention arm, attending every 3&#xa0;months for assessment. The end of study is at 12&#xa0;months. All participants will complete the NEI-VFQ-25, MacDQoL, PHQ9 and EQ-5D-3L questionnaires at baseline and 12&#xa0;months. In addition, all participants and recruiting investigators will complete the Theoretical Framework of Acceptability questionnaire at 12&#xa0;months.<br><br>DISCUSSION: The DORADO study aims to assess the persistence and adherence to and acceptability of a community-based programme for the early detection of nAMD.<br><br>TRIAL REGISTRATION: ISRCTN10005321. Registered on 08 November 2024.}, }
@article {pmid41466814, year = {2025}, author = {Awan, B and Elsaigh, M and Hesham Gamal, M and Elbahnasawy, SE and Badee, M}, title = {Integrating Human Expertise With Artificial Intelligence (AI) Models for Optical Coherence Tomography (OCT) Retinal Fluid and Pathology Quantification: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e100223}, pmid = {41466814}, issn = {2168-8184}, abstract = {Artificial intelligence (AI) and intensive learning show promise in ophthalmology, using optical coherence tomography (OCT) to diagnose conditions such as diabetic retinopathy. However, precise segmentation of retinal fluid remains challenging, especially in atypical cases and low-quality scans. In hospital settings, manual segmentation is time-consuming; however, integrating human expertise with AI could improve efficiency and accuracy in quantifying retinal pathologies. This review assesses the efficacy of human-AI collaborative workflows for enhancing the accuracy, efficiency, and clinical utility of retinal pathology quantification in OCT. We conducted a systematic review of the literature from 2021 to 2025 across three databases: PubMed, Web of Science, and Scopus. This review included nine studies that quantified retinal pathology using human-AI collaborative workflows in OCT. Two independent reviewers screened the records, extracted relevant data, including study design, AI architecture, and performance metrics, and assessed the quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies - 2nd version (QUADAS-2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. This systematic review of nine AI-OCT studies (2021-2025) found that hybrid AI-clinician workflows achieved expert-level reliability for 11 of 13 retinal biomarkers across cohorts of 16-1,097 individuals. AI architectures, including U-Net variants, polypoidal choroidal vasculopathy (PCV)-Net, and custom convolutional neural networks (CNNs), performed well for well-defined features such as retinal layers (Dice 0.94), intraretinal/subretinal fluid (Dice 0.61-0.67), and atrophic areas (F1 0.78-0.89), but struggled with complex biomarkers like sub-retinal pigment epithelium (sub-RPE) lesions (Dice 0.11). Clinician agreement on fluid volumes was strong (Pearson r > 0.85), though volumetric errors increased in atrophic regions. These workflows reduced processing time by over 50% compared with manual grading while improving monitoring precision for neovascular age-related macular degeneration (AMD) and retinitis pigmentosa complications in both single-center and international trial settings. Combining AI quantification with clinician expertise enhances both the accuracy and efficiency of retinal pathology assessments. This integration supports personalized treatment planning and facilitates large-scale research. Hybrid approaches address AI's limitations, highlighting their practicality for clinical use in ophthalmology. We suggest incorporating hybrid AI-human workflows in clinical practice to improve the efficiency and accuracy of OCT analysis. Future developments in AI should focus on standardized training for complex biomarkers, such as sub-RPE lesions.}, }
@article {pmid41466880, year = {2025}, author = {Zhang, J and Xia, T and Zhang, D and Yang, X}, title = {Exploring the Link Between Sleep Duration and Visual Impairment and Major Eye Diseases: National Health and Nutrition Examination Survey 2005-2008.}, journal = {BioMed research international}, volume = {2025}, number = {}, pages = {1229050}, pmid = {41466880}, issn = {2314-6141}, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Vision Disorders/epidemiology/physiopathology ; *Eye Diseases/epidemiology/physiopathology ; Nutrition Surveys ; *Sleep/physiology ; Adult ; Cross-Sectional Studies ; Prevalence ; Glaucoma/epidemiology/physiopathology ; United States/epidemiology ; Visual Acuity ; Sleep Duration ; }, abstract = {OBJECTIVE: This study is aimed at investigating the association between sleep duration and visual impairment, as well as its relationship with major eye diseases, using data from a large-scale population-based survey.<br><br>METHODS: This cross-sectional study investigated the prevalence of visual impairment and major eye conditions among 5231 individuals aged 40 and older, utilizing data from the NHANES 2005-2008 survey. Sleep duration was categorized as short (<&#x2009;7&#x2009;h), normal (7-9&#x2009;h), and long (>&#x2009;9&#x2009;h). Visual impairment was defined as corrected visual acuity <&#x2009;20/40, and major eye diseases included cataract surgery, diabetic retinopathy, age-related macular degeneration, glaucoma, any retinopathy, any ocular disease, and any objectively determined ocular disease. Univariate and multivariate logistic regression were used to assess associations between sleep duration, visual impairment, and major eye diseases. Stratified analyses were further conducted based on diabetes and hypertension status.<br><br>RESULTS: The long sleep group demonstrated a significantly higher prevalence of vision impairment, cataract surgery, glaucoma, as well as any ocular disease and any objectively determined ocular disease compared to the normal and short sleep groups (all p < 0.05). After adjusting for confounders, long sleep duration was significantly associated with visual impairment (OR: 2.44, 95% CI: 1.09-5.49, p = 0.035), glaucoma (OR: 3.38, 95% CI: 1.06-10.8, p = 0.042), and any objectively determined ocular disease (OR: 2.24, 95% CI: 1.08-4.65, p = 0.035). No significant associations were found between short sleep duration and visual impairment or major eye diseases after controlling for confounders. In the nondiabetic population, long sleep was significantly related to glaucoma, any objectively determined ocular disease, and visual impairment. Among hypertensive patients, long sleep was associated with glaucoma.<br><br>CONCLUSION: Long sleep duration is independently associated with visual impairment, glaucoma, and any objectively determined ocular disease. Longitudinal studies are needed to validate current results and explore causal mechanisms.}, }
@article {pmid41467621, year = {2025}, author = {Martins Teixeira, L and Barbosa, MG and Menezes de Faria, F and Ramos, AA and Suemoto, CK and de Moraes Rebello Pinho, PJ and Lima Costa, MF and Ferri, CP}, title = {Association between visual impairment and dementia in older Brazilian adults: findings from the ELSI-Brazil study.}, journal = {Aging &amp; mental health}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/13607863.2025.2606363}, pmid = {41467621}, issn = {1364-6915}, abstract = {OBJECTIVE: To investigate the association between visual impairment (VI)-including self-reported near and distance vision and common ophthalmologic conditions-and dementia in a nationally representative sample of older Brazilian adults.<br><br>METHODS: This study is a secondary analysis using baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), which surveyed 5,249 individuals aged 60&#x2009;years and older. Dementia was identified using an algorithm based on cognitive and functional performance. Visual status was assessed through self-report, distinguishing near and distance VI, along with self-reported diagnoses of ophthalmologic conditions. Logistic regression models adjusted for sociodemographic, clinical, and lifestyle variables were used.<br><br>RESULTS: Dementia was identified in 364 participants (6.9%). Distance VI was associated with dementia (adjusted OR: 1.68; 95% CI: 1.56-2.44), and there was a significant linear trend between worse self-reported distance vision and greater odds of dementia (p&#x2009;=&#x2009;0.003). Neither near VI nor any specific ophthalmologic conditions (cataract with/without surgery, glaucoma, macular degeneration, or diabetic retinopathy) were associated with dementia in the adjusted models.<br><br>CONCLUSION: In this nationally representative sample, self-reported distance VI was associated with dementia. This finding may indicate both a modifiable risk factor and an early marker of cognitive decline, warranting longitudinal research.}, }
@article {pmid41467813, year = {2026}, author = {Zhu, J and Yu, X and Wen, C and Zhang, Y and Kuang, X and Sun, N and Tang, S and Xiao, B and Xiao, S and Wang, X and Wu, K and Zhang, Q and Shen, H}, title = {Thalidomide Synergistically Regulates Cell Cycle and Endoplasmic Reticulum Stress to Alleviate RPE Oxidative Damage Through the E2F2-FBXO5 Pathway.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {1}, pages = {e71387}, doi = {10.1096/fj.202502444R}, pmid = {41467813}, issn = {1530-6860}, support = {2024A1515013099//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2024A03J0264//Scientific and Technological Planning Project of Guangzhou City ()/ ; 2025QZLH06//State Key Laboratory of Ophthalmology (SKLO)/ ; }, mesh = {*Endoplasmic Reticulum Stress/drug effects ; Animals ; *Oxidative Stress/drug effects ; *Thalidomide/pharmacology ; Mice ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; Signal Transduction/drug effects ; *E2F2 Transcription Factor/metabolism ; *Cell Cycle/drug effects ; Mice, Inbred C57BL ; Macular Degeneration/metabolism/drug therapy/pathology ; Male ; }, abstract = {Thalidomide, a glutamate derivative with teratogenicity, possesses anti-inflammatory, immunomodulatory, and anti-angiogenic properties that enable its use in treating refractory diseases unresponsive to conventional therapies. Dry age-related macular degeneration (AMD), characterized by retinal pigment epithelium (RPE) degeneration and lacking effective therapies, represents a significant unmet medical need. Our findings demonstrated that thalidomide significantly restores mitochondrial function, alleviates G2/M phase cell cycle arrest, and suppresses sustained endoplasmic reticulum (ER) stress in oxidatively injured RPE cells. Mechanistically, these effects are coordinated through E2F2 activation, which subsequently regulates FBXO5 expression. Moreover, thalidomide was able to ameliorate oxidative stress-induced retinal structural disorders and RPE degeneration, and improve visual function in mice. In summary, this study elucidates that thalidomide synergistically regulates cell cycle progression and endoplasmic reticulum homeostasis through the E2F2-FBXO5 signaling pathway, providing a new drug candidate and therapeutic target for the prevention and treatment of dry AMD.}, }
@article {pmid41468573, year = {2026}, author = {Spaide, RF}, title = {Pilot Study of Choroidal Synphlebia.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {3}, pages = {410-416}, pmid = {41468573}, issn = {1539-2864}, mesh = {Humans ; Male ; Middle Aged ; Retrospective Studies ; Female ; *Tomography, Optical Coherence/methods ; Pilot Projects ; *Choroid/blood supply ; Aged ; Fluorescein Angiography/methods ; *Central Serous Chorioretinopathy/diagnosis ; Fundus Oculi ; Visual Acuity ; Multimodal Imaging ; Adult ; Aged, 80 and over ; }, abstract = {PURPOSE: To describe the multimodal imaging characteristics and clinical associations of choroidal synphlebia, a newly recognized configuration of the choroidal venous system.<br><br>METHODS: This retrospective study analyzed patients imaged with the DREAM swept-source OCT system (Intalight, San Jose, CA), capable of deep choroidal penetration. Choroidal synphlebia was defined as a confluent vascular structure &#x2265;750 &#xb5; m in smallest lateral or vertical dimension. The multimodal imaging characteristics were evaluated.<br><br>RESULTS: Nineteen eyes of 16 patients (mean age 63.2 years; eight male) were identified. Associated diagnoses included central serous chorioretinopathy in 16 eyes, neovascular age-related macular degeneration in 2, and myopia in 1. Three patients had bilateral involvement. Two morphologic patterns were observed: (1) broad confluence of large choroidal veins forming a lobulated venous lake and (2) a caput medusa-type arrangement with smaller tributaries converging radially into a dilated central channel. The lesions often occurred near presumed choroidal watershed zones. Macular neovascularization was present in seven eyes. In several central serous chorioretinopathy cases, subretinal fluid was resistant to photodynamic therapy but responsive to faricimab.<br><br>CONCLUSION: Choroidal synphlebia represents a distinct choroidal venous phenotype characterized by fusion or coalescence of major veins with a lack of visible vessels in the overlying Sattler's layer and inner choroid. Alterations in the capacitance, resistance, and pressure distribution in the venous drainage system appear to be affected by synphlebia lesions. Recognition of synphlebia may provide insight into choroidal hemodynamics and may help explain atypical or treatment-resistant central serous chorioretinopathy and neovascular presentations.}, }
@article {pmid41469343, year = {2025}, author = {Fedirko, PA and Babenko, TF and Pilmane, M and Medvedovska, NV and Junga, A and Yaroshenko, ZS and Dorichevska, RY and Garkava, NA}, title = {CURRENT ACHIEVEMENTS AND TOPICAL ISSUES IN RADIATION OPHTHALMOLOGY: POST-CHORNOBYL EXPERIENCE.}, journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii}, volume = {}, number = {30}, pages = {126-142}, doi = {10.33145/2304-8336-2025-30-126-142}, pmid = {41469343}, issn = {2313-4607}, mesh = {*Chernobyl Nuclear Accident ; Humans ; *Cataract/etiology/pathology/epidemiology ; *Radiation Exposure/adverse effects ; *Radiation Injuries/epidemiology/pathology/etiology ; Ukraine/epidemiology ; Radiation, Ionizing ; Occupational Exposure/adverse effects ; *Ophthalmology/trends ; *Eye/radiation effects/pathology ; }, abstract = {The Chornobyl disaster - a largescale nuclear accident that caused significant radiation exposure to large populations of people. The work of ophthalmologists who studied its consequences radically changed scientists' understanding of the effects of ionizing radiation on the organ of vision. Before the Chornobyl accident, it was widely believed that the organ of vision was relatively resistant to the effects of ionizing radiation. It was thought that the most likely effect of radiation exposure was radiation cataracts, which were considered a deterministic effect.The objective of this study is analyze epidemiological, clinical, and experimental data on the ophthalmologicaleffects of radiation obtained after the Chоrnobyl disaster. Materials and methods. The criteria for inclusion in the analytical review were peer reviewed publications in the scientometric databases PubMed/MEDLINE, Scopus, Web of Science, and manually selected works devoted to the study of the ophthalmological consequences of the Chornobyl disaster, other radiation incidents, and the consequences of occupational radiation exposure, published in the period after the Chornobyl disaster.Results. Studies conducted after the Chornobyl disaster have significantly changed the understanding of theeffects of ionizing radiation on the vision organ. It has been shown that the eye is extremely sensitive to radiation exposure and is one of the most vulnerable structures of the body. Analyzing the results of longterm post-Chornobyl studies, we can distinguish four groups of ophthalmological diseases that occur in people affected by the Chornobyl disaster: the first group is specific radiation damage to the eye, the appearance of which is possible only as a result of ionizing radiation exposure; the second group is diseases that under normal conditions occur mainly in elderly people and the development of which is accelerated as a result of radiation exposure; the third group is functional changes that were detected in radiationexposed people; and the fourth group includes effects that occurred in people irradiated in utero.}, }
@article {pmid41469516, year = {2025}, author = {Li, D and Ou, Q and Gao, F and Wang, X and Zhu, L and Zhou, Y and Xu, JY and Jin, C and Wang, J and Zhang, J and Li, J and Bi, Y and Lu, L and Xu, GT and Tian, H}, title = {CRX is an intrinsic suppressor of epithelial‒mesenchymal transition in retinal pigment epithelial cells: a promising therapeutic avenue for subretinal fibrosis.}, journal = {Cell death &amp; disease}, volume = {17}, number = {1}, pages = {156}, pmid = {41469516}, issn = {2041-4889}, support = {24ZR1470100//Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)/ ; }, mesh = {*Epithelial-Mesenchymal Transition/genetics ; Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; Fibrosis ; *Trans-Activators/metabolism/genetics ; *Homeodomain Proteins/metabolism/genetics ; Mice ; Signal Transduction ; Macular Degeneration/pathology/metabolism/genetics ; Transforming Growth Factor beta1/metabolism/pharmacology ; Choroidal Neovascularization/pathology/metabolism/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Epithelial Cells/metabolism ; beta Catenin/metabolism ; YAP-Signaling Proteins ; }, abstract = {The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is one of the significant pathogenic mechanisms for the formation of subretinal fibrosis in age-related macular degeneration (AMD). Multiple signaling pathways that promote EMT have been well described, yet the endogenous signaling pathways that inhibit EMT within RPE cells remain largely elusive. In this study, we confirmed the expression of CRX in human RPE cells and human embryonic stem cell-derived RPE (ESC-RPE) cells. By employing sub-culture to disrupt intercellular connections and thereby inhibit the Hippo signaling pathway, combined with TGF-β1 treatment in vitro to mimic the microenvironment for the formation of subretinal fibrosis, it was revealed that Hippo/YAP1 and TGF-β1 synergistically promoted the nuclear translocation of β-catenin, and the latter bound to TCF7 to inhibit the expression of CRX. Overexpression of CRX was capable of suppressing the occurrence of EMT in ESC-RPE cells. CRX exerted its inhibitory effect on EMT partly by upregulating the expression of PPP2R2B. In the laser-induced choroidal neovascularization mouse model, the nuclear translocation of CRX took place in RPE cells, and overexpression of CRX played an inhibitory role in the formation of subretinal fibrosis. This study has identified CRX as an endogenous signaling molecule that inhibits EMT in RPE cells and has provided a new research target and treatment strategy for the treatment of wet AMD and the inhibition of subretinal fibrosis formation.}, }
@article {pmid41470194, year = {2025}, author = {Busquets, MA and Garfinkel, RA and Sambhara, D and Mohan, N and Nahen, K and Benyamini, G and Loewenstein, A}, title = {Home Monitoring for the Management of Age-Related Macular Degeneration: A Review of the Development and Implementation of Digital Health Solutions over a 25-Year Scientific Journey.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470194}, issn = {1648-9144}, mesh = {Humans ; *Macular Degeneration/therapy/diagnosis ; Telemedicine/trends ; Monitoring, Physiologic/methods ; Digital Health ; }, abstract = {The management of age-related macular degeneration (AMD) presents a significant challenge attributable to high disease heterogeneity. Patient realization of symptoms is poor and it is urgent to treat before permanent anatomic damage results in vision loss. This is true for the initial conversion from non-exudative intermediate AMD (iAMD) to exudative AMD (nAMD), and for the recurrence of nAMD undergoing treatment. Starting from the essential requirements that any practical solution needs to fulfill, we will reflect on how persistent navigation towards innovative solutions during a 25-year journey yielded significant advances towards improvements in personalized care. An early insight was that the acute nature of AMD progression requires frequent monitoring and therefore diagnostic testing should be performed at the patient's home. Four key requirements were identified: (1) A tele-connected home device with acceptable diagnostic performance and a supportive patient user interface, both hardware and software. (2) Automated analytics capabilities that can process large volumes of data. (3) Efficient remote patient engagement and support through a digital healthcare provider. (4) A low-cost medical system that enables digital healthcare delivery through appropriate compensation for both the monitoring provider and the prescribing physician services. We reviewed the published literature accompanying first the development of Preferential Hyperacuity Perimetry (PHP) for monitoring iAMD, followed by Spectral Domain Optical Coherence Tomography (SD-OCT) for monitoring nAMD. Emphasis was given to the review of the validation of the core technologies, the regulatory process, and real-world studies, and how they led to the release of commercial services that are covered by Medicare in the USA. We concluded that while during the first quarter of the 21st century, the two main pillars of management of AMD were anti-VEGF intravitreal injections and in-office OCT, the addition of home-monitoring-based digital health services can become the third pillar.}, }
@article {pmid41470237, year = {2025}, author = {Anitua, E and Muruzabal, F and Recalde, S and de la Fuente, M and Reparaz, I and Azkargorta, M and Elortza, F and Alkhraisat, MH}, title = {Proteomic Insights into the Retinal Response to PRGF in a Mouse Model of Age-Related Macular Degeneration.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {12}, pages = {}, pmid = {41470237}, issn = {1648-9144}, support = {ZL-2021/00557//Basque Government/ ; }, mesh = {Animals ; Mice ; Disease Models, Animal ; *Proteomics/methods ; Mice, Inbred C57BL ; *Macular Degeneration/physiopathology/drug therapy ; *Retina/drug effects/physiopathology ; *Intercellular Signaling Peptides and Proteins/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Iodates ; Oxidative Stress/drug effects ; Geographic Atrophy ; }, abstract = {Background and Objectives: The aim of this study is to employ quantitative proteomics to elucidate the molecular mechanism and signaling pathways modulated by plasma rich in growth factors (PRGF) in a murine model of geographic atrophy (GA)-like retinal degeneration. Materials and Methods: C57BL/6J mice were used as a model GA-like retinal degeneration by a single systemic NaIO3 administration. Animals were divided into three groups: Control (PBS), Disease (NaIO3 + PBS), and PRGF-treated (NaIO3 + PRGF). After 7 days, retinas and retinal pigment epithelium were collected for proteomic analysis. Proteins were extracted, digested using the FASP method, and analyzed by Data-Independent Acquisition (DIA-PASEF) mass spectrometry; data were processed with DIA-NN and statistically analyzed with Perseus. Functional pathway analysis was performed using Ingenuity Pathway Analysis. Results: A total of 6511 proteins were identified. The Disease model showed the expected deregulation of pathways related to oxidative stress, inflammation, and fibrosis. Comparison between the PRGF and Control groups showed that PRGF significantly reduced oxidative and cellular stress proteins/pathways. In the same way, when PRGF and Disease groups were compared, PRGF treatment showed a significant reduction in pathways associated with inflammation, oxidative stress, and cellular stress. PRGF also activated several homeostatic pathways not only related to neuroprotective pathways but also with the lipid deposition (drusen) reduction. All these results suggest that PRGF treatment exerts a protective effect against NaIO3-induced retinal damage. Conclusions: These findings suggest that PRGF effectively mitigates the degenerative effects of NaIO3 by activating specific protective and compensatory signaling pathways in the retina. PRGF is indicated as a promising new therapeutic option for ameliorating age-related macular degeneration progression.}, }
@article {pmid41471372, year = {2025}, author = {Park, S and Won, J and Heo, JB and Kang, J and Oh, YW and Park, G and Lee, G and Lee, JH and Song, GY and Kang, W and Oh, S}, title = {The Therapeutic Effect of a Biodegradable Long-Acting Intravitreal Implant Containing CGK012 on Neovascular Age-Related Macular Degeneration by Promoting β-Catenin Degradation.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {12}, pages = {}, pmid = {41471372}, issn = {1424-8247}, support = {RS-2023-00259081//Ministry of Science and ICT, Ministry of Trade, IndKorea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfareustry, and Energy, and Ministry of Health and Welfare/ ; }, abstract = {Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants' in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial-mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28-42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment.}, }
@article {pmid41472698, year = {2025}, author = {Keim, D and Dehne, M and Miller, P and Jérôme, V and Bahnemann, J and Freitag, R}, title = {High-Efficiency l‑PEI-Based Transfection of ARPE-19 Cells Using a Multiparametric Approach and Automated Polyplex Formation with a 3D-Printed Microfluidic System.}, journal = {Chem &amp; bio engineering}, volume = {2}, number = {12}, pages = {695-710}, pmid = {41472698}, issn = {2836-967X}, abstract = {Nonviral gene delivery offers promise for treating age-related macular degeneration (AMD), a major cause of blindness. Genetic modification of retinal pigment epithelium (RPE) cells is a potential therapeutic strategy for AMD. This study presents a multiparametric approach to enhance nonviral transfection of human ARPE-19 cells using linear poly-(ethylenimine) (l-PEI, 25 kDa) as a delivery agent for plasmid DNA (pDNA). The transfection protocol was optimized by adjusting the N/P ratio through nucleic acid concentration, varying polymer density, reducing transfection volume, and minimizing contact time between cells and polyplexes. Under optimized conditions, transfection efficiency (TE) reached 88% with ∼85% viability. A semi-automated method for polyplex formation was developed using a 3D-printed microfluidic system, thereby enabling standardized production. This optimized protocol was successfully adapted to the microfluidic system without compromising TE or viability. This semi-automated approach represents a step toward the scalable and reproducible application of l-PEI-based transfection technologies for future therapeutic use.}, }
@article {pmid41475545, year = {2025}, author = {Sun, D and Tseng, VL and Yu, F and Coleman, AL}, title = {Cardiovascular Risk and Eye Health: A Cohort Study of the Pooled Cohort Equations and Ocular Disease Incidence.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2025.12.021}, pmid = {41475545}, issn = {1549-4713}, abstract = {PURPOSE: We assessed whether the Pooled Cohort Equations (PCE) cardiovascular risk score, used in primary care, is associated with the future age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), retinal vein occlusion (RVO), and hypertensive retinopathy (HTR).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: We used electronic health record data from the All of Us (AoU) Research Program. Participants aged 40 to 79 years had to have complete variables for PCE calculation within a 6-month period between 2009 and 2015. We excluded participants with preexisting atherosclerotic cardiovascular disease or any of the 5 ocular diseases before the baseline PCE period. A total of 35 909 adults were included in this study.<br><br>METHODS: Individual-level PCE score was computed and categorized into 4 PCE risk categories: low (<5%), borderline (5%-7.4%), intermediate (7.5%-19.9%), and high (&#x2265;20%). Time-to-event analyses included Kaplan-Meier curves and univariate and multivariable Cox proportional hazards regression models. The primary multivariable models adjusted for race, body mass index, chronic kidney disease, and education (not included in PCE to avoid overadjustment). Concordance index (C-index) was reported to assess model performance. Sensitivity analyses tested varied follow-up durations (5, 6, and 7 years) and, in a prespecified component-adjustment sensitivity set, sequentially added PCE components (age, smoking, diabetes).<br><br>MAIN OUTCOME MEASURES: Diagnoses of AMD, glaucoma, DR, RVO, or HTR.<br><br>RESULTS: Higher PCE risk categories were significantly associated with increased risk of ocular diseases. In the primary models, compared with the low-risk group, the high-risk group had the highest hazard ratios for AMD (6.22), DR (5.93), glaucoma (2.33), RVO (3.38), and HTR (4.47) (all P < 0.001). Adjusted C-indices were highest for AMD (0.72), DR (0.751), and HTR (0.768), and moderate for glaucoma (0.625) and RVO (0.654). Findings were consistent in different follow-up periods. In component-adjustment sensitivity models, PCE-AMD association was largely explained by age, whereas associations for DR and HTR remained robust.<br><br>CONCLUSIONS: In the AoU population, the single composite metric PCE meaningfully stratifies future risk for multiple ocular diseases, using information already available in primary care. This suggests PCE could be incorporated into primary care settings to identify individuals who would benefit from earlier ophthalmologic evaluation and prevention strategies.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.}, }
@article {pmid41475683, year = {2025}, author = {Bianchi, MJ and Sunness, JS and Applegate, CA}, title = {Reading Speed Patterns in Eyes with Geographic Atrophy and Good Visual Acuity.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2025.12.020}, pmid = {41475683}, issn = {2468-6530}, }
@article {pmid41476611, year = {2025}, author = {Raghavan, D and Jeakle, O and Berry, Y and Victor, M and Thummel, R}, title = {Microglia response and function in a chronic model of photoreceptor damage.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1699271}, pmid = {41476611}, issn = {2296-634X}, abstract = {BACKGROUND: Retinal neurodegenerative diseases, including diabetic retinopathy and age-related macular degeneration, are characterized by the slow, chronic degeneration of photoreceptors. We previously used a chronic low light (CLL) exposure to model slow photoreceptor degeneration in adult zebrafish. Here, we investigate transcriptional, morphological, and functional responses of microglia in the CLL model.<br><br>METHODS: Microglia-specific gene expression analysis was mined from our previously reported 3' RNA-seq data performed at 8 time points during 28 days of CLL exposure. Morphological changes were performed on retinas collected at various time points using immunohistochemistry. Microglial inhibition was accomplished pharmacologically with dexamethasone and genetically using the irf8-/- mutant fish. Finally, we returned the CLL-treated fish to normal light/dark conditions to test whether photoreceptors could recover in the context of chronic stress.<br><br>RESULTS: CLL induced dynamic, time-dependent upregulation of microglia-specific genes consistent with pro-inflammatory and pro-resolving function. Dexamethasone treatment reduced microglial numbers and exacerbated rod and cone outer segment damage, whereas irf8-/- mutants exhibited partial protection against photoreceptor damage. Notably, despite prolonged stress and damage during the CLL exposure, photoreceptor outer segments returned to near-baseline morphology after 28 days of normal light/dark recovery conditions.<br><br>DISCUSSION: Overall, these findings suggest that microglial function in chronic retinal injury is context-dependent as pharmacological and genetic methods of inhibition produced contrasting outcomes depending upon microglial polarization.}, }
@article {pmid41479851, year = {2025}, author = {Zhang, E and Bylund, R and Zhang, A and Massop, D}, title = {Alpha-Gal Syndrome Allergy to Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264251400700}, pmid = {41479851}, issn = {2474-1272}, abstract = {Purpose: To describe a case of allergic reaction to intravitreal (IVT) injection of antivascular endothelial growth factor (anti-VEGF) medications in patients with alpha-gal syndrome. Methods: A single case was evaluated. Results: A 57-year-old woman with a known diagnosis of alpha-gal syndrome was evaluated. Clinical presentation, prior treatment history, and response to different anti-VEGF agents were reviewed. The patient presented with worsening vision in her right eye due to a subfoveal choroidal neovascular membrane secondary to neovascular age-related macular degeneration in the right eye. She had experienced a systemic allergic reaction following an IVT injection of bevacizumab, but subsequently tolerated ranibizumab without any adverse effects, resulting in improvement in her vision. Conclusions: Bevacizumab, aflibercept, and faricimab are recombinant immunoglobulins produced by DNA technology in Chinese hamster ovary cells, which may contain galactose-α-1,3-galactose (alpha-gal), a potential allergen for patients with alpha-gal syndrome. Patients with alpha-gal syndrome may develop allergic reactions to certain IVT anti-VEGF agents derived from mammalian expression systems. Ranibizumab, produced using an Escherichia coli expression and lacking alpha-gal, seems to be a safe and effective option for patients with alpha-gal syndrome requiring IVT anti-VEGF therapy.}, }
@article {pmid41479867, year = {2025}, author = {Priyanka, P and Khullar, S and Singh, M and Morya, AK and Sharma, B and Periasamy, B and Moharana, B and Morya, R}, title = {Role of gut microbiomes in different ocular pathologies: A systematic review.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {4}, pages = {113488}, pmid = {41479867}, issn = {2150-5330}, abstract = {BACKGROUND: The gut microbiome is integral to human health, with emerging research underscoring its potential impact on ocular health through the gut-eye axis. Various ocular disorders, such as dry eye syndrome, retinal vascular diseases, macular degeneration, and glaucoma, may be influenced by gut dysbiosis, which could significantly contribute to their development and progression.<br><br>AIM: To evaluate the influence of the gut microbiome on the pathogenesis and progression of various ocular diseases.<br><br>METHODS: An extensive search of the scientific literature was undertaken by adhering to Preferred Reporting Items for Systematic Reviews &amp; Meta-Analyses standards, using PubMed (MEDLINE), Scopus, EMBASE, and the Cochrane Library as sources to locate studies addressing the relationship between the gut microbiome and human health. To capture all relevant publications, search terms were systematically applied across these major databases, without limiting the search by language or publication date. Inclusion criteria covered randomized controlled trials, non-randomized controlled trial, prospective studies, cross-sectional studies, and case-control studies. Out of the 3077 articles, 36 full texts were included in the review.<br><br>RESULTS: Ocular health appears to be shaped by the gut microbial community through mechanisms such as immune regulation, preservation of the blood-retinal barrier, and the generation of protective metabolites. Disturbances in this microbial balance can provoke measurable alterations in host immunity, providing a plausible immunopathogenic pathway that connects intestinal dysbiosis with eye disease. Both laboratory models and early human data suggest that targeted interventions, including prebiotics, probiotics, synbiotics, and faecal microbiota transfer, hold therapeutic potential.<br><br>CONCLUSION: The gut-eye relationship reflects a multifaceted interaction in which the intestinal microbiome contributes to ocular health through complex biological pathways. Integrating microbiome assessments into diagnostic methods can revolutionize disease management through early detection and targeted interventions. Further, randomised controlled clinical trials are necessary for ocular diseases to prove causal relationships.}, }
@article {pmid41480395, year = {2025}, author = {Zeppieri, M and Visalli, F and Musa, M and Avitabile, A and Giglio, R and Tognetto, D and Gagliano, C and D'Esposito, F and Cappellani, F}, title = {Novel developments in retinal regeneration: Advances and future outlooks in stem cell therapy.}, journal = {World journal of stem cells}, volume = {17}, number = {12}, pages = {111374}, pmid = {41480395}, issn = {1948-0210}, abstract = {Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt disease, are primary contributors to irreversible vision loss globally. Due to the scarcity of effective curative treatments, stem cell therapy has emerged as a revolutionary advancement in ophthalmology. In the last ten years, significant advancements have been achieved in the derivation of retinal pigment epithelium and photoreceptor precursors from human embryonic stem cells and induced pluripotent stem cells, with initial clinical trials indicating safety and potential efficacy. Innovative delivery platforms, such as biodegradable scaffolds, microcarrier suspensions, and minimally invasive subretinal devices, are tackling prior challenges related to cell survival and integration. Simultaneously, gene-edited and patient-specific induced pluripotent stem cells are positioned to surmount immunological and ethical constraints. Future combinatorial strategies that incorporate stem cells with gene therapy, CRISPR-mediated editing, and bioengineered retinal organoids offer potential for personalized and regenerative methodologies. Nonetheless, enduring functional integration, immune tolerance, and oncogenic safety continue to pose significant challenges. To effectively transition from laboratory research to clinical application, collaborative frameworks among academic institutions, biotechnology companies, and regulatory agencies will be crucial for unlocking the complete therapeutic potential of stem cell-based treatments for retinal diseases. Stem cell therapy has transitioned from a distant promise to an advancing reality set to transform retinal care.}, }
@article {pmid41480686, year = {2026}, author = {Oltra, M and Martínez-Santos, M and Ybarra, M and Pires, M and Ceresoni, C and Gomis-Coloma, C and Medina-Trillo, C and Sancho, J and Barcia, J}, title = {miR‑205: A dual regulator of angiogenesis in health and disease (Review).}, journal = {International journal of molecular medicine}, volume = {57}, number = {2}, pages = {}, pmid = {41480686}, issn = {1791-244X}, mesh = {*MicroRNAs/genetics/metabolism ; Humans ; *Neovascularization, Pathologic/genetics/metabolism ; Animals ; Extracellular Vesicles/metabolism/genetics ; *Neovascularization, Physiologic/genetics ; Cell Proliferation ; Angiogenesis ; }, abstract = {The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding sequences that regulate gene expression at the post‑transcriptional level and can be transported in extracellular vesicles (EVs), allowing them to modulate biological processes remotely. miR‑205 is involved in multiple cellular processes, such as proliferation, migration, apoptosis and angiogenesis. In angiogenesis its function is contradictory: On one hand, it can inhibit blood vessel formation by suppressing pro‑angiogenic factors such as VEGF and ANG‑2, as demonstrated in diseases such as psoriasis, thyroid cancer and diabetic retinopathy. However, in other contexts, miR‑205 promotes angiogenesis by inhibiting anti‑angiogenic genes such as PTEN and HITT, facilitating the activation of the PI3K/AKT pathway and cell proliferation in ovarian cancer and thrombosis. Additionally, the present study highlighted the role of EVs in transferring miR‑205 between cells, thereby influencing angiogenesis and disease progression. Studies in myocardial infarction and cancer models have demonstrated that EVs enriched in miR‑205 can affect blood vessel formation and tumor progression. Similarly, in ocular diseases such as macular degeneration and diabetic retinopathy, miR‑205 encapsulated in EVs has shown therapeutic potential by regulating VEGF levels. In conclusion, miR‑205 emerges as a promising therapeutic target for angiogenic diseases. Its application in EV‑based therapy could represent an innovative strategy for treating vascular disorders. However, further studies are needed to fully understand its mechanisms of action and optimize its clinical application.}, }
@article {pmid41481850, year = {2025}, author = {Yuan, M and Alsoudi, A and Alshaikhsalama, A and Rahimy, E}, title = {Systemic medications and their impact on age-related macular degeneration development and progression: a review of current evidence.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001198}, pmid = {41481850}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: This review examines commonly prescribed systemic medications and their possible associations with age-related macular degeneration (AMD) development and progression. With the limitations and risks of current intravitreal therapies, there is growing interest in oral pharmacotherapy for AMD management. The following review synthesizes observational studies, meta-analyses, and ongoing clinical trials to evaluate the potential effects of commonly used systemic medications on AMD.<br><br>RECENT FINDINGS: Metformin demonstrates conflicting evidence, with several meta-analyses and large cohort study showing reduced AMD odds, while a recent randomized phase II trial found no effect on geographic atrophy progression. For statins, emerging evidence suggests that treatment duration exceeding 2&#x200a;years and medium-intensity to high-intensity dosing may confer protection against AMD development. Aspirin demonstrates discordant results between different study designs: two large randomized controlled trials showed no benefit for AMD, while a 10-year observational study suggested protective effects.Fenofibrates show promise in preclinical models but require additional clinical investigation. Danicopan also shows modest effects in complement-related disorders and is currently undergoing a phase 2 trial to evaluate efficacy in patients with geographic atrophy. Finally, dopamine agonists appear to improve visual acuity and reduce subretinal fluid and central retinal thickness in newly diagnosed exudative AMD, as shown in an open-label pilot study, but require further investigation.<br><br>SUMMARY: Multiple systemic medications have highlighted mixed or stage-dependent benefits on AMD development and progression. Some agents such as metformin and aspirin have shown conflicting findings, having been evaluated in randomized trials and large observational studies. Other medications including GLP-1 agonists, dopamine agonists, statins, fenofibrates, and danicopan show early promise in more limited studies, but require further clinical validation.}, }
@article {pmid41482136, year = {2025}, author = {Bala, S and Allan, KC and Decker, NL and Abbass, NJ and Joo, JH and Zhao, A and Talcott, KE and Rachitskaya, AV}, title = {Glucagon-like peptide-1 receptor agonists: What ophthalmologists need to know.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2025.12.007}, pmid = {41482136}, issn = {1879-3304}, abstract = {Initially designed for the treatment of type-2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RA) are multifaceted agents with promising neuroprotective and anti-inflammatory properties. The majority of the research exploring the relationship between GLP-1RA use and ophthalmic disease comes from large database studies or secondary-analysis of randomized controlled trials investigating GLP-1RAs in cardiovascular disease and obesity. Current evidence regarding the impact of GLP-1 receptor agonists on ophthalmic diseases remains inconsistent, with studies reporting both protective and detrimental effects. For example, there are conflicting findings of an effect on diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy, as well as age-related macular degeneration, with GLP-1RA use. In contrast, GLP-1RAs have more consistently demonstrated a protective effect against idiopathic intracranial hypertension, glaucoma and dry-eye disease. Importantly, the majority of the clinical ophthalmic studies are from large electronic health record databases. Overall, limitations in the design of these studies, such as the lack of manual chart review and potential miscoding of diagnosis or treatments, prohibit a more granular analysis of comprehensive ocular endpoints. As a heterogenous medication class with differing structures, potencies, and mechanisms of action, we outline the ophthalmic effects of all Food and Drug Administration-approved GLP-1RAs. We discuss the proposed mechanisms of ocular effects and GLP-1RA use, examine the current literature investigating the impact of GLP-1RAs on ophthalmic disease, discuss the effects of specific GLP-1RAs, and outline the perioperative considerations of this medication class.}, }
@article {pmid41482231, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can Omega-3 Fatty Acids Serve as a Preventive Strategy for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis.}, journal = {The Journal of nutrition}, volume = {156}, number = {2}, pages = {101289}, pmid = {41482231}, issn = {1541-6100}, mesh = {Humans ; *Macular Degeneration/prevention &amp; control ; *Fatty Acids, Omega-3/administration &amp; dosage/therapeutic use ; Dietary Supplements ; Aged ; Docosahexaenoic Acids ; Eicosapentaenoic Acid ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. While anti-vascular endothelial growth factor (anti-VEGF) therapies are available for neovascular AMD (nAMD), effective preventive strategies remain limited. Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have biological plausibility for retinal protection through structural roles in photoreceptor membranes and anti-inflammatory lipid mediator pathways.<br><br>OBJECTIVES: This study aimed to synthesize contemporary evidence regarding omega-3 fatty acids in AMD prevention, with emphasis on subtype-specific associations, differences by omega-3 species, and contrasts between dietary intake and supplementation evidence.<br><br>METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidance and registered the protocol in PROSPERO (CRD420251122413). PubMed, ScienceDirect, and the Cochrane Library were searched from inception to August 2, 2025. Eligible studies included observational studies of dietary &#x3c9;-3 PUFA exposure in adults aged 50 years or older with AMD outcomes. Random-effects models models were used to pool adjusted effect estimates comparing the highest versus lowest &#x3c9;-3 exposure categories. Prespecified subgroup analyses were performed by AMD subtype (early AMD, advanced AMD, nAMD, and geographic atrophy [GA]) and &#x3c9;-3 species (EPA, DHA, and alpha-linolenic acid [ALA]). Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Publication bias was evaluated using funnel plots and Egger's regression test.<br><br>RESULTS: Eighteen studies were included. Higher &#x3c9;-3 intake was associated with reduced odds of AMD overall (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96; p = 0.01), with moderate heterogeneity (I&#xb2; = 61%). Subtype analyses demonstrated stronger associations for nAMD (OR 0.57, 95% CI 0.40-0.81) and GA (OR 0.65, 95% CI 0.45-0.94), and a smaller association for early AMD (OR 0.83, 95% CI 0.72-0.97), whereas advanced AMD was not significantly different between high and low intake groups (OR 0.81, 95% CI 0.49-1.33; p = 0.41). In &#x3c9;-3 species analyses, higher EPA intake was associated with lower AMD odds (OR 0.61, 95% CI 0.38-0.97; p = 0.04), while DHA showed a borderline association (OR 0.73, 95% CI 0.53-1.01; p = 0.05); ALA was not associated with benefit (OR 1.00, 95% CI 0.84-1.20; p = 0.96). Time-to-event pooling showed no significant long-term risk reduction (hazard ratio [HR] 0.98, 95% CI 0.84-1.15; p = 0.83). Funnel plot asymmetry was observed, and Egger's test suggested small-study effects (p = 0.04).<br><br>CONCLUSIONS: Higher dietary intake of marine-derived &#x3c9;-3 PUFAs is associated with reduced odds of AMD. However, long-term risk reduction was not demonstrated in time-to-event analyses, and small-study effects were suggested. These findings support the possibility that dietary patterns emphasizing &#x3c9;-3-rich seafood may contribute to AMD risk reduction, whereas the effectiveness of isolated &#x3c9;-3 PUFA supplementation for AMD prevention remains uncertain and warrants confirmation in future prospective studies and larger randomized controlled trials with long-term follow-up.}, }
@article {pmid41483391, year = {2026}, author = {Peng, Y and Zhang, Y and Kam, KW and Ho, M and Sezto, S and Au, S and Yim, CC and Zhang, X and Ng, MPH and Ip, P and Young, A and Pang, CP and Tham, CC and Chen, LJ and Yam, JC}, title = {Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {41483391}, issn = {2509-2723}, support = {14102422//General Research Fund/ ; C7149-20G//Collaborative Research Fund/ ; 11220206//Health and Medical Research Fund/ ; 10210246//Health and Medical Research Fund/ ; 09202466//Health and Medical Research Fund/ ; 82425017//National Natural Science Foundation of China/ ; 82171089//National Natural Science Foundation of China/ ; WW/SC/rc/SIEF2324/0366/24vw//Strategic Impact Enhancement Fund/ ; TL/JF/rc/SIEF2223/0759/23vw//Strategic Impact Enhancement Fund/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at enrollment. Among them, 53,059 with at least one follow-up FP assessment comprised the trajectory cohort. Participants were categorized as nonfrail, prefrail, or frail based on their FP scores. Annualized frailty progression (ΔFP/year) was estimated via linear regression. Cox models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD. During a median follow-up of 11.8 years in the baseline cohort, 13,428 incident AMD cases (2.9%) were documented. Prefrail (HR:1.14; 95% CI:1.10-1.18) and frail (HR:1.36; 95% CI: 1.26-1.47) individuals had significantly higher AMD risks compared to nonfrail participants. In the frailty trajectory analysis with a median follow-up duration of 3.3 years, 852 incident AMD cases (1.6%) were recorded. Each 1-point FP increase conferred 28% higher AMD risk (HR: 1.28; 95% CI: 1.18-1.38), while each 0.1-point/year ΔFP increase independently elevated risk by 15% (HR: 1.15; 95% CI: 1.10-1.21). Compared to stable nonfrail, prefrailty aggravation showed highest AMD risk (HR: 2.26; 95% CI: 1.51-3.37), followed by frailty alleviation (HR: 1.73; 95% CI: 0.98-3.04) and frailty maintenance (HR: 1.72; 95% CI: 0.86-3.41). Progressive frailty trajectories, independent of baseline status, is associated with increased incident AMD risk. Early interventions targeting frailty progression may mitigate AMD risk in aging populations.}, }
@article {pmid41484209, year = {2026}, author = {Donato, L and Zerti, D and Babiloni-Chust, I and Passacantando, M and Flati, V and Feligioni, M and Carl, M and Rinaldi, C and Poggi, L and D'Angelo, R and Maccarone, R}, title = {Comprehensive transcriptomic analysis reveals canonical and novel pathways modulated by nanoceria in mammalian retinal degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {3689}, pmid = {41484209}, issn = {2045-2322}, support = {2022PWMW5A//Ministry of University and Research (MUR, Italy) through the PRIN (Progetti di Rilevante Interesse Nazionale) 2022 grant/ ; }, mesh = {Animals ; *Cerium/pharmacology/administration &amp; dosage/chemistry ; Rats ; *Retinal Degeneration/genetics/metabolism/drug therapy/pathology ; Gene Expression Profiling ; Signal Transduction/drug effects ; *Transcriptome/drug effects ; Disease Models, Animal ; Retina/metabolism/drug effects/pathology ; Oxidative Stress/drug effects ; Nanoparticles ; Male ; Light/adverse effects ; }, abstract = {Retinal neurodegenerative diseases such as Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa cause irreversible vision loss due to the limited regenerative capacity of the mammalian retina. Cerium oxide nanoparticles (nanoceria) are emerging therapeutics against oxidative stress and inflammation, major drivers of photoreceptor degeneration, and have demonstrated morphological and functional neuroprotection in preclinical models. However, the genome-wide transcriptional mechanisms underlying these effects remain incompletely characterized. We performed retinal transcriptomic analysis in a rat AMD model induced by intense light and treated intravitreally with nanoceria. Six groups were analyzed: control, light damage, vehicle, nanoceria, vehicle + light damage, and nanoceria + light damage. Light damage activated inflammatory and apoptotic programs, with upregulation of cytokines (Tnf, Il6, Il1b, Ccl2) and downregulation of photoreceptor genes (Rho, Pde6a/b, Gnat1). Nanoceria treatment counteracted these effects, suppressing pro-inflammatory mediators, restoring antioxidative genes (Nfe2l2, Gclc, Sod2), and enhancing neuroprotective factors (Bdnf, Cntf, Ngf). Pathway analyses revealed inhibition of TNF/NF-κB/IL-17 signaling and activation of PI3K-Akt, JAK-STAT, and neurotrophin pathways. Unexpectedly, nanoceria also modulated amino acid and insulin metabolism (Ass1, Cps1, Insr, Irs1, Slc2a4) and reactivated transcription factors (Ascl1, Sox2, Notch1) typically silent in adult retina. Our findings highlight nanoceria as a multifunctional therapeutic that mitigates retinal degeneration by coordinating oxidative, inflammatory, and regenerative responses. Together with prior morphological and functional validations, these results support the translational potential of nanoceria for treating retinal neurodegenerative diseases.}, }
@article {pmid41484254, year = {2026}, author = {Askarinejad, A and Lip, GYH and Lip, PL}, title = {An association between atrial fibrillation and age-related macular degeneration: looking beyond mere coincidence.}, journal = {Eye (London, England)}, volume = {40}, number = {3}, pages = {285-287}, pmid = {41484254}, issn = {1476-5454}, }
@article {pmid41486361, year = {2026}, author = {Kim, JH and Park, SM and Choi, SI and Kim, DI and Sohn, J and Lee, WK}, title = {Short-term outcomes and choroidal morphological changes following aflibercept therapy in pachychoroid neovasculopathy.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {1798}, pmid = {41486361}, issn = {2045-2322}, mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Female ; Male ; *Choroid/drug effects/pathology/blood supply ; Middle Aged ; *Choroidal Neovascularization/drug therapy/pathology ; Aged ; Treatment Outcome ; Visual Acuity/drug effects ; Tomography, Optical Coherence ; Prospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Adult ; Retina/drug effects/pathology ; }, abstract = {To evaluate the short-term outcomes and choroidal morphological changes after three monthly aflibercept injections for pachychoroid neovasculopathy (PNV). Twenty-nine treatment-naïve patients with PNV were enrolled in this prospective phase IV clinical trial. All patients received three monthly injections of aflibercept. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured at baseline and at week 12 (4 weeks after the third injection). Additionally, changes in the subfoveal choroidal thickness (SCT), largest choroidal vessel diameter, and area of the choriocapillaris-Sattler's and Haller's layers between baseline and week 12 were assessed. The BCVA improved from 67.5 ± 10.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 74.3 ± 10.7 letters at week 12. CRT decreased from 348.5 ± 77.4 μm at baseline to 254.3 ± 72.9 μm at week 12. Complete resolution of the retinal fluid was observed in 86.2% of cases at week 12. At baseline and 12 weeks, the SCT measured 388.3 ± 77.4 μm and 344.9 ± 91.9 μm, respectively, while the diameter of the largest choroidal vessel measured 280.3 ± 62.0 μm and 247.8 ± 57.6 μm, respectively. The areas of the choriocapillaris-Sattler's layer and Haller's layer at the corresponding time points were 0.56 ± 0.14 mm[2] and 0.57 ± 0.14 mm[2], and 1.56 ± 0.42 mm[2] and 1.40 ± 0.45 mm[2], respectively. Aflibercept loading injections for PNV resulted in both short-term visual and anatomical improvements. Notably, the reduction in the area of Haller's layer and choroidal vessel diameter after treatment suggests that aflibercept exerts an impact on this region of the choroid.}, }
@article {pmid41488355, year = {2025}, author = {Zhang, Q and Zhang, H and Shi, X and Li, J and Wang, C and Zhou, H and Shan, C}, title = {Noninvasive transcranial brain stimulation for eye diseases and visual dysfunctions: A systematic review of RCTs.}, journal = {iScience}, volume = {28}, number = {12}, pages = {114111}, pmid = {41488355}, issn = {2589-0042}, abstract = {Noninvasive transcranial brain stimulation (NTBS) has emerged as a potential therapeutic approach for eye diseases and visual dysfunctions. This systematic review evaluates the evidence from 23 randomized controlled trials examining the application of NTBS, including transcranial electrical stimulation and transcranial magnetic stimulation, in conditions such as amblyopia, myopia, visual field defects, glaucoma, diabetic retinopathy, macular degeneration, and blepharospasm. Studies assessed outcomes such as visual acuity, contrast sensitivity, and visual perception, with variable effects observed across trials. Most studies reported no serious adverse events, indicating that NTBS is safe and feasible. However, conclusive evidence regarding its efficacy remains elusive due to varied interventions, inconsistent outcome measures, and methodological limitations. Future research with higher methodological rigor is needed to optimize stimulation parameters and explore integration with adjunctive therapies.}, }
@article {pmid41490049, year = {2025}, author = {Dor, O and Cohen, M and Shahar-Gonen, M and Loewenstein, A and Peto, T and Wright, D and Shor, R and Havilio, M and Benyamini, G and Wen, Q and Shomron, N and Zur, D}, title = {Anti-VEGF Therapy Switching in Neovascular Age-Related Macular Degeneration: Insights from Automated Volumetric Retinal Fluid Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004756}, pmid = {41490049}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the efficacy of switching from bevacizumab to ranibizumab or aflibercept in neovascular age-related macular degeneration (nAMD) using automated volumetric retinal fluid analysis.<br><br>METHODS: This retrospective study included 186 eyes with nAMD showing inadequate response after &#x2265;3 bevacizumab injections. Patients were switched to a second-line anti-VEGF agent and categorized as early (3-5 injections) or late (&#x2265;6 injections) switchers. Optical coherence tomography (OCT) scans were analyzed using the Notal-OCT Analyzer (NOA&#x2122;), an AI-based algorithm for retinal fluid quantification. Parameters included total retinal fluid (TRF), intraretinal fluid (IRF) volume, subretinal fluid (SRF) volume, pigment epithelial detachment (PED) volume, central subfield thickness (CST), and visual acuity (VA), assessed at baseline, post-bevacizumab, and following three injections of the new agent.<br><br>RESULTS: Early switchers showed an increase in TRF from 105nL to 158nL after bevacizumab, then a reduction to 20nL post-switch (p<0.001); PED volume decreased post-switch (p=0.010). Late switchers showed fluid reductions both after bevacizumab and post-switch (TRF: p<0.001; PED: p=0.007). CST significantly improved only in early switchers (p=0.004), while VA changes were not statistically significant.<br><br>CONCLUSIONS: Automated fluid analysis reliably quantifies treatment response in nAMD. Early switchers showed worsening after bevacizumab, while late switchers had partial responses. These findings highlight the potential of automated analysis to support more individualized, data-driven treatment strategies. Prospective studies are required to confirm impact on patient outcomes.}, }
@article {pmid41490202, year = {2025}, author = {Peschaut, T and Seidel, G and Sommer, M and Kruger, M and Nadvornik, C and Werkl, PJ}, title = {Recurrent sterile endophthalmitis following intravitreal Faricimab: A case report.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001854}, pmid = {41490202}, issn = {1937-1578}, abstract = {PURPOSE: Despite its low risk profile and high efficacy described in several studies, there appears to be an increasing number of reports describing sterile inflammatory reactions following intravitreal administration of Faricimab. Purpose of this case report is to highlight the occurrence of recurrent sterile endophthalmitis following repeated intravitreal Faricimab administration, emphasizing the need for awareness and careful monitoring of this adverse reaction.<br><br>METHODS AND RESULTS: We present the case of an 83-year-old caucasian woman, who was treated with intravitreal Faricimab for neovascular age-related macular degeneration (nAMD) in her left eye (OS). Shortly after the first administration, she experienced progressive, painless visual deterioration, along with a pronounced inflammatory reaction in the anterior and posterior segments, including granulomatous keratic precipitates. Based on these findings, the diagnosis of endophthalmitis was made. Following hospital admission, immediate treatment led to resolution of the condition and recovery of visual acuity.On the first day after the second administration of Faricimab, the patient again experienced painless visual deterioration accompanied by a severe inflammatory reaction OS. Immediate treatment once more resulted in resolution of the condition and recovery of visual acuity. In both instances, no microbial growth was detected in fungal cultures or aerobic and anaerobic cultures from aqueous humor and vitreous samples.<br><br>CONCLUSION: We present a case of recurrent endophthalmitis in the same patient following two intravitreal administrations of Faricimab. Considering the clinical presentation and course, as well as the microbiological findings, a sterile inflammatory reaction is likely in both instances.}, }
@article {pmid41490387, year = {2025}, author = {Franco, JJ and Wubben, TJ}, title = {Emerging solutions for neovascular age-related macular degeneration.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001199}, pmid = {41490387}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: To summarize emerging therapeutic strategies for neovascular (wet) age-related macular degeneration (nAMD), with emphasis on recent translational and clinical developments.<br><br>RECENT FINDINGS: The nAMD treatment landscape is rapidly evolving. Gene therapies (e.g. ABBV-RGX-314, ADVM-022, and 4D-150) have demonstrated sustained intraocular anti-VEGF expression with reduced injection burden in phase 2 and 3 programs, validating the 'biofactory' concept. Tyrosine kinase inhibitors delivered via intravitreal or suprachoroidal implants (e.g. EYP-1901, OTX-TKI, and CLS-AX) show potential for twice-yearly or less frequent dosing. Moreover, emerging therapeutic approaches increasingly target non-VEGF pathogenic pathways, reflecting a shift toward mechanistically diverse vascular stabilization and neuroprotection strategies. These include multitargeted biologics that couple anti-angiogenic and anti-inflammatory effects (e.g. KSI-501, IBI-302, and AG-73305), as well as agents modulating FGF2 signaling, Wnt activation, complement regulation, and cellular metabolism.<br><br>SUMMARY: Therapeutic innovation in nAMD is transitioning from incremental refinements in intravitreal anti-VEGF delivery to strategies aimed at extending durability or targeting alternative contributory pathways. Long-term safety, efficacy, and durability will determine which of these candidates redefine standard care.}, }
@article {pmid41490968, year = {2026}, author = {Mastropasqua, R and Quarta, A and Passamonti, M and Lorenzi, C and Ruggeri, ML and Gironi, M and Persavalli, C and Belloni Baroni, L and De Santis Ciacci, C and Aloia, R and Della Penna, N and Toto, L and Carpineto, P and Mastropasqua, L}, title = {Macular pigment optical density following lutein scleral iontophoresis in intermediate age-related macular degeneration: A six-month pilot study.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328403}, pmid = {41490968}, issn = {1468-2079}, abstract = {PURPOSE: To evaluate the effects of scleral iontophoresis lutein delivery on macular pigment optical density (MPOD), retinal anatomy and function in patients with intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This prospective pilot study included 15 phakic eyes from patients with iAMD. All participants underwent a single session of trans-scleral iontophoresis with a liposomal lutein formulation. MPOD, central macular thickness (CMT), choroidal vascularity index (CVI) and retinal sensitivity (RS) were assessed at baseline (T0), and at 1&#x2009;month (T1), 3&#x2009;months (T2) and 6&#x2009;months (T3).<br><br>RESULTS: MPOD showed a significant overall change across time points (&#x3c7;&#xb2;=11.01, p=0.012), with significant differences between T1 and T3 (p=0.006) and T2 and T3 (p=0.018). CMT significantly decreased at T3 compared with earlier visits (p&#x2264;0.002). RS declined at early time points (T1 and T2 vs T0; p=0.027&#x2009;and p=0.002, respectively), while CVI exhibited modest reductions by T2 and T3 (p=0.021&#x2009;and p=0.017). A significant inverse correlation was found between &#x394;MPOD and &#x394;RS at T2-T0 (&#x3c1;=-0.520, p=0.035). Best-corrected visual acuity remained stable across all visits.<br><br>CONCLUSIONS: The inverse correlation between MPOD change and RS decline at 3&#x2009;months raises the possibility that early augmentation of MP may provide a protective functional effect. These data support the short-term feasibility of scleral iontophoresis for targeted lutein delivery.}, }
@article {pmid41491306, year = {2026}, author = {Kikushima, W and Sakurada, Y and Fukuda, Y and Yoneyama, S and Kotoda, Y and Tsuru, DV and Kashiwagi, K}, title = {Brolucizumab versus aflibercept in treating exudative age-related macular degeneration: a 12-month pro re nata regimen.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4739}, pmid = {41491306}, issn = {2045-2322}, abstract = {We compared 12-month treatment outcomes of intravitreal injections of brolucizumab (IVBr) with aflibercept (IVA) for treatment-naïve exudative age-related macular degeneration (AMD). Patients were given three monthly IVBr or IVA injections and were followed up monthly for 12 months. Additional injections were given if exudation or hemorrhage recurred. The study included 339 eyes in 339 patients divided into the IVBr or IVA groups. In both groups, central retinal thickness (CRT) and subfoveal choroidal thickness significantly decreased, and best-corrected visual acuity (BCVA) significantly improved at the 12-month visit. BCVA improvement was similar in both groups (P = 0.27). Age, baseline BCVA, and thickness of the central retina and subfoveal choroid were associated with the 12-month BCVA. The proportion of patients who did not require additional injections was 33% in the IVBr and 30% in the IVA group (P = 0.58). The number of additional injections showed a trend favoring IVBr over IVA but the difference was insignificant (P = 0.055). Age, risk alleles of ARMS2 A69S, and baseline CRT were associated with shorter retreatment-free period. In conclusion, IVBr achieved similar visual and anatomic treatment outcomes to IVA with a trend toward requiring fewer additional injections during 12-month follow-up of as-needed regimen for exudative AMD.}, }
@article {pmid41491515, year = {2026}, author = {Wang, JX and Wei, WB}, title = {[Research status of subretinal fibrosis in age-related macular degeneration].}, journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology}, volume = {62}, number = {1}, pages = {66-72}, doi = {10.3760/cma.j.cn112142-20250804-00330}, pmid = {41491515}, issn = {0412-4081}, support = {82220108017, 82141128//National Natural Science Foundation of China/ ; 2024-1-2052//The Capital Health Research and Development of Special/ ; Z201100005520045//Science &amp; Technology Project of Beijing Municipal Science &amp; Technology Commission/ ; SZSM202311018//Sanming Project of Medicine in Shenzhen/ ; }, mesh = {*Macular Degeneration/pathology ; Humans ; Animals ; Fibrosis ; *Retina/pathology ; Disease Models, Animal ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals aged 65 years and older. In the advanced stage of the disease, subretinal fibrotic scars develop, leading to irreversible vision impairment. The formation of subretinal scars is driven by interactions among various cellular and molecular components, involving multiple pathological processes including immune responses and inflammatory reactions; however, the exact underlying mechanism remains elusive. This review summarizes the current animal models and experimental studies employed to investigate its mechanism and explore novel therapeutic targets.}, }
@article {pmid41492569, year = {2026}, author = {Faghihi, S and Eshkoly-Lior, T and Feo, A and Sarraf, D}, title = {Atypical presentation of macular serpiginous choroiditis masquerading as age related macular degeneration.}, journal = {American journal of ophthalmology case reports}, volume = {41}, number = {}, pages = {102491}, pmid = {41492569}, issn = {2451-9936}, abstract = {PURPOSE: To describe a case of macular serpiginous choroiditis (SC) masquerading as age related macular degeneration.<br><br>METHOD: Multimodal imaging (MMI), including ultra-widefield fundus autofluorescence and fluorescein and indocyanine green angiography werer performed. Cross-sectional and en face optical coherence tomography (OCT) and OCT angiography (OCTA) facilitated the correct diagnosis of this masquerade condition.<br><br>RESULTS: A 57-year-old woman, with a history of long-standing vision loss in the left eye (OS), presented with acute vision loss in the right eye (OD). Color fundus photography showed a focal macular lesion central OD and an irregular atrophic macular scar central OS. OCT OD displayed large drusenoid lesions in the macula OD and a macular scar OS. OCTA showed evidence of inner choroidal ischemia central OD corresponding to the drusenoid lesions without shadow artifact OD. A diagnosis of macular serpiginous choroiditis was rendered OD and the patient was started on immunomodulatory therapy (IMT) including oral steroids and increasing dosages of mycophenolate therapy. After three months of follow-up, the visual acuity remarkably improved, the drusenoid lesions completely resolved on OCT, and choroidal ischemia completely regressed on OCTA OD.<br><br>CONCLUSION: Placoid disorders can masquerade as AMD. We present an unusual case of macular serpiginous choroiditis with new onset drusenoid lesions driven by inner choroidal ischemia on OCTA and with resolution following IMT. OCTA can be an invaluable tool to correctly diagnose placoid conditions which is essential to guide therapeutic considerations.}, }
@article {pmid41493078, year = {2026}, author = {Zobor, D and Munk, MR}, title = {Distinguishing Inherited Retinal Disease From Age-Related Macular Degeneration: Clinical Red Flags, Diagnostic Strategy, and the Expanding Role of Genetic Testing.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {54}, number = {1}, pages = {3-5}, doi = {10.1111/ceo.70055}, pmid = {41493078}, issn = {1442-9071}, }
@article {pmid41493658, year = {2026}, author = {Tan, X and Kang, J and Zhao, H and Fang, F and Xia, Y and Luo, C and Zou, Y and Li, Y}, title = {GPR40 Attenuates Age-Related Macular Degeneration by Suppressing Retinal Microglial NLRP3 Inflammasome Activation Via ERK Signaling.}, journal = {Inflammation}, volume = {49}, number = {1}, pages = {29}, pmid = {41493658}, issn = {1573-2576}, support = {82360213//the National Natural Science Foundation of China/ ; 202305AC160073//the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202401AY070001-172/174//the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; 2024Y927//Yunnan Provincial Department of Education Scientific Research Fund Project/ ; }, mesh = {Animals ; *Receptors, G-Protein-Coupled/metabolism ; *Microglia/metabolism/drug effects/pathology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; *Macular Degeneration/metabolism/prevention &amp; control/chemically induced/pathology ; Mice ; *Inflammasomes/metabolism ; *MAP Kinase Signaling System/physiology/drug effects ; *Retina/metabolism/pathology ; Mice, Inbred C57BL ; }, abstract = {Retinal neuroinflammation is a key pathological feature of age-related macular degeneration (AMD), primarily driven by aberrant microglial cell activation. The expression and role of G-protein-coupled receptor 40 (GPR40), in AMD remain unclear. To investigate this pathology, we established a sodium iodate-induced mouse model of non-exudative AMD and performed in vitro experiments using LPS-stimulated microglial cells. The results showed that activation of the GPR40 receptor significantly promoted the polarization of microglial cells from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, effectively inhibiting neuroinflammation. Mechanistic studies revealed that GPR40 negatively regulates the ERK signaling pathway, inhibiting NLRP3 inflammasome activation and the release of pro-inflammatory cytokines such as IL-1β and TNF-α. In both in vivo and in vitro experiments, GPR40 activation protected photoreceptors by suppressing neuroinflammation caused by excessive microglial activation. In conclusion, this study reveals, for the first time, the critical role of GPR40 in regulating retinal neuroinflammation and its molecular mechanism. It highlights the potential therapeutic value of targeting the GPR40-ERK signaling axis to control the neuroinflammatory cascade and delay the progression of AMD and other retinal degenerative diseases.}, }
@article {pmid41494750, year = {2026}, author = {Balser, S and Capsius, B and Hole, R and Papp, A and Preissinger, N and Rozenknop, A and Tiko, T}, title = {Randomised, double-masked trial to compare the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41494750}, issn = {2397-3269}, mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Double-Blind Method ; Male ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; Aged ; *Biosimilar Pharmaceuticals/administration &amp; dosage/therapeutic use/adverse effects ; Intravitreal Injections ; *Visual Acuity ; Middle Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Biosimilars are helping to reduce the cost burden of treatment and widen patient access to therapies. This multicentre trial compared the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: Patients aged &#x2265;50 years with newly diagnosed nAMD and a best-corrected visual acuity (BCVA) between 20/40 and 20/200 Snellen equivalent were randomised (1:1) to double-masked treatment with 2&#x2009;mg FYB203 or EU-approved reference aflibercept by intravitreal injection every 4 weeks for three doses (baseline, weeks 4 and 8) then every 8 weeks up to week 48. The primary efficacy endpoint was the change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 in the study eye. Therapeutic equivalence of FYB203 and reference aflibercept was demonstrated if, depending on the regulatory requirement with respect to the significance level, the two-sided 90.4% and 95.2%&#x2009;CIs were within the predefined equivalence interval of (-3.5 to 3.5) ETDRS letters.<br><br>RESULTS: A total of 433 patients received treatment with FYB203 (n=215) or reference aflibercept (n=218). Mean improvement in BCVA from baseline to week 8 was 6.6 ETDRS letters with FYB203 and 5.6 ETDRS letters with reference aflibercept, with an estimated mean treatment difference of 1.0 and the two-sided 90.4%&#x2009;CI (-0.3 to 2.2) and 95.2%&#x2009;CI (-0.6 to 2.5) fully contained within the pre-defined equivalence margins, confirming therapeutic equivalence between FYB203 and reference aflibercept. Safety and immunogenicity profiles were similar between groups.<br><br>CONCLUSION: Although conducted during the COVID-19 pandemic in a potentially vulnerable elderly population and affected by geopolitical disruption in Ukraine, mitigation measures minimised the overall impact of these events. FYB203 demonstrated therapeutic equivalence to reference aflibercept in patients with nAMD, supporting similar clinical performance across all approved indications.<br><br>TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04522167; EudraCT: 2019-003923-39.}, }
@article {pmid41495013, year = {2026}, author = {Li, H and Weiss, CE and Pandiyan, VP and Nanni, D and Liu, T and Kung, PW and Tan, B and Barathi, VA and Schmetterer, L and Sabesan, R and Ling, T}, title = {Optoretinography reveals rapid rod photoreceptor movement upon rhodopsin activation.}, journal = {Light, science &amp; applications}, volume = {15}, number = {1}, pages = {58}, pmid = {41495013}, issn = {2047-7538}, support = {I010/2024 [2082/44/2024]//Singapore Eye Research Institute (SERI)/ ; RS19/20; RG28/21//Ministry of Education - Singapore (MOE)/ ; NMRC/CG/C010A/2017; MOH-001748-00//MOH | National Medical Research Council (NMRC)/ ; Startup Grant//Nanyang Technological University (NTU)/ ; unrestricted grant//Research to Prevent Blindness (RPB)/ ; P30 EY001730/EY/NEI NIH HHS/United States ; L40 AI172024/AI/NIAID NIH HHS/United States ; NRF-CRP24-2020-0001//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; L30 AI172024/AI/NIAID NIH HHS/United States ; NMRC/CG/M010/2017/Pre-Clinical; NMRC/CG21APR1010-SAMURAI/Pre-Clinical Core Platform/2021_SERI//MOH | National Medical Research Council (NMRC)/ ; U01EY032055; EY029710//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; NRF-NRFF14-2022-0005//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; R01 EY029710/EY/NEI NIH HHS/United States ; U01 EY032055/EY/NEI NIH HHS/United States ; }, abstract = {Rod photoreceptors are essential for vision under dim light conditions and are highly vulnerable in retinal degenerative diseases. Here, we demonstrate that both human and rodent rods undergo a minute and rapid contraction of their outer segments upon photoisomerization, the first step of phototransduction. The contraction is explained as an electromechanical manifestation of the rod early receptor potential generated in the disk membranes, which is challenging to access in electrophysiology. The in vivo optical imaging of light-evoked electrical activity in rodent rods was facilitated by an ultrahigh-resolution point-scan optical coherence tomography (OCT) system, combined with an unsupervised learning approach to separate the light-evoked response of the rod outer segment tips from the retinal pigment epithelium-Bruch's membrane complex. In humans, an adaptive optics line-scan OCT facilitated high-speed recordings in rods. The non-invasive in vivo optical imaging of rhodopsin activation extends the diagnostic capability of optoretinography, and may facilitate personalized, objective assessment of rod dysfunction and visual cycle impairment in inherited and age-related macular degeneration.}, }
@article {pmid41497268, year = {2026}, author = {Gong, X and Feng, J and Han, Y and Tang, G and Yin, Y and Li, J and Liu, Y and Zhang, J and Song, J and Bi, H}, title = {Research progress on glycolytic reprogramming in ophthalmic diseases.}, journal = {PeerJ}, volume = {14}, number = {}, pages = {e20478}, pmid = {41497268}, issn = {2167-8359}, mesh = {Humans ; *Glycolysis ; *Eye Diseases/metabolism ; Animals ; *Retina/metabolism ; Uveal Neoplasms/metabolism ; Energy Metabolism ; Uveal Melanoma ; Melanoma/metabolism ; Glaucoma/metabolism ; Cellular Reprogramming ; }, abstract = {The retina is one of the most energy-demanding tissues in the human body. Retinal energy metabolism is primarily dominated by aerobic glycolysis, with more than 80% of the glucose consumed being converted to lactic acid. As a highly energy-consuming tissue, the metabolic characteristics of the retina, especially aerobic glycolysis, are essential for maintaining retinal cell function during normal physiological processes. However, in disease states, this metabolic balance is disrupted, leading to a range of pathological changes. There is currently growing evidence that metabolic reprogramming is a pathological cause of diseases such as retinal degeneration, uveal melanoma, and glaucoma. This article reviews the mechanisms involved in metabolic reprogramming in ocular diseases and describes relevant therapeutic targets. Despite the many advances, the regulatory mechanisms of metabolic reprogramming in ophthalmic diseases still need to be thoroughly investigated, and new therapeutic strategies are expected to be developed based on this in the future.}, }
@article {pmid41497650, year = {2025}, author = {Pandala, N and De Melo Haefeli, L and Khan, A and Steffan, H and Miller, J and Stone, EM and Han, IC and Lavik, EB and Mullins, RF and Tucker, BA}, title = {Acriflavine delivery via Polyurethane nanocapsules to treat neovascular age-related macular degeneration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.22.695712}, pmid = {41497650}, issn = {2692-8205}, abstract = {Choroidal neovascularization is a complication associated with retinal diseases such as age-related macular degeneration (AMD), a leading cause of vision loss in the developed world. Choroidal neovascular membrane (CNVM) refers to the abnormal growth of blood vessels in the retina which results in exudation and/or hemorrhage, leading to photoreceptor damage and vision loss. Currently first-line treatment for CNVM include intravitreal injections of vascular endothelial growth factor (VEGF)-binding antibodies that prevent the growth of these leaky blood vessels. Unfortunately, anti-VEGF drugs often require frequent injections, and prolonged VEGF inhibition has been associated with retinal atrophy and decreased long term effectiveness in some patients. This study presents the use of Acriflavine, a small molecule HIF1α inhibitor loaded polyurethane nanocapsules to treat CNVM in a rat model. Fourteen days following laser injury and intravitreal drug administration, CMVM size was significantly reduced in acriflavine nanocapsule and free acriflavine treated animals as compared to drug free controls. Moreover, acriflavine nanocapsules reduce CNVM incidence compared to drug free controls by approximately 25%. Among the different delivery routes tested, intravitreal delivery of acriflavine nanocapsules was found to be superior to subretinal and suprachoroidal delivery for reducing CNVM area without causing significant damage to the neural retina. This paper presents the synthesis, characterization and the effectiveness of the polyurethane based acriflavine delivery system in treating choroidal neovascularization.}, }
@article {pmid41497719, year = {2025}, author = {Zhang, M and Wang, Y and Feng, L and Zhang, P and Li, Y and Chen, H}, title = {Massive Hemorrhage in PCV Is Associated With Lower-Than-Normal VEGF Level and Dramatically Elevated Inflammatory Cytokine Levels in Aqueous Mingxuan.}, journal = {Journal of ophthalmology}, volume = {2025}, number = {}, pages = {9272271}, pmid = {41497719}, issn = {2090-004X}, abstract = {PURPOSE: To compare the aqueous cytokine profile in polypoidal choroidal vasculopathy (PCV) with or without massive hemorrhage and typical neovascular age-related macular degeneration (nAMD).<br><br>METHODS: The present comparative study included 81 treatment-na&#xef;ve eyes from 75 patients (PCV with massive hemorrhage 20 eyes, PCV without massive hemorrhage 19 eyes, typical nAMD 19 eyes, and cataract control 23 eyes). 10 cytokines (VEGF, IL-6, IL-8, MCP-1, ICAM-1, VCAM-1, IP-10, G-CSF, and IFN-&#x3b3;, IL-10) in the aqueous humor were measured by cytometric bead array.<br><br>RESULTS: VEGF levels in PCV with massive hemorrhage (median 5.20&#x2009;pg/mL) were significantly lower than that in PCV without massive hemorrhage (median 34.76&#x2009;pg/mL, p = 0.003) and typical nAMD (median 43.88&#x2009;pg/mL, p < 0.001). They were even lower than that in normal cataract controls (median 22.02&#x2009;pg/mL, p = 0.037). Multiple inflammatory cytokines were dramatically elevated in PCV with massive hemorrhage. IL-6, IL-8, MCP-1, ICAM-1, and IP-10 levels were significantly higher in PCV with massive hemorrhage than that in the other three groups. VCAM-1 levels were significantly higher in PCV with massive hemorrhage than that in typical nAMD and in control. G-CSF and IFN-&#x3b3; levels were significantly higher in PCV without massive hemorrhage than that in control. IL-10 levels were significantly higher in PCV with massive hemorrhage than that in typical nAMD.<br><br>CONCLUSIONS: This pilot study showed that PCV with massive hemorrhage had a lower-than-normal VEGF level in aqueous humor and inflammation may be actively involved in the pathogenesis of massive hemorrhage in PCV.}, }
@article {pmid41499325, year = {2026}, author = {Karam, M and Baeshen, M and Alfuzaie, R and Mohammad, M and Alshatti, A and Samet, A and Paez-Escamilla, M and Sun, V}, title = {Efficacy of Faricimab in Neovascular Age-Related Macular Degeneration: A Single-Arm Systematic Review and Meta-Analysis.}, journal = {Ophthalmic research}, volume = {69}, number = {1}, pages = {43-55}, pmid = {41499325}, issn = {1423-0259}, mesh = {Humans ; *Visual Acuity ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence ; Treatment Outcome ; Macula Lutea/pathology ; Antibodies, Bispecific ; }, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss and requires long-term anti-vascular endothelial growth factor therapy. This study aimed to evaluate the efficacy and safety of faricimab in patients with nAMD.<br><br>METHODS: This systematic review and meta-analysis were performed according to the PRISMA guidelines to identify studies assessing faricimab in nAMD. Primary outcomes included visual acuity, central macular thickness (CMT), and dry macula rate. Secondary outcomes included macular status, central choroidal thickness (CCT), and complications. A random-effects model was used to calculate pooled mean with 95% confidence intervals.<br><br>RESULTS: Out of the 365 studies identified, 21 studies were included, comprising a total sample size of 1,864 eyes of 1,791 patients. Post-operatively, there was a statistically significant improvement in corrected distance visual acuity (standardized mean difference [SMD]: -0.122, 95% p = 0.039) and CMT (SMD: -3.672, p = 0.010). Similarly, there was a significant improvement in the rate of dry macula at the final follow-up visit (event rate: 0.529; p < 0.05). For the secondary outcomes, there was a statistically significant improvement in CCT (SMD: -0.199, p = 0.026) and in the rate of macular exudates (0.452, p < 0.05), specifically intraretinal fluid (0.140, p < 0.05) and subretinal fluid (0.271, p < 0.05). Complications secondary to faricimab injections included hemorrhagic pigment epithelial detachment with a rate of 0.120 (p < 0.05) and retinal pigment epithelium tear with a rate of 0.025 (p < 0.05).<br><br>CONCLUSIONS: The use of faricimab injection in patients with nAMD is safe and effective, resulting in significant improvements in a myriad of visual measures and OCT parameters.}, }
@article {pmid41499990, year = {2026}, author = {Chen, C and Wang, C and Li, H and Wang, T and Jiao, X}, title = {Sweet poison for the eyes: High-Fructose diets as drivers of metabolic disruption and ocular diseases - Insights and therapeutic horizons.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110852}, doi = {10.1016/j.exer.2026.110852}, pmid = {41499990}, issn = {1096-0007}, mesh = {Humans ; *Fructose/adverse effects ; *Eye Diseases/metabolism/etiology ; Metabolic Syndrome/metabolism ; Animals ; *Diet/adverse effects ; }, abstract = {Excess consumption of added sugars, commonly delivered through sucrose and high-fructose corn syrup, has increased in parallel with obesity, metabolic syndrome, and type 2 diabetes. These systemic metabolic disturbances are consistently associated with a range of ocular conditions. However, whether high-fructose intake exerts independent and fructose-specific effects on ocular tissues remains uncertain, because most human evidence is indirect, often mediated through metabolic syndrome phenotypes, and frequently confounded by mixed dietary exposures and total energy intake. This review synthesizes mechanistic pathways that are plausibly enriched by fructose biology, including hepatic fructose metabolism with ATP depletion and uric acid generation, oxidative and inflammatory signaling, altered lipid handling, and gut barrier and microbiome perturbations. We evaluate how these systemic changes may intersect with ocular surface homeostasis, retinal neurovascular integrity, intraocular pressure regulation, and choroidal and macular vulnerability. Across dry eye disease, diabetic retinopathy, glaucoma-related outcomes, age-related macular degeneration and choroidal neovascular responses, and cataract, we distinguish fructose-specific exposure studies from metabolic syndrome only and mixed diet reports, and we emphasize limitations related to exposure definition, replication, and translation to humans. Overall, current evidence supports the view that excess fructose may amplify ocular susceptibility in metabolically stressed states, but direct causal links in humans remain preliminary. We conclude by outlining methodological priorities and testable study designs needed to clarify fructose-specific contributions to ocular disease risk. Some experimental findings, particularly those related to ocular-surface responses, originate from single research groups and require independent replication, underscoring that current evidence remains preliminary and hypothesis-generating.}, }
@article {pmid41500346, year = {2026}, author = {Dal Cortivo, G and Longo, C and Müller, B and Avesani, A and Pacchiana, R and Weller, M and Marino, V and Lytvynchuk, L and Stieger, K and Dell'Orco, D}, title = {Protein delivery to the eye: assessing therapeutic potential across inner and outer retina.}, journal = {International journal of pharmaceutics}, volume = {690}, number = {}, pages = {126568}, doi = {10.1016/j.ijpharm.2026.126568}, pmid = {41500346}, issn = {1873-3476}, mesh = {Animals ; Swine ; *Retina/metabolism ; *Guanylate Cyclase-Activating Proteins/administration &amp; dosage/metabolism ; Mice ; Liposomes ; Mice, Inbred C57BL ; Drug Delivery Systems ; Humans ; Protein Transport ; }, abstract = {Protein-based therapeutics represent a promising approach for treating diseases of the retina, yet effective delivery systems and translational models remain limited. We developed a robust ex vivo framework utilizing murine and porcine retinal explants to investigate protein delivery mechanisms for both peripheral and central retinal regions. Using guanylate cyclase-activating protein-1 (GCAP1) as a retina-specific model protein and mCardinal2 as a non-retina-specific control, we demonstrated spontaneous protein internalization and accumulation in photoreceptors and ganglion cells following single-dose administration. In murine explants, myristoylated GCAP1 exhibited sustained retention and appropriate subcellular targeting in rod photoreceptors over 96 h without inducing tissue damage. Porcine explants, which better recapitulate human macular architecture, revealed differential protein trafficking dependent on post-translational modifications. Retinal tissue showed preferential uptake and retention of retina-specific proteins over foreign proteins, suggesting sophisticated protein-specific recognition mechanisms. Liposomal encapsulation enhanced initial uptake of non-retina-specific proteins but did not improve long-term retention. This experimental platform provides a valuable tool for screening protein therapeutics, optimizing delivery formulations, and investigating protein-selective cellular uptake mechanisms, with direct implications for developing treatments for inherited retinal degenerations, age-related macular degeneration, and optic nerve pathologies.}, }
@article {pmid41500399, year = {2026}, author = {Wang, Y and Liu, X and Zeng, S and Yang, W and Cao, F and Hou, S}, title = {The role and mechanism of post-translational modifications (PTMs) in immune-related eye diseases.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110851}, doi = {10.1016/j.exer.2026.110851}, pmid = {41500399}, issn = {1096-0007}, mesh = {Humans ; *Protein Processing, Post-Translational/physiology ; *Eye Diseases/immunology/metabolism ; Animals ; *Eye Proteins/metabolism ; }, abstract = {Post-translational modifications (PTMs) encompass the spectrum of chemical covalent alterations that proteins undergo after being synthesized from mRNA. These modifications typically involve the covalent bonding of chemical groups or small protein molecules to the amino acid backbones or side chains. Currently, over 650 types of PTMs have been identified, including significant ones such as phosphorylation, ubiquitination, SUMOylation, methylation, acetylation, glycosylation, among other novel varieties like lactylation. However, a systematic review of PTMs associated with immune-mediated ocular diseases remains conspicuously absent in current literature. To fully understand the role of PTM in immune eye diseases, this review systematically introduces the regulatory mechanisms and functions of several important PTMs. Furthermore, this review also encapsulates the mechanisms of PTMs in several pivotal immune-related ocular conditions, specifically uveitis, age-related macular degeneration (AMD), dry eye disease (DED), and diabetic retinopathy (DR). By integrating current evidence, this work not only clarifies the pathogenic contributions of specific PTMs but also identifies their potential as therapeutic targets. Finally, we discuss future research directions and the challenges of translating PTM-based interventions into clinical practice for ocular immune disorders.}, }
@article {pmid41501669, year = {2026}, author = {Luo, Y and Xia, Y and Gong, X and Hao, M and Wei, Q and Liao, L}, title = {GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {12}, pmid = {41501669}, issn = {1471-2415}, abstract = {OBJECTIVE: To synthesize the current preclinical and clinical evidence on the utility and potential mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a therapeutic strategy for major ophthalmic diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration.<br><br>METHODS: A comprehensive literature search was conducted to synthesize the current preclinical and clinical evidence. Electronic databases including PubMed, Embase, and Web of Science were searched from inception until August 2025 using keywords such as &#x201c;GLP-1 receptor agonist,&#x201d; &#x201c;diabetic retinopathy,&#x201d; &#x201c;glaucoma,&#x201d; &#x201c;age-related macular degeneration,&#x201d; &#x201c;ocular disease,&#x201d; and &#x201c;neuroprotection.&#x201d; The search focused on identifying preclinical studies, large-scale retrospective cohort studies, and post-hoc analyses of major clinical trials that evaluated the utility and potential mechanisms of GLP-1RAs in ophthalmic diseases. Studies were screened for relevance based on title and abstract, and full texts were retrieved for detailed assessment.<br><br>RESULTS: Despite heterogeneity in study designs and populations, a largely consistent association was found between GLP-1RA use and a reduced incidence of glaucoma. For diabetic retinopathy, the evidence was nuanced, indicating potential long-term neurovascular protection but also a risk of transient early worsening. For age-related macular degeneration, findings were dichotomous, suggesting a protective effect against non-exudative forms but a potential increased risk for neovascular disease.<br><br>CONCLUSION: GLP-1RAs show significant promise as a potential disease-modifying therapy for neurodegenerative and inflammatory eye diseases, acting through both systemic metabolic improvements and direct ocular mechanisms, representing a paradigm shift beyond their metabolic indications.}, }
@article {pmid41501830, year = {2026}, author = {Fang, J and Huang, Y and Li, B and Du, Y}, title = {Role and regulation of kinases in age-related macular degeneration.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {227}, pmid = {41501830}, issn = {1479-5876}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of chronic blindness in the elderly and causes retinal pigment epithelium (RPE) and photoreceptor cells to degenerate and die. However, the specific pathogenic mechanism of AMD has yet to be explored. The development of new AMD therapeutics is urgently required.<br><br>MAIN BODY: Studies have shown that kinases are increasingly important in AMD pathogenesis and treatment. Inhibition of apoptosis in retinal cells, such as RPE cells, maintenance of normal cellular metabolism, and preservation of normal autophagy are among the pathways involved in treating AMD. This is associated with kinase-related pathways, such as the PI3K/Akt, MAPK/ERK, JAK/STAT, mTOR, Ang-Tie, and AMPK signaling pathways.<br><br>CONCLUSIONS: In this review, we highlight recent advances in kinase-related pathways in treating AMD, to provide new directions for the prevention and treatment of AMD.}, }
@article {pmid41502314, year = {2026}, author = {Lee, S and Choi, J and Yu, SY and Kim, K}, title = {Quantitative optical coherence tomography angiography biomarkers Following a Switch to Brolucizumab in Neovascular age-related macular degeneration.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2025.0144}, pmid = {41502314}, issn = {2092-9382}, abstract = {PURPOSE: To evaluate functional and anatomical outcomes, including vessel morphology parameters on swept-source optical coherence tomography angiography (SS-OCTA), in eyes with neovascular age-related macular degeneration (nAMD) switched to brolucizumab.<br><br>METHODS: This retrospective study included 37 eyes with nAMD that were switched from other anti-vascular endothelial growth factor (VEGF) agents to intravitreal brolucizumab. Best-corrected visual acuity (BCVA), injection intervals, central subfield thickness (CST), pigment epithelial detachment (PED) and presence of retinal fluid were compared between baseline and 12 months post-switch. SS-OCTA images were analyzed to quantify macular neovascularization (MNV) area, vessel density, fractal dimension (FD), and lacunarity.<br><br>RESULTS: Switching to brolucizumab significantly extended injection intervals and reduced CST, PED height and retinal fluid, while maintaining BCVA at 12 months. Quantitative OCTA analysis showed reductions in MNV area and FD following the switch. When compared with the preceding 12 months of other anti-VEGF therapy, FD still showed a significant reduction after brolucizumab treatment (p = 0.019). Intraocular inflammation occurred in 1 eye and resolved with topical corticosteroids.<br><br>CONCLUSIONS: Intravitreal brolucizumab demonstrated favorable anatomical improvements and maintained visual outcomes over 12 months. Quantitative OCTA biomarkers, particularly FD, may serve as imaging indicators of disease activity and treatment response in eyes with nAMD undergoing a therapy switch.}, }
@article {pmid41503694, year = {2026}, author = {Hua, Z and Zhu, Q and Yang, J and Tang, M and Yin, J and Zhan, D}, title = {Mendelian Randomization Study of Age-Related Macular Degeneration and Inflammatory Bowel Disease.}, journal = {Current eye research}, volume = {51}, number = {4}, pages = {461-469}, doi = {10.1080/02713683.2025.2602902}, pmid = {41503694}, issn = {1460-2202}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Macular Degeneration/genetics/epidemiology ; *Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; *Inflammatory Bowel Diseases/genetics/complications/epidemiology ; Risk Factors ; C-Reactive Protein/metabolism ; Male ; }, abstract = {PURPOSE: To investigate the causal relationship between age-related macular degeneration (AMD) and inflammatory bowel disease (IBD) by Mendelian randomization (MR) analysis.<br><br>METHODS: The single nucleotide polymorphism data of IBD and AMD were obtained from the Integrative Epidemiology Unit (IEU) Open genome-wide association study database. MR analysis contained MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. Sensitivity analysis was executed to ensure the reliability of results, containing heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Multivariable Mendelian randomization analysis was carried out to investigate potential confounding factors such as C-reactive protein, smoking, vitamin D deficiency. Genes corresponding to the instrumental variables (IVs) and functional enrichment analysis were executed.<br><br>RESULTS: MR analysis showed a positive correlation between IBD and AMD (P&#x2009;<&#x2009;0.05, OR > 1). Sensitivity analyses also did not reveal heterogeneity and horizontal pleiotropy. C-reactive protein, smoking, and vitamin D deficiency had no significant effect on AMD (P&#x2009;>&#x2009;0.05). Genes corresponding to IVs were mainly associated with monocyte differentiation, cytokine receptor activity, etc., and act on signaling pathways such as Th17 cell differentiation, and there was a complex network of molecular-cell regulation.<br><br>CONCLUSION: Our study explored and demonstrated the causal relationship between IBD and AMD through MR analysis, which provided an important reference and direction for future research and treatment related to AMD.}, }
@article {pmid41504873, year = {2026}, author = {Stettler, I and Romano, F and Nigalye, A and Lains, I and Choi, H and Ding, X and Bennett, CF and Overbey, KM and Ploumi, I and Garg, I and Katz, R and Kasetty, M and Vingopoulos, F and Vavvas, DG and Miller, JW and Husain, D and Miller, JB}, title = {Assessing the role of macular pigment optical volume in non-neovascular age-related macular degeneration: associations with rod-mediated dark adaptation and disease progression.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {963-973}, pmid = {41504873}, issn = {1435-702X}, mesh = {Humans ; Disease Progression ; Female ; Male ; Cross-Sectional Studies ; Aged ; *Tomography, Optical Coherence/methods ; *Dark Adaptation/physiology ; *Fluorescein Angiography/methods ; *Macular Pigment/metabolism ; Follow-Up Studies ; *Macular Degeneration/diagnosis/physiopathology/metabolism ; *Macula Lutea/pathology/diagnostic imaging/metabolism ; Middle Aged ; Fundus Oculi ; *Visual Acuity ; Aged, 80 and over ; *Retinal Rod Photoreceptor Cells/physiology ; }, abstract = {PURPOSE: To characterize macular pigment optical volume (MPOV) across non-neovascular age-related macular degeneration (AMD) stages and in healthy controls, and to explore its associations with dark adaptation (DA) time and long-term AMD progression.<br><br>DESIGN: Cross-sectional and longitudinal observation study including patients with non-neovascular AMD (early, intermediate, advanced) per Beckman classification and age-similar controls with no retinal disease. All eyes had good-quality dual-wavelength autofluorescence imaging (Spectralis Investigational MPOD Module).<br><br>METHODS: DA was assessed using the AdaptDx[&#xae;] extended protocol (LumiThera, Poulsbo, WA). MPOV was calculated for three concentric circles centered on the fovea at radii of 1&#xb0;, 2&#xb0;, and 6&#xb0;. AMD progression was determined through consultation of follow-up clinical and imaging data. Mixed-effects linear regression models evaluated baseline differences between AMD and control eyes, and across non-neovascular AMD stages. Progression risk was assessed using mixed-effectsCox proportional hazards models adjusted for age, AREDS2 use, lens opacities, and fellow eye status.<br><br>RESULTS: Our analysis included 110 AMD eyes (58 patients; median age 72, 56.9% female) and 51 control eyes (26 patients; median age 64, 53.9% female). AMD eyes had significantly higher MPOV than controls when calculated at all eccentricities (1, 2, and 6&#xb0;, all p<0.01). In controls, higher MPOV at all eccentricities was associated with shorter DA time (p<0.05) - a relationship not observed in AMD eyes. Of 108 AMD eyes with follow-up (median, 53.1 months), 24 eyes (22.9%) progressed to a more advanced stage. Higher MPOV values at all eccentricities were independently associated with increased progression risk (all p<0.05) CONCLUSIONS: AMD eyes show greater MPOV values than controls, especially in intermediate stages. While MPOV correlated with better DA performance in healthy eyes, this relationship was absent in AMD, suggesting a more complex interaction in diseased retina.}, }
@article {pmid41508137, year = {2026}, author = {Rubio, AP and Dunn, J and Borthwick, J and Saunders, S and Tochel, C and Anderson, H and Coull, L and Javidi, M and Cloete, H and McTrusty, A and Penny, J and MacGillivray, T and Tatham, AJ and Jackson, T and Porteous, C and Strang, N and Dhillon, B and Bernabeu, MO}, title = {Beyond the dataset: integrating public voices in data science.}, journal = {Research involvement and engagement}, volume = {12}, number = {1}, pages = {2}, pmid = {41508137}, issn = {2056-7529}, support = {TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; }, abstract = {The digitalisation of health data has helped drive initiatives like the Scottish Collaborative Optometry-Ophthalmology Network eResearch (SCONe), which links retinal images from community optometry practices with other routinely collected health data to enhance disease detection. As data-driven approaches expand throughout the healthcare system, patient and public involvement and engagement (PPIE) is increasingly recognised as essential for improving the quality, relevance, and acceptability of health research. However, despite growing endorsement, challenges remain, including inconsistent terminology, varying levels of involvement, limited implementation guidance, and a lack of evidence on its impact. These challenges are even more pronounced in data science, particularly within large-scale research, where PPIE is often underreported, leaving the field without a clear framework for meaningful implementation. This article offers a reflective account of the challenges and barriers encountered by SCONe in developing a PPIE strategy. By documenting this process, it provides insights into the complexities of implementing PPIE in large research consortia and offers practical guidance for future initiatives seeking to enhance the impact and relevance of public partnerships in large scale data science research.}, }
@article {pmid41509408, year = {2025}, author = {Chacin Ruiz, EA and Swindle-Reilly, KE and Ford Versypt, AN}, title = {Modeling and Design of Multi-layered Cylindrical Microcapsules for Intravitreal Controlled Release.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.29.696951}, pmid = {41509408}, issn = {2692-8205}, abstract = {Chronic diseases often require repeated oral or local administration, which can compromise patient compliance. In wet age-related macular degeneration (AMD), current therapies rely on intravitreal injections of anti-vascular endothelial growth factor agents every four to six weeks to maintain therapeutic drug levels. Controlled-release drug delivery systems offer a promising alternative by reducing injection frequency and extending drug release. In this study, we developed a continuum diffusion model to describe drug transport through porous polymeric microcapsules, implemented using the finite element method in COMSOL Multiphysics. The case study focused on cylindrical microcapsules fabricated with either a single polycaprolactone (PCL) layer or a bi-layered chitosan-PCL structure, tested at two capsule sizes and three salt leaching concentrations. Bovine serum albumin and bevacizumab were used as model drugs. Parameter estimation was performed using published release data, with a progressive fitting strategy that carried forward parameters from simpler systems into more complex designs. The model reproduced experimental release profiles across formulations and identified key transport parameters governing release dynamics, including porosity, tortuosity, and mass transfer rates. Design exploration revealed that polymer thickness was the dominant factor controlling release, while addition of the chitosan layer moderated the initial burst and extended therapeutic delivery. This framework demonstrates how computational modeling can reduce experimental burden, guide design optimization, and support the development of long-acting intravitreal drug delivery systems to treat wet AMD by linking drug release kinetics to design variables.}, }
@article {pmid41509480, year = {2025}, author = {Alizadeh, AM and Lin, B and Seiler, M and Lyon, DC}, title = {Restoration of Higher-Order Cortical Processing in Rat V2 by Retinal Sheet Transplants in Degenerated Rats.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41509480}, issn = {2692-8205}, support = {P30 EY034070/EY/NEI NIH HHS/United States ; R01 EY032948/EY/NEI NIH HHS/United States ; R01 EY031834/EY/NEI NIH HHS/United States ; P50 GM076516/GM/NIGMS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of central vision loss, and effective treatment options are limited once photoreceptors and the retinal pigment epithelium (RPE) are lost. In advanced stages, vision restoration requires strategies that replace or bypass degenerated retinal circuitry. Retinal sheet transplantation using fetal neural retinal tissue has emerged as a promising intervention, demonstrating long-term survival, integration with the host retina, and partial restoration of light-driven responses. We previously showed that such transplants can restore fundamental visual response properties in the primary visual cortex (V1) of rapidly degenerating rats. However, it remains unclear whether restored retinal input can support higher-order cortical computations that depend on the integration of classical and extra-classical receptive field mechanisms. In this study, we extend this investigation by evaluating whether fetal retinal sheet transplants can restore extra-classical surround modulation in neurons of higher visual areas (V2). Fetal retinal sheets (E18-E19) derived from donor rats were transplanted into one eye of Rho-S334ter line-3 rats at ages P41-P78, when rod degeneration is nearly complete and cones are largely nonfunctional. Animals were assessed 2.2-9.3 months post-surgery using in vivo extracellular single-unit recordings from V2, optokinetic testing, OCT imaging, and histology. Control groups included normal-vision rats, age-matched degenerated rats (AMC), and sham-operated line-3 rats. Transplants survived long term, developed laminated and rosetted photoreceptor structures, and integrated with the host retina. Optokinetic testing revealed significant improvement in spatial acuity in transplanted eyes compared with degenerated controls beginning at three months post-surgery. Transplanted rats exhibited a markedly higher proportion of visually responsive V2 neurons than degenerated animals (21.0% vs. 8.2%). They also showed significantly shorter response latencies and larger visually evoked response amplitudes, indicating improved transmission of retinal signals to the cortex. To quantify surround suppression, neurons were tested with sinusoidal gratings confined to the classical receptive field and gratings extended to full-field size. Transplanted rats displayed robust surround suppression properties similar to normal controls, including significantly reduced firing rates and narrower tuning under full-field conditions. A Support Vector Machine (SVM) classifier trained on net responses to CRF and FF stimulus sizes reliably distinguished control and transplanted neurons from degenerated ones but could not separate control from transplant, further indicating similar response properties in these two groups. These findings provide the first demonstration that retinal sheet transplants restore not only basic visual responses but also higher-order cortical mechanisms involving extra-classical surround suppression. This recovery of surround suppression in V2 suggests that transplanted retinal tissue can re-establish functionally meaningful circuits capable of supporting complex visual processing. The results underscore the therapeutic potential of retinal sheet transplantation for advanced retinal degenerative disease and provide the first evidence of surround suppression in the rat V2.}, }
@article {pmid41510605, year = {2026}, author = {Ma, C and Su, J and Liu, J and Zhao, T and Li, X and Cai, S and Ji, X and Wu, J and Wang, L and Xu, D}, title = {Discovery of (3R,4R)-15: An Advanced Factor B Inhibitor Entering Phase 3 for Complement-Mediated Diseases.}, journal = {Journal of medicinal chemistry}, volume = {69}, number = {2}, pages = {867-894}, doi = {10.1021/acs.jmedchem.5c03532}, pmid = {41510605}, issn = {1520-4804}, mesh = {Humans ; Animals ; Mice ; *Complement Factor B/antagonists &amp; inhibitors ; Structure-Activity Relationship ; Atypical Hemolytic Uremic Syndrome/drug therapy ; *Drug Discovery ; Hemoglobinuria, Paroxysmal/drug therapy ; *Complement Inactivating Agents/pharmacology/pharmacokinetics/chemistry/therapeutic use ; Complement Pathway, Alternative/drug effects ; }, abstract = {The alternative pathway (AP) of the complement system plays a critical role in the pathogenesis of various human diseases, including age-related macular degeneration (AMD), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and several glomerular diseases. Although the approved drug Iptacopan is available, it requires twice-daily oral dosing, resulting in suboptimal patient compliance. Using a scaffold-hopping strategy, we identified the clinical candidate (3R,4R)-15, which exhibits potent inhibitory activity against factor B (FB) and the AP, with IC50 values of 10.2 nM and 59.3 nM, respectively. Furthermore, this compound exhibits significantly improved pharmacokinetic properties, including an oral bioavailability of 69.2% in mice. Preliminary clinical studies indicate that (3R,4R)-15 has promising efficacy in patients with PNH. Its once-daily dosing regimen also offers the potential to markedly improve patient compliance. (3R,4R)-15 is currently in Phase 3 trials evaluating its efficacy for the treatment of PNH.}, }
@article {pmid41510735, year = {2026}, author = {Fnu, G and Bhatt, P and Gupta, SV and Sharma, P and Sutariya, V}, title = {Formulation Development and In vitro Characterization of Nanoparticles of Pazopanib for Wet Macular Degeneration.}, journal = {Current drug delivery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672018385478251124140833}, pmid = {41510735}, issn = {1875-5704}, abstract = {INTRODUCTION: One of the primary causes of severe vision loss globally is age-related macular degeneration (AMD), and the mainstay of therapies for neovascular diseases is intravenous administration of anti-VEGF (vascular endothelial growth factor) drugs. The goal of this research is to create an effective delivery of anti-VEGF drugs to overcome the challenges associated with current therapy and adverse effects arising from repetitive intravitreal injections.<br><br>METHODS: Pazopanib (PZ) nanoparticles (NPs) have been generated to deliver the anti-VEGF drug to the posterior segment of the eye over an extended period via intravitreal injection. They were subsequently investigated for physicochemical and in vitro studies.<br><br>RESULTS: The PZ NPs were found to be nano-sized with a particle size of 132.1 &#xb1; 1.4 nm and a PDI of 0.125 &#xb1; 0.023. The results showed that the zeta potential was -20.12 &#xb1; 2.7 mV and the entrapment efficiency was 33.9 &#xb1; 2.5%. Up to seven days of controlled drug release was observed in an in vitro drug release study. The PZ NPs were further assessed for cell cytotoxicity, cellular uptake, and anti- VEGF assays in in vitro cell culture investigations employing human retinal pigment epithelium cells (ARPE-19). In vitro cell culture tests revealed that, in comparison to the drug solution, the PZ NPs formulation was well taken up by the cells and less cytotoxic, as well as exhibited greater antiangiogenic efficacy by inhibiting VEGF expression for an extended period of time.<br><br>DISCUSSION: The NPs demonstrated sustained drug release, driven by their controlled degradation kinetics. Increased potential intensity enhanced electrostatic repulsion, thereby improving NP stability. The low entrapment efficiency of PZ in the NPs was likely due to drug diffusion during emulsification and poor compatibility with the hydrophilic polymer matrix. For in vitro studies, ARPE-19 cells were selected due to their retinal pigment epithelial (RPE)-like properties, making them suitable for AMD drug testing. Efficacy (ELISA) assessments revealed that NP formulations had a stronger inhibitory effect than free drug solutions.<br><br>CONCLUSION: The proposed PZ NPs were successfully developed, characterized, and demonstrated potential application in the treatment of AMD.}, }
@article {pmid41510773, year = {2026}, author = {Bazan, NG}, title = {Elovanoids: linking nutrition to neuroprotection.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {29}, number = {2}, pages = {111-122}, doi = {10.1097/MCO.0000000000001198}, pmid = {41510773}, issn = {1473-6519}, mesh = {Humans ; *Neuroprotection ; *Docosahexaenoic Acids/metabolism/pharmacology ; *Neuroprotective Agents/pharmacology ; Animals ; Antioxidants/metabolism ; Macular Degeneration/prevention &amp; control ; Diet ; Aging ; }, abstract = {PURPOSE OF REVIEW: Elovanoids are homeostatic lipid mediators derived from the very long-chain n-3 polyunsaturated fatty acids, which are in turn derived from docosahexaenoic acid (DHA). The aim of this review is to summarize the latest research on these lipid mediators.<br><br>RECENT FINDINGS: Elovanoids beneficially modulate thioredoxin reductase 1, a key component in the activation of the cellular glutathione antioxidant system. Elovanoids prevent oligomeric amyloid-beta-induced senescence and inflammaging in retinal pigment epithelium and other cells. Rod cells' ability to use DHA to produce elovanoid precursors is decreased in age-related macular degeneration, a disease that causes photoreceptor loss and blindness.<br><br>SUMMARY: Elovanoids are molecular guardians of nervous system integrity that introduce a new aspect of neuroprotective signaling by serving as an initial line of defense when neural cell homeostasis is jeopardized. Appropriate diet contributes to healthy aging by providing the precursor (DHA) that favors elovanoid-mediated neuroprotection in conditions including stroke, traumatic brain injury, macular degeneration, Alzheimer's, and Parkinson's.}, }
@article {pmid41511370, year = {2026}, author = {Park, S and Song, YS and Feng, X and Sorenson, CM and Sheibani, N}, title = {Caffeine Mitigates Adenosine-Mediated Angiogenic Properties of Choroidal Endothelial Cells Through Antagonism of A1 Adenosine Receptor and PI3K-AKT Axis.}, journal = {Cells}, volume = {15}, number = {1}, pages = {}, pmid = {41511370}, issn = {2073-4409}, support = {P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; Research Award//Arthur and Nancy Nesbit AMD fund/ ; P30 CA014520/CA/NCI NIH HHS/United States ; AMD Research Award//Carl Marshall Reeves &amp; Mildred Almen Reeves Foundation/ ; EY030076/EY/NEI NIH HHS/United States ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; R21 EY034646/EY/NEI NIH HHS/United States ; Endoument Fund//Retina Research Foundation/ ; Unrestricted award to the Department of Ophthalmology and Visual Science//Research to Prevent Blindness/ ; AMD Research Award//The Edward N. &amp; Della L. Thome Memorial Foundation/ ; R01 EY030076/EY/NEI NIH HHS/United States ; }, mesh = {*Endothelial Cells/drug effects/metabolism/pathology ; *Caffeine/pharmacology ; Animals ; *Choroid/pathology/blood supply ; Humans ; *Phosphatidylinositol 3-Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; *Adenosine/metabolism/pharmacology ; *Receptor, Adenosine A1/metabolism ; Mice ; }, abstract = {Aging reduces the tissue regenerative capacity, promotes chronic inflammation, and contributes to neurodegenerative diseases, including age-related macular degeneration (AMD). AMD is a leading cause of vision loss in older adults and manifests as dry (atrophic) or wet (neovascular) disease. Although dry AMD is more prevalent, neovascular AMD (nAMD) causes the most severe vision impairment and remains a major public health burden. Oxidative stress-mediated inflammation and dysfunction of retinal pigment epithelium (RPE) cells and choriocapillaris drive early AMD. Neovascular AMD is marked by pathologic choroidal neovascularization (CNV), driven largely by dysregulated VEGF signaling. Anti-VEGF therapies are the current standard of care for nAMD but require frequent intravitreal injections, carry procedure-related risks, and are ineffective in a substantial subset of patients, underscoring the need for new therapeutic approaches. Caffeine, a widely consumed and well-tolerated adenosine receptor antagonist, has emerging relevance in vascular regulation and inflammatory signaling. Extracellular ATP and its metabolites, including adenosine, accumulate under stress and act through purinergic receptors to influence angioinflammatory processes. We recently showed that systemic caffeine administration suppressed CNV in vivo, an effect partly reproduced by the adenosine receptor A2A antagonist Istradefylline. Here, we investigated the cell-autonomous effects of caffeine on mouse choroidal endothelial cells, focusing on its role as an adenosine receptor antagonist and its potential to inhibit pathological neovascularization.}, }
@article {pmid41512710, year = {2026}, author = {Shanidze, NM and Agathos, CP and Ellmers, TJ and Young, WR}, title = {Links between central visual field loss and movement processing during walking.}, journal = {Gait &amp; posture}, volume = {125}, number = {}, pages = {110095}, pmid = {41512710}, issn = {1879-2219}, support = {90REGE0018/ACL/ACL HHS/United States ; K99 EY026994/EY/NEI NIH HHS/United States ; R00 EY026994/EY/NEI NIH HHS/United States ; T32 EY025201/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Walking/physiology ; *Postural Balance/physiology ; Middle Aged ; Case-Control Studies ; *Visual Fields/physiology ; Aged ; Attention/physiology ; Gait/physiology ; *Vision Disorders/physiopathology ; Contrast Sensitivity/physiology ; Adult ; }, abstract = {BACKGROUND: Central visual field loss (CFL) is the most common irreversible visual impairment in aging and is associated with higher fall risk and concerns about falling. This study explored the links between CFL severity, functional balance, and walking-related attentional processing implicated in reduced gait performance.<br><br>METHODS: In Study 1, 29 individuals with CFL and 29 age-matched controls completed the Timed Up and Go (TUG) test. In Study 2, 10 CFL participants and 10 controls performed the TUG while acceleration data were collected from head and trunk IMUs. For both studies, we assessed visual impairment severity (contrast sensitivity) and participants' attentional processing during walking (Gait-Specific Attentional Profile, G-SAP).<br><br>RESULTS: Both groups showed positive correlations between TUG duration and G-SAP subscales. G-SAP scores were lower in CFL participants with worse contrast sensitivity indicating reduced cognitive processing during walking. Worse contrast sensitivity was also associated with greater head and trunk acceleration and acceleration variability during walking, suggesting reduced gait stability. Higher rumination and conscious movement processing scores also correlated with improved segmental control in CFL.<br><br>SIGNIFICANCE: Increased cognitive processing of gait is associated with impaired functional balance. This association appears to be reversed in CFL, with severe visual deficit diverting cognitive resources from movement control. This altered strategy may prioritise the acquisition and processing of visuospatial information in CFL. The observed postural instability with increasing CFL severity and a lack of excessive cognitive involvement in movement control suggest heightened gait-specific attention could be leveraged for balance and gait training in CFL.}, }
@article {pmid41512983, year = {2026}, author = {Lishinsky-Fischer, N and Gharra, S and Nitzan, I and Chowers, I and Levy, J}, title = {Reduced Risk of Non-Neovascular AMD in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Propensity-Matched Cohort Study.}, journal = {American journal of ophthalmology}, volume = {284}, number = {}, pages = {153-160}, doi = {10.1016/j.ajo.2025.12.035}, pmid = {41512983}, issn = {1879-1891}, mesh = {Humans ; Female ; Male ; *Immune Checkpoint Inhibitors/therapeutic use ; Retrospective Studies ; Aged ; Middle Aged ; Incidence ; *Propensity Score ; Follow-Up Studies ; Risk Factors ; Aged, 80 and over ; *Neoplasms/drug therapy ; Melanoma/drug therapy ; *Macular Degeneration/epidemiology/prevention &amp; control/diagnosis ; }, abstract = {PURPOSE: To evaluate whether immune checkpoint inhibitors (ICIs), which modulate T-cell activity in cancer therapy, influence the risk of developing age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Adults aged &#x2265;60 years with a history of cancer, identified from the TriNetX Global Collaborative Network. Only patients who remained alive throughout the follow-up period were included.<br><br>METHODS: Two cohorts were constructed: patients who received ICIs and those who did not. Sub-analyses were conducted for patients with melanoma and for those with metastatic disease. Propensity score matching (1:1) was performed using demographic and clinical covariates. Kaplan-Meier estimates and Cox proportional hazards models assessed the association between ICI exposure and AMD incidence over 5 years.<br><br>MAIN OUTCOME MEASURES: Incidence of non-neovascular and neovascular AMD after ICI therapy.<br><br>RESULTS: After matching, 36,037 patients were included in each cohort. ICI-treated patients had a significantly lower risk of developing non-neovascular AMD (hazard ratio [HR], 0.77; 95% CI, [0.63, 0.93]; log-rank P = .0084) over a 5-year follow-up. No significant association was observed between ICI exposure and neovascular AMD. The protective association persisted in melanoma and metastatic subgroups.<br><br>CONCLUSIONS: In this large, multicenter cohort, ICI therapy was associated with a reduced risk of non-neovascular AMD in older adults with cancer. These findings suggest a potential protective role of T-cell modulation in AMD pathogenesis and highlight the need for further research into the retinal effects of ICIs.}, }
@article {pmid41513432, year = {2026}, author = {Zhou, J and He, Y and Wang, J and Wu, H and Huang, X and Cao, J and Tham, YC and Zhang, C and Cheng, CY and Ye, J}, title = {Exposure-wide approaches identifying modifiable factors for age-related macular degeneration.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328446}, pmid = {41513432}, issn = {1468-2079}, abstract = {PURPOSE: The present study aimed to systematically investigate modifiable factors for age-related macular degeneration (AMD) using novel exposure-wide strategies in a large cohort, and then assess the preventability of AMD.<br><br>METHODS: Using data from the UK Biobank (UKB), a total of 331 modifiable factors from seven categories were included. Exposures were first screened using Cox proportional hazards models with each examined individually, and associated exposures were then tested in a mutually adjusted model for final validation. We calculated joint effect scores by combining validated exposures based on the category and tested the joint associations with AMD. We eventually estimated population attributable fraction to assess the overall preventability of AMD.<br><br>RESULTS: A total of 478&#x2009;867 UKB participants were included. After a median of 13.63 years of follow-up, 10&#x2009;903 (2.28%) were diagnosed with incident AMD. Among all 331 modifiable factors, 177 passed the exposure-wide association scan, with 34 exposures remaining statistically significant after mutual adjustment, distributed in 5 categories. Joint effects of these categories were significantly associated with AMD even among populations with higher AMD Polygenic Risk Score. Overall, we estimated that 30.4%-45.1% of AMD cases could be prevented by intervening in these factors.<br><br>CONCLUSIONS: Modifiable factors across multiple categories are associated with AMD, and active interventions targeting these factors can reduce AMD incidence by 30.4%-45.1%. This study also underscores the need for a systematic approach in uncovering modifiable factors and providing population-level knowledge basis for disease prevention.}, }
@article {pmid41513729, year = {2026}, author = {Song, JR and Park, UC and Lee, CS and Cho, JJ and Kim, JY and Baek, SC and Jeong, A and Sharma, A and Kim, JH and Sagong, M and Woo, SJ and , }, title = {Real-world outcomes of ranibizumab biosimilars in various retinal diseases: a Korean multi-center experience-ROSE Korea Study.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4220}, pmid = {41513729}, issn = {2045-2322}, support = {RS-2024-00512384//Ministry of Health and Welfare/ ; }, mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage/adverse effects ; Male ; Female ; Republic of Korea ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage/adverse effects ; Aged ; Retrospective Studies ; Middle Aged ; Intravitreal Injections ; Treatment Outcome ; *Retinal Diseases/drug therapy ; Visual Acuity/drug effects ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Macular Degeneration/drug therapy ; Macular Edema/drug therapy ; }, abstract = {This study aims to investigate efficacy and safety of ranibizumab biosimilars (Amelivu[®] and LucenBS[®]) across retinal diseases in Korean clinical practice. This retrospective, multicenter study enrolled 1153 eyes from 1075 patients across five centers in South Korea between May 2022 and October 2024. Patients received intravitreal ranibizumab biosimilars for neovascular age-related macular degeneration, retinal vein occlusion with macular edema, diabetic macular edema, and other retinal diseases. Treatment-naïve eyes comprised 408 cases (35.4%), while 745 eyes (64.6%) had prior anti-VEGF treatment. Amelivu was administered to 1007 eyes with 3.1 ± 1.9 injections over 10.2 ± 6.1 months; LucenBS to 146 eyes with 3.1 ± 2.0 injections over 12.0 ± 4.9 months. Amelivu demonstrated significant BCVA(logMAR) improvements from baseline (0.63 ± 0.62) to 12 months (0.55 ± 0.61, P < 0.01). LucenBS maintained logMAR VA from 0.64 ± 0.63 to 0.63 ± 0.68 at 12 months (P = 0.40). Both biosimilars achieved significant CMT reductions through 12 months: Amelivu from 398.0 ± 169.4 μm to 323.0 ± 128.8 μm (P < 0.01); LucenBS from 368.7 ± 172.0 μm to 306.0 ± 144.1 μm (P < 0.01). Treatment-naïve eyes showed superior CMT reduction (111.8 μm) compared to previously treated eyes (53.5 μm). Only one injection-related adverse event occurred: asymptomatic anterior chamber cells in the Amelivu group, resolving with topical treatment. Ranibizumab biosimilars demonstrated visual stabilization and significant anatomical improvements across retinal diseases with excellent safety profiles.}, }
@article {pmid41513975, year = {2026}, author = {Cozzi, M and Airaldi, M and Barbieri, L and Sadda, SR and Staurenghi, G and Corvi, F}, title = {The impact of macular neovascularization development on geographic atrophy progression.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {264}, number = {4}, pages = {983-990}, pmid = {41513975}, issn = {1435-702X}, }
@article {pmid41514281, year = {2026}, author = {Almansa-García, AC and Armento, A and Cao, B and Petremann-Dumé, AS and Salmaso, S and Caliceti, P and Henes, C and Bolz, S and Kilger, E and Süsskind, D and Ueffing, M and Arango-Gonzalez, B}, title = {Safety and neuroprotective efficacy of the VCP inhibitor ML240 in large-animal and human retinal explants: a preclinical ex vivo study.}, journal = {BMC medicine}, volume = {24}, number = {1}, pages = {54}, pmid = {41514281}, issn = {1741-7015}, support = {AR1432/2-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Humans ; *Retina/drug effects/pathology ; Swine ; *Valosin Containing Protein/antagonists &amp; inhibitors ; *Neuroprotective Agents/pharmacology/adverse effects ; Macaca ; }, abstract = {BACKGROUND: Retinal degenerative diseases represent a complex global health problem due to their significant impact on patients' daily lives and their highly heterogeneous pathogenesis, which challenges therapeutic development. Despite this complexity, many diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), share common features, including disrupted proteostasis, oxidative stress, and inflammatory responses, eventually leading to photoreceptor (PR) degeneration and vision loss. The inhibition of valosin-containing protein (VCP) has emerged as a promising mutation-independent therapeutic strategy for RP. However, clinical translation requires rigorous validation in models that closely reflect human retinal physiology.<br><br>METHODS: Organotypic retinal explants from porcine, macaque, and human donors were placed in an in vitro culture setup and treated with ML240, a selective VCP inhibitor, delivered either as a free compound or encapsulated in mPEG5kDa-cholane. Photoreceptor survival was assessed via TUNEL assay, outer nuclear layer (ONL) row quantification, and immunostaining. Retinal inflammation was evaluated by microglial staining. A dose-response study was performed to determine safety margins across species, and additional retinal markers were used to assess the preservation of non-photoreceptor retinal cell populations.<br><br>RESULTS: Porcine retinal explants exhibited progressive photoreceptor degeneration under ex vivo conditions. Treatment with ML240, particularly when formulated with mPEG5kDa-cholane, significantly reduced photoreceptor cell death and microglial activation. Macaque and human explants exhibited minimal to no signs of degeneration. Treatment did not affect morphological or histological features of the explant, demonstrating the safety of ML240 in the primate retina.<br><br>CONCLUSIONS: VCP inhibition via ML240 demonstrates an uncompromised safety profile in porcine, macaque, and human retinal explants. In addition, the neuroprotective activity of ML240 was evident in porcine tissue. Formulation with mPEG5kDa-cholane enhances the overall performance of the compound, supporting its use for future clinical application as a mutation-independent therapeutic approach for retinal degenerative diseases.}, }
@article {pmid41515537, year = {2025}, author = {Desmettre, T and Ledesma-Gil, G and Paques, M}, title = {Diagnostic Performance of Ring Aperture Retro Mode Imaging for Detecting Pigment Migration in Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, pmid = {41515537}, issn = {2075-4418}, abstract = {Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns-including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen-were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice.}, }
@article {pmid41516080, year = {2025}, author = {Bhandari, SK and Lee, S and Kim, HJ}, title = {Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516080}, issn = {1422-0067}, support = {20230632//the Bisa Research Grant of Keimyung University/ ; }, mesh = {Humans ; Animals ; *Geographic Atrophy/pathology/metabolism/drug therapy/etiology/therapy ; Disease Models, Animal ; *Macular Degeneration/pathology/metabolism/etiology/drug therapy ; Oxidative Stress ; Mitochondria/metabolism ; }, abstract = {Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD-accounting for more than 85% of cases-progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies-including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches-and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD.}, }
@article {pmid41517415, year = {2025}, author = {Rodriguez-Vidal, C and Galletero Pandelo, L and Martínez-Alday, N and Bande, M and Blanco Teijeiro, MJ}, title = {Ultrasound-Enhanced Assessment of Vitreous Status in Exudative AMD: Associations with Neovascular Phenotypes, Treatment Burden, and Functional Outcomes.}, journal = {Journal of clinical medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41517415}, issn = {2077-0383}, abstract = {Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters-including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness-along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = -0.27; 95% CI -0.42 to -0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings.}, }
@article {pmid41517652, year = {2022}, author = {Ledesma-Gil, G and Otero-Marquez, O and Alauddin, S and Tong, Y and Tai, K and Lloyd, H and Koci, M and Scolaro, M and Pillai, C and Ye, C and Govindaiah, A and Bhuiyan, A and Dhamoon, MS and Deobhakta, A and Lema, G and Narula, J and Rosen, RB and Yannuzzi, LA and Freund, KB and Smith, RT}, title = {Subretinal drusenoid deposits are strongly associated with coexistent high-risk vascular diseases.}, journal = {BMJ open ophthalmology}, volume = {7}, number = {1}, pages = {}, pmid = {41517652}, issn = {2397-3269}, abstract = {BACKGROUND/AIMS: Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs).<br><br>METHODS: Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by &#x3c7;[2] test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates.<br><br>RESULTS: The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9&#xd7;10[-9], OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8&#xd7;10[-5], 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%.<br><br>CONCLUSIONS: High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.}, }
@article {pmid41518379, year = {2026}, author = {Mhmud, H and Vermeulen, JP and Adanc, B and Klevering, JBJ and Groenink-Lindenhovius, C and Tigchelaar, OAM and Ponsioen, TL and Klaver, CCW and Witmer, AN}, title = {Real-world treatment outcomes of aflibercept versus bevacizumab for neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41518379}, issn = {1435-702X}, }
@article {pmid41518383, year = {2026}, author = {Tanaka, F and Mino, T and Moriguchi, Y and Nagahama, H and Sakai, H and Tamura, M and Akiba, M and Enaida, H}, title = {Exploratory investigation of OCTA-VISTA for longitudinal monitoring of neovascular age-related macular degeneration treatment.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41518383}, issn = {1435-702X}, support = {22K09792//KAKENHI/ ; }, }
@article {pmid41519100, year = {2026}, author = {Naux, G and Bellot, L and Le Pabic, E and Mouriaux, F and Maucourant, Y}, title = {[Efficacy and safety of switching from Eylea® and Lucentis® to Ranivisio® in exudative age-related macular degeneration and its impact on treatment costs].}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {2}, pages = {104757}, doi = {10.1016/j.jfo.2025.104757}, pmid = {41519100}, issn = {1773-0597}, mesh = {Humans ; *Ranibizumab/economics/adverse effects/administration &amp; dosage/therapeutic use ; Aged ; Male ; Female ; Intravitreal Injections/economics ; Aged, 80 and over ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/economics/administration &amp; dosage/adverse effects/therapeutic use ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/economics ; *Drug Substitution/economics/adverse effects ; Angiogenesis Inhibitors/economics/administration &amp; dosage/adverse effects/therapeutic use ; *Macular Degeneration/drug therapy/economics ; Middle Aged ; Health Care Costs/statistics &amp; numerical data ; Retrospective Studies ; }, abstract = {INTRODUCTION: The goal of this study was to investigate the efficacy and safety of therapeutic switch of intravitreal injections (IVT) from ranibizumab 10mg/mL (Lucentis®) and aflibercept 40mg/mL (Eylea®) to FYB201 (Ranivisio®) in exudative age-related macular degeneration (AMD). This study includes an analysis of the direct medical cost of managing exudative AMD. The data studied included the mean injection interval in the year preceding the switch and the 9 months following, the longest dry interval over this period, the change in central retinal thickness, tolerance data, the sum of visit costs, treatment costs and an estimate of transportation costs.<br><br>MATERIALS AND METHODS: Fifty-nine eyes of 46 patients treated for exudative AMD were included. Twenty-one eyes were treated with Lucentis&#xae; and 38 eyes with Eylea&#xae; before being switched to Ranivisio&#xae; between February 2023 and May 2024. The primary endpoint was the change in mean inter-injection interval in the pre-switch year versus the mean inter-injection interval in the 3 to 9 months post-switch.<br><br>RESULTS: Patients received a mean of 7.5 IVT of anti-VEGF per eye in the pre-switch year, with a mean inter-injection interval of 6.2 weeks in Treat-and-Extend (TaE) schedule. The switch resulted in an extension of the mean inter-injection interval to 7.1 weeks (P=0.0004) and an extension of the longest dry interval (7.5 versus 6.39, P=0.0057) in the following 3 to 9 months. A reduction in central retinal thickness was observed at 3 months (247&#x3bc;m versus 261&#x3bc;m, P=0.0067), and no adverse effects were noted. In the year prior to switch, total medical costs per patient amounted to &#x20ac;9,397, with &#x20ac;6,542.00 (70%) in medication costs, &#x20ac;2,035.50 (21%) in ophthalmologic follow-up costs and &#x20ac;819.60 (9%) in transportation costs. After the switch, with a mean Ranivisio&#xae; inter-injection interval of 7.1 weeks, the annual treatment cost per eye was estimated at &#x20ac;2,388.00 for 7.33 annual IVTs.<br><br>DISCUSSION: This study is consistent with data in the literature demonstrating the benefits of therapeutic switches in extending inter-injection intervals and improving retinal dryness, probably due to this method being a work-around for tachyphylaxis.<br><br>CONCLUSION: Switching from Eylea&#xae; and Lucentis&#xae; to Ranivisio&#xae; is effective in exudative AMD, with a good safety profile, and could help to reduce treatment costs.}, }
@article {pmid41519378, year = {2026}, author = {Jeong, H and Eppel, PS and Kaelber, DC and Singh, RP and Talcott, KE}, title = {Malabsorption Syndromes and Risk of Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.002}, pmid = {41519378}, issn = {2468-6530}, abstract = {PURPOSE: Despite mechanistic links connecting malnutrition and gut microbiome with retinal health, clinical research exploring the relationship between malabsorption syndromes and age-related macular degeneration (AMD) remains limited. This study compared the risks of AMD diagnosis in patients with and without various malabsorption syndrome diagnoses.<br><br>DESIGN: Retrospective cohort study of aggregated, deidentified patient data from multiple health care organizations across the United States using the TriNetX US Collaborative Research Network in November 2025.<br><br>PARTICIPANTS: Adults with a cataract-related International Classification of Diseases (ICD) encounter diagnosis codes and no baseline AMD ICD encounter diagnosis codes were divided into groups based on the presence of ICD encounter diagnosis codes for celiac disease, ulcerative colitis (UC), Crohn's disease (CrD), chronic pancreatitis (CP), and short bowel syndrome (SBS). Within the CP cohort, patients with pancreatic enzyme replacement therapy (PERT) prescription orders were subanalyzed. For each cohort, a corresponding control cohort of patients without the respective ICD encounter diagnosis codes was created.<br><br>METHODS: The study and control cohorts were propensity-matched 1:1 on demographic factors, comorbidities, and disease-related conditions and prescription orders. The matched cohorts were compared on the risk of having AMD ICD encounter diagnoses.<br><br>MAIN OUTCOME MEASURES: Risk ratios (RRs) and 95% confidence intervals (CIs) of having an AMD ICD encounter diagnosis code with an accompanying retinal OCT Common Procedural Terminology code. Significance was defined as CI &#x2264;0.9 or &#x2265;1.1.<br><br>RESULTS: Compared with controls without inflammatory bowel diseases, the CrD cohort (n = 9537, RR = 1.42, CI = 1.15-1.74), but not the UC cohort (n = 15,039, RR = 1.28, CI = 1.09-1.51), had a higher risk of having early/intermediate AMD. Chronic pancreatitis was associated with an increased risk of AMD (n = 12,856, RR = 1.82, CI = 1.53-2.16), even in the PERT subset (n = 3812, RR = 1.83, CI = 1.35-2.48). Short bowel syndrome (n = 3747) was associated with an increased risk of advanced/exudative AMD (RR = 1.98, CI = 1.31-2.98), but not early/intermediate AMD (RR = 1.28, CI = 0.96-1.71). Celiac disease was not associated with increased AMD risk (n = 9315, RR = 1.09, CI = 0.88-1.35).<br><br>CONCLUSIONS: Chronic noninfectious causes of malabsorption syndromes-CrD, CP, and SBS-may represent underrecognized risk factors of AMD. This explorative study adds clinical evidence for a potential role of the gut-retina axis in the pathogenesis of AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41519383, year = {2026}, author = {Chang, A and Sun, X and Iida, T and Lai, TYY and Wong, TY and Cheung, CMG and Lee, WK and Zhang, X and Schulze, A and Schmidt-Ott, UM and Zhao, M and Hasanbasic, Z and Leal, S and Chen, SJ and , }, title = {Intravitreal aflibercept 8 mg versus 2 mg in Asian patients with neovascular age-related macular degeneration: 48-week analysis of the Phase 3 PULSAR trial.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {15}, number = {1}, pages = {100278}, doi = {10.1016/j.apjo.2026.100278}, pmid = {41519383}, issn = {2162-0989}, mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; Male ; Female ; Aged ; *Visual Acuity ; Middle Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Tomography, Optical Coherence ; Dose-Response Relationship, Drug ; Aged, 80 and over ; Follow-Up Studies ; Double-Blind Method ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Asian People ; Time Factors ; Fluorescein Angiography ; }, abstract = {PURPOSE: To evaluate 1-year efficacy and safety of aflibercept 8 mg in Asian patients with neovascular age-related macular degeneration (nAMD) in the PULSAR (NCT04423718) trial.<br><br>DESIGN: Subgroup analysis of the Phase 3 PULSAR trial.<br><br>METHODS: Patients aged &#x2265;&#x202f;50 years with nAMD were randomized to receive intravitreal aflibercept 8&#x202f;mg every 12 (8q12) or 16 (8q16) weeks, or aflibercept 2&#x202f;mg every 8 weeks (2q8), following 3 initial monthly injections. Outcomes included change from baseline in best-corrected visual acuity (BCVA) and central subfield retinal thickness (CRT), durability, and safety at week (W) 48.<br><br>FINDINGS: Overall, 234 Asian patients participated and received study treatment (8q12 [n&#x202f;=&#x202f;74], 8q16 [n&#x202f;=&#x202f;77], and 2q8 [n&#x202f;=&#x202f;83]). At W48, the least squares (LS) mean (95&#x202f;% CI) BCVA change from baseline was +&#x202f;9.9 (6.9, 12.9), +&#x202f;9.2 (7.1, 11.2), and +&#x202f;7.6 (4.7, 10.5) letters in the 8q12, 8q16, and 2q8 groups, respectively. The LS mean (95&#x202f;% CI) change in CRT from baseline to W48 for the 8q12, 8q16, and 2q8 groups was -141 (-152, -129), -156 (-167, -146), and -142 (-155, -129) &#xb5;m, respectively. Most patients receiving 8q12 (85&#x202f;%) or 8q16 (87&#x202f;%), maintained their randomized dosing interval, through W48. The safety profile of aflibercept 8&#x202f;mg was comparable to aflibercept 2&#x202f;mg.<br><br>CONCLUSIONS: Aflibercept 8&#x202f;mg was effective and well tolerated in Asian patients with nAMD, with demonstrated improvements in functional and anatomic outcomes comparable to aflibercept 2&#x202f;mg at W48. Aflibercept 8&#x202f;mg outcomes were achieved with fewer injections than with aflibercept 2&#x202f;mg, consistent with overall PULSAR results.}, }
@article {pmid41519611, year = {2026}, author = {Cornejo-Uixeda, S and Borrás-Blasco, J and Valcuende-Rosique, A and Gil, LP and Monteagudo-Martinez, N and Merino, V}, title = {Dosing interval optimization and persistence with faricimab in age-related macular degeneration: An observational study in real-world clinical practice.}, journal = {Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.farma.2025.12.002}, pmid = {41519611}, issn = {2171-8695}, abstract = {OBJECTIVE: To evaluate treatment persistence and dosing interval extension with faricimab in neovascular age-related macular degeneration (nAMD) in real-world practice.<br><br>METHODS: Retrospective observational study conducted in a tertiary hospital (March 2024-March 2025). Patients receiving faricimab (treatment-na&#xef;ve or pre-treated with anti-VEGF therapy), with &#x2265;1 post-loading dose, were included. Dosing intervals were analyzed at baseline, 6 and 12&#x202f;months, Adherence was assessed with the medication possession ratio (MPR), with >80% considered adherent. Persistence was defined as the time from treatment initiation to discontinuation or end of follow-up. Persistence was estimated using Kaplan-Meier survival analysis.<br><br>RESULTS: We included 129 patients (148 eyes), mean age 74.5&#x202f;&#xb1;&#x202f;8.85&#x202f;years; 55% were female. A total of 39 patients (30.2%) were treatment-na&#xef;ve and 90 (69.8%) were pretreated. At 12&#x202f;months, 48.8% of na&#xef;ve and 55.5% of pretreated patients achieved 8-12&#x202f;weeks intervals. Mean persistence was 12.2&#x202f;months (SD 0.2; 95% CI: 11.8-12.6). The median was not reached by the end of the study. Persistence rate was 93% at 6 and 12&#x202f;months. Only one patient discontinued due to inefficacy. No serious adverse events or endophthalmitis occurred.<br><br>CONCLUSIONS: Faricimab showed excellent persistence and extended dosing intervals in real-world practice. This is the first study specifically evaluating faricimab real-world persistence in nAMD.}, }
@article {pmid41519739, year = {2026}, author = {Thomsen, AK and Steffensen, MA and Gotfredsen, K and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL}, title = {CD8+ T cell aging is associated with macular neovascularization area change in neovascular age-related macular degeneration: a prospective cohort study.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {66}, pmid = {41519739}, issn = {1471-2415}, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is characterized by formation of macular neovascularization (MNV). The aging immune system plays an important role in nAMD pathogenesis. Loss of the costimulatory markers CD27 and CD28 on T cells and increased T cell differentiation is associated with immunosenescence and proinflammatory T cell activation. In this study we investigate the association between MNV area change following anti-VEGF treatment and the aging T cell profile in nAMD patients.<br><br>METHODS: This prospective cohort study included treatment-na&#xef;ve nAMD patients. Participants were examined with optical coherence tomography angiography at time of diagnosis and following loading dose to assess the MNV area change. A blood sample was analyzed for circulating aging T cell profile with flow cytometry for the costimulatory markers CD27, CD28, and CD56, as well as T cell differentiation (na&#xef;ve, central memory, and effector memory) of CD4+&#x2009;and CD8+&#x2009;T cells.<br><br>RESULTS: 54 eyes of 54 patients were included. A significant association was found between a reduction of MNV area and a reduction of the CD8+CD27- T cell proportion (&#x3b2;, 0.71; 95% CI, 0.17 to 1.26; P&#x2009;=&#x2009;0.035), as well as CD8+CD28- T cell proportion (&#x3b2;, 0.72; 95% CI, 0.20 to 1.23; P&#x2009;=&#x2009;0.035). A non-significant negative trend was observed between MNV area change and CD8&#x2009;+&#x2009;na&#xef;ve T cells (P&#x2009;=&#x2009;0.099).<br><br>CONCLUSION: Our results suggest that a less advanced aging T cell profile characterized by lower levels of CD8+CD27- and CD8+CD28- T cells is associated with a greater reduction of MNV area following anti-VEGF treatment in treatment-na&#xef;ve nAMD patients.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-025-04570-2.}, }
@article {pmid41520064, year = {2026}, author = {Hanson, RLW and Airody, A and Sivaprasad, S and McKibbin, M and Morland, AB and Peto, T and Chakravarthy, U and Gale, RP and , }, title = {Early detection of neovascular age-related macular degeneration in the second eye reduces intravitreal treatment burden: FASBAT report 2.}, journal = {Eye (London, England)}, volume = {40}, number = {4}, pages = {493-497}, pmid = {41520064}, issn = {1476-5454}, support = {OAP030A2401T//Novartis | Novartis Pharmaceuticals UK Limited (Novartis UK)/ ; }, mesh = {Humans ; Intravitreal Injections ; Visual Acuity/physiology ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Tomography, Optical Coherence ; Aged ; Male ; Female ; *Wet Macular Degeneration/diagnosis/drug therapy/physiopathology ; Ranibizumab/administration &amp; dosage ; Early Diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Bevacizumab ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; }, abstract = {BACKGROUND/OBJECTIVES: To investigate if early detection of neovascular age-related macular degeneration (nAMD) in the second eye is associated with a reduced number of intravitreal treatments compared with the first eye using data from the EDNA/FASBAT trial.<br><br>SUBJECTS/METHODS: Post-hoc analysis of 117 participants receiving standard clinical care during the FASBAT study. Assessments were at enrolment and at an average of 18.9 (SD&#x2009;=&#x2009;10.2) and 30.5 (SD&#x2009;=&#x2009;9.7) months in the first eye. Assessment of the second eye was made at the onset of nAMD (as participants were monitored for conversion) and at 12- and 24-months. The annualised injection rate for first eyes and the actual rate for second eyes are reported alongside visual acuity (VA) and optical coherence tomography (OCT) characteristics.<br><br>RESULTS: In second eyes the annualised number of treatments was lower both in year 1 (second eyes mean&#x2009;=&#x2009;6.4, SD&#x2009;=&#x2009;3.4 vs mean&#x2009;=&#x2009;7.2, SD&#x2009;=&#x2009;1.9 in first eyes) and in year 2 (second eyes mean&#x2009;=&#x2009;5.8, SD&#x2009;=&#x2009;2.9; versus mean&#x2009;=&#x2009;6.2, SD&#x2009;=&#x2009;2.7 in first eyes). Second eyes had better VA at the point of conversion to nAMD (mean&#x2009;=&#x2009;74.1, SD&#x2009;=&#x2009;9.9) compared with the first eyes at baseline (mean&#x2009;=&#x2009;55.6, SD&#x2009;=&#x2009;15.3) which was maintained until 24 months (second eye: mean&#x2009;=&#x2009;73.6, SD&#x2009;=&#x2009;9.9; first eye: mean&#x2009;=&#x2009;53.2, SD&#x2009;=&#x2009;19.3). Highly reflective material was detected less frequently in second eyes compared to first eyes at clinical visits.<br><br>CONCLUSIONS: Compared to first eyes, early detection of nAMD in the second eye is beneficial in terms of better maintenance of visual acuity, reduced intravitreal treatment burden, and improved anatomical findings after 2 years of treatment.}, }
@article {pmid41520727, year = {2026}, author = {Zhu, S and Zhang, J and Jiang, X and Peng, C and Liu, H and Qian, F}, title = {Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease.}, journal = {Advanced drug delivery reviews}, volume = {230}, number = {}, pages = {115773}, doi = {10.1016/j.addr.2026.115773}, pmid = {41520727}, issn = {1872-8294}, mesh = {Humans ; *Biological Products/administration &amp; dosage/therapeutic use ; *Eye Diseases/drug therapy ; Animals ; Intravitreal Injections ; }, abstract = {Posterior segment ocular diseases (e.g., age-related macular degeneration and diabetic retinopathy, etc.) often necessitate frequent intravitreal (IVT) injections of biologics, due to the rapid drug clearance and formidable ocular barriers. While molecular engineering strategies and high-concentration protein formulations could extend the administration intervals to a certain extent, they are confronted with critical challenges, protein aggregation, high viscosity, and limited duration. This has spurred the development of innovative biologics-device combination products, which represent a paradigm shift towards prolonged therapy. This comprehensive review examines the latest advancements of these combination platforms, including refillable implants (e.g., SUSVIMO®), encapsulated cell technology (e.g., ENCELTO™), and recombinant adeno-associated virus (rAAV) vectors (e.g., LUXTURNA®). The progress in biologics - device combination technologies has significantly reduced the frequency of ocular injections. However, substantial hurdles, such as instability caused by material-biologics interactions, potential risks during the sterilization and manufacturing processes, safety risks, and the evolving regulatory landscape, still need to be addressed. Achieving a balance between the stability of biologics and advanced device design, enhancing long-term safety, and developing responsive smart systems with real-time monitoring and feedback capabilities remain crucial for the advancement of next-generation ophthalmic therapies.}, }
@article {pmid41524001, year = {2026}, author = {Lischke, R and Krause, SM and Rauchegger, T and Haas, G and Koubek, M and Nowosielski, Y and Rehak, M}, title = {Intraocular inflammation after intravitreal injection of faricimab-a case series including one case of bilateral choroidal involvement.}, journal = {International journal of ophthalmology}, volume = {19}, number = {1}, pages = {185-192}, pmid = {41524001}, issn = {2222-3959}, abstract = {AIM: To report and analyze cases of sterile intraocular inflammation (IOI) following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).<br><br>METHODS: This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy. Comprehensive clinical evaluation was performed, including slit-lamp examination, intraocular pressure (IOP) measurement, fluorescein and indocyanine green angiography (ICGA), and laboratory tests. Inflammatory responses were treated with topical or systemic corticosteroids, and patients were monitored for visual acuity and inflammatory activity.<br><br>RESULTS: The incidence of IOI was 0.8% per patient (Innsbruck) and 0.23% (Czechia), with inflammation typically occurring between the third and sixth injection (mean interval: 10d post-injection). Inflammatory presentations ranged from anterior uveitis to posterior segment involvement. One notable case demonstrated novel choroidal hypofluorescent lesions on angiography, suggesting deeper ocular involvement. The mean patient age was 76y; five of six affected patients were female. All cases responded to local and systemic corticosteroids, with full recovery of initial visual acuity.<br><br>CONCLUSION: Sterile IOI after faricimab appears to be a rare but relevant adverse event. Although the incidence falls within expected ranges for anti-vascular endothelial growth factor (anti-VEGF) agents, the observed choroidal involvement represents a potentially new safety signal. Prompt diagnosis and corticosteroid therapy are effective in all cases. Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.}, }
@article {pmid41524032, year = {2026}, author = {Chu, J and Haddadin, RI and Gill, M}, title = {Successful Cataract Surgery in a Patient with a Port Delivery System Implant for Diabetic Macular Edema.}, journal = {Case reports in ophthalmology}, volume = {17}, number = {1}, pages = {26-31}, pmid = {41524032}, issn = {1663-2699}, abstract = {INTRODUCTION: The Port Delivery Platform (PDS) with ranibizumab is a novel, surgically implanted device designed for continuous intraocular anti-VEGF delivery, approved for neovascular age-related macular degeneration and other retinal vascular diseases, including diabetic macular edema (DME) and diabetic retinopathy. While it can reduce treatment burden, the PDS implant introduces unique surgical considerations, particularly during subsequent ocular procedures.<br><br>CASE PRESENTATION: We report a case of successful cataract extraction and intraocular lens implantation in a 72-year-old female with a PDS implant for DME, enrolled in the Pagoda trial. Cataract surgery was performed via clear corneal incisions while carefully avoiding manipulation of the conjunctiva or implant. The procedure was uneventful, and the implant remained stable intraoperatively and postoperatively. The patient experienced improved visual acuity and underwent an uncomplicated implant refill after 15 days with confirmation of adequate implant coverage at the 6-month follow-up.<br><br>CONCLUSION: This case highlights key surgical considerations to preserve implant integrity and conjunctival health during cataract surgery in eyes with PDS implants. To our knowledge, this is the first report of cataract surgery in a PDS-implanted eye outside a clinical trial, emphasizing that standard phacoemulsification techniques can be safely adapted with proper precautions in this context.}, }
@article {pmid41524223, year = {2026}, author = {Kong, L and Han, X and Qi, S and Li, D and Zhang, J and Zhang, L and Zhang, S and Jiang, Q and Yan, B and Zhao, C}, title = {MSC-Derived Exosomal lnc-AGT-3: A Novel Anti-Angiogenic Target in Age-Related Macular Degeneration Through p53 Signaling Pathway.}, journal = {Aging cell}, volume = {25}, number = {2}, pages = {e70377}, pmid = {41524223}, issn = {1474-9726}, support = {82530031//National Natural Science Foundation of China/ ; 82020108006//National Natural Science Foundation of China/ ; 82501299//National Natural Science Foundation of China/ ; //Open Research Funds of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University./ ; }, mesh = {Humans ; *Exosomes/metabolism ; *RNA, Long Noncoding/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism ; *Mesenchymal Stem Cells/metabolism ; Signal Transduction ; *Macular Degeneration/genetics/metabolism/pathology ; Animals ; Mice ; *Angiogenesis Inhibitors/pharmacology ; Choroidal Neovascularization/genetics/pathology ; Male ; Female ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision impairment in elderly populations, characterized by pathological angiogenesis beneath the macula. Although anti-VEGF therapies have demonstrated clinical effectiveness, significant challenges including drug resistance and the need for frequent intravitreal injections persist. As natural nanovesicles, exosomes derived from mesenchymal stem cell (MSC) can mediate intercellular communication, making them an attractive alternative for modulating cellular processes. This study explored the anti-angiogenic effects of MSC-derived exosomes in nAMD, with particular emphasis on the role of a specific exosomal lncRNA lnc-AGT-3. Our results showed that lnc-AGT-3 expression was reduced in both nAMD patients and choroidal neovascularization (CNV) models, and its overexpression effectively inhibited pathological angiogenesis in vitro and in vivo. Mechanistically, lnc-AGT-3 enhanced the p53 signaling pathway by blocking the ubiquitination and degradation of p53 and ultimately inhibited neovascularization, a process potentially linked to its direct interaction with heterogeneous nuclear ribonucleoprotein K (hnRNP K). Our findings position MSC-derived exosomes enriched with lnc-AGT-3 as an innovative therapeutic paradigm for nAMD, acting through p53 pathway modulation to potentially overcome current treatment limitations.}, }
@article {pmid41524233, year = {2026}, author = {Li, Y and Zhang, Y and Wong, G and Kam, KW and Ho, M and Au, S and Zhang, XJ and Ng, MP and Ip, P and Young, AL and Pang, CP and Tham, CC and Chen, LJ and Yam, JC}, title = {Associations between the Mediterranean lifestyle and incident age-related eye diseases: a longitudinal analysis from the UK Biobank.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04015}, pmid = {41524233}, issn = {2047-2986}, mesh = {Humans ; Female ; Male ; Aged ; United Kingdom/epidemiology ; Middle Aged ; Longitudinal Studies ; *Macular Degeneration/epidemiology ; *Glaucoma/epidemiology ; *Cataract/epidemiology ; Incidence ; *Diet, Mediterranean/statistics &amp; numerical data ; Prospective Studies ; Biological Specimen Banks ; Risk Factors ; Life Style ; UK Biobank ; }, abstract = {BACKGROUND: The Mediterranean lifestyle (MEDLIFE) is generally considered to have a positive effect on several health outcomes. However, little is known about its impact on age-related eye diseases. We aimed to assess the effect of MEDLIFE on the risk of three such diseases: cataract, glaucoma, and age-related macular degeneration (AMD).<br><br>METHODS: We included 113&#x2009;829 participants from the UK Biobank who were free of age-related eye diseases at baseline and followed them up prospectively for disease occurrence. Adherence to MEDLIFE was assessed using 25 items, categorised under three blocks: 'Mediterranean food consumption' (block 1), 'Mediterranean dietary habits' (block 2), and 'physical activity, rest, social habits' (block 3). We used a Cox proportional hazard model to examine the associations of the MEDLIFE index and each of its blocks with incident age-related eye diseases.<br><br>RESULTS: During a median follow-up of 10.5 years, 9954 cases of cataract, 1956 cases of glaucoma, and 1736 cases of AMD were identified. We noted an inverse association between the MEDLIFE index and new-onset cataract (P-value for trend&#x2009;=&#x2009;0.005). A one-point increment in the MEDLIFE score was associated with a 1.5% (95% confidence interval (CI)&#x2009;=&#x2009;0.7-2.3) reduction in the risk of cataract, and with a 2.4% (95% CI&#x2009;=&#x2009;0.5-4.3) reduction in AMD incidence. Analysis of MEDLIFE blocks indicated that block 2 (hazard ratio (HR)&#x2009;=&#x2009;0.97; 95% CI&#x2009;=&#x2009;0.95-0.99) and block 3 (HR&#x2009;=&#x2009;0.97; 95% CI&#x2009;=&#x2009;0.95-0.99) were associated with lower risk of cataract. Block 2 was further related to reduced risk of AMD (HR&#x2009;=&#x2009;0.95; 95% CI&#x2009;=&#x2009;0.91-0.99). Although we found no association between the MEDLIFE index and incident glaucoma, block 3 was associated with lower glaucoma risk (HR&#x2009;=&#x2009;0.94; 95% CI&#x2009;=&#x2009;0.90-0.98).<br><br>CONCLUSIONS: Higher adherence to MEDLIFE was associated with decreased incidence of cataract and AMD, while the 'physical activity, rest, and social interactions' block was related to a lower risk of glaucoma. Our findings suggest that MEDLIFE may serve as a potential behavioural intervention for preventing age-related eye diseases.}, }
@article {pmid41524752, year = {2026}, author = {Kilani, A and Vogt, D and Moysidi, V and Assaf, A and Wolf, A and Vounotrypidis, E}, title = {VEGF-inhibitor switch trial in poor-responsive neovascular age-related macular degeneration: assessing brolucizumab vs. faricimab: VISTA study.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41524752}, issn = {1435-702X}, abstract = {PURPOSE: To compare short-term (12 weeks) and long-term (48 weeks) anatomical and functional outcomes after switching to brolucizumab (BRZ) or faricimab (FAR) under a treat-and-extend (TAE) regimen without an initial loading phase in eyes with poor-responsive neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective, single-center study included eyes with poor-responsive nAMD previously treated with anti-VEGF agents that were switched to BRZ or FAR between 2022 and 2025. Functional outcomes (best-corrected visual acuity [BCVA]) and anatomical parameters (central subfield thickness [CST], fibrovascular pigment epithelial detachment [fvPED] height, intraretinal/subretinal fluid [IRF/SRF], subretinal hyperreflective material [SHRM]) were assessed at baseline, week 12, and week 48. Injection frequency, interval extension, and safety were recorded.<br><br>RESULTS: Sixty-six eyes (41 BRZ, 25 FAR) were included. At 12 weeks, BCVA remained stable (BRZ 0.49 logMAR, FAR 0.40; p&#x2009;=&#x2009;0.10). CST decreased significantly in both groups, greater with BRZ (243&#xa0;&#x3bc;m vs. 280&#xa0;&#x3bc;m; p&#x2009;=&#x2009;0.04). Mean injections (2.95 vs. 3.2; p&#x2009;=&#x2009;0.12) and intervals (5.9 vs. 5.6 weeks; p&#x2009;=&#x2009;0.90) were comparable; no intraocular inflammation (IOI) occurred. At 48 weeks, BCVA was numerically better with FAR (0.20 vs. 0.49 logMAR; p = 0.08). CST reduction was sustained andcomparable (259 &#xb5;m vs. 260 &#xb5;m; p = 0.50). FAR achieved greater fvPED reduction (110 &#xb5;m vs. 160 &#xb5;m; p = 0.022). BRZ required fewer injections (6.3 vs. 7.2; p = 0.009) with similar intervals (9.4 vs. 9.9 weeks; p = 0.80). Mild IOI occurred in two BRZ eyes (4.9%) and none with FAR.<br><br>CONCLUSIONS: In poor-responsive nAMD, switching to BRZ or FAR under a TAE regimen without upload achieved stable vision, sustained CST reduction, and comparable treatment burden over one year. FAR showed greater fvPED regression and a slight functional trend, while BRZ achieved faster fluid resolution with fewer injections.}, }
@article {pmid41524889, year = {2026}, author = {Chen, S and Wang, G and Guan, X and Wang, C and Xiao, Y and Li, X and Hong, S and Zhou, Y and You, Y and Fu, Y and Wang, Y and Zhang, Y and Zhao, H and Zhang, Y and Cheng, Y and Guo, H and Xie, H}, title = {Air pollutants, genetic susceptibility, and the risk of age-related macular degeneration: a large prospective cohort study.}, journal = {European journal of epidemiology}, volume = {41}, number = {2}, pages = {185-196}, pmid = {41524889}, issn = {1573-7284}, support = {82373667//National Natural Science Foundation of China/ ; 82171025//National Natural Science Foundation of China/ ; 2018YFC2000203//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Macular Degeneration/epidemiology/genetics ; Female ; Male ; *Air Pollutants/analysis/adverse effects ; *Genetic Predisposition to Disease ; Prospective Studies ; *Air Pollution/adverse effects/analysis/statistics &amp; numerical data ; Particulate Matter/analysis/adverse effects ; Aged ; Middle Aged ; *Environmental Exposure/adverse effects ; Risk Factors ; United Kingdom/epidemiology ; Nitrogen Oxides/analysis/adverse effects ; Proportional Hazards Models ; Nitrogen Dioxide/analysis/adverse effects ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. However, evidence regarding the relationship between air pollution and AMD is limited, and the modifying effect of genetic susceptibility on this association remains unknown. A total of 445,237 participants without AMD at baseline were included from the UK Biobank. The concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM2.5, PM10, PM2.5-10) were collected by using land-use regression models. Air pollution score (APS) was constructed through summing each pollutant weighted by the regression coefficients with AMD from single-pollutant model. Cox proportional hazard models were used to evaluate hazard rations (HRs) and 95% confidence intervals (95%CIs) of associations between air pollutants and polygenic risk score (PRS) with incident AMD. During a median follow-up of 13.83 years, we observed 9,635 incident AMD events. The HR (95%CI) of incident AMD for each standard deviation increase in NO2, NOx, PM2.5, PM10, and APS were 1.04(1.02, 1.06), 1.03(1.01, 1.05). 1.04(1.02, 1.07), 1.02(1.00, 1.04), and 1.04(1.02, 1.06), respectively. Significant additive interaction effects of NO2, NOx, PM2.5-10, APS and PRS with incident risk of AMD were observed, with the relative excess risk due to the interaction (RERI), attributable proportion (AP), and their 95% CIs of 0.10(0.01, 0.18) and 0.05(0.01, 0.11) for NO2, 0.11(0.01, 0.19) and 0.05(0.02, 0.10) for NOx, 0.15(0.06, 0.23) and 0.08(0.03, 0.13) for PM2.5-10, and 0.12(0.03, 0.20) and 0.06(0.01, 0.11) for APS, respectively. Compared with participants exposed to low level of above air pollutants and low PRS, those exposed to high air pollution and high PRS had almost double incident risk of AMD [HR(95%CI) ranged from 1.83(1.68, 1.99) to 2.03(1.86, 2.21)]. Long-term exposure to air pollutants NO2, NOx, PM2.5, and PM10 showed positive associations with increased risk of AMD, which could be further enhanced by genetic susceptibility.}, }
@article {pmid41525679, year = {2026}, author = {Bindi, J and Choi, R}, title = {Novel Surgical Approach to Submacular Hemorrhage in the Setting of Extensive Pan-retinal Photocoagulation.}, journal = {Retinal cases &amp; brief reports}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICB.0000000000001865}, pmid = {41525679}, issn = {1937-1578}, abstract = {PURPOSE: To describe a novel surgical approach for managing submacular hemorrhage (SMH) in the setting of extensive panretinal photocoagulation (PRP) where conventional displacement techniques are limited by chorioretinal adhesions.<br><br>METHODS: We report the case of a 73-year-old monocular woman with neovascular age-related macular degeneration (AMD) and dense PRP scars who presented with an acute, fovea-involving SMH. A modified pars plana vitrectomy (PPV) was performed using submacular tissue plasminogen activator (tPA), perfluorocarbon liquid (PFCL) tamponade to direct blood toward three small retinotomies, active aspiration, and silicone oil placement.<br><br>RESULTS: This strategy achieved substantial clot evacuation and anatomic resolution. The patient's final visual acuity improved to 20/200.<br><br>CONCLUSION: Multiple small retinotomies with PFCL-assisted drainage may serve as a viable alternative surgical technique for SMH in eyes with extensive PRP scarring, where retinal adhesions preclude conventional displacement methods.}, }
@article {pmid41526441, year = {2026}, author = {Agarwal, D and Bhargava, A and Alsharif, MH and Saeed, S and Alsharif, NHM}, title = {Automatic diagnosis of age-related macular degeneration using machine learning and image processing techniques.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {5037}, pmid = {41526441}, issn = {2045-2322}, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults. Detecting AMD early can prevent the irreversible damage caused in later stages. Most existing methods detect drusens as a preliminary step for AMD detection, which is quite challenging as the drusens are present alongside other exudates in the retina. This paper presents a system for early diagnosis of dry AMD that does not rely on detecting drusens and integrates handcrafted features with machine learning and image processing techniques. The system performs several image processing tasks, including pre-processing a color fundus photograph of the retina, macula detection, Region-of-Interest (RoI) selection around the macula, and feature extraction from the RoI. Several texture and color features of the macula region are extracted and analyzed using t-test and ReliefF feature selection algorithms. Supervised classification techniques such as Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes Classifier (NBC), and Multi-Layer Perceptron (MLP) are trained on the selected features with stratified 10-fold cross-validation to classify retinal images as normal or AMD. The system’s performance is evaluated based on accuracy, error, recall, specificity, precision, and F1-score. Classifiers are trained and tested on three feature sets: texture, color, and a combination of both. The proposed system achieves excellent results with texture features and the SVM classifier, attaining accuracies of 98.89% and 95.43% on the STARE and ODIR datasets, respectively.}, }
@article {pmid41527550, year = {2026}, author = {Wu, P and Lin, M and Chen, Q and Chew, EY and Lu, Z and Peng, Y and Dong, H}, title = {AMD-Mamba: A Phenotype-Aware Multi-modal Framework for Robust AMD Prognosis.}, journal = {Machine learning in medical imaging. MLMI (Workshop)}, volume = {16241}, number = {}, pages = {150-160}, pmid = {41527550}, support = {R21 EY035296/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, making effective prognosis crucial for timely intervention. In this work, we propose AMD-Mamba, a novel multi-modal framework for AMD prognosis, and further develop a new AMD biomarker. This framework integrates color fundus images with genetic variants and socio-demographic variables. At its core, AMD-Mamba introduces an innovative metric learning strategy that leverages AMD severity scale score as prior knowledge. This strategy allows the model to learn richer feature representations by aligning learned features with clinical phenotypes, thereby improving the capability of conventional prognosis methods in capturing disease progression patterns. In addition, unlike existing models that use traditional CNN backbones and focus primarily on local information, such as the presence of drusen, AMD-Mamba applies Vision Mamba and simultaneously fuses local and long-range global information, such as vascular changes. Furthermore, we enhance prediction performance through multi-scale fusion, combining image information with clinical variables at different resolutions. We evaluate AMD-Mamba on the AREDS dataset, which includes 45,818 color fundus photographs, 52 genetic variants, and 3 socio-demographic variables from 2,741 subjects. Our experimental results demonstrate that our proposed biomarker is one of the most significant biomarkers for the progression of AMD. Notably, combining this biomarker with other existing variables yields promising improvements in detecting high-risk AMD patients at early stages. These findings highlight the potential of our multi-modal framework to facilitate more precise and proactive management of AMD.}, }
@article {pmid41528844, year = {2026}, author = {Wang, SK and Li, J and Nair, S and Kosaraju, R and Chen, Y and Zhang, Y and Kundaje, A and Liu, Y and Wang, N and Chang, HY}, title = {Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116814}, pmid = {41528844}, issn = {2211-1247}, support = {RM1 HG007735/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/genetics/pathology ; *Choroid/metabolism/pathology ; *Enhancer Elements, Genetic/genetics ; *Single-Cell Analysis/methods ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Genome-wide association studies (GWASs) of AMD have identified dozens of risk loci that may house disease targets. However, variants at these loci are largely noncoding, making it difficult to assess their function and whether they are causal. Here, we present a single-cell gene expression and chromatin accessibility atlas of human retinal pigment epithelium (RPE) and choroid to systematically analyze both coding and noncoding variants implicated in AMD. We employ HiChIP and activity-by-contact modeling to map enhancers in these tissues and predict cell and gene targets of risk variants. We further perform allele-specific self-transcribing active regulatory region sequencing (STARR-seq) to functionally test variant activity in RPE cells, including in the context of complement activation. Our work nominates pathogenic variants and mechanisms in AMD and offers a rich and accessible resource for studying diseases of the RPE and choroid.}, }
@article {pmid41529041, year = {2026}, author = {Helmy, YA and Rahman, NK and Rahman, KT and Groppe, M and Bindra, MS and Latasiewicz, M}, title = {Comparison of intravitreal and subretinal tPA for acute submacular haemorrhage: A retrospective study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251413662}, doi = {10.1177/11206721251413662}, pmid = {41529041}, issn = {1724-6016}, abstract = {PurposeThis study compares the anatomical and functional outcomes of two treatments for acute submacular haemorrhage (SMH): pars plana vitrectomy with subretinal recombinant tissue plasminogen activator (tPA) and gas tamponade versus intravitreal tPA and gas injection.MethodsA retrospective single-centre study was conducted of patients treated for acute SMH at Buckinghamshire Healthcare NHS Trust between January 2016 and December 2022. Patients received either intravitreal tPA and gas ± anti-VEGF (Group A) or pars plana vitrectomy with subretinal tPA and gas tamponade ± anti-VEGF (Group B). The primary outcome was anatomical success, defined as displacement of haemorrhage from the fovea. Secondary outcomes were visual acuity (VA) improvement, central foveal thickness (CFT) reduction, and complication rates.ResultsEighty eyes from 73 patients (mean age: 79.8 ± 11.5 years; 57.5% female) were analysed, with 53 eyes in Group A and 27 in Group B. Anatomical success was achieved in 71.6% of Group A and 77.8% of Group B. VA improved in 66% of Group A and 63% of Group B. CFT decreased by over 50% in both groups. No statistically significant differences were found between the two treatment groups and in anatomical or functional improvement.ConclusionIn this real-world study, both approaches effectively displaced SMH and improved vision with comparable outcomes, suggesting that treatment selection may be best determined by patient-specific and logistical factors.}, }
@article {pmid41529093, year = {2026}, author = {Maatouk, CM and Hyman, MJ and Shah, A and Smith, SR and Yehia, M and Moir, J and Gonnah, R and Flores, A and Hariprasad, S and Skondra, D}, title = {Association Between Metformin and Other Diabetic Medications and Five-year Onset of New Neovascular Age-related Macular Degeneration Diagnosis.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {2}, pages = {102-111}, doi = {10.3928/23258160-20251110-01}, pmid = {41529093}, issn = {2325-8179}, mesh = {Humans ; *Metformin/therapeutic use ; Male ; Female ; *Hypoglycemic Agents/therapeutic use ; Aged ; Case-Control Studies ; Middle Aged ; *Wet Macular Degeneration/diagnosis/epidemiology ; *Diabetic Retinopathy/drug therapy/complications ; Retrospective Studies ; Follow-Up Studies ; Aged, 80 and over ; Time Factors ; }, abstract = {BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration (nAMD) is a sight-threatening condition with growing prevalence, but few therapies exist to prevent its development. This study investigates whether metformin reduces the odds of new nAMD diagnosis.<br><br>PATIENTS AND METHODS: This was a case-control study using a nationwide insurance claims database of patients ages 55 and older with newly diagnosed nAMD from January 2008 to December 2019. Multivariable conditional logistic regression was utilized to determine how various exposures impacted the odds of new nAMD diagnosis.<br><br>RESULTS: Among 55,080 cases with new nAMD diagnosis and 55,066 matched controls, any metformin exposure reduced 5-year odds of new nAMD diagnosis compared to individuals not on metformin (odds ratio [OR]: 0.94; 95% CI: 0.90 to 0.99). Insulin and sulfonylurea exposures were also protective. These findings were consistent in subgroup analyses of patients with diabetes without diabetic retinopathy.<br><br>CONCLUSION: Metformin may reduce the 5-year odds of developing nAMD, particularly in diabetic patients without diabetic retinopathy.}, }
@article {pmid41529750, year = {2026}, author = {Arokia Vijaya Anand, M and Yang, CJ and Wang, WL and Yao, CH and Lai, JY}, title = {Marine-derived polysaccharides enhance the drug delivery mechanism in the management of ocular diseases: A review.}, journal = {International journal of biological macromolecules}, volume = {340}, number = {Pt 2}, pages = {150199}, doi = {10.1016/j.ijbiomac.2026.150199}, pmid = {41529750}, issn = {1879-0003}, mesh = {Humans ; *Polysaccharides/chemistry/therapeutic use/pharmacology ; *Eye Diseases/drug therapy ; *Drug Delivery Systems/methods ; *Aquatic Organisms/chemistry ; Animals ; *Drug Carriers/chemistry ; Drug Liberation ; Nanoparticles/chemistry ; }, abstract = {Ocular drug delivery remains significantly challenging due to complex anatomical and physiological barriers, poor bioavailability, and inefficient drug absorption. These limitations highlight the requirement for advanced delivery systems to overcome the ocular barrier and enable efficacious therapeutic outcomes. This review explores the potential of marine-derived polysaccharides as innovative carriers for ocular applications, emphasizing their potential as drug-delivery mechanisms to enhance drug retention, permeation, and bioavailability through advanced nanoplatforms. Polysaccharides such as κ-carrageenan, agarose, alginate, chitosan, hyaluronic acid, heparan sulfate, and chondroitin sulfate possess physicochemical, biocompatible, biodegradable, and mucoadhesive properties, making them ideal materials for ocular drug delivery. Notably, marine-derived polysaccharides have been reported to significantly improve ocular delivery performance, achieving up to a 3-fold increase in corneal permeability, higher drug accumulation in the aqueous humor (>47% vs. ∼20%), and approximately 3.6-3.8-fold enhancement in precorneal retention, while also enabling intelligent systems such as pH- and light-responsive drug release. These polymers have been engineered into various delivery platforms, including nanoparticles, micelles, dendrimers, nanosuspensions, hydrogels, and implants. Such systems promote sustained (long-acting), targeted (site-specific), and intelligent (stimuli-responsive) drug release, thereby significantly enhancing precorneal retention and therapeutic efficacy. These approaches are particularly relevant for treating various corneal diseases, including glaucoma, diabetic retinopathy, ocular inflammation, and age-related macular degeneration. The article also emphasizes the potential of emerging strategies to transform ocular drug delivery by offering customizable, stimuli-responsive, and patient-friendly therapeutic options. However, further in-depth research is crucial to optimize formulations, evaluate long-term safety, and address regulatory challenges for successful clinical translation.}, }
@article {pmid41531643, year = {2025}, author = {Das, D and Chawla, B and Lomi, N and Grover, S and Narayan, A}, title = {AI in the Shadows: Unveiling the Strengths and Blind Spots of Medios AI Retinal Screening in Cancer Care.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99002}, pmid = {41531643}, issn = {2168-8184}, abstract = {Introduction Artificial intelligence (AI) is increasingly being integrated into ophthalmic diagnostics, offering potential for efficient screening of common retinal diseases. The Medios AI system by Remidio (Singapore, Singapore), designed for use with a smartphone-based fundus camera, claims to detect diabetic retinopathy (DR), age-related macular degeneration (ARMD), and glaucoma. However, its performance in complex clinical settings such as ocular oncology remains underexplored. This study aims to evaluate both the diagnostic capabilities and limitations of the Medios AI system when applied to a diverse cohort of oncology patients. Materials and methods An observational study was conducted over three months in an ocular oncology clinic. Ninety-eight cancer patients (196 eyes) underwent fundus photography using the Remidio smartphone-based fundus imaging system. The images were analyzed using the Medios AI algorithm. AI-generated findings were compared with clinical evaluations by an experienced ophthalmologist to identify diagnostic concordance and discrepancies. Additional attention was paid to the system's imaging capabilities, including its ability to capture wide-field or montage images. Result The AI system accurately identified glaucomatous cupping in three patients, flagged two cases of DR, and detected signs of ARMD in two patients-all consistent with clinical examination. However, eight patients with leukemic retinopathy were incorrectly flagged as having DR, revealing a lack of specificity in distinguishing vascular retinal pathologies. The system also failed to detect optic atrophy, a critical neuro-ophthalmic finding in oncology patients. A technical limitation was also noted: the inability of the Remidio system to generate montage or wide-field images, restricting visualization of the peripheral retina. Conclusion While the Medios AI system demonstrates promise in identifying common retinal pathologies such as DR, ARMD, and glaucoma, its limitations are significant in the oncology context. The inability to distinguish similar hemorrhagic retinopathies, failure to detect optic nerve atrophy, and lack of wide-field imaging capabilities underscore the need for cautious implementation. Integration of AI tools must be accompanied by expert clinical oversight, especially in specialized settings where retinal presentations are complex and atypical.}, }
@article {pmid41532690, year = {2026}, author = {Wagner, M and Leutloff, CJ and Rauscher, FG}, title = {A Simulation Procedure for Stereological Correction of Early AMD Lesion Sizes Observed in Single OCT-B-Scans.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {1}, pages = {21}, pmid = {41532690}, issn = {2164-2591}, mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/diagnostic imaging/pathology ; Aged ; Female ; Male ; Computer Simulation ; Aged, 80 and over ; Middle Aged ; }, abstract = {PURPOSE: Early lesions caused by age-related macular degeneration (AMD) are imaged by optical coherence tomography (OCT) in unprecedented detail. Most probably, however, the sampling plane of an OCT scan meets a given lesion noncentrally, and the observed sizes of its diameter, cross-sectional area, and volume must be stereologically corrected.<br><br>METHODS: Stereological corrections are obtained by a simulation procedure, which is applied to the leading scans in a consecutive sample of 100 early AMD participants.<br><br>RESULTS: Mean corrections for lesion diameter, cross-sectional area and volume amount to +9.1%, +32.0%, and +46.6%, respectively. After correction, AMD stage classifications with respect to the 125-&#xb5;m diameter cutpoint had to be changed for seven participants.<br><br>CONCLUSIONS: Simulation results confirm that for lesions pictured and measured in OCT scans - regardless of the accuracy of OCT imaging - stereological correction of observed sizes is compelling and unavoidable.<br><br>TRANSLATIONAL RELEVANCE: Categorial AMD classifications based on observed OCT data must be reexaminated after stereological correction.}, }
@article {pmid41533007, year = {2026}, author = {Li, J and Wang, T and Lu, W and Jishkariani, D and Tsourkas, A and Kaja, S and Vining, KH and Thussananutiyakul, J and Spence, A and Nair, RM and Dunaief, JL and Mitchell, CH}, title = {PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.}, journal = {American journal of physiology. Cell physiology}, volume = {330}, number = {2}, pages = {C509-C523}, doi = {10.1152/ajpcell.00494.2025}, pmid = {41533007}, issn = {1522-1563}, support = {EY001538//HHS | NIH | National Eye Institute (NEI)/ ; //Research to Protect Blindness/ ; //Richard A Perritt MD Charitable Foundation/ ; EY013434//HHS | NIH | National Eye Institute (NEI)/ ; //This work was partially supported by the Collaborative Research Grant (KV) from the Institute of Regenerative Medicine at the University of Pennsylvania&amp;&#xa0;and the REgeneration and ReSToration of Function/ ; //Illinois Society for the Prevention of Blindness (ISPB)/ ; R01 EY013434/EY/NEI NIH HHS/United States ; EY015537//HHS | NIH | National Eye Institute (NEI)/ ; //Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology/ ; //Penn Undergraduate Research Mentoring Program (PURM)/ ; R01 EY015537/EY/NEI NIH HHS/United States ; //Eversight/ ; }, mesh = {*Lysosomes/metabolism/drug effects ; *Nanoparticles/chemistry/metabolism ; *Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Humans ; Hydrogen-Ion Concentration ; *Carbocyanines/chemistry/metabolism ; Retinal Pigment Epithelium/metabolism/drug effects ; Induced Pluripotent Stem Cells/metabolism/drug effects ; Cell Line ; }, abstract = {Lysosomal dysfunction and elevated lysosomal pH are hallmark features of age-related neurodegenerative diseases including age-related macular degeneration (AMD), Alzheimer's disease (AD), and Parkinson's disease (PD). Restoring lysosomal acidity is important for maintaining enzymatic degradation, preventing protein aggregation, and reducing cellular waste accumulation in degenerating tissues. Acidic nanoparticles represent a promising therapeutic strategy to normalize lysosomal pH; however, accurate monitoring of their delivery, retention, and dosage is critical for rigorous evaluation. To address this, we developed fluorescently labeled poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles conjugated with Cyanine3 amine (Cy3). Nanoparticle uptake was systematically optimized, achieving over 90% delivery to lysosomes of induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells, although uptake rates varied among adjacent cells. Once internalized, nanoparticles demonstrated remarkable stability, with no detectable change in concentration, distribution, or size for at least 28 days. iPS-RPE cells exhibited higher nanoparticle internalization compared with the ARPE-19 cell line and optic nerve head astrocytes. The capacity of the nanoparticles to restore function to stressed lysosomes was confirmed by their ability to reacidify lysosomes, restore cathepsin B activity, and increase the levels of active cathepsin D. The nanoparticles also reduced the levels of LC3II in astrocytes treated with chloroquine, indicating that they can also restore autophagy rates. In summary, this study demonstrates the value of Cy3 labeling for enhanced nanoparticle tracking to lysosomes. The findings also identify PLGA nanoparticles as powerful tools for restoring degradative lysosomal function and autophagy in cells undergoing lysosomal stress.NEW &amp; NOTEWORTHY Tools that restore acidic pH in compromised lysosomes can enhance autophagy and waste clearance in degenerative disorders characterized by excessive accumulation. Here, we describe the synthesis of lysosome-targeted nanoparticles composed of poly(d,l-lactide-co-glycolide) (PLGA) polymers covalently bound to the fluorescent dye Cyanine3 amine (Cy3). These Cy3-PLGA nanoparticles enable precise tracking of lysosomal delivery and demonstrate sustained long-term retention within lysosomes, supporting their potential for future applications aimed at restoring lysosomal pH in aging and degenerating diseases.}, }
@article {pmid41533847, year = {2026}, author = {Miladinovic, A and Biscontin, A and Ajcevic, M and Kresevic, S and Accardo, A and Tognetto, D and Inferrera, L}, title = {Neurosymbolic AI Framework for Explainable Retinal Disease Classification From OCT Images.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {1}, pages = {6}, pmid = {41533847}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/classification/diagnostic imaging/diagnosis ; *Neural Networks, Computer ; Retrospective Studies ; Deep Learning ; }, abstract = {PURPOSE: Accurate classification of retinal diseases such as dry age-related macular degeneration, wet AMD, epiretinal membrane, full-thickness macular hole (MH), lamellar MH, and central serous chorioretinopathy (CSC) is essential for effective treatment and clinical decision-making. Traditional deep learning models, however, often struggle with imbalanced datasets and lack interpretability, limiting their translational applicability in ophthalmology.<br><br>METHODS: We propose a neurosymbolic framework that integrates a convolutional neural network (CNN) with a symbolic reasoning layer based on expert-defined clinical rules. A total of 10,846 optical coherence tomography images were retrospectively collected and categorized into seven diagnostic classes: dry AMD, wet AMD, epiretinal membrane, full-thickness MH, lamellar MH, central serous chorioretinopathy, and healthy retinas.<br><br>RESULTS: Our neurosymbolic model achieved macro-precision 0.83, recall 0.82, and F1 0.81, on internal dataset, having slightly better performance than the CNN (0.64/0.83/0.68). On the external dataset, it retained superior performance, macro-precision 0.85, recall 0.79, F1 0.78, versus the CNN (0.73/0.64/0.59).<br><br>CONCLUSIONS: Our hybrid neurosymbolic framework introduces a unified paradigm that couples symbolic reasoning with a conventional CNN, improving diagnostic performance while delivering transparent, clinically interpretable decisions. It is particularly effective for rare and complex conditions that often challenge end-to-end deep learning models.<br><br>TRANSLATIONAL RELEVANCE: By integrating symbolic clinical logic with visual pattern recognition, the neurosymbolic model fosters trust in artificial intelligence-assisted diagnostics and supports precise, explainable decision-making in retinal care.}, }
@article {pmid41533856, year = {2026}, author = {Owsley, C and McGwin, G and Gao, L and Clark, ME and Gooden, L and Thomas, TN and Goerdt, L and Curcio, CA}, title = {Natural History of Visual Function Changes Over Three Years in Normal Aging and in Early and Intermediate Age-Related Macular Degeneration: ALSTAR2.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {1}, pages = {16}, pmid = {41533856}, issn = {2164-2591}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Macular Degeneration/physiopathology ; Aged ; *Visual Acuity/physiology ; Female ; Male ; Contrast Sensitivity/physiology ; *Aging/physiology ; Middle Aged ; Dark Adaptation/physiology ; Aged, 80 and over ; }, abstract = {PURPOSE: The purpose of this study was to evaluate change in visual functions over 3 years in normal macular health, and early and intermediate age-related macular degeneration (AMD) including tests of rod-, cone-, and mixed rod-cone-mediated visions; and to evaluate whether visual function change over 3 years meets the minimal clinically important difference (MCID), defined as meaningful to patients in everyday life.<br><br>METHODS: Eight visual functions were evaluated at baseline and 3-year follow-up (acuity, low luminance acuity, photopic and mesopic contrast sensitivity, mesopic and scotopic light sensitivity, and rod-mediated dark adaptation [RMDA] at 5 degrees and 12 degrees). The Age-Related Eye Disease Study (AREDS) 9-step classification system defined AMD severity.<br><br>RESULTS: In normal aging and intermediate AMD, 6 of 8 visual functions had statistically significant worsening over 3 years; mesopic contrast sensitivity and mesopic light sensitivity, respectively, showed no change. In early AMD, five of eight visual functions showed worsening over time, with photopic and mesopic contrast sensitivity and scotopic sensitivity unchanged. The largest percentage of eyes in each group meeting MCID was RMDA at 5 degrees or 12 degrees (38%-55%). The lowest percentage of eyes meeting MCID was visual acuity and photopic contrast sensitivity (0%-10%).<br><br>CONCLUSIONS: Whereas most visual functions evaluated have statistically significant worsening over 3 years in normal aging to intermediate eyes, the percentage of eyes reaching MCID was low for most visual functions except RMDA, which met MCID for almost half the eyes.<br><br>TRANSLATIONAL RELEVANCE: The natural history of change in visual function over time in normal aging to intermediate AMD should be characterized in terms of MCID, not only statistical significance.}, }
@article {pmid41533868, year = {2025}, author = {Guo, S and Gao, L and Cao, D and Huang, H and Ye, D and Lin, J and Meng, J and Xue, J and Li, Z and Li, J and Cheng, H}, title = {The Prevalence of Malnutrition and Early-Stage Age-Related Macular Degeneration: Using Three Nutritional Scoring Systems.}, journal = {Translational vision science &amp; technology}, volume = {14}, number = {12}, pages = {25}, pmid = {41533868}, issn = {2164-2591}, mesh = {Humans ; *Macular Degeneration/epidemiology/diagnosis ; Female ; Male ; Aged ; *Malnutrition/epidemiology/diagnosis/complications ; Prevalence ; *Nutritional Status ; Middle Aged ; *Nutrition Assessment ; Aged, 80 and over ; Choroid/pathology/blood supply/diagnostic imaging ; }, abstract = {PURPOSE: To investigate the interrelationships among malnutrition, choroidal parameters, and early-stage age-related macular degeneration (AMD), particularly the reticular pseudodrusen (RPD) phenotype, and to assess the predictive value of three nutritional scores.<br><br>METHODS: A total of 177 eyes were included in the study, categorized into control (n = 54), AMD (n = 55), and AMD-RPD (n = 68) groups based on fundus features. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI). Choroidal vascular index (CVI) and choroidal thickness (ChT) were measured.<br><br>RESULTS: Nutritional scores indicated a progressive decline in nutritional status from control to AMD to AMD-RPD. Compared with the control group, both AMD and AMD-RPD individuals had significantly worse CONUT, GNRI, and PNI scores (all P &#x2264; 0.01). Compared with the AMD group, AMD-RPD had significantly lower GNRI and PNI scores (both P < 0.001). CVI was positively correlated with GNRI (r = 0.308, P < 0.001) and PNI (r = 0.284, P < 0.001). The predictive value of all three nutritional scores for both AMD and AMD-RPD was demonstrated, with GNRI and PNI showing utility in differentiating RPD from AMD.<br><br>CONCLUSIONS: Malnutrition is associated with early-stage AMD phenotypes and choroidal vascular abnormalities may underlie this link. GNRI and PNI may help identify high-risk RPD individuals and support early nutritional assessment and intervention.<br><br>TRANSLATIONAL RELEVANCE: Integrating these nutritional scores may enhance collaboration between ophthalmologists and dietitians, enabling better detection and management of AMD and RPD in clinical practice.}, }
@article {pmid41533899, year = {2026}, author = {Yasuda, H and Nakamura, S and Shirakawa, A and Kuse, Y and Shimazawa, M}, title = {Inhibition of Pathological Mitochondrial Fission in Retinal Pigment Epithelium Mitigates Choroidal Neovascularization.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {4}, pmid = {41533899}, issn = {1552-5783}, mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/prevention &amp; control/drug therapy ; *Mitochondrial Dynamics/drug effects/physiology ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Mice ; *Quinazolinones/pharmacology ; Disease Models, Animal ; Blotting, Western ; Fluorescein Angiography ; *Mitochondria/metabolism ; Cells, Cultured ; Dynamins/metabolism ; Male ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {PURPOSE: Mitochondria are highly dynamic organelles that continuously undergo fission and fusion, and their dysfunction is associated with various age-related disorders. This study aimed to elucidate the role of mitochondrial fission in the development of choroidal neovascularization (CNV), a hallmark of neovascular age-related macular degeneration (AMD), and to evaluate the therapeutic potential of its pharmacological inhibition.<br><br>METHODS: The murine CNV model was created by laser photocoagulation using C57BL/6J mice. Expression changes of mitochondrial fission-related protein during CNV development were examined using western blotting and immunofluorescence. To assess the effectiveness of pharmacological inhibition of mitochondrial fission, the effects of mitochondrial division inhibitor-1 (Mdivi-1) and mitochondrial fusion promoter (M1) were evaluated by CNV area measurement, fluorescein angiography, and western blot analysis. The pro-angiogenic mechanisms associated with mitochondrial fission were further investigated in RPE cells cultured under hypoxic condition.<br><br>RESULTS: In a murine laser-induced CNV model, mitochondrial fission-related proteins increased in the retinal pigment epithelium (RPE)-choroid complex, and the high expression of phosphorylated dynamin-related protein 1 (DRP1) was observed in RPE cells surrounding the CNV lesion. Additionally, intravitreal injection of Mdivi-1 or M1 suppressed CNV formation, vascular leakage, and pro-angiogenic factor production. In RPE cells exposed to hypoxia, DRP1-mediated mitochondrial fission was rapidly activated, accompanied by increased mitochondrial reactive oxygen species production. Moreover, inhibition of mitochondrial fission suppressed mitochondrial bioenergetic dysfunction and the upregulation of vascular endothelial growth factor.<br><br>CONCLUSIONS: These findings support that pharmacological inhibition of activated mitochondrial fission could serve as a potential therapeutic approach for neovascular AMD.}, }
@article {pmid41533907, year = {2026}, author = {Veernala, I and Cuamatzi-Castelan, AS and Rajesh, A and Gong, J and D'Souza, GJ and Lavine, JA}, title = {Levodopa Suppresses Choroidal Neovascularization Through a Tyrosinase-Dependent Dual Mechanism.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {8}, pmid = {41533907}, issn = {1552-5783}, mesh = {Animals ; *Levodopa/pharmacology/therapeutic use ; *Choroidal Neovascularization/drug therapy/metabolism/prevention &amp; control/pathology ; Mice ; *Monophenol Monooxygenase/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Dopamine D2/agonists/metabolism ; Choroid/drug effects ; Dopamine Agonists/pharmacology ; Signal Transduction ; }, abstract = {PURPOSE: Levodopa (L-DOPA), a precursor for melanin and dopamine, has been linked to reduced intravitreal injection burden and delayed onset of neovascular age-related macular degeneration (AMD). Further, L-DOPA and dopamine receptor D2 (DRD2) agonists inhibit laser-induced choroidal neovascularization (CNV). However, the contributions of endogenous versus exogenous L-DOPA signaling, their effects in alternative CNV models, and the contributions of DRD2 versus GPR143, the receptor for L-DOPA, signaling remain unresolved.<br><br>METHODS: Choroidal sprouting assays (CSA) were performed using wild-type (WT) and tyrosinase-mutant (Tyr-/-) mice with and without dopamine pathway agonists and antagonists. CNV number and area were measured in pigmented Vldlr-/- and albino Vldlr-/-Tyr-/- mice with and without L-DOPA or the DRD2 agonist quinpirole.<br><br>RESULTS: Endogenous L-DOPA deficiency (Tyr-/-) did not affect CSA sprouting or CNV in Vldlr-/- mice. Exogenous L-DOPA suppressed angiogenesis ex vivo in both WT and Tyr-/- choroidal explants in a dose-dependent manner. In vivo, L-DOPA reduced CNV lesion number, lesion area, and macrophage infiltration in albino but not pigmented Vldlr-/- mice. Dopamine and quinpirole produced modest anti-angiogenic effects, and eticlopride partially reversed L-DOPA inhibition in choroidal explants. Quinpirole suppressed CNV lesion number, lesion area, and macrophage infiltration in pigmented Vldlr-/- mice.<br><br>CONCLUSIONS: Our findings show that L-DOPA's anti-angiogenic effects are exogenous, more effective in tyrosinase-mutant mice, and mediated by both the DRD2 and non-DRD2 pathways, potentially GPR143. The saturation of GPR143 signaling in pigmented eyes provides a mechanistic basis for reduced responsiveness, highlighting the importance of pigmentation biology in the development of L-DOPA-based therapeutics.}, }
@article {pmid41533916, year = {2026}, author = {Lyu, A and Mungalsingh, MA and Silva, AE and Khan, S and Labreche, T and Leat, SJ and Woo, GC and Woo, S and Thompson, B and Cheong, AMY}, title = {Transcranial Direct Current Stimulation Does Not Enhance Perceptual Learning of Chinese Character Reading in Adults With Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {16}, pmid = {41533916}, issn = {1552-5783}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Contrast Sensitivity/physiology ; *Learning/physiology ; *Macular Degeneration/physiopathology/therapy ; *Reading ; *Transcranial Direct Current Stimulation/methods ; Visual Acuity/physiology ; Visual Cortex/physiology ; *Visual Perception/physiology ; Language ; }, abstract = {PURPOSE: Macular degeneration impairs central vision, compelling patients to use their peripheral vision for reading, which is difficult due to reduced spatial resolution and crowding. Although perceptual learning improves reading, single-session anodal transcranial direct current stimulation (a-tDCS) over the visual cortex has shown inconsistent outcomes, with transient improvements observed in English reading but no benefit for Chinese reading in macular degeneration patients. This randomized controlled trial investigated whether combining multi-session a-tDCS with perceptual learning enhances Chinese reading performance in these patients compared to sham stimulation.<br><br>METHODS: Twenty Chinese-reading patients with macular degeneration (39-90 years old) were randomized to receive either active (n = 10) or sham (n = 10) a-tDCS during six sessions of rapid serial visual presentation (RSVP) reading training. Trained outcomes (RSVP reading) and untrained functions (sentence reading, crowding, contrast sensitivity, and visual acuity) were compared at baseline, 1 day, and 1 month post-training.<br><br>RESULTS: Perceptual learning significantly improved RSVP reading speed (P < 0.001) in both groups, with effects lasting at least a month. No additive effect of active versus sham a-tDCS was observed (group &#xd7; time P = 0.99). Transfer effects to untrained functions were limited to visual acuity and critical print size for sentence reading.<br><br>CONCLUSIONS: Perceptual learning enhances Chinese reading performance in individuals with macular degeneration, but a-tDCS confers no additional benefit. This contrasts with previous results where non-invasive brain stimulation enhanced English reading in macular degeneration. The results emphasize the need for more refined neuromodulation strategies for improving logographic reading.}, }
@article {pmid41533927, year = {2025}, author = {Li, Q and Liu, D and Zhang, M}, title = {Obstructive Sleep Apnea Accelerates Progression of Intermediate Age-Related Macular Degeneration: A Three-Year Prospective Cohort Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {59}, pmid = {41533927}, issn = {1552-5783}, mesh = {Humans ; Female ; Male ; Disease Progression ; *Sleep Apnea, Obstructive/complications/physiopathology/diagnosis ; Prospective Studies ; Aged ; Middle Aged ; Visual Acuity/physiology ; Follow-Up Studies ; Polysomnography ; *Macular Degeneration/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/physiopathology ; Risk Factors ; Geographic Atrophy/diagnosis ; Fluorescein Angiography ; }, abstract = {PURPOSE: Obstructive sleep apnea (OSA) and age-related macular degeneration (AMD) share pathophysiological mechanisms involving oxidative stress and inflammation. We investigated whether OSA accelerates AMD progression in patients with intermediate AMD.<br><br>METHODS: This prospective cohort study enrolled 470 patients aged &#x2265;50 years with intermediate AMD and age-matched healthy controls. After baseline polysomnography and multimodal retinal imaging, 470 participants were enrolled and stratified into AMD+OSA (n = 185), AMD-noOSA (n = 185), and healthy controls (n = 100). Of these, 391 completed the 36-month follow-up (AMD+OSA n = 153; AMD-noOSA n = 158; controls n = 80). The primary endpoint was composite AMD progression (central geographic atrophy, neovascular AMD, or &#x2265;15-letter vision loss) over 36 months. Secondary endpoints included changes in visual acuity, drusen volume, and geographic atrophy area.<br><br>RESULTS: Of 391 participants completing follow-up (83.2% retention), the AMD+OSA group showed significantly higher progression rates. The primary endpoint occurred in 31.4% (48/153) of AMD+OSA versus 15.2% (24/158) of AMD-noOSA patients (P = 0.002). Visual acuity worsened by 0.15 versus 0.06 logarithm of the minimum angle of resolution (P < 0.001), and drusen volume increased by 0.05 versus 0.02 mm3 (P < 0.001), respectively. Cox regression revealed a dose-dependent relationship: mild OSA (hazard ratio [HR] = 1.45; 95% confidence interval [CI], 0.95-2.20; P = 0.08), moderate OSA (HR = 2.10; 95% CI, 1.35-3.28; P = 0.001), and severe OSA (HR = 2.80; 95% CI, 1.75-4.47; P < 0.001) versus no OSA.<br><br>CONCLUSIONS: OSA is an independent, dose-dependent risk factor for accelerated AMD progression. Screening and treating OSA in patients with intermediate AMD may represent a novel strategy to preserve vision.}, }
@article {pmid41533930, year = {2025}, author = {Kato, N and Haruta, M and Arai, R and Nagae, A and Sato, K and Furushima, K and Yoshida, S}, title = {Association of Molar Dose and Early Retinochoroidal Blood Flow Changes After Intravitreal Anti-Vascular Endothelial Growth Factor Therapy.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {56}, pmid = {41533930}, issn = {1552-5783}, mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Recombinant Fusion Proteins/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Female ; Male ; *Choroid/blood supply ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Regional Blood Flow/physiology/drug effects ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Aged, 80 and over ; *Retinal Vessels/physiopathology/physiology ; Dose-Response Relationship, Drug ; Laser-Doppler Flowmetry ; *Wet Macular Degeneration/drug therapy/physiopathology ; Fluorescein Angiography ; Middle Aged ; Blood Flow Velocity ; Follow-Up Studies ; Visual Acuity ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: The purpose of this study was to evaluate short-term intraocular blood flow changes post-intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in patients with neovascular age-related macular degeneration (nAMD), compare reductions across 4 agents (brolucizumab, faricimab, aflibercept 2 mg, and aflibercept 8 mg), and examine correlations between each agent's molar dose and the magnitude of 30-minute blood flow change.<br><br>METHODS: This retrospective series included 61 eyes with nAMD (15 treated with brolucizumab, 15 with faricimab, 15 with aflibercept 2 mg, and 16 with aflibercept 8 mg). Laser speckle flowgraphy quantified mean blur rate (MBR) at the optic nerve head vessels (ONH MBR-vessel) and choroid (CHOR MBR) before and 30 minutes post-injection. Percent changes (%ONH MBR-vessel, %CHOR MBR) were compared among groups, and correlations with molar dose were assessed.<br><br>RESULTS: In the aflibercept 8 mg group, the mean percent changes were -11.2% &#xb1; 11.2% for ONH MBR-vessel (P = 0.001) and -13.7% &#xb1; 7.5% for CHOR MBR (P < 0.001). Pairwise comparisons showed no significant differences in %ONH MBR-vessel between aflibercept 8 mg and other agents. The reduction in %CHOR MBR was significantly greater with aflibercept 8 mg than with aflibercept 2 mg (P = 0.019). Molar dose was not significantly correlated with %ONH MBR-vessel, whereas %CHOR MBR showed a significant negative association with molar dose (Spearman &#x3c1; = -0.395, P = 0.002).<br><br>CONCLUSIONS: Aflibercept 8 mg produced a significant 30-minute reduction in ocular blood flow. Choroidal flow reduction was greater than with aflibercept 2 mg and negatively correlated with molar dose, suggesting a concentration-dependent hemodynamic effect.}, }
@article {pmid41533943, year = {2025}, author = {Kramer, A and Rinsky, B and Elbaz-Hayoun, S and Khateb, S and Jaouni, T and Jaskoll, S and Tiosano, L and Durst, R and Chowers, I}, title = {Altered High-Density Lipoprotein Expression Pattern in the Aqueous Humor From Eyes With Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {66}, number = {15}, pages = {73}, pmid = {41533943}, issn = {1552-5783}, mesh = {Humans ; *Aqueous Humor/metabolism ; Male ; Female ; Aged ; *Lipoproteins, HDL/metabolism ; Proteomics/methods ; Chromatography, Liquid ; Aged, 80 and over ; Tandem Mass Spectrometry ; *Wet Macular Degeneration/metabolism ; Middle Aged ; *Macular Degeneration/metabolism ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is associated with altered protein expression in the aqueous humor (AH). We aim to perform an unbiased proteomic analysis of the AH to identify proteomic signatures characterizing the disease's neovascular AMD (nAMD) and non-neovascular AMD (nnAMD) stages.<br><br>METHODS: AH samples were collected from eyes with nAMD (n = 39), nnAMD (n = 30), and healthy control eyes (n = 36). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the AH proteome; differentially expressed proteins underwent functional analysis. Serum high-density lipoprotein cholesterol (HDL-C) levels were correlated with AH high-density lipoprotein (HDL) pathway proteins.<br><br>RESULTS: Seventeen proteins were upregulated and five were downregulated in nAMD eyes compared with healthy controls. Enriched pathways include the fibrinogen complex, the complement alternate, the spherical HDL particle, and the serine protease inhibitor. Forty-six proteins were upregulated in nAMD versus nnAMD, whereas nine were downregulated. Enriched pathways included the spherical HDL particle, peptidase S1A, membrane attack complex, Sushi domain, and complement alternate pathway. No differentially expressed proteins were found between nnAMD and control eyes. Upregulated proteins associated with the spherical HDL particle pathway in nAMD, including apolipoprotein A-I, apolipoprotein A-II, and paraoxonase 1, exhibited a negative correlation with serum HDL-C levels (r = -0.43, P = 0.012; r = -0.37, P = 0.031; and r = -0.52, P = 0.002, respectively).<br><br>CONCLUSIONS: HDL-associated proteins exhibit increased expression in AH of nAMD eyes, independent of serum HDL-C levels. These findings suggest that serum HDL-C may not accurately reflect ocular HDL particle levels, highlighting the role of retinal lipid dysregulation in nAMD.}, }
@article {pmid41534822, year = {2026}, author = {Zahran, L and Elnabawy, RH}, title = {Key optogenetic advances in retinal prostheses: A comparative narrative review.}, journal = {Brain research}, volume = {1874}, number = {}, pages = {150166}, doi = {10.1016/j.brainres.2026.150166}, pmid = {41534822}, issn = {1872-6240}, mesh = {*Optogenetics/methods ; Humans ; *Visual Prosthesis/trends ; Retinal Ganglion Cells/physiology ; Animals ; Retina ; Retinitis Pigmentosa/therapy ; }, abstract = {This narrative review examines optogenetic strategies for retinal prostheses, which represent an advanced step in vision restoration, particularly for patients with retinitis pigmentosa and age-related macular degeneration. This review highlights the use of optogenetic stimulation to target high-density retinal ganglion cells (RGCs), focusing on developments like the FlexLED device. Opsins such as ChR2, ReaChR, and ChrimsonR, engineered for light sensitivity and faster responses, are critical for enhancing vision restoration. Combining optogenetic and electrical stimulation improves the reproducibility and specificity of RGC responses. Neuroimaging techniques like adaptive optics scanning laser ophthalmoscopy (AOSLO) help monitor cell activity, aiding in the development of visual repair methods. However, challenges remain in improving opsin sensitivity, gene delivery techniques, and ensuring long-term efficacy of retinal responses in patients. This review emphasizes the potential of optogenetic retinal prostheses to offer lasting, effective vision rehabilitation, significantly improving the quality of life for patients. This narrative review emphasizes that further research is needed to overcome current obstacles, such as improving opsin sensitivity and gene delivery techniques, to ensure long-term, effective vision restoration in patients.}, }
@article {pmid41535097, year = {2026}, author = {Carlà, MM and Crincoli, E and Catania, F and De Luca, L and Giannuzzi, F and Boselli, F and Gambini, G and Mateo, C and Rizzo, S}, title = {Advanced analysis of leading large language models for diagnostic accuracy in retinal imaging.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-327634}, pmid = {41535097}, issn = {1468-2079}, abstract = {BACKGROUND/AIMS: To evaluate and compare the diagnostic capabilities of advanced large language models (LLMs) in interpreting ophthalmological fundus images across diverse pathologies.<br><br>METHODS: We evaluated eight leading multimodal LLMs (GPT-4.5, Claude 3.7 Sonnet, Grok-2, Deepseek Cognition V2, Qwen2 72B, Gemini 2.0 Pro, Llama 3 405B and Mixtral 8&#xd7;22B) on their ability to interpret 100 fundus images representing various ophthalmological conditions. Performance was assessed using validated charts for diagnostic accuracy, specificity, sensitivity, consistency, relevance and explanation quality.<br><br>RESULTS: GPT-4.5 achieved the highest overall diagnostic accuracy (65.0%), followed by Gemini 2.0 Pro (63.0%). All models showed varied performance across pathology categories, with rhegmatogenous pathologies being most accurately identified (Gemini 2.0 Pro: 81.3%, GPT-4.5: 75.0%) and myopic maculopathy (mean accuracy 21.8%) being particularly challenging. The remaining models performed significantly worse: Deepseek Cognition V2 (52.0%), Claude 3.7 Sonnet (52.0%), Qwen2 72B (49.0%), Llama 3 405B (48.0%), Grok-2 (47.0%) and Mixtral 8&#xd7;22B (46.0%). Lower-performing models frequently declined to provide diagnoses, with refusal rates from 8.0% (Claude 3.7 Sonnet) to 19.0% (Mixtral 8&#xd7;22B).<br><br>CONCLUSION: Current LLMs show promising but limited capabilities in ophthalmological image interpretation. While performance on common conditions like retinal detachments and age-related macular degeneration is moderately good, significant challenges remain with rare conditions, myopic pathologies and complex vascular disorders. The competitive performance between GPT-4.5 and Gemini 2.0 Pro, with each excelling in different pathology categories, suggests that leveraging their complementary strengths might offer improved diagnostic support.}, }
@article {pmid41535412, year = {2026}, author = {García Cruz, MC and Flores Márquez, A and Morilla Ortega, A and Moreno Gutiérrez, J&#xc1; and Barranco Rodríguez, M and Escarramán Reyes, J and García Casares, N and Chinchurreta Capote, A}, title = {Resilience and vision-related quality of life in advanced age-related macular degeneration: a brief clinical report.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {733-734}, pmid = {41535412}, issn = {1476-5454}, }
@article {pmid41536214, year = {2026}, author = {Wu, J and Su, B and Fan, Z and Zhan, H}, title = {Genetically predicted high-density lipoprotein traits and pan-disease risk: a systematic review.}, journal = {Epidemiologic reviews}, volume = {48}, number = {1}, pages = {}, doi = {10.1093/epirev/mxag001}, pmid = {41536214}, issn = {1478-6729}, mesh = {Humans ; *Lipoproteins, HDL/genetics/blood ; Mendelian Randomization Analysis ; Biomarkers/blood ; Risk Factors ; }, abstract = {High-density lipoprotein (HDL) is a highly heterogeneous lipoprotein with multiple physiological functions. However, observational studies present conflicting evidence regarding its association with various diseases. This review systematically summarizes evidence from Mendelian randomization (MR) studies to investigate the causal relationships between HDL-related biomarkers and a wide spectrum of disease outcomes. We systematically searched multiple databases up to November 2024. The causal relationship between HDL and 158 diseases was studied. Findings reveal that the role of HDL is highly disease-specific. Genetically predicted higher HDL levels are protective against most circulatory and digestive system diseases. Conversely, however, they are associated with an increased risk of certain conditions, including breast cancer, intracerebral hemorrhage, and age-related macular degeneration. The MR analyses revealed inconsistent and sometimes conflicting findings for several disease outcomes, notably Alzheimer's disease. This review underscores the context-dependent nature of HDL's effects, which may be driven by factors like HDL particle heterogeneity and functional transformation into a pro-inflammatory state. Future research should move beyond concentration-based metrics to focus on HDL functionality and precise subtyping to fully understand its role in disease etiology.}, }
@article {pmid41536240, year = {2026}, author = {Němec, P and Vysloužilová, D and Hejsek, L and Němčanský, J and Studnička, J}, title = {Best Practices for Age-Related Macular Degeneration (AMD) Therapy.}, journal = {Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti}, volume = {82}, number = {Ahead of Print}, pages = {1-9}, doi = {10.31348/2026/2}, pmid = {41536240}, issn = {1211-9059}, mesh = {Humans ; *Macular Degeneration/diagnosis/therapy/classification ; }, abstract = {Age-related macular degeneration is one of the leading causes of severe loss of sight in developed countries. Diagnostic procedures have developed dramatically in recent years, and modern imaging methods have contributed to improved options for population screening, targeted diagnostics, and monitoring of the treatment process. At the same time, new treatment options have also been developing rapidly. The recommended procedures summarize the current knowledge with the aim of unifying procedures for the diagnosis, classification, and treatment of age-related macular degeneration (AMD).}, }
@article {pmid41537428, year = {2026}, author = {Lucenteforte, E and Ng, SM and Saulle, R and Hoad, G and Schillinger, R and Virgili, G}, title = {Anti-vascular endothelial growth factor (anti-VEGF) agents for neovascular age-related macular degeneration (nAMD): a network meta-analysis.}, journal = {The Cochrane database of systematic reviews}, volume = {1}, number = {1}, pages = {CD016298}, pmid = {41537428}, issn = {1469-493X}, mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bevacizumab/therapeutic use ; *Biosimilar Pharmaceuticals/therapeutic use ; *Macular Degeneration/drug therapy ; Network Meta-Analysis as Topic ; Randomized Controlled Trials as Topic ; Ranibizumab/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the comparative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents and their biosimilars for people with neovascular age-related macular degeneration (nAMD), and provide a relative ranking of interventions using network meta-analysis (NMA) methods, considering differences in treatment intensity.}, }
@article {pmid41537758, year = {2026}, author = {Cheung, R and Trinh, M and Duong, A and Chen, S and Ng, D and Schiller, G and Hodge, C and Nivison-Smith, L}, title = {Prognostic Ability of Automated RPE Sinuosity for Late AMD Supersedes Qualitative Outer Retinal Band Assessment.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {33}, pmid = {41537758}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; Female ; Male ; Aged ; Prognosis ; *Macular Degeneration/diagnosis ; Disease Progression ; Follow-Up Studies ; Aged, 80 and over ; Middle Aged ; Visual Acuity ; }, abstract = {PURPOSE: Outer retinal band integrity strongly predicts late age-related macular degeneration (AMD), however, it is often assessed subjectively and vulnerable to intergrader variability. This study quantifies retinal pigment epithelium (RPE) sinuosity from automated segmentations of a commercially available optical coherence tomography (OCT) and its ability to predict late AMD.<br><br>METHODS: Consecutive patients with intermediate AMD who progressed to late disease (n = 69) or remained stable (n = 198) were recruited. Outer retinal band integrity was measured quantitatively using RPE sinuosity, calculated as the ratio of RPE:RPE-fit line length across macular B-scans. RPE sinuosity was measured in the foveal B-scan alongside the mean, maximum, and median values across the five central B-scans. The RPE and ellipsoid zone (EZ) continuity was graded qualitatively, as well as other AMD biomarkers currently used for prognostication. Adjusted odds ratios for progression were calculated for each variable.<br><br>RESULTS: Mean follow-up time was 3.15 years (1.93 years). Pigmentary abnormalities (P = 0.001), subretinal drusenoid deposits (SDDs; P > 0.0001), drusen volume (P = 0.01), and late AMD in the fellow eye (P = 0.001) were present in a higher proportion of progressor than stable eyes at baseline. Median RPE sinuosity was the strongest predictor of progression within 5 years (2.52 [1.14-5.55]) and across the study period (2.35 [1.25-4.43]). No qualitative measures could predict late AMD within any time frame.<br><br>CONCLUSIONS: RPE sinuosity outperformed qualitative outer retinal band integrity assessments for late AMD prediction and is a reliable, repeatable evaluation method. Verifying these results using different OCT devices in a prospective cohort is needed to determine whether the feature can enhance late AMD risk models and improve clinical management.}, }
@article {pmid41538072, year = {2026}, author = {Zong, Y and Liu, J and Yang, M and Zhang, J and Zou, Y and Ye, Z and Deng, J and Gu, W and Du, J and Ohno-Matsui, K and Kamoi, K}, title = {Advances in microneedle Technology for Treatment of retinal degenerative diseases: a narrative review.}, journal = {Biomedical microdevices}, volume = {28}, number = {1}, pages = {5}, pmid = {41538072}, issn = {1572-8781}, mesh = {Humans ; *Needles ; Animals ; *Retinal Degeneration/drug therapy/therapy ; *Drug Delivery Systems/instrumentation ; }, abstract = {Retinal degenerative diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), present significant therapeutic challenges due to the complex anatomical and physiological barriers of the posterior eye. Conventional drug delivery methods, particularly intravitreal injections, are often limited by their invasiveness, rapid drug clearance, and burden on patient compliance. Microneedle technology has emerged as a paradigm-modifying approach for ocular drug delivery, offering a minimally invasive platform to bypass barriers like the blood-retinal barrier while targeting specific ocular tissues. This narrative review provides a critical overview of the latest advancements in microneedle technology for treating retinal degeneration, evaluating diverse configurations-including solid, hollow, dissolvable, coated, and hydrogel-forming designs-and their efficacy in facilitating suprachoroidal, intravitreal, and subretinal administration. Recent clinical trials highlighted in this review demonstrate promising results regarding safety, delivery efficiency, and patient acceptability. However, the translation from bench to bedside still faces hurdles in scale-up production, regulatory standardization, and long-term stability assessment. We discuss these technological challenges and explore future developments, such as the integration of smart materials and personalized approaches, emphasizing the potential of microneedle systems to revolutionize treatment paradigms through precise, controlled delivery to the posterior eye segments.}, }
@article {pmid41538667, year = {2025}, author = {Soares, TS and Cristino, ADS and Silva, AF and Santos, LRD}, title = {Optical coherence tomography angiography for the diagnosis of choroidal neovascularization in age-related macular degeneration: a systematic review.}, journal = {Einstein (Sao Paulo, Brazil)}, volume = {23}, number = {}, pages = {eRW1521}, pmid = {41538667}, issn = {2317-6385}, mesh = {Humans ; *Choroidal Neovascularization/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Sensitivity and Specificity ; *Macular Degeneration/diagnostic imaging/complications ; Aged ; Middle Aged ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To evaluate the diagnostic accuracy of optical coherence tomography angiography for the identification of choroidal neovascularization in age-related macular degeneration.<br><br>METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. A literature search of the PubMed/MEDLINE, Scientific Electronic Library Online (SciELO), EMBASE, Cochrane Library, CAPES Periodicals, and LILACS scientific databases was conducted to identify relevant full-text articles published in English and Portuguese from January 2012 to January 2025. To comprehensively evaluate the effectiveness and the performance of optical coherence tomography angiography in terms of sensitivity and specificity, fundus fluorescein angiography (the gold standard for detecting choroidal neovascularization) was used as the comparator. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) 2 tool was used to assess methodological quality and risk of bias.<br><br>RESULTS: Eleven articles were included in the systematic review. The patients' mean age ranged from 58.5 to 79.7 years. The sensitivity ranged from 50.0% to 94.0%, and the specificity ranged from 67.6% to 100.0%. The risk of bias was low, and the methodological quality of the studies was good, suggesting that optical coherence tomography angiography holds promise for the diagnosis of choroidal neovascularization.<br><br>CONCLUSION: Optical coherence tomography angiography exhibited high sensitivity and specificity, demonstrating its potential for the detection of choroidal neovascularization in patients with age-related macular degeneration. However, current scientific evidence suggests that optical coherence tomography angiography is not superior to fundus fluorescein angiography and should not be used as a substitute. Extended and affordable protocols to analyze different subtypes of choroidal neovascularization and the performance of optical coherence tomography angiography devices should be evaluated.<br><br>CRD420251046669.}, }
@article {pmid41539007, year = {2026}, author = {Cohen, BA and Fhima, J and Meisel, M and Meital, B and Nakayama, LF and Berkowitz, E and Behar, JA}, title = {Ophthalmology foundation models for clinically significant age macular degeneration detection.}, journal = {Physiological measurement}, volume = {47}, number = {3}, pages = {}, doi = {10.1088/1361-6579/ae3936}, pmid = {41539007}, issn = {1361-6579}, mesh = {*Macular Degeneration/diagnostic imaging/diagnosis ; Humans ; *Ophthalmology ; Supervised Machine Learning ; }, abstract = {Objective. Self-supervised learning (SSL) has enabled vision transformers (ViTs) to learn robust representations from large-scale natural image datasets, enhancing their generalization across domains. In retinal imaging, foundation models pretrained on either natural or ophthalmic data have shown promise, but the benefits of in-domain pretraining remain uncertain.Approach. To investigate this, we benchmark six SSL-pretrained ViTs on seven digital fundus image (DFI) datasets totaling 70 000 expert-annotated images for the task of moderate-to-late age-related macular degeneration (AMD) identification.Main results. Our results show that DINOv2, pretrained on natural images, shows similar performance than domain-specific models. These findings highlight the value of foundation models in improving AMD identification, and challenge the assumption that in-domain pretraining is necessary.Significance. We present our model AMDNet, which performs state-of-the-art out-of-domain AUROCs on six public datasets. Furthermore, we release BRAMD, an open-access dataset (n = 587) of DFIs with AMD labels from Brazil. Project page:www.aimlab-technion.com/lirot-ai.}, }
@article {pmid41542493, year = {2026}, author = {Shang, P and Hoang, J and Hong, E and Geng, Z and Ambrosino, H and Abnoosian, E and Zhu, X and Ma, M and Wei-Navarro, NA and Webber, B and Qu, J and Montezuma, SR and Agbaga, MP and Dutton, JR and Ferrington, DA}, title = {Complement Factor H (Y402H) polymorphism for age-related macular degeneration alters retinal lipids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.06.697989}, pmid = {41542493}, issn = {2692-8205}, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is associated with multiple risk factors and involves death of the retinal pigment epithelium (RPE). We investigated how the Y402H polymorphism of Complement Factor H (CFH) and cigarette smoke extract (CSE), major AMD genetic and environmental risks, affect lipid metabolism in RPE differentiated from induced pluripotent stem cells (iPSC-RPE) that were derived from human donors genotyped for low-risk (LR) or high-risk (HR) CFH. Results from discovery-based (lipidomics, proteomics) and targeted (mitochondrial fatty acid oxidation (FAO)) assays found significant genotype-dependent differences under basal conditions include higher free fatty acids and cholesterol esters in HR cells. CSE induced differences in proteins regulating lipid handling, lipolysis, and inflammation. Lower FAO in HR cells was observed in multiple donors and pairs of parent/isogenic edited lines compared with LR lines. CSE induced lipid accumulation, lipid composition remodeling, and upregulation of proteins involved in lipid synthesis/hydrolysis, production of bioactive lipid mediators, and metabolism of ceramide and cholesterol. These results elucidate putative mechanisms driving pathology in RPE harboring CFH Y402H.}, }
@article {pmid41543675, year = {2026}, author = {El Alili, M and van de Laar, CJ and de Greeff, JPF and Vromans, JGF and van Asten, F and Bosmans, JE}, title = {Budget Impact of Faricimab in Neovascular Age-Related Macular Degeneration in the Netherlands: A Systematic Review and Meta-Analysis of Injection Count.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {591-639}, pmid = {41543675}, issn = {2193-8245}, abstract = {INTRODUCTION: Frequent anti-vascular endothelial growth factor (anti-VEGF) injections for the treatment of neovascular age-related macular degeneration (nAMD) burden patients and healthcare systems. Faricimab may reduce this burden, but robust data are lacking. This study aimed to systematically quantify the injection frequency reduction with faricimab compared to anti-VEGF agents and estimate Dutch budget impact.<br><br>METHODS: A systematic review of studies on patients with nAMD switching to faricimab was conducted in PubMed. A hybrid approach using artificial intelligence (NotebookLM) and manual verification was employed for data extraction and risk of bias assessment. A random-effects meta-analysis determined the pooled mean difference in annual injections. A budget impact analysis estimated direct medical costs (drug and administration costs) over a 1-year time horizon using Dutch data.<br><br>RESULTS: A meta-analysis of 19 real-world studies (2231 patients) was conducted. Patients switched to faricimab for persistent fluid or to extend treatment intervals, resulting in a significant mean reduction of 2.65 injections in the first year (from 9.70 to 7.05; 95% confidence interval -&#x2009;3.36 to -&#x2009;1.93). The base-case analysis projected annual savings of approximately &#x20ac;79&#xa0;million, corresponding to 96,235 fewer injections nationwide. Scenario analyses showed that substantial savings (&#x20ac;16 to &#x20ac;75&#xa0;million) can be achieved when using faricimab in second- and third-line settings, although replacing first-line bevacizumab would increase costs.<br><br>CONCLUSIONS: Switching patients to faricimab reduced the injection frequency by two to three injections in the first year. Although evidence certainty was limited by statistical heterogeneity, the reduction was consistent across studies. Although replacing first-line bevacizumab increases costs, substantial savings are achievable in later lines. Strategic positioning of faricimab in the second-line yields significantly higher savings compared to third-line use, and could significantly lower the clinical, patient, and economic burden of nAMD care in the Netherlands. These findings provide quantified, real-world evidence to inform Dutch clinical practice and healthcare policy.}, }
@article {pmid41543898, year = {2026}, author = {Singh, KK and Jin, Y and Hu, MW and Palazzo, I and Cano, M and Hoang, T and Bhutto, I and Wang, S and Sinha, D and Blackshaw, S and Qian, J and Handa, JT}, title = {Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {3}, pages = {e2505412123}, pmid = {41543898}, issn = {1091-6490}, support = {EY033765//HHS | NIH | National Eye Institute (NEI)/ ; EY031594//HHS | NIH | National Eye Institute (NEI)/ ; EY035805//HHS | NIH | National Eye Institute (NEI)/ ; EY031594//HHS | NIH | National Eye Institute (NEI)/ ; EY036173//HHS | NIH | National Eye Institute (NEI)/ ; EY031779//HHS | NIH | National Eye Institute (NEI)/ ; EY001765//HHS | NIH | National Eye Institute (NEI)/ ; Stein award//Research to Prevent Blindness (RPB)/ ; EY034571//HHS | NIH | National Eye Institute (NEI)/ ; M2020166//BrightFocus Foundation (BFF)/ ; None//Maryland Stem Cell Research Fund (MSCRF)/ ; None//Foundation Fighting Blindness (FFB)/ ; None//Edward N. and Della L. Thome Memorial Foundation (Thome Memorial Foundation)/ ; }, mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Mice ; *Macular Degeneration/pathology/genetics/metabolism ; Humans ; Aging/genetics/pathology ; Epigenesis, Genetic ; Mice, Inbred C57BL ; Male ; Cigarette Smoking/adverse effects ; Female ; }, abstract = {Cigarette smoking induces epigenetic changes that can cause degenerative heterogeneity with aging and disease. In disease such as age-related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is a powerful risk factor for AMD, we hypothesized that smoke induces epigenetic-mediated degenerative RPE heterogeneity. We administered cigarette smoke condensate (CSC) to young and aged mice. Using snRNA-seq and single nuclear ATAC sequencing, we identified distinct healthy and dedifferentiated RPE clusters in both aged vehicle- and young CSC-treated mice. Dedifferentiated RPE had globally decreased chromatin accessibility and expression of genes linked to "hallmarks of aging." Notably, young, dedifferentiated RPE also exhibited a compensatory upregulation of hallmarks of aging-related genes including mitochondrial function and proteostasis while aged dedifferentiated RPE did not, which decreased their survival following CSC treatment, as experimentally verified with TUNEL labeling. Similar populations of dedifferentiated and healthy RPE were identified both in mice exposed to cigarette smoke for 4 mo and in macular RPE from a donor who smoked and another with early AMD, but not from a nonsmoker donor. Degenerative cellular heterogeneity that includes an abnormal cluster can jeopardize cell survival and represents a hallmark of ocular aging.}, }
@article {pmid41544798, year = {2026}, author = {Zhang, M and Ge, Y and Wang, Z and Li, H and Wang, G and Zhang, Y and Wang, X and Hou, H and Meng, L and Wei, L and Meng, D and Wang, L and Sheng, HY and Yin, Y and Mortadza, SAS and Roger, S and Li, J and Ren, F and Jiang, LH}, title = {Insights into the role of the mechanosensitive Piezo1 channel and signaling mechanisms in CNS functions and diseases.}, journal = {Neuroscience and biobehavioral reviews}, volume = {183}, number = {}, pages = {106562}, doi = {10.1016/j.neubiorev.2026.106562}, pmid = {41544798}, issn = {1873-7528}, mesh = {Humans ; *Ion Channels/metabolism ; Animals ; *Central Nervous System/metabolism ; *Central Nervous System Diseases/metabolism ; *Mechanotransduction, Cellular/physiology ; *Signal Transduction/physiology ; Neurodegenerative Diseases/metabolism ; }, abstract = {The mechanosensitive Piezo1 channel is widely distributed in the central nervous system (CNS), expressed by neurons, astrocytes, oligodendrocytes, microglia, neural stem and progenitor cells, retinal ganglion and photoreceptor cells and, moreover, neurovascular and lymphatic endothelial cells, implicating an important role for the Piezo1 channel in the CNS physiology and disease. Indeed, recent studies have disclosed that the Piezo1 channel plays a vital part in mediating or modulating numerous CNS functions, ranging from brain development, synapse function, neurogenesis, axonal (re)generation, axonal pathfinding, astrocyte-neuron communication, axonal myelination, immune response, brain vasculature modelling to cerebrospinal fluid drainage. There is also increasing evidence to indicate critical engagement of the Piezo1 channel in the pathogenesis and progression of multiple debilitating CNS conditions, exemplified by spinal cord injury, stroke and related ischemia/reperfusion brain damage, neurodegenerative diseases, and age-related macular degeneration. Here, we provide a comprehensive overview of the current understanding and highlight the unanswered questions regarding the roles and mechanisms of the Piezo1 channel in CNS functions and diseases, presenting the Piezo1 channel as an attractive therapeutic target to intervene CNS damage and diseases.}, }
@article {pmid41545331, year = {2026}, author = {Polasek, TM and Paneliya, KJ and Lin, T and Mata, NL and Wang, I and Scholl, HP and Lin, J}, title = {Effects of Gastric Acid Suppression, Cytochrome P4503A Inhibition and Induction, and Food on the Pharmacokinetics of Tinlarebant in Healthy Adults.}, journal = {Clinical pharmacology in drug development}, volume = {15}, number = {1}, pages = {e70009}, doi = {10.1002/cpdd.70009}, pmid = {41545331}, issn = {2160-7648}, support = {//Belite Bio Inc/ ; }, mesh = {Humans ; Male ; Adult ; Female ; *Cytochrome P-450 CYP3A Inhibitors/pharmacology/administration &amp; dosage/adverse effects ; *Food-Drug Interactions ; Young Adult ; Middle Aged ; Healthy Volunteers ; *Omeprazole/pharmacology/administration &amp; dosage ; Cytochrome P-450 CYP3A/metabolism ; Area Under Curve ; *Itraconazole/pharmacology/administration &amp; dosage ; Rifampin/pharmacology/administration &amp; dosage ; *Cytochrome P-450 CYP3A Inducers/pharmacology/administration &amp; dosage/adverse effects ; *Proton Pump Inhibitors/pharmacology/administration &amp; dosage ; Drug Interactions ; Administration, Oral ; Adolescent ; }, abstract = {Tinlarebant is an oral retinol binding protein 4 antagonist in clinical development for geographic atrophy, an advanced stage of dry age-related macular degeneration, and Stargardt disease, an inherited juvenile-onset macular degeneration. A randomized, open-label, two-period, interaction study in healthy adults was conducted in four parts to determine the effects of gastric acid suppression (omeprazole 40 mg QD), cytochrome P4503A (CYP3A) inhibition (itraconazole 200 mg BD) and induction (rifampin 600 mg QD), and food on the pharmacokinetics of tinlarebant (5 mg single dose). The effects on tinlarebant exposure were quantified by geometric least squares (GLS) mean Cmax and AUCinf ratios, where GLS mean Cmax or AUCinf with potential perpetrator is divided by GLS mean Cmax or AUCinf without potential perpetrator. Steady-state dosing of omeprazole had no effect on tinlarebant exposure (Cmax ratio = 1.16 and AUCinf ratio = 1.03). The Cmax and AUCinf ratios of tinlarebant following itraconazole dosing were 1.29 and 2.42, respectively. Rifampin co-administration decreased tinlarebant Cmax and AUCinf ratios to 0.53 and 0.19, respectively. Compared with the fasting state, taking tinlarebant with food gave Cmax and AUCinf ratios in the range 1.08-1.22. No unexpected safety signals occurred and tinlarebant was well tolerated in all participants. These data show that the pharmacokinetics of tinlarebant is not significantly altered by gastric acid suppression or food. Dosing patients with tinlarebant and strong CYP3A inhibitors is unlikely to compromise safety based on its pharmacokinetic-pharmacodynamic relationships, but tinlarebant should be contraindicated with strong CYP3A inducers due to potential treatment failure.}, }
@article {pmid41545508, year = {2026}, author = {Jang, B and Lee, CH and Kim, SJ and Yoon, CK and Park, UC and Choi, J and Lee, EK and Kim, YG}, title = {Artificial intelligence based prediction of first recurrence in neovascular age related macular degeneration with validation by 19 experts.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {4440}, pmid = {41545508}, issn = {2045-2322}, mesh = {Humans ; *Artificial Intelligence ; Female ; Aged ; Male ; Recurrence ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy/diagnosis ; ROC Curve ; Aged, 80 and over ; Ophthalmologists ; Middle Aged ; Algorithms ; }, abstract = {This study aimed to investigate the value and difference in predictive performance between ophthalmologists and a previously developed and validated artificial intelligence (AI) model, and to evaluate how AI assistance influences expert decision-making in reliably assessing recurrence prediction of neovascular age-related macular degeneration (nAMD) after anti-vascular endothelial growth factor (VEGF) treatment. 19 experts (nine retinal specialist ophthalmologists and ten non-retinal specialist ophthalmologists) predicted the first recurrence of nAMD within three months based on optical coherence tomography (OCT) images and clinical information. Predictions were made in five sessions with increasing information availability. The AI model used in this study had been developed and validated in our earlier work, and it predicted recurrence using baseline and after the loading phase OCT images. We compared the area under the receiver operating characteristic curve (AUROC), Fleiss' kappa, and Delong's test between expert groups and the AI algorithm. The study included 149 eyes of 130 patients. The AI model achieved an AUROC of 0.744 (95% confidence interval, 0.665-0.822). Expert performance improved across sessions, with AUROCs ranging from 0.562 ± 0.034 to 0.679 ± 0.049. No significant differences were observed between expert groups based on experience or subspecialty. AI-supported decisions showed slightly improved performance in predicting nAMD recurrence compared to human experts, regardless of clinical experience. These results suggest the potential of AI-assistance in predicting recurrence and optimizing treatment strategies for nAMD, which could significantly improve patient counseling and management. This study also highlights the novel contribution of evaluating the impact of AI assistance on ophthalmologists' decision-making in nAMD recurrence prediction.}, }
@article {pmid41545709, year = {2026}, author = {Gale, R and Awad, MH and Bailey, C and Cackett, P and Chhabra, R and Downey, L and Ghanchi, F and Kotagiri, A and Narendran, N and Pearce, I and Peto, T and Sivaprasad, S and Younis, S and Napier, J and Gilbert, R and Ismat, S}, title = {Aflibercept 8 mg treat-and-extend pathway for the treatment of neovascular age-related macular degeneration: guidance from a UK expert panel.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41545709}, issn = {1476-5454}, abstract = {BACKGROUND/OBJECTIVES: Therapies with robust visual outcomes and reduced patient and healthcare system treatment burden are needed amidst the rising incidence of neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg is an additional treatment option with demonstrated potential for extended dosing intervals of up to 24 weeks. The objective of this publication is to introduce a clinical care pathway, developed by expert consensus of experienced UK clinicians, to support best practice with aflibercept 8 mg in nAMD.<br><br>METHODS: A structured, face-to-face roundtable meeting of 13 UK retina specialists was held on 8 October 2024, organised and funded by Bayer. The expert panel reached consensus following review of key clinical trial data and consideration of current NHS clinical practice to provide guidance on the use of intravitreal aflibercept 8&#x2009;mg in nAMD.<br><br>RESULTS: The panel provided recommendations for an aflibercept 8&#x2009;mg treat-and-extend pathway for both treatment-na&#xef;ve and previously treated patients with nAMD. Criteria were developed to guide dosing interval extension, reduction or maintenance based on visual acuity and optical coherence tomography imaging. More detailed guidance includes considerations for switching treatments to or from aflibercept 8&#x2009;mg, monitoring, and discontinuing treatment.<br><br>CONCLUSIONS: Aflibercept 8&#x2009;mg may offer opportunities for longer treatment intervals and reduced patient and clinic burden compared with first-generation agents. The proposed treatment pathway is practical and accounts for variability in healthcare structures and capacity pressures, providing clinicians with flexibility in implementing these recommendations while addressing patient needs.}, }
@article {pmid41545711, year = {2026}, author = {Bailey, C and Lange, C and Munk, MR and Lanzetta, P and Oubraham, H and Machewitz, T and Allmeier, H and Zhang, X and Morgan-Warren, P and Hasanbasic, Z and Chaudhary, V and , }, title = {Infographic: SPECTRUM: study design of the global real-world study of aflibercept 8 mg in the treatment of neovascular age-related macular degeneration and diabetic macular edema.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-025-04140-2}, pmid = {41545711}, issn = {1476-5454}, }
@article {pmid41546875, year = {2026}, author = {Zhang, Y and Gupta, P and Fenwick, E and Man, R and Wong, CMJ and Tan, ACS and Cheung, CMG and Colega, MT and Chong, MF and Lai, JS and Lamoureux, EL}, title = {The Association of Dietary Patterns with Age-Related Macular Degeneration in a Multiethnic Older Singaporean Population.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-10}, pmid = {41546875}, issn = {1423-0267}, abstract = {INTRODUCTION: The associations of dietary patterns and age-related macular degeneration (AMD) have been reported using mostly Western and Japanese populations and evidence in multiethnic Asian populations, with potentially different dietary patterns, is lacking. In this study, we aimed to identify dietary patterns in a multiethnic older Singaporean population and examine their associations with AMD.<br><br>METHODS: This was a cross-sectional analysis of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER) study. Dietary intake was assessed using a 110-item interviewer-administered food frequency questionnaire validated in a Singaporean population. Presence and stage of AMD were categorized using fundus photographs and an established AMD classification. Dietary patterns were generated by applying exploratory factor analysis, and their associations with presence of AMD and stage of AMD were evaluated using adjusted logistic regression models and adjusted multinomial logistic regression models, respectively.<br><br>RESULTS: Of 1,480 Chinese, Malay, and Indian individuals aged &#x2265;60 years (mean 71.3 &#xb1; 7.7), age-standardized prevalence of any, early, and late AMD were 7.1%, 4.8%, and 2.2%. Three dietary patterns were generated: "snacks, fried foods, and refined carbohydrates"; "poultry, meat, and Fish"; and "wholemeal bread, legumes, and nuts." After adjusting for covariates, higher "snacks, fried foods, and refined carbohydrates" pattern scores were associated with higher odds of any AMD (OR = 1.41, 95% CI: 1.02-1.96) and early AMD (OR = 1.63, 95% CI: 1.12-2.37). "Snacks, fried foods, and refined carbohydrates" pattern scores in the highest quartile were associated with higher odds of any AMD (OR = 2.18, 95% CI: 1.01-4.72), compared to the lowest quartile.<br><br>CONCLUSION: Only the "snacks, fried foods, and refined carbohydrates" pattern was associated with AMD in this multiethnic older Singaporean population. These findings may inform the development of dietary guidelines in Singapore for more targeted AMD management, although prospective, longitudinal data are needed.}, }
@article {pmid41547437, year = {2026}, author = {Torres-Villaros, H and Albou, J and Fajnkuchen, F and Couturier, A and Giocanti-Aurégan, A and Massin, P}, title = {Telemedicine-based diabetic retinopathy screening in patients over 70 Years: a French cohort study within the OPHDIAT network.}, journal = {Diabetes &amp; metabolism}, volume = {52}, number = {2}, pages = {101728}, doi = {10.1016/j.diabet.2026.101728}, pmid = {41547437}, issn = {1878-1780}, mesh = {Humans ; *Diabetic Retinopathy/diagnosis/epidemiology ; Aged ; *Telemedicine ; Male ; Female ; Middle Aged ; France/epidemiology ; Adult ; Cohort Studies ; *Mass Screening/methods ; Adolescent ; Young Adult ; }, abstract = {AIM: To assess the outcomes of teleophthalmology-based diabetic retinopathy (DR) screening in individuals over 70 years within the OPHDIAT network and to compare them with those of patients aged 18-69 years.<br><br>METHODS: A cohort of 16,459 diabetic patients, without known DR or with mild non-proliferative DR (NPDR), screened in 2024 in 32 OPHDIAT centers, was included and divided into two groups: < 70 years (n = 13,639) and &#x2265; 70 years (n = 2,820). Two non-mydriatic retinal photographs per eye were analyzed by certified ophthalmologists.<br><br>RESULTS: Among patients aged &#x2265;70 years, 21.3% (95% CI: 19.8-22.8) had any DR, and 6.1% (95% CI: 5.2-6.9) were referred to an ophthalmologist for moderate NPDR or a more severe form of the disease, including suspected macular edema. These proportions did not significantly differ from those found in patients < 70 years: 21.9% (95% CI: 21.2-22.6) and 6.1% (95% CI:5.6-6.5), respectively. Severe NPDR or proliferative DR were rare in both groups (1.0%, 95% CI: 0.6-1.4% vs. 1.7%, 95% CI: 1.5-1.9%, P < 0.001). The proportion of ungradable images was higher in the group &#x2265;70 year (14.4%, 95% CI:13.1-15.7% vs. 6.1%, 95% CI: 5.7-6.5%, P < 0.001), particularly in phakic eyes, although 80% of patients had interpretable images for both eyes. Pupil dilation significantly improved image quality in this group. Screening also allowed detecting other ocular disorders, including age-related macular degeneration and glaucoma, which were more common in the group &#x2265; 70 years (2.1%, 95% CI: 1.5-2.6% vs. 0.6%, 95% CI: 0.4-0.7% P < 0.001).<br><br>CONCLUSION: Teleophthalmology-based DR screening appeared feasible and clinically relevant in patients aged &#x2265;70 years, allowing identifying patients requiring ophthalmologic evaluation, while also detecting other age-related ocular diseases. Pupil dilation is recommended to optimize image quality in this population.}, }
@article {pmid41548484, year = {2026}, author = {Pan, JQ and Chen, JH and Pan, XB}, title = {Alpha-difluoromethylornithine suppresses angiogenesis via the FLI1-CLEC14A-VEGFC pathway in retinal endothelial cells.}, journal = {Biochemical and biophysical research communications}, volume = {800}, number = {}, pages = {153251}, doi = {10.1016/j.bbrc.2026.153251}, pmid = {41548484}, issn = {1090-2104}, mesh = {Humans ; Animals ; *Endothelial Cells/drug effects/metabolism ; *Lectins, C-Type/metabolism/genetics ; *Proto-Oncogene Protein c-fli-1/metabolism/genetics ; *Vascular Endothelial Growth Factor C/metabolism/genetics ; *Retina/drug effects/metabolism/cytology ; Mice ; Signal Transduction/drug effects ; *Neovascularization, Pathologic/metabolism/drug therapy ; Mice, Inbred C57BL ; Angiogenesis ; }, abstract = {Pathological angiogenesis is a leading cause of vision loss in blinding disorders such as age-related macular degeneration, in which anti-VEGF therapies are widely used, yet their limitations necessitate new therapeutic strategies. This study explores the molecular mechanisms through which alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, suppresses angiogenesis in human retinal microvascular endothelial cells (HRMECs). Transcriptome sequencing revealed that DFMO significantly reduced tube formation and downregulated 3839 genes, including C-type lectin domain-containing 14A (CLEC14A) and vascular endothelial growth factor C (VEGFC), both of which are implicated in angiogenic processes. Functional assays demonstrated that CLEC14A knockdown decreased VEGFC expression and impaired angiogenesis, whereas CLEC14A overexpression alleviated DFMO-induced downregulation of VEGFC. Moreover, bioinformatic analyses and dual-luciferase reporter assays identified Friend leukemia virus integration 1 (FLI1) as a direct transcriptional activator of CLEC14A. Knockdown of FLI1, but not STAT3, reduced CLEC14A expression, confirming the critical regulatory role of FLI1. In vivo studies confirmed upregulation of the FLI1-CLEC14A-VEGFC axis in the retina of a mouse model of choroidal neovascularization. In conclusion, these findings reveal that DFMO suppresses retinal angiogenesis via the FLI1-CLEC14A-VEGFC axis. This study provides new insights into the transcriptional regulation of angiogenesis and suggests potential molecular targets for treating neovascular retinal diseases.}, }
@article {pmid41548710, year = {2026}, author = {Lin, V and Lee, W and Kang, EY and Liu, PK and Wang, NK}, title = {Outer retinal tubulation associated with photoreceptor degeneration.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101435}, pmid = {41548710}, issn = {1873-1635}, support = {K99 EY036930/EY/NEI NIH HHS/United States ; R01 EY031354/EY/NEI NIH HHS/United States ; R21 EY037007/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinal Degeneration/pathology/diagnosis ; *Retinal Pigment Epithelium/pathology ; Ophthalmoscopy/methods ; Animals ; *Photoreceptor Cells, Vertebrate/pathology ; }, abstract = {Outer retinal tubulation (ORT) is a distinct structural manifestation of chronic photoreceptor degeneration, observed across a broad spectrum of retinal diseases. Initially described histologically as rosette-like formations, ORT has gained clinical relevance with the advent of high-resolution imaging modalities such as spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AO-SLO), which enable in vivo visualization of its tubular architecture. ORT arises from sustained photoreceptor and retinal pigment epithelium (RPE) injury, leading to the reorganization of surviving cones ensheathed by gliotic Müller cell processes. This review integrates historical, histological, and imaging data to elucidate ORT's cellular composition, formation mechanisms, and disease-specific patterns. We introduce a novel etiological classification of ORT, categorized as degenerative, fibrotic, or edematous ORT according to predominant pathogenic drivers, to facilitate cross-disease comparison and prognostic stratification. Clinically, ORT serves as a non-exudative biomarker of chronic retinal injury, aiding differential diagnosis and informing treatment strategies. In age-related macular degeneration, ORT is associated with subretinal fibrosis and poor visual outcomes; in geographic atrophy, it may signal slower lesion progression. In inherited retinal dystrophies, ORT reflects genotype-specific vulnerabilities and residual photoreceptor survival, with implications for therapeutic targeting. As imaging technologies advance, ORT offers promise as a structural marker of disease chronicity, photoreceptor resilience, and Müller cell plasticity, enhancing diagnostic precision and supporting its role as a meaningful endpoint in clinical trials.}, }
@article {pmid41548795, year = {2026}, author = {Rinaldi, M and Cennamo, G and Fioretto, G and Passaro, ML and De Falco, F and Bertocchi, M and Marotta, M and Chiosi, F and Calabro, F and Strianese, D and Costagliola, C}, title = {Scleral iontophoresis for targeted lutein delivery in intermediate stage dry AMD: Is this a new frontier in age macular degeneration?.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {57}, number = {}, pages = {105356}, doi = {10.1016/j.pdpdt.2026.105356}, pmid = {41548795}, issn = {1873-1597}, mesh = {Humans ; *Iontophoresis/methods ; Aged ; *Lutein/administration &amp; dosage ; Female ; Male ; Pilot Projects ; Prospective Studies ; Sclera/drug effects ; *Macular Degeneration/drug therapy ; Middle Aged ; Visual Acuity/drug effects ; Aged, 80 and over ; }, abstract = {OBJECTIVES: To evaluate the retinal morphofunctional changes in patients with stage 2 age-related macular degeneration (AMD) following scleral iontophoresis for lutein delivery, and to assess its safety.<br><br>METHODS: In this prospective, non-randomized, single-arm pilot study, 30 stage 2 AMD patients (mean age 71.6 &#xb1; 10.88 years) received scleral iontophoresis with a liquid lutein formulation. Comprehensive ophthalmologic assessments-including best-corrected visual acuity (BCVA), macular pigment optical density (MPOD) via one-wavelength reflectometry, and microperimetry (mean sensitivity, mean defect, and fixation stability measured as BCEA)-were performed at baseline and at 6 months. Adverse events were monitored, and ocular surface health was assessed using the Ocular Surface Disease Index (OSDI).<br><br>RESULTS: At 6 months, MPOD significantly increased from 0.169 &#xb1; 0.06 to 0.180 &#xb1; 0.075 density units (p = 0.0313). Mean sensitivity improved from 7.26 &#xb1; 5.13 dB to 8.18 &#xb1; 4.57 dB (p = 0.0179), and mean defect improved from -11.48 &#xb1; 4.90 dB to -10.27 &#xb1; 3.76 dB (p = 0.0207). Fixation stability, as measured by BCEA at 3 standard deviations, significantly decreased (p = 0.0107). No significant change was observed in BCVA, and OSDI scores remained stable. No adverse events were reported.<br><br>CONCLUSIONS: Scleral iontophoresis of lutein is a safe and promising technique to enhance local MPOD and retinal sensitivity in intermediate AMD patients. Further studies with larger cohorts are warranted to confirm these preliminary findings.}, }
@article {pmid41551980, year = {2026}, author = {Xu, J and Cai, T and Li, J and Ge-Zhang, S and Jiang, Z and Cao, M}, title = {Hydrogel-encapsulated antioxidant nanotherapeutics against age-related macular degeneration (AMD) oxidative damage.}, journal = {International journal of pharmaceutics: X}, volume = {11}, number = {}, pages = {100477}, pmid = {41551980}, issn = {2590-1567}, abstract = {Age-related macular degeneration (AMD) is still the main cause of irreversible vision loss, and the current intravitreal injections is limited by frequent administration and short retinal residence time. This review summarizes the latest progress of hydrogel-nanocarrier hybrid systems, aiming at prolonging ophthalmic drug delivery and supporting retinal tissue. We summarized the pathogenesis of AMD, focusing on oxidative stress and degeneration of retinal pigment epithelium (RPE), and investigated inorganic and organic nano-platforms endowed with antioxidant, anti-inflammatory and anti-angiogenesis functions. The design strategy of embedding nanoparticles into injectable or stimulus-responsive hydrogels is discussed. However, challenges remain, including long-term biocompatibility, inflammatory response to degradation products and potential tissue accumulation. Finally, it is emphasized to accelerate clinical translation through comprehensive long-term in vivo safety evaluation, quantitative optimization of release kinetics, standardized evaluation scheme and development of extensible manufacturing process. It is worth noting that this review mainly emphasizes inorganic nanoparticles and extracellular vesicles, but does not discuss other mature organic nanocarriers in detail. These carriers have been widely studied and emphasized by many other reviews.}, }
@article {pmid41552651, year = {2026}, author = {Prasad, M and Vitale, S and Agrón, E and Arunachalam, T and Chew, EY}, title = {Changes in Vision-Related Quality of Life before and after Geographic Atrophy Development in Age-Related Eye Disease Study Participants.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101022}, pmid = {41552651}, issn = {2666-9145}, abstract = {OBJECTIVE: To examine for change in vision-related quality of life before and after geographic atrophy (GA) development.<br><br>DESIGN: A post hoc analysis of a prospective randomized clinical trial.<br><br>PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants with &#x2265;2 study visits 1 year apart at which they completed the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and age-related macular degeneration (AMD) severity gradings available at the VFQ visits.<br><br>METHODS: A masked reading center assessed AMD severity using annual color fundus photographs. Regression spline models with random effects for time and eye-within-participant (SAS 9.4) were used to compare the rate of change in quality of life (difference in slope for each of the 4 quality of life measures) before and after development of GA (with separate models for GA subtypes: central GA [CGA], noncentral GA [NCGA], and any GA). Models were adjusted for age and visual acuity. If neovascular AMD developed after a GA outcome, we censored the subsequent observations.<br><br>MAIN OUTCOME MEASURES: Outcomes included the VFQ composite score calculated as an average score of nonmissing answered items. The method of successive dichotomizations was used to estimate person measures for the overall NEI VFQ-25 and for 2 derived subscales: visual functioning and social-emotional functioning.<br><br>RESULTS: Among AREDS participants with NEI VFQ-25 data available, 358 eyes (298 participants) developed any GA. None of the quality of life measures differed significantly pre- and post-CGA. Rasch-calibrated subscale score for visual function and composite scores declined more quickly after NCGA (difference in slope [post minus pre]: -0.10 logit/yr [95% confidence interval: -0.18, -0.01], P = 0.03; -0.78 points/yr [95% confidence interval: -1.47, -0.08], P = 0.03, respectively) and after any GA (-0.09 logit/yr [95% confidence interval: -0.16, -0.01], P = 0.02; -0.68 points/yr [95% confidence interval: -1.29, -0.07], P = 0.03, respectively).<br><br>CONCLUSIONS: We observed worsening quality of life after development of NCGA and any GA in AREDS participants across several quality of life measures. Development of CGA was not associated with any significant changes in the quality of life measures, possibly due to the smaller sample size and limited power. Our findings highlight the importance of examining the relationship between GA subtypes and different indices of quality of life.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41552657, year = {2026}, author = {Leng, T and Leung, EH and Mukkamala, SK and Taban, MR and Havilio, M and Nahen, K and Mohan, N and Benyamini, G and Keenan, TDL}, title = {Longitudinal Validation of the Artificial Intelligence Algorithm in Home OCT for Age-Related Macular Degeneration-Report 3.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100907}, pmid = {41552657}, issn = {2666-9145}, support = {P30 EY026877/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: Longitudinal validation of the artificial intelligence-based Notal OCT Analyzer (NOA) for identification of clinically significant changes in the trajectories of retinal total hypo-reflective volume (TRO) from daily home OCT (HOCT) self-imaging in eyes with age-related macular degeneration.<br><br>DESIGN: Post hoc analysis of the HOCT Fluid Visualization Agreement Study.<br><br>PARTICIPANTS: Three hundred seventeen eyes of 180 participants who self-imaged daily using the HOCT for 5 weeks.<br><br>METHODS: For each eye study, the ground truth of TRO stability or change was defined by human experts grading the 5-week time series of HOCT volume scans. The TRO trajectory of the 5 weeks was plotted separately for each study eye by NOA. Three approaches to identifying the optimal threshold (OT) for a clinically significant change in TRO were pursued: (1) personalized approach based on the reference change value methodology used in laboratory medicine; (2) optimized uniform approach; (3) uniform approach commonly used of 10 volume units (VU). The personalized approach comprised TRO curve-fitting to evaluate the change in amplitude (signal) and within-subject variations (noise), followed by receiver operating characteristic analysis of the signal-to-noise ratio (SNR) to identify the OT for determination of a clinically significant change in TRO.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC); sensitivity, specificity, and accuracy at the OT.<br><br>RESULTS: Of the 296 trajectories analyzed, 107 (36.1%) were classified as changing and the remaining 189 (63.9%) as stable. The personalized approach had an AUROC of 0.9811 (with 99.1% sensitivity, 89.4% specificity, and 94.2% accuracy), at OT of SNR = 2.42. The optimized uniform approach had an AUROC of 0.9687 (with 94.4% sensitivity, 89.4% specificity, and 91.9% accuracy), at OT of 3.88 VU. The 10 VU uniform approach had 76.6% sensitivity, 94.7% specificity, and 85.7% accuracy.<br><br>CONCLUSIONS: The NOA-generated trajectories permitted highly accurate determination of TRO change vs. stability, with favorable SNR. The personalized approach had higher sensitivity in detecting TRO change at 99.1% than the uniform approaches. Notal OCT analyzer and its trajectories were a reliable tool for identifying clinically relevant changes in retinal fluid status by the quality standards of laboratory medicine.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41552660, year = {2026}, author = {Sun, J and Shen, M and Chen, J and Wu, Y and Zhou, Y and Feng, J and Cheng, Y and Jia, H and Yang, X and Gong, Y and Liu, Y and Wang, H and Wang, RK and Rosenfeld, PJ and Li, T and Wang, F and Sun, X}, title = {Intravitreal Gene Therapy with LX102-C01 in Neovascular Age-Related Macular Degeneration: A Phase I Dose-Escalation Study of 12-Month Safety and Efficacy Outcomes.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100970}, pmid = {41552660}, issn = {2666-9145}, support = {R01 AG060942/AG/NIA NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; R01 EY030564/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks.<br><br>DESIGN: Open-label, single-center, dose-escalation investigator-initiated trial (NCT05831007) with 2 cohorts (3E10 vector genome [vg] and 1E11 vg per eye).<br><br>SUBJECTS: Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of >2 anti-VEGF treatments in the past 6 months with a good response.<br><br>METHODS: All patients received 1 injection of aflibercept 2 weeks before LX102-C01. Dose escalation started with 3E10 vg and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events (AEs) were assessed. Macular choroidal thickness (CT) and vascularity were measured using a 6 &#xd7; 6 mm scan on swept-source OCT angiography imaging.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was AEs at 1 year. The secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST), and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, CT, and choroidal vascularity index (CVI).<br><br>RESULTS: Six eyes of 6 patients were included. There were no LX102-C01-related nonocular AEs. All LX102-C01-related ocular AEs were mild, predominantly anterior inflammation. There was no evidence of vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. The mean choroidal thickness (MCT) decreased from 162.1 &#x3bc;m to 147.1 &#x3bc;m (P = 0.03), but the CVI measurement showed no significant change (P = 0.6) up to 12 months. Changes in the MCT and CVI showed no statistically significant differences compared with the control group receiving standard aflibercept treatment.<br><br>CONCLUSIONS: LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41553279, year = {2026}, author = {Nguyen, VP and Jeong, J and Zhe, J and Zheng, M and Lee, J and Tran, K and Wei, Z and Lee, CH and Paulus, YM}, title = {Silicon Nanoneedle Patches for Painless, Sustained Treatment of Macular Degeneration.}, journal = {ACS biomaterials science &amp; engineering}, volume = {12}, number = {2}, pages = {1269-1285}, doi = {10.1021/acsbiomaterials.5c01783}, pmid = {41553279}, issn = {2373-9878}, mesh = {*Silicon/chemistry ; Animals ; Rabbits ; *Macular Degeneration/drug therapy/pathology ; *Bevacizumab/administration &amp; dosage/therapeutic use/chemistry ; *Choroidal Neovascularization/drug therapy/pathology ; Drug Delivery Systems ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Delayed-Action Preparations/chemistry ; Humans ; }, abstract = {Choroidal neovascularization (CNV) represents a major cause of vision loss in various retinal diseases such as age-related macular degeneration (AMD). Current treatment involves frequent, often monthly, eye injections. The development of minimally invasive, long-term, painless, and effective ocular drug delivery systems is crucial for advancing the treatment of AMD. This study explores a novel method that integrates controllably bioresorbable silicon nanoneedles loaded with bevacizumab (Si NNs-Bev) on a tear-soluble subconjunctival patch for sustained, 1 year ocular drug delivery. The Si NNs-Bev embed into the sclera in a minimally invasive manner, undergoing controlled degradation over one year. This approach facilitates the sustained release of therapeutic agents, enhancing treatment efficacy and reducing treatment burden. Si NNs-Bev for the treatment of CNV are validated in a rabbit model of AMD. The SiNN-Bev patch achieved a sustained therapeutic effect on CNV regression, with a mean reduction of 82% by 4 months that is persistent for at least 1 year with minimal recurrence, which is consistent with the localized drug delivery mechanism facilitated by the transscleral microneedles. These preliminary findings underscore the potential of SiNNs as a platform technology for long-term, sustained ocular therapeutics.}, }
@article {pmid41553889, year = {2026}, author = {Lachinov, D and Pinetz, T and Bogunovic, H}, title = {PINN-EM: Physics-Guided Disease Progression Model of Geographic Atrophy.}, journal = {IEEE transactions on bio-medical engineering}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TBME.2026.3655164}, pmid = {41553889}, issn = {1558-2531}, abstract = {OBJECTIVE: To construct a personalizable spatio-temporal disease progression model of patients with a late dry form of Age-Related Macular Degeneration (AMD), known as Geographic Atrophy (GA).<br><br>METHODS: From a series of retinal optical coherence tomography (OCT) scans, we infer the coefficients for the parametrized partial differential equation (PDE), such that the parametrized PDE best describes the observed imaging data. Acting as a soft constraint, the recovered PDE helps to extrapolate an implicit neural representation (INR) of the GA segmentation map progression. To enable efficient training, we propose an iterative method - PINN-EM, designed to recover coefficients of non-linear PDEs. At each iteration, the method decouples the problem into PDE coefficients fitting and data fitting steps, resembling Expectation Maximization algorithm.<br><br>RESULTS: We extensively tested the proposed method in large-scale experiments using the open-source PDEBench benchmark to validate its performance. Furthermore, we applied the method to the challenging problem of GA progression modeling, where patients exhibit a high variance in GA growth patterns and speed. The proposed spatio-temporal disease progression model outperformed the baselines, even outperforming posterior knowledge models in Dice score for newly affected growth areas.<br><br>CONCLUSION: We demonstrated that the proposed spatio-temporal disease progression model fitted with introduced PINN-EM outperforms existing baselines in synthetic and real clinical applications, highlighting the extrapolation capabilities of the INR models.<br><br>SIGNIFICANCE: The proposed spatio-temporal disease progression model and PINN-EM fitting procedure can be applied across diverse domains facing the challenge of fitting parametrized PDE to the empirical datasets.}, }
@article {pmid41554422, year = {2026}, author = {Kong, L and Qi, S and Han, X and Zhang, J and Zhang, L and Li, D and Jiang, Q and Zhang, S and Zhao, C}, title = {Integrated proteomic profiling of aqueous humor reveals CDC42/RHOA-mediated pathogenic mechanisms in nAMD and PDR.}, journal = {Experimental eye research}, volume = {264}, number = {}, pages = {110871}, doi = {10.1016/j.exer.2026.110871}, pmid = {41554422}, issn = {1096-0007}, mesh = {*Aqueous Humor/metabolism ; Humans ; *Proteomics/methods ; *cdc42 GTP-Binding Protein/metabolism ; Male ; *Diabetic Retinopathy/metabolism ; *rhoA GTP-Binding Protein/metabolism ; Female ; Aged ; *Wet Macular Degeneration/metabolism ; Middle Aged ; }, abstract = {Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR), though clinically distinct, are both sight-threatening ocular disorders driven by pathological neovascularization. However, their shared molecular mechanisms remain poorly characterized. In this study, we performed DIA quantitative proteomic analysis of aqueous humor (AH) from patients with nAMD, PDR, and control. A total of 3186 proteins were identified, in which 877 and 1017 differentially expressed proteins (DEPs) were detected in the nAMD and PDR groups, respectively, compared to control group. Functional enrichment analysis revealed significant involvement of inflammatory and metabolic pathways in both diseases. Notably, the persistent upregulation of cell division cycle 42 (CDC42) and ras homolog family member A (RHOA) in nAMD and PDR, combined with their established role in cytoskeletal remodeling, suggests their significant involvement in pathological angiogenesis. These findings offer novel perspectives on shared pathogenic pathways in neovascular ocular disorders and suggest potential therapeutic targets for further investigation.}, }
@article {pmid41556037, year = {2025}, author = {Kaganovski, A and Rostomian, N and Shrier, E}, title = {Massive Submacular Hemorrhage Following Intravitreal Faricimab Injection for Neovascular Age-Related Macular Degeneration.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99652}, pmid = {41556037}, issn = {2168-8184}, abstract = {We report a case of massive submacular hemorrhage (SMH) in a patient with neovascular age-related macular degeneration (AMD) occurring three days after intravitreal faricimab injection. While faricimab has demonstrated a favorable safety profile and lower hemorrhagic events compared to other anti-vascular endothelial growth factor agents, SMH, in specific, is not listed among the significant adverse events in available clinical trial safety data or in postmarketing pharmacovigilance analyses. This case highlights a new severe hemorrhagic complication that can cause permanent visual damage related to faricimab even in well-monitored patients.}, }
@article {pmid41557066, year = {2026}, author = {Lee, WA and Tsai, DH and Shao, SC and Lai, EC}, title = {Intraocular inflammation incidence and real-world safety of intravitreal faricimab treatment across retinal indications.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41557066}, issn = {1432-1912}, abstract = {This multi-institutional real-world study evaluated the incidence of intraocular inflammation (IOI) following faricimab treatment across major retinal diseases. The study reviewed records of adults treated with faricimab between January 2022 and April 2025 and classified them into four disease cohorts: neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and polypoidal choroidal vasculopathy (PCV). Patients with a recent history of IOI were excluded. In total, 7784 patients were analyzed, including 4085 with nAMD, 1456 with DME, 1057 with RVO, and 1166 with PCV. Mean ages varied by disease group, ranging from 65.5 years in DME to 75.6 years in nAMD, and more than half of all patients had prior intravitreal anti-VEGF therapy. Within 180 days of treatment initiation, the incidence of new-onset IOI was 0.54% with nAMD, 1.24% with DME, 1.23% with RVO, and 1.03% with PCV. Overall, IOI risk ranged from approximately 0.5 to 1.2%, with higher rates observed among patients with DME and RVO. These findings highlight the importance of ongoing pharmacovigilance as newer retinal therapeutics enter clinical practice, and they provide timely evidence to support safety monitoring in real-world ophthalmology settings.}, }
@article {pmid41557187, year = {2026}, author = {Sonntag, SR and Fries, S and Gniesmer, S and Grisanti, S and Miura, Y}, title = {Fluorescence lifetime imaging ophthalmoscopy (FLIO) of patients with neovascular age-related macular degeneration before and after treatment with intravitreal ranibizumab.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41557187}, issn = {1435-702X}, abstract = {PURPOSE: Neovascular age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections improve outcomes, frequent treatments are burdensome and responses vary. This study investigates changes in macular fluorescence lifetime before and after anti-VEGF therapy using fluorescence lifetime imaging ophthalmoscopy (FLIO), and explores FLIO parameters as potential biomarkers for treatment response.<br><br>METHODS: Twenty patients with neovascular AMD underwent FLIO imaging (excitation: 473&#xa0;nm; emission: short spectral channel [SSC]: 498-560&#xa0;nm; long spectral channel [LSC]: 560-720&#xa0;nm) and macular OCT before and 4-6 weeks after ranibizumab injection. Fluorescence lifetime components (mean &#x3c4;m, short &#x3c4;1, long &#x3c4;2), retinal thickness (RT), and best-corrected visual acuity (BCVA, logMAR) were compared. Analysis focused on central (C), inner ring (IR), and outer ring (OR) regions of the ETDRS grid. Spearman correlation was used to assess relationships between parameter changes.<br><br>RESULTS: Changes in FLIO parameters post-treatment varied individually without a consistent trend. However, statistically significant correlations were found between changes in BCVA (&#x2206;logMAR) and changes in &#x3c4;1 in the central area (p&#x2009;=&#x2009;0.030) as well as &#x3c4;2 in the inner ring (p&#x2009;=&#x2009;0.040) in the SSC, with greater BCVA improvement associated with shorter fluorescence lifetimes. No significant correlation was observed between RT and BCVA.<br><br>CONCLUSION: FLIO parameters correlated with visual acuity changes, while retinal thickness did not. This suggests that FLIO may capture treatment-induced alterations beyond structural changes, potentially reflecting metabolic processes. FLIO may therefore serve as a valuable adjunct tool for monitoring anti-VEGF therapy response in neovascular AMD.}, }
@article {pmid41557492, year = {2026}, author = {Rosli, AH and Abdul-Aziz, CB and Siti-Azrin, AH and Zunaina, E}, title = {Evaluation of IL-6 and TNF-α in Tears and Serum in Age-Related Macular Degeneration.}, journal = {Tropical medicine &amp; international health : TM &amp; IH}, volume = {}, number = {}, pages = {}, doi = {10.1111/tmi.70089}, pmid = {41557492}, issn = {1365-3156}, support = {//Malaysian Society of Ophthalmology/ ; }, abstract = {OBJECTIVE: The purpose of this study was to assess the levels of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the tears and serum of patients with age-related macular degeneration, as well as to identify the factors associated with IL-6 and TNF-α levels in tears.<br><br>METHODS: This was a comparative, cross-sectional study involving age-related macular degeneration patients and a control group. Tear samples were collected using Schirmer paper strips, while 3&#x2009;mL of blood was obtained from each patient. IL-6 and TNF-&#x3b1; levels in tears and serum were measured using a commercial human enzyme-linked immunosorbent assay (ELISA) kit. The study analysed the effects of duration of age-related macular degeneration, disease stage, and smoking status on IL-6 and TNF-&#x3b1; levels in tears, aiming to determine their associations.<br><br>RESULTS: A total of 142 patients were recruited for this study, including 56 patients with early age-related macular degeneration, 56 patients with late neovascular age-related macular degeneration, and 30 patients in the control group. Age-related macular degeneration patients exhibited significantly higher mean levels of IL-6 in both tears and serum, as well as TNF-&#x3b1; in serum, compared to the control group, both before and after adjusting for covariates (21.97&#x2009;&#xb1;&#x2009;10.95 vs. 16.06&#x2009;&#xb1;&#x2009;10.00&#x2009;pg/mL, p&#x2009;=&#x2009;0.008 and p&#x2009;=&#x2009;0.014; 12.00&#x2009;&#xb1;&#x2009;6.04 vs. 8.53&#x2009;&#xb1;&#x2009;4.13&#x2009;pg/mL, p&#x2009;=&#x2009;0.004 and p&#x2009;=&#x2009;0.004; 18.58&#x2009;&#xb1;&#x2009;7.90 vs. 13.61&#x2009;&#xb1;&#x2009;4.86&#x2009;pg/mL, p&#x2009;=&#x2009;0.001 and p&#x2009;=&#x2009;0.004, respectively). Within the age-related macular degeneration group, the mean IL-6 level in serum was significantly higher in patients with late neovascular age-related macular degeneration compared to those with early age-related macular degeneration (13.89&#x2009;&#xb1;&#x2009;6.08 vs. 10.11&#x2009;&#xb1;&#x2009;5.41&#x2009;pg/mL, p&#x2009;=&#x2009;0.001). The levels of IL-6 and TNF-&#x3b1; in tears were not associated with the duration of age-related macular degeneration, the stages of age-related macular degeneration, or smoking status.<br><br>CONCLUSION: There are significantly higher levels of IL-6 in both tears and serum, whereas tears and serum TNF-&#x3b1; serve as non-specific biomarkers for age-related macular degeneration. This study could serve as a basis for future research.}, }
@article {pmid41559451, year = {2026}, author = {Dai, Y and Liang, G and Xu, J and Wang, J and Yang, C}, title = {Inflammatory cytokines are not associated with early age-related macular degeneration: a two-sample Mendelian randomisation study.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {715-732}, pmid = {41559451}, issn = {1476-5454}, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Cytokines/genetics/metabolism ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/metabolism ; Genome-Wide Association Study ; }, abstract = {BACKGROUND/OBJECTIVES: Observational research indicated a potential relationship between inflammatory cytokines and early age-related macular degeneration (AMD), but causal associations remain unclear.<br><br>SUBJECTS/METHODS: Using summary data from genome-wide association studies (GWAS) of 41 different inflammatory cytokines and AMD (including early and late stages), we employed a two-sample Mendelian randomisation (MR) design. Analytical methods including inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger were conducted to detect the causal associations. 'mRnd' online analysis tool was used to evaluate the statistical power of MR estimates. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESO), Cochran's Q and leave-one-out method were applied for sensitivity analysis.<br><br>RESULTS: Our study selected 452 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for following analysis. The IVW results showed that inflammatory cytokines, such as IL-10, GCSF, SCF, IL-1ra, SCGFb and MIG were causally associated with AMD, and MIG, SCGFb and Dry AMD were causally related, while IL-1ra, GCSF and Bngf were causally related to Wet AMD. Interestingly, however, our results suggest no strong causal effect between other inflammatory cytokines and AMD. The analysis results did not reveal horizontal pleiotropy or heterogeneity, and the results are considered robust. The approved drugs or kinase inhibitors predicted by DsigDB to be druggable were obtained mainly from target genes such as ALK, F12 and HTR7.<br><br>CONCLUSIONS: Our MR study suggested that specific inflammatory cytokines may have an impact on overall AMD, but no causal relationship was observed with early AMD. The relationship between them needs further study.}, }
@article {pmid41560351, year = {2026}, author = {Bai, J and Li, S and Wang, A and Wang, B and Wan, Z and Li, JJ and Zhou, Y and Jia, R and Jin, H and Gao, P and Ding, X}, title = {Prosaposin is a dual-action therapeutic target for vascular stabilization and neuroprotection.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.01.015}, pmid = {41560351}, issn = {1525-0024}, abstract = {The disruption of vascular homeostasis is a key pathological feature of fundus abnormal vascular diseases, including wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. While anti-vascular endothelial growth factor therapies are widely used, many patients exhibit limited or suboptimal responses. Through proteomic analysis of 173 aqueous humor samples from fundus abnormal vascular disease patients, followed by validation in an independent cohort of 70 samples, this study identifies prosaposin as a potential therapeutic candidate. In vitro, prosaposin mitigated endothelial dysfunction and reduced vascular permeability, while in vivo, it demonstrated anti-angiogenic and anti-inflammatory effects comparable to aflibercept, effectively reducing vascular leakage and retinal edema. Additionally, prosaposin provided neuroprotection by preserving photoreceptor cells. These findings highlight the dual role of prosaposin in maintaining vascular homeostasis and protecting neural tissues, suggesting its potential as an alternative treatment for patients unresponsive to anti-vascular endothelial growth factor therapies.}, }
@article {pmid41561667, year = {2026}, author = {Nunziata, A and Bianco, L and Antropoli, A and Arrigo, A and Bandello, F and Mansour, AM and Battaglia Parodi, M}, title = {ABCA4-associated retinopathy complicated by didanosine-associated retinal toxicity.}, journal = {American journal of ophthalmology case reports}, volume = {41}, number = {}, pages = {102509}, pmid = {41561667}, issn = {2451-9936}, abstract = {PURPOSE: To describe a rare case of severe central and peripheral chorioretinal atrophy in a patient with ABCA4-associated retinopathy and prior didanosine exposure.<br><br>OBSERVATIONS: A 66-year-old man with a 20-year history of Stargardt disease and HIV/AIDS treated with didanosine for almost ten years in the late '90s presented with progressive bilateral visual loss and color desaturation. Best-corrected visual acuity was 20/400 in both eyes. Multimodal imaging revealed extensive retinal pigment epithelium and choroidal atrophy involving both the macula and mid-periphery, with macular thinning and structural damage confirmed on optical coherence tomography. The peripheral atrophy pattern was consistent with known didanosine toxicity, while the macular degeneration was typical of ABCA4-associated disease. Genetic testing identified three heterozygous ABCA4 variants: one pathogenic nonsense mutation, one likely pathogenic missense mutation, and one variant of uncertain significance. Segregation analysis was not possible due to lack of parental samples.<br><br>CONCLUSIONS AND IMPORTANCE: This case suggests that prior mitochondrial-toxic drug exposure may exacerbate the course of inherited retinal dystrophies, producing unusually severe panretinal degeneration. Clinicians should review medication history in patients with inherited retinal diseases and consider long-term retinal monitoring even years after discontinuing potentially toxic agents.}, }
@article {pmid41563466, year = {2026}, author = {Ueffing, M and Lange, C and Schlunck, G and Wolf, J}, title = {[Liquid biopsy proteomics in ophthalmology : A clinical and scientific perspective].}, journal = {Die Ophthalmologie}, volume = {123}, number = {3}, pages = {169-177}, pmid = {41563466}, issn = {2731-7218}, mesh = {Humans ; *Proteomics/methods ; Liquid Biopsy/methods ; *Aqueous Humor/metabolism/chemistry ; *Eye Diseases/diagnosis/pathology/metabolism ; *Eye Proteins/analysis ; *Ophthalmology/trends/methods ; }, abstract = {BACKGROUND: For many patients with age-related macular degeneration, diabetic retinopathy and other partially monogenetic retinal diseases as well as for tumors of the eye that are relatively rare but are usually associated with profound consequences for affected patients, there is still no effective treatment available. Metastatic melanoma, for example, remains poorly predictable with respect to disease progression, response to treatment and outcome. This illustrates the urgent need for a deeper molecular understanding of the disease with the goal to develop novel therapeutic strategies. Liquid biopsies of the aqueous humor represent a promising possibility for molecular analyses in the eyes of patients.<br><br>OBJECTIVE: A&#xa0;clinical and scientific perspective with respect to potential fields of applications of liquid biopsy proteomics in ophthalmology is presented.<br><br>MATERIAL AND METHODS: A systematic literature search was carried out in PubMed and the personal experiences of the authors are presented.<br><br>RESULTS AND CONCLUSION: Aqueous humor proteomics offer a&#xa0;plethora of potential applications in ophthalmology and could become a&#xa0;key factor in personalized ophthalmology. Potential areas of application include the selection of treatment based on the activated biological signalling pathways, the selection of patients for clinical trials as well as the diagnostics, prognosis estimation and monitoring of the response to treatment. In addition, it can be a&#xa0;valuable component of multimodal diagnostics and enable insights into neurodegenerative diseases, such as Alzheimer's or Parkinson's disease.}, }
@article {pmid41564179, year = {2026}, author = {Becker, S and L'Ecuyer Morison, Z and Allen, J and Saeid, S and Sturgis, L and Adderley, A and Koskelainen, A and Vinberg, F}, title = {Healing of ischemic injury in the retina.}, journal = {Science advances}, volume = {12}, number = {4}, pages = {eadx7204}, pmid = {41564179}, issn = {2375-2548}, support = {R43 EY037154/EY/NEI NIH HHS/United States ; T32 EY024234/EY/NEI NIH HHS/United States ; R01 EY031706/EY/NEI NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Retina/pathology/drug effects/metabolism ; *Reperfusion Injury/pathology ; Mice ; *Ischemia/pathology ; Disease Models, Animal ; Oxidative Stress ; Neuroprotective Agents/pharmacology ; }, abstract = {Neuro- and retinal degenerative diseases, including Alzheimer's, stroke, age-related macular degeneration, and central retinal artery occlusion, rob millions of their independence. Studying these diseases in human retinas has been hindered by the rapid loss of neuronal activity after death. While some CNS activity has been restored postmortem, synchronized neuronal transmission beyond 30 min has remained elusive. We overcome this barrier by reviving and sustaining light signal transmission in human retinas recovered up to 4 hours after death and stored for up to 48 hours. We also introduce infrared-based ex vivo imaging for precise sampling, a closed perfusion system for drug testing, and an ex vivo ischemia-reperfusion model in mouse and human retina. This platform enables testing of neuroprotective and neurotoxic effects of drugs targeting oxidative stress and glutamate excitotoxicity. Our advances question the irreversibility of ischemic injury, support preclinical studies in vision restoration, offer insights into treating CNS ischemia, and pave the way for human donor eye transplantation.}, }
@article {pmid41565848, year = {2026}, author = {Irodi, A and Faes, L and Fu, DJ}, title = {Infographic: Efficacy and safety evaluation of multiwavelength photobiomodulation in nonexudative age-related macular degeneration using the Lumithera Valeda Light Delivery System: 13-month results from the LIGHTSITE III trial.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41565848}, issn = {1476-5454}, }
@article {pmid41565850, year = {2026}, author = {Yu, S and Jones, IL and Maunz, A and Bachmeier, I and Albrecht, T and Ebneter, A and Gliem, M and Staurenghi, G and Sadda, SR and Chakravarthy, U and Fauser, S}, title = {Correction: Artificial intelligence-based analysis of retinal fluid volume dynamics in neovascular age-related macular degeneration and association with vision and atrophy.}, journal = {Eye (London, England)}, volume = {40}, number = {4}, pages = {568}, doi = {10.1038/s41433-025-04232-z}, pmid = {41565850}, issn = {1476-5454}, }
@article {pmid41566404, year = {2026}, author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ}, title = {APOE genotype differentially modulates prion pathology in a mouse model.}, journal = {Acta neuropathologica communications}, volume = {14}, number = {1}, pages = {29}, pmid = {41566404}, issn = {2051-5960}, support = {R01 AG067478/AG/NIA NIH HHS/United States ; RF1 AG088226/AG/NIA NIH HHS/United States ; R01 AG0758401/AG/NIA NIH HHS/United States ; }, abstract = {UNLABELLED: APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer’s disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2, ε3/ε3, and ε4/ε4 APOE-TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε422L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε222L mice performed significantly better than ε4/ε422L mice but significantly worse than ε3/ε322L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP[Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε222L and ε3/ε322L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε422L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε422L mice. ε4/ε422L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε222L, with ε3/ε322L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4-affected mechanisms: increased conversion and accumulation of PrP[Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4, the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-025-02207-5.}, }
@article {pmid41567054, year = {2026}, author = {Prod'hom, S and Massa, H and Thumann, G and Malclès, A}, title = {[Ophthalmology : what's new in 2025].}, journal = {Revue medicale suisse}, volume = {22}, number = {946}, pages = {170-173}, doi = {10.53738/REVMED.2026.22.946.48124}, pmid = {41567054}, issn = {1660-9379}, mesh = {Humans ; Macular Degeneration/drug therapy/therapy ; Quality of Life ; Presbyopia/therapy/drug therapy ; *Ophthalmology/trends ; Graves Ophthalmopathy/drug therapy/therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; }, abstract = {Presbyopia, atrophic age-related macular degeneration, and thyroid eye disease are ophthalmic conditions that can significantly affect patients' vision and quality of life. In this article, we present the most recent therapeutic innovations for their management, including the myotic eye drop aceclidine for presbyopia, complement inhibitors (pegcetacoplan, avacincaptad pegol) to slow the progression of atrophic AMD, and teprotumumab, an anti-IGF1-R antibody, to reduce proptosis and diplopia in thyroid eye disease.}, }
@article {pmid41567568, year = {2026}, author = {Patel, HP and Robbins, CB and Karl, JJ and Weng, P and Vajzovic, L and Fekrat, S}, title = {Corrigendum to "Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration" [Ophthalmology Science. 2025;5:100796].}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100976}, doi = {10.1016/j.xops.2025.100976}, pmid = {41567568}, issn = {2666-9145}, abstract = {[This corrects the article DOI: 10.1016/j.xops.2025.100796.].}, }
@article {pmid41569039, year = {2026}, author = {Guénot, J and Verghese, P}, title = {Cue combination for depth perception in macular degeneration: Motion parallax augments disparity.}, journal = {Journal of vision}, volume = {26}, number = {1}, pages = {11}, pmid = {41569039}, issn = {1534-7362}, support = {R01 EY027390/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Depth Perception/physiology ; Male ; Female ; *Cues ; *Macular Degeneration/physiopathology ; *Motion Perception/physiology ; *Vision Disparity/physiology ; Aged ; Middle Aged ; *Vision, Binocular/physiology ; Scotoma/physiopathology ; Sensory Thresholds/physiology ; Photic Stimulation/methods ; Aged, 80 and over ; Visual Fields/physiology ; }, abstract = {In macular degeneration (MD), depth perception from binocular disparity is impacted in regions with vision loss in either eye, but monocular cues like motion parallax remain available. This study investigates whether combining motion parallax with disparity improves depth perception and compensates for the loss of depth due to central field loss (CFL). Eleven MD participants and 19 controls viewed a horizontal sine-wave corrugation in depth, defined by disparity and/or motion parallax, judging which half-cycle appeared farther away in depth. We measured thresholds for each cue alone and for the two cues combined. In MD participants, cue integration benefits depended on scotoma characteristics. Disparity performance correlated strongly with the size of the stereoblind zone, while motion parallax thresholds showed no significant relation, suggesting preservation despite CFL. MD participants with extensive stereoblind zones showed elevated thresholds for both single cues compared to controls but demonstrated optimal integration when disparity was added to motion parallax. Those with small stereoblind zones achieved control-like thresholds and exhibited optimal or better than predicted integration. However, asymmetric patterns emerged with suboptimal performance when motion parallax was added to threshold disparity. Controls with simulated scotomas maintained stable integration, contrasting with variable patterns in MD. Our results show that individuals with CFL retain significant capacity for depth cue integration, contingent upon residual binocular disparity. Thus, motion parallax emerges as a valuable compensatory cue to improve depth perception in individuals with MD.}, }
@article {pmid41571973, year = {2026}, author = {Mimura, T and Noma, H}, title = {Regional association between PM2.5 exposure and anti-VEGF treatment demand for age-related macular degeneration: a nationwide ecological study in Japan.}, journal = {Environmental science and pollution research international}, volume = {33}, number = {4}, pages = {1416-1429}, pmid = {41571973}, issn = {1614-7499}, mesh = {*Macular Degeneration/drug therapy ; Humans ; *Particulate Matter ; Japan ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Air Pollution ; Intravitreal Injections ; Ranibizumab/therapeutic use ; Air Pollutants ; Aged ; *Environmental Exposure ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in aging populations, and intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the mainstay of its treatment. Recently, environmental air pollution has been proposed as a potential risk factor for ocular diseases. However, few nationwide studies have examined the association between demand for anti-VEGF therapy and environmental factors.<br><br>OBJECTIVE: This study aimed to investigate the relationship between intravitreal anti-VEGF treatment volume and air pollution indicators across all prefectures in Japan using a nationwide database.<br><br>METHODS: Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we extracted data for the fiscal year 2020 on the number of intravitreal brolucizumab injections administered to AMD patients, as well as the total number of anti-VEGF intravitreal injections (including brolucizumab, ranibizumab, and aflibercept) for macular diseases across 48 prefectures. Brolucizumab was approved only for AMD during this year, allowing us to use its usage as a proxy for AMD cases. Environmental data, including average annual concentrations of PM2.5 (&#x3bc;g/m[3]), sulfur oxides (SOX), nitrogen oxides (NOX), and particulate matter dust (PMD; m[3]N/h), were obtained from the Ministry of the Environment. We then analyzed the correlation between anti-VEGF injection volumes per 10,000 persons aged 60 and older and air pollution indicators for each prefecture.<br><br>RESULTS: A strong positive correlation was observed between the number of brolucizumab injections (AMD-specific indicator) and total anti-VEGF injections (non-specific indicator) (r&#x2009;=&#x2009;0.82, p&#x2009;<&#x2009;0.001). Both were significantly correlated with PM2.5 concentrations (brolucizumab: r&#x2009;=&#x2009;0.25, p&#x2009;=&#x2009;0.045; total anti-VEGF: r&#x2009;=&#x2009;0.37, p&#x2009;=&#x2009;0.005). In contrast, no significant correlations were found with SOX (brolucizumab: r&#x2009;=&#x2009;-0.28, p&#x2009;=&#x2009;0.969; total anti-VEGF: r&#x2009;=&#x2009;-0.13, p&#x2009;=&#x2009;0.802), NOX (r&#x2009;=&#x2009;-0.06, p&#x2009;=&#x2009;0.656; r&#x2009;=&#x2009;0.11, p&#x2009;=&#x2009;0.224), or PMD (r&#x2009;=&#x2009;0.03, p&#x2009;=&#x2009;0.430; r&#x2009;=&#x2009;0.14, p&#x2009;=&#x2009;0.180). Moreover, PM2.5 showed no meaningful correlations with SOX, NOX, or PMD.<br><br>CONCLUSION: This nationwide analysis revealed a significant association between regional PM2.5 levels and the use of anti-VEGF intravitreal injections for macular diseases. No such relationship was observed for SOX, NOX, or PMD. These findings suggest that PM2.5 may contribute to the regional demand for AMD treatment, highlighting the need for further investigation into the impact of air pollution on ocular health.}, }
@article {pmid41572339, year = {2026}, author = {Wang, Y and Ma, H and Ge, J and Chen, K and Chen, K and Ye, H and Pan, X and Wang, X and Xia, J and Shen, J and Cheng, T and Cui, H and Sheng, Y}, title = {Senescence-induced endothelial-to-mesenchymal transition accelerates the subretinal fibrosis in neovascualr age-related macular degeneration.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {251}, pmid = {41572339}, issn = {1479-5876}, support = {82401265//National Natural Science Foundation of China/ ; SDCX-ZG-202503121//Postdoctoral Innovation Project of Shandong Province/ ; }, mesh = {Animals ; *Cellular Senescence/genetics/drug effects ; Fibrosis ; Mice, Inbred C57BL ; *Macular Degeneration/pathology/genetics ; Humans ; Endothelial Cells/pathology/metabolism/drug effects ; *Epithelial-Mesenchymal Transition ; *Retina/pathology ; Mice ; Rats ; Rats, Inbred BN ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Male ; Choroidal Neovascularization/pathology ; }, abstract = {BACKGROUND: Subretinal fibrosis remains the severe vision loss in neovascular age-related macular degeneration (nAMD), yet effective treatments are still deficient. Cellular senescence and endothelial-to-mesenchymal transition (EndMT) have been implicated in nAMD pathogenesis.<br><br>METHODS: We analyzed single-cell RNA sequencing data to investigate the role of senescent choriocapillary endothelial cells (CapECs) in subretinal fibrosis. In vitro assays were performed to validate the link between senescence and EndMT. We utilized Brown-Norway rats and INK-ATTAC mice with laser-induced subretinal fibrosis to evaluate the therapeutic effects of senolytic treatment (dasatinib plus quercetin, D&#x2009;+&#x2009;Q) or selective clearance of p16[INK4A]-positive cells. Additionally, young (2-3 months) and old (18 months) C57BL/6J mice were compared to assess the influence of aging on EndMT and fibrosis.<br><br>RESULTS: Our results revealed that CapECs in nAMD exhibited elevated SenMayo gene set variation analysis (GSVA) scores, and upregulated differentially expressed genes (DEGs) were enriched in senescence and mesenchymal transition pathways. A higher proportion of senescence-like CapECs (17.68%) was observed in nAMD, which also showed increased mesenchymal scores and TGFB1 expression. Senescent endothelial cells in laser-induced fibrotic models and bleomycin/doxorubicin-treated human umbilical vein endothelial cells underwent enhanced EndMT. Early intervention with D&#x2009;+&#x2009;Q or removal of p16[INK4A]-positive cells markedly reduced subretinal fibrosis and restored retinal function. Furthermore, endothelial cells from old mice exhibited heightened EndMT and more severe subretinal fibrosis compared to those from young mice.<br><br>CONCLUSIONS: The accumulation of senescent endothelial cells promotes subretinal fibrosis via EndMT in nAMD. Targeting these cells represents a promising therapeutic strategy for mitigating fibrosis-associated vision loss.}, }
@article {pmid41572720, year = {2026}, author = {Jo, Y and Gouya, C and Mieler, WF and Kang-Mieler, JJ}, title = {Advancements and challenges in ophthalmic microneedles to treat eye diseases.}, journal = {Drug delivery}, volume = {33}, number = {1}, pages = {2617688}, pmid = {41572720}, issn = {1521-0464}, mesh = {Humans ; *Needles ; *Drug Delivery Systems/methods/instrumentation ; *Eye Diseases/drug therapy ; Administration, Ophthalmic ; Animals ; }, abstract = {By 2050, more than 61 million people worldwide are expected to lose their vision due to conditions like age-related macular degeneration, glaucoma, diabetic retinopathy, and uveitis (Bourne et al. 2021). This anticipated rise highlights the urgent need for more effective treatment options. While progress continues in developing new pharmacological agents, treating ocular diseases with these therapies remains particularly challenging due to the eye's unique and complex anatomy. This is largely due to the limitations of current drug delivery methods, including systemic administration, topical delivery application, transscleral/periocular drug delivery, and intravitreal injections, which are associated with low bioavailability, side effects, and rapid drug clearance. Given these challenges, microneedles have emerged as a promising alternative. Their minimally invasive nature and ability to precisely target the anterior and posterior segments make them well suited for enhancing therapeutic outcomes while reducing systemic exposure and potential side effects, as well as improving patient adherence (Kang-Mieler et al. 2017; Gadziński et al. 2022). The purpose of this review is to discuss recent advancements, key challenges, and strategies for microneedle-based ocular drug delivery systems, with an emphasis on their potential to treat both anterior and posterior eye diseases.}, }
@article {pmid41572870, year = {2026}, author = {Wu, J and Shan, S and Zhou, J and Li, Y and Ke, Q and Zhu, L and Rudan, I and Song, P and , }, title = {National, regional, and provincial prevalence of age-related macular degeneration in China in 2020: an updated systematic review and modelling study.}, journal = {Journal of global health}, volume = {16}, number = {}, pages = {04062}, pmid = {41572870}, issn = {2047-2986}, mesh = {Humans ; China/epidemiology ; *Macular Degeneration/epidemiology ; Prevalence ; Aged ; Aged, 80 and over ; Middle Aged ; Adult ; Male ; Female ; }, abstract = {BACKGROUND: The burden of age-related macular degeneration (AMD) has steadily increased in recent decades. We aimed to estimate the prevalence of AMD, including its subtypes, among individuals aged 40-89 years in China.<br><br>METHODS: We conducted an updated literature search in the CNKI, Wanfang, Chinese Science and Technology Journal Database, PubMed, Embase, and MEDLINE for studies published between 27 June 2016 and 30 July 2024 that reported on the prevalence of AMD in China. We also included data from the 2017 China AMD Study. We utilised a multi-level mixed-effects meta-regression model to estimate age- and sex-specific prevalence of any AMD and its subtypes at the national level. For any AMD, we additionally conducted random-effects meta-analyses to pool odds ratios for associated factors, after which we incorporated these estimates into an associated factor-based model to estimate prevalence at regional and provincial levels.<br><br>RESULTS: We included 40 articles, of which 24 contributed data for modelling analysis. The estimated national prevalence in China in 2020 was 4.70% (95% CI&#x2009;=&#x2009;3.40, 6.46) for any AMD, 4.06% (95% CI&#x2009;=&#x2009;2.92, 5.60) for early AMD, and 0.64% (95% CI&#x2009;=&#x2009;0.48, 0.86) for late AMD, including 0.30% (95% CI&#x2009;=&#x2009;0.25, 0.37) for geographic atrophy and 0.34% (95% CI&#x2009;=&#x2009;0.23, 0.49) for neovascular AMD. These corresponded to 32.42 million cases (95% CI&#x2009;=&#x2009;23.43, 44.54) with any AMD, 28.00 million (95% CI&#x2009;=&#x2009;20.15, 38.61) with early AMD, 4.42 million (95% CI&#x2009;=&#x2009;3.28, 5.93) with late AMD, 2.09 million (95% CI&#x2009;=&#x2009;1.71, 2.52) with geographic atrophy, and 2.33 million (95% CI&#x2009;=&#x2009;1.57, 3.41) with neovascular AMD. Regionally, the highest prevalence and number of cases was observed in Southwest China (5.95%; 95% CI&#x2009;=&#x2009;4.48, 7.81) and South Central China (10.68 million; 95% CI&#x2009;=&#x2009;7.60, 14.82), respectively. At the provincial level, Hainan and Guangdong exhibited the highest prevalence (7.64%; 95% CI&#x2009;=&#x2009;4.61, 12.22) and the largest number of individuals affected (3.50 million; 95% CI&#x2009;=&#x2009;2.34, 5.13), respectively.<br><br>CONCLUSIONS: We observed a substantial burden of AMD in Mainland China, with variations across subtypes, regions, and provinces. These findings underscore a need for targeted public health strategies to address AMD in the context of ageing.<br><br>REGISTRATION: PROSPERO: CRD420251080685.}, }
@article {pmid41573440, year = {2025}, author = {Mangrio, SM and Faisal, S and Malik, Z and Naeem, A and Saeed, U}, title = {Unilateral Ptosis and Bulbar Symptoms as the Initial Presentation of Late-Onset Acetylcholine Receptor Antibody-Positive Myasthenia Gravis Mimicking Acute Ischemic Stroke in an 82-Year-Old Man.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e99832}, pmid = {41573440}, issn = {2168-8184}, abstract = {Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. In older adults, it may present with bulbar and ocular symptoms that resemble acute stroke. Ocular myasthenia is typically asymmetric and often bilateral; persistent unilateral ptosis in this context can be misleading. An 82-year-old man with type 2 diabetes mellitus, chronic kidney disease, cataracts, and macular degeneration presented with a two-week history of fatigable dysphagia, slurred speech, and new-onset unilateral left ptosis. Symptoms were worse towards the end of the day. He denied diplopia and limb weakness. On examination, he was alert with marked left ptosis, mild left facial weakness, and normal limb strength and gait. A working diagnosis of ischemic stroke was made. Computed tomography of the head, magnetic resonance imaging of the brain with magnetic resonance angiography, and carotid Doppler ultrasound showed no acute vascular pathology. Speech and language therapy assessment demonstrated moderately dysarthric but functional speech and a safe swallow using compensatory strategies. ENT review was arranged as a safety assessment to exclude structural lesions or throat pathology in view of his recent swallowing difficulty, sensation of food sticking on the left side, and intermittent nasal speech later in the day; flexible nasal endoscopy was normal. Neurology review noted fluctuating bulbar symptoms with isolated unilateral ptosis, normal extraocular movements, and a normal limb examination, raising suspicion for myasthenia gravis. Pyridostigmine was started with rapid improvement in ptosis, speech, and swallowing. By the following day, both eyes were open, and he was seen reading, although transient recurrence of ptosis was observed during reassessment, consistent with fatiguability. Computed tomography of the chest excluded thymoma. During brief withdrawal of pyridostigmine for neurophysiology, unilateral ptosis and dysphagia recurred. Nerve conduction studies and limited single-fibre electromyography were non-diagnostic. Subsequent serology confirmed positive acetylcholine receptor antibodies (13.8) and negative anti-MuSK antibodies. He was treated with pyridostigmine and oral prednisolone with gastric and bone protection and close monitoring of glycaemic control. At follow-up, he remained asymptomatic, with full resolution of unilateral ptosis and bulbar symptoms. Persistent unilateral ptosis with fluctuating bulbar symptoms in an elderly patient, normal neuroimaging, and preserved limb strength should prompt consideration of myasthenia gravis despite an initial stroke pathway. As most cases classically present before the age of 50-60 years, this presentation in an 82-year-old man also illustrates very late-onset acetylcholine receptor antibody-positive disease. This case highlights that unilateral ocular involvement does not exclude myasthenia gravis and that close attention to fatigability and symptom evolution can prevent misdiagnosis and support timely, appropriate treatment.}, }
@article {pmid41576663, year = {2026}, author = {Liu, W and Wang, L and Jiang, S}, title = {FGF21 protects retinal pigment epithelium from sodium iodate-induced injury: Association with inhibition of ferroptosis and the NRF2/GPX4 pathway.}, journal = {Experimental eye research}, volume = {265}, number = {}, pages = {110883}, doi = {10.1016/j.exer.2026.110883}, pmid = {41576663}, issn = {1096-0007}, mesh = {*Ferroptosis/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Iodates/toxicity ; *Fibroblast Growth Factors/pharmacology ; Animals ; *NF-E2-Related Factor 2/metabolism ; Mice ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; Macular Degeneration/metabolism/prevention &amp; control ; Signal Transduction ; Lipid Peroxidation ; Cell Line ; Blotting, Western ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness, with retinal pigment epithelium (RPE) cell death representing a central pathological event. Ferroptosis, an iron-dependent form of regulated cell death, has recently been implicated in RPE degeneration. Although fibroblast growth factor 21 (FGF21) has demonstrated cytoprotective effects in various contexts, its specific role and mechanism in RPE protection, particularly concerning ferroptosis, remain unexplored. This study investigated the protective effect of FGF21 against sodium iodate (NaIO3)-induced damage and its underlying mechanism, with a focus on ferroptosis. In vitro, NaIO3 treatment induced significant injury in ARPE-19 cells, which was effectively rescued by FGF21 co-treatment. The protective efficacy of FGF21 was comparable to that of the specific ferroptosis inhibitor Ferrostatin-1. Mechanistically, FGF21 alleviated intracellular iron overload in ARPE-19 cells by modulating the expression of iron regulators (CD71 and FPN1), reduced lipid peroxidation, and restored glutathione levels. Mechanistic exploration revealed that FGF21 treatment was associated with the upregulation of NRF2 and HO-1 and, crucially, with the attenuation of GPX4 downregulation. In a NaIO3-induced mouse model of retinal degeneration, FGF21 administration significantly preserved retinal structure, as evidenced by the maintained outer nuclear layer and total retinal thickness in optical coherence tomography (OCT) and histological analyses. Consistent with the cellular findings, FGF21 upregulated GPX4, NRF2, and HO-1 protein expression in retinal tissues. Our findings demonstrate that FGF21 protects ARPE-19 cells and the retina from NaIO3-induced damage. Its protective profile is closely associated with the mitigation of key ferroptosis hallmarks and correlates with the modulation of the NRF2/GPX4 antioxidant axis. This study provides novel insights and important preclinical evidence supporting further investigation into FGF21 as a potential therapeutic agent for ferroptosis-related retinal degenerative diseases.}, }
@article {pmid41577329, year = {2026}, author = {Lee, J and Han, M and Wang, K and Butler, LR and Sinclair, DA}, title = {Epigenetic reprogramming for ocular aging and disease: Mechanisms, biomarkers, and the road to the clinic.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101442}, doi = {10.1016/j.preteyeres.2026.101442}, pmid = {41577329}, issn = {1873-1635}, mesh = {Humans ; *Epigenesis, Genetic/physiology ; *Aging/genetics/physiology ; Animals ; Biomarkers/metabolism ; *Cellular Reprogramming ; DNA Methylation ; }, abstract = {The eye's visual function relies on retinal neural cells that are long-lived, post-mitotic, and possess minimal regenerative capacity. These combined properties render them exceptionally vulnerable to the cumulative damage that drives age-related functional decline. Accumulating evidence now implicates epigenetic alterations, such as aberrant DNA methylation and histone modifications, not merely as correlates of aging but as fundamental drivers of aging and disease. These changes disrupt the stable gene expression programs required to maintain cellular identity and function, thereby contributing to the pathogenesis of irreversible blinding diseases like glaucoma and age-related macular degeneration (AMD). Unlike immutable genetic mutations, the reversible nature of these epigenetic marks offers a novel therapeutic paradigm. Epigenetic reprogramming, a strategy involving the transient expression of Yamanaka factors or chemical cocktails, provides a powerful means to reset this dysregulated epigenetic landscape and restore cells to a more youthful state. Compelling preclinical studies have validated this approach by demonstrating vision restoration in models of optic neuropathy through the rejuvenation of damaged and aged neurons. This review provides a comprehensive overview of ocular aging from an epigenetic perspective, examines the promise and potential concerns of epigenetic reprogramming, and discusses the future of rejuvenation therapies in ophthalmology.}, }
@article {pmid41577331, year = {2026}, author = {Chung, YC and Alhelaly, M and Nittala, MG and Velaga, SB and He, Y and Haines, JL and Pericak-Vance, MA and Stambolian, D and Sadda, SR}, title = {OCT Risk Factors for Progression to Late-Stage Age-Related Macular Degeneration in the Amish Eye Study.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.010}, pmid = {41577331}, issn = {2468-6530}, abstract = {PURPOSE: To characterize the prevalence of some critical OCT biomarkers-including cuticular drusen and acquired vitelliform lesions (AVLs)-and to identify their relative risk for progression to late age-related macular degeneration (AMD) over 2 years in subjects with early or intermediate AMD in the Amish Eye Study.<br><br>DESIGN: Prospective, observational, longitudinal, population-based cohort study.<br><br>PARTICIPANTS: This study included 276 eyes from 171 subjects with early or intermediate AMD at baseline who completed the 2-year follow-up.<br><br>METHODS: Baseline OCT scans were evaluated for the presence of cuticular drusen, AVLs, subretinal drusenoid deposits (SDDs), high drusen volume (defined as &#x2265;0.2 mm[3] within the central 5 mm), intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDCs), thick/thin double-layer sign (DLS), and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). Subfoveal choroidal thickness (SFCT) was also measured.<br><br>MAIN OUTCOME MEASURES: Incidence of late AMD (geographic atrophy or macular neovascularization) at 2 years as determined by multimodal imaging (OCT, color fundus photography, and confocal fundus autofluorescence).<br><br>RESULTS: By 2 years of follow-up, 26 eyes (10.7%) progressed to late AMD. The most prevalent baseline features in this cohort, in descending order, were cuticular drusen (52.3%), IHRF (17.3%), hDC (16.0%), thin DLS (11.9%), SDD (8.2%), iRORA (7.8%), AVL (7.0%), and high drusen volume (2.5%). The mean SFCT was 243.23 &#xb1; 75.45 &#x3bc;m. Univariate analysis demonstrated that the presence of thick DLS, iRORA, AVL, SDD, IHRF, hDC, and SFCT was associated with an increased risk of progression. In multivariate regression, only the presence of iRORA (odds ratio [OR], 29.60; 95% confidence interval [CI], 6.86-127.84; P < 0.001) and AVL (OR, 15.90; 95% CI, 3.24-78.00; P < 0.001) remained significant, whereas the presence of IHRF showed borderline significance (OR, 4.71; 95% CI, 1.00-22.16; P = 0.050).<br><br>CONCLUSIONS: In this cohort, the presence of iRORA and AVL was independently associated with progression to late AMD over 2 years. Although cuticular drusen were highly prevalent, their presence, as assessed in this study, was not significantly associated with an increased risk of progression to late AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41578078, year = {2026}, author = {Bansal, M and Singh, P and Mehta, RK and Laul, RS and Rana, P and Shah, U and Vohra, R and Desai, S and Bhomaj, S and Patwardhan, S and Manoher, JM and Sapar, A and Parwal, S and Amabde, AK and Shroff, R and Natesh, S and Biswas, RK and D, LR and Sinha, BP and C K, M and Patel, E and Kamble, A and Bhende, P and Patil, S and Shah, A and Narula, R and Kumari, B and Bathula, L and Kirtane, S and Darji, B and Doshi, M and Parmar, D}, title = {A Phase III Randomized Trial Comparing Efficacy, Safety, and Immunogenicity of ZRC-3285 vs. Eylea[®] in Patients with Wet Age-Related Macular Degeneration.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {803-816}, pmid = {41578078}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aims to evaluate the efficacy, safety, and immunogenicity of ZRC-3285 (aflibercept biosimilar) with Eylea[®] (aflibercept) in patients with neovascular (wet) age-related macular degeneration (nAMD).<br><br>METHODS: This phase&#xa0;III, multicenter, double-blind study was conducted across 27 sites in India and randomized (2:1) patients with nAMD into either the test aflibercept (ZRC-3285, Zydus Lifesciences Ltd.) or Eylea[&#xae;] (Regeneron Pharmaceuticals, Inc.) groups. All 184 enrolled patients (122 and 62 in the ZRC-3285 and Eylea[&#xae;] groups, respectively) were included in the modified intend-to-treat (mITT) population. ZRC-3285 or Eylea[&#xae;] was administered by intravitreal injection at a dose of 2&#xa0;mg (0.05&#xa0;mL) on days&#xa0;1, 29, and 57. The primary objective was to assess non-inferiority of ZRC-3285 versus Eylea[&#xae;] in treating nAMD and was evaluated by determining the proportion of patients who lose fewer than 15 letters from baseline visual acuity over 12&#xa0;weeks using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Secondary objectives included comparison of additional efficacy outcomes, immunogenicity, and safety.<br><br>RESULTS: Over 12&#xa0;weeks, all patients in the ZRC-3285 (122, 100%) and Eylea[&#xae;] (62, 100%) groups showed loss of fewer than 15 letters, demonstrating non-inferiority [95% confidence interval (CI) not evaluable (NE); p&#x2009;=&#x2009;NE)] of ZRC-3285 to Eylea[&#xae;]. The proportion of patients who gained more than 15 letters in best corrected visual acuity (BCVA) over 12&#xa0;weeks and the mean changes in BCVA, choroidal neovascularization (CNV), and central retinal thickness (CRT) were similar in both arms.<br><br>CONCLUSION: Efficacy, immunogenicity, and safety profiles of ZRC-3285 were found to be similar to those of Eylea[&#xae;].<br><br>TRIAL REGISTRATION: Clinical trial Registry of India (CTRI): CTRI/2023/09/057655 [Registered on 14/09/2023].}, }
@article {pmid41578358, year = {2026}, author = {Pellegrini, M and Adamo, GG and Cartabellotta, A and Talli, PM and Crisafulli, S and Parmeggiani, F and Mura, M}, title = {Add-on implantation of the smaller-incision new generation implantable miniature telescope (SING IMT™) in pseudophakic eyes.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {28}, pmid = {41578358}, issn = {2056-9920}, abstract = {BACKGROUND: To describe a novel surgical technique for add-on sulcus implantation of the Smaller-Incision New Generation Implantable Miniature Telescope (SING IMT™) in pseudophakic eyes with end-stage age-related macular degeneration (AMD).<br><br>METHODS: Two pseudophakic patients with bilateral end-stage AMD underwent add-on SING IMT&#x2122; implantation in the ciliary sulcus. Pre- and postoperative evaluations included best-corrected distance visual acuity (BCDVA), anterior segment OCT (AS-OCT), corneal endothelial cell counts, and subjective visual function assessments, with follow-up to 6 months.<br><br>RESULTS: Both surgeries were uneventful. The devices remained stable and well-centered with no significant inflammation, corneal decompensation, or intraocular pressure elevation. BCDVA improved by 3&#x2013;4 ETDRS lines, and both patients reported improved daily visual function. Corneal endothelial loss was <&#x2009;5% at 6 months.<br><br>CONCLUSIONS: Add-on sulcus implantation of the SING IMT&#x2122; in pseudophakic eyes is surgically feasible and well tolerated, expanding the potential indications of this visual rehabilitation device to a broader AMD population.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-025-00797-9.}, }
@article {pmid41581044, year = {2026}, author = {Ranga, D and Kaur, S and Nallabelli, N and Sharma, SP and Tigari, B and Dogra, M and Katoch, D and Sharma, SK and Singh, R and Singh, N}, title = {Impact of age-related maculopathy susceptibility 2, high-temperature requirement A serine peptidase 1, and complement factor H genetic variants on clinical phenotypes of age-related macular degeneration.}, journal = {Indian journal of ophthalmology}, volume = {74}, number = {2}, pages = {279-285}, pmid = {41581044}, issn = {1998-3689}, mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism ; *Complement Factor H/genetics/metabolism ; Male ; Female ; *Polymorphism, Single Nucleotide ; Tomography, Optical Coherence ; Aged ; Phenotype ; *Macular Degeneration/genetics/diagnosis/epidemiology/metabolism ; Fluorescein Angiography ; Genotype ; *Proteins/genetics/metabolism ; India/epidemiology ; Middle Aged ; *Genetic Predisposition to Disease ; *DNA/genetics ; Fundus Oculi ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. This study investigated the association of single-nucleotide polymorphisms (SNPs) in ARMS2, HTRA1, and CFH with AMD and its clinical phenotypes and systemic cytokine profiles in a North Indian population.<br><br>METHOD: A total of 113 AMD patients and 99 controls were genotyped using TaqMan assays. All patients underwent detailed ophthalmic evaluations, including optical coherence tomography (OCT), fundus photography, and angiography-based imaging. Serum cytokine levels were quantified using bead-based multiplex immunoassay and analyzed via flow cytometry. Statistical analyses were performed using SPSS v23.0, employing t-tests, ANOVA, and Mann-Whitney U tests.<br><br>RESULTS: Significant associations were observed between AMD and control for risk alleles in ARMS2 (36.3% vs 10.1%, P = 0.001), HTRA1 (37.2% vs 33.3%, P = 0.003), and CFH (27.4% vs 13.1%, P = 0.001). Genotype-phenotype correlations revealed that heterozygous and homozygous risk genotypes were significantly associated with hallmark AMD features such as pigment epithelial detachment (PED), choroidal neovascular membrane (CNVM), large drusen, and retinal pigment epithelium (RPE) atrophy. Cytokine profiling showed significantly reduced levels of erythropoietin (EPO) in AMD patients and granulocyte colony-stimulating factor (G-CSF) in controls (P = 0.044 and P = 0.023).<br><br>CONCLUSION: This study establishes novel genotype-phenotype correlations for ARMS2, HTRA1, and CFH SNPs in a North Indian cohort, linking heterozygous/homozygous risk alleles to distinct AMD clinical features. Reduced EPO and G-CSF levels suggest impaired neuroprotective/anti-inflammatory mechanisms, revealing dual pathways in AMD pathogenesis. By integrating these findings with global data, future efforts can deepen our understanding of AMD's complex etiology and improve patient outcomes worldwide.}, }
@article {pmid41581636, year = {2026}, author = {Wu, F and Xu, K and Zhao, Y and Wang, W and Yang, H and Li, Y and Zheng, G and Li, Z and Xia, Y and Liu, Y and Wu, H and Bai, S}, title = {Associations of Cardiovascular-Kidney-Metabolic Syndrome With Age-Related Macular Degeneration Risk.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {1-7}, doi = {10.1016/j.ajo.2026.01.023}, pmid = {41581636}, issn = {1879-1891}, abstract = {PURPOSE: No study has explored the longitudinal association between cardiovascular-kidney-metabolic (CKM) syndrome and age-related macular degeneration (AMD). We aimed to investigate the associations between CKM syndrome, genetic predisposition, and AMD risk.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: A total of 319,638 participants from the UK Biobank who did not have AMD at baseline.<br><br>METHODS: CKM syndrome was diagnosed based on the presence of chronic kidney disease, cardiovascular disease, and metabolic risk factors. We categorized participants into stages 0 to 4 according to their CKM syndrome status. A genetic risk score was used to estimate genetic predisposition to AMD. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AMD.<br><br>MAIN OUTCOME MEASURES: AMD incidence.<br><br>RESULTS: During a median follow-up of 12.5 years, 4982 AMD cases were identified. After multivariable adjustment, the HRs (95% CIs) for AMD were 1.15 (1.02-1.30), 1.25 (1.13-1.38), 1.22 (1.08-1.38), and 1.48 (1.30-1.68) for participants in CKM stage 1, 2, 3, and 4, respectively, compared to those in CKM stage 0. No significant interaction between genetic predisposition and CKM syndrome was observed (P for interaction = .06). Joint analyses showed that compared to those with CKM stage 0 and low genetic predisposition, individuals with CKM stage 4 and high genetic predisposition exhibited the highest risk of AMD (HR = 2.67, 95% CI: 2.22-3.33).<br><br>CONCLUSIONS: Poor CKM health was positively associated with AMD risk, independent of genetic predisposition.}, }
@article {pmid41582022, year = {2026}, author = {Wang, L and Liu, H and Liu, C}, title = {Comment on "A deep learning approach for the screening of referable age-related macular degeneration - Model development and external validation".}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2026.01.049}, pmid = {41582022}, issn = {0929-6646}, }
@article {pmid41582115, year = {2026}, author = {Kose, H and Ozkan, B and Kanli, A and Karabas, LV and Akpinar, G and Kasap, M and Sumer, F}, title = {Correction: Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.}, journal = {BMC geriatrics}, volume = {26}, number = {1}, pages = {100}, pmid = {41582115}, issn = {1471-2318}, }
@article {pmid41582270, year = {2026}, author = {Fukuda, Y and Sakurada, Y and Kotoda, Y and Kikushima, W and Kashiwagi, K}, title = {Two year outcomes of as needed brolucizumab therapy in exudative age related macular degeneration with or without pachychoroid phenotype.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {6183}, pmid = {41582270}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; Aged ; Phenotype ; Treatment Outcome ; Visual Acuity/drug effects ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Macular Degeneration/drug therapy/pathology ; Aged, 80 and over ; Follow-Up Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; }, abstract = {Brolucizumab is a second-generation vascular endothelial growth factor (VEGF) inhibitor. To date, there have been no reports comparing treatment outcomes between exudative age-related macular degeneration with or without the pachychoroid phenotype using a second-generation VEGF inhibitor. The present study compared two-year as-needed brolucizumab treatment outcomes in patients with and without pachychoroid phenotypes. Sixty-six eyes completed two years of follow-up, and 14 and 52 eyes were classified into the pachychoroid and non-pachychoroid phenotypes, respectively. At 24 months, best-corrected visual acuity (BCVA) significantly improved in both groups, from 0.30 ± 0.29 to 0.12 ± 0.21 in the pachychoroid phenotype and 0.43 ± 0.36 to 0.31 ± 0.37 in the non-pachychoroid phenotype (p = 0.014 and 0.0013, respectively). At the 24-month follow-up, there were significantly fewer eyes requiring retreatment in the pachychoroid phenotype than in the non-pachychoroid phenotype (50% vs. 83%, p = 0.03). Although the number of additional injections was comparable between the two groups in the first 12 months (1.2 ± 1.4 vs. 1.7 ± 1.6, p = 0.29), the number of additional injections was significantly lower in the pachychoroid phenotype than in the non-pachychoroid phenotype (1.5 ± 2.4 vs. 3.2 ± 2.6, p = 0.0098) in the second 12 months. In the 24-month as-needed brolucizumab treatment group, the response to the pachychoroid phenotype was favorable, with significant BCVA improvement and fewer additional injections, particularly in the second 12 months.}, }
@article {pmid41582411, year = {2026}, author = {}, title = {Highlighting Eye Health for National Age-Related Macular Degeneration Awareness Month.}, journal = {Nursing}, volume = {56}, number = {2}, pages = {63}, doi = {10.1097/NSG.0000000000000329}, pmid = {41582411}, issn = {1538-8689}, }
@article {pmid41584094, year = {2026}, author = {Hunt, PW and Olshen, AB and Murad, N and Ambayec, GC and Sezgin, E and Schneider, MF and Jabs, DA}, title = {Erratum to "Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS" [Ophthalmol Sci. 2025;5:100794].}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100974}, doi = {10.1016/j.xops.2025.100974}, pmid = {41584094}, issn = {2666-9145}, abstract = {[This corrects the article DOI: 10.1016/j.xops.2025.100794.].}, }
@article {pmid41584096, year = {2026}, author = {Chakravarthy, U and Csincsik, L and Teo, KYC and Munk, MR and Grewal, DS and Guymer, RH and Jaffe, GJ and Peto, T and Sadda, SR and Staurenghi, G and Cheung, CMG and , }, title = {Standardization of Imaging Criteria for Detecting Macular Fibrosis in Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101027}, pmid = {41584096}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.<br><br>DESIGN: Systematic discussion and grading exercise assessing multiple imaging modalities.<br><br>PARTICIPANTS: Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.<br><br>METHODS: An international panel assessed the advantages and limitations of 5 imaging modalities-color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence-for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed.<br><br>MAIN OUTCOME MEASURES: Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.<br><br>RESULTS: Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87.<br><br>CONCLUSIONS: The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41584098, year = {2026}, author = {Weng, CY and Blinder, KJ and Hall, EF and Rosenthal, WN}, title = {Personalizing Personalized Medicine: The Pursuit of Optimal Thresholds in the Home OCT Artificial Intelligence Algorithm for Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101017}, pmid = {41584098}, issn = {2666-9145}, }
@article {pmid41585411, year = {2026}, author = {Sun, Y and Huang, J and Zhang, Z and Chen, Z and Li, Z and Wu, F and Wang, Z and Wu, T and Yi, G and Meng, F and Wu, S}, title = {Protective Effects of Bone Mineral Density on Age-Related Macular Degeneration: A Mendelian Randomization Study.}, journal = {International journal of endocrinology}, volume = {2026}, number = {}, pages = {6619808}, pmid = {41585411}, issn = {1687-8337}, abstract = {INTRODUCTION: Observational studies have established the connection between a decrease in bone mineral density (BMD) and an increased susceptibility to age-related macular degeneration (AMD). However, the cause-and-effect link of this correlation remains uncertain. This study employed Mendelian randomization (MR) methods to examine the causality between BMDs and AMD.<br><br>MATERIALS AND METHODS: The GEnetic Factors for OSteoporosis (GEFOS) Consortium, UK Biobank, and FinnGen Biobank offered summary statistics for BMD and AMD. We adopted an array of quality control procedures to screen for eligible instrumental single nucleotide polymorphisms (SNPs). The inverse variance weighting (IVW) algorithm was the most trustworthy approach in MR analyses. Furthermore, we employed additional analytical methods such as MR-Egger and weighted median (WM) for confirming the soundness of the present MR outcomes.<br><br>RESULTS: The findings indicated that genetically predicted total body BMD (TB-BMD, IVW: OR&#x2009;=&#x2009;0.772, 95% CI&#x2009;=&#x2009;0.642-0.928, p = 0.006), lumbar spine BMD (LS-BMD, IVW: OR&#x2009;=&#x2009;0.739, 95% CI&#x2009;=&#x2009;0.583-0.937, p = 0.013), femoral neck (FN-BMD, WM: OR&#x2009;=&#x2009;0.626, 95% CI&#x2009;=&#x2009;0.432-0.906, p = 0.013), and TB-BMD (age over 60, MR-Egger, OR&#x2009;=&#x2009;0.383, 95% CI&#x2009;=&#x2009;0.163-0.902, p = 0.041) were associated with lower odds of wet AMD. No significant causal relationship can be found between other BMDs and Wet-AMD, or between BMDs and Dry-AMD.<br><br>CONCLUSION: Our MR analysis supported the causal correlation between genetically predicted BMD and Wet-AMD. As to Dry-AMD, it was not causally related to BMD. Our study complemented the evidence from previous observational surveys and emphasized the extraordinary importance of monitoring BMD for preventing and treating AMD.}, }
@article {pmid41587414, year = {2026}, author = {Ramulu, S and Sindal, MD and Thotakura, M and Vaidya, MV and Venkatesh, R and Ramulu, PY}, title = {Patients with age-related macular degeneration face impairment in activities of daily living.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/08164622.2026.2616034}, pmid = {41587414}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Age-related macular degeneration can lead to significant visual impairment in older individuals. These can significantly impact their day-to-day life, and understanding these limitations is crucial for healthcare providers.<br><br>BACKGROUND: The aim of this work is to determine impairment of activities of daily living secondary to visual impairment caused by age-related macular degeneration in a South Indian population.<br><br>METHODS: In this prospective cross-sectional study, the instrumental activities of daily living questionnaire was administered to participants with uniocular or binocular visual impairment due to age-related macular degeneration, and controls who did not have any significant ocular or retinal pathology.<br><br>RESULTS: The study recruited 90 participants in each arm, where those with age-related macular degeneration were older. More participants with age-related macular degeneration (92.2%) had impairment with one or more activities of daily living as compared to controls (55.6%,p&#x2009;<&#x2009;0.001). The age-related macular degeneration group faced a median of 4 (IQR 2-8) impairments and could perform 53.3% with difficulty, 39.4% with assistance and 7.3% activities could not be completed. In the age-related macular degeneration group, those with unilateral disease had 8.95-fold (p&#x2009;<&#x2009;0.001) greater level of impairment, while those with bilateral disease has a 10.72-fold (p&#x2009;=&#x2009;0.001) greater level of impairment as compared to controls.<br><br>CONCLUSION: Visual impairment due to age-related macular degeneration has a significant impact on activities of daily living. The patients often need assistance in completing their activities. Care in age-related macular degeneration needs to involve rehabilitation and help in carrying out daily activities in addition to treatment for visual benefits.}, }
@article {pmid41587655, year = {2026}, author = {Faurite, C and Michaud, C and Olivier, P and Gallice, M and Chiquet, C and Soler, V and Berry, I and Cottereau, BR and Peyrin, C}, title = {Enhancing peripheral scene recognition through spatial frequency training: Behavioral evidence from macular degeneration and healthy aging.}, journal = {Neuropsychologia}, volume = {223}, number = {}, pages = {109377}, doi = {10.1016/j.neuropsychologia.2026.109377}, pmid = {41587655}, issn = {1873-3514}, mesh = {Humans ; Male ; Female ; *Macular Degeneration/rehabilitation/physiopathology/psychology/complications ; Aged ; Middle Aged ; *Healthy Aging/physiology/psychology ; Photic Stimulation ; *Pattern Recognition, Visual/physiology ; Aged, 80 and over ; *Recognition, Psychology/physiology ; *Space Perception/physiology ; *Aging ; }, abstract = {Macular degeneration (MD) causes central vision loss and leads to long-term reorganization of visual functions. Central vision loss in MD severely reduces access to high spatial frequencies (HSF) that convey fine visual details, while low spatial frequencies (LSF) remain relatively accessible through peripheral vision and may support compensatory processing. This study investigated whether repeated training in categorizing filtered scenes improves peripheral scene recognition by enhancing spatial frequency processing. Ten MD patients and ten age- and gender-matched controls performed a scene categorization task (indoor vs. outdoor) using LSF or HSF images. Both groups completed a 12-session training protocol: patients performed the task at their preferred retinal location (PRL), and controls fixated with their fovea and viewed stimuli through an individualized artificial scotoma matched to their paired patient. Before training, MD patients showed a marked deficit for HSF scenes compared to controls, and a milder deficit for LSF scenes. After training, patients exhibited a significant improvement in categorizing LSF scenes, and an improvement specifically limited to HSF outdoor scenes, suggesting enhanced use of preserved peripheral information and partial compensation for the HSF deficit. Older controls also showed reduced performance for HSF scenes in peripheral vision, and similarly benefited from training. These results highlight the potential of perceptual training to enhance peripheral visual processing in MD patients, particularly by leveraging coarse visual cues. They support the idea that such protocols may be beneficial not only for visual rehabilitation in MD but also for preserving visual-cognitive functions in normal aging.}, }
@article {pmid41590921, year = {2026}, author = {Lopukhova, EA and Idrisova, GM and Mukhamadeev, TR and Voronkov, GS and Kutluyarov, RV and Topolskaya, EP}, title = {A Hierarchical Deep Learning Architecture for Diagnosing Retinal Diseases Using Cross-Modal OCT to Fundus Translation in the Lack of Paired Data.}, journal = {Journal of imaging}, volume = {12}, number = {1}, pages = {}, pmid = {41590921}, issn = {2313-433X}, abstract = {The paper focuses on automated diagnosis of retinal diseases, particularly Age-related Macular Degeneration (AMD) and diabetic retinopathy (DR), using optical coherence tomography (OCT), while addressing three key challenges: disease comorbidity, severe class imbalance, and the lack of strictly paired OCT and fundus data. We propose a hierarchical modular deep learning system designed for multi-label OCT screening with conditional routing to specialized staging modules. To enable DR staging when fundus images are unavailable, we use cross-modal alignment between OCT and fundus representations. This approach involves training a latent bridge that projects OCT embeddings into the fundus feature space. We enhance clinical reliability through per-class threshold calibration and implement quality control checks for OCT-only DR staging. Experiments demonstrate robust multi-label performance (macro-F1 =0.989±0.006 after per-class threshold calibration) and reliable calibration (ECE =2.1±0.4%), and OCT-only DR staging is feasible in 96.1% of cases that meet the quality control criterion.}, }
@article {pmid41591569, year = {2026}, author = {Heidari, Z and Mirghorbani, M and Abounoori, M and Ebrahimibesheli, K and Tabarestani, M and Khabazkhoob, M and Yousefi, S and Modjtahedi, BS}, title = {Vitreoretinal disease detection using artificial intelligence: a systematic review and meta-analysis.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {77}, pmid = {41591569}, issn = {1573-2630}, mesh = {Humans ; *Artificial Intelligence ; *Retinal Diseases/diagnosis ; *Vitreous Body/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: Early detection of vitreoretinal diseases (VRDs) is critical for preventing vision loss, and currently relies on the examination and interpretation of multimodal imaging techniques. Artificial intelligence (AI) is emerging as a powerful tool to detect abnormalities in vitreoretinal morphology and ideally detect changes at earlier stages to allow for intervention. This meta-analysis evaluates and summarizes the diagnostic performance of AI models in the detection of VRDs using retinal imaging systems.<br><br>METHODS: This study was registered in PROSPERO (CRD42023450207). A comprehensive electronic search of PubMed/MEDLINE, EMBASE, and Web of Science was conducted by three independent reviewers up to August 2023. Study validity was assessed using the QUADAS-2 tool, which evaluates risk of bias across four domains and applicability concerns across three domains. Eligible articles were categorized into nine VRD subgroups-age related macular degeneration, diabetic retinopathy, retinal vascular diseases, retinal dystrophies, Cystoid macular edema, vitreoretinal interface disorders, retinal detachment, Central serous chorioretinopathy, and myopic retinopathy-and included in the meta-analysis. Pooled estimates of accuracy (PEA), sensitivity (PESen), and specificity (PESpe) were calculated for all selected studies.<br><br>RESULTS: A total of 195 studies were included in the final analysis, yielding an overall PEA of 95.76% (95% CI: 95.0-96.47), PESen of 91.94% (95% CI: 90.72-93.08) and PESpe of 96.09% (95% CI: 95.27-96.79). In the subgroup analysis, most AI models had a PEA&#x2009;>&#x2009;90%, especially convolutional neural networks (CNN), followed by support vector machine (SVM) and random forest (RF).<br><br>CONCLUSIONS: AI diagnostic tools, particularly CNNs, have demonstrated robust performance in VRDs detection. However, results from studies with limited generalizability should be applied cautiously in real-world settings. Further exploration of emerging models, such as large language models (LLMs), is recommended.}, }
@article {pmid41592857, year = {2026}, author = {Wang, Z and Xu, C and Wang, L and Qiang, W and Li, Y and Li, D and Xu, F and Zhang, Y and Jiang, J and Li, Z}, title = {Evaluating reasoning large language models with human-like thinking in ophthalmic question answering.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41592857}, issn = {2397-3269}, mesh = {Humans ; *Ophthalmology/education ; *Thinking/physiology ; *Language ; *Educational Measurement/methods ; Large Language Models ; }, abstract = {OBJECTIVES: To evaluate the performance of reasoning large language models (LLMs) with human-like thinking in ophthalmic question answering.<br><br>METHODS: We evaluated two state-of-the-art open-source reasoning LLMs (DeepSeek-R1 and QwQ-32B) and one conventional non-reasoning LLM (LLaMA-3.3-70B-Instruct) models on ophthalmology questions, assessing not only answer accuracy (ACC) but also the quality of their reasoning processes. First, we curated MedQA-Eye, a dataset of 967 ophthalmology questions across 10 subspecialties, 3 scenarios, 5 medical entities and 3 languages. Second, we proposed a novel framework considering human thinking patterns essential to medical practice to evaluate the thinking performance of reasoning LLMs on MedQA-Eye.<br><br>RESULTS: DeepSeek-R1 demonstrated superior overall ACC (90.59%, 95% CI 88.59% to 92.27%) to LLaMA-3.3-70B-Instruct (87.90%, 95%&#x2009;CI 85.69% to 89.81%, p=0.015) and QwQ-32B (84.28%, 95%&#x2009;CI 81.85% to 86.44%, p<0.001) with performance varying across subspecialties. Analysis of reasoning LLMs revealed incorrect logical inference as the primary point of failure, accounting for 93.41%-94.74% of incorrectly answered questions. We further quantified semantic uncertainty in reasoning LLM thinking as a predictor of answer reliability. DeepSeek-R1 exhibited lower semantic uncertainty (1.04&#xb1;3.63) compared with QwQ-32B (4.31&#xb1;40.70), p<0.001.<br><br>CONCLUSION: Reasoning LLMs demonstrated superior performance in ophthalmology question answering, with DeepSeek-R1 achieving the highest ACC. Our findings demonstrate that reasoning LLM can better simulate human-like thinking processes compared with conventional non-reasoning LLM, suggesting its potential for more trustworthy LLM systems in ophthalmology.}, }
@article {pmid41593166, year = {2026}, author = {Lee, JH and Lee, SY and Jang, B and Kim, YG and Yoon, CK and Park, UC and Park, KH and Lee, EK}, title = {OCT biomarkers as predictors of treatment interval in neovascular age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {6504}, pmid = {41593166}, issn = {2045-2322}, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults. Treat-and-extend (T&amp;E) regimen for anti-vascular endothelial growth factor therapy are widely used to individualize treatment, yet substantial variability exists in achievable treatment intervals, and reliable baseline predictors remain unclear. This study investigates the association between baseline optical coherence tomography (OCT) biomarkers and treatment interval in eyes with nAMD treated with intravitreal aflibercept using a T&amp;E regimen in real-world clinical settings. This retrospective study analyzed 174 treatment-naïve eyes with nAMD of 167 patients from an initial screening of 536 eyes of 333 patients. Baseline OCT biomarkers were evaluated. Subretinal fluid, intraretinal fluid, and pigment epithelial detachments were automatically quantified using convolutional neural network-based segmentation algorithms. Correlations between OCT measurements and < q12 weeks intervals at 52 weeks were analyzed. Of the 174 eyes included, 78 (44.8%) were treated at intervals < q12 weeks at 12 months. Retinal angiomatous proliferation (RAP) (odds ratio [OR], 2.896; 95% confidence interval [CI], 1.045 − 8.022; p = 0.041), absence of intra/subretinal hemorrhage (OR, 0.381; 95% CI, 0.165 − 0.880; p = 0.024), and longer disruption of external limiting membrane (ELM) (OR, 1.094; 95% CI, 1.018 − 1.176; p = 0.014) and ellipsoid zone (EZ) (OR, 1.066; 95% CI, 1.011 − 1.124; p = 0.018) were significantly associated with < q12 weeks interval, whereas quantitative fluid measurements were not significantly associated with dosing interval. Baseline structural OCT biomarkers were associated with treatment interval requirements in nAMD managed with a T&amp;E regimen, suggesting their potential value for early identification of patients likely to require more intensive treatment.}, }
@article {pmid41594154, year = {2026}, author = {Yoon, T and Kang, D}, title = {Efficient Ensemble Learning with Curriculum-Based Masked Autoencoders for Retinal OCT Classification.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, pmid = {41594154}, issn = {2075-4418}, support = {RS-2023-00249104//National Research Foundation of Korea (NRF) through a grant funded by the Korean government (MSIT)/ ; }, abstract = {Background/Objectives: Retinal optical coherence tomography (OCT) is essential for diagnosing ocular diseases, yet developing high-performing multiclass classifiers remains challenging due to limited labeled data and the computational cost of self-supervised pretraining. This study aims to address these limitations by introducing a curriculum-based self-supervised framework to improve representation learning and reduce computational burden for OCT classification. Methods: Two ensemble strategies were developed using progressive masked autoencoder (MAE) pretraining. We refer to this curriculum-based MAE framework as CurriMAE (curriculum-based masked autoencoder). CurriMAE-Soup merges multiple curriculum-aware pretrained checkpoints using weight averaging, producing a single model for fine-tuning and inference. CurriMAE-Greedy selects top-performing fine-tuned models from different pretraining stages and ensembles their predictions. Both approaches rely on one curriculum-guided MAE pretraining run, avoiding repeated training with fixed masking ratios. Experiments were conducted on two publicly available retinal OCT datasets, the Kermany dataset for self-supervised pretraining and the OCTDL dataset for downstream evaluation. The OCTDL dataset comprises seven clinically relevant retinal classes, including normal retina, age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), retinal vein occlusion (RVO), retinal artery occlusion (RAO), and vitreomacular interface disease (VID) and the proposed methods were compared against standard MAE variants and supervised baselines including ResNet-34 and ViT-S. Results: Both CurriMAE methods outperformed standard MAE models and supervised baselines. CurriMAE-Greedy achieved the highest performance with an area under the receiver operating characteristic curve (AUC) of 0.995 and accuracy of 93.32%, while CurriMAE-Soup provided competitive accuracy with substantially lower inference complexity. Compared with MAE models trained at fixed masking ratios, the proposed methods improved accuracy while requiring fewer pretraining runs and reduced model storage for inference. Conclusions: The proposed curriculum-based self-supervised ensemble framework offers an effective and resource-efficient solution for multiclass retinal OCT classification. By integrating progressive masking with snapshot-based model fusion, CurriMAE methods provide high performance with reduced computational cost, supporting their potential for real-world ophthalmic imaging applications where labeled data and computational resources are limited.}, }
@article {pmid41594936, year = {2026}, author = {Zhang, YY and Sun, QF and Bai, W and Yao, J}, title = {Retinal Astrocytes: Key Coordinators of Developmental Angiogenesis and Neurovascular Homeostasis in Health and Disease.}, journal = {Biology}, volume = {15}, number = {2}, pages = {}, pmid = {41594936}, issn = {2079-7737}, support = {82271107//National Natural Science Foundation of China/ ; K2023060//Jiangsu Provincial Health Commission Medical Research Key Project/ ; JX10414318//Postgraduate Research and Practice Innovation Program of Jiangsu Province/ ; }, abstract = {Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood-retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity.}, }
@article {pmid41598159, year = {2025}, author = {Kudasiewicz-Kardaszewska, A and Ozimek, MA and Urbański, T and Jamontt, K and Tkaczenko, A and Bonińska, K and Cisiecki, S}, title = {Combined Pharmacological and Pneumatic Displacement Therapy for Sub-Macular Haemorrhage Secondary to Age-Related Macular Degeneration: A Case Series and Review of the Literature.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, pmid = {41598159}, issn = {2075-1729}, abstract = {PURPOSE: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September 2025. All patients received intravitreal alteplase (100 &#xb5;g) and C3F8 gas, followed by aflibercept (2 mg or 8 mg) within a treat-and-extend regimen. BCVA- and OCT-based anatomical changes were recorded at baseline, 7-14 days, 1 month, 3 months, and 6 months. BCVA changes were analysed using repeated-measures testing.<br><br>RESULTS: Mean BCVA improved from 0.99 &#xb1; 0.21 logMAR at baseline to 0.89 &#xb1; 0.20 at 7-14 days, 0.80 &#xb1; 0.20 at 1 month, 0.60 &#xb1; 0.18 at 3 months, and 0.53 &#xb1; 0.20 at 6 months (p < 0.05 for overall change). Eight eyes (80 percent) showed restoration of foveal contour, while two developed foveal atrophy. No major adverse events occurred.<br><br>CONCLUSION: Combined intravitreal alteplase and C3F8, followed by aflibercept, may provide favourable short-term visual and anatomical improvement in SMH secondary to nAMD. Early intervention appears beneficial, but larger controlled studies are needed to confirm these findings.}, }
@article {pmid41598179, year = {2025}, author = {Li, B and Addo, EK and Chang, FY and Guo, S and Awuni, M and Conway, E and Ying, J and Ramos, D and Bernstein, PS}, title = {Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {1}, pages = {}, pmid = {41598179}, issn = {2075-1729}, support = {EY-11600, EY-14800//NIH grants EY-11600, EY-14800, by the BrightFocus Foundation, and by unrestricted departmental funds from Research to Prevent Blindness/ ; }, abstract = {Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study examined the effect of carotenoid supplementation on circulating HDL cholesterol levels. Serum lipid profiles were measured in 20 participants from the Lutein and Zeaxanthin in Pregnancy (L-ZIP) trial, which enrolled 40 pregnant women. In addition to standard prenatal supplements, half received 10 mg of lutein and 2 mg of zeaxanthin daily from the first trimester, and half received a placebo. Carotenoid supplementation significantly increased HDL cholesterol in the third trimester, with no changes in total cholesterol, LDL cholesterol, or triglycerides (TG) across trimesters. To further evaluate individual carotenoids, serum lipids were analyzed in macular pigment transgenic mice fed lutein, zeaxanthin, or β-carotene for one month. All three carotenoids significantly increased HDL cholesterol and reduced TG levels, with the effect ranking as zeaxanthin > lutein > β-carotene. These findings suggest that carotenoid supplementation modulates the serum lipid profile-elevating HDL cholesterol and lowering TG-which may contribute to protection against AMD and other lipid-associated diseases.}, }
@article {pmid41598388, year = {2026}, author = {Ongun, GT and Yağcı, R}, title = {The Effect of Intravitreal Ranibizumab Injection on Retinal Nerve Fiber Layer Thickness and Optic Disc Parameters.}, journal = {Journal of clinical medicine}, volume = {15}, number = {2}, pages = {}, pmid = {41598388}, issn = {2077-0383}, abstract = {Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the clinical records of 60 patients who received intravitreal ranibizumab injections for macular edema secondary to AMD, DME, or RVO between October 2014 and January 2016. All patients received intravitreal ranibizumab at a dose of 0.5 mg. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were recorded at baseline and during follow-up. RNFL thickness and optic disc parameters were assessed using optical coherence tomography (OCT) and Heidelberg Retina Tomograph III (HRT-3). Measurements were obtained before treatment and at 1 week, 1 month, 3 months, and 6 months after injection. Comparisons were performed within and between disease groups. Results: Of the 60 patients, 31 (51.7%) had DME, 20 (33.3%) had AMD, and 9 (15.0%) had RVO. Best-corrected visual acuity improved significantly during the follow-up period. Mean RNFL thickness measured by OCT showed a significant reduction in the DME and RVO groups (p = 0.0001 and p = 0.043, respectively). In contrast, no significant changes in RNFL thickness were detected using HRT-3, and no consistent alterations in other optic disc parameters were observed. Changes in optic disc parameters varied among disease groups. Conclusions: Intravitreal ranibizumab treatment was associated with a reduction in mean RNFL thickness measured by OCT in patients with DME and RVO during a six-month follow-up period, whereas no corresponding RNFL thinning was detected using HRT-3 in any disease group. The observed optic disc parameter changes appeared to be disease specific. Given the absence of untreated control eyes and the exclusion of patients with glaucoma, these findings apply only to non-glaucomatous eyes and should not be extrapolated to patients with glaucoma. Further prospective studies with larger cohorts, appropriate control groups, and longer follow-up durations are warranted to clarify the long-term effects of anti-VEGF therapy on the optic nerve.}, }
@article {pmid41598408, year = {2026}, author = {Sarna, M and Waszczykowska, A}, title = {Submacular Hemorrhage Management: Evolving Strategies from Pharmacologic Displacement to Surgical Intervention.}, journal = {Journal of clinical medicine}, volume = {15}, number = {2}, pages = {}, pmid = {41598408}, issn = {2077-0383}, support = {no//Medical University of Lodz/ ; }, abstract = {Background: Submacular hemorrhage (SMH) is a vision-threatening condition most associated with neovascular age-related macular degeneration (nAMD), although it may also arise from polypoidal choroidal vasculopathy, pathological myopia, retinal vascular diseases, trauma, and systemic factors. Rapid management is essential because subretinal blood induces photoreceptor toxicity, clot organization, and fibroglial scarring, leading to irreversible visual loss. The choice and urgency of treatment depend on hemorrhage size, duration, and underlying pathology, and the patient's surgical risk category, which can influence the invasiveness of the selected procedure. This review aims to provide an updated synthesis of recent advances in the surgical and pharmacological management of SMH, focusing on evidence from the past five years and comparing outcomes across major interventional approaches. Methods: A narrative review of 27 recent clinical and multicentre studies was conducted. The included literature evaluated pneumatic displacement (PD), pars plana vitrectomy (PPV), subretinal or intravitreal recombinant tissue plasminogen activator (rtPA), anti-VEGF therapy, and hybrid techniques. Studies were analyzed about indications, surgical methods, timing of intervention, anatomical and functional outcomes, and complication and patient risk stratification. Results: Outcomes varied depending on the size and duration of hemorrhage, as well as the activity of underlying macular neovascularization. PD with intravitreal rtPA was reported as effective for small and recent SMH. PPV combined with subretinal rtPA, filtered air, and anti-VEGF therapy demonstrated favorable displacement and visual outcomes in medium to large hemorrhages or those associated with active nAMD. Hybrid techniques further improved clot mobilization in selected cases. Across studies, delayed intervention beyond 14 days correlated with reduced visual recovery due to blood organization and photoreceptor loss. Potential risks, including recurrent bleeding and rtPA-associated toxicity, were reported but varied across studies. Conclusions: Management should be individualized, considering hemorrhage characteristics and surgical risk. Laser therapy, including PDT, may serve as an adjunct in the perioperative or postoperative period, particularly in PCV patients. Early, tailored intervention typically yields the best functional outcomes.}, }
@article {pmid41599848, year = {2026}, author = {Abouhish, H and Shalaby, L and Elzayat, O and Peddireddy, N and Tawfik, A}, title = {Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, pmid = {41599848}, issn = {2072-6643}, mesh = {Animals ; *Retinal Degeneration/prevention &amp; control/etiology ; Mice, Inbred C57BL ; *Vitamin B 12 Deficiency/blood ; Homocysteine/blood ; Vitamin B 12/administration &amp; dosage/blood/pharmacology ; Mice ; *Vitamin B Complex/pharmacology/administration &amp; dosage ; *Blood-Retinal Barrier/drug effects/metabolism ; *Carbon/metabolism ; Disease Models, Animal ; Male ; Cystathionine beta-Synthase/genetics ; Vitamin B 6/administration &amp; dosage ; }, abstract = {BACKGROUND/OBJECTIVES: Vitamin B12 deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B6, B9, and B12) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice.<br><br>METHODS: C57BL/6- Wild-type (WT) and cbs[+/-] mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (-)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12-16 weeks, the success of the diet regimes was confirmed by observing serum B12 deficiency in the B-Vit (-) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (-) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels.<br><br>RESULTS: The B-vitamin deficiency caused significant drop in serum vitamin B12 and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation.<br><br>CONCLUSIONS: a long-term deficiency of vitamins B6, B9, and B12 can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration.}, }
@article {pmid41601821, year = {2025}, author = {Zhang, S and Zhang, X and Wang, Z and Shi, W and Ren, Z and Wang, Y and Jia, Q and Li, Y and Guo, Y and Li, Z}, title = {Multimodal imaging for early drusen detection: RM-SLO as a promising imaging approach.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1703332}, pmid = {41601821}, issn = {2296-858X}, abstract = {PURPOSE: This study aimed to evaluate the diagnostic performance of retro-mode scanning laser ophthalmoscopy (RM-SLO) in detecting drusen compared to conventional multimodal imaging. Additionally, it sought to explore the imaging characteristics of RM-SLO for early age-related macular degeneration (AMD).<br><br>METHODS: In this cross-sectional study, 192 patients (263 eyes) were examined using color fundus photography (CFP), optical coherence tomography (OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), and RM-SLO. Three retinal specialists independently reviewed all images for the presence of drusen. Detection rates across modalities were compared using Cochran's Q-test, and imaging characteristics of hard and soft drusen were described.<br><br>RESULTS: RM-SLO detected drusen in 102 eyes (38.78%). This detection rate was significantly higher compared to other methods such as OCT (22.05%), CFP (8.37%), FFA (5.32%), and FAF (4.18%) (all p&#x202f;<&#x202f;0.0001 vs. RM-SLO). OCT was superior to CFP, FAF, and FFA (p&#x202f;<&#x202f;0.0001); CFP had statistically significant differences from FFA and FAF (p&#x202f;=&#x202f;0.039; p&#x202f;=&#x202f;0.001). While FFA did not reveal any statistically significant differences from FAF (p&#x202f;=&#x202f;0.453). RM-SLO provided a clear pseudo-three-dimensional visualization, enabling the identification of both hard and soft drusen, including small lesions that were not captured by other modalities.<br><br>CONCLUSION: RM-SLO demonstrates superior sensitivity and imaging clarity for drusen detection compared to conventional multimodal approaches. Its ability to visualize small and morphologically distinct drusen highlights its potential as a promising tool for early AMD screening and clinical management.}, }
@article {pmid41601834, year = {2025}, author = {Jiang, L and Jiang, X and Shi, X and Hu, X and Song, C and Yang, W and Tong, Y}, title = {Educational performance of TikTok short videos for age related macular degeneration and its link to user engagement.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1751545}, pmid = {41601834}, issn = {2296-858X}, abstract = {BACKGROUND: To systematically evaluate the information quality, reliability, and content characteristics of short videos related to age-related macular degeneration on the Chinese mainland version of TikTok, filling the research gap in this field and providing references for ophthalmic health education and platform information governance.<br><br>METHODS: This cross-sectional study was conducted on October 15, 2025, by searching the keyword "" on TikTok. The top 200 videos under "comprehensive ranking" were screened, and 196 videos meeting the eligibility criteria were ultimately included. Content integrity was evaluated following the American Academy of Ophthalmology guidelines and the Goobie framework. Video quality was assessed using the DISCERN instrument and the PEMAT-A/V tool. Statistical analyses were performed in IBM SPSS Statistics 27.0, with inter-rater reliability measured by the intraclass correlation coefficient. Differences among groups and associations between variables were examined using ANOVA and correlation analysis.<br><br>RESULTS: The overall quality of the included videos was moderate, with a median DISCERN tool score of 48.00 and a median Overall quality score of 3.00. The Understandability score was relatively high (median 84.62%), whereas the Actionability score was lower (median 75.00%). Videos uploaded by the Non-Profit group showed the highest quality (mean DISCERN tool score 59.13 &#xb1; 2.50), followed by the Medical group. The Non-Medical and For-Profit groups demonstrated the lowest quality, with statistically significant differences among groups (P < 0.05). Quality metrics were moderately positively correlated with user engagement metrics. The correlation coefficients between reliability and engagement were r = 0.48-0.54 (P < 0.05). Video duration showed a mild positive correlation with both quality and engagement (r = 0.23-0.30, P < 0.05). Inter-rater reliability was good (intraclass correlation coefficient = 0.839-0.947, P < 0.001).<br><br>CONCLUSION: Age-related macular degeneration videos on TikTok showed moderate overall quality, with content emphasizing clinical concerns but neglecting basic knowledge. Information quality varied by uploader source, with non-profit organizations and medical professionals providing most high-quality content. Higher-quality videos tended to receive greater user engagement, suggesting that platform algorithms may preferentially spread better educational material. These findings provide empirical support for improving science communication on this disease and strengthening information quality management on digital platforms.}, }
@article {pmid41602785, year = {2026}, author = {Khorrami-Nejad, M and Naroo, SA and Oklla, A and Narooie-Noori, F}, title = {Blue-light-filtering spectacle lenses in managing vision-related symptoms: an updated review.}, journal = {Therapeutic advances in ophthalmology}, volume = {18}, number = {}, pages = {25158414251412798}, pmid = {41602785}, issn = {2515-8414}, abstract = {Blue light, emitted by natural and artificial sources such as digital screens, has raised concerns regarding its impact on ocular health, visual comfort, and circadian rhythms. Prolonged exposure has been linked to digital eye strain (DES), visual fatigue, potential retinal damage, and sleep disturbances. Blue-light-filtering spectacle lenses have been developed to mitigate these effects by reducing short-wavelength blue light transmission, but their efficacy remains debated. Studies indicate that these lenses have minimal or no significant impact on contrast sensitivity, color discrimination, and task performance, with visual outcomes comparable to standard lenses. While some research suggests minor benefits in reducing DES and visual fatigue in specific populations, most studies report no significant differences. This highlights the multifactorial nature of DES. Experimental evidence supports the potential for blue-light-filtering spectacle lenses to reduce oxidative stress and phototoxicity in retinal cells, which may offer protection against retinal damage and age-related macular degeneration (ARMD). Additionally, these lenses show promise in neurological and psychological domains, including reduced migraine frequency, alleviation of mania symptoms, and improved sleep quality through circadian rhythm regulation. However, subjective sleep improvements are often not supported by objective measures. In summary, blue-light-filtering spectacle lenses may provide benefits in retinal protection, sleep regulation, and neurological health. However, their effectiveness in reducing visual fatigue, enhancing task performance, and preventing ARMD remains inconclusive. Further research with standardized methodologies and larger sample sizes is needed to clarify their clinical and everyday utility.}, }
@article {pmid41603251, year = {2026}, author = {Li, M and Yue, Y and Wu, S and He, X and Song, J and Ma, S and Zhang, H and Xu, C and Chen, S and Huang, Y and Xie, S and Yan, H}, title = {DNA Nanoflower LYTACs Enable Efficient VEGF Degradation and Verteporfin Loading for Combined Therapy of Wet Age-Related Macular Degeneration.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {13}, number = {16}, pages = {e15852}, doi = {10.1002/advs.202515852}, pmid = {41603251}, issn = {2198-3844}, support = {82330031//National Natural Science Foundation of China/ ; 32270892//National Natural Science Foundation of China/ ; TJYXZDXK-3-004A//Tianjin Key Medical Discipline Construction Project/ ; }, mesh = {*Verteporfin/pharmacology/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/metabolism ; Animals ; *Wet Macular Degeneration/drug therapy/metabolism ; Humans ; *Photochemotherapy/methods ; Photosensitizing Agents/pharmacology ; Choroidal Neovascularization/drug therapy ; *DNA ; Mice ; Lysosomes/metabolism ; Aptamers, Nucleotide ; }, abstract = {Wet age-related macular degeneration (wAMD), characterized by pathological choroidal neovascularization (CNV), is a leading cause of irreversible vision loss in the elderly. The current standard treatment-anti-vascular endothelial growth factor (VEGF) therapy-effectively manages neovascularization in many patients. However, some experience suboptimal responses, and frequent intravitreal injections raise safety concerns. Photodynamic therapy is another effective option for treating wAMD, but it can lead to an increase in reactive VEGF after the procedure, resulting in CNV recurrence. In response to these challenges, we propose an integrated approach that combines a DNA nanoflower VEGF degrader with photodynamic therapy. The DNA nanoflower consists of numerous aptamer-based lysosome-targeted chimaera (LYTAC) units, which drive extracellular VEGF in the lesion area to the lysosome for degradation. Simultaneously, the DNA nanoflower acts as a carrier for verteporfin (VER), a clinically used photosensitizer. The resulting nanoflower, named NF@VER, generates reactive oxygen species under near-infrared light to induce endothelial cell death. These combined effects on endothelial cells effectively block VEGF-induced CNV in vivo, without causing noticeable side effects. Overall, this innovative approach presents a precise and effective strategy for treating wAMD, reducing the risk of VEGF reactivation-induced CNV recurrence, and minimizing the systemic side effects associated with photodynamic therapy.}, }
@article {pmid41603341, year = {2026}, author = {Wang, S and Wang, C and Hong, H and Tang, C and Yu, J and Wang, Q}, title = {An integrative multi-omics study reveals glutamine metabolism dysregulation connecting Alzheimer's disease and age-related macular degeneration.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {110}, number = {2}, pages = {795-809}, doi = {10.1177/13872877261418263}, pmid = {41603341}, issn = {1875-8908}, mesh = {*Alzheimer Disease/metabolism/genetics ; *Glutamine/metabolism ; Animals ; Humans ; Mice ; Metabolomics/methods ; *Macular Degeneration/metabolism/genetics ; Mice, Transgenic ; Mendelian Randomization Analysis ; Male ; Gene Expression Profiling ; Female ; Multiomics ; }, abstract = {BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) are two common neurodegenerative diseases with many similar pathological features, but their shared metabolic characteristics have not been fully elucidated.ObjectiveThis study aims to explore the shared metabolic pathways between AD and AMD using an integrated multi-omics strategy.MethodsWe incorporated Mendelian randomization (MR), bulk and single-cell transcriptomics, and targeted metabolomics to investigate the metabolic links.ResultsThrough MR, we found elevated genetically inferred glutamine concentrations were correlated with a lower likelihood of AD but a higher likelihood of AMD. Using transcriptomic profiling, we detected 19 common differentially expressed genes associated with glutamine and glutamate metabolism, such as GLS. Analysis of single-cell RNA sequencing data revealed that GLS displays distinct cell-type expression patterns. Targeted metabolomic profiling in APP/PS1 mice at 5 months of age provided additional evidence for alterations in glutamine metabolism. The degree of metabolic changes in the eyes was higher than that in the cortex and hippocampus, and the prominent eyes may be an early indicator of neurodegenerative metabolic dysfunction.ConclusionsOverall, these findings suggest that glutamine metabolism disorders represent a convergent mechanism between AD and AMD. Our findings shed light on the overlapping metabolic pathways linking AD and AMD, underscoring the value of ocular biomarkers as promising tools for early disease detection.}, }
@article {pmid41603556, year = {2026}, author = {Owsley, C and Gao, L and Gooden, L and Thomas, TN and Pu, J and Crosson, JN and Curcio, CA and McGwin, G and Kwon, M}, title = {Preserved Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration and Marked Loss in Late Stage: ALSTAR2.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {1}, pages = {58}, pmid = {41603556}, issn = {1552-5783}, support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; Aged ; *Contrast Sensitivity/physiology ; Female ; Male ; Cross-Sectional Studies ; Visual Acuity/physiology ; Aged, 80 and over ; Middle Aged ; Disease Progression ; *Macular Degeneration/physiopathology ; *Wet Macular Degeneration/physiopathology ; *Geographic Atrophy/physiopathology ; }, abstract = {PURPOSE: To cross-sectionally compare parameters from the quick contrast sensitivity function (qCSF)-area under the log CSF (AULCSF) and sensitivity at each spatial frequency-in older eyes with normal macular health and early, intermediate, and late AMD. Our purpose was to determine whether qCSF could be a promising functional outcome measure in interventions designed to slow AMD progression from aging to late AMD.<br><br>METHODS: qCSF contrast sensitivity was measured at 1.0 to 18 cycles per degree (cyc/deg). Models evaluated the impact of diagnostic group on the AULCSF and individual spatial frequencies, adjusting for age and lens status. The AREDS nine-step classification system defined AMD presence and severity.<br><br>RESULTS: Eight hundred twenty-three eyes were studied: 383 normal macular health, 203 early AMD, 208 intermediate AMD, and 29 late AMD (23 geographic atrophy, six neovascular AMD). AULCSF decreased with increasing AMD severity; this was mostly attributable to the late AMD eyes having lower AULCSF than other groups. Late AMD eyes had significantly worse sensitivity at 1 and 1.5&#xa0;cyc/deg compared to all other groups, with other groups having similar sensitivity. At frequencies near or just beyond the CSF peak (3-12&#xa0;cyc/deg), late AMD eyes again had the worst sensitivity, with intermediate AMD eyes having slightly worse sensitivity than early AMD eyes. There were no group differences at 18&#xa0;cyc/deg.<br><br>CONCLUSIONS: The qCSF will be most useful in trials studying the transition from intermediate AMD to late-stage AMD, rather than in studying the transition from aging to early and intermediate AMD.}, }
@article {pmid41604455, year = {2026}, author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE}, title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons in Caenorhabditis elegans.}, journal = {Molecular biology of the cell}, volume = {37}, number = {3}, pages = {ar24}, pmid = {41604455}, issn = {1939-4586}, support = {R35 GM145312/GM/NIGMS NIH HHS/United States ; }, mesh = {*Caenorhabditis elegans/metabolism/cytology/genetics ; Animals ; *Caenorhabditis elegans Proteins/metabolism/genetics ; *Cilia/metabolism/ultrastructure ; *Neuroglia/metabolism ; Humans ; *Sensory Receptor Cells/metabolism ; }, abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and Caenorhabditis elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for noncanonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.}, }
@article {pmid41607454, year = {2026}, author = {Walia, S and Morya, AK}, title = {Psychiatric disorders linked to visual impairment: A review of mental health challenges and interventions across age groups.}, journal = {World journal of psychiatry}, volume = {16}, number = {1}, pages = {111118}, pmid = {41607454}, issn = {2220-3206}, abstract = {The intersection of visual impairment and mental health has profound effects on quality of life and warrants attention from healthcare providers, educators, and policymakers. With 20 million children under the age of 14 affected globally, older adults also experience significant psychological impact including depression, anxiety, and cognitive impairment. The implications of vision-related challenges extend far beyond mere sight. Depression and anxiety, exacerbated by social isolation and reduced physical activity, underscore the need for comprehensive interventions that address both medical and psychosocial dimensions. By recognizing the profound impact of ocular morbidities like strabismus, myopia, glaucoma, and age-related macular degeneration on mental health and investing in effective treatments and inclusive practices, society can pave the way for a healthier, more equitable future for affected individuals. There is evidence that myopic children experience a higher prevalence of depressive symptoms compared to their normal peers, and interventions like the correction of strabismus can enhance psychological outcome - demonstrating the value of an integrated management approach.}, }
@article {pmid41612003, year = {2026}, author = {Bartolomeo, N and Kalyvianakis, KK and Schuetz, YP and Nascimbeni, AC and Castro, DG and Crozat, B and Barry, MP and Ambresin, A}, title = {Early Outcomes of Intravitreal Aflibercept 8 mg in Eyes Previously Treated with Aflibercept 2 mg for Neovascular Age-Related Macular Degeneration with AI-Based Biomarker Quantification.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {831-842}, pmid = {41612003}, issn = {2193-8245}, abstract = {INTRODUCTION: To evaluate the early outcomes of aflibercept 8 mg (afl8) treatment in patients with neovascular age-related macular degeneration (nAMD) previously treated with aflibercept 2 mg (afl2).<br><br>METHODS: A retrospective, observational, monocentric Swiss study. Patients with nAMD who had received&#x2009;&#x2265;&#x2009;3 consecutive afl2 injections and switched to afl8 because of persistent or recurrent fluids, or to extend treatment intervals, were included in the study. All patients started a loading phase of 3-monthly afl8 injections, followed by a treat-and-extend regimen. Outcome measures included changes in best-corrected visual acuity (BCVA), maximal pigment epithelial detachment (PED) height, central subfield thickness (CST), optical coherence tomography (OCT) biomarkers quantified using artificial intelligence, and treatment intervals until month 6.<br><br>RESULTS: Fifty-two eyes of 44 patients who concluded the loading phase were included in this analysis. Mean age was 80.2&#x2009;&#xb1;&#x2009;8.5&#xa0;years; 73% of patients were females. At month 6, BCVA was unchanged, PED and CST height experienced a significant decrease by - 18.5&#x2009;&#xb1;&#x2009;12.9&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0005) and - 14.0&#x2009;&#xb1;&#x2009;3.5&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0042), respectively. Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and PED decreased (IRF: 4.4&#x2009;&#xb1;&#x2009;15.6-3.8 nl; SRF: 15.7&#x2009;&#xb1;&#x2009;35.7-10.3&#x2009;&#xb1;&#x2009;34.0 nl; PED: 268.2&#x2009;&#xb1;&#x2009;423.2-252.2&#x2009;&#xb1;&#x2009;484.1 nl). Mean treatment intervals increased by 1.7&#x2009;&#xb1;&#x2009;0.5&#xa0;weeks from the last assigned interval and by 0.6&#x2009;&#xb1;&#x2009;0.2&#xa0;weeks from previous maximal fluid-free intervals after switching (p&#x2009;=&#x2009;0.0005 and p&#x2009;=&#x2009;0.18, respectively). One mild vitritis was observed and resolved with vitrectomy and topical drops without decreased visual acuity.<br><br>CONCLUSION: Our real-world study supports the potential short-term benefits of afl8 in improving anatomical and durability outcomes in patients with recurrent nAMD. These findings also highlight the added value of data-driven evaluations. Long-term studies are needed to confirm the effectiveness and durability of afl8 in this population.}, }
@article {pmid41613191, year = {2025}, author = {Shanidze, NM and Velisar, A}, title = {Cancellation of the vestibulo-ocular reflex during smooth pursuit in patients with maculopathy.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1632527}, pmid = {41613191}, issn = {1664-2295}, support = {K99 EY026994/EY/NEI NIH HHS/United States ; R00 EY026994/EY/NEI NIH HHS/United States ; R01 EY036172/EY/NEI NIH HHS/United States ; }, abstract = {INTRODUCTION: Macular degeneration is associated with loss of central vision, including the fovea. Central visual field loss is associated with impaired smooth pursuit eye movements, and the associated scotoma can lead to target disappearance which may or may not be transient. While smooth pursuit in and of itself does not require a foveal position signal, suppression of the vestibuloocular reflex (VOR) needed during combined eye and head pursuit relies on the fovea for appropriate calibration. Prior work has shown that target extinction during, or even at the beginning of the trial does not affect the dynamics of the eye or head responses necessary for pursuit. These findings suggest that the potential disappearance of the target into the scotoma during pursuit can be overcome, particularly when both eye and head movements are used. The objective of this study was to test the hypothesis that head-unrestrained smooth pursuit deficits in CFL are at least partially related to individuals' inability to cancel their VOR.<br><br>METHODS: We performed a secondary analysis of a previously published data set of head restrained and unrestrained pursuit of a 10 &#xb0;/s target in 7 individuals with maculopathy (56-89 years) and 7 age-matched controls (61-78 years). We used a two-parameter linear regression model to quantify the eye-only pursuit (Kfix) and VOR (Kv) contributions to determine whether participants were able to effectively cancel the VOR to improve pursuit gain.<br><br>RESULTS: We observed reduced pursuit velocities in the head-unrestrained versus restrained smooth pursuit condition (Kfix < 1), particularly in the control group (CFL: Kfix = 0.90 &#xb1; 0.16; Control: Kfix = 0.74 &#xb1; 0.08). For VOR cancellation, Kv estimates did not deviate from -1 for either of our groups (CFL: Kv = -0.92 &#xb1; 0.09; Control: Kv = -0.98 &#xb1; 0.20), suggesting complete cancellation of the VOR during head-unrestrained pursuit. For the self-generated VOR experiment, participants in both groups had similar, near-one VOR gains (CFL: GainVOR = -1.00 &#xb1; 0.05; Control: GainVOR = -1.03 &#xb1; 0.02).<br><br>DISCUSSION: We confirmed that VOR responses to actively generated head movements were similarly intact in both groups. Our analyses of the pursuit data indicate that, regardless of visual function older adults attenuate eye-driven pursuit when the head is unrestrained (as compared to the restrained condition), and those with CFL fail to exploit residual VOR cancellation, helping to explain their persistent gaze-tracking deficits.}, }
@article {pmid41613944, year = {2025}, author = {Marmorstein, AD and Scruggs, BA and Knudsen, T and Hill, M and Kopp, FN and Trncic, E and Korda, D and Atherton, E and Berger, A and Finnemann, SC and Gandhi, J and Iezzi, R}, title = {Degradable fibrin hydrogels for transplantation of iPSC-derived retinal pigment epithelial cell monolayers.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1739620}, pmid = {41613944}, issn = {2296-634X}, abstract = {Death or dysfunction of retinal pigment epithelium (RPE) cells occurs in age-related macular degeneration (AMD) and certain inherited retinal dystrophies (IRDs). Induced-pluripotent stem cell (iPSC) derived-RPE have been used in early-stage clinical trials to treat AMD and IRDs by injecting them as a cell suspension or monolayers. While RPE transplant shows therapeutic potential, issues ranging from failure to repopulate the entire treatment area, clumping and monolayer folding, and a foreign body response to the support have been reported. We've shown that RPE can be grown on high concentration (>30 mg/mL) degradable fibrin hydrogels, and that cell free fibrin hydrogels implanted in the subretinal space degrade without causing inflammation. Here we describe manufacture and surgical implantation of degradable fibrin hydrogels carrying iPSC-RPE into a porcine model of geographic atrophy (GA). Large (15.25 × 58.42 × 0.2 mm) fibrin gel blanks were produced by injection molding, and iPSC-RPE were grown on their surface. Using a mechanical punch, the blank was subdivided into 1.5 × 5.0 × 0.2 mm doses, which fit a custom tool used for storage and surgical placement. Following aseptic packaging, RPE and gels were stable at 37 °C for at least 7 weeks. When transplanted into a pig model of GA, the fibrin scaffold degraded in <1 month and the iPSC-RPE provided partial rescue from GA as assessed by preservation of photoreceptors and blood flow in the choriocapillaris. We conclude that iPSC-RPE delivered on degradable fibrin hydrogels represent a potentially safe and effective approach to RPE transplantation.}, }
@article {pmid41615526, year = {2026}, author = {Ciarmatori, N and Cartabellotta, A and Adamo, GG and Biffi, C and Talli, PM and Pellegrini, M and Mura, M}, title = {Bilateral implantation of extended depth of focus intraocular lens in patients with early or intermediate age-related macular degeneration.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {87}, pmid = {41615526}, issn = {1573-2630}, support = {Investigator Initiated Trial Grant (IIT#75441181)//Alcon/ ; }, mesh = {Humans ; Male ; Female ; Prospective Studies ; *Visual Acuity/physiology ; Aged ; *Lenses, Intraocular ; *Macular Degeneration/complications/surgery/physiopathology/diagnosis ; *Vision, Binocular/physiology ; *Depth Perception/physiology ; *Lens Implantation, Intraocular/methods ; Patient Satisfaction ; Aged, 80 and over ; Prosthesis Design ; Middle Aged ; Follow-Up Studies ; Refraction, Ocular/physiology ; *Phacoemulsification/methods ; }, abstract = {PURPOSE: To evaluate the visual outcomes, dysphotopsia profile, and patient satisfaction following bilateral implantation of the AcrySof IQ Vivity intraocular lens (IOL) in patients with early or intermediate age-related macular degeneration (AMD).<br><br>METHODS: Prospective, single-center study. 24 patients (48 eyes) with bilateral cataract and early or intermediate AMD who underwent bilateral implantation of the AcrySof IQ Vivity IOL. The primary outcome was monocular corrected distance visual acuity (mCDVA). Secondary endpoints were distance-corrected and unaided monocular and binocular visual acuity at 4&#xa0;m, 66&#xa0;cm, and 40&#xa0;cm, monocular defocus curve, subjective dysphotopsia (McAlinden QoV questionnaire) and haloes perception (Aston Halometer), visual function (Catquest-9SF), and spectacle independence (IOLSAT).<br><br>RESULTS: At 3&#xa0;months postoperatively, mCDVA improved significantly from 0.30 to 0.00 logMAR (p&#x2009;<&#x2009;0.001). Binocular uncorrected distance and intermediate visual acuities of&#x2009;&#x2264;&#x2009;0.2 logMAR were achieved by 23 (95.8%) and 17 (70.8%) patients, respectively. The defocus curve showed visual acuity of 0.2 logMAR across a range of&#x2009;+&#x2009;1.40 D to -1.72 D. Bothersome dysphotopsias significantly decreased, with QoV scores improving from 58.5 (IQR: 26.1-66.5) to 0.00 (IQR: 0.00-14.3) (p&#x2009;<&#x2009;0.05). The mean halo eccentricity was 0.50&#x2009;&#xb1;&#x2009;0.08 degrees. Spectacle independence was reported by 22 (91.7%), 20 (83.3%), and 13 (54.2%) patients for distance, intermediate, and near tasks, respectively. Overall, 22 (91.7%) patients reported postoperative satisfaction.<br><br>CONCLUSION: The AcrySof IQ Vivity IOL demonstrated favourable outcomes in patients with early or intermediate AMD, offering a meaningful range of spectacle-free vision with minimal photic phenomena.}, }
@article {pmid41617934, year = {2026}, author = {Bo, N and Ding, Y}, title = {Estimation of the interpretable heterogeneous treatment effect with causal subgroup discovery in survival outcomes.}, journal = {Lifetime data analysis}, volume = {32}, number = {1}, pages = {11}, pmid = {41617934}, issn = {1572-9249}, support = {R01GM141076/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Macular Degeneration/drug therapy/genetics ; Treatment Outcome ; Survival Analysis ; Computer Simulation ; Precision Medicine/methods ; Randomized Controlled Trials as Topic ; Antioxidants/therapeutic use ; Treatment Effect Heterogeneity ; }, abstract = {Estimating heterogeneous treatment effects (HTE) for survival outcomes has gained increasing attention in precision medicine, as it captures variations in treatment efficacy among patients or subgroups. However, most existing methods conduct post-hoc subgroup identifications rather than simultaneously estimating HTE and identifying causal subgroups. In this paper, we propose an interpretable HTE estimation framework that integrates meta-learners with tree-based methods to estimate the conditional average treatment effect (CATE) for survival outcomes and identify predictive subgroups simultaneously. We evaluated the performance of our method through extensive simulation studies. We also demonstrated its application in a large randomized controlled trial (RCT) for age-related macular degeneration (AMD), a progressive polygenic eye disease, to estimate the HTE of an antioxidant and mineral supplement on time-to-AMD progression and to identify genetically defined subgroups with enhanced treatment effects. Our method offers a direct interpretation of the estimated HTE and provides evidence to support precision healthcare.}, }
@article {pmid41617984, year = {2026}, author = {Bailey, C and Lange, C and Chaudhary, V and Lanzetta, P and Oubraham, H and Kirchner, M and Machewitz, T and Allmeier, H and Zhang, X and Hasanbasic, Z and Munk, MR and , }, title = {SPECTRUM: early clinical experience from the first global real-world study of aflibercept 8 mg in patients with neovascular age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {735-738}, pmid = {41617984}, issn = {1476-5454}, }
@article {pmid41618563, year = {2026}, author = {Cui, M and Cheng, SY and Liang, J and McGowan, J and Xu, M and Xu, G and Luo, L and Wu, J and Harman, CD and Jacobson, AL and Kapeller, LE and Mayes, MA and Namkung, S and Sharma, T and Leland, TB and Zhang, F and Yip, M and Rossmiller, B and Xue, T and Chen, X and Boonying, W and Lotun, A and Wang, D and Su, Q and Xie, J and Wei, Y and Rothstein, AM and Gregory-Ksander, MS and Komaromy, A and Tian, B and Lin, H and Punzo, C and Tai, PWL and Gao, G}, title = {Modification of the VP1u region boosts transduction of adeno-associated virus vectors for ocular gene therapy.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, pmid = {41618563}, issn = {1525-0024}, support = {UH3 HL147367/HL/NHLBI NIH HHS/United States ; UG3 HL147367/HL/NHLBI NIH HHS/United States ; R01 HL097088/HL/NHLBI NIH HHS/United States ; P01 HL131471/HL/NHLBI NIH HHS/United States ; U19 AI149646/AI/NIAID NIH HHS/United States ; R21 AI183080/AI/NIAID NIH HHS/United States ; R01 AI121135/AI/NIAID NIH HHS/United States ; R01 NS076991/NS/NINDS NIH HHS/United States ; R01 HL152723/HL/NHLBI NIH HHS/United States ; }, abstract = {Adeno-associated virus (AAV) capsids that can confer efficient and safe gene therapy of the retina remain unmet needs. In this study, we isolated a library of natural capsids from human tissues and identified two variants that conferred strong transduction of retinal tissues following intravitreal injections into mice and non-human primates. Interestingly, the defining amino acids among the two variants are located within the luminal VP1 unique (VP1u) region of the capsid. Combining these defining residues into a single capsid (AAV2.MC1) had an additive effect. We demonstrated that the MC1 modification enhances intracellular trafficking and nuclear entry. Importantly, we provide proof of concept that the AAV2.MC1 capsid can deliver an anti-vascular endothelial growth factor (VEGF) transgene to treat wet age-related macular degeneration. Finally, we demonstrate that the modification can also be grafted onto other AAV serotypes to boost baseline transduction. These findings open up new avenues for capsid modification through targeted alterations of the VP1u region.}, }
@article {pmid41619168, year = {2026}, author = {Raczynska, D and Ernest, J and Baumane, K and Sagong, M and Akiyama, K and Rauschning, W and Vajas, A and Nowosielska, A and Dusova, J and Majtánová, N and Oleksy, P and Kuneva, I and Resch, M and Lange, N and Briede, E and Bajdik, B and Jeong, A and Kozub, B and Papp, A}, title = {Therapeutic Equivalence of Eyluxvi (Aflibercept) to Eylea in Neovascular Age-Related Macular Degeneration: ALTERA Trial (Randomized).}, journal = {Ophthalmology and therapy}, volume = {15}, number = {2}, pages = {887-899}, pmid = {41619168}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aimed to evaluate the efficacy and safety of Eyluxvi, an aflibercept biosimilar, compared with reference Eylea in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This phase&#xa0;3, multicenter, randomized, double-masked, parallel-group study enrolled 431 patients at 79 sites across 12 countries. Patients were randomized 1:1 to receive intravitreal Eyluxvi or Eylea (2&#xa0;mg) every 4&#xa0;weeks through week&#xa0;12, then every 8&#xa0;weeks through week&#xa0;48. The primary endpoint was change from baseline in best corrected visual acuity (BCVA) at week&#xa0;8.<br><br>RESULTS: The week&#xa0;8 least-squares mean BCVA change was 5.771 letters with Eyluxvi vs 7.863 letters with Eylea (difference -&#x2009;2.092 [95% confidence interval (CI) -&#x2009;3.431 to -&#x2009;0.753]). This equivalence was maintained through week&#xa0;52. Week&#xa0;52 adjusted mean changes were comparable for central subfield thickness (CST) (difference -&#x2009;4.742&#xa0;&#x3bc;m [95%&#xa0;CI -&#x2009;22.006 to 12.521]) and choroidal neovascularization (CNV) area (difference 0.233&#xa0;mm[2] [95%&#xa0;CI -&#x2009;0.724 to 1.191]). Safety profiles and immunogenicity were similar between groups.<br><br>CONCLUSION: This study demonstrated therapeutic equivalence between Eyluxvi and Eylea in nAMD treatment, with comparable anatomical outcomes and safety profiles. These findings support the development of Eyluxvi as an aflibercept biosimilar, potentially increasing treatment accessibility for patients with nAMD.<br><br>TRIAL REGISTRATION: EudraCT Identifier 2021-004530-11.}, }
@article {pmid41619249, year = {2026}, author = {Hiles, JD and Deri, O and Sishtla, K and Bear, JC and Cockcroft, JK and Opara, EI and Al-Kinani, AA and Alany, RG and Corson, TW and Schwikkard, SL}, title = {Sulphur Analogues of Homoisoflavonoids as Potential Treatments for Neovascular Eye Diseases.}, journal = {ChemMedChem}, volume = {21}, number = {2}, pages = {e202500824}, pmid = {41619249}, issn = {1860-7187}, support = {R01EY025641/MH/NIMH NIH HHS/United States ; RGPIN-2025-04563//Retina Research Foundation, Canada Foundation for Innovation, and Natural Sciences and Engineering Research Council/ ; }, mesh = {Humans ; *Angiogenesis Inhibitors/chemistry/pharmacology/chemical synthesis ; Cell Proliferation/drug effects ; *Isoflavones/chemistry/pharmacology/chemical synthesis ; Endothelial Cells/drug effects ; Structure-Activity Relationship ; Cell Line ; *Sulfur/chemistry/pharmacology ; Molecular Structure ; *Neovascularization, Pathologic/drug therapy ; Dose-Response Relationship, Drug ; Cyclooxygenase 2/metabolism ; }, abstract = {Treatment of neovascular eye diseases like age-related macular degeneration require a compound that is not toxic to ocular cells, that can reduce inflammation and inhibit angiogenesis. Homoisoflavonoids, naturally occurring compounds isolated primarily from the Hyacinthaceae sub-family of plants, have shown promise as anti-inflammatories and inhibitors of angiogenesis. A series of sulphur analogues, (3-benzylidene thiochroman-4-ones), were synthesised via a three-step procedure. These compounds were evaluated for selectivity towards endothelial cells over non-endothelial cells and their ability to inhibit COX-II over COX-I.Their potential anti-angiogenic activity was assessed using the Matrigel tube formation assay. (3Z)-3-[(3-bromophenyl)methylidene]-6-methoxy-2,3-dihydro-4H-1-benzothiopyran-4-one (10) was most active with respect to anti-proliferation against human retinal endothelial cells (HREC cells) (GI50 3.07 μM). All demonstrated selectivity with all GI50 values against retinal pigment epithelial cell line ARPE-19 >100 µM, with the exception of (3Z)-6-bromo-3-[(4-nitrophenyl)methylidene]-2,3-dihydro-4H-1-benzothiopyran-4-one (12), which was not toxic to either. (3Z)-3-[(3-bromophenyl)methylidene]-6-methoxy-2,3-dihydro-4H-1-benzothiopyran-4-one (10) showed significant reduction in angiogenesis properties in a Matrigel-based tube formation assay (38.79%, 5 µM, 56.41%, 10 µM). (3Z)-6-bromo-3-[(3-bromophenyl)methylidene]-2,3-dihydro-4H-1-benzothiopyran-4-one (7) was found to be the most active against COX-II with inhibition of 22.7 % (4.35 nM). The 3-benzylidene thiochroman-4-ones show promise as antiangiogenic agents, but limited selectivity to COX-II over COX-I.}, }
@article {pmid41620512, year = {2026}, author = {Alqassab, AIM and Luque-Nieto, M&#xc1; and Mohammed, MA}, title = {Identification of multiple ocular diseases using a hybrid quantum convolutional neural network with fundus images.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {6798}, pmid = {41620512}, issn = {2045-2322}, support = {PID2023-146540OB-C43//Ministerio de Ciencia e Innovaci&#xf3;n/ ; }, mesh = {Humans ; *Neural Networks, Computer ; *Fundus Oculi ; *Eye Diseases/diagnosis/diagnostic imaging ; Diabetic Retinopathy/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Convolutional Neural Networks ; }, abstract = {Ocular diseases remain a major cause of vision impairment globally, making early and accurate diagnosis essential. This study presents a novel diagnostic model for identifying seven common ocular conditions age-related macular degeneration, glaucoma, hypertension, diabetic retinopathy, myopia, cataracts, and other pathologies using clinical fundus images. To improve image quality, Anisotropic Diffusion Filtering and Wavelet Transform are applied for hue and contrast enhancement. Data imbalance is addressed through targeted augmentation techniques. The core of the model is a hybrid Quantum Convolutional Neural Network (QCNN), which integrates quantum convolutional pooling into a classical CNN architecture to boost feature extraction and classification. Evaluated on the OIA-ODIR dataset, the proposed model outperformed benchmarks such as Fundus-DeepNet, Inception-v4, VGG16 with SGD, and ResNet-101. It achieved 94% classification accuracy, along with substantial gains in precision, recall, and F1-score. These results confirm the model's effectiveness and its potential for supporting early, multi-disease ocular diagnosis in clinical settings.}, }
@article {pmid41620804, year = {2026}, author = {Li, K and Tang, J and Zhang, Z and Li, X and Zheng, Y and Jiang, D and Sun, J}, title = {Global burden and cross-country inequalities of age-related eye diseases from 1990 to 2021: a comprehensive analysis of temporal trends and socioeconomic disparities.}, journal = {Eye and vision (London, England)}, volume = {13}, number = {1}, pages = {4}, pmid = {41620804}, issn = {2326-0254}, support = {LMS26F020026//Natural Science Foundation of Zhejiang Province/ ; }, abstract = {BACKGROUND: Age-related eye diseases (AREDs) are leading causes of visual impairment worldwide. With global population aging, understanding their epidemiological trends and socioeconomic disparities is crucial for public health planning and equitable resource allocation.<br><br>METHODS: We conducted a secondary epidemiological analysis of AREDs using data from the Global Burden of Disease (GBD) Study 2021. We evaluated years lived with disability (YLDs) and age-standardized YLD rates (ASYR) and conducted trend analysis using Joinpoint regression. Cross-country inequalities were assessed using the slope index of inequality (SII) and concentration index, with correlation and regression analyses examining associations with the socio-demographic index (SDI).<br><br>RESULTS: Global YLDs for AREDs increased from 78.503 to 100.006, while ASYR decreased from 112.815 to 92.803 per 100,000 populations between 1990 and 2021. Despite a global increase in the relative burden of glaucoma, both absolute and relative inequalities for age-related macular degeneration (AMD) and cataracts decreased. Low-SDI countries showed slight improvements in reducing these inequalities. The SII for AREDs improved in lower-SDI countries between 1990 and 2021, with reductions in AMD (from&#x2009;-&#x2009;9.250 to&#x2009;-&#x2009;6.033), cataract (from&#x2009;-&#x2009;258.131 to&#x2009;-&#x2009;173.762), and glaucoma (from&#x2009;-&#x2009;21.090 to&#x2009;-&#x2009;20.064). The concentration index for AMD and cataract decreased from&#x2009;-&#x2009;0.167 and&#x2009;-&#x2009;0.335 in 1990 to&#x2009;-&#x2009;0.129 and&#x2009;-&#x2009;0.272 in 2021, respectively, while the concentration index for glaucoma increased from&#x2009;-&#x2009;0.208 to&#x2009;-&#x2009;0.263, Regional disparities in the AREDs burden were evident, with most regions showing improved inequality in lower-SDI countries as reflected in both the SII and concentration index.<br><br>CONCLUSIONS: Despite global improvements in the relative burden of AREDs, significant socioeconomic and geographical inequalities persist, particularly in low-SDI regions. Targeted public health strategies and strengthened eye care systems are urgently needed to address these disparities and achieve equitable eye health outcomes worldwide.}, }
@article {pmid41621805, year = {2026}, author = {Sarraf, D and Corvi, F and Rosenfeld, PJ and Ach, T and Blodi, B and Bottoni, F and Cozzi, M and Chakravarthy, U and Chew, EY and Csaky, K and Cukras, C and Curcio, CA and Ferris, FL and Freund, KB and Grunwald, J and Guymer, RH and Holz, FG and Jaffe, GJ and Liakopoulos, S and Lim, TH and Monés, JM and Owsley, C and Pagliarini, S and Pauleikhoff, D and Schmitz-Valckenberg, S and Spaide, RF and Sparrow, J and Tadayoni, R and Tufail, A and Viola, F and Fraser, S and Staurenghi, G and Sadda, SR}, title = {Standardizing Measurement of Complete Retinal Pigment Epithelial and Outer Retinal Atrophy-Classification of Atrophy Meeting Report 8.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.017}, pmid = {41621805}, issn = {2468-6530}, abstract = {PURPOSE: To highlight the role of en face OCT in the measurement of choroidal hypertransmission defects (hyperTDs) in complete retinal pigment epithelial and outer retinal atrophy (cRORA), and to refine the definition of retinal pigment epithelium (RPE)-related alterations associated with cRORA.<br><br>DESIGN: Consensus meeting.<br><br>PARTICIPANTS: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists.<br><br>METHODS: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed the role of en face OCT in the assessment of cRORA. A structured study was conducted, consisting of an exercise to assess en face OCT cases, reviewed jointly during the eighth CAM meeting, and to explore the utility of this advanced tool for disease staging and progression. Additionally, definitions previously applied to RPE abnormalities were discussed and refined leading to modifications. The current report summarizes the methods used during the consensus meeting and the outcomes achieved as pertains to the application of en face OCT for cRORA grading and simplification of the RPE assessment criteria.<br><br>MAIN OUTCOME MEASURES: Defining the role of en face OCT in the detection and quantification of hyperTDs, improving classification of cRORA, and refining the terminology related to RPE alterations to enhance grading consistency.<br><br>RESULTS: During the consensus case discussions, high levels of agreement were achieved for hyperTD detection using en face OCT. The CAM group affirmed the role of en face OCT as a critical adjunct to traditional B-scan analysis, for more precise measurement of the area of cRORA lesions and for distinguishing threshold cRORA from smaller incomplete retinal pigment epithelial and outer retinal atrophy lesions. Additionally, merger of RPE attenuation and RPE disruption into a unified category termed "abnormal RPE band" significantly reduced interreader variability, leading to greater consistency among graders.<br><br>CONCLUSIONS: The integration of en face OCT with cross sectional B-scan imaging enhances the accurate classification and area measurement of early atrophic alterations in age-related macular degeneration, improving diagnostic consistency and lesion assessment. The consensus panel's adoption of the abnormal RPE band term as a unified category for RPE abnormalities may reduce confusion regarding the definition of RPE degeneration and has the potential to improve interreader variability.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41621806, year = {2026}, author = {Xiao, JF and Hyman, MJ and Moir, J and Yehia, M and Hariprasad, S and Flores, A and Skondra, D}, title = {Association of Metformin Use and New-Onset International Classification of Diseases Coding of Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.01.019}, pmid = {41621806}, issn = {2468-6530}, abstract = {PURPOSE: To investigate whether metformin use is associated with decreased odds of new-onset International Classification of Diseases (ICD) coding of neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Case-control study.<br><br>PARTICIPANTS: A total of 22,205 cases with new-onset ICD coding of nAMD and 22,126 matched controls without age-related macular degeneration (AMD) were identified in the Merative MarketScan Research Databases between 2008 and 2017. A subgroup of patients diagnosed with diabetes included 6664 cases and 5513 controls.<br><br>METHODS: Cases with new-onset ICD coding of nAMD were propensity score matched to controls without AMD. Multivariable conditional logistic regression analyzed the association between new-onset ICD coding of nAMD and metformin use controlling for: (1) AMD risk factors, including diabetes, diabetic retinopathy, hyperlipidemia, obesity, and smoking; (2) exposures to other antidiabetic medications, including insulin, sulfonylureas, glitazones, meglitinides, other diabetic medications, and statins; and (3) the number of antidiabetic medications.<br><br>MAIN OUTCOME MEASURES: Adjusted odds ratios (aORs) of new-onset ICD coding of nAMD for any metformin use and cumulative 2-year metformin dose in grams.<br><br>RESULTS: Any metformin use was associated with decreased adjusted odds of new-onset nAMD (aOR, 0.84; 95% confidence interval [CI], 0.74-0.95). In an exploratory dosing analysis, associations across cumulative-dose categories were heterogeneous, with the largest magnitude in the middose range (between 271 and 600 g; aOR, 0.73; 95% CI, 0.63-0.85); because adherence cannot be verified from claims, dose-response findings are interpreted as hypothesis-generating. These associations persisted among diabetic patients (any metformin use: aOR, 0.83; 95% CI, 0.72-0.94; 271 to 600 g: aOR, 0.72; 95% CI, 0.61-0.85; >1080 g: aOR, 0.85; 95% CI, 0.72-0.999). Any metformin use in diabetic patients without retinopathy was associated with decreased odds of new-onset ICD nAMD (aOR, 0.79; 95% CI, 0.69-0.92); however, this association was absent in diabetic patients with retinopathy.<br><br>CONCLUSIONS: In this claims-based analysis, metformin use was associated with lower odds of incident ICD-coded nAMD, and an exploratory dosing analysis suggests a low-to-moderate cumulative dose may be associated with the greatest decrease. These associations persisted among diabetic patients without retinopathy. Causal inference is limited by the observational design, potential diagnostic misclassification, imperfect exposure measurement, and residual confounding. Replication with validated case definitions, active-comparator new-user designs, and adjudicated outcomes is warranted.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41622023, year = {2026}, author = {Hart, KM and Ayton, LN and Wu, Z}, title = {Developing age-related macular degeneration recommendations for clinical optometrists via a modified Delphi study.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/08164622.2025.2610977}, pmid = {41622023}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Clear, evidence-based guidelines support optometrists in diagnosing and managing age-related macular degeneration, a leading cause of vision loss in older adults. This condition is an increasing focus of clinical care due to expanding treatment options and evolving imaging technologies.<br><br>BACKGROUND: Clinical practice guidelines support consistent, evidence-based care in optometry and play a critical role in guiding the diagnosis and management of chronic eye diseases. This paper discusses the methodological approach used to develop age-related macular degeneration guidelines, emphasising the modified Delphi approach used to refine and formally establish recommendations.<br><br>METHODS: Recommendations were developed from a literature review and draft guideline. An expert working group of optometrists (n&#x2009;=&#x2009;9) participated in a three-round Delphi process, rating their agreement with the draft recommendations using a 6-point Likert scale across two survey rounds, followed by a virtual meeting to discuss and re-vote on unclear or contentious items. Quantitative and qualitative measures during the first two rounds of the Delphi survey guided recommendation refinement and inclusion for discussion in round 3. Consensus for inclusion was defined as a mean score &#x2265;5 and &#x2265;80% agreement.<br><br>RESULTS: Out of 37 initial recommendations, 25 (68%) were accepted and included in the final guideline. Consensus was achieved for recommendations concerning clinical classification, assessment and management strategies. Round 3 discussions helped resolve uncertainties and refine recommendations wording, particularly regarding nutritional supplements and clinical biomarkers for progression. Adoption of the Delphi approach demonstrated the value of both quantitative and qualitative feedback.<br><br>CONCLUSION: The feasibility and value of using a modified Delphi method to develop optometric clinical practice guidelines is demonstrated. The process supported the inclusion or exclusion of recommendations in a systematic way with the final guideline offering contemporary, practice-relevant guidance for the diagnosis and management of age-related macular degeneration.}, }
@article {pmid41622390, year = {2026}, author = {Chen, X and Shi, W and Zhu, Y and Li, K and Xia, Y and Wu, H and Hu, T and Qin, C and Wei, W}, title = {PF protects retinal pigment epithelial cells from oxidative injury by enhancing mitophagy through a CUL3-dependent AMPK/ULK1 pathway.}, journal = {Archives of pharmacal research}, volume = {49}, number = {2}, pages = {242-261}, pmid = {41622390}, issn = {1976-3786}, support = {QN202414//Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; GSPYY2023009//Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; }, mesh = {*Mitophagy/drug effects ; *Autophagy-Related Protein-1 Homolog/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Oxidative Stress/drug effects ; Humans ; Animals ; *AMP-Activated Protein Kinases/metabolism ; Protein Serine-Threonine Kinases/metabolism ; *Cullin Proteins/metabolism ; Signal Transduction/drug effects ; Mice ; AMP-Activated Protein Kinase Kinases ; Hydrogen Peroxide ; Cell Line ; Mice, Inbred C57BL ; *Intracellular Signaling Peptides and Proteins/metabolism ; Dose-Response Relationship, Drug ; Male ; }, abstract = {Mitophagy dysfunction is a critical contributor to retinal pigment epithelial (RPE) cell damage during the progression of retinal degenerative diseases, including age-related macular degeneration (AMD). In this study, we investigated the effects of paeoniflorin (PF) on mitophagy in RPE cells, with a particular focus on the CUL3/LKB1/AMPK/ULK1 signaling pathway. ARPE-19 cells were treated with different concentrations of PF to evaluate cytotoxicity, and its protective effects were further examined in H2O2-induced oxidative stress models in vitro and in sodium iodate (NaIO3)-induced RPE injury models in vivo. Protein levels of CUL3, apoptosis-related factors, mitophagy markers, and components of the LKB1/AMPK/ULK1 pathway were assessed by western blotting, and mitophagy was visualized using MitoTracker labeling. Cycloheximide (CHX) and coimmunoprecipitation (Co-IP) assays were performed to analyze the interaction between CUL3 and LKB1. PF treatment enhanced mitophagy in H2O2-stimulated ARPE-19 cells, whereas Parkin knockdown markedly attenuated this effect. In oxidatively damaged cells, PF promoted AMPK and ULK1 phosphorylation, increased mitophagy-associated protein expression, and alleviated mitochondrial dysfunction; these protective effects were abolished by pharmacological inhibition of AMPK or ULK1. In addition, CUL3 overexpression significantly attenuated PF-induced mitophagy activation and reduced PF-associated phosphorylation of LKB1, AMPK, and ULK1. Mechanistically, PF downregulated CUL3 expression, while CUL3 promoted the ubiquitination and degradation of LKB1. Silencing CUL3 induced mitophagy in H2O2-treated cells, whereas concurrent knockdown of CUL3 and LKB1 abolished this effect. In vivo, PF mitigated RPE cell loss, enhanced mitophagy, and activated the CUL3/LKB1/AMPK/ULK1 signaling pathway in the retinal tissues of NaIO3-induced mice. Collectively, these findings indicate that PF protects against RPE injury in an NaIO3-induced AMD-like model by downregulating CUL3 expression and activating LKB1/AMPK/ULK1-mediated mitophagy.}, }
@article {pmid41622479, year = {2026}, author = {Løkken, JFT and Moe, MC and Sæther, EM and Jørstad, &#xd8;K}, title = {Beyond drug price: A comparison of overall costs of anti-vascular endothelial growth factor therapy alternatives for neovascular age-related macular degeneration in Norway.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70069}, pmid = {41622479}, issn = {1755-3768}, support = {//Bayer Norway/ ; }, abstract = {PURPOSE: Norwegian guidelines designate off-label Avastin as the first-line intravitreal therapy for neovascular age-related macular degeneration (nAMD) because of its well-documented clinical efficacy and low price. However, this overlooks non-drug costs, which increase with injection frequency. We evaluated whether newer, longer-acting agents offer greater long-term cost-efficiency by reducing total costs despite higher drug prices in a Norwegian setting.<br><br>METHODS: We developed a 2-year cost-minimization model that included pharmaceutical, consultation and administrative and patient-related costs in Norway; the pharmaceutical cost component incorporated the routine practice of splitting vials into prefilled syringes in hospital pharmacies. The model compared four nAMD monotherapies, Avastin, Eylea 2&#x2009;mg, Eylea 8&#x2009;mg and Vabysmo, as well as the common practice of switching treatment-resistant patients from Avastin to Eylea 2&#x2009;mg. We derived injection frequencies from clinical trials (for monotherapies) or observational data (for switching) and conducted one-way sensitivity analyses to identify key cost drivers.<br><br>RESULTS: Over 2&#x2009;years, the switching regimen had the highest per-patient cost (146&#x2009;722 NOK), followed by Eylea 2&#x2009;mg (100&#x2009;481 NOK), Vabysmo (93&#x2009;207 NOK), Avastin (86&#x2009;262 NOK) and Eylea 8&#x2009;mg (68&#x2009;738 NOK). Avastin had the lowest drug cost, but its high injection frequency increased non-drug costs. Sensitivity analyses showed that injection frequency strongly influenced total costs for high-priced drugs, while patient time had a substantial impact for Avastin.<br><br>CONCLUSION: In our model, longer-acting agents reduced injection frequency and decreased overall treatment costs. These findings suggest that adopting longer-acting monotherapy could improve cost-efficiency in long-term nAMD management in Norway.}, }
@article {pmid41624137, year = {2025}, author = {Rusciano, D and Bagnoli, P}, title = {The controversial role of nutraceuticals vs. drugs in proliferative retinopathies.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1727089}, pmid = {41624137}, issn = {1662-4548}, abstract = {Neovascular eye diseases, notably age-related macular degeneration and diabetic retinopathy, remain major causes of vision loss despite advances in pharmacological management. The proliferation of abnormal retinal blood vessels leads to the loss of retinal cells and progressive visual dysfunction. Anti-VEGF therapies have revolutionized treatment; however, their efficacy is incomplete, they require repeated administration, and resistance or suboptimal responses are not uncommon. These limitations have stimulated interest in additional therapeutic approaches, both inspired by preclinical research and aimed at improving the management of systemic conditions that contribute to neovascular pathologies. Beyond conventional pharmacology, nutraceuticals have attracted attention for their proposed mechanisms-enhancement of antioxidant defenses, modulation of inflammatory cascades, and potential interference with angiogenic signaling-which provide a molecular rationale for their application in ocular disease. This review critically examines the dual landscape of current pharmacological strategies and nutraceutical approaches, analyzing how the latter might enhance retinal resilience and vascular stability in the early stages of disease. The novelty of this work lies in juxtaposing the mechanistic underpinnings of nutraceuticals with the clinical shortcomings of anti-VEGF therapy, thereby identifying opportunities for integrative therapeutic perspectives. Nevertheless, nutraceuticals cannot replace pharmacological treatment in advanced disease; rather, they may offer incremental benefits in early-stage or high-risk patients, contingent upon timely preventive diagnosis. Until more robust clinical evidence and regulatory oversight are established, nutraceuticals should be regarded as adjunctive components within personalized care models-supporting, but not substituting for, established pharmacological interventions.}, }
@article {pmid41626424, year = {2026}, author = {Mukherjee, S and Wu, D and Emde, LV and Vance, E and Ji, M and Emamverdi, M and De Silva, T and Thavikulwat, AT and Kalpathy-Cramer, J and Domalpally, A and Cukras, CA and Keenan, TDL}, title = {ReticularNet: Automated Pixel-Level Segmentation of Reticular Pseudodrusen on Near-Infrared Reflectance Images by Deep Learning.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101038}, pmid = {41626424}, issn = {2666-9145}, abstract = {OBJECTIVE: Reticular pseudodrusen (RPD) represent an important biomarker in age-related macular degeneration (AMD) but are difficult to grade and often assessed only for presence or absence, without quantitative or spatial analysis of RPD burden. The objective was to develop and validate a deep learning model for pixel-level RPD grading on near-infrared reflectance (NIR) images, which are commonly acquired in clinical practice and the most accurate en face detection modality.<br><br>DESIGN: Deep learning model development study.<br><br>PARTICIPANTS: Five hundred eight images of 117 eyes (70 participants) with or without RPD, over a wide range of AMD severities.<br><br>METHODS: The ground truth grading pipeline comprised reading center multimodal grading for RPD presence and NIR annotation with RPD contours, followed by pixel-level NIR annotation of all individual RPD lesions. The data set was split 80:20 into training and test sets. A DeepLabv3-ResNet-18 segmentation deep learning model ("ReticularNet") was trained to perform pixel-level grading of RPD on NIR images. Its performance was compared with that of 4 ophthalmologists.<br><br>MAIN OUTCOME MEASURES: Dice similarity coefficient (DSC); intraclass correlation coefficient (ICC) for RPD lesion number, pixel area, and contour area.<br><br>RESULTS: For pixel-level grading, ReticularNet achieved a mean DSC of 0.36 (standard deviation 0.16). This was significantly higher than the mean DSC of each ophthalmologist (0.03, 0.13, 0.19, and 0.23; P &#x2264; 0.02 for each) and of all ophthalmologists together (P < 0.0001). ReticularNet had ICCs of 0.44 (lesion number), 0.56 (pixel area), and 0.61 (contour area), with no significant underestimation or overestimation (P &#x2265; 0.24). These values were numerically higher than the ICCs of each ophthalmologist, who had ICC ranges of -0.08 to 0.23, -0.05 to 0.40, and -0.09 to 0.58, respectively, and significant underestimation in almost all cases. For all 3 parameters, ReticularNet's ICC was significantly higher than that of all specialists considered together (P &#x2264; 0.02).<br><br>CONCLUSIONS: ReticularNet achieved automated pixel-level grading of RPD on NIR images. Its grading was superior to that of 4 ophthalmologists, across a variety of metrics. We are making the code/models available for research use. Improved access to quantitative and spatial RPD grading should lead to improved understanding of these lesions as important biomarkers of retinal disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41626425, year = {2026}, author = {Chen, ZJ and Yu, J and Ho, M and Ng, DSC and Brelen, ME and Young, AL and Yam, JCS and Tham, CC and Pang, CP and Chen, LJ}, title = {The CFH-CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101043}, pmid = {41626425}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H-complement factor H related 5 (CFH-CFHR5) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.<br><br>DESIGN: Case-control genetic association study.<br><br>PARTICIPANTS: A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.<br><br>METHODS: A total of 17 candidate SNPs were initially selected from the CFH-CFHR5 region; after excluding 5 SNPs that deviated from Hardy-Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at P < 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at P < 0.05 for haplotype tests (adjusted using 10 000 permutations).<br><br>MAIN OUTCOME MEASURES: Associations between individual SNPs and haplotypes in the CFH-CFHR5 locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.<br><br>RESULTS: The tagging SNP, rs12144939, for the CFHR3/1 deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, P = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, P = 6.29 &#xd7; 10[-4]), rs423641 in CFHR1 (OR = 0.74, P = 0.0038), and rs10922152 in CFHR5 (OR = 1.55, P = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas CFH rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, P = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning CFHR4, CFHR2, and CFHR5 (OR = 1.81, permutation P = 0.0099) and haplotype G-A-G within CFHR5 (OR = 1.56, permutation P = 0.025) were specifically associated with PCV.<br><br>CONCLUSIONS: This study validates the association of the CFHR3/1 deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the CFH-CFHR5 locus, characterized by associations at rs12144939, rs423641 (CFHR1), and rs10922152 (CFHR5), as well as risk haplotypes unique to PCV. These findings underscore the critical role of CFH-related genes in PCV and provide new insights into its genetic mechanisms.<br><br>FINANCIAL DISCLOSURES: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41626488, year = {2026}, author = {Wang, Y and Chen, S and Cao, Y and Wen, X and Fu, C and Liang, J and Luo, Q and Liu, Q}, title = {Molecular Dynamics and Experimental Validation of Natural Products from Chuanxiong Rhizoma as VEGFR2 Inhibitors for nAMD Therapy.}, journal = {ACS omega}, volume = {11}, number = {3}, pages = {3949-3964}, pmid = {41626488}, issn = {2470-1343}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Neovascular AMD (nAMD) is a significant subtype of AMD, responsible for the blindness of over 90% of patients with AMD. The hallmark of nAMD is choroidal angiogenesis dysregulation, a condition that can result in severe inflammation, leakage, and bleeding, ultimately leading to a precipitous decline in visual acuity. Inhibition of the vascular endothelial growth factor (VEGF) pathway has been proven to be an effective therapeutic strategy for this disease. Intraocular injection of anti-VEGF macromolecule drugs is a clinical therapy for this disease, but it has shortcomings, such as severe side effects, high cost, long treatment cycle, and complex administration methods. Consequently, the identification of novel small-molecule drugs and the development of innovative delivery mechanisms are of paramount importance for the treatment of this condition. Chuanxiong Rhizoma (CX), a type of traditional Chinese medicine (TCM), has been employed in the treatment of vascular-related diseases. Contemporary pharmacological research has demonstrated that CX contains a substantial quantity of natural compounds that exhibit anti-VEGF activity. In this study, we employed molecular simulation docking and molecular dynamics (MD) to examine the anti-VEGFR2 effects of 10 natural compounds derived from CX. Sorafenib was selected as the reference ligand, which is a marketed VEGFR2 inhibitor for cancer treatment. As a DFG-out inhibitor, sorafenib stabilizes the inactive conformation of the kinase by binding to an allosteric site near the ATP-binding pocket. In our research, natural products exhibiting a strong binding affinity were identified using computer-simulated docking technology and detailed binding sites were predicted. The findings of the research indicate that apigenin exhibits the strongest affinity for the VEGFR2 receptor with the formation of three hydrogen bonds. The molecular docking results indicate that the CYS919 and ASP1046 amino acid residues of VEGFR2 are the primary groups that form hydrogen bonds with the ligands. Furthermore, the AutoQSAR module of Schrödinger Suite predicted apigenin to have the highest predicted pIC50 value among the ten candidate compounds, suggesting its potential for significant VEGFR2 inhibitory activity. A subsequent MD simulation revealed that the binding of apigenin to the protein was more stable, and the conformation was stronger. According to the ADMET prediction results, apigenin is characterized by low toxicity. To ascertain the capacity of apigenin to impede the proliferation of choroidal angiogenesis, the choroid sprouting assay was utilized as a methodological framework. An in vitro experiment demonstrated that apigenin can significantly inhibit the growth of choroidal vessels in a dose-dependent manner. The present study was conducted with the objective of assessing the potential of natural products in the treatment of nAMD. In addition, the study offered valuable insights for the development of new natural agents.}, }
@article {pmid41627332, year = {2026}, author = {Kado Abdalkader, R and Kawakami, S and Takashima, Y and Fujita, T}, title = {Development of a 3D-printed microfluidic chip for retinal organoid-endothelial co-culture.}, journal = {Lab on a chip}, volume = {26}, number = {4}, pages = {965-975}, doi = {10.1039/d5lc00939a}, pmid = {41627332}, issn = {1473-0189}, mesh = {Coculture Techniques/instrumentation ; Humans ; *Organoids/cytology/metabolism ; *Printing, Three-Dimensional ; *Lab-On-A-Chip Devices ; *Endothelial Cells/cytology/metabolism ; *Retina/cytology ; Induced Pluripotent Stem Cells/cytology ; Retinal Pigment Epithelium/cytology ; }, abstract = {Pathological angiogenesis, such as that observed in wet age-related macular degeneration (AMD), is difficult to reproduce in vitro using human-relevant models. Although organ-on-chip (OoC) systems incorporating retinal pigment epithelium (RPE) and endothelial barriers have been reported, models integrating human retinal organoids with vascular networks remain limited. Here, we present a fully 3D-printed microfluidic platform for co-culture of human induced pluripotent stem cell (hiPSC)-derived retinal organoids containing intrinsic RPE regions with endothelial cells. The device, fabricated from flexible thermoplastic polyurethane (TPU) on a transparent polyvinyl chloride (PVC) substrate, supports three-dimensional co-culture within a fibrin-Matrigel matrix. In this system, endothelial cells formed organized vascular networks that localized around RPE-associated regions of retinal organoids without direct tissue invasion. Organoid-endothelial co-culture resulted in increased VEGF secretion, while exogenous VEGF further enhanced endothelial localization near RPE regions without affecting organoid growth. Functional assays using fluorescent dextran and rhodamine-labeled liposomal nanoparticles demonstrated spatially restricted and time-dependent transport along vascularized regions adjacent to the organoid interface. This retinal organoid-on-chip provides a simple and robust in vitro platform for studying retinal-vascular interactions and vascular-mediated transport processes.}, }
@article {pmid41627545, year = {2026}, author = {Cheng, X and Zeng, X and Liu, S and Liu, C and Liu, Y and Xu, G}, title = {Shared diagnostic biomarkers and diagnostic models of age-related macular degeneration and systemic lupus erythematosus.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {95}, pmid = {41627545}, issn = {1573-2630}, support = {U2267220//Yulong Liu/ ; }, mesh = {Humans ; *Lupus Erythematosus, Systemic/diagnosis/genetics/metabolism ; *Macular Degeneration/diagnosis/genetics/metabolism ; *Biomarkers/metabolism ; Gene Expression Profiling ; Mendelian Randomization Analysis ; }, abstract = {PURPOSE: This study aimed to investigate the potential link between age-related macular degeneration (AMD) and systemic lupus erythematosus (SLE), exploring whether AMD may share underlying autoimmune mechanisms with SLE. The objective was to identify shared core genes and potential diagnostic biomarkers for both diseases.<br><br>METHODS: We utilized GEO datasets to develop diagnostic models and performed differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning techniques-LASSO regression, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE)-to identify common key genes between AMD and SLE. Mendelian randomization analysis was conducted to validate the potential causal relationship between AMD and the identified essential genes. Single-cell RNA sequencing data were analyzed to explore the expression patterns of shared biomarkers at the cellular level. The expression level of the identified biomarker was validated using reverse transcription quantitative polymerase chain reaction and Western blotting.<br><br>RESULTS: Several shared core genes were identified as associated with both AMD and SLE. The Mendelian randomization study confirmed a potential correlation between AMD and these essential genes. Single-cell transcriptomic analysis revealed distinct expression profiles of these markers across relevant cell types, supporting their role in disease pathology.<br><br>CONCLUSION: Our findings suggest that AMD and SLE share key genetic features, supporting the hypothesis that AMD may have an autoimmune component. These shared genes hold promise as potential therapeutic targets and diagnostic biomarkers for both diseases.}, }
@article {pmid41629364, year = {2026}, author = {Spörri, L and Studer, JM and Kreuzer, M and Rotzetter, J and Schärer, D and Largiadèr, CR and Jaggi, D and Zinkernagel, MS and Zysset-Burri, DC}, title = {Linking the microbiome to the complement system in geographic atrophy.}, journal = {NPJ genomic medicine}, volume = {11}, number = {1}, pages = {}, pmid = {41629364}, issn = {2056-7944}, support = {CF10000044-EPFL SCR0237812//Foundation Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique F&#xe9;d&#xe9;rale de Lausanne), Lausanne, Switzerland/ ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the aged population with the late stage geographic atrophy (GA). Risk factors for AMD include age, genetic variants in the complement system, nutritional factors, and alterations in the gut microbiome (GM). To identify taxonomic and functional differences in the microbiome associated to disease pathophysiology and genetic risk factors, this study investigated the GM and the ocular surface microbiome (OSM) of GA patients compared to healthy controls by whole-metagenome shotgun sequencing. 16 AMD-associated SNPs were genotyped from blood samples using TaqMan assays and Sanger sequencing. While GA patients showed differences in the GM, and altered metabolic pathways including inosine 5'-phosphate degradation, NAD salvage, and ketogenesis, no alterations in the OSM were found. Genetic analysis associated SNP rs1061170 in the complement factor H gene with GA. These findings suggest that microbial alterations may contribute to GA through inflammation and oxidative stress.Registry: ClinicalTrials.gov, NCT02438111, Registration date: 28 April 2015, and NCT04658238, Registration date: 01 December 2020.}, }
@article {pmid41629572, year = {2026}, author = {Kindo, H and Hosokawa, MM and Ouchi, C and Matoba, R and Morita, T and Hayashi, J and Morizane, Y}, title = {Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41629572}, issn = {1613-2246}, abstract = {PURPOSE: To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.<br><br>RESULTS: Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to &#x2265;8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.<br><br>CONCLUSIONS: Switching to aflibercept 8&#x202f;mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching.}, }
@article {pmid41630010, year = {2026}, author = {Cassavia Junior, ASF and Bellanda, V and Audi, LO and Barbosa, GCS and Caravelas, RAM and Volpe, GJ and Moreira, HT and Schmidt, A and Jorge, R}, title = {Assessing the prevalence of extensive macular atrophy with pseudodrusen-like appearance in patients with rheumatic fever-associated valvular heart disease: a cross-sectional study.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {31}, pmid = {41630010}, issn = {2056-9920}, abstract = {BACKGROUND: Extensive macular atrophy with pseudodrusen-like appearance (EMAP) is a rare retinal disorder characterized by bilateral macular atrophy and subretinal drusenoid deposits (SDDs), typically occurring earlier and progressing faster than age-related macular degeneration. A possible association between EMAP and rheumatic fever (RF) has been proposed, but its prevalence in this population remains unclear.<br><br>METHODS: In this cross-sectional study, 118 patients (236 eyes) with valvular disease secondary to RF were prospectively screened at a tertiary cardiology clinic. EMAP was defined by vertically predominant macular atrophy with SDDs and exclusion of alternative diagnoses. Multimodal imaging included spectral-domain optical coherence tomography and fundus autofluorescence. Demographic, clinical, and cardiologic parameters were descriptively analyzed between patients with and without EMAP, and compared between those with and without SDDs using appropriate statistical tests.<br><br>RESULTS: Two patients (1.69%; 95% confidence interval [CI], 0.47&#x2013;5.97%) met diagnostic criteria for EMAP. Both were women aged 62 and 73 years, with RF onset during childhood and long disease duration (54 and 62 years). SDDs were identified in 12 patients (10.17%; 95% CI, 5.91&#x2013;16.94%), including both EMAP cases. Patients with SDDs were significantly older (p&#x2009;=&#x2009;0.007), had longer RF duration (p&#x2009;=&#x2009;0.032), and received a greater cumulative benzathine penicillin prophylaxis burden (p&#x2009;=&#x2009;0.029).<br><br>CONCLUSIONS: EMAP is uncommon among patients with RF-associated valvular disease, suggesting that additional genetic or environmental factors may be necessary for disease manifestation. The prevalence of SDDs highlights potential subclinical retinal involvement associated with chronic systemic inflammation in this patient population.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-026-00805-6.}, }
@article {pmid41630283, year = {2026}, author = {Chen, J and Chen, T and Zhao, C and Bao, Z and Liu, H}, title = {Mendelian randomization study of causality between 35 blood and urine biomarkers and age-related eye diseases.}, journal = {Medicine}, volume = {105}, number = {5}, pages = {e47286}, pmid = {41630283}, issn = {1536-5964}, mesh = {Humans ; Mendelian Randomization Analysis ; *Biomarkers/urine/blood ; Macular Degeneration/urine/genetics/blood ; Cataract/urine/genetics/blood ; *Eye Diseases/urine/blood/genetics ; Glaucoma/urine/genetics/blood ; Diabetic Retinopathy/urine/genetics/blood ; Causality ; }, abstract = {Age-related eye diseases (AREDs) are a group of age-related visual degenerative diseases characterized by insidious and gradual onset. Identification of biomarkers associated with the early stage of AREDs is particularly important to delay its progression. This study aimed to evaluate the causal relationship between 35 blood and urine biomarkers and AREDs, thereby providing new insights into disease mechanisms and potential therapeutic targets. Two-sample Mendelian randomization (MR) was used to clarify the causal relationship between blood and urine biomarkers and AREDs. We classified AREDs into 4 types: age-related cataract (SC), age-related macular degeneration, glaucoma, and diabetic retinopathy. Inverse variance weighting method was used as the main analysis method, Cochran Q test, MR-Egger intercept, and leave-one-out test were used to investigate whether there was heterogeneity and pleiotropy of MR results. And the results were corrected by false discovery rate. Through MR analysis, this study provides the first systematic genetic evidence regarding the associations between blood and urine biomarkers and 4 AREDs. Specifically, our findings suggest a causal effect of 1 biomarker on SC, support causal roles of 3 biomarkers in age-related macular degeneration, and indicate causal relationships for 3 biomarkers with diabetic retinopathy. The reliability of these results was bolstered by a series of sensitivity analyses. This study strengthened the link between specific blood and urine biomarkers and the risk of AREDs. It has enhanced our understanding of the pathogenesis of AREDs and may guide the development of targeted prevention, diagnosis, and treatment strategies.}, }
@article {pmid41631247, year = {2026}, author = {Hsiao, YJ and Li, H and Xue, CC and Chong, CCY and Zhu, E and Yuan, Q and Yu, M and Cheung, CMG and Fan, Q and Sabanayagam, C and Tham, YC and Cheng, CY}, title = {Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {101036}, pmid = {41631247}, issn = {2666-9145}, abstract = {PURPOSE: To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).<br><br>DESIGN: Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.<br><br>PARTICIPANTS: Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed.<br><br>METHODS: Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if P < 0.05 in the primary model and in &#x2265;2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD.<br><br>MAIN OUTCOME MEASURES: Causal associations between eGFR and advanced AMD.<br><br>RESULTS: In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01-1.25; P = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01-4.08; P = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, P = 2.29 x 10[-33] for AMD; P = 2.29 x 10[-13] for eGFR).<br><br>CONCLUSIONS: Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41632207, year = {2026}, author = {Nimmo, J and Bright, M and Yang, Z and Nicholls, LE and Morgan, BP and Daskoulidou, N and Zelek, WM}, title = {Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {37}, number = {1}, pages = {33}, pmid = {41632207}, issn = {1432-1777}, abstract = {The brain and eye share striking anatomical, physiological, and immunological similarities. Both are protected by specialised vascular barriers, the blood-brain barrier (BBB) and blood-retinal barrier (BRB) respectively, that maintain homeostasis through tightly regulated cellular and molecular mechanisms. Increasing evidence implicates complement dysregulation as a key driver of neurodegeneration in both organs, contributing to disorders such as Alzheimer’s disease (AD), and age-related macular degeneration (AMD). Genetic and molecular studies highlight overlapping mechanisms, with variants in complement regulators influencing susceptibility to both retinal and brain pathologies. Locally synthesised complement components modulate glial activation, vascular integrity, and synaptic remodelling at both sites and, when dysregulated, contribute to chronic inflammation, synapse loss and neuronal degradation. Despite these shared pathways, therapeutic development has progressed asymmetrically; several complement therapeutics are already in the clinic for AMD and other ocular pathologies, while none are yet in use for brain diseases. This is in part a consequence of the accessibility of the eye where complement targeted drugs can be directly delivered and impact on pathology monitored, difficult in the brain. Lessons learned from the eye, including local delivery to overcome challenges of barrier penetration, may help accelerate development of complement therapeutics for the brain. Here we present a brief perspective that integrates current understanding of complement-mediated mechanisms across brain and eye, emphasising clues from convergent pathophysiology and ocular translational successes.}, }
@article {pmid41632222, year = {2026}, author = {Kim, JY and Lee, J and Oh, SB and Kim, C and Park, YH}, title = {α-Crystallins and vascular endothelial growth factor in aqueous humor of patients with neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41632222}, issn = {1613-2246}, support = {ZC23TISI0770//Seoul St. Mary's Hospital, Catholic University of Korea/ ; RS-2023-00253065//National Research Foundation/ ; }, abstract = {PURPOSE: This study investigated aqueous humor (AH) levels of α-crystallins and vascular endothelial growth factor (VEGF) in patients with neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Prospective study.<br><br>METHODS: AH samples were collected from treatment-na&#xef;ve phakic nAMD patients before the first and third anti-VEGF injections and from cataract patients without retinal disease as controls. &#x3b1;B-crystallin, &#x3b1;A-crystallin, and VEGF levels were quantified using enzyme-linked immunosorbent assay. Patients were classified as good responders (achieved remission) or poor responders (persistent intraretinal or subretinal fluid) according to response after three consecutive monthly anti-VEGF injections.<br><br>RESULTS: A total of 28 eyes from 24 nAMD patients and 27 eyes from 23 controls were analyzed. nAMD showed higher &#x3b1;B-crystallin and VEGF, but similar &#x3b1;A-crystallin levels versus controls (P < 0.001, P = 0.002, and P = 0.721, respectively). In nAMD eyes, after two anti-VEGF injections, &#x3b1;B-crystallin and &#x3b1;A-crystallin remained unchanged, whereas VEGF decreased (P = 0.057, P = 0.182, and P = 0.017, respectively). Among nAMD eyes, 20 eyes from 18 patients were good responders and 8 from 6 were poor responders. Good responders demonstrated reductions in &#x3b1;B-crystallin and VEGF (P = 0.016 and P = 0.002, respectively), whereas poor responders showed no significant changes (P = 0.249 and P = 0.075, respectively). In untreated nAMD eyes, &#x3b1;B-crystallin and VEGF levels showed a positive correlation (P = 0.010).<br><br>CONCLUSION: In nAMD, AH &#x3b1;B-crystallin levels were elevated compared with controls. Among good responders to anti-VEGF therapy, &#x3b1;B-crystallin levels decreased. Moreover, &#x3b1;B-crystallin levels showed a positive correlation with VEGF.}, }
@article {pmid41632743, year = {2026}, author = {Belloni Baroni, L and Toto, L and Formenti, F and Passamonti, M and Quarta, A and Ruggeri, ML and Aloia, R and Di Nicola, M and Mastropasqua, R}, title = {Long-Term Follow-Up of Faricimab Intravitreal Injections in Naïve Neovascular Age-Related Macular Degeneration.}, journal = {Ophthalmic research}, volume = {69}, number = {1}, pages = {74-82}, pmid = {41632743}, issn = {1423-0259}, mesh = {Humans ; Intravitreal Injections ; Female ; Male ; Follow-Up Studies ; *Visual Acuity/physiology ; Tomography, Optical Coherence ; Aged ; Fluorescein Angiography ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Time Factors ; Treatment Outcome ; Fundus Oculi ; Prospective Studies ; Antibodies, Bispecific ; }, abstract = {INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes at the 44-week follow-up in patients with naïve neovascular age-related macular degeneration (nAMD) treated with faricimab intravitreal injections (IVIs).<br><br>METHODS: Fifty-four eyes of 54 patients with na&#xef;ve active macular neovascularization and nAMD were enrolled at the Ophthalmology Clinic of University "G. d'Annunzio," Chieti-Pescara, Italy. All patients were scheduled for faricimab IVI. Each patient underwent complete ophthalmic examination including best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts and optical coherence tomography. All measurements were evaluated at baseline, at week 20 and then according to fixed retreatment interval up to week 44. Fluorescein angiography and indocyanine green angiography were also performed at baseline. Main outcome measures were changes in BCVA, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), intraretinal fluid presence, subfoveal subretinal fluid presence and thickness, the presence of pigment epithelial detachments (PEDs), and its maximum height (PED-MH).<br><br>RESULTS: BCVA improved and CMT reduced significantly from baseline to week 44 (p = 0.002 and p = 0.020, respectively) in the overall sample with a higher significant improvement from baseline to week 20 (p < 0.001 for both parameters) and no additional significant improvement from week 20 to week 44 in the overall sample (p = 0.348 and p = 0.146, respectively). At week 20, 72.3% of patients were in the Q12/Q16 interval. Patients in the Q8 interval showed significant improvement in BCVA (p < 0.001) and significant reduction of CMT (p = 0.008) from baseline to week 44, respectively. PED-MH as well showed a significant reduction from baseline to week 44 (p < 0.001). Patients in the Q12 interval showed significant improvement in BCVA (p = 0.030) and significant reduction of CMT, SFCT, and PED-MH from baseline to week 36 (p < 0.001). Patients in the Q16 interval showed significant reduction of BCVA during follow-up (p = 0.026). CMT, SFCT, and PED-MH were significantly reduced from baseline to week 44 (p < 0.001).<br><br>CONCLUSION: Faricimab showed efficacy in the treatment of na&#xef;ve nAMD patients with an improvement of many anatomical and functional parameters at 44 weeks, allowing the maintenance of a treatment regimen for most patients equal to or greater than 12 weeks.}, }
@article {pmid41633199, year = {2026}, author = {Hayashi, K and Kobayashi, M and Mori, K and Nakagawa, Y and Watanabe, B and Masuya, T and Ashimori, A and Higashijima, F and Yoshimoto, T and Morita, T and Murai, T and Kirihara-Kojima, S and Kimura, K}, title = {A novel prohibitin inhibitor acts as a dual inhibitor of angiogenesis and fibrosis.}, journal = {Biochemical and biophysical research communications}, volume = {805}, number = {}, pages = {153386}, doi = {10.1016/j.bbrc.2026.153386}, pmid = {41633199}, issn = {1090-2104}, mesh = {Prohibitins ; *Repressor Proteins/antagonists &amp; inhibitors/metabolism/genetics ; Animals ; Humans ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; Fibrosis ; Mice ; *Angiogenesis Inhibitors/pharmacology ; Mice, Inbred C57BL ; Cells, Cultured ; Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/drug effects ; *Neovascularization, Pathologic/drug therapy ; Mitochondria/drug effects/metabolism ; Angiogenesis ; }, abstract = {We previously showed that the benzoylphenylurea derivative BPU17 inhibits epithelial-mesenchymal transition and acts as an antifibrotic agent. This compound acts as a prohibitin (PHB) inhibitor by directly binding to PHB1. This binding disrupts the interaction between PHB1 and PHB2, leading to mild mitochondrial dysfunction. Here, we investigated the effect of BPU17 on angiogenesis using primary cultures of human vascular and microvascular endothelial cells, as well as a mouse model of choroidal neovascularization (CNV). A series of studies has shown that BPU17 inhibits angiogenesis both in vitro and in vivo. The molecular mechanism is that BPU17 inhibits serum response factor (SRF)/CArG box-mediated transcription by repressing the expression of SRF and its cofactor myocardin-related transcription factors (MRTF-A and -B [MRTF]). This defect causes the downregulation of adaptor and cell adhesion molecules such as vinculin and integrins, leading to the inhibition of angiogenesis. This inhibitory effect is closely associated with mild mitochondrial dysfunction, and siRNA-mediated knockdown of PHB1 similarly inhibits angiogenesis. Given that age-related inflammatory responses and subsequent choroidal neovascularization (CNV) contribute to the development of neovascular age-related macular degeneration (nAMD), this novel PHB inhibitor holds promise as a treatment for nAMD through its dual inhibitory effects on angiogenesis and fibrosis.}, }
@article {pmid41633707, year = {2026}, author = {Patel, SS and Boyer, DS and Loewenstein, A and Clark, J and Zhu, L and Tang, J and Desai, D}, title = {Safety and tolerability of avacincaptad pegol in combination with ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration: results from a phase 1 and phase 2a study.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41633707}, issn = {2397-3269}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/adverse effects/pharmacokinetics ; Male ; Female ; Aged ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Drug Therapy, Combination ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Polyethylene Glycols/administration &amp; dosage/pharmacokinetics/adverse effects ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Tomography, Optical Coherence ; }, abstract = {OBJECTIVE: To assess the safety and tolerability of avacincaptad pegol (ACP), a Food and Drug Administration-approved therapy for geographic atrophy, administered in combination with ranibizumab, an approved therapy for neovascular age-related macular degeneration (nAMD), in patients with nAMD.<br><br>METHODS: The phase 1 study (NCT00709527) was a two-part, ascending-dose and parallel-group, open-label trial that assessed the safety, tolerability and pharmacokinetic profile of monthly intravitreal injections of ACP (0.03, 0.3, 1, 2, 3&#x2009;mg) in combination with ranibizumab (0.5&#x2009;mg) on the same day in treatment-na&#xef;ve patients with nAMD (n=43 patients received a maximum of 6 injections). The phase 2a study (NCT03362190) was an open-label trial assessing the 6-month safety of intravitreal injections of ACP administered in combination with ranibizumab in treatment-na&#xef;ve patients with nAMD (n=64). Patients received either ACP 2&#x2009;mg or 4&#x2009;mg either 14 days or 1&#x2009;month apart, given on the same day or 2&#x2009;days after ranibizumab. Primary outcome measures were safety and tolerability.<br><br>RESULTS: During the phase 1 study, there were no dose-limiting toxicities at any dose level. In both studies, ocular treatment-emergent adverse events were mostly mild or moderate, with the most reported events related to the injection procedure. There were no clinically significant increases in intraocular pressure or cumulative increases with multiple injections over time. There were no safety issues identified through measurement of visual acuity.<br><br>CONCLUSIONS: Coadministration of ACP and ranibizumab in treatment-na&#xef;ve patients with nAMD was well tolerated across different dosing regimens with no new safety issues based on results from two independent studies.}, }
@article {pmid41633708, year = {2026}, author = {Romdhoniyyah, DF and Alshukri, A and Parry, DG and Harding, S and Beare, NAV}, title = {Metformin and incidence of age-related macular degeneration in people with diabetes: a population-based 5-year case-control study.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41633708}, issn = {2397-3269}, mesh = {Humans ; *Metformin/therapeutic use ; *Macular Degeneration/epidemiology/diagnosis/prevention &amp; control ; Male ; Female ; Incidence ; *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology ; Aged ; Case-Control Studies ; Middle Aged ; *Hypoglycemic Agents/therapeutic use ; Disease Progression ; *Diabetic Retinopathy/drug therapy/diagnosis/epidemiology ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Metformin has been identified as a potential treatment for age-related macular degeneration (AMD). Photographic screening for diabetic retinopathy provides an opportunity to conduct a case-control study with systematic AMD grading. We aimed to investigate associations between metformin use and incidence and progression of AMD at different grades.<br><br>METHODS AND ANALYSIS: We randomly sampled 2600 participants from 10&#x2009;336 people aged &#x2265;50 years with diabetes who attended retinopathy screening in 2011 (baseline) and were enrolled to the Individualised Screening for Diabetic Retinopathy study. 2545 of these participants had type 2 diabetes and gradable fundus photographs at baseline, which were graded using modified age related eye disease study grading. We used data including those on metformin prescription from general practitioner records. We used multivariate logistic regression to investigate associations between metformin and incidence or progression of early, intermediate and late AMD.<br><br>RESULTS: Of 2545 participants, 2089 attended and had gradable fundus images on year 5. Metformin was associated with reduced incidence of intermediate AMD by 5 years after adjusting for confounders (complete record OR 0.63, 95%&#x2009;CI 0.43 to 0.92, p=0.02). In univariate analysis, metformin was associated with reduced incidence of late AMD (OR 0.43, 95% CI 0.21 to 0.88, p=0.02) but this did not remain significant after adjusting for age and sex. The numbers progressing to late AMD were small. There was no association between metformin and the incidence of early AMD.<br><br>CONCLUSION: We have found a significant association between metformin use and reduction in incidence of intermediate AMD by 37% in people with diabetes over 5 years. Previous epidemiological studies of metformin and AMD have used secondary data on AMD. In this observational study, there were baseline differences between groups, although significant findings remained after adjusting for important confounders. Given metformin's anti-ageing therapeutic effects, the reduction in risk is plausible and warrants prospective clinical trials.}, }
@article {pmid41634481, year = {2026}, author = {Cheung, CMG and Kikushima, W and Teo, KYC}, title = {Initial Experiences of Switching to Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration and Polypoidal Chorodal Vasculopathy in an Asian Population.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1057-1068}, pmid = {41634481}, issn = {2193-8245}, support = {NMRC/LCG23 May/0032//National Medical Research Council Singapore Open Fund Large Collaborative Grant/ ; 24-Jan-0005//STaR/ ; }, abstract = {INTRODUCTION: Recent advances in the development of antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD) include the approval of aflibercept 8 mg, which delivers four times the previously commercially available dose. A longer durability of aflibercept 8 mg compared with 2 mg was reported in the clinical trial results. However, there are limited data in patients switching to aflibercept 8 mg from other agents in clinical practice. This study reports the initial real-world experience of consecutive patients switched to aflibercept 8 mg.<br><br>METHODS: Consecutive eyes with previously treated nAMD receiving aflibercept 8&#xa0;mg switched from other agents were retrospectively reviewed. Patients were switched either owing to suboptimal control of disease activity (efficacy group) or to potentially extend treatment intervals (durability group). The main outcome measures included change in optical coherence tomography (OCT)-based anatomical parameters, including central subfield thickness (CST) and presence of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) before and after switching. In addition, quantification of OCT biomarkers was performed using the RetinAI Discovery algorithm.<br><br>RESULTS: A total of 30 eyes from 29 patients were identified. Among the 25 eyes in the efficacy group, 20 eyes remained on aflibercept 8&#xa0;mg through to the last follow-up visit. Median CST showed a significant reduction from 291 (275-301) &#xb5;m to 279 (269-289) &#xb5;m (p&#x2009;=&#x2009;0.02). Volumetric analysis showed a significant reduction in SRF volume, a small nonsignificant increase in IRF volume, and a trend toward reduction in PED volume. The five eyes in the durability group had no SRF, IRF, or hemorrhage at the time of switching and remained stable during the follow-up period.<br><br>CONCLUSIONS: These results provide early experience of aflibercept 8&#xa0;mg in a clinical cohort in hard-to-treat patients. The current analysis demonstrated favorable anatomical outcomes after switching in most patients, with no safety signals.}, }
@article {pmid41634482, year = {2026}, author = {Grimaldi, G and Bartolomeo, N and Garweg, JG and Pfister, IB and Schild, C and Peyla, A and Tillmann, A and De Oliveira Figueiredo, EC and Spitznagel, T and Kitay, AM and Gabathuler, F and Zweifel, S and Kurz-Levin, MM and Ebneter, A and Somfai, GM and Eandi, CM and Munk, MR and Ambresin, A and Menghini, M}, title = {One-Year Real-World Outcomes of Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1069-1082}, pmid = {41634482}, issn = {2193-8245}, abstract = {INTRODUCTION: This study reports the 1-year efficacy of aflibercept 8 mg (afl8) in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: An observational, retrospective case series from nine centers of the Swiss Retina Research Network including treatment-na&#xef;ve eyes with nAMD started on intravitreal afl8. Changes in visual acuity (VA), macular thickness, pigment epithelial detachment (PED) height, and retinal fluids were evaluated over 12&#xa0;months and compared with baseline. Treatment intervals and safety data were recorded along with subgroup analyses based on macular neovascularization type, loading-phase completion, and treatment regimen.<br><br>RESULTS: A total of 91 eyes met the inclusion criteria. After 1 year of treatment, VA changed by&#x2009;+&#x2009;1.0&#x2009;&#xb1;&#x2009;13.2 letters (p&#x2009;=&#x2009;0.018), mean CST changed by -110.0&#x2009;&#xb1;&#x2009;130.9&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001), and mean PED height changed by -71.2&#x2009;&#xb1;&#x2009;104.8&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). After 12&#xa0;months, 66.2% of eyes demonstrated a complete absence of macular fluids. Mean treatment interval was 13.9&#x2009;&#xb1;&#x2009;7.9&#xa0;weeks, with 56.1% of eyes being extended to&#x2009;&#x2265;&#x2009;12&#xa0;weeks with an anatomy-driven approach. No functional or anatomical differences were observed between eyes receiving a clean loading phase and in terms of different macular neovascularization (MNV) subtypes. Two adverse events were observed.<br><br>CONCLUSIONS: The first 1-year real-world experience with afl8 in patients with nAMD revealed a robust anatomical response but only a variable and limited visual gain over 12&#xa0;months due to a ceiling effect. Our findings confirm the fast and sustained macular drying reported from clinical trials, allowing for extended treatment intervals without compromising safety and efficacy.}, }
@article {pmid41636066, year = {2026}, author = {Lei, Y and Yang, J and Li, Y and Xiao, B and Lai, D and Qiu, Q}, title = {Radiotherapy for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/02713683.2026.2621179}, pmid = {41636066}, issn = {1460-2202}, abstract = {PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) drugs have limitations in the treatment of neovascular age-related macular degeneration (nAMD). This study aims to evaluate the efficacy and safety of radiotherapy combined with anti-VEGF therapy versus anti-VEGF monotherapy in the treatment of nAMD.Methods: This systematic review and meta-analysis (PROSPERO registration number: CRD420251010811) searched PubMed, Embase, Cochrane, Web of Science, LILACS, ISRCTN registry, and ClinicalTrials.gov up to February 25, 2025. Two radiotherapy modalities were analyzed: epimacular brachytherapy (EBM) and stereotactic radiotherapy (SRT). The primary outcome was the proportion of participants who lost more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 and 24 months. A total of four studies were included, yielding 7 articles for meta-analysis.<br><br>RESULTS: For EBM combined with anti-VEGF therapy, compared with anti-VEGF monotherapy, there was a higher risk of losing more than 15 ETDRS letters at 12 months (relative risk [RR] 2.36, 95% confidence interval [CI] 1.49-3.74) and 24 months (RR 2.39, 95% CI 1.68-3.39). The difference in best-corrected visual acuity (BCVA) was 0.10 logarithm of the minimum angle of resolution (logMAR) (95% CI 0.05-0.15) at 12 months and 0.17 logMAR (95% CI 0.13-0.21) at 24 months. For SRT combined with anti-VEGF therapy, there was a greater risk of losing more than 15 ETDRS letters at 24 months (RR 1.75, 95% CI 1.12-2.74) compared with anti-VEGF monotherapy; however, the SRT group required 2.10 fewer ranibizumab injections than the sham-irradiation group (mean difference [MD] -2.10, 95% CI -2.97 to -1.22).<br><br>CONCLUSION: Epimacular brachytherapy (EBM) combined with anti-VEGF therapy may worsen patient outcomes and increase the risk of adverse events. In contrast, stereotactic radiotherapy (SRT) combined with anti-VEGF therapy does not improve visual acuity but can reduce the frequency of anti-VEGF injections, potentially alleviating the treatment burden for patients with nAMD.}, }
@article {pmid41636413, year = {2026}, author = {Cinque, F and Pas, JAAH and de Breuk, A and Heesterbeek, T and Klaver, CCW and Hoyng, CB and Lechanteur, YTE and van Heugten, CM}, title = {Visual Acuity Provides a More Meaningful Measure of Vision-Related Functioning Than Mesopic Microperimetry in Age-Related Macular Degeneration Patients: A Cross-Sectional Study.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {2}, pages = {5}, pmid = {41636413}, issn = {2164-2591}, mesh = {Humans ; Cross-Sectional Studies ; *Visual Acuity/physiology ; Female ; Male ; *Visual Field Tests/methods ; Aged ; *Macular Degeneration/physiopathology/diagnosis ; *Visual Fields/physiology ; *Mesopic Vision/physiology ; Aged, 80 and over ; Middle Aged ; Retina/physiopathology ; Surveys and Questionnaires ; }, abstract = {PURPOSE: Mesopic microperimetry is a promising tool to evaluate retinal function in clinical trials. Although visual function (VF), the ability to perform vision-related tasks, relates strongly to visual acuity (VA) in patients with age-related macular degeneration, the relationship between mesopic microperimetry and VF remains unclear.<br><br>METHODS: A cross-sectional study in patients with age-related macular degeneration was performed. VF was measured by questionnaire using a subset of the National Eye Institute 25-Item Visual Function Questionnaire. The macular integrity assessment microperimeter, was used with a 4-2 staircase strategy with a 10&#xb0; diameter circular grid containing 37 loci. Three interpretations of the retinal sensitivity data were calculated: the mean of the 37 thresholds (mean sensitivity [MS]), the percent-reduced threshold (PRT), and the log-transformed candela mean (MS cd log). MS, PRT, and MS cd log were tested via stepwise hierarchical linear regression and R2.<br><br>RESULTS: We analyzed data from 102 patients (64 females [61%]; mean age, 71.8 &#xb1; 11.2 years). VF was explained best by VA (MS; R2 VA = 0.38, MS cd log; R2 VA = 0.38, PRT; R2 VA = 0.39). All retinal sensitivities contributed significantly to total R2. In the MS cd log model (total adjusted R2 = 0.52) the combined contribution of variance explained by VA and MS cd log was 46% (partial adjusted R2 = 0.46).<br><br>CONCLUSIONS: Mesopic microperimetry is associated with VF but VA provides a more meaningful estimation of this same construct. These results suggest that VA provides stronger evidence of clinical efficacy.<br><br>TRANSLATIONAL RELEVANCE: This study relates functional tests to daily vision-related functioning.}, }
@article {pmid41636834, year = {2026}, author = {Mesfin, Y and Salvi, A and Arnal, L and Langlotz, C and Mahajan, V and Ludwig, CA}, title = {Shaping the future of myopia: artificial intelligence for vitreoretinal complications of high and pathologic myopia.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41636834}, issn = {1435-702X}, support = {E. Matilda Ziegler Foundation for the Blind//E. Matilda Ziegler Foundation for the Blind/ ; NEI P30-EY026877//Stanford P30 Vision Research Core Grant/ ; K23EY035741//National Eye Institute K23 Grant/ ; Research to Prevent Blindness, Inc//Research to Prevent Blindness, Inc/ ; }, abstract = {PURPOSE: The global impact of myopia extends far beyond individual ocular health, posing significant challenges to healthcare systems worldwide. Artificial intelligence (AI), particularly deep learning (DL) applied to ophthalmic imaging, offers a promising strategy to ease constraints posed by the myopia epidemic by detecting subtle structural changes early. Here we describe the current literature on AI for detecting retinal sequelae of myopia, including retinal detachments (RD), myopic macular degeneration (MMD), and myopic traction maculopathy (MTM), with attention to imaging modality and model task (classification vs. segmentation).<br><br>METHODS: A literature search was conducted to identify studies using DL to detect RD, MMD, and MTM across ophthalmic imaging modalities (including OCT and fundus photography, and where available fluorescein angiography and ultrasonography).<br><br>RESULTS/FINDINGS: We reviewed 28 studies that piloted DL models usingclassification and/or segmentation approaches for RD (10 studies), MMD (12 studies), and MTM (6 studies). Reported performance for RD ranged from area under the curve (AUC) 86-100%, accuracy 79.3-98.9%, sensitivity 77.1-97.6%, and specificity 79.7-100%. For MMD, performance ranged from AUC 86-100%, accuracy 85.3-99.8%, sensitivity 37.1-97.8%, and specificity 91.5-99.9%. For MTM, performance ranged from AUC 93.8-99.7%, accuracy 94.3-99.3%, sensitivity 74.5-98.4%, and specificity 84.8-99.7%. Across studies, there was substantial heterogeneity in case definitions, datasets, and evaluation methods, and external validation was inconsistently reported. Many earlier studies used CNN-based architectures, while more recent work increasingly incorporates transformer-based backbones and pretrained or foundation models.<br><br>CONCLUSION: Researchers have demonstrated excellent results for developing DL models that accurately classify and segment retinal pathologies associated with myopia. However, despite strong performance, additional work is needed to translate these models into clinical use, including robust external validation, calibration for clinical decision-making, and prospective evaluation, particularly for longitudinal prognostication of incident complications in pathologic myopia.}, }
@article {pmid41638110, year = {2026}, author = {Amin, R and Kaiser, PK}, title = {Tyrosine kinase inhibitors for wet age-related macular degeneration: The current developmental landscape.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {393}, number = {3}, pages = {103803}, doi = {10.1016/j.jpet.2026.103803}, pmid = {41638110}, issn = {1521-0103}, abstract = {Age-related macular degeneration (AMD) is a leading cause of permanent vision loss in older patients worldwide. The neovascular (wet) AMD is characterized by abnormal choroidal neovascularization driven by vascular endothelial growth factor (VEGF), platelet-derived growth factor, and Tie2 signaling pathways, leading to retinal damage and progressive vision decline. Current standard-of-care anti-VEGF therapies aim to limit choroidal neovascularization through extracellular targeting of cytokines involved in the VEGF signaling pathway implicated in angiogenesis. Although these existing therapies can be effective, many patients face a high treatment burden of multiple intraocular injections, which can negatively impact compliance, safety, and long-term efficacy. Tyrosine kinase inhibitors (TKIs) aim to address these limitations by offering longer durability, broad-spectrum targeting of angiogenic pathways, and a reduction in treatment burden through intracellular targeting of angiogenic pathways. With multiple pharmaceutical TKI candidates advancing through clinical trials and showing promising data, this class of drugs could lead to a shift in future treatment options for patients with wet AMD. Despite the progress TKIs have made, there have yet to be any candidates approved for wet AMD treatment. Much of the existing evidence is from early-phase and short-term studies, and questions remain about long-term efficacy and safety compared to current standard-of-care anti-VEGF therapies. Nevertheless, with multiple candidates advancing through phase III clinical trials, TKIs have the potential to emerge as a next-generation treatment class that may transform the wet AMD therapeutic landscape. SIGNIFICANCE STATEMENT: Given the chronic nature of wet age-related macular degeneration and the limitations of current anti-vascular endothelial growth factor therapies, tyrosine kinase inhibitors have emerged as a promising class of anti-angiogenic agents. This review highlights the recent clinical developments in this evolving therapeutic landscape.}, }
@article {pmid41638748, year = {2026}, author = {Vougioukalou, S and Read, SM and Csontos, JK and Jones, A and Jaber, A and Sharma, A and Balaskas, K}, title = {Comparing community-based monitoring to hospital-based care of patients with quiescent age-related macular degeneration: a qualitative study of patient and practitioner perspectives on acceptability and access.}, journal = {BMJ open}, volume = {16}, number = {2}, pages = {e101379}, pmid = {41638748}, issn = {2044-6055}, mesh = {Humans ; Qualitative Research ; Female ; Aged ; Male ; *Macular Degeneration/therapy ; *Community Health Services ; *Patient Acceptance of Health Care ; *Attitude of Health Personnel ; *Health Services Accessibility ; Aged, 80 and over ; Middle Aged ; Patient Satisfaction ; Hospitals ; }, abstract = {OBJECTIVES: This process evaluation explores patient and healthcare professional acceptability of community-based monitoring versus hospital-based care for patients with quiescent neovascular age-related macular degeneration (QnAMD).<br><br>DESIGN: Qualitative process evaluation was conducted as part of a randomised controlled trial.<br><br>SETTING: Six hospitals and six community-based practices.<br><br>PARTICIPANTS: 25 patients and 16 healthcare professionals (ophthalmologists and optometrists). This approach helped differentiate between common issues and those specific to community-based monitoring.<br><br>INTERVENTION: The Quality-Assured Follow-Up of QnAMD by non-medical practitioners trial aimed to examine whether non-medical practitioners follow-up patients with QnAMD in the community in a safe and clinically and cost-effective way. The process evaluation aimed to examine whether the intervention was acceptable by patients and professionals. The process evaluation was based on interviews which contained open-ended questions focused on patient experience and confidence in community-based care, issues concerning the practicalities of the organisation and management of the clinic, and resources including IT and digital equipment. The theory of acceptability framework was used to interpret the findings.<br><br>RESULTS: Patients reported positively on the experience of receiving QnAMD services in the community and highlighted staff professionalism and clear communication. Key themes were the proximity of care provision for patients, IT interoperability and the real-world costs of running the service. Some patients randomised to the hospital showed preference for the intervention to take place in the hospital, mediated mainly by prior experience of hospital care and travel distance. The location of the clinic and transport routes affected the experience of attending appointments, with strong preference expressed for proximity to one's home. Inaccessibility due to non-modifiable internal building structures in the community and parking in hospital eye services was reported by a small proportion of patients. Healthcare professionals reported positively about their ability to deliver QnAMD services in community settings but raised concerns about the compatibility of technological infrastructure that facilitates the sharing of optical coherence tomography image and video files. Some optometrists were also concerned about the financial sustainability of the intervention after the end of the trial due to the costs involved in the administration of QnAMD follow-up care.<br><br>CONCLUSIONS: The delivery of QnAMD services in the community by non-medical personnel was broadly accepted by both patients and practitioners. This implies that non-medical practitioners can follow up patients with QnAMD in the community in a safe way. Further research would be needed to establish whether similar results would be obtained during routine practice outside a research project and whether the long-term follow-up for QnAMD would be financially sustainable for independent as well as chain community optometry practices.<br><br>TRIAL REGISTRATION NUMBER: NCT03893474.}, }
@article {pmid41641369, year = {2026}, author = {Wang, N and Luo, L and Yang, X}, title = {The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10876}, pmid = {41641369}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.}, }
@article {pmid41641466, year = {2026}, author = {Veerman, D and Cuartas-Vélez, C and Gensheimer, T and van Dorp, T and van der Meer, A and Bosschaart, N}, title = {Label-free assessment of a microfluidic vessel-on-chip model with visible-light optical tomography reveals structural changes in vascular networks.}, journal = {Lab on a chip}, volume = {26}, number = {6}, pages = {1901-1914}, pmid = {41641466}, issn = {1473-0189}, mesh = {Humans ; *Lab-On-A-Chip Devices ; *Tomography, Optical Coherence ; *Light ; *Tomography, Optical/instrumentation ; *Microfluidic Analytical Techniques/instrumentation ; }, abstract = {Microvascular dysfunction is characterized by impaired structure and function of small blood vessels, contributing to disease-related tissue and organ damage, such as in the retina. Optical coherence tomography is a widely used clinical technology to detect, monitor and diagnose disorders of the retina and choroid, such as diabetic retinopathy, macular degeneration, and various inherited retinal diseases. Currently, there are limited experimental platforms that correlate observed changes in clinical metrics with underlying mechanisms of disease progression. Organ-on-chips have the potential to offer a platform for correlative studies. Previous studies have demonstrated that the three-dimensional complexity of the microvasculature can be captured in a vessel-on-chip. Yet, current vessel-on-chip imaging analysis is based on end-point read-outs that provide limited dynamic information and do not have direct correlation with imaging techniques used in the clinic. Therefore, there is a need for clinically relevant, label-free, real-time imaging technologies. In this work, we show that optical coherence tomography can fulfill this need by providing non-invasive, label-free imaging of vascular networks-on-chip. We show that optical coherence tomography can detect and can be used to quantify changes in vascular network structures over multiple days, both during vascular network development and in response to disease-associated conditions. Our results indicate that optical coherence tomography has the potential to become a standard read-out for monitoring dynamic processes in organ-on-chips. In the future, these read-outs may enable the correlation of clinical metrics, thereby providing deeper insights in the pathophysiology of diseases, for example of the retina.}, }
@article {pmid41641772, year = {2026}, author = {Salkar, A and Palanivel, V and Basavarajappa, D and Heng, B and Schulz, A and Gupta, V and Graham, S and Mirzaei, M and You, Y}, title = {Retinal glial cells in glaucoma and age-related retinal diseases: Inflammatory responses, disease transitions, and translational perspectives.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01905}, pmid = {41641772}, issn = {1673-5374}, abstract = {Microglia, Müller cells, and astrocytes play a crucial role in maintaining retinal structure, homeostasis, and neuronal function. In disease, they undergo reprogramming that drives chronic inflammation and neurodegeneration. Unique to the retina, these glial cells occupy specialized niches and interact closely with the blood-retinal barrier, creating distinct vulnerabilities. We summarized the glial activation mechanisms, shared triggers, including oxidative stress, metabolic dysfunction, aging, and systemic inflammation, as well as key pathways, such as nuclear factor kappa-B, mitogen-activated protein kinase, Janus kinase/signal transducer and activator of transcription, the inflammasome, and the complement system. Disease-specific responses in glaucoma, age-related macular degeneration, diabetic retinopathy, and vascular occlusions were compared, highlighting the heterogeneity of gliosis and its impact on neuronal and vascular pathology. We also discussed emerging human-derived platforms alongside proteomics approaches, highlighting their utility for mechanistic insights and discovering biomarkers. Despite advances, critical gaps remain in understanding glial-glial interactions and in developing robust models focused on glia. Despite these advances, major gaps remain in our understanding of glial-glial communication, state transitions, and their temporal relationship to neurodegeneration. Moreover, the lack of experimental models explicitly designed to interrogate glial biology continues to limit translational progress. Addressing these challenges will be essential to reposition glial cells as central drivers of retinal disease rather than secondary responders. A strategic shift toward glia-centered models, integrative multi-omics analyses, and human-relevant systems holds promise for advancing biomarker discovery and developing targeted therapeutic strategies that aim to modulate glial dysfunction and preserve vision.}, }
@article {pmid41641862, year = {2026}, author = {Chambon, C and Picard, E and Zola, M and Aichedo, S and Lebon, C and Youale, J and Matet, A and Bousquet, E and Ferreira, C and Kowalczuk, L and Théron, L and Behar-Cohen, F}, title = {Proteomic Signature in Men with Central Serous Chorioretinopathy.}, journal = {Journal of proteome research}, volume = {25}, number = {3}, pages = {1761-1774}, doi = {10.1021/acs.jproteome.5c01233}, pmid = {41641862}, issn = {1535-3907}, mesh = {Humans ; Male ; *Proteomics/methods ; *Central Serous Chorioretinopathy/blood/metabolism/pathology ; Middle Aged ; Adult ; Oxidative Stress ; Tandem Mass Spectrometry ; *Proteome ; Case-Control Studies ; Chromatography, Liquid ; Complement Activation ; Complement System Proteins/metabolism/genetics ; Biomarkers/blood ; }, abstract = {To explore systemic contributors to central serous chorioretinopathy (CSCR) pathogenesis, we performed untargeted serum proteomics in 60 male CSCR patients (30 acute, 30 chronic) and 60 age-matched controls using label-free LC-MS/MS with stringent statistical pairing. Among 242 abundant proteins identified, 27 (11.5%) were significantly different in CSCR, converging on pathways of complement activation, coagulation, oxidative stress, immune regulation, and response to external stimuli. Complement cascade components (C1QA, C1S, C3, C4B, C8A/B/G, CFB) were upregulated, while the regulators CFHR1 and CFHR2 were decreased, contrary to age-related macular degeneration. Oxidative stress-related proteins (haptoglobin, hemoglobin subunits, peroxiredoxin-2) were elevated, consistent with prior evidence of systemic redox imbalance in CSCR. Tetranectin (CLEC3B) decreased and attractin (ATRN) increased in CSCR were validated by ELISA. Multiplex immunofluorescence on the human retina localized tetranectin to Müller cells, including the outer limiting membrane, and to the RPE and attractin to photoreceptor segments, retinal pigment epithelium, Bruch's membrane, and the choriocapillaris, supporting potential roles of both proteins at the retina-choroid interface. A distinct systemic proteomic signature in patients with CSCR highlights complement dysregulation, oxidative stress, and stress responses to external stimuli and identifies tetranectin and attractin as candidate biomarkers, which should further be validated in other cohorts.}, }
@article {pmid41642030, year = {2026}, author = {Su, IL and Yeh, KL and Lee, CY and Lin, SC and Chiang, CY and Chen, CJ and Chen, WY and Tseng, CC and Lu, YC and Kuan, YH}, title = {Irigenin Modulates BL-Induced Pyroptosis in Retinal Pigment Epithelial Cells Through p38 MAPK and NFκB Pathways.}, journal = {Journal of biochemical and molecular toxicology}, volume = {40}, number = {2}, pages = {e70723}, pmid = {41642030}, issn = {1099-0461}, support = {NSTC113-2320-B-040-014-MY3//National Science and Technology Council, Taiwan/ ; NCHU-CSMU-11408//National Chung Hsing University and Chung Shan Medical University/ ; R110-030//Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program/ ; CSMU-TSMH-112-02//Chung Shan Medical University and Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital/ ; }, mesh = {Humans ; *Pyroptosis/drug effects/radiation effects ; *NF-kappa B/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *p38 Mitogen-Activated Protein Kinases/metabolism ; *Isoflavones/pharmacology ; Cell Line ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Epithelial Cells/metabolism/pathology/drug effects ; Inflammasomes/metabolism ; Signal Transduction/drug effects ; *MAP Kinase Signaling System/drug effects ; }, abstract = {Age-related macular degeneration (AMD), a primary cause of vision loss among older adults, is strongly associated with inflammatory processes. The current study aimed to elucidate the protective effects of irigenin, an isoflavonoid recognized for its anti-inflammatory, antioxidative, antiapoptotic, and anticancer activities, against blue light (BL)-induced damage in N-retinyl-N-retinylidene ethanolamine (A2E)-laden human adult retinal pigment epithelial (A2E-laden ARPE-19) cells. Pretreatment with irigenin markedly mitigated BL-induced cytotoxicity and preserved epithelial barrier function in a concentration-dependent manner. Moreover, irigenin significantly inhibited the expression of proinflammatory cytokines and activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, as evidenced by decreased expression of NLRP3, ASC, and both full-length and cleaved forms of gasdermin D (GSDMD), along with reduced caspase-1 activity. Further mechanistic analyses indicated that irigenin effectively suppressed the activation of the nuclear factor kappa B (NFκB) signaling pathway, as evidenced by phosphorylation of NFκB and inhibitor of NFκB (IκB)α, and both activation and translocation of NFκB, along with reduced phosphorylation of p38 mitogen-activated protein kinase (MAPK). These findings underscore the potential of irigenin to ameliorate BL-induced retinal pigment epithelial cell damage via modulation of inflammation and pyroptosis pathways, suggesting its therapeutic value for preventing AMD.}, }
@article {pmid41642305, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {How do genetic polymorphisms influence the efficacy of age-related macular degeneration treatments? A systematic review and meta-analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41642305}, issn = {1435-702X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) has considerable global burden, being a major cause of vision loss. Subsequently, genetic predisposition holds a role in this case by contributing to disease susceptibility. Polymorphisms in genes such as Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) play a key role as risk factors for AMD. This systematic review and meta-analysis synthesizes existing evidence to investigate and quantify the association between these polymorphisms and the actual risk of AMD. Additionally, the paper sets to unravel the prevalence of high- and low-risk genotypes among AMD patients.<br><br>METHODS: In accordance with PRISMA guidelines, we conducted a systematic search of PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library databases to identify relevant studies. We included primary studies that involved patients diagnosed with AMD and assessed genetic polymorphisms of CFH (Y402H, rs1061170), ARMS2 (A69S, rs10490924), and we included studies evaluating CFH Y402H and ARMS2 A69S in relation to AMD susceptibility and extracted any available data on anti VEGF treatment response for narrative synthesis. The analytical series considered random effects models to perform the associated meta-analyses. Study heterogeneity was assessed using the I&#xb2; statistic measure as a standard assessment within the studies. The odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure.<br><br>RESULTS: The literature search obtained 1,420 studies from which 10 satisfied the eligibility criterion. The meta-analysis utilized eight studies. The association between CFH Y402H polymorphism and AMD risk indicated that the risk of AMD among risk allele carriers was OR 2.25 (95% CI: 1.27-4.00, p&#x2009;=&#x2009;0.006). ARMS2 polymorphisms demonstrated a strong genetic association to the risk of AMD with an OR of 4.05 (95% CI: 1.79-9.16, p&#x2009;<&#x2009;0.001). In the second meta-analysis evaluating genotype prevalence, the random-effects model showed an OR of 1.439 (95% CI: 0.929-2.231, p&#x2009;=&#x2009;0.103), suggesting a variable but moderate prevalence of high-risk genotypes among AMD patients (I&#xb2; = 95.7%, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: This meta-analysis confirms the significant association between CFH and ARMS2 polymorphisms and AMD susceptibility, emphasizing their role in disease pathogenesis. The findings highlight the potential for genetic screening in AMD risk assessment and personalized treatment strategies. However, substantial heterogeneity across studies underscores the need for standardized methodologies and further research into gene-environment interactions. Integrating genetic risk assessment into clinical practice may improve early detection and targeted interventions for AMD.}, }
@article {pmid41642581, year = {2026}, author = {Bellanda, V and Schulgit, MJ and Barbosa, GCS and Mohan, N and Arline, A and Bala, S and Kaelber, DC and Srivastava, SK and Sharma, S}, title = {Relative Risk of Neovascular Age-Related Macular Degeneration Following Cataract Surgery.}, journal = {JAMA ophthalmology}, volume = {144}, number = {3}, pages = {281-284}, pmid = {41642581}, issn = {2168-6173}, }
@article {pmid41642651, year = {2026}, author = {Lewis, TR and Castillo, CM and Phan, S and Shores, CR and Hayase, KK and Kim, KY and Ellisman, MH and Alekseev, O and Burns, ME and Arshavsky, VY}, title = {Adam9-deficient retinal pigment epithelium pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI196705}, pmid = {41642651}, issn = {1558-8238}, support = {K99 EY033763/EY/NEI NIH HHS/United States ; R00 EY033763/EY/NEI NIH HHS/United States ; }, abstract = {Vision begins in the outer segment compartment of photoreceptor cells, which is constantly renewed through the addition of membrane material at its base and ingestion of mature membranes at its tip by the retinal pigment epithelium (RPE). The close apposition of outer segments to the RPE is believed to be critical for maintaining this renewal process. Yet, in several retinal diseases, expansion of the subretinal space separating photoreceptors from the RPE does not immediately impact photoreceptor functionality. Here, we analyzed outer segment function and renewal in the Adam9 knockout mouse characterized by a major expansion of the subretinal space. Surprisingly, photoreceptor-RPE separation affected neither the sensitivity of photoreceptor light-responses nor the normal rate of outer segment renewal in this mouse prior to the onset of photoreceptor degeneration. The latter is achieved through the formation of elongated RPE "pseudopods" extending across the enlarged subretinal space to ingest outer segment tips. This work suggests that pseudopod formation may underlie the persistence of photoreceptor function in human diseases accompanied by photoreceptor-RPE separation, such as vitelliform macular dystrophy or age-related macular degeneration associated with subretinal drusenoid deposits.}, }
@article {pmid41643859, year = {2026}, author = {Castro-Fernández, DC and Cañizo-Outeriño, A and Cuartero-Martínez, A and Gil-Martinez, M and Mondelo-Garcia, C and González-Barcia, M and Álvarez-Barrios, A and Fernández-Ferreiro, A}, title = {A systematic review on age-related macular degeneration: New insights from multi-omics studies.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.02.001}, pmid = {41643859}, issn = {1879-3304}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries and a growing global health concern. The multifactorial nature of AMD calls for integrative multi-omics approaches. We summarize studies employing multi-omics in AMD. A comprehensive search in PubMed and Scopus databases identified 561 records with multi-omics criteria, of which duplicates, unrelated and unavailable articles were excluded, resulting in 33 reports. Quality was assessed following the Office of Health Assessment and Translation (OHAT) method, and data was synthesized through standardized evidence tables. Across the reviewed reports, multi-omics approaches were applied to non-clinical and clinical samples, including ocular and systemic fluids. Methodological trends included the widespread use of causal inference approaches (e.g., Mendelian randomization and Bayesian colocalization) and increasing adoption of spatial and single-cell resolution techniques. Converging molecular patterns consistently suggested inflammation, complement activation, angiogenesis, lipid dysregulation, and mitochondrial dysfunction as key processes underlying AMD. Integration of genetic risk with proteomic and metabolomic alterations, enabled the identification of candidate diagnostic and prognostic biomarkers such as carboxyethylpyrrole and PRMT3. Additionally, this review revealed opportunities for personalized medicine in AMD patient stratification, improvement of prediction models, and therapeutic personalization; however, heterogeneity was noted across studies, particularly regarding sample source (systemic vs. ocular), analytical platforms, integration strategies, and ancestry representation. Despite this variability, this review illustrates how integrating multiple omics layers provides a comprehensive and multidimensional understanding of AMD pathology, advancing research towards better diagnosis, prognosis, and therapeutics for these patients.}, }
@article {pmid41646332, year = {2026}, author = {Huang, J and Nittala, MG and Corradetti, G and Chung, YC and Quarta, A and Abbasgholizadeh, R and Soylu, C and Chujo, S and Velaga, SB and Sadda, SR}, title = {Spatial Distribution of Cuticular Drusen and its Association with Category-Specific Progression Risk in Intermediate AMD.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41646332}, issn = {2693-5015}, support = {R01 EY023164/EY/NEI NIH HHS/United States ; R01 EY030614/EY/NEI NIH HHS/United States ; }, abstract = {OBJECTIVES: To investigate the spatial distribution pattern of cuticular drusen using en face OCT and determine its relationship with 2-year progression of age-related macular degeneration (AMD).<br><br>METHODS: This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enrolled in the Amish Eye Study who completed two years of follow-up. Multimodal imaging, including volume spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three Early Treatment Diabetic Retinopathy Study (ETDRS) grid zones using ImageJ. K-means clustering analysis was used to categorize distribution patterns. Firth's penalized logistic regression evaluated association between cuticular drusen distribution categories and progression to late AMD at 2 years.<br><br>RESULTS: Cuticular drusen exhibited a concentric pattern within 6x6mm macular area. Mean (SD) density was highest in central zone (6.14 (3.89) count/mm2). Cluster analysis classified eyes into predominantly central (57.5%), predominantly peripheral (32.2%), and diffuse (10.3%) categories. Over 2 years, 5 eyes progressed to late AMD, 4 of which belonged to predominantly peripheral group. Firth logistic regression demonstrated that predominantly peripheral category had significantly increased risk of AMD progression compared to low-risk groups (predominantly central and diffuse), with an odds ratio of 7.2 (95% CI: 1.2-74.2, p=0.027).<br><br>CONCLUSIONS: The spatial distribution of cuticular drusen exhibits a concentric, centrally-weighted pattern. A predominantly peripheral distribution of cuticular drusen is significantly associated with progression to late AMD over two years. This quantifiable distribution pattern may serve as a novel high-risk biomarker for advanced AMD.}, }
@article {pmid41646411, year = {2026}, author = {Tom, E and Gao, F and Franco, CN and Wong, A and Kemmerer, N and Wang, Z and Xu, Q and Zhuang, Y and Du, SW and Palczewska, G and Palczewski, K and Budin, I and Shi, X and Bonilha, VL and Schöeneberg, J and Wahlin, KJ and Albrecht, LV and Skowronska-Krawczyk, D}, title = {Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41646411}, issn = {2693-5015}, support = {P30 EY025585/EY/NEI NIH HHS/United States ; F30 EY035146/EY/NEI NIH HHS/United States ; R01 EY009339/EY/NEI NIH HHS/United States ; P30 EY034070/EY/NEI NIH HHS/United States ; T32 GM008620/GM/NIGMS NIH HHS/United States ; T32 EY032448/EY/NEI NIH HHS/United States ; F30 EY033642/EY/NEI NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; U01 EY034594/EY/NEI NIH HHS/United States ; }, abstract = {The abundance and stoichiometry of membrane lipid species vary across a cell's lifespan and metabolic state. In the retinal pigment epithelium (RPE), age-related alterations in lipid composition contribute to vision loss and diseases such as age-related macular degeneration (AMD), yet the molecular drivers of these changes remain unclear. Here, we show that age-dependent remodeling of the composition and biophysical properties of the plasma membrane compromises membrane integrity and function. Remarkably, rather than undergoing cell death, affected cells activate a lysosome-dependent plasma membrane repair program to preserve barrier integrity. While this adaptive response may protect RPE structure under metabolic stress, it also drives spatially polarized release of lysosomal contents that potentially can contribute to extracellular matrix remodeling and sub-RPE deposit formation during aging and AMD. Finally, we demonstrate that supplementation with the direct product of the aging-associated lipid elongase ELOVL2 alleviates these phenotypes, providing direct evidence for a critical role of ELOVL2-mediated PUFA elongation in healthy aging. Taken together, our results propose a model in which age-dependent decline in PUFA elongation disrupts the balance between membrane flexibility and stability, initiating a compensatory cycle of membrane stress and repair.}, }
@article {pmid41646664, year = {2026}, author = {Wang, X and Hoshi, S and Kadomoto, S and Liu, R and Ip, M and Sarraf, D and Sadda, SR and Zhang, Y}, title = {Cuticular Drusen Associated Photoreceptor and RPE Optical Property Perturbation Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {41646664}, support = {R01 EY024378/EY/NEI NIH HHS/United States ; R01 EY034218/EY/NEI NIH HHS/United States ; }, abstract = {PURPOSE: To characterize microscopic alteration of photoreceptors and RPE surrounding cuticular drusen in age-related macular degeneration (AMD) using multimodal imaging, including high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO).<br><br>METHODS: Eyes with early to intermediate AMD and predominantly cuticular drusen underwent color fundus photography, infrared reflectance, fundus autofluorescence, optical coherence tomography (OCT), and AOSLO. Cuticular drusen were identified using multimodal imaging and classified into three OCT-defined phenotypes. Cone photoreceptor reflectivity was assessed on AOSLO. A subset of eyes underwent longitudinal AOSLO and OCT imaging.<br><br>RESULT: Nineteen eyes from 12 subjects aged 70.3 &#xb1; 5.8 years were studied. Six eyes had longitudinal follow-up imaging. A total of 3177 cuticular drusen were evaluated and classified into 3 types based on cross sectional OCT imaging. AOSLO revealed corresponding phenotype-dependent cone reflectivity alterations associated with the 3 types of cuticular drusen. Type 1: Maintained cone reflectivity overlying the drusen on a hyporeflective background. Type 2: Cone reflectivity loss overlying the cuticular drusen. Type 3: Cones are predominantly not visible over the cuticular drusen. Lesion diameters were 52.62 &#xb1; 9.38 &#x3bc;m (Type 1), 71.88 &#xb1; 12.39 &#x3bc;m (Type 2), and 124.72 &#xb1; 20.94 &#x3bc;m (Type 3). All lesions were accompanied by hypertransmission in the choroid on OCT. Longitudinal imaging showed that localized outer retinal reflectivity reduction on AOSLO preceded the detection of new cuticular drusen on OCT.<br><br>CONCLUSIONS: Cellular-resolution multimodal imaging demonstrates progressive, phenotype-specific disruption of the photoreceptor-RPE complex associated with cuticular drusen in AMD. Early AOSLO-detected reflectivity changes preceding OCT-visible lesions highlight the sensitivity of adaptive optics imaging for identifying early outer retinal alterations and for advancing understanding of the biogenesis of cuticular drusen.}, }
@article {pmid41646887, year = {2026}, author = {Fabian-Jessing, BK and Askou, AL and Jakobsen, TS and Adsersen, RL and Lindholm, AB and Køllner Bjerre, AK and Alsing, S and Bek, T and Aagaard, L and Corydon, TJ}, title = {AAV-mediated multiple gene therapy combining VEGFA-targeting miR-agshRNAs and PEDF for the suppression of choroidal neovascularization.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {1}, pages = {102833}, pmid = {41646887}, issn = {2162-2531}, abstract = {Common ophthalmic diseases, including age-related macular degeneration (AMD), generally have a complex pathogenesis involving multiple pathways and varying involvement of specific cell types. This provides a strong rationale for developing novel gene therapy platforms that allow cell-specific up- and down-regulation of multiple targets while contained within standard adeno-associated viral vectors (AAVs). Hence, we engineered a tunable expression cassette with two pri-miR-embedded, Ago2-dependent shRNAs (miR-agshRNAs) units enabling dual target silencing, and intron embedment allowing downstream protein expression. With this platform, we demonstrated additive Vegfa knockdown, concurrent silencing of Vegfa and mTOR, and simultaneous expression of pigment epithelium-derived factor (PEDF) from a single promoter. Following the subretinal injection of AAV5 vectors encoding Vegfa-targeting miR-agshRNAs and PEDF into the murine retina, profound Vegfa suppression and strong PEDF expression were observed. Notably, laser-induced choroidal neovascularization (CNV) was significantly reduced in the therapeutic groups, with the multi-targeting vector achieving the highest level of CNV suppression. Collectively, our data demonstrated robust anti-angiogenic effects of multiple gene therapies, suggesting a "one-and-done" AAV-based delivery of cross-species anti-VEGFA RNAi therapeutics together with PEDF as a valuable tool for the management of neovascular AMD (nAMD) and other complex neovascular ocular diseases.}, }
@article {pmid41648145, year = {2026}, author = {Patel, MK and Piedade, W and Famulski, JK}, title = {Cdhr1a and pcdh15b link photoreceptor outer segments with inner segment calyceal processes revealing a potential mechanism for cone-rod dystrophy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41648145}, issn = {2692-8205}, support = {P20 GM103436/GM/NIGMS NIH HHS/United States ; }, abstract = {Cone rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell photoreceptor degeneration and subsequently of rod photoreceptors. Mutations in CDHR1, a photoreceptor specific cadherin have been found to be associated with the incidence of cone-rod dystrophy and recapitulated in mouse CDHR1 knockouts. However, the molecular function of CDHR1 remains unknown. CDHR1 has been shown to localize at the leading edge of murine rod nascent outer segment (OS) making junctions to an unknown partner in the inner segment. Using Structured Illumination Microscopy (SIM), we observed that the localization of zebrafish cdhr1a extends from basal nascent OS discs above the periciliary ridge of the inner segment to a considerable length along the OS, akin to calyceal process (CPs). When labeling the CPs using pcdh15b, a CP specific cadherin, we observed that cdhr1a at the leading edge of OS juxtaposes with pcdh15b in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, and various rodent PRCs indicating conservation. Importantly, using immunoprecipitation and K652 cell aggregation assays we demonstrate that pcdh15b and cdhr1a can interact and potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a zebrafish cdhr1a mutant line (cdhr1a [fs*146]) and analyzed CRD progression at high temporal resolution. Homozygous cdhr1a [fs*146] mutants begin to exhibit minor cone OS morphology defects starting at 15 dpf (days post fertilization) and severe OS disruption and cell loss by 3 months. Rod OS defects were delayed until 3-6 months. Furthermore, we show that loss of cdhr1a function leads to disorganization and shortening of CPs coinciding with cone outer OS defects which is significantly exacerbated when combined with the loss of pcdh15b. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs to maintain proper OS homeostasis thus revealing a potential novel mechanism for CRD.}, }
@article {pmid41649508, year = {2026}, author = {Muranyi, DS and Molling, J and Hammer, U and Habermann, A and Lehmann, G and Luci, E and Buchwald, C and Hammer, T}, title = {[Real-life data of the IVI interval after switching to faricimab therapy].}, journal = {Die Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41649508}, issn = {2731-7218}, abstract = {BACKGROUND: For neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents currently represents the standard of care. Both treatment intervals and the choice of the optimal agent are critical determinants of therapeutic outcomes.<br><br>OBJECTIVE: This study evaluated the effect of switching from established anti-VEGF agents (ranibizumab, bevacizumab or aflibercept) to faricimab on injection intervals in patients with nAMD or DME.<br><br>MATERIAL AND METHODS: Data were collected in a&#xa0;routine outpatient ophthalmology practice. Inclusion criteria were: (I)&#xa0;treatment according to a&#xa0;treat-and-extend protocol, (II)&#xa0;at least six intravitreal injections prior to switching to faricimab and (III)&#xa0;at least three subsequent faricimab injections. To assess disease-specific effects, patients were stratified into nAMD and DME subgroups.<br><br>RESULTS: A&#xa0;total of 86&#xa0;patients with a&#xa0;mean of 37&#xa0;prior injections were included. The mean injection interval before switching to faricimab was 44&#xa0;days. In the nAMD subgroup (n&#x202f;=&#x2009;74, mean age 72&#xa0;years), the interval significantly increased from 46&#xa0;to 53&#xa0;days (mean difference 7.45 days, p&#x202f;<&#x2009;0.05). In the DME subgroup (n&#x202f;=&#x2009;12, mean age 65&#xa0;years), the interval significantly increased from 42&#xa0;to 57&#xa0;days (mean difference 15.25 days, p&#x202f;<&#x2009;0.05). The effect size was moderate (Cohen's&#xa0;d&#x202f;=&#x2009;0.56) with high statistical power (99.93%).<br><br>CONCLUSION: Switching to faricimab resulted in a&#xa0;significant extension of treatment intervals in both indications, with patients with DME deriving the greatest benefit. Limitations include the small sample size and potential selection bias. These findings suggest an improved benefit-risk profile through reduced injection frequency. Additional real-world data and meta-analyses may help identify biomarkers to further individualize anti-VEGF therapy in the future.}, }
@article {pmid41650065, year = {2026}, author = {Kong, H and Li, J and Lou, J and Zhang, Y and Li, M and Chen, Y and Wang, Y and Tao, T}, title = {A 2-step, 2-sample Mendelian randomization study of gut microbiota, blood metabolites and dry age-related macular degeneration.}, journal = {Medicine}, volume = {105}, number = {6}, pages = {e47527}, pmid = {41650065}, issn = {1536-5964}, support = {Y202148025//Scientific Research Fund of Zhejiang Provincial Education Department/ ; Y202456684//Scientific Research Fund of Zhejiang Provincial Education Department/ ; 2023RC081//Medical Scientific Reasearch Foundation of Zhejiang Province/ ; 2025708925//Medical Scientific Reasearch Foundation of Zhejiang Province/ ; 2024RC-QN-02//Ningbo Health Youth Technical Backbone Talent Development Program/ ; 2023HMJQ25//Zhu Xiu Shan Talent Project of Ningbo No.2 Hospital/ ; }, mesh = {Humans ; Mendelian Randomization Analysis/methods ; *Gastrointestinal Microbiome/genetics ; Genome-Wide Association Study ; *Macular Degeneration/genetics/blood ; Aged ; *Geographic Atrophy/genetics/blood ; }, abstract = {Dry age-related macular degeneration (dAMD) is the leading cause of blindness among elderly people in developed countries. The main objective of this study is to investigate the causal relationship between gut microbiota (GM), blood metabolites, and dAMD among European participants. Based on the genome-wide association analysis database, double sample Mendelian randomization (MR) analysis was performed on GM, blood metabolites, and dAMD. The inverse-variance weighted method is used to estimate the causal relationship between GM, blood metabolites, and dAMD, while multiple methods are employed to eliminate pleiotropy and heterogeneity. A 2-step MR analysis quantitatively assessed the effect of metabolite-mediated GM on dAMD. In MR analysis, 15 GM were found to be associated with increased or decreased risk of dAMD, and 18 blood metabolites were found to be associated with increased or decreased risk of dAMD. Our research also found that the potential association between GM and dAMD may be mediated by blood metabolite levels, specifically, ADpSGEGDFXAEGGGVR levels accounted for 38.9% of the causal pathway from genus Parasutterella to dAMD. Our research findings indicate that certain GM and blood metabolites can affect the onset of dAMD, and increasing the abundance of genus Parasottella can increase the risk of dAMD through the mediation of ADpSGEGDFXAEGGGVR levels.}, }
@article {pmid41650530, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Comparative effectiveness and safety landscape of anti-VEGF therapies for neovascular age-related macular degeneration: Insights from a systematic review and network meta-analysis.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {196}, number = {}, pages = {118881}, doi = {10.1016/j.biopha.2025.118881}, pmid = {41650530}, issn = {1950-6007}, mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage/therapeutic use ; Network Meta-Analysis as Topic ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Treatment Outcome ; Ranibizumab/adverse effects/administration &amp; dosage ; Visual Acuity/drug effects ; Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; Randomized Controlled Trials as Topic ; Receptors, Vascular Endothelial Growth Factor ; *Macular Degeneration/drug therapy ; Bevacizumab/adverse effects/administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; }, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.<br><br>METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to September 2025 identified randomized controlled trials (RCTs) and observational studies comparing at least two anti-VEGF agents in nAMD. Eligible studies reported outcomes of best-corrected visual acuity (BCVA) change, visual gain &#x2265;&#x202f;15 letters, mortality, or arteriothrombotic events. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. A frequentist network meta-analysis estimated mean differences (MD) and odds ratios (OR) with 95&#x202f;% confidence interval (CI). The protocol was registered in PROSPERO (CRD42025631298).<br><br>RESULTS: Sixteen studies involving 6758 participants (follow-up 3-24 months) met the inclusion criteria. For BCVA improvement, Aflibercept had the highest surface under the cumulative ranking curve (SUCRA) ranking (0.80), although all agents showed similar mean differences that were not statistically significant: aflibercept (MD 0.80; 95&#x202f;% CI -1.20-2.80), Ranibizumab (0.64; -1.87-3.15), Bevacizumab (0.60; -2.02-3.22), Faricimab (2.20; -0.69-5.09), and Brolucizumab (4.20; -5.97-14.36). The larger point estimate for Brolucizumab reflects imprecision rather than superior visual efficacy. Mortality was lowest with Aflibercept (risk ratio (RR) 0.76; 95% CI 0.41-1.55). For arteriothrombotic events, no statistically significant differences were observed between anti-VEGF agents. Comparisons between Aflibercept and Bevacizumab (RR 1.11; 95% CI 0.60-2.07), aflibercept and Ranibizumab (RR 0.77; 95% CI 0.49-1.21), and Bevacizumab and Ranibizumab (RR 0.88; 95% CI 0.60-1.30) showed wide confidence intervals, reflecting substantial imprecision. Certainty of evidence (GRADE) ranged from moderate to low.<br><br>CONCLUSION: All anti-VEGF agents stabilize or improve vision in nAMD. Aflibercept may provide the most favorable efficacy-safety balance, Faricimab offers promising durability, and Brolucizumab demonstrates large visual gains with potential safety concerns. Further head-to-head and long-term real-world studies are needed to optimize individualized treatment strategies.}, }
@article {pmid41653377, year = {2026}, author = {Manders, EA and van Der Wel, V and Schlingemann, R and Hollak, CEM and de Visser, SJ}, title = {Repurposing biosimilars, rethinking costs: a framework for sustainable drug pricing for repurposed bevacizumab for intravitreal injections.}, journal = {The European journal of health economics : HEPAC : health economics in prevention and care}, volume = {}, number = {}, pages = {}, pmid = {41653377}, issn = {1618-7601}, abstract = {Bevacizumab, originally developed by Genentech under the brand name Avastin[®] as an anti-cancer drug, has gained widespread off-label use in ophthalmology due to its similar mechanism of action to other anti-VEGF treatments and its significantly lower cost compared to available on label alternatives for ophthalmological indications. While off-label bevacizumab has been standard in clinical practice for over a decade, recently, a repurposed formulation (brand name: Lytenava[®], Outlook Therapeutics Ltd), developed specifically for vascular retinal conditions, received marketing approval from the European Medicines Agency. This raises questions about what the price for a repurposed formulation should reasonably be, reflecting the efforts to obtain regulatory approval. This paper examines potential cost-based-plus pricing for such a repurposed formulation of bevacizumab using a novel pricing framework across four scenarios. By evaluating the pricing structure through an analysis of critical cost components, including, among others, research and development expenditures, manufacturing costs, and cost-of-capital, the study proposes a price range of €73 to €177 per injection. The explicit breakdown of these cost components provides valuable insights into the economic structure of repurposed biosimilars like bevacizumab, emphasizing how a cost-based-plus pricing model can support more transparent and informed negotiations between pharmaceutical companies and healthcare payers. Ultimately, this approach contributes to the development of pricing strategies that balance affordability for healthcare systems with sustainable returns for manufacturers while fostering the broader development of repurposed treatments. The findings of this paper aim to advance the dialogue on equitable pricing for repurposed therapies.}, }
@article {pmid41654128, year = {2026}, author = {Zhao, J and Montenegro, D and Cheng, S and Kim, HJ and Sparrow, JR}, title = {More insights from Abca4[-/-] mouse models of recessive Stargardt disease.}, journal = {The Journal of biological chemistry}, volume = {302}, number = {3}, pages = {111261}, pmid = {41654128}, issn = {1083-351X}, abstract = {Mutations in the ABC transporter ABCA4 (ABC, subfamily A, member 4) are responsible for recessive Stargardt disease 1 (STGD1), a juvenile form of macular degeneration. In preclinical and clinical studies, it has been shown that deficiency in ABCA4 leads to accelerated formation of the toxic bisretinoid fluorophores that form as the product of nonenzymatic reactions of retinaldehyde with phosphatidylethanolamine (2:1 ratio). Here, by comparing photoreceptor cell viability in albino versus agouti Abca4[-/-] mice and by dark-rearing albino Abca4[-/-] mice, we show that photoreceptor cell degeneration in the Abca4[-/-] mouse is at least partially driven by light. Elevated vitamin A in chow and a high-fat diet reduced photoreceptor cell viability. Phosphatidylethanolamine and N-retinylidiene-phosphatidylethanolamine were reduced, as were steady-state levels of retinoid in light-adapted eyes. As expected, bisretinoids, measured as short-wavelength fundus autofluorescence (AF), were elevated in both pigmented and albino Abca4[-/-] mice. Hyperautofluorescent puncta in fundus AF images colocalized in spectral domain optical coherence tomography scans with aberrant hyper-reflectivity that occupied photoreceptor-attributable bands and extended anteriorly to interrupt the ellipsoid zone and external limiting membrane. In epifluorescence images of Abca4[-/-] retina, retinal pigment epithelium was autofluorescent because of bisretinoid accumulation. Occasionally, AF lesions extended anteriorly from the retinal pigment epithelium to a horizontal band exhibiting less pronounced AF at the level of photoreceptor inner and outer segments. These lesions did not colocalize with IBA1 (ionized calcium-binding adaptor molecule)-labeled microglia. The hyperautofluorescent foci that presented as hyper-reflective lesions in spectral domain optical coherence tomography form in photoreceptor inner segments and are reminiscent of fundus flecks in STGD1.}, }
@article {pmid41654857, year = {2026}, author = {Forte, P and Ferro Desideri, L and Nassisi, M and Milanesi, F and Feo, A and Bagnasco, I and Iglesia, SM and Forte, G and Scandella, D and Roccatagliata, F and Fontana, V and Eandi, CM and Iester, M and Jolly, JK and Zinkernagel, MS and Viola, F and Nicolò, M}, title = {Drusen-specific dark adaptation profiles in intermediate age-related macular degeneration.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {34}, pmid = {41654857}, issn = {2056-9920}, abstract = {AIMS: To investigate the influence of macular drusen phenotypes on dark adaptation (DA) in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This cross-sectional, multicentric study enrolled 57 eyes of 43 iAMD patients. Drusen were subclassified as cuticular, soft, reticular pseudodrusen (RPD), or combined soft&#x2009;+&#x2009;RPD based on multimodal imaging. Dark adaptometry (AdaptDx; 20-minute test-time) assessed DA function through rod intercept time (RIT), last measured log sensitivity (LMLS; primary outcome) and area under the DA curve (AUDAC; secondary outcome). OCT volumes (30&#xb0;x20&#xb0; field) were analyzed using an AI-enhanced algorithm providing a quantification of chorioretinal layers and pigment epithelium detachments (PED) volumes. Multivariable tobit and linear regression analyzed associations between drusen phenotypes and DA outcomes.<br><br>RESULTS: Drusen phenotype distribution was: cuticular 13 eyes (22.8%), soft 13 eyes (22.8%), isolated RPD 21 eyes (36.8%), and combined soft&#x2009;+&#x2009;RPD 10 eyes (17.5%). Nearly all eyes reaching RIT within the 20-minute test ceiling (10 of 11 eyes) had cuticular drusen, which showed preserved rod function (LMLS: 2.9&#x2009;&#xb1;&#x2009;0.2 log-units; AUDAC: 10.3&#x2009;&#xb1;&#x2009;3.2 log-units&#xb7;min; RIT: 14.9&#x2009;&#xb1;&#x2009;4.5 min) despite presenting the highest PED volumes (301&#x2009;&#xb1;&#x2009;152 nL). Conversely, isolated RPD demonstrated most severe dysfunction (LMLS: 1.7&#x2009;&#xb1;&#x2009;0.3; AUDAC: 23.7&#x2009;&#xb1;&#x2009;5.39). Soft drusen showed intermediate impairment (LMLS: 2.2&#x2009;&#xb1;&#x2009;0.2; AUDAC: 18.4&#x2009;&#xb1;&#x2009;2.4). Drusen phenotype was the most significant predictor of DA outcomes in both regression models (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Dark adaptometry reveals distinct patterns of DA impairment across drusen phenotypes, necessitating precise drusen classification when dark adaptometry serves as a functional endpoint in iAMD clinical trials. Future studies should employ extended test protocols (40-minute ceiling) to confirm these findings.<br><br>CLINICAL TRIAL NUMBER: Not applicable.}, }
@article {pmid41655020, year = {2026}, author = {Gardner, A and Wang, S and Daniels, A and Li, D and Wu, C and Lin, L and Hong, C and Zhao, SR and Born, RT and Kruczek, K and Weist, G and Barrio Real, L and Wicks, J and Nayal, M and Carter, A and Ott, C and Haurigot, V and Cepko, CL}, title = {AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.02.005}, pmid = {41655020}, issn = {1525-0024}, abstract = {Dry age-related macular degeneration is the most frequent cause of visual impairment in individuals over age 50 in developed countries. It is characterized by deposits of oxidized proteins and lipids and results in progressive loss of high-acuity vision. One major risk factor is smoking, which causes oxidative stress in many tissues, including the eye. We previously showed that an adeno-associated viral vector expressing human NRF2 (AAV8/Best1-NRF2), a transcription factor that regulates responses to oxidative damage, slowed degeneration in mouse models of another blinding disorder, retinitis pigmentosa, which also includes oxidative stress. Here, our AAV8/Best1-NRF2 vector was tested in a model of oxidative stress wherein sodium iodate was injected systemically, as this is often used to model dry age-related macular degeneration. Sodium iodate causes acute oxidative damage to the retinal pigment epithelial cells, which provide support to the photoreceptor cells. In addition, this toxin ultimately leads to photoreceptor death. Subretinal injection of AAV8/Best1-NRF2 led to protection of the retinal pigment epithelium and photoreceptors, as well as preservation of visual function, in rat and mouse sodium iodate models. AAV8/Best1-NRF2 may serve as an effective gene-agnostic therapy for diseases with oxidative stress, including dry age-related macular degeneration.}, }
@article {pmid41655333, year = {2026}, author = {Guo, R and Huang, Y and Zhang, X and Qin, M and Sun, H and Jin, X and Xu, J and Kang, Y and Li, K and Zhou, Y and Nan, K and Zheng, Y and Liu, S}, title = {Long-term suppression of retinal degeneration with anti-VEGF agents-loaded hollow mesoporous silica nanoparticles.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {262}, number = {}, pages = {115527}, doi = {10.1016/j.colsurfb.2026.115527}, pmid = {41655333}, issn = {1873-4367}, mesh = {*Silicon Dioxide/chemistry ; *Nanoparticles/chemistry/ultrastructure ; Animals ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Porosity ; Receptors, Vascular Endothelial Growth Factor ; Humans ; *Ranibizumab/pharmacology/chemistry/administration &amp; dosage ; *Recombinant Fusion Proteins/pharmacology/chemistry/administration &amp; dosage ; Cell Proliferation/drug effects ; Choroidal Neovascularization/drug therapy/pathology ; Cell Movement/drug effects ; Particle Size ; *Retinal Degeneration/drug therapy/pathology ; *Angiogenesis Inhibitors/pharmacology/chemistry ; Mice ; Intravitreal Injections ; Mice, Inbred C57BL ; }, abstract = {Age-related macular degeneration (AMD) that leads to degeneration of the overlying photoreceptor in the macula and consequent loss of central vision is the leading cause of irreversible blindness in elderly population. Since vascular endothelial growth factor (VEGF) is pivotal for stimulating neovascularization, monthly intravitreal (IVT) injections of anti-VEGF agents have been used for eliminating neovascularization. However, repeated monthly IVT injections could cause side effects and serious complications. Herein, we report the development of two kinds of anti-VEGF agents (Ranibizumab (Ran) and Aflibercept (Afl))-loaded hollow mesoporous silica nanoparticles for effective treatment of AMD. The designed nanoparticles show no toxicity for both in vitro and in vivo, and could significantly inhibit VEGF-induced proliferation and cell migration. Long-term in vivo experiments in the laser photocoagulation induced choroidal neovascularization (CNV) model for wet AMD show that these nanoparticles effectively inhibit VEGF-induced neovascularization leakage and formation at least 8 weeks upon one IVT injection and therefore are a promising treatment strategy for AMD.}, }
@article {pmid41655655, year = {2026}, author = {Liu, H and Sun, X and Liu, J and Chang, Z}, title = {Exploring the causal relationship between osteoporosis and age-related macular degeneration: Evidence from observational studies and mendelian randomization.}, journal = {Experimental gerontology}, volume = {215}, number = {}, pages = {113060}, doi = {10.1016/j.exger.2026.113060}, pmid = {41655655}, issn = {1873-6815}, mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics/epidemiology/etiology ; *Osteoporosis/complications/genetics/epidemiology ; Observational Studies as Topic ; Female ; Genome-Wide Association Study ; Risk Factors ; Male ; Aged ; Genetic Predisposition to Disease ; }, abstract = {OBJECTIVE: This study aimed to systematically investigate the association between osteoporosis (OP) and age-related macular degeneration (AMD), including its subtypes, by integrating observational evidence with causal inference approaches.<br><br>METHODS: We first conducted a systematic literature search and meta-analysis of relevant observational studies up to August 2025 to evaluate the observational association between OP and AMD. Subsequently, using summary data from genome-wide association studies, we performed a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal relationship between OP and four AMD subtypes. The primary causal estimates were derived using the inverse variance weighted method, and multiple sensitivity analyses were conducted to verify the robustness of the results.<br><br>RESULTS: The meta-analysis, which included three studies, indicated that osteoporosis increases the risk of AMD in women (OR: 1.46; 95% CI: 1.12-1.91, P&#xa0;=&#xa0;0.0049). Under Bonferroni correction, the MR analysis showed that genetically predicted osteoporosis significantly increased the risk of dry AMD (IVW OR: 1.26; 95% CI: 1.10-1.44, P&#xa0;=&#xa0;0.00087. Bayesian weighted MR OR: 1.25; 95% CI: 1.05-1.49, P&#xa0;=&#xa0;0.01162.), while no significant causal effects were observed for wet, early, or late AMD. Reverse MR analysis did not indicate any causal effect of AMD on OP. No significant horizontal pleiotropy or heterogeneity was detected in any of the analyses.<br><br>CONCLUSION: Osteoporosis may increase the risk of AMD in women. The MR analysis provides some genetic evidence supporting a potential causal link between osteoporosis and dry AMD. In clinical practice, patients with osteoporosis-particularly elderly women-should be considered at potential high risk for dry AMD, and early fundus screening may facilitate the early detection and intervention of dry AMD.}, }
@article {pmid41655724, year = {2026}, author = {Song, SY and Le, DD and Lee, M and Cho, SS and Park, DH}, title = {Camellia japonica hyperoside exhibits anti-age-related macular degeneration effects in an ARPE-19 cell model by inhibiting apoptosis via JNK-Nrf2/HO-1 activation.}, journal = {Journal of ethnopharmacology}, volume = {362}, number = {}, pages = {121305}, doi = {10.1016/j.jep.2026.121305}, pmid = {41655724}, issn = {1872-7573}, mesh = {Apoptosis/drug effects ; Humans ; Heme Oxygenase-1/metabolism ; NF-E2-Related Factor 2/metabolism ; *Camellia/chemistry ; Cell Line ; *Quercetin/pharmacology/analogs &amp; derivatives/isolation &amp; purification ; Plant Extracts/pharmacology ; Antioxidants/pharmacology/isolation &amp; purification ; Plant Leaves ; Retinal Pigment Epithelium/drug effects ; }, abstract = {Camellia japonica is recognized for its edible and therapeutic value in East Asia, and has anti-inflammatory, antioxidative, and antiasthmatic properties. However, the active compound and the modes of action are unclear.<br><br>AIM OF THE STUDY: To evaluate the anti-AMD effect of hyperoside isolated from the leaves and twigs of Camellia japonica and to explore the underlying mechanisms using an ARPE-19 AMD cell model.<br><br>MATERIAL AND METHODS: The hyperoside content in the extracts was evaluated using feature-based molecular network and UHPLC-MS/MS system. Network pharmacology was used to predict the interactions of hyperoside with AMD-related signaling pathways and the underlying mechanisms. For in vitro evaluation of the anti-AMD effects, ARPE-19&#xa0;cells were divided into six treatment groups: CON, no treatment; A2E, AMD induction using 30&#xa0;&#x3bc;M A2E and 20&#xa0;mW/cm[2] blue light treatment; Lutein, treatment with 25&#xa0;&#x3bc;M lutein as a positive control; and three Hyperoside groups, treated with 37.5, 75, or 150&#xa0;&#x3bc;M hyperoside. The antiapoptotic effect of hyperoside was evaluated using flow cytometry and TUNEL assays, and the intrinsic apoptotic pathway proteins (Bcl-xL, Bad, and Bim) were analyzed via western blotting. The interactions of hyperoside with JNK and p38 MAPKs were determined using western blotting, and molecular docking. The antioxidative effect of hyperoside was measured via DPPH and ABTS radical scavenging assays; Nrf2/HO-1 activation and SOD-1 stimulation were analyzed using western blotting and immunofluorescence assay. The anticarbonyl effect (4-HNE and MDA) was measured using western blotting.<br><br>RESULTS: Hyperoside was nontoxic to ARPE-19&#xa0;cells up to 150&#xa0;&#x3bc;M. It dose-dependently decreased A2E and blue light-induced AMD in ARPE-19&#xa0;cells by upregulating the antiapoptotic Bcl-2 protein (Bcl-xL) and downregulating the proapoptotic Bcl-2 proteins (Bad and Bim). Hyperoside dephosphorylated JNK and p38 MAPKs in a dose-dependent manner, eradicated DPPH and ABTS radicals, and activated Nrf2/HO-1 and SOD-1. It also decreased the levels of 4-HNE and MDA.<br><br>CONCLUSION: We conclude that C. japonica hyperoside could be a promising anti-AMD drug.}, }
@article {pmid41655766, year = {2026}, author = {Ambresin, A and Chaudhary, V and Gale, R and Koh, AHC and London, NJS and Patel, PJ and Tan, ACS and Hill, L and Kotecha, A and Margaron, P and Singer, M and , }, title = {Potential 20-Week Faricimab Dosing in Wet Age-Related Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.001}, pmid = {41655766}, issn = {2468-6530}, }
@article {pmid41655974, year = {2026}, author = {Gillies, M and Hashimoto, Y and Nazari, R and Arnold, J and Wang, B and Barry, R and Ferrier, R and Game, J and Barthelmes, D}, title = {Twelve-Month Real-World Outcomes of Faricimab for Treatment-Naive Neovascular AMD in Australia.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.70072}, pmid = {41655974}, issn = {1442-9071}, support = {1195021//National Health and Medical Research Council/ ; //Bayer/ ; //Roche/ ; //Macular Disease Foundation Australia/ ; }, abstract = {BACKGROUND: To provide insights into the effectiveness and safety of faricimab for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A retrospective cohort study using a prospectively-designed registry. Treatment-na&#xef;ve eyes with nAMD in Australia starting treatment with faricimab between Jan 2023-Sep 2024 were included. Controls were treatment-na&#xef;ve eyes starting with aflibercept 2&#x2009;mg before 2022. Visual acuity (VA), macular neovascularisation activity, time to first inactivity, number of injections, injection intervals and number of visits at 12&#x2009;months were investigated. Eyes treated with faricimab versus aflibercept 2&#x2009;mg were compared using overlap weighting. The main outcome measure was the 12-month VA change.<br><br>RESULTS: Twenty-three practitioners treated 160 eyes with a 4-letter gain in VA (mean, 61.5-65.5 letters) and 48% attaining a dosing interval of &#x2265;&#x2009;12&#x2009;weeks, although 22% were still treated at <&#x2009;8 weekly intervals. The small proportion (6.9%) of eyes switching to another agent had improved vision but were mostly active when switching off faricimab. Eyes received 7.2 injections (mean) at 7.4 visits (mean), receiving treatment at 98% of visits indicating a strongly proactive treatment regimen. Most (71%) lesions became inactive by 12&#x2009;months with a mean time to inactivation of 10.3&#x2009;weeks. Eyes starting faricimab had a significantly higher inactivation rate with more eyes reaching the last injection interval of &#x2265;&#x2009;12&#x2009;weeks than those starting aflibercept 2&#x2009;mg.<br><br>CONCLUSIONS: These findings indicate that faricimab is safe and effective for treatment-naive eyes with nAMD. Faricimab had a stronger effect on nAMD lesion activity than aflibercept 2&#x2009;mg.}, }
@article {pmid41658256, year = {2025}, author = {Candan, O and Uney, G and Hazirolan, D and Unlu, N and Acar, MA}, title = {A 5-Year Analysis of Optical Coherence Tomography Biomarkers in The Visual Outcomes of an As-Needed Treatment Algorithm for Neovascular Age-Related Macular Degeneration.}, journal = {Beyoglu eye journal}, volume = {10}, number = {4}, pages = {226-234}, pmid = {41658256}, issn = {2587-0394}, abstract = {OBJECTIVES: This study aimed to predict the visual course of patients with neovascular age-related macular degeneration by analyzing data from a 5-year observational study and to identify biomarkers that have an impact on visual prognosis.<br><br>METHODS: The present study comprised a total of 104 patients who received the PRN treatment regimen between March 2015 and March 2021. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. Multinomial logistic regression models were used to determine predictors of BCVA at 12, 24, and 60 months.<br><br>RESULTS: Better BCVA and thicker macula at baseline, decreased BCVA at month 3, and persistence of IRF at month 3 were correlated with decreased BCVA at month 12 (all p<0.05). At 24 month, a decline in BCVA was associated with specific baseline characteristics, including better BCVA, absence of pigment epithelial detachment (PED), and presence of intraretinal cystoid fluid (IRF) (all p<0.01). Similarly, decreased BCVA and thicker macula in the 3rd month were associated with worse BCVA. At the 60-month visit, better baseline BCVA, absence of PED, presence of IRF at baseline, and persistence of IRF at month 3 were associated with a reduction in BCVA (all p<0.05). The visual prognosis had no correlation with the number of injections.<br><br>CONCLUSION: This 5-year real-life study identified prognostic markers that cause a decline in visual acuity. The use of these markers has the potential to be valuable in preserving visual gain, irrespective of the number of injections.}, }
@article {pmid41658600, year = {2026}, author = {Zhang, X and Wang, Z and Li, Z and Zhan, Z}, title = {The mechanisms, epidemiology, and clinical implications of thyroid hormones and age-related macular degeneration: a narrative review.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1765758}, pmid = {41658600}, issn = {2296-858X}, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults. Thyroid hormones (THs) are essential endocrine regulators of development and metabolic homeostasis, and increasing evidence suggests that TH signaling is involved in retinal physiology and AMD pathogenesis. Experimental studies have demonstrated that excessive TH signaling exacerbates oxidative stress, mitochondrial dysfunction, and apoptosis in retinal pigment epithelium (RPE) cells and photoreceptors, whereas inhibition of TH signaling confers retinal protection in animal models of dry AMD. Genetic evidence from Mendelian randomization analyses further indicates that genetically predicted higher free thyroxine (FT4), per one standard deviation increase, is associated with an increased risk of AMD (OR 1.19, 95% CI 1.06-1.33), while no causal association has been established for thyroid-stimulating hormone (TSH). Consistently, large population-based cohort studies, including the Rotterdam Study, have reported a positive association between circulating FT4 levels and the incidence of AMD. In this narrative review, we summarize and critically evaluate recent advances from basic experimental, genetic, and clinical studies on the relationship between thyroid hormones and AMD, discuss potential biological mechanisms underlying this association, and highlight current limitations and future research directions.}, }
@article {pmid41658807, year = {2026}, author = {Jayadev, C and Talwar, D and Bhende, M and Narayanan, R and Gupta, V and Chakraborty, D and Deka, S and Manayath, G and Banker, A}, title = {Expert Opinion on the First-Line Management of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in India: The Role of Faricimab.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e100779}, pmid = {41658807}, issn = {2168-8184}, abstract = {This expert opinion article summarizes deliberations from a focused panel discussion involving nine retina specialists on the clinical utility of faricimab in managing neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). The discussion explored evolving understanding of the multifactorial disease mechanisms, including pathways beyond vascular endothelial growth factor-A, and the rationale for dual inhibition strategies. Experts shared their clinical perspectives on faricimab use in diverse patient profiles, treatment sequencing, and individualized dosing approaches to achieve durable disease control. Practical considerations around early initiation, optimization of treatment intervals, and real-world applicability were also discussed. The insights highlight expert-derived strategies for integrating faricimab as a first-line treatment into clinical practice, emphasizing its role in achieving vascular stability and the improved durability of treatment response. Overall, the panel concluded that faricimab represents a clinically valuable first-line therapeutic option for nAMD and DME, enabling individualized, durable disease control in routine practice.}, }
@article {pmid41660488, year = {2026}, author = {Blair, JPM and Guymer, RH and Krzemińska-Ściga, A and De Zanet, S and Ciller, C and Apostolopoulos, S and Wu, Z}, title = {Geographic Atrophy Structure-Function Relationships Based on Loss of OCT Outer Retinal Bands and Fundus Autofluorescence.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101035}, pmid = {41660488}, issn = {2666-9145}, abstract = {PURPOSE: To examine the association between the loss of the OCT outer retinal bands and deep visual sensitivity losses quantified by defect-mapping microperimetry (DMP).<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: Fifty individuals with geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: All participants underwent DMP testing-a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single presentations of 10 decibel stimuli-with 208 locations sampled within the central 8&#xb0; radius region. Participants also underwent OCT and fundus autofluorescence (FAF) imaging. OCT scans were automatically segmented to detect regions of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss, and FAF images were manually annotated for GA. The extent of these parameters in the central 8&#xb0; radius region where DMP testing was performed, and at each individual test location, was derived through image coregistration for evaluating structure-function associations.<br><br>MAIN OUTCOME MEASURES: Global structure-function correlation between the proportion of locations missed on DMP testing and the extent of loss of the structural parameters based on Spearman rank correlation coefficient (&#x3c1;), and spatial agreement between the presence of structural changes and missed stimuli on DMP testing at individual test locations based on the Dice similarity coefficient (DSC).<br><br>RESULTS: There were strong global structure-function correlations based on loss of the OCT outer retinal bands (&#x3c1; = 0.85-0.86), similar to what was seen with FAF-defined GA (&#x3c1; = 0.89; P &#x2265; 0.326). However, the spatial agreement between OCT-defined EZ and ELM loss with missed stimuli on DMP testing (DSC = 0.64 for both) was higher than that seen with RPE loss (DSC = 0.60) and FAF-defined GA (DSC = 0.62; P = 0.008 for both), but the structure-function spatial agreement was similar between RPE loss and FAF-defined GA (P = 0.152).<br><br>CONCLUSIONS: Spatial agreement with pointwise deep visual sensitivity losses was comparable based on OCT-defined RPE loss and FAF-defined GA, but higher based on EZ and ELM loss. These findings confirm the expected functional relevance of these automatically derived OCT-defined parameters and support their utility as tools for monitoring GA progression.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41661268, year = {2026}, author = {Schwämmle, ME and Blatz, KM and Bucher, F}, title = {[Extracellular vesicles and their potential in ophthalmology].}, journal = {Die Ophthalmologie}, volume = {123}, number = {3}, pages = {192-200}, pmid = {41661268}, issn = {2731-7218}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Eye Diseases/diagnosis/metabolism ; Biomarkers/analysis/metabolism ; *Ophthalmology/trends/methods ; }, abstract = {BACKGROUND: Extracellular vesicles (EV), especially small EV and microvesicles, are considered promising biomarkers as they transport molecular information from their tissue of origin and can thus reflect pathological processes. They are increasingly being investigated as biomarkers in ocular diseases.<br><br>OBJECTIVE: The aim of this study was to present the current state of knowledge on the role of EV as biomarkers for ocular diseases, to compare sample sources and to discuss the associated methodological challenges as well as clinical perspectives.<br><br>MATERIAL AND METHODS: This work is based on a&#xa0;literature search of current original articles and reviews, complemented by tabular overviews of identified EV-associated markers for ocular diseases.<br><br>RESULTS: The potential of EV as biomarkers for ocular diseases is currently being studied in tears, aqueous humor, vitreous humor, blood and urine. Alterations in EV concentration and size as well as disease-specific signatures have been reported. Numerous EV-associated molecules, particularly microRNA (miRNA) and proteins, have been proposed for diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, myopia and ocular tumors.<br><br>CONCLUSION: Although EV hold great promise as diagnostic and prognostic tools in ophthalmology, validated markers and standardized isolation and detection methods are still lacking. Key challenges include lipoprotein contamination, limited sample volumes and interindividual variability (e.g. age, sex, fasting status). In the future, after overcoming these technical challenges, small EV and microvesicles could serve as liquid biopsy tools for screening, disease monitoring and personalized management of ocular diseases.}, }
@article {pmid41663366, year = {2026}, author = {Wang, Q and Wang, Y and Chen, L and Huang, J and Cai, T and Lin, Y and Liu, J and Liu, J and Zhu, J and Li, R and Luo, D and Ding, X}, title = {Extraocular delivery of bioswitchable tri-miR-22-loaded tetrahedral DNA nanostructures for intraocular neovascular and neurodegenerative repair.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {50}, pmid = {41663366}, issn = {2059-3635}, support = {82271092//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024A03J0171//Guangzhou Municipal Science and Technology Project/ ; }, mesh = {Animals ; Humans ; *MicroRNAs/genetics/pharmacology/chemistry/administration &amp; dosage ; Mice ; Human Umbilical Vein Endothelial Cells ; *Nanostructures/chemistry/administration &amp; dosage ; *DNA/chemistry/genetics/pharmacology ; *Choroidal Neovascularization/genetics/pathology/drug therapy/therapy ; *Diabetic Retinopathy/genetics/pathology/drug therapy/therapy ; *Macular Degeneration/genetics/pathology/drug therapy/therapy ; *Retinal Neovascularization/genetics/pathology ; }, abstract = {Ocular neovascular and neurodegenerative diseases, such as diabetic retinopathy and age-related macular degeneration, are characterized by abnormal angiogenesis, vascular leakage, and progressive retinal neurodegeneration, ultimately leading to irreversible vision loss. Here, we present a tetrahedral framework DNA-based bioswitchable Tri-miR-22 mimic delivery system (BiRDS), which is specifically engineered for extraocular administration. In vitro, BiRDS can penetrate the cell membrane within 24 h and accumulate extensively in the cytoplasm. Through transscleral-choroidal-retinal penetration, BiRDS achieves robust delivery to the choroid and retina within 18 h without the need for intravitreal injection in mice. The BiRDS can effectively inhibit the proliferation, tube formation and migration abilities of human umbilical vein endothelial cells. In murine models of choroidal neovascularization and oxygen-induced retinopathy, BiRDS not only suppresses retinal pathological neovascularization with efficacy comparable to that of current anti-VEGF agents, but also possesses unique effects that current agents lack, such as improved retinal perfusion and preserved neuronal integrity, thereby contributing to the protection of visual function. Furthermore, transcriptomic profiling and molecular validation revealed that BiRDS exerts its therapeutic efficacy by inhibiting the Wnt/β-catenin pathway, a key driver of mediating the aforementioned pathological processes. This study highlights BiRDS as a next-generation RNA nanotherapy with broad clinical potential, offering site specific, multitargeted modulation via a minimally invasive and patient-friendly route.}, }
@article {pmid41663777, year = {2026}, author = {El-Darzi, N and Dorweiler, TF and Mast, N and Busik, J and Pikuleva, IA}, title = {Retinal phenotype of APOB100 transgenic mice on a Western diet with human-like hyperlipidemia and cholesterol crystals in the retina and choroid.}, journal = {Lab animal}, volume = {55}, number = {3}, pages = {83-94}, pmid = {41663777}, issn = {1548-4475}, support = {EY018383//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; P30 EY011373/EY/NEI NIH HHS/United States ; EY011373//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY018383/EY/NEI NIH HHS/United States ; EY025383//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; }, mesh = {Animals ; *Apolipoprotein B-100/genetics/metabolism ; *Cholesterol/metabolism ; Mice, Transgenic ; *Diet, Western/adverse effects ; *Hyperlipidemias/metabolism ; *Choroid/metabolism/pathology ; *Retina/metabolism/pathology ; Mice ; *Macular Degeneration/metabolism/etiology ; Humans ; Phenotype ; Mice, Inbred C57BL ; Male ; }, abstract = {Drusen and subretinal drusenoid deposits, the pathognomonic lesions for age-related macular degeneration (AMD), are rich in cholesterol. Yet, AMD is not consistently linked to plasma lipids. Here wild-type and human apolipoprotein B100-expressing (APOB100) mice were put on a Western type of diet for 13 months and then assessed for plasma lipid profile, high-density lipoprotein (HDL) heterogeneity, status of intraretinal and choroidal vasculatures, retinal structure, function, levels of cholesterol and other sterols, lipid and cholesterol distribution and expression of cholesterol-related genes. The dietary effects were more pronounced in APOB100 mice, which had human-like hyperlipidemia and different subpopulations of HDL3, than in wild-type mice. In addition, the APOB100 retina showed increased cholesterol input from the systemic circulation, higher cholesterol content, more cholesterol crystals, elevated expression of HDL-related genes, lipid accumulation in the retinal pigment epithelium and Bruch's membrane, and impaired function compared with the wild-type retina. Remarkably, in both genotypes, cholesterol crystals were detected in the choroid, piercing toward Bruch's membrane and leading to macrophage infiltration. Our data indicate how plasma lipid profile could be linked to AMD and that cholesterol crystals in the choroid should be further investigated as contributors to AMD development and progression.}, }
@article {pmid41664225, year = {2026}, author = {Saito, M and Imaizumi, K}, title = {One-year results of the intravitreal administration of faricimab in patients with naïve type 3 macular neovascularization.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {38}, pmid = {41664225}, issn = {2056-9920}, abstract = {BACKGROUND: To clarify the efficacy of the intravitreal injections of faricimab and the change in vascular morphology of retinal-retinal anastomosis (RRA) after treatment in patients with type 3 macular neovascularization (MNV).<br><br>METHODS: We retrospectively reviewed 20 consecutive eyes with treatment-naive type 3 MNV in 14 Japanese patients (mean age, 81.8 years) at different stages. All patients were treated with 3 or 4 consecutive monthly intravitreal injections of faricimab and then they were followed by a &#x201c;treat and extend, then fix&#x201d; regimen in the maintenance phase over a 12-month follow-up.<br><br>RESULTS: The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) levels improved significantly (P&#x2009;<&#x2009;0.01) from 0.87 at baseline to 0.64 at 12 months. Optical coherence tomography angiography (OCTA) findings confirmed RRA in 16 (84.2%) of the 19 eyes, except for the eye with stage 1 at baseline, and 15 (93.8%) of the 16 eyes demonstrated the presence of vascular continuity at 12 months. No progression of retinal pigment epithelium (RPE) atrophy was observed in any of the 3 eyes with RPE atrophy at baseline, and newly developed RPE atrophy was seen in 4 (23.5%) of the 17 eyes without RPE atrophy at baseline. All 20 eyes had dry macula and showed no other complications at 12 months.<br><br>CONCLUSIONS: Intravitreal faricimab injections significantly improved VA, achieved dry macula, and nearly normalized the vessels on the RRA in most patients with type 3 MNV during the 12-month study period.}, }
@article {pmid41664540, year = {2026}, author = {da Silva, CN and Inoue, TT and França Dias, M and Fialho, SL and Silva-Cunha, A}, title = {Intravitreal implants for drug delivery: clinical efficacy, safety, and translational perspectives.}, journal = {Expert opinion on drug delivery}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/17425247.2026.2629545}, pmid = {41664540}, issn = {1744-7593}, abstract = {INTRODUCTION: Chronic retinal disorders such as age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and noninfectious uveitis are among the leading causes of irreversible visual loss worldwide. Their management depends on repeated intravitreal injections of anti-VEGF agents or corticosteroids, which, despite proven efficacy, are associated with high treatment burden and cumulative risks. Sustained-release intravitreal drug delivery systems (DDSs) are effective strategies to prolong therapeutic activity, enhance bioavailability, minimize adverse events, and improve patient adherence.<br><br>AREAS COVERED: This review provides an overview of the evolution, clinical efficacy, and translational potential of intravitreal DDSs, from nonbiodegradable implants to biodegradable systems. Advances in polymeric design, hydrogels, in situ forming systems, and 3D-printed architecture, are discussed alongside emerging clinical candidates. Key formulation, preclinical, and regulatory barriers to clinical translation are also examined. Comprehensive search on PubMed, Scopus, Web of Science, ClinicalTrials.gov, and regulatory repositories was performed (data published up to December 2025).<br><br>EXPERT OPINION: Intravitreal DDSs are redefining ocular pharmacotherapy by offering prolonged, localized drug release. However, further innovation in polymer design, bioerodible materials, and sterilization methods is essential to balance safety, efficacy, and manufacturability. Integration of precision medicine and next-generation biomaterials will be key to achieving fully optimized, minimally invasive retinal therapies.}, }
@article {pmid41665064, year = {2026}, author = {Tunon-Robinson, I and Zhang, R and Nguyen, AK}, title = {Visual Acuity Outcomes Following Intravitreal Biological Drug-Induced Retinal Vasculitis: An Intelligent Research in Sight Registry Retrospective Exploratory Analysis.}, journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics}, volume = {}, number = {}, pages = {10807683251412321}, doi = {10.1177/10807683251412321}, pmid = {41665064}, issn = {1557-7732}, abstract = {PURPOSE: This retrospective exploratory study examines the visual acuity outcomes following a retinal vasculitis (RV) event possibly associated with intravitreal (IVT) biological drugs using a large ophthalmic registry, to gain a better understanding of RV's impact on vision in real-world clinical settings.<br><br>METHODS: An ophthalmic registry was used in a retrospective exploratory analysis and focused on subjects who received IVT anti-VEGF and anticomplement therapies. We excluded eyes with RV in the visual acuity analysis that had received more than one IVT biological drug within 2 months before the diagnosis of RV to increase confidence that a single biological drug was possibly associated with the RV event.<br><br>RESULTS: A total of 1,998,399 subjects received IVT injections of biological drugs, and 2,115 subjects were diagnosed with RV in at least 1 eye. A total of 436 subjects (531 eyes total) were coded as having RV. There was a 78% increase in eyes that became legally blind (&#x2264;20/200 Snellen equivalent) and 46% increase in eyes reading 0 letters (&#x2264;count fingers vision) following the RV event.<br><br>CONCLUSIONS: In the real world, the number of legally blind eyes substantially increased following the RV diagnosis. Given the retrospective and exploratory nature of this study, all interpretations should be made cautiously, including any suggested association between biological therapy and the occurrence of RV, and prospective studies are necessary to confirm these associations. Further research is indicated to improve the safety of biological therapies for retinal diseases and minimize the risk of serious complications such as RV.}, }
@article {pmid41665215, year = {2026}, author = {Argun, M and Nazıroğlu, M}, title = {Selenium Nanoparticles Protect Retinal Pigment Epithelial Cells Against Experimental Age-Related Macular Degeneration-Induced Mitochondrial Oxidative Toxicity and Apoptosis Through the Modulation of the TRPM2 Channel.}, journal = {Journal of biochemical and molecular toxicology}, volume = {40}, number = {2}, pages = {e70738}, doi = {10.1002/jbt.70738}, pmid = {41665215}, issn = {1099-0461}, support = {//BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry LTD, Isparta, T&#xfc;rkiye/ ; }, mesh = {*TRPM Cation Channels/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology/prevention &amp; control/drug therapy ; *Apoptosis/drug effects ; *Selenium/pharmacology/chemistry ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Mitochondria/metabolism/pathology/drug effects ; *Oxidative Stress/drug effects ; Cell Line ; *Nanoparticles/chemistry ; }, abstract = {Excessive Ca[2+] influx leads to mitochondrial oxidative injury and cell death, contributing to the development of age-related macular degeneration (AMD). The protective role of selenium nanoparticle (SeNPs), through inhibition of ADP-ribose- and hydrogen peroxide (H2O2)-induced TRPM2 cation channel stimulation, was recently reported in human retinal pigment epithelial 19 (ARPE-19) cells for hypoxia-induced oxidative cytotoxicity and cell death, but not for AMD. We aimed to investigate the protective effects of SeNPs through inhibition of TRPM2 on AMD (sodium iodate [NaI])-induced oxidative injury, cell death, and apoptosis in ARPE-19 cells. The ARPE-19 cells were divided into four main groups: control (CNT), SeNPs (2.5 μg/mL for 24 h), AMD (10 mM NaI for 24 h) and AMD + SeNPs. The AMD treatment increased TRPM2 current density and cytosolic Ca[2+] and Zn[2+] fluorescence intensities, as well as the percentage of cell death. It also elevated apoptotic markers (caspases 3, 8, and 9) and oxidative stress markers (mitochondrial membrane dysfunction, oxygen free radicals, and lipid peroxidation), while decreasing antioxidants (glutathione and glutathione peroxidase), cell viability and the number of live cells. TRPM2 stimulation further increased these markers. When SeNPs and TRPM2 antagonists were used to treat the AMD-induced increase in TRPM2 activation, they increased antioxidants and cell viability while decreasing oxidative stress and cell death markers. In conclusion, SeNP treatment reduced AMD-induced mitochondrial oxidative cytotoxicity and cell death by inhibiting TRPM2-mediated Ca[2+] signaling. SeNP represents a potential therapeutic option for AMD-induced retinal disorders linked to abnormal oxygen free radical production and Ca[2+] influx.}, }
@article {pmid41666372, year = {2026}, author = {Kim, E and Song, SJ}, title = {FOCAL CHOROIDAL EXCAVATIONS IN A SCREENING COHORT: FUNDUS VISIBILITY AND STRUCTURAL REMODELING IN YOUNGER ADULTS.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004796}, pmid = {41666372}, issn = {1539-2864}, abstract = {PURPOSE: To determine how fundus visibility relates to optical coherence tomography (OCT)-derived morphologic and topographic features of focal choroidal excavation (FCE) and to evaluate systemic and ocular associations in a health-screening cohort.<br><br>METHODS: We analyzed 19,048 individuals undergoing health examinations with spectral-domain OCT and fundus photography. FCEs were classified as fundus-visible or fundus-invisible. A 1:2 propensity score matching (age/sex) was performed to compare participants with FCE against non-FCE controls. Generalized estimating equations were used to analyze lesion characteristics, systemic comorbidities, and ocular parameters including intraocular pressure (IOP), choroidal thickness, and macular degeneration.<br><br>RESULTS: We identified 252 FCE lesions in 192 participants (1.0%). Compared to matched controls, the FCE group showed no significant differences in systemic comorbidities but had significantly lower IOP (P = 0.026), greater choroidal thickness (P < 0.001), and a higher prevalence of macular degeneration (P = 0.002). Among FCEs, fundus-visible lesions had greater median horizontal diameter (681.0 vs 518.0 &#xb5;m; P < 0.001) and depth (69.5 vs 45.0 &#xb5;m; P < 0.001), were located closer to the fovea (611.5 vs 1385.0 &#xb5;m; P < 0.001), and exhibited higher rates of steep slopes (62.5% vs 42.7%; P = 0.002) and outer nuclear layer thickening (61.7% vs 31.5%; P < 0.001) compared to fundus-invisible lesions.<br><br>CONCLUSION: FCE is associated with distinct ocular profiles, including lower IOP and increased choroidal thickness, independent of systemic risk factors. Fundus visibility indicates larger, deeper, and paramacular lesions with specific structural alterations, underscoring the need to recognize subtle fundoscopic irregularities for early OCT detection.}, }
@article {pmid41667492, year = {2026}, author = {Huang, W and Qin, L and Xu, M and Zheng, H and Gan, Y and Pei, S and Wu, R and Liu, Y and Zhong, J and Ni, G}, title = {Comprehensive 3D Optical Coherence Tomography Dataset for AMD and DME: Facilitating Deep-Learning-Based 3D Segmentation.}, journal = {Scientific data}, volume = {13}, number = {1}, pages = {224}, pmid = {41667492}, issn = {2052-4463}, support = {61905036//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021T140090, 2019M663465//China Postdoctoral Science Foundation/ ; }, mesh = {*Tomography, Optical Coherence ; *Deep Learning ; *Macular Degeneration/diagnostic imaging ; Humans ; *Imaging, Three-Dimensional ; *Macular Edema/diagnostic imaging ; *Diabetic Retinopathy/diagnostic imaging ; }, abstract = {Age-related macular degeneration (AMD) and diabetic macular edema (DME) are vision-threatening pathologies for which optical coherence tomography (OCT) provides high-resolution three-dimensional imaging, facilitating comprehensive diagnostic evaluation. Three-dimensional (3D) visualization and precise 3D segmentation of lesions enable accurate assessment of morphology, dimensions, and spatial relationships, thereby enhancing clinical analysis and disease management. However, the lack of a 3D dataset for AMD and DME significantly limits the reliability, robustness, and applicability of deep learning-based 3D segmentation techniques in this field. Here, we present an OCT dataset comprising 224 volumetric images, including 122 for AMD and 102 for DME, annotated with pigment epithelial detachment and intraretinal fluid. We propose a novel 3D segmentation network based on the BiFormer Block, which employs Bi-Level Routing Attention to capture local context and long-range dependencies. Experiments demonstrated that the proposed dataset and network will facilitate the exploration and validation of novel 3D segmentation methods for AMD and DME.}, }
@article {pmid41667658, year = {2026}, author = {Shah, J and Gerendás, L and Serhan, H and Ahmed, H and Festok, M and Mahrous, MA and Kovacs, KD and Kiss, S}, title = {Association between PCSK9 inhibitor use and risk of age-related macular degeneration.}, journal = {Eye (London, England)}, volume = {40}, number = {5}, pages = {739-740}, pmid = {41667658}, issn = {1476-5454}, }
@article {pmid41667660, year = {2026}, author = {Sadeghi, E and Gandhi, P and Davis, E and Singh, SR and Ibrahim, MN and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J}, title = {Three-dimensional choroidal vessels assessment in age-related macular degeneration: a follow-up study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41667660}, issn = {1476-5454}, abstract = {PURPOSE: This study evaluated longitudinal choroidal vascular changes in dry age-related macular degeneration (dAMD) eyes using a three-dimensional (3D) algorithm.<br><br>METHODS: Patients underwent swept-source optical coherence tomography during two follow-up visits. Choroidal boundaries and vessels were segmented using the ResUNet model and Phansalkar thresholding. 3D choroidal maps were created and divided into five sectors. Mean choroidal vessel diameter (MChVD), inter-vessel distance (IVD), volumetric choroidal thickness (ChT), and choroidal vascularity index (CVI) were measured in both visits.<br><br>RESULTS: This retrospective cohort study included 30 eyes with AMD. The mean age was 72.8&#x2009;&#xb1;&#x2009;9.55 years. The mean follow-up duration was 11.6&#x2009;&#xb1;&#x2009;5.02 months. The mean MChVD increased 16.4&#x2009;&#xb5;m (6.8%) over time (239.2&#x2009;&#xb1;&#x2009;19.8 to 255.6&#x2009;&#xb1;&#x2009;28.2&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.003), particularly in the nasal and temporal sectors (P&#x2009;<&#x2009;0.05). The mean IVD increased 21.8&#x2009;&#xb5;m (10.8%) over time (201.8&#x2009;&#xb1;&#x2009;29.0 to 223.7&#x2009;&#xb1;&#x2009;38.2&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.009), which was significant in the nasal, temporal, and superior sectors (P&#x2009;<&#x2009;0.05). The ChT showed a decreasing trend, though not statistically significant (190.7&#x2009;&#xb1;&#x2009;58.0 to 183.4&#x2009;&#xb1;&#x2009;56.8&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.051). The CVI remained stable during follow-up (0.358&#x2009;&#xb1;&#x2009;0.034 vs. 0.357&#x2009;&#xb1;&#x2009;0.040, P&#x2009;=&#x2009;0.933). MChVD positively correlated with the IVD (r&#x2009;=&#x2009;+0.501, P&#x2009;=&#x2009;0.005). ChT exhibited a negative correlation with IVD (r&#x2009;=&#x2009;-0.426, P&#x2009;=&#x2009;0.019).<br><br>CONCLUSION: Eyes with dry AMD showed increased MChVD and IVD along with decreased ChT, and we hypothesise that these changes may reflect progressive small-vessel atrophy accompanied by compensatory dilation of larger choroidal vessels during follow-up.}, }
@article {pmid41669763, year = {2026}, author = {Venkatesh, R and Biradar, P and Malwe, G and Prabhu, V and Hande, P and Kathare, R and Raj, P and Roy, R and Yadav, NK and Jayadev, C}, title = {Anti-VEGF safety in evolution: A comprehensive review of ocular and systemic considerations.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_3284_25}, pmid = {41669763}, issn = {1998-3689}, abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed the management of retinal and choroidal vascular diseases, delivering substantial and sustained visual benefits across neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. As treatment paradigms have evolved toward chronic, often lifelong therapy with repeated injections, attention has increasingly shifted from short-term procedural safety to a broader evaluation of ocular and systemic adverse events. Among these, intraocular inflammation (IOI) has emerged as the most debated ocular safety signal, ranging from mild, self-limited sterile inflammation to rare but vision-threatening occlusive retinal vasculitis. At the same time, systemic adverse events remain biologically plausible yet uncommon in the general population. This review provides a contemporary, clinically oriented synthesis of anti-VEGF safety, emphasizing that IOI and systemic events are not uniform drug effects but reflect complex interactions among drug-specific properties, delivery factors, disease substrate, patient susceptibility, and immunogenicity. We outline a mechanistic framework distinguishing acute sterile inflammation driven by innate immune activation from delayed vasculitic phenotypes associated with adaptive immune responses and anti-drug antibodies. A structured five-pillar susceptibility model is proposed to contextualize risk modifiers, alongside phenotype-driven management and prevention strategies. Systemic safety considerations are reviewed with attention to agent-specific pharmacokinetics, high-risk patient phenotypes, and cumulative exposure. By integrating mechanistic insights with clinical phenotyping, risk stratification, and preventive strategies, this review aims to support informed, individualized decision-making. A balanced, prevention-focused approach enables clinicians to preserve the transformative benefits of anti-VEGF therapy while maintaining a high standard of long-term ocular and systemic safety.}, }
@article {pmid41669765, year = {2026}, author = {Liu, W and Li, W and Wang, D and Wu, P and Jiang, J and Liu, Z and Chen, X}, title = {Ferroptosis in retinal pigment epithelial cells: Current status and future developments.}, journal = {Indian journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.4103/IJO.IJO_2875_25}, pmid = {41669765}, issn = {1998-3689}, abstract = {Retinal pigment epithelial (RPE) cells play a crucial role in maintaining the normal function of the retina. In recent years, research on ferroptosis-a novel iron-dependent form of cell death-in RPE cells has gradually attracted attention. This article reviews the mechanisms of ferroptosis in RPE cells, including iron metabolism imbalance, lipid peroxidation, and functional impairment of the glutathione-glutathione peroxidase 4 (GSH-GPX4) system. It explores the association between ferroptosis in RPE cells and retinal diseases such as age-related macular degeneration and Stargardt disease. Additionally, it analyzes the future challenges in current research on ferroptosis in RPE cells, such as gaining in-depth understanding of complex regulatory networks and developing precise intervention strategies, so as to provide new insights and directions for the prevention and treatment of retinal diseases.}, }
@article {pmid41670698, year = {2026}, author = {Hashiya, N and Maruko, I and Maruko, R and Kakehashi, M and Kawahara, K and Nishihara, S and Iida, T}, title = {Increased intraocular pressure immediately after aflibercept 8 mg intravitreal injection for neovascular age-related macular degeneration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41670698}, issn = {1435-702X}, }
@article {pmid41671246, year = {2026}, author = {Zeng, J and Shang, W and Ren, P and Ke, X and Zhao, Y and Liu, G and Liu, J and Lu, F and Jiang, X}, title = {Expression of aqueous cytokines and their correlation with retinal morphological biomarkers in nAMD patients.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0342259}, pmid = {41671246}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *Aqueous Humor/metabolism ; *Cytokines/metabolism ; Biomarkers/metabolism ; Aged ; Middle Aged ; *Retina/pathology/metabolism ; Tomography, Optical Coherence ; *Macular Degeneration/metabolism/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Cataract/metabolism ; }, abstract = {OBJECTIVE: Neovascular age-related macular degeneration (nAMD) is characterized by pathological neovascularization in the macula, leading to irreversible central vision loss. This study aimed to evaluate cytokine profiles in the aqueous humor of nAMD patients and explore correlation between specific cytokines, clinical characteristics, and retinal morphological features.<br><br>METHODS: Our protocol was registered on Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2500106190 and approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (ID: 20231375). A total of 94 patients with nAMD and 34 cataract patients as the control group were enrolled. Aqueous humor samples were collected before anti-VEGF treatment or cataract surgery, and analyzed using cytometric bead array (CBA) for cytokines (MCP-1, ICAM-1, VCAM-1, CA-1, &#x3b2;-FGF, PPK/PK, and VEGF). Retinal structural biomarkers were assessed using optical coherence tomography (OCT), with statistical analysis performed to evaluate correlations between cytokine levels and retinal morphology.<br><br>RESULTS: Compared to cataract patients, nAMD patients exhibited elevated levels of CA-1, PPK/PK, ICAM-1, VCAM-1, and MCP-1 (P&#x2009;<&#x2009;0.05). Baseline best-corrected visual acuity (BCVA) was reduced in nAMD patients with intraretinal fluid (IRF) or pigmentation compared to those without (P&#x2009;<&#x2009;0.05). Visit BCVA also deteriorated in patients with fibrosis (P&#x2009;<&#x2009;0.05). Additionally, central foveal thickness (CTR) was significantly thinner in patients with PED or SRF (P&#x2009;<&#x2009;0.05). Visit BCVA demonstrated positive correlations with baseline BCVA (r&#x2009;=&#x2009;0.689, P&#x2009;<&#x2009;0.001). In contrast, the presence of fibrosis and elevated MCP-1 concentration was associated with a poorer visual outcome. In correlation analysis, &#x3b2;-FGF exhibited a negative correlation with CA-1, PPK, ICAM-1. VCAM-1 and MCP-1.<br><br>CONCLUSION: In this cross-sectional study, the presence of IRF was significantly associated with reduced BCVA in nAMD patients. Baseline BCVA emerged as a critical predictor of visual prognosis in nAMD. Notably, retinal fibrosis development and elevated MCP-1 level linked to worse clinical outcomes, underscoring their potential as therapeutic targets. While recent anti-VEGF injections decreased VEGF levels in aqueous humor of nAMD patients, the impact of these agents on other cytokines remain unclear, suggesting a need for adjunct therapies to address multifaceted pathogenic pathways.}, }
@article {pmid41672305, year = {2026}, author = {Li, HL and Xu, Y and Mo, JS and Zhao, XY and Zhong, CL and Jia, ZW and Wang, XL and Zhao, BC and Chen, YM and Zheng, KW and Zhang, XL and Wang, QP}, title = {Single intravitreal injection of lipid nanoparticles delivering circular mRNA of nicotinamide phosphoribosyltransferase protects against dry AMD.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {392}, number = {}, pages = {114691}, doi = {10.1016/j.jconrel.2026.114691}, pmid = {41672305}, issn = {1873-4995}, mesh = {*Nicotinamide Phosphoribosyltransferase/genetics/administration &amp; dosage ; Animals ; *RNA, Circular/administration &amp; dosage ; *Nanoparticles/administration &amp; dosage/chemistry ; Intravitreal Injections ; Humans ; *Macular Degeneration/prevention &amp; control ; Mice, Inbred C57BL ; NAD/metabolism ; Male ; Mice ; *RNA, Messenger/administration &amp; dosage ; Lipids/chemistry ; Liposomes ; }, abstract = {Age-related nicotinamide adenine dinucleotide (NAD[+]) deficiency is implicated in numerous pathologies, including dry age-related macular degeneration (AMD). Current NAD[+]-boosting strategies, reliant on precursors like nicotinamide mononucleotide (NMN), necessitate repeated dosing and offer transient effects, limiting therapeutic utility. Here, we address this critical limitation by developing a single-dose therapy using circular mRNA (circ-mRNA) to deliver functional nicotinamide phosphoribosyl transferase (NAMPT), the essential rate-limiting enzyme in NAD[+] salvage. Engineered via permuted intron-exon (PIE) splicing, our circNAMPT exploits the exceptional stability and persistent translation capacity inherent to circular RNA scaffolds. Encapsulation in β-sitosterol-optimized lipid nanoparticles (LNPs) ensures robust intracellular delivery. In vitro, circNAMPT-LNP drives sustained NAMPT expression and prolonged NAD[+] elevation, circumventing precursor limitations. In a stringent sodium iodate-induced dry AMD model, a single intravitreal circNAMPT-LNP injection matched the neuroprotective efficacy of 14 consecutive daily intraperitoneal NMN doses confirmed by histological integrity and functional preservation. This work establishes engineered circ-mRNAs as a transformative platform for durable, single-dose therapeutic protein delivery and demonstrates potential as a disease-modifying therapy for dry AMD. Its applicability extends broadly to systemic disorders driven by NAD[+] deficiency in aging.}, }
@article {pmid41673898, year = {2026}, author = {Licht, A and Mavris, Y and Latz, C and Schuster, AK and Ponto, KA and Mirshahi, A}, title = {Lost to follow-up while undergoing intravitreal injection therapy: barriers to adherence in a real-world setting.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41673898}, issn = {2056-9920}, abstract = {BACKGROUND: Intravitreal anti‑VEGF therapy is effective, yet real‑world outcomes are limited by non persistence. We investigated patient‑reported reasons for discontinuation under pro-re-nata therapy protocol.<br><br>METHODS: This ambispective real-world study at a German eye hospital evaluated patients receiving intravitreal therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), or neovascular age related macular degeneration (nAMD) using the pro re nata (PRN) protocol. Patient records were reviewed, and those meeting lost to follow up (LTFU) criteria (no injections or visits within 3&#x2009;months) were contacted via written letter and phone. When patients were reached surveys to assess reasons for LTFU, perceived treatment burden, mobility, and comorbidities were completed.<br><br>RESULTS: Of 657 cases, 347 (52.8%) met the LTFU- criteria, 25 of which were medically indicated. Despite multiple attempts, contact and data collection was successful for only 39 patients (response rate: 12%), major part was unwilling or unable to participate. The most common reasons for discontinuation were subjective lack of treatment need (56%), perception of being &#x201c;fully treated&#x201d; (33%), fear of injections (26%), travel difficulties (28%), and time burden (15%). Despite these barriers, 52% of patients reported that the treatment was &#x201c;not burdensome at all,&#x201d; while 3 patients (8%) continued therapy elsewhere.<br><br>CONCLUSIONS: In this exploratory, single-centre cohort, a significant portion of patients had effectively disengaged from IVI care and were unreceptive to delayed outreach. Outcome-related perceptions and organizational hurdles were key, actionable barriers. Future strategies to improve adherence should focus on proactive follow-ups shortly after therapy discontinuation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-026-00808-3.}, }
@article {pmid41674610, year = {2026}, author = {Hoshi, S and Wang, X and Kadomoto, S and Liu, R and Ip, M and Sadda, SR and Sarraf, D and Zhang, Y}, title = {Early Photoreceptor Disruption in Emerging Subretinal Drusenoid Deposits Detected by Adaptive Optics Imaging.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.01.28.26344907}, pmid = {41674610}, abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are a distinct entity in age-related macular degeneration (AMD) and associated with photoreceptor impairment during progression. Their early impact on photoreceptors remains incompletely understood. This study examined photoreceptor reflectivity during the phase when SDDs were not clinically detectable on optical coherence tomography (OCT) using adaptive optics scanning laser ophthalmoscopy (AOSLO).<br><br>DESIGN: Longitudinal observational study.<br><br>PARTICIPANTS: Patients with intermediate AMD.<br><br>METHODS: Six eyes of four patients with intermediate AMD and predominantly SDDs underwent multimodal imaging 3-4 times over 3.5 years. Individual SDDs were graded using an OCT-based 3-stage system at each time point. Cross-sectional retinal structure and photoreceptor reflectivity at the location where the new SDDs developed during follow-up were evaluated using OCT and AOSLO.<br><br>MAIN OUTCOME MEASURES: Photoreceptor reflectivity change prior to and during SDD development.<br><br>RESULTS: Forty-eight retinal locations where new dot-type SDDs developed during follow-up were identified. AOSLO revealed reduced photoreceptor reflectivity in these regions before OCT demonstrated clinically evident deposits (stage &#x2265; 1) between the ellipsoid zone and the retinal pigment epithelium at the corresponding sites. The mean time to development of stage 1, stage 2, and stage 3 SDDs was 11.78 &#xb1; 5.01, 17.40 &#xb1; 6.08, and 18.72 &#xb1; 4.08 months, respectively.<br><br>CONCLUSIONS: High-resolution adaptive optics confocal imaging enables detection of photoreceptor optical property alterations at a stage when SDDs are not yet evident on OCT. This finding underscores the exceptional sensitivity of photoreceptors to minimal structural or functional perturbations during SDD formation and defines an early window for potential intervention.}, }
@article {pmid41674807, year = {2026}, author = {Wu, E and Du, K and Thomas, T and Shin, C and Jiang, J and Navidzadeh, J and Hasan, N and Yao, J and Zhang, M and Sahel, J and Chhablani, J}, title = {Neoplasms Associated with the Onset of Age-Related Macular Degeneration: A Case-Control Study Using the All of Us Cohort.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {41674807}, issn = {2693-5015}, support = {OT2 OD026556/OD/NIH HHS/United States ; U2C OD023196/OD/NIH HHS/United States ; OT2 OD025315/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; OT2 OD026549/OD/NIH HHS/United States ; OT2 OD025337/OD/NIH HHS/United States ; OT2 OD025277/OD/NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; OT2 OD023205/OD/NIH HHS/United States ; T32 GM144300/GM/NIGMS NIH HHS/United States ; }, abstract = {PURPOSE: This study investigated the association between prior diagnoses of neoplasms and the onset of age-related macular degeneration (AMD).<br><br>METHODS: A retrospective case-control study was conducted using health records from 2 724 individuals in the All of Us Program, a longitudinal cohort of U.S. adults. Odds ratios (OR) and Fisher's exact tests were used to evaluate associations between neoplasms and AMD in a matched cohort. Kaplan-Meier survival analysis assessed how neoplasms affected time to AMD onset.<br><br>RESULTS: Benign neoplasms of the colon (OR: 1.90, 95% CI: 1.55-2.33), skin (OR: 1.46, 95% CI: 1.16-1.84), and rectum (OR: 2.90, 95% CI: 1.53-5.48) showing the strongest and statistically significant associations with AMD. Patients with these benign neoplasms also developed AMD earlier. Although malignant neoplasms of skin of face (OR: 1.97, 95% CI: 1.11-3.49), prostate (OR: 1.47, 95% CI: 0.98-2.22), and breast (OR: 1.39, 95% CI: 0.95-2.02) were also more frequent in AMD patients, these associations were not as significant.<br><br>CONCLUSION: Insights into the associations between neoplasms and earlier AMD onset may help ophthalmologists identify at-risk patients and enable earlier intervention. These findings suggest shared pathophysiological mechanisms, such as chronic inflammation and vascular dysfunction, may contribute to both tumour formation and AMD development.}, }
@article {pmid41675446, year = {2026}, author = {Yavari, N and Gupta, AS and Mitsios, A and Hung, JH and El-Feky, D and Nguyen, CD and Yasar, C and Anover, FA and Saengsirinavin, AO and Mobasserian, A and Akhavanrezayat, A and Elaraby, O and Zhang, X and Than, NTT and Toth, AB and Agarwal, D and Lin, J and Or, C and Nguyen, QD}, title = {Bilateral hemorrhagic occlusive retinal vasculitis and panuveitis following intravitreal faricimab injection: A clinicopathologic case study.}, journal = {American journal of ophthalmology case reports}, volume = {41}, number = {}, pages = {102532}, pmid = {41675446}, issn = {2451-9936}, abstract = {PURPOSE: To describe the clinicopathological study of severe bilateral intraocular inflammation following intravitreal (IVT) injection of faricimab in a patient with neovascular age-related macular degeneration (nAMD).<br><br>OBSERVATION: An 80-year-old Caucasian female with bilateral nAMD presented with blurry vision and ocular pain after receiving bilateral IVT injections of faricimab on separate days from different lots. The patient experienced significant reduction in her visual acuity, from 20/40 to counting-fingers in the right eye and from 20/50 to hand-motion in the left eye; intraocular pressure (IOP) was elevated in both eyes at 48&#xa0;mmHg and 49&#xa0;mmHg. Anterior segment examination revealed bilateral diffuse mutton-fat keratic precipitates and fundus examination revealed bilateral vitreous opacities. Fluorescein angiography demonstrated optic disc leakage and bilateral hemorrhagic occlusive vasculitis. Following initial management with systemic corticosteroid, a subsequent unilateral subconjunctival dexamethasone implant, and pars plana vitrectomy, ocular inflammation subsided significantly along with the normalization of IOP. Cytology examination of vitreous samples showed the presence of chronic inflammatory cells in the vitreous.<br><br>CONCLUSION: The case highlights the clinical presentation, detailed findings, and successful treatment strategy for hemorrhagic occlusive retinal vasculitis and panuveitis induced by IVT injection of faricimab. Cytopathology analysis of vitreous samples provides novel insights regarding inflammatory mechanisms underlying this rare but potentially sight-threatening complication.}, }
@article {pmid41675764, year = {2026}, author = {Habib, E and Hajj, F}, title = {ROFI: a deep learning-based ophthalmic sign-preserving and reversible patient face anonymizer.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {2}, pages = {2116-2117}, pmid = {41675764}, issn = {2049-0801}, abstract = {Ophthalmic diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, and inherited retinal dystrophies remain leading causes of visual impairment worldwide, necessitating accurate diagnosis and longitudinal monitoring. Modern ophthalmology increasingly relies on facial and ocular imaging, yet the integration of artificial intelligence (AI) into these workflows raises significant privacy concerns. ROFI (Reversible Ophthalmic Face Image anonymizer) is a novel deep learning-based framework designed to anonymize patient facial features while preserving ophthalmic signs essential for diagnosis. By employing weakly supervised learning and neural identity translation, ROFI achieves high accuracy in retaining ocular disease markers while ensuring reversibility for authorized clinical review. Comparative studies demonstrate that anonymized images maintain diagnostic fidelity for retinal disease classification, while AI-based intraoperative guidance systems further enhance surgical precision and patient safety. Despite these advances, challenges remain regarding dataset diversity, external validation, bias, and cost-effectiveness, particularly in resource-limited settings. Future strategies should emphasize multicenter validation, integration into electronic health records, and awareness campaigns to promote adoption. ROFI represents a significant step toward balancing patient privacy with diagnostic accuracy, offering a scalable solution for secure, AI-driven ophthalmic care.}, }
@article {pmid41675859, year = {2026}, author = {Habib, E and Hajj, F}, title = {Nanocarrier-based CircRNA therapeutics in inherited retinal dystrophies.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {2}, pages = {2104-2105}, pmid = {41675859}, issn = {2049-0801}, abstract = {Inherited retinal dystrophies (IRDs) are a genetically diverse group of progressive blinding disorders with limited curative options. Despite advances in gene therapy, most IRD subtypes remain untreatable due to genetic heterogeneity and delivery challenges. Circular RNAs (circRNAs), a class of stable non-coding RNAs, have emerged as novel modulators of retinal gene expression. Recent developments in nanocarrier technology enable targeted delivery of circRNA mimics and inhibitors to retinal tissues, offering a promising therapeutic alternative. These platforms utilize lipid nanoparticles, polymeric micelles, and exosomes to bypass the blood-retinal barrier and enhance cellular uptake. Preclinical studies demonstrate restoration of photoreceptor survival pathways and delayed retinal degeneration in murine IRD models. Additionally, circRNA nanotherapy has shown efficacy in related retinal conditions such as age-related macular degeneration and diabetic retinopathy. However, translational hurdles, including invasive delivery routes, off-target effects, and regulatory gaps, limit clinical adoption. Nanocarrier-mediated circRNA modulation represents a next-generation strategy for precision therapy in IRDs, with potential to reshape the future of retinal disease management.}, }
@article {pmid41676410, year = {2025}, author = {Deng, Z and Bu, Y and Hou, T}, title = {Visual impairment and frailty: insights from genetic correlation and Mendelian randomization.}, journal = {Archives of medical science : AMS}, volume = {21}, number = {6}, pages = {2513-2521}, pmid = {41676410}, issn = {1734-1922}, abstract = {INTRODUCTION: Visual impairment (VI) is associated with frailty in observational studies, but whether this relationship is causal remains uncertain. This study aimed to investigate the genetic correlation and causal associations between genetically predicted VI and frailty using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC).<br><br>MATERIAL AND METHODS: Genome-wide association studies provided summary data for VI subtypes (glaucoma, cataracts, diabetic retinopathy, age-related macular degeneration, hypermetropia, myopia) and frailty measures (frailty index (FI) and fried frailty score (FFS)). LDSC was used to estimate genetic correlations, and MR was conducted using inverse-variance weighted (IVW) as the primary method, supplemented by MR-Egger and weighted median. Sensitivity analyses, including radial MR, Cochran's Q test, MR-Egger intercept, and MR-PRESSO, were used to assess pleiotropy and heterogeneity.<br><br>RESULTS: Significant genetic correlations were found between VI, cataracts, age-related macular degeneration, and frailty. Suggestive correlations were identified between myopia and FI. MR analysis showed increased FI and FFS risks with other cataracts (FI: p = 0.0324; FFS: p = 0.027) and diabetic retinopathy (FI: p < 0.001; FFS: p = 0.0119). Visual disturbances were associated with increased FI risk (p = 0.0101), while age-related macular degeneration elevated FFS risk (p = 0.0251). Reverse analysis revealed that frailty also increased susceptibility to VI. No causal relationships were found for other eye diseases, and analyses showed no evidence of pleiotropy or heterogeneity.<br><br>CONCLUSIONS: This study highlights significant genetic associations and bidirectional causal relationships between VI and frailty. Future research should include multiethnic populations and larger datasets to further explore these mechanisms.}, }
@article {pmid41677389, year = {2026}, author = {Youssif, AA and Liu, P and Gaczkowski, D and Quaggin, SE and Jin, J and Thomson, BR}, title = {A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {2}, pages = {16}, pmid = {41677389}, issn = {2164-2591}, support = {P30 CA060553/CA/NCI NIH HHS/United States ; P30 DK114857/DK/NIDDK NIH HHS/United States ; R01 EY025799/EY/NEI NIH HHS/United States ; R01 EY032609/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Angiopoietin-1/pharmacology ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Receptor, TIE-2/metabolism ; Recombinant Fusion Proteins/pharmacology ; Angiogenesis ; }, abstract = {PURPOSE: The angiopoietin (ANGPT) pathway, comprised of the ANGPT ligands and their receptor Tie2, mediates angiogenesis and is a compelling target for neovascular age-related macular degeneration (nvAMD). Tie2 phosphorylation by ANGPT1 is associated with vascular stability and may be protective in nvAMD. In contrast, ANGPT2 potentiates angiogenesis and the bispecific ANGPT2/VEGF blocking antibody Faricimab has recently been approved for nvAMD. However, despite clear links between the ANGPT pathway and nvAMD and the success of Faricimab, poor characteristics of existing ANGPT1-based therapies have hindered their adoption as an alternate targeting strategy.<br><br>METHODS: Hepta-ANGPT1 is an ANGPT1-mimetic fusion protein with improved activity, solubility, and half-life, addressing limitations of earlier mimetics. Here we used laser-induced and RNV3 (JR5558) models of mouse choroidal neovascularization (CNV) to investigate Hepta-ANGPT1 in CNV and explore its potential as a therapy for nvAMD.<br><br>RESULTS: Hepta-ANGPT1 induced robust Tie2 phosphorylation in the choroid and did not lead to angiogenesis in healthy eyes. However, after laser CNV, we observed increased neovascularization in Hepta-ANGPT1-treated eyes, as well as increased number and size of neovascular lesions in treated RNV3 mice, indicating that Hepta-ANGPT1 potentiated angiogenesis. In contrast, CNV lesion size was smaller in Tie2 knockout mice, and no Hepta-ANGPT1-mediated increase was observed in knockout animals, confirming specificity.<br><br>CONCLUSIONS: Although previous studies have found ANGPT1 to be protective in mouse CNV, Tie2 activation is pro-angiogenic in other tissues, including the cornea and iridocorneal angle. Hepta-ANGPT1 induced a similar effect in CNV, suggesting that under certain conditions, Tie2 activation can be detrimental in this disease.<br><br>TRANSLATIONAL RELEVANCE: Understanding the contexts under which Tie2 activation is beneficial and where it is harmful will be critical to successful development of new Tie2-activating drugs for nvAMD.}, }
@article {pmid41677821, year = {2026}, author = {Christou, EE and Ivanova, T and Patton, N and Moussa, G and Kiraly, P and Huelin, FJ and MacLaren, RE and Jalil, A}, title = {A literature review of macular holes in age-related macular degeneration: insights into the pathogenesis, prognosis and surgical outcomes.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41677821}, issn = {1435-702X}, }
@article {pmid41679584, year = {2026}, author = {Saeidifard, S and Saltykova, IV and Gerner-Mauro, KN and Schill, AW and Larin, KV and Poché, RA}, title = {Brillouin microscopic assessment of retinal stiffness during reactive Müller gliosis.}, journal = {Experimental eye research}, volume = {266}, number = {}, pages = {110926}, doi = {10.1016/j.exer.2026.110926}, pmid = {41679584}, issn = {1096-0007}, mesh = {Animals ; Female ; Male ; Mice ; Elasticity ; *Ependymoglial Cells/metabolism/pathology ; *Gliosis/metabolism/pathology/physiopathology ; Mice, Inbred C57BL ; Microscopy/methods ; N-Methylaspartate ; *Retina/metabolism/pathology/physiopathology ; Cytoskeletal Proteins/metabolism ; Extracellular Matrix Proteins/metabolism ; }, abstract = {Increased retinal stiffness is associated with reactive gliosis, fibrosis, and extracellular matrix remodeling-hallmarks of early retinal damage in conditions such as age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. In this study, we demonstrate that Brillouin microscopy can detect stiffness changes in the damaged mouse retina that coincide with reactive Müller gliosis. Using acute retinal slice cultures, we generated two-dimensional Brillouin maps of both NMDA-damaged and untreated control retinas. Raw spectral images were processed to calculate the Brillouin frequency shift (BFS), which serves as a readout of tissue stiffness. Within 24 h of NMDA treatment, damaged retinas exhibited a significant increase in BFS relative to controls, indicating a rapid rise in retinal stiffness following neuronal cell death. While this biomechanical change likely reflects multiple cellular and molecular contributions, we show that the Brillouin signal localizes within the radial domain of Müller glia. These findings, along with single-cell mRNA sequencing analysis of damaged retinas, suggest that reactive Müller glia are key contributors to the observed increase in retinal stiffness. Collectively, our results establish Brillouin microscopy as a powerful tool to spatially resolve stiffness changes in the retina during neurodegeneration, provide a rationale for probing the specific mechanisms underlying these biomechanical alterations, and support the further development of Brillouin imaging as an in vivo platform for detecting early retinal pathology.}, }
@article {pmid41679663, year = {2026}, author = {Shu, Q and Lin, Y and Su, W and Peng, H and Wang, X}, title = {Exendin-4 alleviates Aβ1-40-induced apoptosis and calcium dysregulation in RPE cells through the CHP1/NHE1 complex.}, journal = {Biochemical pharmacology}, volume = {247}, number = {}, pages = {117789}, doi = {10.1016/j.bcp.2026.117789}, pmid = {41679663}, issn = {1873-2968}, mesh = {Animals ; *Apoptosis/drug effects/physiology ; *Exenatide/pharmacology ; *Calcium/metabolism ; Mice ; Mice, Inbred C57BL ; *Amyloid beta-Peptides/toxicity/antagonists &amp; inhibitors ; Humans ; *Retinal Pigment Epithelium/drug effects/metabolism ; *Peptide Fragments/toxicity/antagonists &amp; inhibitors ; Male ; Dose-Response Relationship, Drug ; Cell Line ; *Cation Transport Proteins/metabolism ; Macular Degeneration/metabolism/drug therapy ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment in elderly individuals and is influenced by various factors, such as age, genetics, and environmental conditions. While research into therapies for dry AMD is rapidly advancing, effective interventions are still lacking, underscoring the urgent need for new drug development. Recent studies have highlighted the multifaceted pharmacological activities of Exendin-4 (EX-4), including its anti-inflammatory, antioxidant, and antiapoptotic properties, along with its role in maintaining calcium homeostasis. The precise effects of EX-4 on AMD and its immediate target remain unclear. In this study, we investigated whether EX-4 could protect against Aβ1-40-induced AMD and explored the underlying mechanism. Our findings indicated that pretreatment with EX-4 alleviated apoptosis and restored calcium homeostasis both in vivo and in vitro. To identify the target of EX-4, we employed proteome microarrays and pulldown LC‒MS/MS analyses. Our results revealed that EX-4 bound to Calcineurin-like EF-hand protein 1(CHP1), reducing CHP1 protein expression in a concentration-dependent manner. This interaction led to a subsequent reduction in apoptosis and the normalization of intracellular Ca[2+] levels through the CHP1/NHE1 complex. Furthermore, we demonstrated that the inhibitory effects of EX-4 on apoptosis and calcium signaling were reversed by knocking down or overexpressing CHP1 in vitro. Finally, in AMD mice with CHP1-deficient retinas, the beneficial effects of EX-4 on apoptosis and calcium signaling were partially attenuated. In summary, our results suggest that the interaction of EX-4 with CHP1 has therapeutic potential for AMD, likely through alleviating apoptosis and restoring calcium homeostasis.}, }
@article {pmid41680690, year = {2026}, author = {Mesen, S and Yılmaz, MN}, title = {Investigation of pan-immune inflammatory value in patients with age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41680690}, issn = {1471-2415}, mesh = {Humans ; Female ; Male ; Retrospective Studies ; Aged ; Tomography, Optical Coherence ; *Wet Macular Degeneration/immunology/blood/diagnosis ; Aged, 80 and over ; Monocytes/pathology ; Neutrophils/pathology ; C-Reactive Protein/metabolism ; *Geographic Atrophy/immunology/blood/diagnosis ; Middle Aged ; Lymphocytes/pathology ; Leukocyte Count ; *Inflammation/immunology/blood ; *Macular Degeneration/immunology ; Triglycerides/blood ; }, abstract = {PURPOSE: The purpose of this study was to evaluate the systemic pan-immune inflammatory value (PIV) in wet and dry cases of age-related macular degeneration.<br><br>METHODS: Patients diagnosed with AMD between 2020 and 2025 were retrospectively identified. The participants were divided into the wet AMD, dry AMD, and control groups. Their complete blood count (CBC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and C-reactive protein data were obtained. Neutrophil-to-lymphocyte, monocyte-to-lymphocyte, platelet-to-lymphocyte, and neutrophil-to-HDL ratios were calculated. The PIV was calculated as follows: (neutrophil &#xd7; platelet &#xd7; monocyte/lymphocyte count). The central macular and subfoveal choroidal thicknesses were measured manually from the spectral domain optical coherence tomography (OCT) images.<br><br>RESULTS: Of the 72 cases included in the study, 25 were wet AMD, 26 were dry AMD, and 21 were controls. According to the statistical analysis, the white blood cell count (7.89&#x2009;&#xb1;&#x2009;1.82 vs. 6.66&#x2009;&#xb1;&#x2009;1.75), neutrophil count (5.02&#x2009;&#xb1;&#x2009;1.42 10[9]/L vs. 4.11&#x2009;&#xb1;&#x2009;1.35 10[9]/L), monocyte count (0.64&#x2009;&#xb1;&#x2009;0.16 10[9]/L vs. 0.49&#x2009;&#xb1;&#x2009;0.18 10[9]/L), and PIV (414.31&#x2009;&#xb1;&#x2009;268.02 vs. 270.33&#x2009;&#xb1;&#x2009;161.84) were higher in the wet AMD group than in the dry AMD group. The monocyte count (0.64&#x2009;&#xb1;&#x2009;0.16 10[9]/L vs. 0.49&#x2009;&#xb1;&#x2009;0.17 10[9]/L) and PIV (414.31&#x2009;&#xb1;&#x2009;268.02 vs. 270.13&#x2009;&#xb1;&#x2009;127.84) were higher in the wet AMD cases than in the control group. No statistically significant difference was found between the dry AMD and control groups.<br><br>CONCLUSION: In our study, the PIV was statistically significantly higher in the wet AMD group than in the dry AMD and control groups. Obtaining CBC data is a highly cost-effective and practical method for calculating PIV. PIV calculation can be helpful in the follow-up of patients with AMD, especially those at high risk of converting from dry AMD to wet AMD.}, }
@article {pmid41680791, year = {2026}, author = {Chen, KY and Chan, HC and Chan, CM}, title = {Can MicroRNAs serve as reliable biomarkers and novel therapeutic targets in age-related macular degeneration? A systematic review and meta-analysis.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {}, pmid = {41680791}, issn = {1479-5876}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, affecting 196 million people globally with projections reaching 288 million by 2040. Its pathogenesis involves oxidative stress, chronic inflammation, angiogenesis, and retinal pigment epithelium (RPE) dysfunction. MicroRNAs (miRNAs)—highly stable, non-coding post-transcriptional regulators—have emerged as key modulators of AMD-related pathways, including nuclear factor kappa B mediated inflammation (miR-146a, miR-155), angiogenesis (miR-23a, miR-27a), and RPE homeostasis (miR-204, miR-211). Dysregulation of miRNAs across the retina, serum, plasma, and vitreous may offer diagnostic and therapeutic potential. This systematic review and meta-analysis evaluated the diagnostic accuracy, differential expression, and functional relevance of miRNAs in AMD.<br><br>METHODS: A comprehensive literature search was performed across all major databases, including PubMed, Embase, Web of Science, Google Scholar, Scopus, and the Cochrane Library, as well as additional sources identified through websites and citation searching, covering all records from database inception to 15th June 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), with protocol registration in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420251101982). Eligible studies included human case-control studies, in vitro/in vivo AMD models, and miRNA-based therapeutic investigations. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), the Office of Health Assessment and Translation tool (OHAT), the SYstematic Review Centre for Laboratory animal Experimentation tool (SYRCLE), and a modified Toxicological data Reliability Assessment Tool (ToxRTool). Meta-analyses were performed using fixed or random-effects models based on heterogeneity. Outcomes included pooled AUC values, standardized mean differences (SMD), pooled mean miRNA expression, and distribution of up- vs. down-regulated miRNAs.<br><br>RESULTS: Twenty-two studies were included. Differentially expressed miRNAs were consistently reported, with miR-34a (up to 6.3-fold), miR-146a (2.1&#x2013;6.3-fold), miR-155, miR-19a, miR-410, and miR-126 among the most recurrent. Diagnostic accuracy meta-analysis demonstrated a pooled area under the receiver operating characteristic curve of 0.749 (95% CI: 0.713&#x2013;0.781). Individual AUCs included: vitreous ratio AUC 0.977, plasma AUC 0.914, miR-27a-3p 0.925, miR-29b-3p 0.757, and miR-195-5p 0.766. Pooled SMD comparing AMD vs. controls was 0.296 (p&#x2009;<&#x2009;0.001). Mean pooled miRNA expression in AMD was 0.296 (SE 0.0313), with highest levels in miR-486-5p (0.8016), miR-423-3p (0.7329), and miR-885-5p (0.6759). Up-vs-down-regulation analysis showed balanced distribution (pooled effect 0.520, p&#x2009;=&#x2009;0.505). Functional studies demonstrated restoration of TREM2 after miR-34a inhibition and rescue of RPE phagocytosis via miR-184 modulation. Publication bias was significant in two outcomes but corrected estimates remained directionally consistent.<br><br>CONCLUSION: Multiple miRNAs show consistent dysregulation in AMD and display moderate diagnostic accuracy, particularly miR-27a-3p, miR-146a, miR-34a, and vitreous-derived miRNA panels. Several miRNAs regulate key pathogenic pathways&#x2014;including inflammation, angiogenesis, and impaired RPE function&#x2014;supporting their potential as biomarkers and therapeutic targets. Large, standardized, multi-center studies are required to validate these findings and advance miRNA-based diagnostics and therapeutics toward clinical translation.<br><br>TRANSLATIONAL RELEVANCE: This study bridges the gap between molecular biomarker discovery and clinical application in AMD. It highlights the feasibility of incorporating miRNA profiling into AMD diagnostics and supports the future development of miRNA-targeted therapies for personalized treatment strategies.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07593-x.}, }
@article {pmid41681737, year = {2026}, author = {Bepery, C and Rahaman, GMA and Debnath, R and Saha, S and Islam, MS and Abir, MEI and Sarker, SK}, title = {BanglaOCT2025: A Population-Specific Fovea-Centric OCT Dataset with Self-Supervised Volumetric Restoration Using Flip-Flop Swin Transformers.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681737}, issn = {2075-4418}, abstract = {Background: Age-related macular degeneration (AMD) is a major cause of vision loss, yet publicly available Optical Coherence Tomography (OCT) datasets lack demographic diversity, particularly from South Asian populations. Existing datasets largely represent Western cohorts, limiting AI generalizability. Moreover, raw OCT volumes contain redundant spatial information and speckle noise, hindering efficient analysis. Methods: We introduce BanglaOCT2025, a retrospective dataset collected from the National Institute of Ophthalmology and Hospital (NIOH), Bangladesh, using Nidek RS-330 Duo 2 and RS-3000 Advance systems. We propose a novel preprocessing pipeline comprising two stages: (1) A constraint-based centroid minimization algorithm automatically localizes the foveal center and extracts a fixed 33-slice macular sub-volume, robust to retinal tilt and acquisition variability; and (2) A self-supervised volumetric denoising module based on a Flip-Flop Swin Transformer (FFSwin) backbone suppresses speckle noise without requiring paired clean reference data. Results: The dataset comprises 1585 OCT volumes (202,880 B-scans), including 857 expert-annotated cases (54 DryAMD, 61 WetAMD, and 742 NonAMD). Denoising quality was evaluated using reference-free volumetric metrics, paired statistical analysis, and blinded clinical review by a retinal specialist, confirming preservation of pathological biomarkers and absence of hallucination. Under a controlled paired evaluation using the same classifier with frozen weights, downstream AMD classification accuracy improved from 69.08% to 99.88%, interpreted as an upper-bound estimate of diagnostic signal recoverability rather than independent generalization. Conclusions: BanglaOCT2025 is the first clinically validated OCT dataset representing the Bengali population and establishes a reproducible fovea-centric volumetric preprocessing and restoration framework for AMD analysis, with future validation across independent and multi-centre test cohorts.}, }
@article {pmid41681740, year = {2026}, author = {Ozturk, M and Ağın, A}, title = {Choriocapillaris Flow and Retinal Vascular Fractal Dimension in Dry Age-Related Macular Degeneration.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681740}, issn = {2075-4418}, abstract = {Background/Objective: To evaluate the association between optical coherence tomography angiography (OCTA)-derived choriocapillaris flow (CCflow), retinal vascular fractal dimension (FD), and drusen burden in eyes with dry age-related macular degeneration (AMD). Methods: This retrospective study included 113 eyes from 73 patients with dry AMD. Eyes were classified into large and small drusen groups based on median drusen area. OCTA-derived CCflow and FD indices of the superficial and deep capillary plexuses were analyzed. Patient-level clustered analyses were performed using linear mixed-effects and generalized estimating equation models to account for inter-eye correlation. Results: Eyes with large drusen showed significantly lower CCflow compared with those with small drusen (p < 0.001), whereas FDsup did not differ between groups, and FDdeep demonstrated only a near-significant trend toward higher values. CCflow was moderately and negatively correlated with drusen area (ρ = -0.452, p < 0.001), whereas FDdeep showed no significant correlation in unadjusted analyses (ρ = 0.137, p = 0.148). In patient-level age-adjusted multivariable models accounting for inter-eye dependency, CCflow remained independently associated with drusen burden, while FDdeep demonstrated an independent association only after adjustment for age. Conclusions: Reduced CCflow is independently associated with increased drusen burden in dry AMD. FD metrics provide complementary descriptive information regarding microvascular remodeling but do not function as independent biomarkers. CCflow may serve as a robust quantitative indicator of early choroidal compromise in dry AMD.}, }
@article {pmid41681815, year = {2026}, author = {Gołębiewska, J and Jędrzejewska, IK and Mędrzycka, J and Przybyś, M and Różycki, R}, title = {Non-Exudative Macular Neovascularization in Various Acquired Macular Degenerations with Double- and Triple-Layer Sign on OCT.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {3}, pages = {}, pmid = {41681815}, issn = {2075-4418}, abstract = {Background/Objectives: To investigate the rate of exudative progression over time in patients with non-exudative macular neovascularization (NE-MNV) associated with various acquired macular degenerations presenting with a double-layer sign (DLS) or triple-layer sign (TLS) on optical coherence tomography (OCT), and to identify potential predictors of this progression. Methods: Fifty-one eyes of fourty-nine patients with a DLS or TLS on OCT images were identified. OCT angiography (OCTA) was performed to detect NE-MNV, and only eyes with confirmed NE-MNV were included in the final analysis. Central macular thickness (CMT), choroidal thickness (CT), morphology of the abnormal vessels, the duration of follow-up, progression to active exudative MNV, and the status of the contralateral eye were assessed. Results: The final analysis included 32 eyes of 30 participants with NE-MNV. The median observation period was 46 months. The causes of NE-MNV were age- related macular degeneration (AMD) in 59.38% of eyes, pachychoroid epitheliopathy (PPE) in 37.50%, and other causes in 3.12%. Exudation developed in 15.62% of eyes (median time to onset: 24 months), predominantly in the AMD subgroup. Abnormalities in the fellow eye were present in 59.38% of cases. Neither age nor other factors, including sex, cause of MNV, CMT, CT, MNV morphology, or fellow eye status, were statistically significant predictors of progression to active MNV (p = 0.67, p > 0.99, p = 0.62, p = 0.09, p = 0.09, p = 0.2, p = 0.62, resp.). Conclusions: NE-MNV is an asymptomatic condition that may occur in the course of various retinal diseases. While DLS and TLS demonstrate high sensitivity and specificity for the diagnosis of NE-MNV, their presence does not always indicate concurrent MNV. Multimodal imaging is essential for accurate monitoring of these patients and detection of potential disease progression.}, }
@article {pmid41683651, year = {2026}, author = {Chao, WW and Chao, HW and Chao, HM}, title = {Combined Therapy Versus Fortified Anti-VEGF Monotherapy in Type C Polypoidal Choroidal Vasculopathy: Long-Term Outcomes and Exploratory Biomarker Insights.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683651}, issn = {1422-0067}, mesh = {Humans ; Male ; Female ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Biomarkers/metabolism ; Middle Aged ; Retrospective Studies ; Aged ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Photochemotherapy/methods ; Treatment Outcome ; *Choroidal Neovascularization/drug therapy/metabolism ; Visual Acuity ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Choroid/blood supply/pathology ; Ranibizumab/therapeutic use ; Polypoidal Choroidal Vasculopathy ; }, abstract = {While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of the standard one) anti-VEGF combined with PDT versus fortified anti-VEGF monotherapy and to investigate biomolecular profiles and disease relationships among PCV, neovascular age-related macular degeneration (nvAMD), and central serous chorioretinopathy (CSCR). The goal was to identify novel pathways to inform future therapeutic strategies, including hypoxia-inducible factors (HIF)-1α inhibitors. This retrospective cohort study included 23 eyes with indocyanine green-confirmed type C PCV. One eye treated with transpupillary thermotherapy was not included in the following two groups. Patients received either combined therapy (PDT + fortified-dose anti-VEGF; n = 12) or fortified-dose anti-VEGF monotherapy (n = 10). Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary outcomes included injection burden and recurrence. Exploratory analyses examined aqueous biomarkers, including VEGF, placental growth factor (PlGF), β-catenin, HIF-1α, and Wnt1 across PCV, CSCR, and nvAMD to identify novel therapeutic targets. Significant (p = 0.003/p = 0.005) median CRT reduction was similar (p = 0.468) between groups (combined/monotherapy: 137.5 µm/106.5 µm). BCVA (median [Q1, Q3]) change in logarithm of the minimum angle of resolution (LogMAR) was not statistically significant (p = 0.279), with 0.25 [0.00, 0.98] in the combined group versus 0.00 [-0.03, 0.28] in the monotherapy group. Treatment burden of anti-VEGFs per person per year was lower with combined therapy (1.16 ± 0.47# PDT + 2.81 ± 0.92# anti-VEGF injections) compared with monotherapy (4.61 ± 1.49# injections). Six eyes demonstrated recurrence at a mean of 15.5 months. Incomplete regression of polyps and branching vascular networks was observed in all eyes. Exploratory biomarker analysis revealed significantly (p < 0.05) higher VEGF and PlGF levels in nvAMD compared with PCV. nvAMD also demonstrated significantly (p < 0.05) higher β-catenin and lower HIF-1α levels relative to PCV and CSCR, while no significant biomarker differences were observed between PCV and CSCR. Combined therapy or monotherapy with fortified anti-VEGFs reduced treatment burden and achieved significant anatomical improvement but did not yield superior functional outcomes, highlighting the therapeutic difficulty of type C PCV. Biomarker profiling revealed shared hypoxia-related mechanisms between PCV and CSCR, with elevated HIF-1α compared to nvAMD indicating a "preliminary" possible role for HIF-1α inhibitors. Differential expression of these biomarkers highlights additional molecular pathways that may inform future targeted interventions.}, }
@article {pmid41683853, year = {2026}, author = {Gong, X and Örge, FH}, title = {Glucagon-like Peptide-1 Receptor Agonists and Ocular Disease: Mechanisms, Evidence and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683853}, issn = {1422-0067}, mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Eye Diseases/drug therapy/metabolism ; Diabetic Retinopathy/drug therapy/metabolism ; Macular Degeneration/drug therapy/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Glaucoma/drug therapy/metabolism ; Hypoglycemic Agents/therapeutic use ; }, abstract = {Ocular diseases, including glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), remain major global causes of irreversible vision loss. Despite advances in clinical management, current therapies insufficiently address the shared metabolic, inflammatory, vascular, and neurodegenerative mechanisms underlying these conditions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes and obesity, have emerged as multi-target candidates for ocular therapeutics due to their pleiotropic anti-inflammatory, antioxidant, vasculoprotective, and neuroprotective properties. Preclinical studies consistently demonstrate that GLP-1RAs preserve blood-retina barrier integrity, suppress pathological angiogenesis, mitigate oxidative and inflammatory stress, and protect retinal neurons from degeneration. Complementary clinical and real-world evidence shows a robust and reproducible reduction in glaucoma risk among GLP-1RA users across diabetic and non-diabetic populations. By contrast, findings for DR and AMD are more heterogeneous and appear context-dependent, with potential benefits most evident in early or non-exudative disease stages. Emerging safety considerations-including reports of nonarteritic anterior ischemic optic neuropathy and early DR worsening in the setting of rapid glycemic improvement-highlight the need for careful interpretation, individualized risk assessment, and appropriate ophthalmic monitoring. This review synthesizes molecular mechanisms, experimental data, clinical and pharmacoepidemiologic evidence, and safety signals to critically evaluate the therapeutic potential of GLP-1RAs in ocular disease. We also outline key translational challenges, including the need for ocular-targeted delivery strategies, prospective ophthalmology-specific trials, and precision-medicine approaches to determine when and how GLP-1RAs can be safely advanced as disease-modifying treatments in ophthalmology.}, }
@article {pmid41683912, year = {2026}, author = {Rusciano, D and Gagliano, C and Avitabile, A and Maya-Vetencourt, JF}, title = {Targeted RNA Degradation by RIBOTACs: A Novel Therapeutic Avenue for Ophthalmic Diseases.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683912}, issn = {1422-0067}, mesh = {Humans ; Animals ; *Eye Diseases/genetics/drug therapy/therapy/metabolism ; *RNA Stability/drug effects ; *Ribonucleases/metabolism ; }, abstract = {Ophthalmic diseases, including inherited retinal dystrophies, age-related macular degeneration (AMD), and glaucomatous neuropathies, are often driven by the expression of pathogenic proteins or dysfunctional non-coding RNAs that are currently considered 'undruggable' with conventional small-molecule therapeutics. The emerging strategy of Ribonuclease-Targeting Chimeras (RIBOTACs) offers a revolutionary approach to address this therapeutic gap. RIBOTACs are heterobifunctional small molecules designed to bind a specific target RNA with one moiety and recruit a latent endogenous ribonuclease, such as RNase L, with the other, thereby catalyzing the RNA's degradation. This targeted degradation can potentially halt the production of mutant proteins, eliminate toxic gain-of-function RNAs, or modulate key regulatory pathways involved in angiogenesis, inflammation, and apoptosis-core processes in many blinding diseases. This review explores the immense potential of applying RIBOTAC technology to ophthalmology, discussing prospective targets such as mutant alleles in retinitis pigmentosa, VEGF transcripts in neovascular AMD, and inflammatory mediators in uveitis. We will also address the unique challenges and opportunities for RIBOTAC development in the eye, including delivery strategies to overcome ocular barriers, the need for high specificity to avoid off-target RNA degradation, and the optimization of pharmacokinetic properties for intraocular administration. With continued innovation, RIBOTACs are poised to evolve into a robust therapeutic platform, expanding the druggable genome and enabling precise, durable treatments for a range of currently intractable ophthalmic conditions.}, }
@article {pmid41684578, year = {2025}, author = {Tong, L and Zhan, Q and Zhang, L}, title = {Age-related macular degeneration in the context of an update from the Global Burden of Disease Study 2019.}, journal = {Archives of medical science : AMS}, volume = {21}, number = {6}, pages = {2441-2449}, pmid = {41684578}, issn = {1734-1922}, abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of central vision loss, with an increasing prevalence related to a growing economic burden. Understanding the epidemiological changes of AMD is essential for targeting the resource allocation of medicine, interventions, and the economy.<br><br>MATERIAL AND METHODS: The global prevalence and years lived with disability of AMD by sociodemographic index (SDI), sex, and age groups from 1990 to 2019 based on the Global Burden of Disease Study 2019 were retrieved and utilized to estimate epidemiological changes.<br><br>RESULTS: The global AMD population increased significantly from 3581.33 thousand in 1990 to 7792.53 thousand in 2019, and the years lived with disability significantly increased from 296.77 thousand years to 564.06 thousand years. The AMD burden was higher among females (57.77% to 59.20%), the elderly (65-74 years old), and individuals in high-middle and middle SDI regions from 1990 to 2019. The most significant increase in global burden occurred between 2014 and 2019. The age-standardized rate was predicted to remain stable, but the AMD case number was predicted to increase over the next 20 years. Tobacco use was the major diminishing risk factor.<br><br>CONCLUSIONS: The present study demonstrated the increasing AMD burden in the past 30 years and predicted the increasing change of AMD prevalence in the next 20 years in the context of the aging global population. Disease burdens, including case number and age-standardized rate, were higher among females, the elderly, and individuals in high-middle and middle SDI regions. The present findings will contribute to healthcare investment and policymaking.}, }
@article {pmid41686445, year = {2026}, author = {Hussey, KA and Eldred, KC and Guy, B and Santiago, CP and Zhang, JS and Glass, I and Reh, TA and Blackshaw, S and Goff, LA and Johnston, RJ}, title = {A cell fate specification and transition mechanism for human foveolar cone subtype patterning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {7}, pages = {e2510799123}, pmid = {41686445}, issn = {1091-6490}, support = {G2019300//BrightFocus Foundation (BFF)/ ; R01 EY030872/EY/NEI NIH HHS/United States ; DRG 32-20//Damon Runyon Cancer Research Foundation (DRCRF)/ ; F31EY033656//HHS | NIH | National Eye Institute (NEI)/ ; TA-RM-0620-0788-463 UWA//Foundation Fighting Blindness (FFB)/ ; DGE-1746891//NSF | NSF Graduate Research Fellowship Program (GRFP)/ ; GT15994//HHMI (HHMI)/ ; 2022-MSCRFD-5895//Maryland Stem Cell Research Fund (MSCRF)/ ; R01EY031685//HHS | NIH | National Eye Institute (NEI)/ ; R01EY030872//HHS | NIH | National Eye Institute (NEI)/ ; R24HD000836//HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; R01EY036173//HHS | NIH | National Eye Institute (NEI)/ ; }, mesh = {Humans ; *Retinal Cone Photoreceptor Cells/metabolism/cytology ; Organoids/metabolism/cytology ; Cell Differentiation ; Signal Transduction ; Retinoic Acid 4-Hydroxylase/metabolism/genetics ; Tretinoin/metabolism ; Retina/metabolism ; Iodide Peroxidase/metabolism/genetics ; }, abstract = {In the central region of the human retina, the high-acuity foveola is notable for its dense packing of green (M) and red (L) cones and absence of blue (S) cones. To identify mechanisms that pattern cones in the foveola, we examined human fetal retinas and differentiated retinal organoids. During development, sparse S-opsin-expressing cones are initially observed in the foveola. Later in fetal development, the foveola contains a mix of cones that either coexpress S- and M/L-opsins or exclusively express M/L-opsin. In adults, only M/L cones are present. Two signaling pathway regulators are highly and continuously expressed in the central retina: Cytochrome P450 26 subfamily A member 1 (CYP26A1), which degrades retinoic acid (RA) and Deiodinase 2 (DIO2), which promotes thyroid hormone (TH) signaling. Both CYP26A1 mutant organoids and high RA conditions increased the number of S cones and reduced the number of M/L cones in retinal organoids. In contrast, sustained TH signaling promoted the generation of M/L-opsin-expressing cones and induced M/L-opsin expression in S-opsin-expressing cones, showing that cone fate is plastic. Our data suggest that CYP26A1 degrades RA to specify M/L cones and limit S cones and that continuous DIO2 expression sustains high levels of TH to transition S-opsin-expressing cones into M/L cone fate, resulting in the foveola containing only M/L cones. Given the vulnerability of the foveola in macular degeneration and other retinal disorders, these findings provide a mechanistic framework for engineering organoids for therapeutic applications.}, }
@article {pmid41687120, year = {2026}, author = {Nascimento, LM and Louzada, RN and Amaral, DC and Jacometti, R and Viegas Mendonça, VP and Chamis, B and Pereira Gonzalez, JV and Lessa, CT and Ribeiro Monteiro, ML and Ferrara, D}, title = {Associations Between Sleep Disorders and Age-related Macular Degeneration: A Systematic Review and Meta-analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004800}, pmid = {41687120}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the relationship between sleep disorders, including insomnia and obstructive sleep apnea (OSA), personal chronotype, and age-related macular degeneration (AMD).<br><br>METHODS: We systematically reviewed articles in PubMed, EMBASE, and Web of Science that provided information on AMD and sleep disorders, whether qualitative or quantitative. We systematically screened the abstracts of potentially eligible studies and subsequently assessed the full-text reports of those deemed relevant in detail. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.<br><br>RESULTS: Twenty-two studies were included in our final review. OSA was associated with a higher risk of AMD, based on seven studies (HR 1.43; 95% CI 1.14-1.79 p < 0.001; I2 = 96%). The analysis showed a statistically significant association between the morning person chronotype and an increased odds of AMD (OR 1.19; 95% CI 1.10-1.30; p < 0.001; I2 = 0%). We found little to no association between sleep duration and insomnia.<br><br>CONCLUSION: Our meta-analyses, although based on a limited number of studies, indicate that sleep disorders, particularly OSA, are associated with increased odds of developing AMD. However, further research is needed to understand how sleep duration affects disease progression and to determine the benefits of treating sleep disorders for AMD.}, }
@article {pmid41687798, year = {2026}, author = {Kikushima, W and Gilead, N and Sherif, MZA and Zhang, C and Jiang, Z and Sun, C and Ong, C and Hong, CH and Teo, KYC and Chakravarthy, U and Cheung, CMG}, title = {Prevalence and Associated Features of Reticular Pseudodrusen in Neovascular Age-Related Macular Degeneration in an Asian Population.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {95-105}, doi = {10.1016/j.ajo.2026.02.011}, pmid = {41687798}, issn = {1879-1891}, abstract = {PURPOSE: To investigate the prevalence and associated features of reticular pseudodrusen (RPD) in an Asian cohort with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, observational, cross-sectional study.<br><br>SUBJECTS: A total of 353 patients presenting with treatment-na&#xef;ve unilateral nAMD.<br><br>METHODS: Patients presenting with treatment-na&#xef;ve unilateral nAMD who enrolled in the Asian AMD Phenotyping study between 2015 and 2025 were reviewed. All patients underwent protocolized imaging, which included color fundus photography, spectral-domain optical coherence tomography (SD-OCT), and fluorescein and indocyanine green angiography. Images were evaluated for drusen, and RPD were considered present based on SD-OCT. Patients with ungradable eyes due to extensive neovascular changes or poor image qualities were excluded. Baseline characteristics of patients with RPD were compared with those with soft/cuticular or no drusen.<br><br>MAIN OUTCOME MEASURES: The prevalence and associated features of RPD. The systemic and ocular parameters were compared among the patients with RPD, soft/cuticular drusen, and no drusen.<br><br>RESULTS: Among 353 eligible patients (706 eyes), RPD were found in 68 eyes in 51 patients (9.6% per eye, 14.4% per patient). Patients with RPD were older compared with those with soft/cuticular or no drusen (P = .0005 and P < .0001, respectively). Eyes with RPD showed thinner choroidal thickness and higher prevalence of type 3 macular neovascularization (MNV) (odds ratio, 6.94, P = .01) compared with those with soft/cuticular or no drusen.<br><br>CONCLUSIONS: This is one of the largest series evaluating the prevalence of RPD in nAMD in the Asian population. Our findings suggest that ethnicity mainly impacts the prevalence of RPD. However, among patients with RPD, regardless of their ethnicity, there is a strong association with thin choroid and type 3 MNV.}, }
@article {pmid41687799, year = {2026}, author = {Browning, DJ}, title = {The Trouble With Photodynamic Therapy.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {261-265}, doi = {10.1016/j.ajo.2026.02.002}, pmid = {41687799}, issn = {1879-1891}, abstract = {PURPOSE: To examine the role of photodynamic therapy (PDT) in the treatment of retinal disease and the obstacles to use in the United States for evidence-based indications.<br><br>DESIGN: Perspective essay.<br><br>METHODS: This article includes a historical summary, example case report, and relevant literature review.<br><br>RESULTS: PDT has been approved by the US Food and Drug Administration for use in neovascular age-related macular degeneration (AMD), but has been superseded by anti-vascular endothelial growth factor drugs and is rarely used for this indication. It is regularly used in polypoidal choroidal vasculopathy (PCV) without reimbursement difficulty because PCV is acknowledged to be a form of AMD. It is effective for serous retinal detachment associated with choroidal hemangioma. Because this is a rare indication, insurers generally authorize its use. It is the most effective treatment for chronic central serous retinopathy (CSR), a relatively common indication; however, authorization from insurers is difficult to obtain, leading to avoidable loss of vision because patients often will not or cannot pay chargemaster prices. Many retina specialists eschew PDT because the expense in time and the laser does not balance the difficulties with reimbursement and the comparative advantage of allocating their time in other ways.<br><br>CONCLUSIONS: In the United States, finding a retina specialist who performs PDT is challenging for patients with diseases for which it is indicated. Obtaining coverage for CSR is difficult for retina specialists treating patients with CSR in the United States, but not internationally. As a result, delayed or no treatment for cases indicated leads to avoidable loss of vision. A suggested solution is that insurers agree to cover PDT for chronic CSR at a rate equal to 1.3 times Medicare reimbursement for neovascular AMD.}, }
@article {pmid41688763, year = {2026}, author = {Kim, TH and Kwon, CY and Song, JY and Yoo, HC}, title = {AAV-based gene therapies for neovascular AMD.}, journal = {Gene therapy}, volume = {}, number = {}, pages = {}, pmid = {41688763}, issn = {1476-5462}, support = {RS-2024-00412879//National Research Foundation of Korea (NRF)/ ; 2021R1C1C2006283//National Research Foundation of Korea (NRF)/ ; RS-2024-00403169//Korea Basic Science Institute (KBSI)/ ; 2024//Chung-Ang University (CAU)/ ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision loss in the elderly, driven by choroidal neovascularization and dysregulated vascular endothelial growth factor (VEGF) signaling. While anti-VEGF injections have transformed management, their frequent administration imposes a substantial burden on patients and limits adherence. Adeno-associated virus (AAV)-based gene therapy offers sustained intraocular delivery of anti-angiogenic agents with a single treatment, potentially overcoming these limitations. This review summarizes the rationale for AAV use in ocular gene therapy, compares major delivery routes, and highlights leading clinical candidates, including RGX-314, ADVM-022, 4D-150, and NG101. Advances in vector engineering, promoter optimization, and immune modulation are discussed alongside key challenges such as preexisting immunity and inflammation. Future directions include next-generation capsids, combination regimens, and precision patient selection. Collectively, these developments position AAV-based gene therapy as a promising strategy to redefine the therapeutic landscape of nAMD.}, }
@article {pmid41690011, year = {2026}, author = {Zhao, P and Ansaripour, R and Singh, D and Rong, G and Young, MJ and Carrier, RL}, title = {Novel explant model for human retinal progenitor cell transplantation.}, journal = {Biochemical and biophysical research communications}, volume = {807}, number = {}, pages = {153432}, doi = {10.1016/j.bbrc.2026.153432}, pmid = {41690011}, issn = {1090-2104}, mesh = {Humans ; *Retina/cytology ; Animals ; *Stem Cell Transplantation/methods ; Swine ; Hydrogels/chemistry ; Cell Survival ; *Stem Cells/cytology ; Cell Movement ; Alginates/chemistry ; }, abstract = {Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, have led to vision loss for millions worldwide. While stem/progenitor cell transplantation shows promise, its clinical application is limited by poor survival, efflux, and low integration of transplanted cells. Biopolymer scaffolds have been explored to improve viability and differentiation, but most in vitro assessments rely on simplified or endpoint analyses that fail to capture dynamic behaviors. Retinal explant models, which preserve tissue architecture and neuronal connections, provide a more physiologically relevant platform. However, conventional explant models are often limited to endpoint analyses and lack real-time monitoring capabilities. Here, we developed a novel explant model for human retinal progenitor cell (hRPC) transplantation using porcine retinal tissue slice, agarose hydrogel, and confocal microscope with an incubation cage. Retinal tissue slices exhibited comparable viability before and after imaging. Alginate-based hydrogels containing hRPCs were injected adjacent to photoreceptor or ganglion cell layer of cross-sectional retinal tissue slices, enabling visualization of the cells' position relative to retinal tissue slice over time. Real-time confocal imaging tracked key cellular behaviors, including migration, attachment, invasion, viability, and apoptosis. Injected hRPCs displayed random movement within the bulk alginate hydrogel and localized attachment or invasion at the hydrogel-tissue interface. Notably, laminin-incorporated alginate hydrogels promoted cell clustering and facilitated deeper invasion into retinal tissue compared with single cells.}, }
@article {pmid41692178, year = {2026}, author = {Yaldo, L and Ngo, A and Yaldo, M and Abdelaal, A and Ong, J and Kiryakoza, L and Sengillo, J}, title = {Obstructive sleep apnea and risk of age-related macular degeneration: A systematic review and meta-analysis.}, journal = {American journal of ophthalmology}, volume = {285}, number = {}, pages = {276-287}, doi = {10.1016/j.ajo.2026.02.016}, pmid = {41692178}, issn = {1879-1891}, abstract = {TOPIC: We evaluated whether obstructive sleep apnea (OSA) is associated with an increased risk of age-related macular degeneration (AMD). The population included adults with and without OSA. Outcomes included overall AMD risk and AMD stage-specific outcomes, including neovascular AMD (nAMD), non-neovascular AMD, late AMD with geographic atrophy (GA), and anti-VEGF therapy requirement.<br><br>CLINICAL RELEVANCE: AMD is a leading cause of irreversible vision loss worldwide. OSA, characterized by intermittent hypoxia, oxidative stress, and vascular dysregulation, shares key pathogenic mechanisms with AMD. Understanding whether OSA increases AMD risk could help identify high-risk populations for earlier detection, monitoring, and intervention.<br><br>METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, and Scopus were searched to June 27, 2025, supplemented by Google Scholar and citation tracking. Eligible studies reported AMD outcomes in both OSA and non-OSA groups. Methodological quality was assessed using the National Institutes of Health Quality Assessment Tool. Random-effects models were used to pool odds ratios (ORs) and adjusted hazard ratios (aHRs). Certainty of evidence was evaluated with the GRADE framework. The protocol was registered in PROSPERO (CRD420251119881).<br><br>RESULTS: Eight studies (3,536,314 participants; 207,130 with OSA) were analyzed. In crude analyses, OSA was associated with higher odds of AMD (OR = 1.45; 95%CI: 1.13-1.84; low certainty) with similar increases for nAMD (OR = 1.76; 95%CI: 1.06-2.93; low certainty) and non-neovascular AMD (OR = 1.95; 95%CI: 1.04-3.66; low certainty). No significant associations were observed in subgroups without confounder adjustment (low certainty) or with regression adjustment (low certainty), whereas propensity-score matched studies indicated higher odds (OR = 1.92; 95%CI: 1.05-3.52; low certainty). Adjusted analyses confirmed the association (aOR = 1.44; 95%CI: 1.11-1.77; moderate certainty) with no heterogeneity. Time-to-event analyses showed an increased hazard of AMD (aHR = 1.66; 95%CI: 1.13-2.19; low certainty), though stage-specific analyses for neovascular and non-neovascular AMD were not significant (very low certainty).<br><br>CONCLUSION: OSA may be associated with an increased risk of AMD, though the certainty of evidence ranges from moderate to very low. Variability in diagnostic criteria for OSA and AMD, high heterogeneity in several analyses, and reliance on observational data limit the strength of inference.}, }
@article {pmid41692264, year = {2026}, author = {Zhang, Z and Wang, H and Pan, S and Han, W and Liu, M and Chen, Y and Li, X and Zhan, Y and Wu, H and Yao, J and Yang, J and Wu, F}, title = {Enhancing mouse fundus imaging with OCT embedding medium: Prolonging imaging duration and improving image quality.}, journal = {Experimental eye research}, volume = {266}, number = {}, pages = {110914}, doi = {10.1016/j.exer.2026.110914}, pmid = {41692264}, issn = {1096-0007}, mesh = {Animals ; *Tomography, Optical Coherence/methods ; Mice ; *Fundus Oculi ; Disease Models, Animal ; Mice, Inbred C57BL ; *Macular Degeneration/diagnostic imaging/diagnosis ; *Retinal Vessels/diagnostic imaging ; Fluorescein Angiography/methods ; *Image Enhancement/methods ; }, abstract = {Fundus diseases are common and serious ophthalmic conditions, including macular degeneration, diabetic retinopathy, glaucoma, and others, which can lead to severe vision loss. Mice, widely used as experimental animal models, play a crucial role in ophthalmic disease research. However, existing mouse fundus imaging techniques encounter several challenges during prolonged, high-precision imaging, such as corneal whitening, poor optical quality, and motion artifacts. In this study, we propose an innovative method based on an OCT embedding medium that, when applied to the mouse corneal surface, improves the alignment between the eye and the OCT lens. This method effectively reduces stray light (flare)and motion artifacts while slowing corneal dehydration. It significantly enhances the quality of mouse fundus imaging and extends imaging duration, particularly in the age-related macular degeneration (AMD) mouse model, where it improves retinal blood vessel visualization. This approach provides a novel technical solution for ophthalmic research and holds potential for clinical applications.}, }
@article {pmid41692319, year = {2026}, author = {Karami, S and Charpentier, P and Landreville, S and Proulx, S}, title = {Pigment epithelium-derived factor and osteopontin protect human retinal pigment epithelial cells from oxidative stress in 2D and 3D models.}, journal = {Free radical biology &amp; medicine}, volume = {247}, number = {}, pages = {435-447}, doi = {10.1016/j.freeradbiomed.2026.02.034}, pmid = {41692319}, issn = {1873-4596}, mesh = {Humans ; *Nerve Growth Factors/metabolism/pharmacology/genetics ; *Serpins/metabolism/pharmacology/genetics ; *Oxidative Stress/drug effects ; *Eye Proteins/metabolism/pharmacology/genetics ; *Osteopontin/metabolism/pharmacology/genetics ; *Retinal Pigment Epithelium/metabolism/cytology/drug effects ; NF-E2-Related Factor 2/metabolism/genetics ; Reactive Oxygen Species/metabolism ; Cells, Cultured ; Lipid Peroxidation/drug effects ; Epithelial Cells/metabolism/drug effects ; Melanocytes/metabolism ; Iodates/toxicity ; }, abstract = {Retinal pigment epithelial (RPE) cells are particularly vulnerable to oxidative stress. Neighboring choroidal melanocytes (CMs) secrete trophic factors, such as pigment epithelium-derived factor (PEDF) and osteopontin (OPN), which may mitigate oxidative damage in RPE cells. Herein, we investigated the ability of PEDF and OPN to protect RPE cells from extended NaIO3-induced oxidative stress damage. Primary human RPE cells were seeded on plastic (2D culture) or on a 3D tissue-engineered choroidal stroma (TECS) containing (or not) CMs. PEDF or OPN was added before, during, and after 5 days of NaIO3 exposure. Analyses included assessment of PEDF and OPN expression, intracellular reactive oxygen species (ROS), lipid peroxidation, mitochondrial superoxide, cell death, antioxidant capacity (TAC) and p-Nrf2 nuclear translocation. Adding exogenous PEDF to the growth media stimulated de novo PEDF secretion by RPE cells, whereas OPN concentration detected in the growth media corresponded to the amount added. PEDF and OPN levels were consistently lower in the growth media of 3D TECS compared to the 2D cultures. Oxidative stress significantly increased intracellular ROS, lipid peroxidation, and RPE cell death in both 2D and 3D cultures, which were reduced by PEDF or OPN supplementation. Oxidative stress and PEDF or OPN supplementation did not alter the TAC of RPE cells. PEDF or OPN supplementation promoted p-Nrf2 nuclear translocation in RPE cells on plastic, even without oxidative stress, whereas this response was not observed in 3D TECS cultures. Adding CMs to the 3D TECS did not influence p-Nrf2 nuclear translocation in RPE cells. Overall, PEDF and OPN supplementation significantly protected human RPE cells against NaIO3-induced oxidative stress damage. In 3D TECS, CMs secreted insufficient levels of PEDF and OPN for RPE cells to manage oxidative stress-induced damage. These findings demonstrate that exogenous supplementation with PEDF and OPN proteins may be beneficial for oxidative-stress related eye diseases.}, }
@article {pmid41692377, year = {2026}, author = {Vidal-Oliver, L and Garzone, D and Schloesser, L and Thiele, S and Pfau, M and Harmening, WM and Ameln, J and Dolz-Marco, R and Cuenca, N and Ortuño-Lizaran, I and Wu, Z and Guymer, RH and Finger, RP}, title = {Structural photoreceptor evaluation in age-related macular degeneration. A comprehensive review of methods and clinical significance.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101447}, doi = {10.1016/j.preteyeres.2026.101447}, pmid = {41692377}, issn = {1873-1635}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis/pathology ; *Photoreceptor Cells, Vertebrate/pathology ; Retinal Pigment Epithelium/pathology ; Clinical Relevance ; }, abstract = {Age-related macular degeneration (AMD) is a disease that primarily affects the outer retina, with progressive photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE). Advances in imaging now enable photoreceptor changes to be detected and quantified with unprecedented sensitivity, whereas comparable biomarkers of RPE dysfunction remain less developed. As such, photoreceptor-based biomarkers are increasingly considered potential surrogates for current clinical trial endpoints. This review examines the current imaging modalities-particularly optical coherence tomography (OCT) and modalities enhanced by adaptive optics (AO) -used to evaluate photoreceptor structure in AMD. We explore the intrinsic value of parameters such as outer nuclear layer thickness, external limiting membrane integrity, photoreceptor inner and outer segment thickness, ellipsoid zone (EZ) integrity, and EZ reflectivity on OCT, and cone density and regularity on AO imaging, highlighting their potential and limitations. While OCT-based metrics are the most accessible in clinical settings, their clinical utility is hampered by inconsistent segmentation protocols and methodological heterogeneity. AO imaging offers unmatched resolution but faces practical barriers to widespread adoption. The field is moving in a promising direction with emerging computational tools and artificial intelligence improving accuracy and scalability. However, progress is contingent on establishing consensus definitions, standardized acquisition and analysis protocols, and normative datasets. Future efforts should focus on translating high-resolution imaging into robust, reproducible biomarkers that can be widely adopted in both clinical practice and therapeutic development.}, }
@article {pmid41693903, year = {2026}, author = {Patel, Y and Baumann, B and Merkle, C}, title = {Blood flow analysis of retinal neovascularisations in a VLDLR mouse model using contrast-enhanced optical coherence tomography.}, journal = {Biomedical optics express}, volume = {17}, number = {2}, pages = {991-1010}, pmid = {41693903}, issn = {2156-7085}, abstract = {Age-related macular degeneration (AMD) is a major cause of global blindness that affects millions worldwide. Certain forms of AMD cause neovascularisations (NVs), which form retinal-choroidal anastomoses. This disrupts healthy haemodynamic patterns, and early detection and treatment are crucial for preserving vision. Here, we employ a custom-built optical coherence tomography (OCT) imaging system to investigate these NVs in a very low-density lipoprotein receptor (VLDLR) knockout mouse model. Mice were imaged before, during, and after contrast agent injection, aiming to enhance our understanding of the NV haemodynamics. Doppler signal analysis techniques were employed to calculate flow velocities within individual NVs. Flow rates pre- and post-injection were determined based on these velocity measurements. Particle tracking was performed on two NVs for a comparative analysis with the Doppler velocity measurements. Both methods of measuring flow velocities showed good agreement post-contrast injection. The analysis of post-injection flow rates from the NVs revealed diverse behaviours. Some NVs exhibited stable flow rates over time, while others showed signs of instability, with flow rates changing substantially or even changing flow direction at different time points. Additionally, it was observed at multiple time points that flow from certain NVs moved from the choroid to the retina at the same time that other NVs displayed flow in the opposite direction. These observations suggest complex interactions between choroidal and retinal vascular networks in diseases like AMD. Further characterisation using contrast-enhanced Doppler OCT may improve our understanding of neovascular haemodynamics.}, }
@article {pmid41694220, year = {2026}, author = {Li, J and Ma, Y and Hu, M and Zhang, Q and Wang, A and Tang, Q and Guo, Q and Huang, B}, title = {PANoptosis-Related Diagnostic Biomarkers in Non-Neovascular Age-Related Macular Degeneration: An Integrative Transcriptomic and Experimental Study.}, journal = {Genetics research}, volume = {2026}, number = {}, pages = {8903808}, pmid = {41694220}, issn = {1469-5073}, mesh = {Humans ; Animals ; *Macular Degeneration/genetics/diagnosis/pathology ; *Transcriptome/genetics ; Mice ; Biomarkers/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Gene Expression Profiling ; Female ; Male ; Retina/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD), particularly its non-neovascular (dry) form, is a progressive retinal disorder that causes central vision loss and substantial impairment in daily life. Inflammation and immune dysregulation are recognized as core drivers of AMD, yet the contribution of PANoptosis, a form of programmed cell death that integrates pyroptosis, apoptosis, and necroptosis, remains unclear. In this study, we integrated human single-cell transcriptomic and bulk microarray datasets from the retina and retinal pigment epithelium-choroid to characterize PANoptosis-related transcriptional changes in dry AMD. Dimensionality reduction, cell-type annotation, and PANoptosis gene-set scoring revealed a distinct PANoptosis signature enriched in AMD, with particularly strong activation in myeloid populations. By combining differential expression analysis with machine learning-based feature selection, we identified four PANoptosis-related genes (PON2, BNIP3, EPHB6, and TPD52) that robustly distinguished AMD from control samples and were associated with an altered immune microenvironment. Genetic instrument analysis further suggested a positive association between TPD52 expression and AMD risk. At the cellular level, our data highlighted macrophages, especially pro-inflammatory M1-like macrophages, as key coordinators of PANoptosis-related pathways in dry AMD. To validate these findings in vivo, we used a sodium iodate-induced mouse model of dry AMD and observed significant dysregulation of PON2, BNIP3, EPHB6, and TPD52 in the retina by RT-qPCR, consistent with the human transcriptomic results and supporting their involvement in retinal degeneration and inflammation. Together, these findings implicate PANoptosis as an important and previously underappreciated component of dry AMD pathophysiology, define a four-gene PANoptosis-related signature with diagnostic potential, and suggest new molecular targets for therapeutic intervention.}, }
@article {pmid41694267, year = {2026}, author = {Pan, L and Deng, J and Yang, J and Wang, M and Chen, Z and Wang, T and Li, Y}, title = {Causal effects of antibody-mediated immunity to pathogens on five ophthalmic diseases: a Mendelian randomization study.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10906}, pmid = {41694267}, issn = {1535-3699}, mesh = {Humans ; Mendelian Randomization Analysis ; *Eye Diseases/immunology/genetics ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; }, abstract = {While immune responses related to infections have been linked to ocular diseases, their causal role remains to be established. This study aimed to assess the causal relationship between antibody-mediated immune responses to infectious agents and five ocular conditions: chronic iridocyclitis (CIR), scleritis, wet age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. We performed a two-sample Mendelian randomization (MR) analysis using GWAS data to assess causality between antibody responses to 46 pathogens and five ophthalmic diseases. The instrumental variables were Single nucleotide polymorphisms (SNPs). Causal estimates were primarily generated via the inverse-variance weighted method, supplemented by MR-Egger and weighted median methods. A Bonferroni-corrected threshold of P < 2.17 × 10[-4] was applied. Sensitivity analyses included Cochran's Q, MR-Egger, and MR-PRESSO for heterogeneity and pleiotropy. Reverse MR was performed to assess bidirectionality. Forward MR identified causal effects of infection-induced immune responses on ocular diseases. Epstein-Barr virus (EBV) ZEBRA antibodies were positively correlated with CIR, whereas Varicella zoster virus glycoproteins E and I antibodies were associated with scleritis and DR as risk factors. Genetically predicted anti-polyomavirus 2 IgG seropositivity (JCV IgG+) was identified as a risk factor for DR, wet AMD and glaucoma. In contrast, The EBV EBNA-1 antibody is associated with DR, wet AMD, and glaucoma as a protective factor, whereas the EBV VCA18 antibody is negatively associated with wet AMD. Reverse MR analysis indicated that DR may elevate JCV VP1 antibody levels. This study provides the first genetic evidence of a causal link between pathogen-specific immune responses and ocular diseases, offering a foundation for targeted immunomodulatory and personalized therapies.}, }
@article {pmid41694669, year = {2026}, author = {Reinisalo, M and Helisalmi, S and Koskela, A and Küblbeck, J and Liukkonen, M and Mutikainen, M and Cree, AJ and Griffiths, H and Papp, A and Seitsonen, S and Immonen, I and Soininen, H and Urtti, A and Hiltunen, M and Winiarczyk, M and Resch, M and Ratnayaka, JA and Lotery, AJ and Kaarniranta, K and Honkakoski, P}, title = {Functional polymorphisms in pigmentation-related genes MC1R and DCT display population-specific association with wet age-related macular degeneration.}, journal = {Biochemistry and biophysics reports}, volume = {45}, number = {}, pages = {102477}, pmid = {41694669}, issn = {2405-5808}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Age-related macular degeneration (AMD) is among the leading causes of vision loss. Factors increasing the risk of AMD include aging, smoking, cardiovascular diseases and heritability. Although melanin pigment is known to protect retinal homeostasis, the link between pigmentation-related genes and AMD is unclear. We investigated associations between 26 variations in six pigmentation-related genes and wet AMD risk in a Finnish population, followed by replication in the United Kingdom (UK), Hungarian and Polish cohorts, totaling 775 patients and 959 controls. Associations of genetic components with smoking and body mass index (BMI) were tested in the Finnish and UK cohorts. The functionality of candidate variants in human retinal pigment epithelial (RPE) cells was evaluated using gene promoter analysis and gene silencing. Non-coding variants, rs1407995 in the dopachrome tautomerase (DCT) intron and rs3212351 in the melanocortin-1 receptor (MC1R) promoter, were associated with wet AMD in the Finnish cohort. The variant rs3212351 disrupts a binding site for transcription factor MITF and reduces MC1R expression in RPE cells. Unlike in the Finnish cohort, the data regarding the MC1R variant suggested a protective association in the Polish cohort. The incidence of AMD increased with age in all cohorts. Smoking increased AMD risk in the cohorts studied. Sex and BMI showed no associations. These findings suggest that variations in DCT and MC1R genes known to affect skin and eye pigmentation may also play a role in development of wet AMD. The observed population differences may be related to variable pigmentation traits.}, }
@article {pmid41697345, year = {2026}, author = {Fukuda, Y and Notomi, S and Shiose, S and Maehara, Y and Yuge, K and Kiyohara, K and Yasaka, Y and Mori, K and Ishikawa, K and Murakami, Y and Sonoda, KH}, title = {Wide-field choroidal thickness changes after loading-phase anti-VEGF therapy in treatment-naïve neovascular AMD.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41697345}, issn = {1435-702X}, support = {JP24KJ1780//Japan Society for the Promotion of Science/ ; JP25K12836//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: While it is known that anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) leads to a reduction in choroidal thickness in the macula, changes in peripheral choroidal thickness remain unclear. This study aimed to evaluate choroidal thickness changes following three monthly intravitreal injections of aflibercept and faricimab in treatment-naïve nAMD.<br><br>METHODS: Treatment-na&#xef;ve nAMD patients receiving three consecutive monthly injections as the loading phase were enrolled in this study. Wide-field swept-source OCT was used to quantify regional choroidal thickness. In the 1:1 propensity score matching, sex, age, baseline best-corrected visual acuity, axial length, and nAMD subtypes were selected as covariates.<br><br>RESULTS: A total of 142 eyes from 142 patients were included, with 71 eyes receiving aflibercept and 71 eyes receiving faricimab. Significant reductions in choroidal thickness were observed in both central and peripheral areas, with the most pronounced changes occurring in the central 3&#xa0;mm-subfield. After propensity score matching, choroidal thickness change rates were compared between the two drug groups. In the central 3&#xa0;mm-subfield, aflibercept was associated with a significantly greater reduction in choroidal thickness compared with faricimab. No significant differences were observed in other subfields.<br><br>CONCLUSION: This study highlights the importance of considering both central and peripheral choroidal changes when evaluating the impact of different anti-VEGF therapies in nAMD.}, }
@article {pmid41699676, year = {2026}, author = {Yang, H and Liu, B and Zhang, Y and Zhang, Z and Tan, H and Li, X}, title = {Caffeine intake and late dry age-related macular degeneration: tea's protective role-insights from NHANES and Mendelian randomization.}, journal = {International journal of retina and vitreous}, volume = {12}, number = {1}, pages = {}, pmid = {41699676}, issn = {2056-9920}, support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; }, abstract = {BACKGROUND: Although caffeine is widely consumed and has demonstrated neuroprotective effects, its role in age-related macular degeneration (AMD) remains unclear, particularly across disease subtypes and dietary sources such as tea and coffee.<br><br>METHODS: We analyzed 2005-2008 NHANES data using weighted logistic regression and restricted cubic splines to assess the dose-response relationship between caffeine intake and the prevalence of early and late AMD. Two-sample Mendelian randomization (MR) using GWAS summary statistics was employed to evaluate causal effects of tea and coffee consumption on AMD subtypes. Furthermore, a two-step MR approach was utilized to identify potential immune-mediated pathways.<br><br>RESULTS: NHANES data showed that caffeine intake was inversely associated with late AMD (fully adjusted OR&#x2009;=&#x2009;0.65, 95% CI: 0.44-0.96). Dose-response modeling revealed an L-shaped nonlinear relationship (P for nonlinear&#x2009;=&#x2009;0.046), indicating that the protective effect of caffeine plateaued once daily intake exceeded approximately 110-150&#xa0;mg. MR analysis further supported a causal protective association between tea consumption and dry AMD, including geographic atrophy (OR&#x2009;=&#x2009;0.44, 95% CI: 0.20-0.97), which may be partially attributable to immunological mechanisms, specifically the downregulation of secretory regulatory T cells (% of CD4&#x2009;+&#x2009;Tregs) and CD45RA- CD4&#x2009;+&#x2009;T cell (% of CD4&#x2009;+&#x2009;T cell). In contrast, coffee consumption showed no significant effect.<br><br>CONCLUSIONS: Tea, a specific source of caffeine typically corresponding to moderate intake levels, may confer protection against dry AMD, including geographic atrophy, potentially through modulation of immune cell profiles. These findings suggest a potential preventive strategy and warrant further clinical investigation.}, }
@article {pmid41699888, year = {2026}, author = {Samoila, L and Farcasanu, A and Simon, S and Bodoki, E and Samoila, O and Vostinaru, O and Dinte, E and Bodoki, AE and Iudean, D and Muresan, C and Clichici, S}, title = {Noninvasive 11.7-T Magnetic Resonance Spectroscopy and Imaging Reveals Retinal Metabolic Alterations Induced by Blue Light Exposure.}, journal = {NMR in biomedicine}, volume = {39}, number = {3}, pages = {e70240}, pmid = {41699888}, issn = {1099-1492}, support = {352/390028/23.09.2021//Romanian Ministry of European Investment and Projects (MIPE)/ ; G-2024-71962/23.10.2024//Romanian Ministry of European Investment and Projects (MIPE)/ ; 390005/23.10.2024//Ministry of Research, Innovation and Digitalization (MCID)/ ; }, mesh = {Animals ; *Retina/metabolism/radiation effects/diagnostic imaging ; *Light ; Male ; Rats ; Magnetic Resonance Spectroscopy/methods ; Oxidative Stress/radiation effects ; *Proton Magnetic Resonance Spectroscopy ; Blue Light ; }, abstract = {The eye is a complex structure, with multiple systems involved in focusing and detecting light. Among them, the retina, an integral component of the central nervous system, is considered the most vital and exhibits the highest metabolic activity among all tissues in the human body. It interacts with light, and excessive exposure, especially to blue light, is prone to produce degeneration, mainly through oxidative reactions. This mechanism is involved in age-related macular degeneration or diabetic retinopathy. Animal research is important, considering the high prevalence of these diseases; yet noninvasive procedures involving this research are lacking so far. Our objective was to apply an animal model of oxidative stress and monitor the metabolic changes using 11.7-T [1]H-magnetic resonance spectroscopy ([1]H-MRS). We exposed adult rats to high intensity blue light, at 440 nm (6000 lx) and investigated retinal metabolic changes up to 48 h post exposure. The acquired spectrum highlighted the presence of several essential retinal metabolites, including lipids (alkyl chain CH2), lactate, N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), taurine (Tau), creatine (Cre), and glucose (Glc). Blue light induced specific changes, relatable to oxidative stress, and [1]H-MRS allowed us to follow the dynamic metabolic changes post exposure. This is the first in vivo spectroscopic study of the retinal tissue in which no animals were sacrificed. To validate the in vivo metabolite assignments, localized ex vivo [1]H-MRS was performed on eyes from separate animals that had not been exposed to blue light.}, }
@article {pmid41699987, year = {2026}, author = {Li, ZY and Yang, D and Huang, Y and Li, Y and Zhao, T and Xu, Y}, title = {Dynamin-Related Protein 1-Dependent Disruption of Mitochondrial Homeostasis Drives Blue Light-Induced Epithelial-Mesenchymal Transition in Retinal Aging.}, journal = {Aging cell}, volume = {25}, number = {2}, pages = {e70416}, pmid = {41699987}, issn = {1474-9726}, support = {#2023A1515012397//Natural Science Foundation of Guangdong Province/ ; #2023A03J0899//Guangzhou Science and Technology Projects/ ; }, mesh = {*Epithelial-Mesenchymal Transition/radiation effects ; Animals ; Humans ; *Dynamins/metabolism ; *Mitochondria/metabolism/radiation effects ; Mice ; *Homeostasis/radiation effects ; *Light/adverse effects ; *Retinal Pigment Epithelium/metabolism/pathology ; Mitochondrial Dynamics/radiation effects ; *Retina/pathology/metabolism/radiation effects ; *Aging ; Macular Degeneration/pathology/metabolism ; Oxidative Stress ; Blue Light ; }, abstract = {Age-related macular degeneration (AMD) stands as a leading cause of blindness in the elderly, yet the fundamental aging processes that underpin its pathogenesis remain incompletely defined. The dysfunction of retinal pigment epithelial (RPE) cells is a central event in AMD, a process that shares key hallmarks with broader cellular aging, particularly the progressive decline in mitochondrial function. In this study, we investigated how a common environmental stressor-blue light-triggers a key pathological transformation, epithelial-mesenchymal transition (EMT), in RPE cells by specifically disrupting mitochondrial dynamics, a core pillar of cellular aging. Using an in vitro model of human RPE cells, we demonstrated that blue light exposure induces a marked shift in mitochondrial dynamics towards excessive fission. This imbalance directly resulted in mitochondrial dysfunction, elevated oxidative stress, and served as the critical driver for the initiation of EMT. Importantly, pharmacological inhibition of the mitochondrial fission GTPase Dynamin-related protein 1 (Drp1) with Mdivi-1 effectively restored mitochondrial network homeostasis, rescued mitochondrial function, and fully reversed the EMT phenotype. These findings were corroborated in a mouse model of blue light-induced retinal damage, where Drp1 inhibition successfully preserved retinal light responses, mitigated structural degeneration, and slowed disease progression. Our study demonstrates that Drp1-mediated excessive mitochondrial fission drives EMT in RPE cells under blue light, linking this mechanism to AMD progression. Consequently, targeting mitochondrial dynamics to maintain cellular homeostasis emerges as a promising and broadly applicable geroscience-based strategy for mitigating age-related tissue dysfunction.}, }
@article {pmid41700798, year = {2026}, author = {Trinh, M and Borrelli, E and Reibaldi, M and Foti, C and Nivison-Smith, L}, title = {Inner Retinal Reflectivity Loss and Concurrent Thickening Predict Short-Term Conversion to Neovascular AMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {2}, pages = {34}, pmid = {41700798}, issn = {1552-5783}, mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Retinal Ganglion Cells/pathology ; Case-Control Studies ; *Wet Macular Degeneration/diagnosis ; Nerve Fibers/pathology ; Aged, 80 and over ; Disease Progression ; Visual Acuity ; Middle Aged ; Follow-Up Studies ; *Retina/pathology ; }, abstract = {PURPOSE: To examine inner retinal changes preceding conversion from intermediate age-related macular degeneration (iAMD) to exudative neovascular AMD (nAMD), using topographic optical coherence tomography (OCT) reflectivity and thickness analysis.<br><br>METHODS: This retrospective case-control study included 60 individual eyes with iAMD (30 converters and 30 non-converters to nAMD within 1 year). Baseline macular OCT scans were segmented for the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Raw linear reflectivity (normalized against vitreous intensity) and thickness were extracted from 48 &#xd7; 48 grids. Primary outcomes were differences in reflectivity (%) and thickness (&#xb5;m) between converters and non-converters, adjusted for person-level factors. Secondary outcomes examined retinal macrovascular metrics and odds of conversion (odds ratios [ORs]), further adjusted for traditional AMD factors.<br><br>RESULTS: Converters showed global reductions in reflectivity across the RNFL (-6.24%), GCL (-2.01%), and IPL (-1.58%), with modest RNFL thickening (4.48&#xa0;&#xb5;m). Topographic analyses revealed nasal reflectivity loss in all layers and localized thickening in the nasal RNFL and paracentral GCL/IPL (P < 0.0001). Macrovascular metrics did not differ between groups. Global and topographic reflectivity loss strongly predicted conversion (univariable ORs up to 1.85 per 1% decrease; 95% confidence interval [CI], 1.38-2.72). RNFL thickening was also predictive (univariable ORs up to 1.64 per 1-&#xb5;m increase; 95% CI, 1.25-2.32). Both metrics remained significant in multivariable models, whereas drusen volume, pigmentary abnormalities, and fellow-eye status did not.<br><br>CONCLUSIONS: Inner retinal reflectivity loss with mild thickening is a strong predictor of short-term progression to nAMD. These OCT-derived biomarkers showed stronger associations with conversion than traditional risk factors and may improve short-term risk stratification and monitoring.}, }
@article {pmid41701337, year = {2026}, author = {Gilead, N and Chong, YJ and Lim, J and Teo, KYC and Ohno-Matsui, K and Cheung, CMG}, title = {ROLE OF INFLAMMATION IN ATROPHY DEVELOPMENT AND PROGRESSION IN PATHOLOGIC MYOPIA.}, journal = {Retina (Philadelphia, Pa.)}, volume = {46}, number = {3}, pages = {465-476}, doi = {10.1097/IAE.0000000000004697}, pmid = {41701337}, issn = {1539-2864}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; Disease Progression ; *Myopia, Degenerative/diagnosis/physiopathology/complications ; Atrophy/etiology ; *Tomography, Optical Coherence/methods ; Middle Aged ; Aged ; Fluorescein Angiography/methods ; Follow-Up Studies ; Inflammation ; Visual Acuity ; Fundus Oculi ; Adult ; }, abstract = {PURPOSE: To describe the progression of atrophy in pathologic myopia eyes with prior retinal inflammatory lesions consistent with punctate inner choroidopathy.<br><br>METHODS: Retrospective case series of 21 eyes with pathologic myopia and resolved retinal inflammatory lesions compared with 26 noninflamed controls (14 fellow eyes; 12 external myopic eyes with pre-existing patchy atrophy). The primary outcome was annual atrophy-area change (mm2/year) on multimodal imaging. Secondary outcomes included incident/enlarging atrophy, multifocal versus unifocal appearance, and META-PM category progression. Group comparisons used Welch t tests and Fisher exact tests; an age-adjusted linear regression examined independent associations.<br><br>RESULTS: Over 5.2 &#xb1; 3.2 years in inflamed eyes and 5.3 &#xb1; 2.4 years in controls, patchy atrophy progressed faster with inflammation (0.76 &#xb1; 0.67 vs. 0.38 &#xb1; 0.47 mm2/year; P = 0.03). Among eyes starting in myopic macular degeneration Category 1 to 2, incident atrophy occurred in 14 of 14 (100%) inflamed versus 4 of 11 (36.4%) controls (P < 0.01). Overall atrophy activity (new or enlarging) was 21 of 21 (100%) in inflamed eyes versus 19 of 26 (73.1%) controls (P < 0.01). Multifocal atrophy was more frequent with inflammation (15/21, 71.4%) than in controls (6/26, 23.1%; P < 0.01). In age-adjusted regression, inflammation remained independently associated with faster atrophy expansion (&#x3b2; = 0.41 mm2/year; 95% CI, 0.04-0.78; P = 0.033).<br><br>CONCLUSION: In pathologic myopia, prior retinal inflammation is independently associated with more frequent multifocal involvement, higher risk of incident atrophy, and a substantially faster atrophy-expansion. Beyond mechanical factors, inflammation seems to be a key driver of atrophic progression in this population.}, }
@article {pmid41701438, year = {2026}, author = {Zhang, X and Liu, ZL and Lin, X and Sun, SN and Shi, D and Tian, L and Li, Y and Jin, ZB}, title = {Wnt signaling dysregulation drives Stargardt disease pathogenesis.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {41701438}, issn = {1869-1889}, abstract = {Stargardt disease, the most common inherited juvenile macular degeneration, is primarily caused by ABCA4 mutations, yet the cellular origin of pathology remains debated. Here, we identify a critical role for Wnt signaling dysregulation, specifically non-canonical Wnt pathway suppression, in driving retinal pigment epithelium (RPE) dysfunction as a central mechanism of disease. Using patient-derived iPSC-RPE harboring distinct ABCA4 mutations, we demonstrate that ABCA4 loss disrupts RPE hexagonal morphology, reduces pigmentation, and aberrantly activates neural retinal differentiation. Mechanistically, transcriptomic and functional analyses revealed pronounced downregulation of non-canonical Wnt signaling (e.g., Wnt5a), which correlated with epithelial disorganization and ectopic neurogenesis. Notably, while canonical Wnt activation failed to rescue these pathological defects, pharmacological stimulation of non-canonical Wnt signaling restored RPE integrity and suppressed neural transdifferentiation in a mutation-dependent manner. These findings not only redefine ABCA4 as a regulator of epithelial Wnt crosstalk but also unveil a divergence in Wnt pathway vulnerability among patients. Our work positions non-canonical Wnt agonism as a therapeutic strategy for Stargardt and underscores the broader imperative for mutation-tailored interventions in inherited retinal diseases. By revealing phenotypic convergence on Wnt signaling dysregulation in ABCA4-deficient RPE, this study provides a framework for understanding epithelial-pathway-driven degeneration, with implications for AMD, fibrosis, and developmental disorders characterized by polarity loss.}, }
@article {pmid41703113, year = {2026}, author = {Frank-Publig, S and Buehl, W and Mares, V and Fuchs, P and Coulibaly, LM and Eidenberger, A and Scheschy, U and Faustmann, G and Gumpinger, M and Sükei, E and Bogunovic, H and Reiter, GS and Sacu, S and Schmidt-Erfurth, U}, title = {Artificial Intelligence-based characterization of therapeutic response in fluid types and volumes influencing retinal function in neovascular age-related macular degeneration.}, journal = {Scientific reports}, volume = {16}, number = {1}, pages = {}, pmid = {41703113}, issn = {2045-2322}, abstract = {UNLABELLED: In the real world, there are variable treatment strategies and therapeutic effects of anti-VEGF therapy in neovascular age-related macular degeneration (nAMD). To investigate mechanisms of fluid resolution in pretreated and treatment-naïve eyes, we aimed to compare treatment response through assessment of fluid types, distribution and volumes. 289 eyes of 289 real-world patients with active nAMD were included in a randomized phase III clinical trial (EudraCT-Number: 2019-003133-42). For this subanalysis, data from baseline and month 1 was collected in 285 eyes. All eyes received treatment at baseline, OCT imaging (Spectralis, Heidelberg Engineering, Germany) and standardized functional testing at both visits. Subretinal fluid (SRF), intraretinal fluid (IRF), pigment epithelial detachment (PED) were automatically quantified. Absolute and relative fluid resolution and BCVA changes were compared. Treatment-naïve eyes had higher IRF volumes before treatment and a higher reduction of IRF (p < 0.01), with no differences for SRF and PED. Accordingly, treatment-naïve patients had a significantly higher gain of BCVA with + 4.6 letters compared to + 1.2 letters (p < 0.01). Precise quantification and compartment distinctions of retinal fluid revealed treatment-naïve eyes showed greater resolution rates for IRF with consecutive significant visual improvement, suggesting that IRF dynamics are particularly relevant and volume-related, especially in the acute phase.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-40138-w.}, }
@article {pmid41703247, year = {2026}, author = {Lolli, I and Pignataro, MG and Termite, AC and Ribezzi, G and Boscia, G and Borrelli, E and Reibaldi, M and Alessio, G and Boscia, F and Viggiano, P}, title = {The progressive journey of poor-responder neovascular AMD: tracking structural evolution and visual decline over time.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41703247}, issn = {1476-5454}, abstract = {PURPOSE: To characterise the natural history of poor-responder neovascular age-related macular degeneration (AMD) by tracking structural evolution and visual decline over time.<br><br>METHODS: This retrospective longitudinal study analysed 70 eyes of 70 treatment-naive neovascular AMD patients who completed loading dose therapy, received &#x2265;7 injections in the first year, and experienced &#x2265;10 ETDRS letter visual acuity (BCVA) loss from post-loading baseline. Spectral-domain OCT imaging and BCVA were evaluated at three timepoints: baseline (post-loading), 10-letter loss, and worst visual outcome. Multivariate regression analysis identified independent predictors of visual acuity at each timepoint. Primary structural parameters assessed included macular atrophy, subretinal fibrosis, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, central retinal thickness (CRT), and fluid parameters.<br><br>RESULTS: Mean follow-up was 38.5&#x2009;&#xb1;&#x2009;22.8 months. Macular atrophy progression was dramatic (7.1%&#x2009;&#x2192;&#x2009;41.4%&#x2009;&#x2192;&#x2009;81.4%, p&#x2009;<&#x2009;0.001) and subretinal fibrosis increased substantially (11.4%&#x2009;&#x2192;&#x2009;25.7%&#x2009;&#x2192;&#x2009;57.1%, p&#x2009;<&#x2009;0.001). CRT showed paradoxical biphasic evolution (262.6&#x2009;&#x2192;&#x2009;278.6&#x2009;&#x2192;&#x2009;252.0&#x2009;&#x3bc;m). Multivariate analysis revealed three distinct phases: no independent predictors at baseline, comprehensive multi-pathway model at 10-letter loss with subretinal fibrosis (&#x3b2;&#x2009;=&#x2009;-0.536), hyperreflective material (&#x3b2;&#x2009;=&#x2009;-0.350), and intraretinal fluid (&#x3b2;&#x2009;=&#x2009;-0.223) as independent predictors (R&#xb2;&#x2009;=&#x2009;0.428), and fibrotic dominance at worst outcome where subretinal fibrosis emerged as the sole predictor (&#x3b2;&#x2009;=&#x2009;-0.469, R&#xb2;&#x2009;=&#x2009;0.220). CRT showed no predictive value across all timepoints.<br><br>CONCLUSIONS: Poor-responder neovascular AMD follows a three-phase evolutionary journey with subretinal fibrosis as the dominant independent predictor of visual decline. These findings demand a paradigmatic shift toward qualitative structural assessment focusing on fibrotic changes rather than thickness-based monitoring.}, }
@article {pmid41703248, year = {2026}, author = {Viggiano, P and Borrelli, E and Giannaccare, G and Reibaldi, M and Boscia, F}, title = {Response to: 'Comment on: 'Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results".}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41703248}, issn = {1476-5454}, }
@article {pmid41703599, year = {2026}, author = {Yu, J and Zhang, Y and Gao, YL and Xu, JM and Chen, H and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ}, title = {Metabolic vulnerability index and MetaboHealth score as risk factors for age-related macular degeneration in a large-scale prospective cohort.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-026-07863-2}, pmid = {41703599}, issn = {1479-5876}, }
@article {pmid41704651, year = {2026}, author = {Wong, MW and Li, H and Dan, YS and Lor, SC and Soh, R and Hoang, QV and Chong, RS}, title = {Associations between Intraocular Pressure or Glaucoma Medication with Axial Length and Pathologic Myopia Incidence and Progression.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101061}, pmid = {41704651}, issn = {2666-9145}, abstract = {OBJECTIVE: To investigate the relationship between intraocular pressure (IOP) and antiglaucoma medications on both the incidence and progression of myopic macular degeneration (MMD), posterior staphyloma and axial length (AXL) elongation in highly myopic (HM) eyes.<br><br>DESIGN: A retrospective multiethnic cohort study with cross-sectional and longitudinal analyses.<br><br>Nine hundred eighty-eight HM eyes from 518 multi-ethnic subjects assessed at the Singapore National Eye Centre (2017-2022). Eyes with glaucoma or on existing IOP-lowering therapy were excluded from the primary analyses. Secondary cross-sectional and longitudinal analyses included eyes with glaucoma to explore medication effects.<br><br>METHODS: Intraocular pressure was measured with noncontact tonometry. Logistic and linear regression models assessed associations between IOP and MMD/staphyloma presence and progression and AXL elongation. Multivariate analysis was performed to identify independent predictors of progression, including effects of antiglaucoma medication use.<br><br>MAIN OUTCOME MEASURES: Presence and progression of MMD and staphyloma, current AXL, and AXL elongation as determined by imaging and clinical examination. Progression was defined by changes in MMD grade, atrophic lesions, or structural staphyloma features over time.<br><br>RESULTS: In nonglaucomatous eyes, IOP was not significantly associated with the presence or progression of MMD, staphyloma, or AXL (all P > 0.05). Across all eyes, longer AXL was correlated with earlier spectacle onset, worse visual acuity, longer anterior chamber depth, presence of tilted disc, superior peripapillary atrophy, vitreomacular traction, staphyloma, epiretinal membrane, dome- or saddle-shaped macula, and lacquer crack (P < 0.05). In longitudinal analyses, baseline glaucoma medication use was significantly associated with reduced AXL elongation over time (&#x3b2; = -0.077, P = 0.036), independent of IOP, whereas tilted disc and staphyloma presence predicted greater elongation (P < 0.05). Myopic macular degeneration and staphyloma progression were primarily associated with structural factors, including presence of sloped fovea, macular retinoschisis, epiretinal membrane, and dome- or saddle-shaped macula at baseline (P < 0.05).<br><br>CONCLUSIONS: Intraocular pressure was not associated with pathologic myopia-related structural changes or AXL in HM eyes. In contrast, use of antiglaucoma medications was associated with reduced AXL elongation. These findings suggest the potential for IOP-independent pharmacologic modulation of AXL in HM eyes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41705769, year = {2026}, author = {Huang, L and Cong, L and Grzybowski, A}, title = {Tobacco-Attributable Age-Related Macular Degeneration Vision Impairment in Japan: A National and Prefecture-Level Analysis From 1990 to 2040.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {2}, pages = {23}, pmid = {41705769}, issn = {2164-2591}, mesh = {Humans ; Japan/epidemiology ; *Macular Degeneration/epidemiology/etiology ; Male ; Female ; Aged ; Prevalence ; Disability-Adjusted Life Years ; *Vision Disorders/epidemiology/etiology ; Aged, 80 and over ; Middle Aged ; Cost of Illness ; Global Burden of Disease ; }, abstract = {PURPOSE: This study aimed to analyze the spatiotemporal burden of vision impairment due to age-related macular degeneration (AMD) in Japan from 1990 to 2021, projecting to 2040.<br><br>METHODS: Using data from the Global Burden of Disease (GBD) study, we systematically analyzed the prevalence, disability-adjusted life years (DALYs), and temporal trends of vision impairment due to AMD in Japan from 1990 to 2021 and projected disease burden to 2040. We also quantified the burden of vision impairment due to AMD attributable to tobacco.<br><br>RESULTS: From 1990 to 2021, the number of AMD-related vision impairment cases increased by 159% to 93,310 (95% uncertainty interval [UI], 78,103-112,033); DALYs increased by 134% to 8907 (95% UI, 5984-12,298). However, the age-standardized prevalence rates declined from 22.3 to 19.73 per 100,000, and DALY rates decreased from 2.34 to 1.94. Prevalence was slightly higher in females, although the DALY rate difference was minimal. Burden disparities across all 47 prefectures were small. The contribution of tobacco to age-standardized DALYs decreased by 36.3%. Projections to 2040 estimate a 42.51% increase in total cases, with a rise in the age-standardized prevalence rate among males but a decline continuing among females.<br><br>CONCLUSIONS: Despite an increase in absolute cases, age-standardized rates of AMD-related vision impairment in Japan declined from 1990 to 2021, likely due to universal health insurance coverage and effective tobacco control policies. This supports ongoing investment to alleviate the burden in an aging society.<br><br>TRANSLATIONAL RELEVANCE: Translating 30-year population data, this study shows that tobacco control and healthcare equity reduce AMD-related vision impairment burden, informing vision loss prevention in aging societies.}, }
@article {pmid41707077, year = {2026}, author = {Pandya, BU and Mihalache, A and Huang, RS and Jhaveri, A and Cao, X and Ballios, B and Felfeli, T}, title = {Effectiveness and Safety of Biosimilar Anti-Vascular Endothelial Growth Factor for Retinal Diseases: A Systematic Review and Meta-Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004807}, pmid = {41707077}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the comparative effectiveness and safety of biosimilar anti-vascular endothelial growth factor (VEGF) versus reference anti-VEGF intravitreal injections for the treatment of retinal diseases.<br><br>METHODS: A systematic review and meta-analysis was performed on studies identified through searches of OVID MEDLINE, Embase, and the Cochrane Library between January 2015 and September 2024. Studies evaluating effectiveness and/or safety outcomes of biosimilar anti-VEGF were included. Meta-analysis was performed with a random effects model. Risk of bias (ROB) assessment was performed with the Joanna Briggs Institute (JBI) tools, and certainty of evidence was evaluated with the GRADE criteria.<br><br>RESULTS: A total of 25 studies were included in the meta-analysis. Diagnoses studied were neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and polypoidal choroidal vasculopathy. There were no significant differences in final visual acuity (VA), change in VA, final retinal thickness (RT), change in RT, and incidence of adverse events over a follow-up duration of 12-63.6 weeks. Subgroup analyses of randomized controlled trials, observational studies, AMD, DME, and agent-specific analysis (aflibercept and ranibizumab) were not significant. Findings are supported by evidence of moderate to high certainty as per the GRADE tool. There was a low to moderate ROB in the included study as per the JBI tool.<br><br>CONCLUSION: Biosimilar anti-VEGF is comparable to reference anti-VEGF with respect to safety profile and visual outcomes. Future research should prioritize including diverse patient populations and adopting standardized, extended follow-up periods to enhance the assessment of long-term safety and effectiveness of biosimilars.}, }
@article {pmid41707600, year = {2026}, author = {Posnic, A and Vaast, M and Poinas, A and Le Pabic, E and Bellamy, JP and Delhay, C and Faure, S and Le Rouic, JF and Henry, A and Lebreton, O and Masse, H and Guillaumie, T and Fournier, I and Mainguy, A and Le Lez, ML and Khanna, RK and George, A and Pipelart, V and Bernard, Y and Grimbert, P and Mazhar, D and Benzerroug, M and Briend, B and Clement, M and Jammes-Veaux, HP and Posnic, MP and Bonissent, A and Guyot, C and Rousseau, N and Trinh Van Dam, B and Bellot, L and Ferron, R and Le Meur, G and Mouriaux, F and Weber, M and Maucourant, Y and Ducloyer, JB}, title = {Extension of the intravitreal injection interval after switching to faricimab in patients with exudative AMD: The multicenter FAR WEST study.}, journal = {Journal francais d'ophtalmologie}, volume = {49}, number = {3}, pages = {104795}, doi = {10.1016/j.jfo.2026.104795}, pmid = {41707600}, issn = {1773-0597}, abstract = {PURPOSE: To assess whether switching to faricimab allowed extending injection intervals without exudation in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.<br><br>METHODS: FAR WEST was a multicenter, observational retrospective cohort study, including patients with nAMD treated with intravitreal anti-VEGF injections (IVI) for at least one year prior to switching to faricimab. Data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M6 follow-up visit. The switch strategy (whether an induction phase was performed or not) was left to the practitioner's discretion.<br><br>RESULTS: A total of 814&#xa0;eyes of 705&#xa0;patients were included in 23&#xa0;centers. The recurrence-free IVI interval increased significantly from 5.6&#xa0;weeks at M0 to 7.2&#xa0;weeks at M6 (+1.6&#xa0;weeks, P<0.0001). The proportion of exudative patients decreased by 37% (P<0.0001). Among 228&#xa0;refractory cases at M0, 88 (39%) achieved a dry macula at M6. A greater interval extension was found in patients who underwent immediate extension. No significant differences were observed in terms of age, time since first injection, type of neovascularisation, or pre-switch IVI interval. The intraocular inflammation rate was 0.6% (n=5).<br><br>CONCLUSION: Switching to faricimab allowed for significantly extending the recurrence-free IVI interval and decreasing the proportion of exudative patients in this cohort. Significant extension was found in a wide range of patients, including those without a loading phase. Further controlled prospective studies are needed to assess the value of a loading phase when switching to faricimab. Safety outcomes were consistent with prior studies.}, }
@article {pmid41708012, year = {2026}, author = {Stuard Sambhariya, W and Bowes Rickman, C and D'Amore, PA and Corradetti, G and Hageman, GS and Howell, GR and Marola, OJ and Phatnani, H and Philp, NJ and Sinha, D and Toomey, CB and Stone, F and Eberhart, C and Handa, JT}, title = {Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.}, journal = {Progress in retinal and eye research}, volume = {111}, number = {}, pages = {101449}, pmid = {41708012}, issn = {1873-1635}, support = {R01 EY031594/EY/NEI NIH HHS/United States ; R01 EY033765/EY/NEI NIH HHS/United States ; R01 EY035805/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Cerebral Amyloid Angiopathy/metabolism/pathology ; *Amyloid beta-Peptides/metabolism ; *Macular Degeneration/metabolism/pathology ; *Cholesterol/metabolism ; *Inflammation/metabolism/pathology ; *Apolipoproteins E/metabolism ; *Complement System Proteins/metabolism ; Alzheimer Disease/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are neurodegenerative conditions that afflict millions of elderly people around the world. AMD is a progressive retinal disorder that leads to central vision loss whereas AD primarily causes cognitive decline and behavioral changes. While each disease has distinct clinical manifestations, the accumulation of extracellular amyloid-β is a common histopathologic finding. Similarly, cerebral amyloid angiopathy (CAA), a vascular condition that can exist independent or with AD, is characterized by the accumulation of amyloid-β in cerebral blood vessels. While significant investigation of the pathophysiologic links between AMD and AD has been conducted, the underlying similarities and differences in the pathobiology of AMD and CAA has not been considered. In this review, we discuss the common pathological features of these two conditions. We then discuss the similar pathobiology that involves cholesterol metabolism, apolipoprotein E, amyloid-β, and complement mediated inflammation. At the same time, we discuss key differences in their pathobiology. This discussion sheds new perspective and insights of their pathobiology.}, }
@article {pmid41709128, year = {2026}, author = {Öncül, H and Dertsiz Kozan, B and Dağ, U and Çağlayan, M and Alakuş, MF and Temel, C and Utlu, ES}, title = {Evaluation of primary care physicians' knowledge, attitudes, and awareness levels regarding age-related macular degeneration.}, journal = {BMC primary care}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12875-026-03228-2}, pmid = {41709128}, issn = {2731-4553}, }
@article {pmid41709226, year = {2026}, author = {Villarruel Hinnerskov, JM and Nielsen, MK and Thomsen, AK and Steffensen, MA and Honoré, B and Vorum, H and Nissen, MH and Sørensen, TL}, title = {Complement regulatory proteins are associated with progression rate of geographic atrophy secondary to age-related macular degeneration.}, journal = {Immunity &amp; ageing : I &amp; A}, volume = {23}, number = {1}, pages = {}, pmid = {41709226}, issn = {1742-4933}, abstract = {BACKGROUND: Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive degenerative disease leading to irreversible vision loss in elderly individuals. The complement system, including the alternative pathway (AP) forms an essential part of the innate immune system. Since dysregulation of the complement system has been strongly associated with the development and progression of GA, we sought to investigate the expression of specific regulators of the complement system, known as complement regulatory proteins (Cregs), in relation to progression rate (PR) of disease in patients with GA.<br><br>RESULTS: Using flow cytometry, we determined the proportion of Cregs on peripheral blood leukocytes drawn from patients with GA. Patients were genotyped for risk-associated SNP (CFH rs1061170, ARMS2 rs10490924) and serial fundus autofluorescence images were used to determine the PR of atrophic lesions. Patients with fast GA progression had a lower proportion of CD59 on CD8&#x2009;+&#x2009;T cells compared to patients with slow progression of disease (p&#x2009;=&#x2009;0.025), suggesting that dysregulated CD59 could be involved in progression of GA. Patients with high-risk CFH genotypes had a higher proportion of CD59 on classical monocytes compared to patients carrying the low-risk genotype (p&#x2009;=&#x2009;0.044).<br><br>CONCLUSION: Our findings indicate that GA progression is associated with dysregulation of complement regulators, and Cregs could serve as a novel target for treatment of GA. However, further studies are needed to elucidate their role in GA pathogenesis and to evaluate their potential as future complement-targeting drugs.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-026-00562-y.}, }
@article {pmid41710168, year = {2026}, author = {Estreicher, A and Biedka, K and Błaszczyk, K and Wesołowski, M and Bulski, J and Sobaś, AE and Ziobro, O and Maj, FJ and Sornat, KB and Klasa, AM and Żełabowski, K and Karwacki, J and Sebzda, T}, title = {The Amsler Grid in Everyday Practice: A Review of Its Role and Limitations in Primary Care.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {542357}, pmid = {41710168}, issn = {1177-5467}, abstract = {This narrative review provides a comprehensive overview of current evidence on the use of the Amsler grid as a simple and cost-effective tool for detecting central visual field defects, particularly in macular disorders such as age-related macular degeneration (AMD). Despite the availability of advanced imaging techniques like optical coherence tomography (OCT), the grid remains valuable in primary care and home monitoring due to its accessibility and ease of use. This review includes studies evaluating its diagnostic performance, clinical applications, and recent digital adaptations, with a focus on early detection and patient self-monitoring. It facilitates early detection of visual disturbances, enabling timely diagnosis and intervention. The test is applicable in various retinal conditions, including AMD, diabetic macular edema, central serous chorioretinopathy, and epiretinal membrane. Although its diagnostic accuracy varies depending on the condition and stage, clinical studies support its reliability as an adjunctive tool in everyday practice. Recent developments include mobile and web-based platforms, as well as integration with artificial intelligence, which may enhance diagnostic accuracy, enable longitudinal monitoring, and improve patient adherence. Early detection is crucial for preserving vision and reducing the global burden of visual impairment.}, }
@article {pmid41711523, year = {2026}, author = {He, R and Ding, W and Cao, J and Guo, C and Li, X and Xiao, G}, title = {Ergothioneine: Evaluation of a Novel Antioxidant for Targeting Ocular Oxidative Stress.}, journal = {Current eye research}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/02713683.2026.2618755}, pmid = {41711523}, issn = {1460-2202}, abstract = {PURPOSE: To evaluate ergothioneine (EGT), a naturally occurring amino acid and endogenous antioxidant, as a novel therapeutic agent for oxidative stress-related ocular diseases. This evaluation specifically aimed to address the challenge of targeted ocular delivery by assessing EGT's antioxidant potency, stability, ocular tolerance, and crucially, its ability to reach the posterior segment (fundus) via topical administration.<br><br>METHODS: This study evaluated EGT as a novel ocular antioxidant by examining its radical scavenging capacity (DPPH assay compared to glutathione, astaxanthin, and coenzyme Q10), stability (at 40&#x2009;&#xb0;C/75% relative humidity for six months using HPLC), ocular tolerance (using a New Zealand rabbit model), and fundus delivery efficiency (topical D9-EGT eye drops quantified by LC-MS/MS).<br><br>RESULTS: EGT demonstrated significantly superior radical scavenging activity, exhibiting 6.4-fold and 46-fold higher rates than glutathione and coenzyme Q10, respectively, at 50&#x2009;ppm. It also showed excellent stability, retaining over 97% of its initial concentration after six months, and caused no ocular irritation at any tested concentration (score 0). Importantly, topical administration of EGT resulted in effective fundus delivery, with peak concentrations reached at 0.5&#x2009;h post-application (1181&#x2009;&#xb1;&#x2009;56&#x2009;ng/g), confirming successful penetration through corneal and scleral barriers. These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops.<br><br>CONCLUSION: These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops. By overcoming key delivery limitations, EGT presents a promising therapeutic strategy for oxidative stress-related ocular diseases such as age-related macular degeneration and diabetic retinopathy. Further studies are warranted to evaluate its long-term efficacy and clinical translation potential.}, }
@article {pmid41712059, year = {2026}, author = {Barbosa, M and Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Barry, MP and Ambresin, A}, title = {Loading dose and 12-month outcomes in treatment-naïve patients with neovascular age-related macular degeneration treated with faricimab, with AI-based analysis of fluid dynamics.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {124}, pmid = {41712059}, issn = {1573-2630}, mesh = {Humans ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography/methods ; *Artificial Intelligence ; Hydrodynamics ; Dose-Response Relationship, Drug ; Time Factors ; Fundus Oculi ; Middle Aged ; Subretinal Fluid ; Antibodies, Bispecific ; }, abstract = {PURPOSE: To evaluate the effects of loading dose and 12 months of faricimab treatment on visual function, retinal anatomy, and fluid dynamics in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients received intravitreal faricimab 6&#xa0;mg monthly (to Month 4) followed by personalized treat-and-extend regimens allowing 4-week interval adjustments. Best-corrected visual acuity (BCVA), retinal anatomy, and fluid dynamics (evaluated using an artificial intelligence-based automated fluid quantification system) were assessed monthly to Month 4, then at Months 6, 9, and 12.<br><br>RESULTS: Fifty-one patients (57 study eyes; mean [SD] BCVA: 66.5 [13.4] letters; mean [SD] central retinal thickness [CRT]: 340.7 [84.7] &#x3bc;m at baseline) were enrolled. Significant improvements in mean BCVA (+&#x2009;3.3 letters; P&#x2009;<&#x2009;0.001) and CRT (-&#x2009;70.5&#xa0;&#x3bc;m; P&#x2009;<&#x2009;0.001) were observed by Month 4. Maximal pigment epithelium detachment (PED) height reduced significantly from baseline to Month 4. Improvements were maintained to Month 12. Intra- and subretinal fluid and PED volumes were significantly reduced versus baseline at all time points. At Month 12, 73.3% of patients were on treatment intervals of 12&#xa0;weeks or longer. Three adverse events were observed, including one mild intraocular inflammation.<br><br>CONCLUSION: Treatment with faricimab resulted in rapid and sustained functional and anatomical improvements in treatment-na&#xef;ve nAMD.}, }
@article {pmid41712218, year = {2026}, author = {Pitcher, JD and Koh, AHC and Tan, CS and Vakharia, P and Dagincourt, N and Patel, S and Yang, M and Margaron, P and Gallego-Pinazo, R}, title = {Rapid Fluid Resolution and Durability With Faricimab in Neovascular Age-Related Macular Degeneration.}, journal = {JAMA ophthalmology}, volume = {144}, number = {3}, pages = {269-272}, pmid = {41712218}, issn = {2168-6173}, mesh = {Humans ; *Subretinal Fluid/drug effects/metabolism ; Double-Blind Method ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Male ; Female ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins ; Treatment Outcome ; Fluorescein Angiography ; Dose-Response Relationship, Drug ; Follow-Up Studies ; Middle Aged ; Antibodies, Bispecific ; }, abstract = {IMPORTANCE: In the TENAYA and LUCERNE randomized clinical trials (RCTs), approximately 80% of study participants with treatment-naive neovascular age-related macular degeneration (nAMD) achieved at least every-12-week faricimab dosing at week 112. Subsequent post hoc analyses showed more rapid drying with faricimab compared with aflibercept, 2 mg, during the initial head-to-head dosing phase (weeks 0-12).<br><br>OBJECTIVE: To investigate whether rapid drying with faricimab, specifically intraretinal fluid (IRF) and subretinal fluid (SRF) resolution through week 12, is associated with later treatment durability.<br><br>This is a post hoc analysis of faricimab-treated study participants from the TENAYA and LUCERNE RCTs, which were randomized, double-masked, multicenter, noninferiority studies of the efficacy and safety of faricimab, 6 mg, up to every 16 weeks vs aflibercept, 2 mg, every 8 weeks. Study participants in this post hoc analysis were those who had treatment-naive nAMD and were in the faricimab arm of TENAYA and LUCERNE. Data analysis was performed from July 2024 to December 2025.<br><br>INTERVENTION: Faricimab, 6 mg, up to every 16 weeks after 4 loading doses (received once every 4 weeks). Following disease activity assessments at week 20 or 24, participants received fixed dosing up to every 16 weeks until week 60 and then a treat-and-extend-based dosing regimen.<br><br>MAIN OUTCOMES AND MEASURES: Multinomial logistic regression modeling was used to test the association between resolution of IRF and SRF through week 12 and the faricimab treatment interval at week 20 or 24 (the first opportunity to extend treatment intervals) and at week 112 (study completion).<br><br>RESULTS: This analysis included 552 participants with their dosing interval at week 20 or 24 available (265 participants with IRF and SRF resolution and 287 without resolution); among them, 478 patients had their dosing interval at 112 weeks available (223 participants with IRF and SRF resolution and 255 without resolution). Study participants with IRF and SRF resolution through week 12, compared with those without resolution through week 12, were more likely to receive every-16-week dosing than every-8-week dosing (odds ratio [OR], 1.99; 95% CI, 1.23-3.21; P&#x2009;=&#x2009;.005) and to receive every-12-week dosing than every-8-week dosing (OR, 1.77; 95% CI, 1.09-2.87; P&#x2009;=&#x2009;.02) at week 20 or 24, and they were more likely to receive every-16-week dosing than every-8-week dosing at week 112 (OR, 1.76; 95% CI, 1.10-2.83; P&#x2009;=&#x2009;.02).<br><br>CONCLUSIONS AND RELEVANCE: These findings suggest that rapid fluid resolution through week 12 with faricimab may be a predictor of extended durability (dosing intervals of every 12 weeks or longer) in participants with nAMD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03823287 and NCT03823300.}, }
@article {pmid41712907, year = {2026}, author = {Sather, RN and Chiang, T and Moon, JY and Dev, S and Belin, PJ}, title = {Real-World Durability of Aflibercept 8 mg and Faricimab in Initiators Versus Switchers: A Multicenter Retrospective Analysis.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004813}, pmid = {41712907}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate real-world differences in treatment durability, functional, and anatomical outcomes in patients who initiated or switched to aflibercept 8 mg or faricimab.<br><br>METHODS: Patients were categorized into four cohorts: (1) initiators of aflibercept 8 mg, (2) initiators of faricimab, (3) switchers to aflibercept 8 mg, and (4) switchers to faricimab. Switchers were further stratified as early (&#x2264;5 prior injections) or late (>5 injections). Treatment durability was assessed using the mean treatment interval, defined as the average of the three most recent injection intervals before or after the switch. Multivariate linear regression models were used to assess the independent effect of treatment strategy on durability, best-corrected visual acuity (BCVA), and central subfield thickness (CST).<br><br>RESULTS: A total of 10,247 patients (12,501 eyes) with either nAMD, DME, or RVO initiated aflibercept 8 mg or faricimab. Initiators achieved greater mean treatment intervals (10 weeks) than switchers (9 weeks post-switch; p < 0.01). Early switchers showed greater durability and CST reduction (-66 &#xb5;m) than late switchers (-19 &#xb5;m; p < 0.01). Faricimab initiators had greater durability (p < 0.01) and CST reductions (p = 0.01) compared to other cohorts. Medicare coverage was associated with longer durability than Medicare Advantage recipients (p < 0.01).<br><br>CONCLUSION: In this real-world cohort, initiation of faricimab or aflibercept 8 mg was associated with greater treatment intervals and improved anatomical outcomes compared to eyes that were switched from older anti-VEGF agents. These findings support early initiation of these anti-VEGF therapies and that step-therapy delays may compromise clinical outcomes.}, }
@article {pmid41713160, year = {2026}, author = {Ashrafi, S and Sajedi, H}, title = {Task-specific neural networks for medical imaging using pretrained fragments.}, journal = {Computers in biology and medicine}, volume = {204}, number = {}, pages = {111545}, doi = {10.1016/j.compbiomed.2026.111545}, pmid = {41713160}, issn = {1879-0534}, mesh = {Humans ; *Neural Networks, Computer ; Algorithms ; *Image Processing, Computer-Assisted/methods ; *Retina/diagnostic imaging ; }, abstract = {The StitchNet framework introduced a paradigm shift in Neural Architecture Search (NAS) by proposing the construction of neural networks from pre-trained fragments. This approach reduces computational costs and enables task-specific model creation without retraining entire networks. Building on this foundation, our study evaluates the practical application of StitchNet in constructing neural networks tailored to medical image classification tasks. Specifically, we assess its performance on a dataset of retinal images classified into three categories: healthy, dry, and wet AMD (Age-Related Macular Degeneration), namely drusen and choroidal neovascularization (CNV). By employing fragments from five pre-trained networks and integrating techniques such as recurrent neural networks (RNNs) and autoencoders, we aim to validate and enhance StitchNet's capabilities. Our findings demonstrate that while StitchNet achieves competitive accuracy with reduced computational overhead, incorporating domain-specific optimizations further improves its adaptability and efficiency. So, the developed network outperforms a scientist-designed network by 6%. In the next phase, we will explore ways to improve the algorithm's efficiency and minimize the data required for processing. Fully reproducible code here: https://github.com/ShafighAshrafi/stitchnet.}, }
@article {pmid41713794, year = {2026}, author = {Liao, X and Lou, J and Liu, C and Wang, Y and Zhu, G and Ke, Y and Bai, M and Yang, P and Yang, W and Chi, W}, title = {Advancements in OCT and OCTA Imaging for AMD: An In-depth Analysis of Research Hotspots, Emerging Trends, and Technological Innovations.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105402}, doi = {10.1016/j.pdpdt.2026.105402}, pmid = {41713794}, issn = {1873-1597}, abstract = {PURPOSE: To map research hotspots and emerging trends of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) in Age-related Macular Degeneration (AMD) from 2015-2024 using bibliometric analysis.<br><br>METHODS: We searched the Web of Science Core Collection (2015-2024) on January 2025, identified 2,471 English-language articles on OCT/OCTA in AMD, and extracted data on countries, institutions, journals, keywords, and citations. CiteSpace 6.4 and Excel were used for co-occurrence/co-citation analyses and visualization; H-indexes were compiled for countries and institutions.<br><br>RESULTS: Seventy-eight countries/regions contributed to the field; the United States led in publications and H-index, followed by China. Among 200 institutions, the University of California System produced the most studies and showed the highest influence. Publication output increased steadily (R[2]&#x2248;0.69). Core topics clustered around geographic atrophy (GA), choroidal neovascularization (CNV), ranibizumab, OCT, and AMD. Recent keyword bursts highlighted macular neovascularization (MNV), hyperreflective foci (HRF), deep learning, impact, and growth. High-impact literature underscored OCT/OCTA's noninvasive vascular imaging utility, anti-VEGF treatment outcomes, GA progression metrics, and rapid advances in AI-driven detection/segmentation and prognostication. Meta-analyses reported high diagnostic accuracy of OCTA for CNV, while technical challenges (e.g., signal-to-noise) persist. Emerging themes include multimodal integration, biomarkers such as hyperreflective foci for prognosis, and time-series/AI models for predicting GA/CNV trajectories and personalizing treatment intervals.<br><br>CONCLUSION: OCT and OCTA research in AMD has expanded substantially, with the U.S. and leading academic centers driving influence. Integrating AI with OCT/OCTA enables earlier detection, refined phenotyping, and data-informed, personalized management. Advancing precision and standardization will further improve diagnostic accuracy and therapeutic decision-making in AMD.}, }
@article {pmid41714388, year = {2026}, author = {Sadeghi, E and DeCicco, J and Gandhi, P and Hasan, N and DiCenzo, B and Jiang, JY and Rahmanipour, E and Sahel, JA and Eller, AW and Chhablani, J}, title = {Differentiation of macular atrophy secondary to neovascular age-related macular degeneration vs. de novo geographic atrophy: a multimodal analysis.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41714388}, issn = {1476-5454}, abstract = {PURPOSE: To compare macular atrophy following neovascular age-related macular degeneration (nAMD) vs. geographic atrophy (GA) following dry AMD.<br><br>METHODS: We analysed 60 eyes from 44 patients: 30 eyes with de novo GA and 30 with macular atrophy secondary to nAMD. All patients had monthly follow-ups before GA onset and continued for at least two years after. GA was defined as complete retinal pigment epithelium atrophy &#x2265;250&#x2009;&#x3bc;m using OCT scans. OCT biomarkers at GA onset, including central macular thickness (CMT), subfoveal choroidal thickness (SFCT), epiretinal membrane (ERM), double-layer sign (DLS), subretinal hyperreflective material (SRHM), hyperreflective foci (HRF), outer retinal tubulation (ORT), and intraretinal fluid (IRF), were assessed. Chi-square test, Spearman correlation, and linear mixed models were used.<br><br>RESULTS: The mean age was 80.06&#x2009;&#xb1;&#x2009;8.60 years, with 50.0% male. Eyes with nAMD progressed to macular atrophy after 31.38&#x2009;&#xb1;&#x2009;30.72 months and 8.86&#x2009;&#xb1;&#x2009;10.84 anti-vascular endothelial growth factor (VEGF) injections. Compared to de novo GA, eyes with macular atrophy following nAMD had larger baseline atrophic area (3.791&#x2009;&#xb1;&#x2009;2.661&#x2009;mm&#xb2; vs. 1.115&#x2009;&#xb1;&#x2009;0.951&#x2009;mm&#xb2;; P&#x2009;<&#x2009;0.001) and greater atrophy growth (2.646&#x2009;&#xb1;&#x2009;2.014&#x2009;mm&#xb2; vs. 0.652&#x2009;&#xb1;&#x2009;0.722&#x2009;mm&#xb2;; P&#x2009;<&#x2009;0.001), with more frequent ERM, DLS, HRF, SRHM, ORT, and IRF. Atrophy growth correlated with baseline SFCT (r&#x2009;=&#x2009;-0.545, P&#x2009;=&#x2009;0.002) and GA area (r&#x2009;=&#x2009;0.501, P&#x2009;=&#x2009;0.005) but not with the number of anti-VEGF injections (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: Eyes with macular atrophy secondary to nAMD exhibit larger initial atrophic areas and faster progression compared to de novo GA. OCT biomarkers may detect previous exudation, helping identify cases where recently FDA-approved GA therapies may be relatively contraindicated due to prior disease.}, }
@article {pmid41714517, year = {2026}, author = {Shen, Y and Chen, Q and He, X and Agrawal, R and Grzybowski, A and Jin, K and Ye, X}, title = {Automated Report Generation in Ophthalmology: Integrating Artificial Intelligence, Multimodal Imaging, and Clinical Data.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1001-1020}, pmid = {41714517}, issn = {2193-8245}, support = {QZYY-2025-225//Project on Scientific and Technological Research of Traditional Chinese Medicine and Ethnic Medicine in Guizhou Province/ ; gzwkj2025-099//Science and Technology Fund Project of Guizhou Provincial Health Commission/ ; }, abstract = {Artificial intelligence (AI) has emerged as a transformative force in ophthalmology, enabling automated, accurate, and efficient clinical reporting. This review summarizes recent advances in AI-driven report generation, emphasizing the integration of multimodal imaging and clinical data. Deep learning and natural language processing (NLP) models can synthesize information from diverse sources-including fundus photography, optical coherence tomography, fluorescein angiography, and patient records-to generate structured, interpretable, and personalized diagnostic reports. Such systems enhance diagnostic precision, streamline workflow, and reduce interobserver variability. We outline the technological foundations underlying these systems, including convolutional and transformer-based architectures, self-supervised and multimodal learning, and large language models. Representative applications in diabetic retinopathy, glaucoma, cataract, and age-related macular degeneration are discussed, highlighting their clinical value and emerging real-world deployment. Persistent challenges-including data heterogeneity, model interpretability, ethical governance, and clinical integration-are critically reviewed. Finally, we explore future directions such as real-time AI-assisted reporting, predictive and personalized analytics, and global scalability across healthcare ecosystems. Multimodal, explainable, and clinically integrated AI systems hold promise to redefine ophthalmic diagnostics and improve both clinician efficiency and patient outcomes.}, }
@article {pmid41716475, year = {2026}, author = {Al-Latayfeh, M and Aleshawi, A and El-Mulki, OS and Baker, M and Qaddoumi, Z and Attar, D and Alma'aitah, L and Jarrah, EZ and Abu Khalil, Z and Awad, W and Dayeh, MR and Al Beiruti, S and Al-Dwairi, R}, title = {Accuracy and Reproducibility of Different Artificial Intelligence Chatbots' Responses to Patient-Based Vitreoretinal Questions: A Comparative Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {580133}, pmid = {41716475}, issn = {1177-5467}, abstract = {BACKGROUND: Generative artificial intelligence (AI) chatbots are increasingly used by patients and their reliability in complex ophthalmic conditions remains uncertain. This study aimed to compare the accuracy, comprehensiveness, and reproducibility of five AI chatbots-ChatGPT-5.o, DeepSeek R1, Meta AI, Grok 3.0, and Google Gemini 2.5 Pro-in responding to patient-centered vitreoretinal questions.<br><br>METHODS: A total of 135 questions covering diabetic retinopathy, floaters/flashes, age-related macular degeneration, retinal tear/detachment, and vitrectomy were sourced from the American Academy of Ophthalmology "Ask an Ophthalmologist" database. Each question was submitted twice to each chatbot under standardized instructions. Two board-certified vitreoretinal ophthalmologists independently graded responses for accuracy and reproducibility. Accuracy was calculated as the proportion of responses graded "Correct and Comprehensive" or "Accurate but incomplete"; reproducibility was defined as agreement between the two responses.<br><br>RESULTS: ChatGPT-5.o achieved the highest overall accuracy (94%, n=127/135, 95% CI: 89.9%-98.1%) with a reproducibility rate of 96.3% (n=130/135, 95% CI: 93.1%-99.5%). DeepSeek R1 demonstrated the greatest reproducibility (98.5%, n=133/135, 95% CI: 96.5%-100.0%) and high accuracy (92.6%, n=125/135, 95% CI: 88.1%-97.1%). Meta AI showed 91% (95% CI: 86.1%-95.9%) accuracy and 94% (95% CI: 89.9%-98.1%) reproducibility, whereas Grok 3.0 yielded the lowest accuracy (49.6%, n=67/135, 95% CI: 41.2%-58.0%) despite moderate reproducibility (88.1%, n=119/135, 95% CI: 82.7%-93.5%). Google Gemini 2.5 Pro recorded 72.6% (95% CI: 65.1%-80.1%) accuracy and the lowest reproducibility (77%, 95% CI: 69.9%-84.1%). By category, "Vitrectomy" scored the highest across all chatbots (94%, 95% CI: 87.2%-100.0%), followed by "Macular degeneration" (90%, 95% CI: 85.0%-95.0%). However, the category "Diabetic retinopathy" scored the lowest accuracy rate (64.7%, 95% CI: 52.1%-77.3%).<br><br>CONCLUSION: ChatGPT-5.o and DeepSeek R1 approached high accuracy and reproducibility comparable to clinical standards, indicating potential as patient-education tools in vitreoretinal care. However, variability across models and disease categories highlights the need for cautious clinical adoption and continued optimization to ensure safe, reliable information delivery.}, }
@article {pmid41716622, year = {2026}, author = {Rohowetz, LJ and Flynn, HW and Townsend, JH}, title = {A second occurrence of intravitreal injection-associated endophthalmitis 2 years apart.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102525}, pmid = {41716622}, issn = {2451-9936}, abstract = {PURPOSE: This case report describes a patient who developed a second episode of endophthalmitis in the same eye following intravitreal injections administered 2 years apart.<br><br>OBSERVATIONS: An 83-year-old pseudophakic male with a history of neovascular age-related macular degeneration and diabetes mellitus complained of decreased visual acuity and pain in the left eye 1 day after receiving intravitreal aflibercept 2 mg. Best-corrected visual acuity (BCVA) was light perception. The clinical examination revealed signs of endophthalmitis including fibrin and hypopyon while B-scan ultrasonography demonstrated vitreous opacities and membranes. The patient underwent vitreous tap and injection with intravitreal vancomycin, ceftazidime, and dexamethasone. Pars plana vitrectomy with posterior hyaloid detachment was performed the following day due to a relative lack of clinical improvement. Vitreous cultures ultimately demonstrated no growth and BCVA improved to baseline. Anti-VEGF therapy was resumed 3 months after the initial diagnosis of endophthalmitis. Two years later the patient presented with evidence of a second episode of endophthalmitis 4 days after receiving aflibercept 8 mg. Vitreous tap and injection was again performed and cultures revealed growth of Staphyloccoccus epidermidis. The patient demonstrated marked improvement with no evidence of residual inflammation at 2 weeks. Best-corrected visual acuity was 20/50 at 7-month follow-up examination.<br><br>CONCLUSION AND IMPORTANCE: Endophthalmitis is a rare complication of intravitreal injection. The current report describes a patient who developed a second occurrence of endophthalmitis associated with an intravitreal injection 2 years later.}, }
@article {pmid41716779, year = {2026}, author = {Hahn, W and Erffmeier, K and Schulze, M and Zahnert, F and Knake, S and Tsalouchidou, PE}, title = {Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report.}, journal = {Molecular genetics and metabolism reports}, volume = {46}, number = {}, pages = {101296}, pmid = {41716779}, issn = {2214-4269}, abstract = {BACKGROUND: Mutations in COQ8A cause primary coenzyme Q10 deficiency, which can present clinically heterogeneously: Symptoms range from cerebellar ataxia, epilepsy, encephalomyopathy, macular degeneration to nephropathy. High-dose coenzyme Q10 supplementation is widely used, yet there is little evidence on complementary strategies, particularly for non-epileptic features such as cerebellar ataxia.<br><br>CASE PRESENTATION: We report a 46-year-old female with genetically confirmed COQ8A-related coenzyme Q10 (CoQ10) deficiency, presenting with ataxia and epilepsy characterized by myoclonic and bilateral tonic-clonic seizures, who participated in a clinical protocol of ketogenic intermittent fasting, a method of intermittent fasting combined with medium-chain triglycerides (MCT) primarily designed for seizure management. The patient followed a 16:8 intermittent fasting regime combined with MCT intake for three months, followed by three months of all-alone intermittent fasting. Routine blood markers and brain MRI, including diffusion imaging were obtained before and after ketogenic fasting.<br><br>RESULTS: During the study protocol, while no seizure reduction in myoclonic seizures could be observed, ataxia - quantified by the Scale for the Assessment and Rating of Ataxia (SARA) - improved significantly from 8.5 to 6.0 during the interventions. MRI showed a trend suggesting improved cerebellar microstructural integrity.<br><br>CONCLUSIONS: This case highlights the potential of ketogenic intermittent fasting as an adjunct therapy for mitochondrial ataxia. Ketogenic intermittent fasting was associated with clinically meaningful improvement of ataxia in a patient with COQ8A-related CoQ10 deficiency, suggesting that ketogenic dietary strategies may represent a promising adjunct therapeutic approach for mitochondrial ataxia. Future research should assess this intervention in larger patient cohorts to confirm its potential benefits.}, }
@article {pmid41717027, year = {2026}, author = {Cen, S and Li, J and Reilly, J and Chen, J and Jiang, HR and Shu, X}, title = {The therapeutic potential of gypenosides for age-related macular degeneration.}, journal = {Frontiers in nutrition}, volume = {13}, number = {}, pages = {1773391}, pmid = {41717027}, issn = {2296-861X}, }
@article {pmid41717163, year = {2026}, author = {Sourla, E and Zaheer, N and Chavan, R}, title = {Switching From Intravitreal Ranibizumab (Lucentis) to Biosimilar Ranibizumab (Ongavia) Injections: Insights From a Tertiary Care Eye Centre.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e101850}, pmid = {41717163}, issn = {2168-8184}, abstract = {BACKGROUND: Ranibizumab has been widely used to treat retinal conditions such as wet age-related macular degeneration, diabetic macular oedema, and macular oedema secondary to retinal vein occlusions. In 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) approved Ongavia, the first biosimilar of ranibizumab. Ongavia offers comparable efficacy and safety, with a similar side effect profile to the original medication, while being more cost-effective.<br><br>METHOD: The study was conducted in the medical retina department of a tertiary care eye hospital. Data were collected from patients undergoing treatment with intravitreal ranibizumab (Lucentis) who were switched to the ranibizumab biosimilar, Ongavia, between November 2023 and February 2024.&#xa0;This study included two components. The first was a cross-sectional observational survey, in which patients being switched to Ongavia completed a satisfaction questionnaire regarding the information leaflet received and the discussions held about the switch. The second component was a retrospective review to assess the effectiveness and safety of ranibizumab biosimilar Ongavia in patients with wet AMD. After two Ongavia injections, the treatment interval for the next injection was reviewed and compared with the treatment interval with ranibizumab. Similarly, OCT scans before and after the switch were reviewed and compared. Any adverse effects documented in the clinical notes were recorded.<br><br>RESULTS: Out of 121 eyes, 92 eyes (76%) were switched to biosimilar ranibizumab (Ongavia) injections, while 18 eyes (15%) continued receiving ranibizumab injections. Patient satisfaction with the information process was 100%. Eighty-seven eyes of patients with wet AMD received more than two Ongavia injections as per the treat-and-extend protocol. Out of these 87 eyes, in 64 eyes (73.5%), injection intervals were either maintained or extended. The treatment interval was reduced in seven eyes (8%), and nine eyes (10.3%) were switched to a different anti-VEGF medication. No safety concerns were identified with biosimilar ranibizumab.<br><br>CONCLUSIONS: Patient satisfaction with the information process was high, likely due to active involvement in treatment decision-making. The results indicate that the clinical effectiveness of ranibizumab biosimilar Ongavia is comparable to ranibizumab and that it has a similar safety profile. Ongavia could serve as a cost-effective alternative, reducing healthcare system costs while maintaining high standards of patient care.}, }
@article {pmid41717238, year = {2026}, author = {Hwang, Y and Jamil, MU and Woo, KM and Kaiser, SM and Babiker, F and Rosenfeld, PJ and Waheed, NK and Fujimoto, JG}, title = {Large Hypertransmission Defects Exhibit Choriocapillaris Flow Speed Impairment in Nonexudative Age-Related Macular Degeneration.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101060}, pmid = {41717238}, issn = {2666-9145}, abstract = {PURPOSE: To investigate choriocapillaris (CC) blood flow speed in regions associated with hypertransmission defects (hyperTDs) in nonexudative age-related macular degeneration (AMD) using variable interscan time analysis (VISTA) OCT angiography (OCTA).<br><br>DESIGN: Retrospective cross-sectional analysis of a prospectively collected cohort.<br><br>SUBJECTS: Thirty-one eyes from 29 subjects with nonexudative AMD.<br><br>METHODS: Patients with age-related macular degeneration were imaged using a 600 kHz A-scan rate prototype swept-source OCT with a 5 &#xd7; 5 mm field of view and 5 B-scan repeats (1.25 ms interscan time). Hypertransmission defects were traced on choroidal en face projections and categorized by their greatest linear dimension (GLD): large (&#x2265;250 &#x3bc;m), medium (63-250 &#x3bc;m), and small (<63 &#x3bc;m). Choriocapillaris blood flow speed was quantified using VISTA, which measures OCTA signal saturation dynamics across multiple interscan times. Variable interscan time analysis flow speed (VFS) was evaluated at the macula and within hyperTDs. Choriocapillaris flow speed impairment (&#x394;VFS) for each hyperTD was calculated as the difference between its VFS and the macular average. To assess spatial extent, &#x394;VFS was assessed beyond lesion boundaries. Traditional metrics of OCTA signal and flow deficits (FDs) were also evaluated.<br><br>MAIN OUTCOME MEASURES: Choriocapillaris blood flow speed impairment (&#x394;VFS) within and around hyperTDs.<br><br>RESULTS: The macular average CC VFS was 1.47 &#xb1; 0.34 ms[-1], with no significant difference between eyes with (n = 14) and without (n = 17) hyperTDs. A total of 88 hyperTDs were analyzed: 19 large, 28 medium, and 41 small. Large hyperTDs showed significant CC flow impairment (&#x394;VFS = -0.37 &#xb1; 0.18 ms[-1], Padjusted < 0.0001), with impairment extending 100 &#x3bc;m beyond lesion boundaries (Padjusted = 0.0061). Medium-sized hyperTDs demonstrated moderate impairment (&#x394;VFS = -0.30 &#xb1; 0.47 ms[-1], Padjusted = 0.031), while small hyperTDs did not. In linear mixed-effects modeling, large and medium hyperTDs were associated with significant reductions in flow speed (-0.40 ms[-1], P = 0.014; -0.31 ms[-1], P = 0.030, respectively), corresponding to approximately 25% decreases from macular average. OCT angiography signal and FD metrics also detected size-dependent flow impairment.<br><br>CONCLUSIONS: Large hyperTDs in nonexudative AMD exhibit reduced CC flow speed extending beyond the lesion boundary. Longitudinal studies will investigate whether CC flow predicts onset and progression of hyperTDs.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41719023, year = {2026}, author = {Anderer, S}, title = {Cataract Surgery Not Linked With Macular Degeneration Progression.}, journal = {JAMA}, volume = {335}, number = {11}, pages = {930}, doi = {10.1001/jama.2025.26398}, pmid = {41719023}, issn = {1538-3598}, }
@article {pmid41719329, year = {2026}, author = {Li, Y and Jing, M and Wang, W and Lin, W and Zhang, Y and Nie, T and Liu, P and Lu, WN and Chen, Y and Fielding Hejtmancik, J and Zheng, Q and Hou, L and Ma, X}, title = {DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {123}, number = {8}, pages = {e2511926123}, pmid = {41719329}, issn = {1091-6490}, support = {2023YFC2506100//MOST | National Key Research and Development Program of China (NKPs)/ ; 82171065//MOST | National Natural Science Foundation of China (NSFC)/ ; 82571231//MOST | National Natural Science Foundation of China (NSFC)/ ; 82371081//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; Mice ; *Mitochondria/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Endoplasmic Reticulum/metabolism ; Disease Models, Animal ; *HSP70 Heat-Shock Proteins/metabolism/genetics ; Mice, Knockout ; Humans ; *Membrane Proteins/metabolism/genetics ; Calcium/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/genetics ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mice, Inbred C57BL ; *Necroptosis ; Inflammasomes/metabolism ; }, abstract = {Retinal pigment epithelium (RPE) cell damage is a critical factor of age-related macular degeneration (AMD), the leading cause of blindness among the aged population. This study focuses on the AMD susceptible gene, Death associated protein like 1 (DAPL1), and provides insights with significant therapeutic implications. DAPL1-deficient mice exhibit dry AMD-like pathological features, a phenomenon whose mechanisms have remained largely unknown. Here, we reveal that DAPL1 deficiency promotes the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) to cause mitochondrial Ca[2+] overload and dysfunction, which triggers the activation of inflammasomes, leading RPE cells to RIPK1-mediated PANoptosis, an inflammatory programmed cell death, in an experimental dry AMD (dAMD) mouse model. Knockdown of Ripk1 in the Dapl1-/- mice RPE inhibits RPE cell PANoptosis and ameliorates the severity of dAMD pathological features. Conversely, overexpression of DAPL1 inhibits MAM formation and protects RPE cells from PANoptosis in the model. Mechanistically, DAPL1 suppresses MAM formation by downregulating GRP75 expression. This disrupts the formation of the VDAC-GRP75-IP3R axis, which comprises critical tethering proteins responsible for endoplasmic reticulum to mitochondria coupling and Ca[2+] trafficking. Knockdown of Grp75 inhibits the formation of MAM and prevents mitochondrial Ca[2+] overload, improving mitochondrial quality and inhibiting PANoptosis in RPE cells, thereby interrupting the progression of experimental dAMD in Dapl1-deficient mice. These results unveil the role of MAMs regulated by DAPL1 in RPE cell PANoptosis and AMD progression, highlighting targeting MAM formation as a potential therapeutic strategy for treating dAMD.}, }
@article {pmid41720012, year = {2026}, author = {Li, H and Xiong, Y and Zheng, Y}, title = {Hyperoside as a promising multi-target candidate for neovascular age-related macular degeneration. mechanisms involving Wnt/β-catenin signaling, oxidative stress, and inflammation suppression.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {153}, number = {}, pages = {157952}, doi = {10.1016/j.phymed.2026.157952}, pmid = {41720012}, issn = {1618-095X}, mesh = {*Oxidative Stress/drug effects ; Animals ; *Choroidal Neovascularization/drug therapy ; Inflammation/drug therapy ; *Macular Degeneration/drug therapy ; *Wnt Signaling Pathway/drug effects ; Humans ; Mice ; Mice, Inbred C57BL ; Male ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Quercetin/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD), which is primarily characterized by choroidal neovascularization (CNV), encounters limitations with current therapeutic approaches, including treatment resistance and the burden of frequent injections, highlighting the need for exploring novel effective therapeutic agents and their mechanisms for nAMD management. Oxidative stress and inflammation are core pathogenic drivers of CNV in nAMD, and hyperoside (HYP)-a major flavonoid from Cuscuta chinensis, exhibits potent antioxidant and anti-inflammatory activities. These properties position HYP as a promising candidate for addressing the unmet treatment needs of nAMD and warrant further investigation into its mechanism of action in CNV modulation.<br><br>PURPOSE: This study aimed to explore the therapeutic potential of HYP-the main active component of the traditional Chinese herb Cuscuta chinensis Lam., and to elucidate its underlying molecular mechanisms in treating nAMD.<br><br>STUDY DESIGN: A combined in vivo and in vitro experimental strategy was adopted to systematically evaluate the therapeutic efficacy of HYP against nAMD and dissect the mechanistic basis of its action on CNV progression.<br><br>METHODS: This study adopted a multi-dimensional research approach: network pharmacology was first used to predict HYP's multi-target potential in regulating inflammation, oxidative stress, and vascular endothelial growth factor (VEGF) signaling; a murine model of laser-induced CNV was established to evaluate HYP's effects on CNV lesion area, retinal/choroidal damage, and inflammatory infiltration; reactive oxygen species (ROS) levels were detected, the expression of endogenous antioxidant enzymes (Cat, Nqo1, Sod2), Vegf, pro-inflammatory cytokines (Il-1&#x3b2;, Ccl2, Il-6, Tnf-&#x3b1;), and Wnt pathway-related genes (Myc, Plcb2, Rspo1, Wnt7a/7b, Ctnnb1) and protein (&#x3b2;-catenin); lipopolysaccharide (LPS)-stimulated ARPE-19 cells were used to corroborate HYP's antioxidant, anti-inflammatory effects, and Wnt pathway inhibition; molecular docking was employed to analyze the interaction between HYP and &#x3b2;-catenin; pharmacokinetic analysis was conducted to assess HYP's distribution in ocular tissues; and integrated transcriptomic analysis (RNA-seq) and Gene Expression Omnibus (GEO) database data analyses were performed to confirm the role of the Wnt pathway in human AMD and its correlation with intraocular inflammation.<br><br>RESULTS: Network pharmacology predicted that HYP has multi-target potential against inflammation, oxidative stress, and VEGF signaling; in the murine laser-induced CNV model, HYP treatment significantly reduced CNV lesion area, alleviated retinal/chorioretinal damage, and attenuated inflammatory infiltration; mechanistically, HYP effectively scavenged ROS, significantly upregulated the expression of endogenous antioxidant enzymes (Cat, Nqo1, Sod2), and downregulated the expression of Vegf, pro-inflammatory cytokines (Il-1&#x3b2;, Ccl2, Il-6, Tnf-&#x3b1;), key Wnt pathway genes (Myc, Plcb2, Rspo1, Wnt7a/7b, Ctnnb1), and the Wnt pathway's signature protein &#x3b2;-catenin; HYP's antioxidant, anti-inflammatory effects, and Wnt pathway inhibition were corroborated in LPS-stimulated ARPE-19 cells; molecular docking suggested a direct interaction between HYP and &#x3b2;-catenin; pharmacokinetic analysis showed favorable ocular distribution of HYP, supporting its biological relevance; and integrated transcriptomic and GEO data analyses confirmed the involvement of the Wnt pathway in human AMD and its correlation with intraocular inflammation.<br><br>CONCLUSION: Collectively, the findings demonstrate that HYP ameliorates CNV in nAMD through a concerted inhibition of oxidative stress, inflammation, and angiogenesis, primarily by suppressing Wnt/&#x3b2;-catenin signaling, which positions HYP as a promising multi-target candidate for the development of novel nAMD therapies.}, }
@article {pmid41720386, year = {2026}, author = {Yang, X and Xu, W and Xie, H and Guo, X and Zhu, F and Xing, Y and Chen, C}, title = {SREBP1-driven SCD1 protects retinal pigment epithelium from oxidative damage by activating the NRF2/GPX4 axis.}, journal = {Experimental eye research}, volume = {266}, number = {}, pages = {110932}, doi = {10.1016/j.exer.2026.110932}, pmid = {41720386}, issn = {1096-0007}, mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; *Oxidative Stress/physiology ; *Sterol Regulatory Element Binding Protein 1/metabolism/genetics ; *Stearoyl-CoA Desaturase/metabolism/biosynthesis/genetics ; Animals ; *NF-E2-Related Factor 2/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology ; Mice ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Mice, Inbred C57BL ; Disease Models, Animal ; Cell Survival ; Cells, Cultured ; Lipid Peroxidation ; Blotting, Western ; Iodates ; }, abstract = {This study reveals the pivotal role of the Sterol Regulatory Element-Binding Protein 1 (SREBP1)/Stearoyl-CoA Desaturase 1 (SCD1) lipid metabolic axis in protecting retinal pigment epithelium (RPE) against oxidative damage. We demonstrate SCD1 downregulation in age-related macular degeneration (AMD) patient tissues and sodium iodate (SI)-induced models, while its overexpression enhances cell viability and ameliorates oxidative injury. Mechanistically, we uncover a novel pathway where SCD1-derived oleic acid activates the nuclear factor erythroid 2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) signaling cascade, scavenging reactive oxygen species (ROS) and suppressing lipid peroxidation. Notably, oleic acid also mitigated oxidative stress via this pathway without directly promoting cell survival. These results not only elucidate SCD1's crucial protective mechanism in AMD pathogenesis but also establish the SREBP1/SCD1 axis as a promising therapeutic target for developing innovative interventions against retinal degeneration.}, }
@article {pmid41720710, year = {2026}, author = {Cupertino, L and Colon, CG and Kang, A and Kolosky, T and Zhou, J and Levin, MR and Alexander, JL}, title = {Accessibility and readability of Spanish and Portuguese-translated online information about common eye conditions: A cross-sectional content analysis study.}, journal = {Journal of the National Medical Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jnma.2026.01.005}, pmid = {41720710}, issn = {1943-4693}, abstract = {PURPOSE: To evaluate the readability and accountability (reliability, quality, and credibility) of online patient education materials for common eye conditions in English, Portuguese, and Spanish.<br><br>DESIGN: Cross-sectional content analysis SUBJECTS: A total of 192 websites across seven eye diseases were analyzed in three languages: English (n&#x202f;=&#x202f;63), Portuguese (n&#x202f;=&#x202f;67), and Spanish (n&#x202f;=&#x202f;62).<br><br>METHODS: First-page Google search websites for macular degeneration, cataract, diabetic retinopathy, glaucoma, conjunctivitis, uveitis, and dry eye were assessed for readability using Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), and Flesch Reading Ease (FRE). Accountability was evaluated using JAMA and DISCERN benchmarks. Websites were also categorized by source type into: academic, national, private, or crowdsourced. Statistical analyses were done using MANOVA, ANOVA, and Tukey's HSD post-hoc tests.<br><br>MAIN OUTCOME MEASURES: Readability (FKGL, GFI, FRE) and accountability (JAMA, DISCERN) indices RESULTS: English-language websites had significantly more accessible readability scores (mean FKGL 8.1) than Spanish (16.6) and Portuguese (16.0) counterparts (p&#x202f;<&#x202f;0.001). Portuguese websites had the lowest JAMA scores (1.2) and were predominantly authored by private entities. Spanish-language sites showed mixed results, outperforming English in some accountability metrics. Crowdsourced pages like Wikipedia had the highest accountability but poorest readability. Language was a significant predictor for readability and accountability in a multivariate analysis (p&#x202f;<&#x202f;0.001).<br><br>CONCLUSION: Online ophthalmology patient education materials in Portuguese and Spanish demonstrate significantly poorer readability, and in some cases, lower accountability compared to English-language resources, posing a significant barrier for patients with limited English proficiency. Future efforts should focus on developing standardized, multilingual patient education materials that balance readability with content reliability, potentially incorporating tools such as large language models (LLM's), which have shown potential in improving accessibility of non-English health information.}, }
@article {pmid41721855, year = {2026}, author = {Borchert, GA and Charbel Issa, P and Xue, K and MacLaren, RE and Cehajic-Kapetanovic, J and Downes, SM and De Silva, SR}, title = {Geographic atrophy in age-related macular degeneration: phenotypic characterisation for clinical trial consideration.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41721855}, issn = {1435-702X}, abstract = {Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) and a leading cause of central vision loss. Advances in multimodal imaging for GA have improved its phenotypic characterisation, enabling more precise assessment of disease. This is increasingly important for identifying features predictive of progression to inform prognosis and guide patient counselling, enable selection for clinical trials and for disease monitoring both in routine clinical practice and in a research setting. In addition, accurately determining foveal involvement is crucial for selection of patients suitable for emerging therapies. High-resolution imaging is also important to recognise and distinguish GA subtypes such as pachychoroid GA from conventional GA, given their genetic and phenotypic differences and possible variation in response to therapy.Imaging modalities include colour fundus photography, which is widely available and allows an initial assessment of GA lesions. Fundus autofluorescence imaging permits clear visualisation of GA borders and provides an accurate topographical map of GA pattern and extent, whereas near-infrared reflectance imaging may be superior for evaluation of foveal involvement. Optical coherence tomography (OCT) allows for measurement of the ellipsoid zone which may correlate to visual function and permits differentiation between biomarkers such as nascent GA, incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA respectively), and identification of pachychoroid GA. Each of these have important prognostic implications and enable accurate selection for clinical trials, monitoring progression and treatment response. Emerging approaches such as red excitation light and high-resolution OCT, may provide more accurate and reliable assessment of atrophic changes. Alongside these advances, artificial intelligence-based tools show great potential in automating GA detection, characterising of structural biomarkers, measuring progression rates and screening patients for clinical trials, increasingly reliability and reproducibility. A better understanding of the important role of multimodal imaging in the classification and assessment of GA, and detection of factors that affect progression will enable clinicians to advise, monitor and, where possible, appropriately treat this major cause of sight loss.}, }
@article {pmid41722793, year = {2026}, author = {Zhuang, Z and Jia, X and Lin, H and Hu, P and Hu, J}, title = {Bidirectional causal associations between immune cell phenotypes and age-related macular degeneration subtypes: A mendelian randomization study.}, journal = {Experimental gerontology}, volume = {216}, number = {}, pages = {113074}, doi = {10.1016/j.exger.2026.113074}, pmid = {41722793}, issn = {1873-6815}, mesh = {Humans ; Mendelian Randomization Analysis ; Phenotype ; *Macular Degeneration/immunology/genetics ; Genome-Wide Association Study ; Aged ; *Wet Macular Degeneration/immunology/genetics ; Male ; Female ; Finland ; *Geographic Atrophy/immunology/genetics ; Monocytes/immunology ; HLA-DR Antigens ; }, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population, characterized by two primary subtypes: dry AMD (dAMD) and wet AMD (wAMD). While immune mechanisms are implicated in AMD pathogenesis, the causal relationships between specific immune cell phenotypes and AMD subtypes remain incompletely characterized.<br><br>METHODS: Bidirectional two-sample Mendelian randomization (MR) analysis was conducted to evaluate causal associations between 731 immune cell phenotypes and AMD subtypes. Immune cell phenotype data were sourced from publicly available GWAS datasets, encompassing 3757 individuals of European descent. AMD data were obtained from the Finnish Finngen R10 database, including 5239 wAMD cases and 6651 dAMD cases. The inverse-variance weighted (IVW) method was used as the primary analytical approach, complemented by reverse MR analysis to assess bidirectional relationships.<br><br>RESULTS: The MR analysis identified significant causal associations between specific immune cell phenotypes and AMD subtypes. For wAMD, the expression of HLA-DR on CD14[-]CD16[+] monocytes exhibited a positive association (OR&#xa0;=&#xa0;1.11, P&#xa0;=&#xa0;1.65&#xa0;&#xd7;&#xa0;10[-5]), whereas CD25 on CD28[+]CD4[+] T cells showed a negative association (OR&#xa0;=&#xa0;0.87, P&#xa0;=&#xa0;0.70&#xa0;&#xd7;&#xa0;10[-4]). In the case of dAMD, the expression of HLA-DR on CD14[+]CD16[+] monocytes was positively associated with disease risk (OR&#xa0;=&#xa0;1.13, P&#xa0;=&#xa0;0.84&#xa0;&#xd7;&#xa0;10[-6]). Reverse MR analysis revealed that dAMD negatively influenced the expression levels of Effector Memory CD4[-]CD8[-] T cells (OR&#xa0;=&#xa0;0.91, P&#xa0;=&#xa0;0.36&#xa0;&#xd7;&#xa0;10[-4]) and CD28[+]CD4[-]CD8[-] T cells (OR&#xa0;=&#xa0;0.92, P&#xa0;=&#xa0;0.90&#xa0;&#xd7;&#xa0;10[-4]). Notably, no evidence supported a causal effect of wAMD on immune cell phenotypes.<br><br>CONCLUSIONS: Using updated GWAS data, this study confirms subtype-specific immune associations in AMD and reports the first evidence of reverse causality: dAMD may directly modulates adaptive immune cell phenotypes. These findings refine our understanding of AMD immunopathogenesis and highlight potential targets for subtype-specific therapies.}, }
@article {pmid41723148, year = {2026}, author = {Cui, X and Hui, J and Han, Z and Han, Q}, title = {Antioxidant vitamin index and risk of age-related macular degeneration: multicenter validation and clinical translation.}, journal = {npj aging}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41514-026-00348-y}, pmid = {41723148}, issn = {2731-6068}, support = {NKSGZ202305//Nankai University Eye Institute Key Science and Technology Fund/ ; TJYXZDXK-3-004A-3//Tianjin Key Medical Discipline Construction/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults, with oxidative stress as a central driver. We proposed the Antioxidant Vitamin Index (AVI), a composite indicator integrating vitamins A, C, and E to quantify systemic antioxidant nutritional status, and evaluated its association with AMD across three large cohorts: the UK Biobank, NHANES 2005-2008, and a Tianjin clinical cohort. Using Cox proportional hazards models for incident AMD in the UK Biobank and multivariable logistic regression for AMD prevalence in NHANES and Tianjin, complemented by restricted cubic splines, quartile analyses, and machine learning, we consistently observed that higher AVI was independently associated with a lower risk of AMD. Dose-response analyses showed a progressive decline in AMD risk with increasing AVI, and model performance improved when AVI was added to conventional risk factors. Machine learning and SHAP interpretation further identified age and AVI as dominant predictors of AMD. These findings support AVI as a biologically grounded, quantifiable metric with potential for early screening, risk stratification, and nutrition-based prevention of AMD.}, }
@article {pmid41723406, year = {2026}, author = {Moukhadder, HM and Wahoud, N and Hassan, SA and Saade, JS}, title = {A case report of spontaneously resolving Descemet's detachment after cataract surgery.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {}, pmid = {41723406}, issn = {1471-2415}, mesh = {Humans ; Male ; Aged ; *Descemet Membrane/pathology ; Visual Acuity/physiology ; Remission, Spontaneous ; *Cataract Extraction/adverse effects ; *Corneal Diseases/etiology/physiopathology ; *Postoperative Complications ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: To report a case of large central Descemet's membrane detachment (DMD) following cataract surgery and discuss the potential for spontaneous resolution as an alternative to surgical intervention.<br><br>OBSERVATIONS: A 79-year-old male with a history of macular degeneration and ocular hypertension developed a large central DMD following cataract surgery complicated by posterior capsular rupture. The patient initially presented with severe corneal edema and an uncorrected visual acuity (UCVA) of 20/200. Despite medical treatment, the DMD persisted, and surgical intervention was considered at week 4 post-op. However, the patient was lost to follow-up, and the surgery could not be performed. At a six-week follow-up, the DMD had resolved spontaneously, with the patient's UCVA improving to 20/30 and best-corrected visual acuity (BCVA) to 20/20.<br><br>CONCLUSIONS AND IMPORTANCE: This case demonstrates that large central DMDs (Descemet's membrane detachments) can occasionally resolve spontaneously.}, }
@article {pmid41723561, year = {2026}, author = {Wu, L and Rojas, S and Rao, X and Politis, M and Roca, JA and Nehemy, M and Berrocal, MH and Fromow-Guerra, J and Barraza-Lino, K and Lopez, C and Maia, M and Cardenas-Mirón, A and Gabela, G and Baldivieso-Hurtado, O and Gabela, C and Chinchilla, L and Verdaguer, JI and Zas, M and Young, M and García-Aguirre, G and Ramirez-Estudillo, JA and Abreu, N and Flores, M and Velez, W and Baez, Y and Arriola-Lopez, A and Casella, AM}, title = {Early Latin American experience with faricimab for retinal diseases: FARI-LATAM study for the Pan-American collaborative retina study (PACORES) group.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00804-7}, pmid = {41723561}, issn = {2056-9920}, }
@article {pmid41724259, year = {2026}, author = {Han, M and Wei, M and Zhao, J and Yu, Y and Li, J and Li, X and Gou, J and He, H and Tang, X and Kong, J and Yin, T and Zhang, Y}, title = {Butylphthalide nanoemulsion for management of dry age-related macular degeneration via antioxidant and anti-inflammatory mechanisms.}, journal = {International journal of pharmaceutics}, volume = {693}, number = {}, pages = {126702}, doi = {10.1016/j.ijpharm.2026.126702}, pmid = {41724259}, issn = {1873-3476}, mesh = {Animals ; Emulsions ; *Antioxidants/administration &amp; dosage/pharmacokinetics/pharmacology ; *Anti-Inflammatory Agents/administration &amp; dosage/pharmacokinetics/pharmacology ; Mice ; Oxidative Stress/drug effects ; *Macular Degeneration/drug therapy/chemically induced/metabolism/pathology ; Humans ; *Benzofurans/administration &amp; dosage/pharmacokinetics/pharmacology/chemistry ; Mice, Inbred C57BL ; Male ; NF-E2-Related Factor 2/metabolism ; Disease Models, Animal ; Iodates ; NF-kappa B/metabolism ; *Nanoparticles/chemistry ; Reactive Oxygen Species/metabolism ; }, abstract = {Dry age-related macular degeneration (dry AMD) is a posterior ocular segment disease characterized primarily by progressive retinal pigment epithelium degeneration, which is driven largely by oxidative stress. Effective treatment remains challenging owing to limited therapeutic agents and intrinsic physiological barriers that hinder drug delivery to the posterior eye. To address this, we developed a butylphthalide-loaded nanoemulsion (NBP-NE) that exhibits potent reactive oxygen species-scavenging and anti-inflammatory properties. Ex vivo permeation studies and pharmacokinetic analysis revealed that NBP-NE significantly enhances corneal and scleral penetration of butylphthalide (NBP), suggesting improved posterior ocular delivery. Moreover, NBP-NE exhibited robust antioxidant and anti-inflammatory effects in both in vitro and in vivo models, mechanisms associated with upregulation of the Nrf2 pathway and suppression of NF-κB signaling. In a sodium iodate-induced mouse model of dry AMD, topical administration of NBP-NE provided superior retinal morphological and functional protection by effectively attenuating oxidative stress and inflammatory responses. These findings represent the first reported application of NBP for dry AMD therapy and position NBP-NE as a promising noninvasive strategy for managing other oxidative stress-related posterior ocular diseases.}, }
@article {pmid41725834, year = {2026}, author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Wang, YX and Nangia, V and Panda-Jonas, S}, title = {Differentiation Between Moderate Versus High Myopia: The 2-Continent Eye Study.}, journal = {Ophthalmology science}, volume = {6}, number = {2}, pages = {100999}, pmid = {41725834}, issn = {2666-9145}, abstract = {OBJECTIVE: To determine the cutoff value in axial length between moderate myopia versus high myopia in dependence on the prevalence of myopic macular degeneration (MMD).<br><br>DESIGN: Population-based studies conducted in Russia, China, and India.<br><br>PARTICIPANTS: The project included the population-based investigations of the Beijing Eye Study (n = 3325; age: 40+ years), Russian Ural Eye and Medical Study (n = 5586 participants; age: 40+ years), Ural Very Old Study (n = 541; age: 85+ years) and Ural Children Eye Study (n = 4255; age: 6+ years), and Central India Eye and Medical Study (n = 4467; age: 30+ years).<br><br>METHODS: The participants underwent a series of general medical and ophthalmic examinations, including fundus photography and ocular biometry. Myopic macular degeneration was defined according to the Meta-analysis for Pathologic Myopia Study Group.<br><br>MAIN OUTCOME MEASURES: Prevalence of MMD in dependence on axial length.<br><br>RESULTS: The total study population included 36 123 eyes (18 471 individuals) (age: 47.4 &#xb1; 23.4 years; range: 6-100 years) (axial length: 23.2 &#xb1; 1.1 mm; range: 18.22-34.20 mm). In the total study population, higher MMD stage was associated with longer axial length (&#x3b2;: 0.55; B: 0.14; 95% confidence interval [CI]: 0.14-0.15; P < 0.001), older age (&#x3b2;: 0.09; B: 0.001; 95% CI: 0.001-0.001; P < 0.001), female sex (&#x3b2;: 0.12; B: 0.07; 95% CI: 0.06-0.07; P < 0.001), and Indian ethnicity (&#x3b2;: 0.10; B: 0.07; 95% CI: 0.06-0.07; P < 0.001). Higher prevalence of MMD stage 2+ and 3+ correlated with longer axial length (odds ratio [OR]: 9.10; 95% CI: 6.93-11.9; P < 0.001 and OR: 6.90; 95% CI: 5.14-9.26; P < 0.001, respectively), older age (OR: 1.06; 95% CI: 1.04-1.08; P < 0.001 and OR: 1.08; 95% CI: 1.05-1.11; P < 0.001, respectively), and Indian ethnicity (OR: 6.96; 95% CI: 2.70-17.9; P < 0.001 and OR: 3.69; 95% CI: 1.26-10.8; P = 0.02, respectively). The turning points of the regression curves of the associations of axial length with prevalence of MMD stage 2+ and 3+ were located at axial length values of between 26.0 and 26.5 mm, respectively.<br><br>CONCLUSIONS: The axial length-related cutoff for moderate versus high myopia was located approximately at 26.0 and 26.5 mm for the prevalence of MMD stage 2+ and 3+, respectively, with higher values for younger individuals. Myopic macular degeneration prevalence was higher in the Indian cohort.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41726370, year = {2026}, author = {Afarid, M and Baghban, R and Ghasemali, S and Zamani, J and Zareei, A}, title = {In Silico Design and Analysis of a Novel Ranibizumab-derived Peptide against the Vascular Endothelial Growth Factor.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {21}, number = {}, pages = {}, pmid = {41726370}, issn = {2008-2010}, abstract = {PURPOSE: Blocking the interaction between vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) is recognized as an effective strategy for treating neovascular age-related macular degeneration (nAMD). The present research aimed at designing and modelling an anti-VEGF peptide based on ranibizumab for potential application in inhibiting the VEGF/VEGFR2 interaction.<br><br>METHODS: Effective amino acids in the interaction between VEGF and ranibizumab were analyzed using Swiss-PdbViewer (SPDBV), PyMOL, and Chimera software. The effective area in this interaction was determined and applied as a basis to design a peptide. Then, this sequence (containing 25 amino acids) was subjected to random mutagenesis, and the binding affinity of the resulting peptides was analyzed using the ClusPro software. Subsequently, GROMACS v5.0.6 was employed for molecular dynamics (MD) simulations to evaluate the stability of target-ligand complexes. Ultimately, the peptide exhibiting the highest affinity was grafted into the kB1 and MCoTI-II frameworks to enhance the stability.<br><br>RESULTS: This modification resulted in improved peptide-VEGF binding affinity, demonstrating the potential of in silico design for creating effective anti-angiogenic peptides in antiangiogenic therapies.<br><br>CONCLUSION: The findings from this study provide a basis for designing and validating peptide inhibitors against VEGF.}, }
@article {pmid41727089, year = {2026}, author = {Lim, RR and Zhao, E and Hass, DT and Wang, Y and Eminhizer, M and Ortolan, D and Niernberger, S and Tong, A and Nelson, BR and Nazario, M and Adipudi, V and Bharti, K and Hurley, JB and Du, J and Chao, JR}, title = {Nutrient microenvironments reprogram RPE metabolism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.11.705448}, pmid = {41727089}, issn = {2692-8205}, abstract = {Induced pluripotent stem cell-derived retinal pigment epithelium (iPSC RPE) has become a widely used model for studying the mechanisms of age-related macular degeneration (AMD). However, the nutrient composition of currently used RPE culture media is highly variable, posing a major challenge to reproducibility in RPE metabolism and phenotype. We systematically investigate how six distinct nutrient microenvironments shape RPE phenotype, function and metabolism in both iPSC RPE and fetal RPE (fRPE). These included MEMα, DMEM-HG/F12 basal media, physiological human plasma-like medium (HPLM) supplemented with FBS or B27, and X-VIVO 10. Although canonical RPE markers were expressed across all conditions, B27 supplementation and X-VIVO 10 increased RPE cell size, hexagonality, and transepithelial resistance. Culture in HPLM+FBS induced accumulation of lipid droplets and sub-RPE deposits, whereas X-VIVO 10 resulted in the formation of large intracellular vacuoles. B27 supplementation enhanced basal respiration, while X-VIVO 10 increased glycolytic capacity. Amino acid consumption was broadly conserved across media types, including complete depletion of proline in all conditions by 48 hours; however, lipid and nucleotide metabolism varied substantially between conditions. Notably, B27 supplementation in specific media types reversed the net direction of several metabolites, with creatine, serine and taurine shifting from consumption to production, while riboflavin and guanine shifted from production to consumption. These findings establish the nutrient environment as a key determinant of RPE phenotype, function and metabolism. Our work provides a valuable resource for media selection and interpretation of cellular and metabolic phenotypes relevant to RPE disease modeling.}, }
@article {pmid41727524, year = {2026}, author = {Patel, RH and Mothy, D and Boinpally, N and Choudhry, HS and Bhavsar, P and Khouri, AS}, title = {Evaluation of Social Media Short-Form Video Content for Patient Education on Vision-Threatening Diseases.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {8987000}, pmid = {41727524}, issn = {2090-004X}, abstract = {PURPOSE: The rapid spread of unreliable misinformation on vision-threatening diseases can significantly affect the eye health behaviors and outcomes of the patients consuming short-form social media content. This study evaluates short-form videos pertaining to vision-threatening diseases to quantify video quality, content, and popularity.<br><br>METHODS: This cross-sectional study analyzed short-form videos on cataracts, diabetic retinopathy, glaucoma, and age-related macular degeneration from TikTok, Instagram Reels, and YouTube Shorts. A hashtag search identified the first fifty videos on each disease from each social media platform. Two reviewers evaluated them, resolving discrepancies with a third. Outcome measures included number of views, likes, comments, uploader source, content type, modified DISCERN score (0-5 scale), and global quality scale (GQS) score (1-5 scale). Engagement outcomes were summarized descriptively using medians and interquartile ranges, while reliability and quality outcomes were analyzed using one-way ANOVA with Tukey post hoc comparisons.<br><br>RESULTS: TikTok videos demonstrated higher median engagement (views, likes, and comments) compared to Instagram Reels and YouTube Shorts. Videos on cataracts had higher engagement statistics compared to the other vision-threatening diseases across all platforms. Physicians were the most common video source (45%). The most common content categories were treatments/management (36%) and general symptoms (22%). YouTube Shorts had a significantly greater average DISCERN (2.93&#x2009;&#xb1;&#x2009;0.70) and GQS score (3.85&#x2009;&#xb1;&#x2009;1.26) than Instagram Reels and TikTok (p < 0.001). Videos from patients had the lowest mean DISCERN and GQS scores.<br><br>CONCLUSIONS: TikTok had the greatest median engagement levels, while YouTube Shorts had the greatest mean quality and reliability. Videos from patients and philanthropists had lower quality scores, while healthcare professionals and organizations had the highest. Future efforts should understand the patients' perspectives, address misinformation, and improve quality across all social media platforms.}, }
@article {pmid41728315, year = {2026}, author = {Liu, R and Wang, X and Corradetti, G and Soylu, C and Ferrington, DA and Sadda, SR and Zhang, Y}, title = {Adaptive Optics Fluorescence Lifetime Imaging Ophthalmoscopy for Single-Cell-Resolved In Vivo Metabolic and Structural Imaging of the Human Retinal Pigment Epithelium.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.07.26345814}, pmid = {41728315}, abstract = {Fluorescence lifetime imaging ophthalmoscopy permits in vivo assessment of retinal metabolism but has remained limited by insufficient cellular resolution in the human eye. Here we present adaptive optics-enhanced fluorescence lifetime imaging ophthalmoscopy (AOFLIO), a method for single-cell-resolved, in vivo structural and metabolic imaging of the human retinal pigment epithelium (RPE). Through real-time correction of ocular wavefront aberrations, precisely synchronized adaptive optics reflectance and lifetime image acquisition via a phase-locked loop-based timing architecture, and sub-pixel photon registration that localizes individual autofluorescence photons with high spatial precision, AOFLIO directly resolves the RPE cell mosaic and measures autofluorescence decay using the same photons, enabling direct structural-functional correlation at the single-cell level. We demonstrate single-cell RPE lifetime mapping in healthy subjects and reveal altered metabolic signatures and fine characterization of RPE metabolic in age-related macular degeneration. AOFLIO establishes a platform for cellular-scale metabolic imaging in the living human eye.}, }
@article {pmid41731033, year = {2026}, author = {Lamanna, F and Riotto, E and Faes, L and Fu, DJ}, title = {Infographic: ranibizumab for neovascular age-related macular degeneration: the MARINA study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41433-026-04348-w}, pmid = {41731033}, issn = {1476-5454}, }
@article {pmid41731445, year = {2026}, author = {Seweryn, M and Kopel, J and Augustynska, J and Mikołajewicz, A and Toro, MD and Rejdak, R}, title = {Multidimensional evaluation of the potential impact of faricimab availability on healthcare system accessibility for retinal disease treatment in Poland.}, journal = {BMC health services research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12913-026-14231-9}, pmid = {41731445}, issn = {1472-6963}, }
@article {pmid41732606, year = {2026}, author = {Ladki, M and Gupta, PK and Malaya, L and Afrouzian, M}, title = {Dry Age-Related Macular Degeneration and Dense Deposit Disease: A Histopathological Comparison of Macular and Renal Lesions.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102164}, pmid = {41732606}, issn = {2168-8184}, abstract = {Background Dry age-related macular degeneration (AMD) and dense deposit disease (DDD) in the kidney have molecular commonality due to the involvement of the complement system. DDD is a renal disease linked to defects of the complement alternative pathway, and in dry AMD, complement components have been found within drusen. In this study, pathologic features of dry AMD and DDD were studied by light and immunofluorescence microscopy to clarify whether morphologic similarities exist between the two diseases. Methodology Sections were obtained from (1) the macula of four patients with dry AMD; (2) renal biopsies of two DDD patients; (3) the macula from healthy eye donors; and (4) a kidney biopsy of a normal human subject. Sections were stained with hematoxylin and eosin, periodic acid-Schiff (PAS), and periodic-acid-methenamine silver for light microscopy and with C3b antisera for fluorescence microscopy. Results Changes observed in dry AMD specimens included (1) the presence of numerous drusen containing PAS- and silver-positive material; (2) thickening of the Bruch's membrane; (3) thickening of prominent PAS-positive intercapillary pillars; and (4) degeneration and dropouts in the choriocapillaris and dilatation and congestion of vessels in the Sattler's layer. In comparison, changes in the DDD specimens included (1) thickening of the glomerular basement membrane (GBM) and presence of double contours; and (2) mesangial and endocapillary proliferation. C3b was positive in both macular drusen and along the GBM. Conclusions Basement membrane changes in dry AMD share morphological similarities with the GBM changes in DDD, and, in both diseases, C3b is deposited, suggesting that the association between the two diseases possibly reflects a common pathogenesis.}, }
@article {pmid41732778, year = {2026}, author = {Nabil, AS and Gholami, S and Leng, T and Lim, JI and Alam, MN}, title = {Federated Learning for Multi-Disease Ophthalmic Diagnostics Using OCT Angiography.}, journal = {Ophthalmology science}, volume = {6}, number = {3}, pages = {101030}, pmid = {41732778}, issn = {2666-9145}, abstract = {PURPOSE: To conduct a comprehensive systematic evaluation of federated learning (FL) strategies for multi-disease retinal classification using OCT angiography (OCTA), implementing a 2-part experimental framework to establish foundational feasibility and optimize performance under realistic heterogeneous conditions while ensuring privacy preservation.<br><br>DESIGN: Retrospective multi-center FL study using a systematic 2-part experimental design: (1) foundational feasibility evaluation under controlled homogeneous conditions, and (2) comprehensive optimization under realistic heterogeneous conditions using Dirichlet distribution partitioning (&#x3b1; = 0.5).<br><br>PARTICIPANTS: A total of 456 OCTA images from patients with 7 retinal pathologies, with diabetic retinopathy (31.1%) and normal cases (25.2%) comprising the majority, sourced from the public OCTA-500 data set (n = 300) and a private collection from the University of Illinois Chicago (n = 156).<br><br>METHODS: Five FL aggregation strategies (federated averaging [FedAvg], federated proximal [FedProx], federated magnetic resonance imaging [FedMRI], federated Adagrad, and federated Yogi) were systematically evaluated across multiple optimization dimensions: 7 architecture configurations spanning vision transformers, established convolutional neural networks, and hybrid models; 5 transfer learning freezing strategies; 3 local epoch configurations (2, 5, and 10); and scalability analysis across 2, 3, and 5-client federations. Security mechanisms including differential privacy (&#x3b5; = 1.0-8.0) and secure aggregation were integrated and evaluated. Performance was assessed across 3 classification scenarios: 7-class, 4-class modified, and 4-class streamlined.<br><br>MAIN OUTCOME MEASURES: Classification accuracy, receiver-operating-characteristic area under the curve (ROC-AUC), and macro-averaged F1-score with comprehensive privacy-utility analysis and computational efficiency metrics.<br><br>RESULTS: Under controlled conditions, FL achieved superior performance in simplified classifications, with FedAvg, FedProx, and FedMRI reaching 72.09% accuracy versus 69.77% centralized training. Comprehensive optimization identified DenseNet121 as optimal architecture (79.55% accuracy, 89.68% ROC-AUC), with "most" freezing strategy (75% frozen layers) providing 60% training time reduction while maintaining superior performance. Federated proximal demonstrated exceptional resilience to heterogeneity (-11.7% degradation). Bonawitz secure aggregation achieved optimal privacy-utility balance (63.64% accuracy with cryptographic guarantees), whereas differential privacy maintained clinical utility under moderate constraints (&#x3b5; &#x2248; 4-6).<br><br>CONCLUSIONS: This systematic evaluation establishes FL as a comprehensive solution for privacy-preserving multi-institutional OCTA-based disease classification, with careful architectural selection, optimization strategies, and security mechanisms enabling performance that matches or exceeds centralized approaches while maintaining regulatory compliance and clinical utility.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.}, }
@article {pmid41733690, year = {2026}, author = {Ghasemi, M and Ghasemi, A and Behjati, J and Nikkhah, H}, title = {Association between diabetic retinopathy and age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41733690}, issn = {1435-702X}, abstract = {KEY MESSAGES: WHAT IS KNOWN : • Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment, and both share overlapping pathogenic mechanisms such as oxidative stress and vascular dysfunction. • Previous studies exploring the association between DR and AMD have reported inconsistent findings, with some suggesting DR as a risk factor and others reporting a protective association.<br><br>WHAT IS NEW: &#x2022; This is the first systematic review and meta-analysis specifically examining the association between DR and AMD. &#x2022;&#xa0;Our results demonstrate no significant relationship between DR and AMD, despite high between-study heterogeneity&#xa0;and robust sensitivity analyses. &#x2022;&#xa0;The findings highlight that existing evidence is primarily based on unadjusted data, emphasizing the need for well-designed prospective cohort studies that account for confounding variables and treatment effects.}, }
@article {pmid41734820, year = {2026}, author = {Gabrielle, PH and Eid, P and Aho, LS and Kodjikian, L and Souied, E and Uzzan, J and Conart, JB and Delyfer, MN and Creuzot-Garcher, C}, title = {Prognostic Factors in Patients With Submacular Haemorrhage Complicating Age-Related Macular Degeneration: A Post Hoc Analysis of the STAR Study.}, journal = {Clinical &amp; experimental ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ceo.70094}, pmid = {41734820}, issn = {1442-9071}, support = {//Centre Hospitalier R&#xe9;gional universitaire DIJON (CHU DIJON)/ ; }, abstract = {BACKGROUND: To investigate prognostic factors of recent submacular haemorrhage (SMH) complicating neovascular age-related macular degeneration (nAMD) treated with surgery or pneumatic displacement combined with intravitreal injection of anti-vascular endothelial growth factor.<br><br>METHODS: Post hoc analysis of the STAR randomised controlled trial data evaluating the influence of baseline clinical and imaging characteristics on visual outcomes over 6&#x2009;months using multivariate generalised additive mixed models.<br><br>RESULTS: Patients with worse baseline visual acuity (VA) had faster (estimated degree of freedom [EDF]&#x2009;=&#x2009;2.87, p&#x2009;<&#x2009;0.001) and greater predicted visual gain (difference&#x2009;=&#x2009;+21.03 [14.64; 27.42] letters for eyes with 10 vs. 40 letters at baseline, p&#x2009;<&#x2009;0.001) and lower predicted VA at 6&#x2009;months (difference&#x2009;=&#x2009;-8.82 [-15.14; -2.52] letters for eyes with 10 vs. 40 letters at baseline, p&#x2009;<&#x2009;0.001), whereas patients with better baseline VA showed more stable trajectories of predicted visual gain and higher predicted VA at 6&#x2009;months. Thinner SMH (&#x2264;&#x2009;1000&#x2009;&#x3bc;m) was significantly associated with faster (EDF&#x2009;=&#x2009;2.93 for &#x2264;&#x2009;1000&#x2009;&#x3bc;m vs. 2.66 for >&#x2009;1000&#x2009;&#x3bc;m) and greater predicted visual improvement (difference&#x2009;=&#x2009;+13.5 [3.66; 23.39] letters between &#x2264;&#x2009;1000 and >&#x2009;1000&#x2009;&#x3bc;m, p&#x2009;<&#x2009;0.001) and higher predicted final VA (difference&#x2009;=&#x2009;+13.00 [3.11; 22.80] letters between &#x2264;&#x2009;1000 and&#x2009;>&#x2009;1000&#x2009;&#x3bc;m, p&#x2009;<&#x2009;0.001). Interactions between the treatment group and both VA and SMH thickness were non-significant.<br><br>CONCLUSION: Better VA and lower SMH thickness at baseline were significantly associated with better visual outcomes over 6&#x2009;months, independently of treatment arm in SMH complicating nAMD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02557451.}, }
@article {pmid41734823, year = {2026}, author = {Blanco-Fernández, G and Blanco-Fernández, B and Fraga-López, FJ and Luzardo-Álvarez, AM and Fernández-Ferreiro, A and Otero-Espinar, FJ}, title = {Design and evaluation of semi-solid lipid implants for controlled intravitreal release of bevacizumab.}, journal = {International journal of pharmaceutics}, volume = {693}, number = {}, pages = {126714}, doi = {10.1016/j.ijpharm.2026.126714}, pmid = {41734823}, issn = {1873-3476}, mesh = {*Bevacizumab/administration &amp; dosage/chemistry ; Delayed-Action Preparations/chemistry/administration &amp; dosage ; Humans ; *Lipids/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/chemistry ; *Drug Implants/chemistry ; Intravitreal Injections ; Drug Liberation ; Cell Line ; Cell Survival/drug effects ; }, abstract = {Bevacizumab is a monoclonal antibody used intravitreally as an anti-VEGF therapy for some ocular diseases. However, this type of treatment presents some limitations, such as the invasiveness of its administration and the need for frequent injections due to the clearance of the antibody from the vitreous chamber. Semi-solid lipid implants emerge as an attractive possibility for the sustained release of biological drugs like bevacizumab, so they could have great potential for the subsequent treatment of VEGF-dependent degenerative retinal pathologies, such as proliferative diabetic retinopathy or neovascular age-related macular degeneration. In this work, injectable lipid implants were designed based on the lipids Precirol® ATO 5, Tefose® 63, Geleol[TM], and Tefose® 1500. The implants were easy to manufacture by melting and mixing. The surface of the implants was characterized by scanning electron microscopy, while the distribution of bevacizumab inside was characterized by confocal Raman mapping microscopy. Subsequently, the state of the antibody after release was evaluated by Raman Spectroscopy and Attenuated Total Reflection Infrared spectroscopy, showing an unaltered quaternary structure. Furthermore, the implants were able to sustain the antibody release for almost 40 days. Biocompatibility was assessed by assay with ARPE-19 cells. Finally, the calorimetry assay allowed us to refine the best possible formulation for further studies. This type of implant showed suitable properties as a potential therapeutic platform for the treatment of neovascular age-related macular degeneration and proliferative diabetic retinopathy, being injectable, easy to make, homogeneous, having sustained release and being biocompatible.}, }
@article {pmid41735681, year = {2026}, author = {Bodmer, NS and Faes, L and Gross, N and Bachmann, LM and Huber, C and Näpflin, M and Schmid, MK}, title = {Prevalence and patterns of anti-angiogenic treatment discontinuation in neovascular age-related macular degeneration-insights from health claims data.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41735681}, issn = {1476-5454}, abstract = {PURPOSE: To assess patterns and institutional variability of anti-angiogenic treatment discontinuation in neovascular age-related macular degeneration (nAMD) within Switzerland, and to examine the association of digital home monitoring with treatment persistence.<br><br>METHODS: Retrospective observational analysis combined nationwide health insurance claims data (Helsana, n&#x2009;=&#x2009;4840) and clinical data from a major tertiary centre (LUKS, n&#x2009;=&#x2009;1932; nAMD subset n&#x2009;=&#x2009;1387). Discontinuation was defined as no further injections for 31-365 days after the last intravitreal injection (IVI) and classified as supervised (&#x2009;&#x2265;&#x2009;1 follow-up visit in this period) or unsupervised (no follow-up visits in this period). Variability was evaluated among the 20 largest providers and across seven regions. Digital home monitoring's impact on non-persistence was assessed in the clinical cohort.<br><br>RESULTS: Substantial heterogeneity was observed. Supervised discontinuation ranged from 20.7 to 45.7% (pooled proportion 32.0%, 95% confidence interval [CI] 30.2-33.9%) and unsupervised from 10.9 to 25.7% (pooled proportion 18.2%, 95%CI 16.8-19.8%) across centres. In the LUKS cohort, 1-year persistence was 93.7%, dropping to 72.7% by year 4, with unsupervised discontinuation rising from 3.0 to 12.5%. In 100 patients using voluntary digital home monitoring non-persistence was less likely (adjusted OR 0.59, 95%CI 0.35-0.98); among those who discontinued, home-monitoring users were more likely to remain under supervision (74% vs 54%).<br><br>CONCLUSIONS: Treatment discontinuation in nAMD is frequent and demonstrates striking institutional and regional variability. The heterogeneity in discontinuation patterns suggests that treatment persistence may be modifiable through targeted, systematic, and patient-centred interventions. Digital home monitoring may be a promising strategy to support engagement and reduce non-persistence.}, }
@article {pmid41737035, year = {2026}, author = {Jiang, B and Zhang, L and Hong, N and Wen, Y and Li, A and Shi, Y and Dong, F}, title = {Recent Progress in Selenium Nanomedicines for Ocular Diseases.}, journal = {International journal of nanomedicine}, volume = {21}, number = {}, pages = {583175}, pmid = {41737035}, issn = {1178-2013}, mesh = {Humans ; *Selenium/chemistry/therapeutic use/administration &amp; dosage/pharmacokinetics ; *Eye Diseases/drug therapy ; *Nanomedicine/methods ; Animals ; *Nanoparticles/chemistry ; Drug Delivery Systems ; Antioxidants/administration &amp; dosage/therapeutic use ; Quantum Dots/chemistry ; }, abstract = {Vision impairment represents a significant and growing global socioeconomic burden. In the elderly population, cataracts, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are the predominant causes of visual loss. Conventional ophthalmic drug therapies are limited by low bioavailability and dose-related toxicity, highlighting the urgent need for safer and more effective treatments. Selenium (Se), an essential trace element, is critical for antioxidant defense, redox homeostasis, and immune regulation. Although the roles of elemental Se in ocular physiology and diseases are well-documented, its clinical application is constrained by its narrow therapeutic window and poor bioavailability. To overcome these limitations, Se nanoparticles (SeNPs) have emerged as a superior alternative, offering enhanced bioavailability, reduced toxicity, and the capability for targeted drug delivery. Strong preclinical evidence supports the therapeutic potential of Se nanomedicines in models of DR, retinal neovascularization, infectious keratitis, and cataracts. Significantly, the initial stages of clinical translation are in progress, as demonstrated by a pioneering Phase I trial involving CdSe/ZnS quantum dots (QDs) in patients with retinitis pigmentosa (RP), which has shown both tolerability and improvements in visual function. This review provides a comprehensive and up-to-date analysis of Se-based nanomedicines for ocular diseases, based on a literature search of PubMed, Scopus, Web of Science, and Google Scholar. It elucidates how SeNPs uniquely synergize intrinsic multi-mechanistic bioactivities (e.g., antioxidant, anti-angiogenic) with targeted and stimuli-responsive drug delivery, establishing them as versatile nanoplatforms with significant clinical translation potential for complex ocular pathologies. Therefore, further research is essential to optimize their design, elucidate their mechanisms of action, and ultimately facilitate their safe and effective clinical translation.}, }
@article {pmid41737853, year = {2026}, author = {Gulati, S and Coak, E and Mascia, D and Li, K and Ko, S and Bonine, NG}, title = {Cross-Sectional Survey of Real-World Physician Prescribing Practices for Anti-VEGF Agents in the Treatment of Neovascular Age-Related Macular Degeneration and Associated Patient Burden in the United States.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {572019}, pmid = {41737853}, issn = {1177-5467}, abstract = {PURPOSE: This study aimed to address the lack of data on the real-world use of the anti-vascular endothelial growth factor (VEGF)/anti-angiopoietin 2 agent faricimab and purely anti-VEGF agents in neovascular age-related macular degeneration (nAMD) in the United States.<br><br>PATIENTS AND METHODS: Data were derived from the Adelphi Real World nAMD Disease Specific Programme (DSP)&#x2122;, a cross-sectional survey of patients with nAMD and their treating physicians, conducted in the US November 2023-May 2024. Ophthalmologists provided demographic and clinical data as well as reasons for agent and dosing strategy selection, for patients with nAMD, aged &#x2265;55, prescribed anti-VEGF treatment at the time of survey.<br><br>RESULTS: Sixty-four physicians (90.6% retinal specialists), reported on 497 patients (faricimab, n = 89 patients; anti-VEGF, n = 408 patients). Mean (&#xb1; standard deviation) age was 76.0 &#xb1; 8.5, 52.1% were female and 88.5% White. Most common symptoms at survey were blurred vision (faricimab: 56.2%, anti-VEGF: 67.9%), distortion of central vision (faricimab: 44.9%, anti-VEGF: 50.7%) and loss of visual acuity (faricimab: 39.3%, anti-VEGF: 41.9%). Main reasons for agent selection were clinical factors/efficacy (faricimab 89.9%, anti-VEGF: 93.4%), and treatment administration/compliance (faricimab 71.9%, anti-VEGF: 41.4%), which included improved patient compliance and extended dosing intervals. Faricimab was commonly dosed as treat-and-extend (67.4%) and anti-VEGFs as fixed interval (38.5%). Reasons for dosing strategy selection included improvement in visual acuity, patient functionality, clinical evidence and fewer consultations for the patient. Most physicians agreed/strongly agreed that some insurers restrict (84.4%) or deny (85.9%), access to the most appropriate products for patients.<br><br>CONCLUSION: Despite receiving treatment, nAMD patients have substantial remaining symptom and treatment burden. Physicians may choose faricimab over purely anti-VEGF agents for its clinical efficacy and reduced treatment burden. Physicians take both clinical factors and patient burden into account when selecting agents and dosing regimens, while reimbursement concerns hinder prescribing in some patients.}, }
@article {pmid41739393, year = {2026}, author = {Çakır, A and Akkan, F and Kapran, Z and Ünal, M and Şerif, N and Uzundede, T and Karataş, G and Öztürk, M and Dündar, H and Erakgün, T and Alp, MN and Koçak, N and Saatci, AO and Çetin, EN and Durukan, AH and Şahin, M and Muhacir, F and Yeşiltaş, S and Uyar, OM and Emre, S and Şekeroğlu, MA and Önen, M and Bulut, M and Karalezli, A and Kadayıfçılar, S and Özdek, &#x15e; and Doğanay, S and Kaya, M and Öz, &#xd6; and Kaderli, ST and Avcı, R and Şermet, F and Demirel, S and Küçükerdönmez, C and Yıldırım, C and İpek, &#x15e;C and Ayhan, Z and Altan, T and Gürelik, &#x130;G and Görgün, E and Yenerel, NM and Seymenoğlu, G and Vural, E and Sül, S and Çıtırık, M and Özdemir, HB and Cömerter, D and Karabaş, VL and Özdemir, H}, title = {Real-World 6-Month Treatment Outcomes of Faricimab in Turkey: The FARTURK Study.}, journal = {Ophthalmology and therapy}, volume = {15}, number = {3}, pages = {1165-1177}, pmid = {41739393}, issn = {2193-8245}, abstract = {INTRODUCTION: This work aims to evaluate the real-world efficacy and safety of intravitreal faricimab over a 6-month follow-up period.<br><br>METHODS: Data from 38 centers across Turkey were retrospectively analyzed between November 22, 2024, and May 4, 2025. Patients who received at least one intravitreal faricimab injection and had complete ophthalmic and optical coherence tomography (OCT) data with a minimum 1-month follow-up were included. Demographics, diagnosis, macular neovascularization (MNV) subtype, prior treatments, best-corrected visual acuity (BCVA-decimal/ETDRS), central macular thickness (CMT), intra/subretinal fluid, MNV size, injection number, follow-up duration, and ocular/systemic adverse events were recorded at baseline, at week 2, and at month 1 after the first injection, after three injections, and at the final visit.<br><br>RESULTS: A total of 351 eyes from 316 patients were analyzed, including neovascular age-related macular degeneration (nAMD) (72.1%), diabetic macular edema (DME) (18.2%), retinal vein occlusion (RVO) (6.0%), and other MNV subtypes (3.7%). When comparing pre-treatment and final visits, na&#xef;ve eyes showed a CMT reduction of 105.63&#x2009;&#xb1;&#x2009;114.89&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001), while switch eyes had a CMT reduction of 86.58&#x2009;&#xb1;&#x2009;108.36&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). The total ETDRS letter gain from baseline to final visit was 16.3&#x2009;&#xb1;&#x2009;12.08 (p&#x2009;<&#x2009;0.001) in na&#xef;ve eyes and 8.3&#x2009;&#xb1;&#x2009;12.23 (p&#x2009;<&#x2009;0.001) in switch eyes. Intraretinal and subretinal fluid rates significantly decreased (p&#x2009;<&#x2009;0.001), and MNV area contracted on OCTA (p&#x2009;<&#x2009;0.001). Only one mild, self-limited intraocular inflammation case (0.16%) occurred.<br><br>CONCLUSIONS: Faricimab demonstrated rapid and significant anatomical and functional improvements in 6-month real-world data, evident as early as 15&#xa0;days after the initial injection, with a safety profile comparable to phase III trials. These findings support faricimab as a potent and reliable therapeutic option in the real-world management of nAMD and DME, though extended follow-up is needed to assess long-term outcomes.}, }
@article {pmid41740341, year = {2026}, author = {Ling, J and Wang, D and Li, J and Liang, J and Hu, Q and Zhang, Q and Zheng, Y and Lin, B and Lin, X}, title = {Targeting macrophage-mediated clearance of apoptotic cells overcomes anti-VEGF resistance in choroidal neovascularization.}, journal = {International immunopharmacology}, volume = {175}, number = {}, pages = {116410}, doi = {10.1016/j.intimp.2026.116410}, pmid = {41740341}, issn = {1878-1705}, mesh = {Animals ; *Choroidal Neovascularization/drug therapy/immunology/pathology ; *Macrophages/immunology/drug effects ; Apoptosis/drug effects ; Mice ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; Humans ; Endothelial Cells/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; Drug Resistance ; }, abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of severe vision loss in the elderly worldwide. While anti-vascular endothelial growth factor (anti-VEGF) agents are the first-line standard of care, incomplete response to therapy (IRT) occurs in approximately 50% of patients. The microenvironmental factors driving IRT remain poorly understood. This study utilized Stereo-seq technology to construct a single-cell resolution spatial transcriptomic map (ST-map) of the retina-choroid-sclera (RCS) complex in healthy control mice, and in mice with laser-induced choroidal neovascularization (CNV) receiving either no treatment or anti-VEGF therapy. The study aimed to characterize spatial gene expression patterns and cell-cell interactions within the CNV microenvironment that may contribute to therapeutic resistance. The ST-map of the RCS complex identified distinct cellular compositions and gene expression profiles across conditions. In CNV lesions, anti-VEGF treatment induced significant shifts in the gene expression signatures of macrophages (MACs), endothelial cells (ECs), and fibroblasts (Fibros). Spatial analysis defined the proximity relationships within the neovascular niche, identifying specific macrophage-endothelial cell (MAC-EC) interactions implicated in lesion persistence. Specifically, macrophage depletion led to an accumulation of apoptotic ECs in anti-VEGF-treated lesions. In contrast, targeted blockade of CD47 in combination with anti-VEGF therapy enhanced the clearance of apoptotic ECs and achieved superior anti-angiogenic efficacy compared to anti-VEGF monotherapy. Spatial transcriptomics effectively identifies aberrant gene expression and intercellular communication networks within CNV microenvironment. These findings suggest that macrophage-mediated clearance of apoptotic cells plays a critical role in the response to treatment. Combining anti-CD47 agents with anti-VEGF therapy represents a promising strategy to overcome incomplete response and improve visual outcomes in nAMD.}, }
@article {pmid41740720, year = {2026}, author = {Ghannai, S and Ribeiro, E and Pereira, B and Brito, M and Camacho, P}, title = {The potential of DNA methylation as a biomarker for age-related macular degeneration: a systematic review.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502521}, doi = {10.1016/j.oftale.2026.502521}, pmid = {41740720}, issn = {2173-5794}, abstract = {Age-related macular degeneration (AMD) is a multifactorial disease influenced by genetic and environmental factors, yet its pathogenesis remains incompletely understood. DNA methylation, increasingly recognized as a disease indicator, has been linked to AMD and may represent a promising biomarker or therapeutic target. This systematic review, conducted according to PRISMA 2020 guidelines, analyzed 13 studies addressing DNA methylation in AMD populations (2012-2025). Results revealed that 25% reported hypermethylation, 8% hypomethylation, and 41% both patterns, while 15% found no significant differences. Notably, one study described downregulation of DNA methyltransferases in advanced stages compared with early or intermediate AMD. Despite the limited evidence, findings support the relevance of methylation in AMD prognosis and therapy. Further research with robust methodologies is essential to clarify the role of epigenetic mechanisms in disease progression and to explore their potential for guiding targeted therapeutic strategies.}, }
@article {pmid41741701, year = {2026}, author = {Veritti, D and Sarao, V and Martin, AA and Bonini, F and Lanzetta, P}, title = {AI-assisted analysis of early fluid dynamics following aflibercept 8 mg in treatment-naïve neovascular AMD.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41741701}, issn = {1476-5454}, abstract = {PURPOSE: To evaluate early morphological changes following intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration (nAMD) using artificial intelligence (AI)-assisted optical coherence tomography (OCT) segmentation.<br><br>METHODS: Thirty eyes with treatment-na&#xef;ve subfoveal nAMD received three monthly aflibercept 8&#x2009;mg injections. OCT scans were obtained at baseline and days 1, 7, 14, 30, 60, and 90. AI-based segmentation software (Fluid Monitor, RetInSight GmbH) quantified intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) volumes in the central 6-mm area. Morphologic changes were correlated with best-corrected visual acuity (BCVA).<br><br>RESULTS: IRF, SRF, and PED showed distinct reduction patterns. In eyes with IRF (n&#x2009;=&#x2009;22), mean volume decreased by 65% at day 1, 94% at day 14, and 96% at day 90 (p&#x2009;<&#x2009;0.05). Among eyes with SRF (n&#x2009;=&#x2009;28), SRF volume decreased by 18%, 84%, and 99% at days 1, 14, and 90, respectively (p&#x2009;&#x2264;&#x2009;0.002). PED volume declined more gradually among affected eyes (n&#x2009;=&#x2009;23), with mean reductions of 7% at day 1, 34% by day 14, and 53% by day 90 (p&#x2009;&#x2264;&#x2009;0.023). BCVA improved from 51.8&#x2009;&#xb1;&#x2009;14.4 to 62.6&#x2009;&#xb1;&#x2009;14.4 ETDRS letters by day 90 (mean gain +&#x2009;10.8; p&#x2009;<&#x2009;0.001). Multivariate regression identified a significant association between IRF reduction at day 14 and BCVA gain at day 90 (&#x3b2;&#x2009;=&#x2009;-0.018, p&#x2009;=&#x2009;0.036).<br><br>CONCLUSIONS: Aflibercept 8&#x2009;mg induced rapid, compartment-specific morphologic responses in treatment-na&#xef;ve nAMD, with early IRF resolution and significant BCVA improvement. AI-assisted analysis provided detailed pharmacodynamic insights and may support individualised treatment strategies during the loading phase.}, }
@article {pmid41743022, year = {2025}, author = {Trinquet, L and David, T and Chavane, F and Lorenceau, J and Matonti, F}, title = {Frequency tagged multifocal pupillary response fields identify age-related macular degeneration and diabetic retinopathy.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1653938}, pmid = {41743022}, issn = {1662-4548}, abstract = {OBJECTIVES: To quickly characterize multifocal Pupillary Response Fields (mPRF) using frequency tagging and to identify pupillary biomarkers of age-related macular degeneration (AMD) and diabetic retinopathy (DR).<br><br>METHODS: Participants with AMD (N&#x202f;=&#x202f;74), DR (N&#x202f;=&#x202f;56), and healthy controls (HP, N&#x202f;=&#x202f;62) underwent standard ophthalmologic assessments together with a multifocal Pupillary Frequency Tagging test (mPFT). The mPFT test comprised 9 retinal regions whose luminance were sinusoidally modulated at incommensurate temporal frequencies so as to elicit sustained pupillary oscillations over 45&#x202f;s of fixation.<br><br>ANALYSES: The recorded pupillary traces were corrected for blinks and transient artifacts. Features of pupillary dynamics and eye-movements, - eye instability during fixation, pupil light reflex, and spectral components of pupil oscillations - were compared across groups. Statistical analyses were performed for each feature separately using Student t-tests and Cohen's d. The Area under the Curve (AUC) of the Receiver Operating Characteristics (ROC) was computed for different combinations of the extracted features. Pearson's correlation was used to compare spectral power with other functional measures.<br><br>RESULTS: Multifocal Pupillary Response Fields (mPRF) derived from regional spectral power and phase distributions differed significantly between patients and controls, in accordance with the characteristics of each pathology: decreased power for central and paracentral sectors in AMD, diffuse defects in DR. AUCs of ROC performed with relevant features achieved excellent sensitivity (>0.9) and specificity (>0.9) in classifying patients from healthy subjects.<br><br>CONCLUSION: Fast, objective, and easily recorded, mPRF assessments evaluate the functional integrity of retino-pupillary circuits, providing spatiotemporal bio-signatures selective for maculopathies and retinopathies.}, }
@article {pmid41743586, year = {2026}, author = {Veritti, D and Misciagna, M and Teatino, C and Pontoni, C and Blasutig, M and Kuftic, M and Pece, S and Morsanutto, A and Pece, A and Lanzetta, P}, title = {Reducing the Carbon Footprint of Neovascular Age-Related Macular Degeneration Therapy: Environmental Impact of Transitioning to Aflibercept 8 mg.}, journal = {Journal of ophthalmology}, volume = {2026}, number = {}, pages = {9131955}, pmid = {41743586}, issn = {2090-004X}, abstract = {PURPOSE: To quantify and compare the carbon footprint associated with neovascular age-related macular degeneration (nAMD) treatment using real-world intravitreal aflibercept 2-mg injections versus a simulated aflibercept 8-mg regimen with extended dosing intervals.<br><br>METHODS: A life cycle assessment (LCA) combining process-based and input-output methodologies was conducted using real patient data from a tertiary ophthalmic center. The analysis included 101 patients treated with aflibercept 2&#x2009;mg and modeled the environmental impact of transitioning to aflibercept 8&#x2009;mg. The simulated aflibercept 8-mg cohort was generated by replicating the demographic and logistical characteristics of the real-world aflibercept 2-mg population while applying extended dosing intervals. Emissions were estimated in CO2 equivalents (CO2e) and included drug manufacturing, clinical materials, patient transportation, energy use, and waste disposal. Emission factors were derived from Defra and ecoinvent databases.<br><br>RESULTS: Patients treated with aflibercept 2&#x2009;mg generated an average carbon footprint of 1150&#x2009;kg CO2e per treatment cycle (2&#x2009;years), compared to 746&#x2009;kg CO2e for those modeled to receive aflibercept 8&#x2009;mg. This corresponds to an absolute reduction of 404&#x2009;kg CO2e and a relative reduction of 35%. The main driver of emissions was pharmaceutical procurement, followed by patient transportation. The lower injection frequency enabled by aflibercept 8&#x2009;mg significantly reduced both sources of emission.<br><br>CONCLUSIONS: A transition from conventional aflibercept 2-mg therapy to an aflibercept 8-mg regimen with extended dosing intervals reduces the treatment's carbon footprint by over one-third. These findings support the integration of environmental considerations into therapeutic decisions in ophthalmology, particularly for high-frequency procedures, such as intravitreal injections.}, }
@article {pmid41744421, year = {2026}, author = {Jacob, M and Stattin, M and Graf, A and Ebner, A and Ahmed-Balestra, D and Krepler, K and Ansari-Shahrezaei, S}, title = {The impact of fluid on visual acuity in exudative macular neovascularization type 1: A long-term real-life AMD study.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261424054}, doi = {10.1177/11206721261424054}, pmid = {41744421}, issn = {1724-6016}, abstract = {PurposeTo evaluate the dynamics of retinal fluid in eyes compromised by exudative macular neovascularization beneath the retinal pigment epithelium (MNV type 1) secondary to neovascular age-related macular degeneration (nAMD) and its impact on disease control over time.MethodsIn this retrospective single center study, 65 eyes of 65 patients with treatment-naive exudative MNV Type 1 were analyzed for the presence of subretinal fluid (SRF) and intraretinal fluid (IRF) in structural OCT B-scans for three years. All eyes started on three monthly intravitreal anti-VEGF injections followed by a personalized treatment interval. Primary outcome measure was visual acuity score (VAS) change based on fluid dynamics.Results29 (45%) eyes with SRF only started with a VAS of 74 ± 9 letters ETDRS, 20 eyes (31%) with SRF in the beginning that developed additional IRF had an initial VAS of 68 ± 11 letters, and 16 eyes (25%) with both, SRF and IRF measured 63 ± 13 letters at presentation. The VAS of all patients declined significantly (p = 0.003) over time, but no significant VAS change was measured between the groups.ConclusionIRF was regarded as a negative predictive OCT biomarker towards a lower VAS at the beginning but not necessarily during the course of the disease.}, }
@article {pmid41744818, year = {2026}, author = {Amaxilati, E and Chatzimichail, E and Tsiropoulos, GN and Motta, L and Empeslidis, T and Gatzioufas, Z and Panos, GD}, title = {Gene Therapy Advancements in Age-Related Macular Degeneration Treatment.}, journal = {Cells}, volume = {15}, number = {4}, pages = {}, pmid = {41744818}, issn = {2073-4409}, mesh = {Humans ; *Genetic Therapy/methods ; *Macular Degeneration/therapy/genetics ; Animals ; Dependovirus/genetics ; Genetic Vectors ; }, abstract = {Age-related macular degeneration (AΜD) remains a leading cause of irreversible vision loss. Ιn neovascular AΜD (nAΜD), frequent intravitreal anti-VΕGF injections create substantial treatment burden, while approved therapies for geographic atrophy (GA) provide modest slowing of progression. Ocular gene therapy aims to achieve sustained intraocular expression of therapeutic proteins after a single administration. Τhis review summarises the biological rationale, vector platforms, and delivery routes relevant to AΜD, with emphasis on adeno-associated virus (AAV) systems, capsid engineering, and compartment-specific administration (intravitreal, subretinal, and suprachoroidal). We synthesise the clinical landscape for sustained anti-VΕGF expression approaches in nAΜD and complement-modulating strategies for GA, and highlight how trials increasingly prioritise injection-burden reduction, anatomical endpoints, and biomarkers of target engagement. Κey challenges include intraocular inflammation and neutralising antibodies (particularly with intravitreal dosing), variability and durability of transgene expression, surgical risks associated with subretinal delivery, and practical constraints related to manufacturing scale, cost, and long-term safety surveillance for non-removable therapies. Overall, gene therapy offers a plausible route towards durable, mechanism-targeted AΜD management, but its clinical role will depend on robust controlled trials and multi-year follow-up.}, }
@article {pmid41744977, year = {2026}, author = {Zhu, W and Xia, M and He, Y and Huang, Q and Liao, Z and Wang, X and Zhou, X and Duan, X}, title = {Hydrogels as Promising Carriers for Ophthalmic Disease Treatment: A Comprehensive Review.}, journal = {Gels (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {41744977}, issn = {2310-2861}, support = {[2021YFA1101202 and 2021YFA1101200]//the National key research and development program of China/ ; [Grant No. 82501363]//the Young Scientists Fund of the National Natural Science Foundation of China/ ; [Grant No. 82471079]//the National Natural Science Foundation of China/ ; [Grant No. kq2502222]//the Changsha Municipal Natural Science Foundation of China/ ; [Grant No. 2024JJ9020]//the Natural Science Foundation of Hunan Province of China/ ; [2024AAC03823]//the Natural Science Foundation of Ningxia Hui Autonomous Region of China/ ; [Grant No. 2025RC21]//the Science and Technology Plan Project of Yinchuan City of China/ ; }, abstract = {Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye's unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy.}, }
@article {pmid41745467, year = {2026}, author = {Hacker, F and Roider, J and Klettner, A and Dörschmann, P}, title = {Fucoidan from Fucus vesiculosus Protects Retinal Pigment Epithelium from Lipid-Induced Damage Related to AMD.}, journal = {Marine drugs}, volume = {24}, number = {2}, pages = {}, pmid = {41745467}, issn = {1660-3397}, support = {not available//Retinologische Gesellschaft - Dr. Gaide-AMD-Preis/ ; }, mesh = {*Polysaccharides/pharmacology/isolation &amp; purification ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Animals ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; Cell Survival/drug effects ; *Fucus/chemistry ; Oxidative Stress/drug effects ; Cell Line ; Swine ; Lipid Peroxidation/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Fucoidans are natural compounds that exhibit bioactivity against age-related macular degeneration (AMD), the leading cause of central vision loss in industrialized nations. Pathological factors like oxidative stress and lipid peroxidation play vital roles in AMD pathogenesis. Lipid-induced alterations in the retinal pigment epithelium (RPE) contribute to AMD development. In this study, a commercial fucoidan from Fucus vesiculosus (FVs) was tested for its activity regarding lipid-peroxidation-related effects. The human RPE cell line ARPE-19, primary porcine RPE, and RPE/choroid explants were stimulated with erastin, acting as an inducer of lipid peroxidation, and treated with fucoidan. Effects on cell viability (tetrazolium bromide (MTT) or calcein staining), vascular endothelial growth factor (VEGF) and interleukin 8 (IL8) secretion (ELISA), reactive oxygen species (ROS), protein expression (glutathione peroxidase 4 (GPX4), CD59, and retinoid isomerohydrolase (RPE65), analyzed via Western blot), and gene expression (RT-qPCR) were investigated. FVs showed protective effects against erastin-induced reduction in viability (with a 12.7% increase in viability compared to erastin), RPE65 expression (with a 4.2-fold increase compared to erastin), and GPX4 expression (with a 2.3-fold increase compared to erastin) in primary RPE. Erastin-induced VEGF secretion was attenuated by FVs in ARPE-19 and primary RPE (with an up to 1.7-fold reduction compared to erastin). Elevated IL8 levels were reduced by FV treatment in primary RPE (with a 9.1-fold reduction compared to erastin). Induced VEGF in RPE/choroid explants was reduced by FVs (with an up to 2.9-fold reduction compared to erastin), and this reduction was correlated with slight improvements in viability. In conclusion, FVs exerted protective effects against lipid-induced stress. This study reveals further effects of fucoidans against AMD-related pathologies.}, }
@article {pmid41746123, year = {2026}, author = {Wall, K and Fritsch, S and Vaisband, M and Hasenauer, J and Schwenzer, N and von der Emde, L and Jauch, AS and Holz, FG and Curcio, CA and Ach, T}, title = {Near-Infrared Fluorescence Lifetime Imaging Microscopy Reveals Loss of RPE Cell Body Polarity in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {2}, pages = {55}, pmid = {41746123}, issn = {1552-5783}, abstract = {PURPOSE: Retinal pigment epithelium (RPE) cells exhibit a markedly polarized distribution of organelles and membrane specializations. We aimed to determine whether fluorescence lifetime imaging microscopy (FLIM) using different excitation wavelengths reveals altered polarity in age-related macular degeneration (AMD).<br><br>METHODS: Retinal cross-sections from human donors (11 with AMD; 87.9 &#xb1; 4.5 years, and 9 healthy controls; 83.4 &#xb1; 2.7 years) were imaged at the fovea, perifovea, near-, mid-periphery, and ora serrata using FLIM (excitation = 488, 780 nm; 5 regions of interest [ROI; 50 &#xb5;m width] per location). At each location, individual RPE cells were classified as healthy, non-uniform, or pathological. Cell bodies were divided into four equal apical-to-basal compartments to determine the fluorescence lifetime (FLT) gradient. Post-processing included multiexponential decay modeling and phasor analysis. Ordinal logistic regression (LR) and linear mixed-effects models (LMMs) compared healthy and diseased cells.<br><br>RESULTS: In 477 ROIs (3-5 cells/ROI), healthy RPE at 780 nm displayed a distinct intracellular FLT gradient. In 52 pathological ROIs, this was significantly reduced (regression coefficient = -0.029, P = 0.007). Ordinal LR confirmed an association between polarity loss and dysmorphia (log cumulative odds ratio = -6.50, P = 0.033). Mean FLT was shorter in non-uniform (-0.009 nanoseconds [ns], P = 0.03) and pathological RPE (-0.036 ns, P < 0.001) than in healthy RPE. At 488 nm, pathological RPE exhibited prolonged FLT without an apical/basal gradient.<br><br>CONCLUSIONS: At 780 nm, FLIM detects a loss of RPE cell polarity that likely reflects intracellular reorganization and metabolic change. Disruption in NIR-autofluorescence lifetimes may provide an early biomarker for pathological RPE alterations in AMD.}, }
@article {pmid41746581, year = {2026}, author = {Itagaki, K and Mukai, R and Honjo, J and Sekiryu, T}, title = {One-year outcomes of pneumatic displacement for submacular hemorrhage secondary to neovascular age-related macular degeneration.}, journal = {Japanese journal of ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41746581}, issn = {1613-2246}, abstract = {PURPOSE: To investigate the one-year outcomes of pneumatic displacement for submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). We compared cases of polypoidal choroidal vasculopathy (PCV) and non-PCV.<br><br>STUDY DESIGN: A retrospective observational study.<br><br>METHODS: We reviewed the medical records of 76 eyes of 74 patients with SMH secondary to nAMD who underwent pneumatic displacement as initial treatment. The primary outcomes were best-corrected visual acuity (BCVA), complications, and additional treatment.<br><br>RESULTS: We examined 54 eyes with PCV and 22 eyes with non- PCV. Approximately 0.5 mL of 100% sulfur hexafluoride (SF6) gas was injected into the vitreous cavity. After pneumatic displacement, 19 eyes (25%) underwent vitrectomy for complications such as vitreous hemorrhage or retinal detachment. Additionally, 95% of eyes that underwent vitrectomy had hemorrhage extending beyond the arcade vessels at baseline. During the 12 months, the average number of anti-vascular endothelial growth factor (VEGF) injections was 7.0&#xb1;3.6 in PCV cases and 7.0&#xb1;3.3 in non-PCV cases (P=0.74). The mean BCVA at 12 months improved from 0.77&#xb1;0.44 to 0.42&#xb1;0.45 in PCV cases (P<0.01) and from 1.13&#xb1;0.51 to 0.88&#xb1;0.59 in non-PCV cases (P=0.01). The PCV group had better BCVA than the non-PCV group at both time points (P<0.01). In the previously treated group, 100% of non-PCV cases had worsened visual acuity compared to pre-onset SMH, while 62% of PCV cases maintained pre-onset visual acuity (P<0.01).<br><br>CONCLUSION: Pneumatic displacement resulted in superior visual outcomes in the PCV group compared to the non-PCV group for submacular hemorrhage secondary to nAMD. .}, }
@article {pmid41746935, year = {2026}, author = {Nakagawa, N and Igarashi, A and Yokogawa, H and Kobayashi, A and Higashide, T and Yamagami, S and Hayashi, T}, title = {Impact of postoperative macular comorbidity on visual outcomes after Descemet's membrane endothelial keratoplasty: A multicenter analysis.}, journal = {PloS one}, volume = {21}, number = {2}, pages = {e0343883}, pmid = {41746935}, issn = {1932-6203}, abstract = {The aim of this study was to identify the clinical factors associated with postoperative visual acuity following Descemet's membrane endothelial keratoplasty (DMEK), with emphasis on the impact of macular diseases. This retrospective multicenter study included consecutive eyes that underwent DMEK between March 1, 2011, and June 30, 2022, and had available optical coherence tomography findings. Eyes with other ocular diseases causing visual loss were excluded. Overall, 77 eyes of 66 patients were included in the study. Univariable and multivariable regression analyses were performed to identify the predictors of best-corrected visual acuity (BCVA) at the final follow-up. Worse preoperative visual acuity and macular comorbidity were identified as independent predictors of poorer postoperative BCVA. Among macular pathologies, cystoid macular edema was most strongly correlated with reduced vision in the univariable analysis (β = 0.195; p = 0.016). In the subgroup analysis, worse preoperative visual acuity and macular comorbidity remained significant predictors (p < 0.001 and p = 0.023, respectively). Other comorbidities such as epiretinal membrane and wet age-related macular degeneration were not significant predictors. Worse preoperative visual acuity and macular comorbidity are independent risk factors for suboptimal visual recovery after DMEK. These findings highlight the importance of comprehensive preoperative retinal assessment and individualized postoperative management to optimize visual outcomes.}, }
@article {pmid41747809, year = {2026}, author = {Bernardi, E and Chakravarthy, U and Muldrew, KA and Hogg, RE and Wright, DM and Zinkernagel, M and Peto, T and Csincsik, L}, title = {Tomographic Biomarkers Differ by Progression Risk to Late Macular Degeneration.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.011}, pmid = {41747809}, issn = {2468-6530}, }
@article {pmid41747836, year = {2026}, author = {Murati, F and Ghahari, P and Zvavamwe, T and Williams, WW and Curran, K and Peto, T and Lengyel, I and McKay, BS and Kozak, I}, title = {Levodopa in retinal disease: Dopamine pathways, neuroprotective mechanisms, and clinical evidence.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.02.010}, pmid = {41747836}, issn = {1879-3304}, abstract = {We review the role of levodopa (L-DOPA), a dopamine precursor used to treat Parkinson disease, as a candidate for retinal neuroprotection, focusing on retinal dopamine biology, mechanisms of action, and evidence from preclinical and clinical studies. Selected experimental and clinical studies indicate that L-DOPA and related dopaminergic interventions influence multiple retinal pathways relevant to degeneration. L-DOPA, synthesized in the pigmented retinal pigment epithelium, activates GPR143 signaling and promotes the release of neuroprotective factors. In animal studies, L-DOPA supplementation rescued retinal development in albinism and reduced oxidative damage to photoreceptors. Epidemiologic analyses showed that patients on systemic L-DOPA had a delayed onset and a lower incidence of age-related macular degeneration (AMD). Small clinical studies in neovascular AMD demonstrated that adjunctive oral L-DOPA improved vision and reduced the burden of anti-vascular endothelial growth factor injections. Larger controlled trials are needed to define efficacy, optimal dosing, and long-term tolerability. Given its established pharmacology and ability to cross the blood-retinal barrier, L-DOPA is a promising candidate for therapeutic repurposing in ophthalmology.}, }
@article {pmid41748843, year = {2026}, author = {Wang, H and Zhang, J and Li, Y and Suo, Y and Wang, H and Gu, Z and Yan, H and Wang, C and Shao, L and Wei, W and Jin, X}, title = {Chinese Patient Preferences and Trade-Offs for Therapy-Related Attributes of Anti-Vascular Endothelial Growth Factor Agents in Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration: A Discrete Choice Experiment.}, journal = {The patient}, volume = {}, number = {}, pages = {}, pmid = {41748843}, issn = {1178-1661}, abstract = {BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor agents are the first-line treatment for macular edema associated with neovascularization or increased vascular permeability, yet patient adherence remains suboptimal. This study aimed to quantify how patient preferences for therapy-related attributes of anti-vascular endothelial growth factor agents influence trade-offs among effectiveness, safety, required injection regimen, and cost.<br><br>METHODS: A face-to-face survey-based discrete choice experiment was conducted across six Chinese cities from October 2023 to April 2024 among adults with diabetic macular edema or neovascular age-related macular degeneration. Two separate discrete choice experiment sets were developed based on literature review, focus groups, best-worst scaling, and reference to package inserts and clinical trial data. Each patient was asked to choose a preferred alternative from each of the ten choice sets. Mixed logit models estimated patient preference weights for each attribute level, relative attribute importance, and trade-offs between benefits, risks, injection regimens, and cost. Latent class models explored preference heterogeneity.<br><br>RESULTS: A total of 355 participants who passed quality checks, most preferred anti-vascular endothelial growth factor agents with longer or more flexible maintenance-phase injection intervals, greater macular edema reduction, improved visual acuity, lower risk of serious adverse events, and lower cost. For patients with diabetic macular edema, injection frequency was the most important attribute. They were willing to pay an additional &#xa5;5045.26 ($708.60) to extend injection intervals from monthly to treat-and-extend regimen, or accept a 12.97% increased risk, or forgo a 21.76% macular edema reduction, or a 14.76% visual acuity improvement. For patients with neovascular age-related macular degeneration, visual acuity improvement was the most important. They were willing to pay &#xa5;16,586.29 ($2329.54) to improve visual acuity from 20% to 43%, or accept a 17.30% increased risk, or forgo an 18.64% macular edema reduction, or an 11.88% visual acuity improvement. Patients with diabetic macular edema with senior high school education or above, or with cross-region treatment history, placed greater emphasis on visual acuity improvement, while those with more than three prior injections prioritized lower injection frequency.<br><br>CONCLUSIONS: Eliciting individual preferences can support ophthalmologists in making patient-centered recommendations during shared decision making. Understanding trade-offs across different patients is also valuable for pharmaceutical companies and payers. Future research should further explore the balance between cost, risk, and potential benefits that patients are willing to accept.}, }
@article {pmid41749475, year = {2026}, author = {Abdalbaqi, A and Kerur, N and Ohr, MP and Palmer, AF and Swindle-Reilly, KE}, title = {Murine Biocompatibility Evaluation of an Albumin-Derived Complex and Nanoparticle Delivery System for Ocular Applications.}, journal = {Journal of biomedical materials research. Part A}, volume = {114}, number = {3}, pages = {e70058}, doi = {10.1002/jbm.a.70058}, pmid = {41749475}, issn = {1552-4965}, support = {R21EY035038/NH/NIH HHS/United States ; P30EY032857/NH/NIH HHS/United States ; //College of Engineering, Ohio State University/ ; }, mesh = {Animals ; Humans ; *Nanoparticles/chemistry ; Mice ; *Biocompatible Materials/pharmacology/chemistry ; Polymers/chemistry/pharmacology ; Mice, Inbred C57BL ; *Serum Albumin, Human/chemistry/pharmacology ; *Materials Testing ; Heme/chemistry/pharmacology ; Indoles/chemistry/pharmacology ; Retinal Pigment Epithelium/drug effects/metabolism ; Heme Oxygenase-1/metabolism ; Macular Degeneration/drug therapy/pathology ; *Nanoparticle Drug Delivery System/chemistry ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population, with no curative treatment currently available. Current therapies primarily target late-stage symptoms and are limited by their frequent and invasive intravitreal (IVT) injections. To address oxidative stress-induced inflammation mechanisms relevant to early retinal degeneration, we developed a heme-bound human serum albumin (heme-albumin) complex designed to transiently induce heme oxygenase-1 (HO-1), a cytoprotective enzyme with antioxidant and anti-inflammatory effects. Polydopamine nanoparticles (PDA NPs) were selected as a delivery system due to their ability to scavenge reactive oxygen species (ROS) and degrade under oxidative environments. A previous in vitro study demonstrated that heme-albumin-loaded PDA NPs reduce oxidative damage and inflammatory signaling in retinal pigment epithelium (RPE) cells. This study evaluates the in vivo biocompatibility of IVT-administered heme-albumin and unloaded PDA NPs as independent components in a murine model. At the tested doses, both components showed minimal cytotoxicity with preservation of retinal structure, establishing biocompatible dosing for future evaluation in retinal disease models.}, }
@article {pmid41750304, year = {2026}, author = {Delrue, C and Speeckaert, R and Speeckaert, MM}, title = {Molecular Crosstalk in Age-Related Macular Degeneration: Integrating Oxidative Stress, Inflammation, microRNAs, and Genetic Susceptibility Toward Precision Therapeutics.}, journal = {Biomolecules}, volume = {16}, number = {2}, pages = {}, pmid = {41750304}, issn = {2218-273X}, mesh = {Humans ; *Macular Degeneration/genetics/metabolism/therapy/pathology ; *Oxidative Stress ; *MicroRNAs/genetics/metabolism ; *Inflammation/genetics/metabolism/pathology ; *Genetic Predisposition to Disease ; Precision Medicine ; Animals ; }, abstract = {Age-related macular degeneration (AMD) is an increasingly prevalent source of permanent visual impairment in the aging population and is widely accepted as a multi-factorial neurodegenerative disorder of the retina. While there has been significant progress in treating neovascular AMD, there are currently no effective disease-sparing treatments for dry AMD and geographic atrophy. To date, research has begun to reveal the complex relationship between the environment and genetic predisposition in AMD pathogenesis. Various environmental factors responsible for AMD include oxidative stress, mitochondrial dysfunction, inflammation, abnormal complement activation, and epigenetic regulation, which interact dynamically to drive disease progression. This review summarizes recent data and provides a comprehensive model for understanding how these interacting factors lead to the progression of AMD from an early stage to advanced stages with complications associated with the disease. We highlight the central role of retinal pigment epithelial mitochondrial failure and impaired stress resilience as upstream drivers that amplify inflammation and complement-mediated injuries. We also discuss how dysregulated miRNAs and proteomic network remodeling contribute to disease heterogeneity. Emerging therapeutic strategies are reviewed in the context of molecular endotyping and personalized intervention. Finally, we outline future directions toward precision medicine in AMD, emphasizing early disease modification, rational combination therapies, and the need to bridge the translational gaps between molecular discovery and clinical trial design.}, }
@article {pmid41750784, year = {2026}, author = {Luo, WT and Wang, TW}, title = {Performance and Clinical Utility of Deep Learning for Detecting Referable Age-Related Macular Degeneration on Fundus Photographs: A Systematic Review and Meta-Analysis.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {41750784}, issn = {2075-4418}, abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Detection of referable AMD-typically intermediate or advanced disease requiring specialist evaluation-is critical for timely intervention. Deep learning (DL) applied to color fundus photographs has emerged as a potential tool to support large-scale AMD screening. This systematic review and meta-analysis evaluated the diagnostic accuracy of DL algorithms for detecting referable AMD and compared their performance with human graders. Methods: We systematically searched PubMed, Embase, Web of Science, and IEEE Xplore through 18 December 2025. Diagnostic accuracy studies assessing DL algorithms on color fundus photographs for referable AMD in adults were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using an AI-adapted PROBAST framework. Pooled sensitivity and specificity were estimated using a bivariate random-effects model. Clinical utility was evaluated using likelihood ratios, and paired head-to-head comparisons were synthesized using a contrast-based meta-analysis. Results: Fourteen studies were included. DL algorithms achieved a pooled sensitivity of 0.91 (95% CI: 0.86-0.94) and specificity of 0.93 (95% CI: 0.86-0.96), with substantial heterogeneity. The pooled positive and negative likelihood ratios were 12.22 and 0.10, respectively, indicating strong diagnostic utility. In direct comparisons, DL systems showed slightly lower sensitivity but higher specificity than human graders. Conclusions: Deep learning demonstrates high diagnostic accuracy for detecting referable AMD from fundus photographs and may support screening and referral workflows. Further prospective validation and standardized evaluation are needed before widespread clinical implementation.}, }
@article {pmid41752067, year = {2026}, author = {Ozawa, H and Sugano, E and Tabata, K and Kakizaki, T and Sato, A and Takai, Y and Sone, K and Shidomi, M and Ishii, Y and Saito, A and Totuka, K and Ozaki, T and Fukuda, T and Bai, L and Tomita, H}, title = {Pyrroloquinoline Quinone Protects Against Light-Induced Retinal Damage in Association with the Suppression of c-Fos Signalling.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752067}, issn = {1422-0067}, support = {22H00579//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; 21K18278//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; 22K09760//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; 21K09713//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan/ ; }, mesh = {Animals ; *PQQ Cofactor/pharmacology ; *Proto-Oncogene Proteins c-fos/metabolism ; Rats ; *Light/adverse effects ; *Signal Transduction/drug effects ; *Retina/drug effects/metabolism/radiation effects/pathology ; Cell Line ; Humans ; Male ; Rats, Sprague-Dawley ; Oxidative Stress/drug effects ; Macular Degeneration/metabolism/drug therapy/pathology/etiology ; }, abstract = {Age-related macular degeneration (AMD) is a progressive retinal disorder characterised by oxidative stress and inflammation. Although pyrroloquinoline quinone (PQQ) has been reported to exert neuroprotective effects, its specific efficacy in in vivo models of AMD pathophysiology has not yet been elucidated. In this study, we evaluated the protective effects of PQQ against all-trans-retinal (ATR)-induced cytotoxicity in ARPE-19 cells and light-induced photoreceptor degeneration in rats. Pretreatment of ARPE-19 cells with PQQ dose-dependently mitigated ATR-induced cytotoxicity. In the in vivo model, rats received a single intraperitoneal injection of PQQ (2 or 5 mg/kg) 1 h prior to 1000-lux light exposure. Retinal function and morphology were evaluated by electroretinography and haematoxylin-eosin staining, respectively. The 5 mg/kg PQQ group retained significantly greater retinal function than the vehicle group at 3 days postexposure and demonstrated significant preservation of the outer nuclear layer at 7 days postexposure, indicating the suppression of photoreceptor cell death. Western blot analysis detected the dose-dependent suppression of light-induced c-Fos upregulation following PQQ treatment. These findings suggest that the protective effect of PQQ against phototoxic damage is associated with the suppression of c-Fos signalling, thus lending support to the further investigation of PQQ as a potential therapeutic agent for AMD.}, }
@article {pmid41752910, year = {2026}, author = {Nowosielska, A and Rotuski, G}, title = {New Technique of Single-Point Scleral Fixation of the Smaller-Incision New-Generation Implantable Miniature Telescope with an 18-Month Follow-Up Period.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, pmid = {41752910}, issn = {2075-1729}, abstract = {BACKGROUND: The implantable miniature telescope is used to provide functional vision for patients with advanced AMD. However, despite the considerable cost of the device, there are strict criteria to be met for this procedure, since the patients require challenging neuroadaptation afterward, which sometimes fails and leads to the necessity of device explantation. Visual outcomes also depend on the stability of the microtelescope; tilts cause unwanted optical aberrations and can lead to device luxation, with sight-threatening complications.<br><br>CASE REPORT: This case presents a novel technique for fixing the ophthalmic telescope device SING-IMT&#x2122;. A 76-year-old female with pre-operative visual acuity of 15 letters on the ETDRS scale underwent surgery on her left eye. The superior haptic was fixed at the 12 o'clock position with a Prolene 5-0 suture, achieving good postoperative stability. The implant was stable throughout the entire observation period.<br><br>CONCLUSIONS: Implant stability is crucial for maximizing visual potential in patients with advanced AMD selected for the procedure, since visual acuity in the peripheral retina, where the perceived image eventually lands, is much lower than the macula. Therefore, there is a need to standardize surgical approaches and use objective follow-up measures to assess long-term patient satisfaction.}, }
@article {pmid41752939, year = {2026}, author = {Racioppo, P and Wang, ZC and Sadda, SR and Hu, ZJ}, title = {SWAU-Net: Longitudinal Prediction of Geographic Atrophy via Sliding-Window Attention.}, journal = {Life (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {}, pmid = {41752939}, issn = {2075-1729}, support = {R21EY030619/EY/NEI NIH HHS/United States ; }, abstract = {Age-related macular degeneration (AMD) is the leading cause of central vision loss in aging populations. Geographic atrophy (GA) is the advanced, non-neovascular form of AMD. Predicting the longitudinal progression of GA remains a critical challenge in ophthalmic clinical practice and clinical trial design. Forecasting the trajectory of GA is complicated by highly variable growth rates and the inherent scarcity of long-term, high-quality imaging data. To address these challenges, we introduce the Sliding Window Attention U-Net (SWAU-Net), a hybrid architecture that integrates Transformer-based temporal modeling of GA growth with precise spatial modeling of GA location with a U-Net convolutional neural network (CNN). To ensure generalization in the low-data regime, SWAU-Net embeds explicit temporal and geometric consistency priors via a weight-shared Sliding Window Attention core and feature-level regularization that preserves sparse, high-frequency lesion boundaries across frames. Experimental results demonstrate that these structural constraints prevent the model from overfitting to imaging noise, achieving a Growth Mask Dice Similarity Coefficient (DSC) of 0.66 (representing the spatial overlap between the predicted and ground truth lesion expansion regions), a significant improvement over unregularized Transformer and standard recurrent baseline models. Our framework provides a robust tool for predicting GA lesion trajectories, potentially supporting more efficient clinical trial designs and personalized patient monitoring.}, }
@article {pmid41753141, year = {2026}, author = {Parolini, F and Pilotto, E and Midena, E and Midena, G}, title = {Inflammatory Hyperreflective Retinal Foci: An OCT Biomarker of Neuroinflammation in Geographic Atrophy.}, journal = {Journal of clinical medicine}, volume = {15}, number = {4}, pages = {}, pmid = {41753141}, issn = {2077-0383}, abstract = {Background: Inflammatory hyperreflective retinal foci (I-HRF) have been recognized as an optical coherence tomography (OCT) biomarker of aggregates of activated microglial cells. Microglia, the principal resident immune cells, are key players in geographic atrophy (GA) development and progression. Objective: To quantify I-HRF distribution across inner (IR) and outer (OR) retinal layers in GA compared with healthy controls. Methods: Retrospective observational study including patients aged ≥50 years with GA lesion area >1.25 mm[2] and age-matched healthy subjects. GA eyes were classified as bilateral GA (B-GA) or unilateral GA (U-GA; fellow eye with macular neovascularization). Using Spectralis OCT, I-HRF (≤30 μm; RNFL-like reflectivity; no posterior shadowing) were identified and counted across IR and OR. Results: Sixty-eight eyes from 46 patients with GA (B-GA: 49 eyes; U-GA: 19 eyes) and 19 control eyes were studied. I-HRF were higher in IR than in OR in all groups (p < 0.001). I-HRF were higher in GA eyes in both layers compared with controls (p < 0.05). U-GA exhibited higher I-HRF than B-GA in IR (44.32 ± 8.47 vs. 30.10 ± 7.62; p < 0.001), while I-HRF were not significantly different in OR (9.58 ± 3.04 vs. 8.02 ± 3.33; p = 0.081). Conclusions: I-HRF are increased in GA. They are more numerous in IR, consistent with their proposed inflammatory origin. These findings further support the role microglia may play in GA pathology. I-HRF may become an OCT biomarker to track GA-associated neuroinflammation in different GA phenotypes. Longitudinal studies are needed to clarify I-HRF significance in GA progression.}, }
@article {pmid41753180, year = {2026}, author = {Spindler, J and Pfister, IB and Weinberger, A and Garweg, JG}, title = {Prevalence of Polypoidal Choroidal Vasculopathy Beyond Recalcitrant Macular Neovasculopathies in a European AMD Cohort and Therapeutic Response to Brolucizumab.}, journal = {Journal of clinical medicine}, volume = {15}, number = {4}, pages = {}, pmid = {41753180}, issn = {2077-0383}, abstract = {Background: Polypoidal choroidal vasculopathy (PCV) may be underdiagnosed in Europe due to the limited use of indocyanine green angiography (ICGA), in particular, in patients with occult or poorly responsive neovascular age-related macular degeneration (AMD). Based on this, we aimed to assess the prevalence of PCV beyond clinically typical recalcitrant nAMD using OCT criteria, and to report on the anatomical and functional outcomes following a switch to brolucizumab (bro). Methods: This retrospective case series used recently established optical coherence tomography (OCT)-based criteria to differentiate clinically typical nAMD and PCV in eyes with recalcitrant disease requiring treatment every six weeks or less. The aim was to compare the impact of switching to bro on disease activity in patients with recalcitrant nAMD and PCV over 12 months. Descriptive statistics and subgroup comparisons were performed. Data are presented as mean ± standard deviation (SD) as well as median and interquartile ranges (IQR), since data were not normally distributed. Results: Of the 27 eyes examined, 16 (59.3%) presented with typical recalcitrant nAMD and 11 (40.7%) with PCV. Patients with typical nAMD were older (81.4 ± 5.7 vs. 74.7 ± 7.7 years; p = 0.016) and exhibited less fluid (central retinal thickness in typical nAMD: 349.3 ± 95.3 µm; in PCV: 597.1 ± 348.4 µm; p = 0.005). This difference could be attributed to variations in pigment epithelial detachment heights (typical nAMD: 176.5 ± 102.6 µm, PCV: 384.6 ± 284.6 µm; p = 0.023). Twelve months after switching to bro (159 injections), the treatment interval increased from 5.7 ± 1.8 to 12.6 ± 5.1 weeks in nAMD and from 5.5 ± 1.9 to 8.0 ± 1.5 weeks in PCV patients (at switch: p = 0.81; after 12 months: p = 0.040). Visual gains after switching were maintained in two out of three patients with intraocular inflammation (IOI). Conclusions: PCV is remarkably underdiagnosed and overrepresented in the group of eyes with recalcitrant nAMD. Despite the inherent risk of IOI in response to bro, these results support the potential of bro as a third-line option for patients with eyes requiring anti-VEGF treatment every 6 weeks or less, provided that patients are monitored closely.}, }
@article {pmid41753234, year = {2026}, author = {Vagge, A and Baldi, M and Musolino, M and Rivarone, V and Catti, C and Iester, M}, title = {Current and Emerging Strategies for Myopia Control in Children: A Comprehensive Evidence-Based Review.}, journal = {Journal of clinical medicine}, volume = {15}, number = {4}, pages = {}, pmid = {41753234}, issn = {2077-0383}, abstract = {Myopia has emerged as a global public health crisis, with prevalence exceeding 80% in East Asian urban populations and rising rapidly worldwide. High myopia substantially increases the lifetime risk of sight-threatening complications, including myopic macular degeneration, retinal detachment, and glaucoma. Multiple interventions have been investigated to slow myopia progression in children. Behavioral strategies, particularly increased outdoor exposure, demonstrate protective effects against myopia onset and may modestly slow progression, whereas several historically used approaches show no clinically meaningful benefit. Spectacle lens interventions include simultaneous defocus designs (e.g., DIMS, HALT, CARE) and contrast-modulating diffusion optics (DOT) lenses; collectively, these technologies have demonstrated consistent and clinically meaningful reductions in axial elongation across randomized clinical trials. Contact lens modalities, including dual-focus soft lenses and orthokeratology, have also demonstrated substantial efficacy in slowing progression in controlled studies. Low-dose atropine remains a cornerstone pharmacological therapy, particularly at concentrations between 0.01% and 0.05%, offering significant efficacy with minimal side effects. Repeated low-level red-light therapy has shown promising short-term reductions in axial elongation, although long-term safety and rebound effects remain uncertain. Combination therapy targeting complementary optical and pharmacological pathways shows additive benefits, particularly in children inadequately controlled with monotherapy. Contemporary clinical management emphasizes risk stratification based on axial length, age-specific growth targets, and structured longitudinal monitoring. The goal of modern myopia management is not merely to slow progression, but to prevent high myopia and reduce the lifetime burden of vision-threatening complications through a proactive, individualized approach increasingly regarded as the standard of care.}, }
@article {pmid41755782, year = {2026}, author = {Yu, E and Gu, SM and Kim, H and Kim, JG and Hwang, BY and Min, JK and Yun, J}, title = {Celafolin A-1 Ameliorates Subretinal Fibrosis via Inhibition of Crystallin Alpha B in a Laser-Induced Choroidal Neovascularization Mouse Model.}, journal = {Biomolecules &amp; therapeutics}, volume = {34}, number = {2}, pages = {434-447}, pmid = {41755782}, issn = {1976-9148}, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in people over 65 years old. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular AMD (nAMD); however, fibrosis remains an unmet medical need due to the lack of effective medications. This study evaluated eight natural products from Celastrus orbiculatus, which has been reported to have anti-inflammatory effects, for their effects on the fibrotic pathological process as well as choroidal neovascularization (CNV). We investigated the half-maximal inhibitory concentration (IC50) values of these compounds on VEGF and alphasmooth muscle actin (α-SMA, a fibrosis marker) expression-induced by human acute monocytic cell (THP-1) conditioned media in retinal pigment epithelium cells (ARPE-19). Four compounds reduced both VEGF and α-SMA at 10 μM, with three-Celafolin A-1, COFH5645, and COFH543435-showing the highest potency. Intravitreal injections of the compound in a mouse model of CNV induced by laser photocoagulation confirmed its efficacy. Celafolin A-1 significantly reduced α-SMA and VEGF expression and decreased hyper-reflective lesions and CNV areas. Binding affinity measurements using biolayer interferometry identified an interaction between Celafolin A-1 and crystallin alpha B (Cryab), a protein involved in stress responses and fibrosis. Celafolin A-1 reduced the expression levels of Cryab as well as its phosphorylated form at Ser45, indicating that its mechanism involves the regulation of Cryab phosphorylation. Taken together, Celafolin A-1 exhibits dual inhibitory effects on VEGF and fibrosis, suggesting it as a candidate for the treatment of nAMD.}, }
@article {pmid41755917, year = {2026}, author = {Zhang, Y and Wei, C and Stewart, JM}, title = {Transient vitreous opacity following combined intravitreal injection of pegcetacoplan and faricimab-svoa in patients with neovascular age-related macular degeneration and geographic atrophy.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102545}, pmid = {41755917}, issn = {2451-9936}, }
@article {pmid41756519, year = {2026}, author = {John, R and George, MR and Williams, GS and Morgan, T}, title = {How Do Optometrists Approach Directed Questioning on Smoking Status in a Centrally Co-Ordinated, Publicly-Funded National Primary Care Eye Health Service?.}, journal = {Clinical optometry}, volume = {18}, number = {}, pages = {580909}, pmid = {41756519}, issn = {1179-2752}, abstract = {BACKGROUND: Tobacco use is a leading cause of preventable death worldwide, linked to various health issues, including cancers, cardiovascular diseases, and respiratory illnesses. It also adversely affects ocular health, increasing the risk of conditions like Age-Related Macular Degeneration and cataracts. The socioeconomic burden of smoking in the UK is significant, costing the National Health Service between £2.7 and £5.2 billion annually. Smoking cessation improves health outcomes and reduces healthcare costs. Optometrists are well positioned to identify smoking behaviours and offer cessation advice, yet evidence on current practice in Wales is limited.<br><br>METHODS: This cross-sectional study used an anonymous online questionnaire to assess smoking-related practice behaviours among optometrists providing National Health Service optometry services in Wales. The survey captured demographic characteristics, training history, current approaches to smoking status identification and cessation advice, confidence levels, and perceived barriers to discussing smoking with patients.<br><br>RESULTS: A total of 778 optometrists participated, with 96.3% reporting routine assessment of patients' smoking status. Most respondents felt confident discussing the impact of smoking on health; however, barriers like time constraints and perceived patient reluctance were common. Notably, those with longer professional tenures were more likely to view patient reluctance as a barrier (OR 1.46, 95% CI, 0.026-0.050, p < 0.001).<br><br>CONCLUSION: The findings suggest generally positive engagement with smoking cessation among optometrists in Wales, though barriers to patient engagement persist. While training appears to support more proactive practice, further work is needed to understand how optometric interventions influence smoking cessation outcomes and to explore why some practitioners perceive patients as hesitant to discuss health behaviours.}, }
@article {pmid41757049, year = {2026}, author = {Germer, CJ and Williams, S and Fernandes, V and Lima, RE and La Cunza, NR and Tan, LX and Panda, SR and Iorio, E and Elahi, FM and Lakkaraju, A}, title = {Acid sphingomyelinase inhibition restores RPE homeostasis and photoreceptor function in preclinical Stargardt macular degeneration models.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41757049}, issn = {2692-8205}, abstract = {Stargardt disease, which destroys central high-resolution vision in over 2 million people globally, lacks effective therapies. The primary site of damage in Stargardt disease is the retinal pigment epithelium (RPE), which safeguards photoreceptor health and function. Progressive loss of RPE integrity precedes visual deficits, yet insight into mechanisms driving RPE dysfunction and how this influences disease pathogenesis remains elusive. Here, we addressed this in cell-based and pigmented Abca4[-/-] Stargardt mice models using super-resolution imaging, bioinformatics, and biochemical approaches. We show that ceramide accumulation induced by bisretinoid-mediated overactivation of acid sphingomyelinase (ASM) in Abca4[-/-] RPE selectively disrupts Rab GTPases and ESCRT machinery involved in apical membrane trafficking and small extracellular vesicle (EV) biogenesis. Consequently, connexin 43 (Cx43) is misrouted from cell-cell junctions into EVs that are released apically by the RPE. This compromises RPE integrity and promotes subretinal immune cell recruitment, leading to photoreceptor dysfunction. Pharmacological ASM inhibition normalizes EV biogenesis and restores Cx43 localization. Decreasing RPE ceramide safeguards RPE structural integrity, limits subretinal microglia, and improves visual function in Abca4[-/-] mice. This study underscores the importance of the RPE as a communication hub in the retina and identifies ASM as a potential therapeutic target to prevent progressive vision loss.}, }
@article {pmid41757866, year = {2026}, author = {Liao, H}, title = {Brain-derived neurotrophic factor in age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721261427214}, doi = {10.1177/11206721261427214}, pmid = {41757866}, issn = {1724-6016}, abstract = {Age-related Macular Degeneration (AMD) is a leading cause of vision loss. There is no cure for AMD. Current treatments focus on preventing disease progression and preserving vision. In recent years, the role of brain-derived neurotrophic factor (BDNF) in AMD has attracted increasing attention. BDNF is widely involved in the physiology and pathophysiology of the retina. These include the development of photoreceptors during early development and synaptic communication between photoreceptors and retinal neurons. Under pathological conditions, BDNF affects the functions of multiple cell types in the retina including photoreceptors, ganglion cells, Müller cells, microglia cells, amacrine cells, and the retinal pigment epithelium (RPE). Importantly, BDNF does not act alone. Its function relates with other neurotrophic factors such as basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and glial cell derived neurotrophic factor (GDNF). Meanwhile, the dynamic interaction between BDNF, its precursor protein proBDNF and the BDNF receptor TrkB not only affects the survival of retinal cells in AMD but may also guide the treatment strategy. Various approaches have been taken to deliver BDNF in animal models for managing AMD. Despite the exciting progress, challenges remain in implementing BDNF therapy as an effective treatment. In this review, we summarize the current research progress of BDNF in AMD and highlight the issues that need to be addressed before translation into clinical practice.}, }
@article {pmid41759060, year = {2026}, author = {Amoroso, F and Miere, A and Kodjikian, L and Couturier, A and Jean-François, K and Jung, C and Wang, X and Blanco-Garavito, R and Souied, EH}, title = {SD-OCT and OCTA: distinct or additional information on neovascular activity? The COCTAEYL Study.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004815}, pmid = {41759060}, issn = {1539-2864}, abstract = {PURPOSE: This study aimed to compare exudative recurrence features detected by optical coherence tomography angiography (OCTA) with those identified by spectral-domain optical coherence tomography (SD-OCT), considered the gold standard, and to characterize OCTA-derived profiles predictive of recurrence in patients with macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD) treated with aflibercept.<br><br>METHODS: In this prospective observational cohort study, 49 patients were enrolled, yielding data from 686 examinations for concordance analysis between SD-OCT and OCTA. Following a loading phase of three-monthly intravitreal injections of 2 mg Aflibercept, patients were monitored monthly. Both SD-OCT and OCTA were performed at each visit, with intravitreal injections administered bimonthly (fixed regimen) for up to 12 months.<br><br>RESULTS: OCTA demonstrated a sensitivity of 72%, specificity of 27%, positive predictive value (PPV) of 59%, and negative predictive value (NPV) of 40% for detecting exudative activity. The area under the ROC curve (AUC) for OCTA-defined recurrence was 0.49, with an odds ratio (OR) of 0.95 for predicting neovascular activity in the next month (p=0.87). The net benefit (NB) was 0.13 for OCTA versus 0.19 for a general approach strategy. Relying on OCTA for recurrence detection instead of SD-OCT did not reduce unnecessary intravitreal injections.<br><br>CONCLUSION: OCTA and SD-OCT provide complementary information, with OCTA focusing on flow remodeling and SD-OCT highlighting exudative features. OCTA provides complementary vascular flow information to the structural data acquired with SD-OCT, allowing a more comprehensive assessment of neovascular activity, although no modification in management was observed in this cohort.}, }
@article {pmid41759077, year = {2026}, author = {Han, HY and Park, SM and Kim, CG and Cho, HJ and Kim, JH}, title = {Comparison of Initial Loading Injection Outcomes Between Aflibercept 8 mg and Faricimab in Neovascular Age-Related Macular Degeneration.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004819}, pmid = {41759077}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate and compare the initial functional and anatomical outcomes of aflibercept 8 mg and faricimab during the loading phase in treatment-naïve neovascular age-related macular degeneration (AMD).<br><br>METHODS: This retrospective observational study included 100 eyes of 100 patients with treatment-na&#xef;ve neovascular AMD who were administered three consecutive monthly loading injections of either aflibercept 8 mg (aflibercept 8 mg group, n=51) or faricimab (faricimab group, n=49). Changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), as well as complete resolution of subretinal and intraretinal fluids, were compared between groups. Within each group, BCVA and CRT at baseline were compared with values at 3 months.<br><br>RESULTS: In the aflibercept 8 mg group, mean BCVA, measured in logarithm of the minimal angle of resolution (logMAR), improved from 0.59&#xb1;0.51 (Snellen equivalent, 20/77) at baseline to 0.39&#xb1;0.44(20/49) at 3 months(P<0.001). Correspondingly, mean CRT decreased from 450.6&#xb1;157.0 &#xb5;m to 287.3&#xb1;82.3 &#xb5;m(P<0.001). In the faricimab group, mean BCVA improved from 0.62&#xb1;0.47 logMAR(20/83) to 0.45&#xb1;0.38(20/56)(P<0.001), and mean CRT decreased from 442.4&#xb1;163.8 &#xb5;m to 248.5&#xb1;81.2 &#xb5;m(P<0.001). No significant differences were observed between groups in BCVA improvement(P=0.685) or CRT reduction(P=0.320). Complete retinal fluid resolution was observed in 80.4% and 87.8% of patients in the aflibercept 8 mg and faricimab groups, respectively, with no significant difference in fluid resolution between groups(P=0.234).<br><br>CONCLUSIONS: Aflibercept 8 mg and faricimab achieved significant and comparable functional and anatomical outcomes after three loading injections in treatment-na&#xef;ve neovascular AMD, suggesting that either agent may serve as an effective first-line treatment for this condition.}, }
@article {pmid41759572, year = {2026}, author = {Lapaquette, P and Loriot, B and Grégoire, S and Courcet, E and Acar, N and Bringer, MA}, title = {Gut inflammation affects retinal fatty acid composition.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110945}, doi = {10.1016/j.exer.2026.110945}, pmid = {41759572}, issn = {1096-0007}, abstract = {Inflammation and altered lipid metabolism - particularly bioavailability of polyunsaturated fatty acids of the omega-3 series (n-3 PUFAs) - are associated with age-related macular degeneration (AMD). Growing evidence suggests that the gut plays a significant role in regulating retinal physiology. Recent studies have reported that patients with chronic inflammatory bowel diseases (IBD) may have an increased risk of developing AMD. We investigated the influence of colitis on retinal fatty acids, by using a dextran sodium sulfate (DSS)-induced colitis model in mice. Compared to control mice, the retinas of DSS-treated mice exhibited a significantly higher amount of PUFAs, accompanied by a decrease in saturated fatty acids. Both retinal n-6 and n-3 PUFAs were affected by the DSS-induced colitis, including C20:4n-6 (arachidonic acid, the main retinal n-6 PUFA), and C22:6n-3 (docosahexaenoic acid, the main retinal n-3 PUFA), without altering their ratio. Analysis of gene expression involved in fatty acid biosynthesis revealed that, while Elovl2, Elovl4, and Elovl5 expression levels remained unchanged, Fasn expression tended to decrease and Fads2 expression was significantly reduced in the retinas of DSS-treated mice compared to those of controls. Besides, the retinal expression level of genes encoding pro-inflammatory cytokines (Il1b, Il6, Il8 and Tnfa) was not modified by the DSS-induced colitis. Altogether, these results indicate that although retinal cells do not express a pro-inflammatory phenotype, colitis influences the retinal bioavailability of fatty acids. In addition to providing new insights into the potential link between IBD and AMD, this study also supports the concept that gut health influences retinal physiology.}, }
@article {pmid41759744, year = {2026}, author = {Waghmare, PV and Kolekar, KA and Bashir, B and Kumbhar, PS and Patil, KS and Gupta, G and Prasher, P and Jha, SK and Disouza, J and Gurav, SS and Dua, K and Singh, SK}, title = {Advocating gut-retina connection and microbiota mediated pathways in management of age-related macular degeneration: Preclinical to clinical perspective.}, journal = {Ageing research reviews}, volume = {117}, number = {}, pages = {103071}, doi = {10.1016/j.arr.2026.103071}, pmid = {41759744}, issn = {1872-9649}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Macular Degeneration/microbiology/therapy ; Animals ; Probiotics/therapeutic use ; *Retina/metabolism ; Aging ; Dysbiosis ; }, abstract = {Age-related macular degeneration (ARMD) is the primary manifestation of permanent vision loss internationally. Different factors that contribute to ARMD involve ageing, genetic predisposition, oxidative stress, immunological imbalances, aberrations in the breakdown of lipids, and persistent inflammation. Gut microbiota has emerged as the significant cause of ARMD by disrupting systemic immune and inflammatory responses and metabolic homeostasis. Age-related changes in gut microbiota (dysbiosis) cause lowered microbial diversity, enhanced gut permeability, and pro-inflammatory species, leading to macular damage. The healthy gut microbiota containing Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Faecalibacterium prausnitzii, are responsible for maintaining gut homeostasis, protecting the retina, and preventing ARMD progression. In contrast, the elevated population of pathogenic species such as Escherichia coli, Prevotella, Desulfovibrio, Enterococcus faecalis, and Streptococcus salivarius in gut dysbiosis is involved in ARMD progression. This review explores gut microbiota and their dynamics in ageing. The age-dependent gut microbiota variations and potential biological implications for the progression of ARMD are discussed. The review also discusses observations from experimental animals and explores potential microbiome-centered treatment avenues, covering probiotics, synbiotics, dietary remedies, metabolite-based treatment, and fecal microbiota transplantation for managing ARMD. Furthermore, various challenges in the management of gut microbiota-driven ARMD are also briefed with future directions. Thus, a gut microbiota-focused paradigm can offer novel choices for ARMD prevention and treatment.}, }
@article {pmid41760600, year = {2026}, author = {Huang, C and Babu, VS and Bammidi, S and Arnold, JN and Ebeling, M and Widmer, G and Strassburger, P and Lazendic, M and Grüner, S and Koester, J and Dutta, P and Hose, S and Singh, S and Gautam, P and Lad, EM and Westenskow, PD and Kutsyr, O and Csaky, KG and Ghosh, S and Sripathi, SR and Proia, AD and Flores-Bellver, M and Sinha, D and Feenstra, D}, title = {STING activation induces polarized cytokine secretion of IFN-β and IL-17A promoting photoreceptor death and choroidal disruption in age-related macular degeneration.}, journal = {Cell death &amp; disease}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41419-026-08491-w}, pmid = {41760600}, issn = {2041-4889}, support = {1R01EY031594-01A1//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; K99EY033421//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; Launch Award//Maryland Stem Cell Research Fund (MSCRF)/ ; Free Family AMD Research Award//Foundation Fighting Blindness (FFB)/ ; Start-up funding//Johns Hopkins University (Johns Hopkins)/ ; M2024008N//BrightFocus Foundation (BrightFocus)/ ; }, abstract = {Age-related macular degeneration (AMD) represents one of the therapeutic challenges of aging eye diseases. Our investigation reveals the stimulator of interferon genes (STING) pathway as an orchestrator of immune-mediated retinal degeneration, exhibiting biphasic, stage-dependent functionality-providing cytoprotection in healthy tissue but driving pathogenic inflammation during early AMD progression. Through immunohistochemical analysis of human eyes, we demonstrate stage-dependent cytoplasmic STING upregulation with parallel IFN-β activation. Using patient-derived induced pluripotent stem cells-retinal pigment epithelium (iPSC-RPE) from AMD siblings, we discovered polarized cytokine secretion: apical IFN-β triggers photoreceptor apoptosis in human retinal organoids, while basal IL-17A compromises choroidal neovascularization. The Cryba1 conditional knockout (cKO) AMD-like mouse model confirms STING-driven IL-17A expression, while Il17a knock-in mice substantiate vascular alterations. STING activation establishes a pathogenic feed-forward loop between interferons and IL-17A. Single-cell transcriptomics following AAV2-mediated IFN-β overexpression reveals metabolic and phototransduction dysregulation. Both pharmacological STING inhibition with SN-011 and genetic approaches demonstrate therapeutic rescue. Cryba1/Sting double heterozygous (dhet) mice maintain homeostatic gene expression preserving retinal architecture and function. These findings establish STING as the master regulator simultaneously controlling multiple AMD pathologies through spatially organized inflammation, transforming from protective surveillance to pathogenic driver, and identifying a unified therapeutic target with demonstrated functional rescue across multiple experimental paradigms.}, }
@article {pmid41762378, year = {2026}, author = {Tillmann, A and Stillenmunkes, R and Garweg, JG and Cattaneo, J and Bartolomeo, N and Grimaldi, G and Spitznagel, T and De Oliveira Figueiredo, EC and Ambresin, A and Menghini, M and Somfai, GM and Zweifel, S and Fröhlich, J and Artemiev, D and Ebneter, A and Hatz, K and Weinberger, A and Pfister, IB and Schild, C and Eandi, C and Munk, MR and , }, title = {Correction: One-Year Outcomes of Faricimab in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-026-01319-y}, pmid = {41762378}, issn = {2193-8245}, }
@article {pmid41763458, year = {2026}, author = {Sim, SY and Lim, LT and Chaudhary, S and Musa, M and Hamilton, R and Nicholson, L and Pal, B and Saini, P and Mankongcharoen, P and Sen, S}, title = {Update on subthreshold micropulse laser treatment for retinal diseases: A narrative review.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.02.006}, pmid = {41763458}, issn = {1879-3304}, abstract = {Subthreshold micropulse laser (SML) has emerged as a valuable and effective alternative to conventional laser treatments for a variety of retinal diseases, offering therapeutic benefits while minimizing tissue damage. Unlike traditional continuous wave lasers which induce irreversible changes to photoreceptors and retinal pigment epithelial (RPE) cells due to thermal damage, SML delivers energy in short bursts with cooling intervals, maintaining subthreshold temperatures that trigger therapeutic cellular responses without causing visible retinal scarring. We have synthesized the latest evidence on SML's role in managing diabetic macular edema (DME), central serous chorioretinopathy (CSCR), macular edema secondary to retinal vein occlusion, and age-related macular degeneration. Across these conditions, SML demonstrates comparable visual and anatomical outcomes to conventional laser and anti-vascular endothelial growth factor therapies, with notable benefits, including a reduced injection burden in DME and improved choriocapillaris perfusion in CSCR. Additionally, emerging data suggests SML may hold an edge in more complex cases, such as chronic CSCR, pseudophakic macular edema, and dome-shaped maculopathy; however, inconsistencies in laser parameters including wavelength, duty cycle, fluence parameters and spot size continue to pose challenges in standardizing treatment protocols. The "reset theory" of RPE restoration, driven by heat shock protein activation or other described mechanisms, underscores SML's potential to offer sustained, long-term disease control. While current evidence is promising, larger, high-quality studies are still needed to fine-tune treatment settings, improve patient selection strategies, and clarify SML's role alongside other therapies. We provide a comprehensive overview of SML's progress, potential, and future direction in retinal disease management.}, }
@article {pmid41765332, year = {2026}, author = {Benito-Pascual, B and Fernández-Pérez, C and Medina, A and Rojo, D and Arriola-Villalobos, P}, title = {Population survey on visual health in Spain.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {}, number = {}, pages = {502467}, doi = {10.1016/j.oftale.2026.502467}, pmid = {41765332}, issn = {2173-5794}, abstract = {BACKGROUND AND OBJECTIVE: Conducting a national visual health survey and comparing results after 5 years.<br><br>MATERIALS AND METHODS: Cross-sectional study using a computer-assisted telephone interview with a representative sample of Spaniards over 18 years of age (except Ceuta and Melilla). The survey was designed by ophthalmologists, the selection of the sample and the conduct of the interviews (April 2017 and May 2023) was carried out through the company Metroscopia and the analysis of the anonymous data was carried out by researchers. Demographic data, knowledge about glaucoma, use of glasses, perceived visual quality, ophthalmological pathology and ocular treatments were collected.<br><br>RESULTS: 1209 and 600 people were interviewed in 2017 and 2023 respectively. The level of glaucoma awareness went from 80% to 87%. The perceived visual quality was reduced (8.2&#xa0;&#xb1;&#xa0;1.6 to 6.9&#xa0;&#xb1;&#xa0;1.8) and the frequency of access to the ophthalmologist. The prevalence of glasses use increased (50%-62%), dry eye (13%-28%), cataract (9.7%-12.4%), glaucoma (1.9%-4.6%), age-related macular degeneration (7%-11.3%), and diabetic retinopathy (1.2%-1.7%). The use of artificial tears and glaucoma drops also increased (16.9%-32.9% and 1.6%-6%, respectively).<br><br>CONCLUSIONS: The study shows that there has been an increase in self-reporting of eye diseases in recent years in Spain. These types of population surveys can serve to encourage the development of visual health programs aimed at the needs of our country.}, }
@article {pmid41765918, year = {2026}, author = {Padovani-Claudio, DA and Bastarache, L}, title = {Opportunities and challenges in leveraging multiomics and biobanks for vision science.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001209}, pmid = {41765918}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: Emerging biobank resources allow large-scale integration of eye-specific phenotypes with clinical, genomic, and multiomic data. This convergence enables unprecedented opportunities to systematically dissect the genetic architecture, epidemiology, and mechanistic pathways of both rare monogenic and common polygenic diseases. The review aims to critically examine how contemporary data extraction, multiomics, and analytic methodologies are reshaping disease classification, genetic discovery, and translational research in ophthalmology, while highlighting the associated challenges in leveraging these advanced tools.<br><br>RECENT FINDINGS: Recent literature demonstrates the utility of genome-wide and phenome-wide association studies, transcriptomic analyses, and artificial intelligence in uncovering novel risk loci, endophenotypes, and biomarkers relevant to eye diseases. Furthermore, advances in multiancestry sampling show substantial population-specific genetic variation, enriching disease models for conditions such as glaucoma and age-related macular degeneration. Finally. integrative approaches, including Mendelian randomization and enrichment analyses, are helping elucidate shared genetic architecture between ocular and systemic diseases, informing therapeutic target identification, and refining risk prediction models.<br><br>SUMMARY: The convergence of biobank-derived multimodal data and sophisticated analytic techniques is catalyzing a path to personalized medicine in ophthalmology. For these approaches to fully translate into clinical practice ensuring scientifically robust and equitable outcomes, future research must address cohort diversity, mechanistic validation, and practical cost-effectiveness.}, }
@article {pmid41766064, year = {2026}, author = {Martin, J and Ortiz, T and Zafar, S and Kuriyan, AE}, title = {Review of current management of submacular hemorrhage.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41766064}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: Subretinal hemorrhage (SRH) is most commonly associated with neovascular age-related macular degeneration (nAMD) and can cause profound vision loss in the macula through mechanical, toxic, and inflammatory mechanisms. Submacular hemorrhage (SMH) lacks consensus on management. This review summarizes current treatment options, key comparative studies, and ongoing challenges, with emphasis on SMH management.<br><br>RECENT FINDINGS: Antivascular endothelial growth factor (anti-VEGF) therapy remains central to SMH management, with outcomes comparable to surgery in small to moderate hemorrhages. Pneumatic displacement (PD) with or without recombinant tissue plasminogen activator (rtPA) shows the greatest comparative benefit in more extensive SMH. Adjunctive rtPA improves hemorrhage displacement rates, and meta-analyses support its efficacy with anti-VEGF therapy. Pars plana vitrectomy (PPV) remains an option for large or refractory hemorrhages but has not consistently shown superior visual outcomes compared to less invasive modalities.<br><br>SUMMARY: Early intervention is consistently associated with improved outcomes, but there is no universally accepted treatment algorithm. Ongoing randomized trials and advances in multimodal imaging have the potential to refine patient selection and treatment strategies. Future efforts should focus on balancing efficacy, safety, and cost-effectiveness to establish evidence-based guidelines for SMH management.}, }
@article {pmid41767319, year = {2026}, author = {Wei, PY and Wang, XZ and Han, JM}, title = {A bibliometric and visualized analysis of choriocapillaris from 2013 to 2023.}, journal = {International journal of ophthalmology}, volume = {19}, number = {3}, pages = {600-611}, pmid = {41767319}, issn = {2222-3959}, abstract = {AIM: To assess the current research status and emerging trends of the choriocapillaris (CC) by bibliometric analysis.<br><br>METHODS: Publications spanning from January 2013 to May 2023 were retrieved on June 27th, 2023, using the Web of Science Core Collection. Bibliometric and visualized analyses were performed employing the bibliometrix, CiteSpace and VOSviewer.<br><br>RESULTS: A total of 1563 papers met the inclusion criteria, and a publication growth trend was observed. The United States was the leading country in the CC field. Retina and Investigative Ophthalmology &amp; Visual Science stood out as highly impactful and prolific journals. Research topics in the CC field encompassed choroidal neovascularization, choroidal thickness, central serous chorioretinopathy, age-related macular degeneration, myopia, choroidal vascularity index, and diabetic retinopathy, based on the co-citation analysis. The keyword "high myopia" experienced a burst lasting until 2023.<br><br>CONCLUSION: In the past decade, research in the field of CC has flourished due to recent advancements in choroidal imaging; with focus shifting towards elucidating its role in various diseases. This will provide novel insights into managing chorioretinal diseases and vision-preserving interventions.}, }
@article {pmid41767914, year = {2025}, author = {Ni, G and Cao, K and Qin, X and Zeng, X and Wu, R and Wan, L and Zhong, J and Liu, Y}, title = {Advanced 3D retinal lesion segmentation using channel-spatial attention-guided multi-scale feature aggregation.}, journal = {Biomedical optics express}, volume = {16}, number = {5}, pages = {2093-2110}, pmid = {41767914}, issn = {2156-7085}, abstract = {Diabetic macular edema (DME) and age-related macular degeneration (AMD) have emerged as leading causes of vision impairment worldwide; optical coherence tomography (OCT) has proven to be a crucial diagnostic tool for these diseases, for its rapid, non-invasive high-resolution imaging of retinal structures. Further accurate assessment of lesions in retinal OCT images plays a pivotal role in the early diagnosis of DME and AMD. However, current diagnosing of AMD and DME is restricted to utilizations of OCT two-dimensional images, for crucial three-dimensional (3D) lesion information inherent in OCT 3D images cannot be effectively extracted and utilized without appropriate methods. Here, we proposed an innovative deep-learning network characterized by fusing multi-scale feature extraction-aggregation and channel-spatial joint attention for high-accuracy 3D lesion segmentations of DME and AMD. Extensive experiment results demonstrated that our proposed method has commendable 3D segmentation performances and robust generalization capabilities, probably helping to understand DME and AMD diseases better and providing great convenience for clinical diagnosis and treatment.}, }
@article {pmid41768996, year = {2026}, author = {Yang, X and Xu, W and Xie, H and Guo, X and Zhu, F and Xing, Y and Chen, C}, title = {The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration.}, journal = {Frontiers in cell and developmental biology}, volume = {14}, number = {}, pages = {1718715}, pmid = {41768996}, issn = {2296-634X}, abstract = {PURPOSE: Age-related macular degeneration (AMD) involves dysfunction of the retinal pigment epithelium (RPE), where cellular senescence and epithelial-mesenchymal transition (EMT) are key pathological features. The upstream mechanisms linking these processes are not fully understood. This study investigates the potential role of ferroptosis in contributing to senescence-associated EMT in RPE cells.<br><br>METHODS: We utilized an aging mouse model and two cellular models in ARPE-19 cells, induced by D-galactose (D-gal) and low-dose sodium iodate (SI), respectively. Ferroptosis, EMT, and oxidative stress markers were evaluated via immunofluorescence, flow cytometry, and Western blotting. The specific ferroptosis inhibitor Ferrostatin-1 was used to assess the involvement of ferroptosis.<br><br>RESULTS: Aged mouse RPE/choroid complexes and stressed ARPE-19 cells exhibited features of EMT along with increased ferroptosis hallmarks, including lipid peroxidation and iron accumulation. A downregulation of the xCT/GPX4 anti-ferroptotic axis was observed. Pretreatment with Fer-1 alleviated ferroptosis by reducing iron levels and lipid peroxidation, and restored xCT/GPX4 expression. Furthermore, Fer-1 attenuated the EMT phenotype, as evidenced by the restoration of epithelial markers and reduction of mesenchymal markers (Vimentin, &#x3b1;-SMA) in both D-gal and SI models.<br><br>CONCLUSION: Our findings suggest that ferroptosis may contribute to linking RPE senescence with EMT, potentially via oxidative stress pathways. The combined targeting of both senescence and ferroptosis could therefore represent a potential therapeutic strategy for addressing RPE dysfunction and AMD progression.}, }
@article {pmid41771640, year = {2026}, author = {Walker, R and Ellett, L and Norton, D and Rouabhi, H and Coughlan, H and Akthar, F and DaSilva Morgan, K and Tait, R and Lisi, M and Ffytche, D}, title = {Charles Bonnet Syndrome: associations between psychosocial measures and visual hallucination characteristics in the visually impaired.}, journal = {BMJ open ophthalmology}, volume = {11}, number = {1}, pages = {}, pmid = {41771640}, issn = {2397-3269}, mesh = {Humans ; Male ; Female ; *Charles Bonnet Syndrome/psychology ; Middle Aged ; *Quality of Life/psychology ; Aged ; Adult ; *Persons with Visual Disabilities/psychology ; Self Report ; *Hallucinations/psychology ; Anxiety/psychology ; Surveys and Questionnaires ; *Vision Disorders/psychology ; Mental Health ; Aged, 80 and over ; }, abstract = {BACKGROUND/AIMS: The emotional response to Charles Bonnet Syndrome (CBS) (visual hallucinations in individuals with sight loss) is associated with negative affect, suggesting a link between psychological measures and hallucination characteristics. This study set out to investigate whether the association extends to a broader range of hallucination attributes and psychological measures, taking into account clinical factors likely to influence such associations.<br><br>METHODS: 70 participants with self-reported CBS completed an online survey assessing hallucination attributes of frequency, duration, emotional valence, distress, level of control over hallucinations and impact on quality of life (QoL). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale while loneliness was assessed using the University of California Los Angeles (UCLA) Loneliness Scale. All three measures were combined as a mental health factor. Regression models tested relationships between hallucination attributes and mental health, controlling for age, sex assigned at birth, years of sight loss, years experiencing hallucinations, presence of migraine and visual field loss.<br><br>RESULTS: All visual hallucination attributes except level of control were associated with the mental health factor; higher factor scores were associated with more frequent, longer lasting, more unpleasant and more distressing hallucinations and also with a more negative impact of hallucinations on QoL. These associations were independent of years of sight loss and CBS.<br><br>CONCLUSION: Mental health measures are linked to a wider range of CBS attributes than previously recognised, with greater clinical attention required to identify people with CBS who are experiencing psychological difficulties to help provide appropriate treatment and support.<br><br>LIMITATIONS: The study did not include a control group of visually impaired participants without hallucinations and has an uneven representation across age and gender with a small sample size for the sub-group analysis. The study relied on self-reported online data without clinical assessment; details of participants' medication use were not collected.}, }
@article {pmid41772510, year = {2026}, author = {Rao, T and Yang, J and Chen, H and Li, X}, title = {OCT-based morphological prognostic factors for structural improvement after anti-VEGF therapy in wet age-related macular degeneration.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04690-3}, pmid = {41772510}, issn = {1471-2415}, }
@article {pmid41772933, year = {2026}, author = {Rizzo, C and Vannozzi, L and Lupidi, M and Savastano, MC and Borrelli, E and Mastropasqua, R and Panini, F and Crincoli, E and Faraldi, F and Virgili, G and Giansanti, F and Bacherini, D}, title = {Prechoroidal cleft in neovascular age-related macular degeneration (AMD): A narrative review of pathophysiology, clinical implications and prognosis.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70095}, pmid = {41772933}, issn = {1755-3768}, abstract = {The prechoroidal cleft (PC) is a hyporeflective space visualized on optical coherence tomography (OCT), typically located within the pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD). Although its pathogenesis is not yet fully understood, proposed mechanisms include fluid accumulation secondary to macular neovascularization (MNV), contractile forces from fibrovascular tissue and chronic structural remodelling of the outer retinal layers. This narrative review synthesizes the current evidence regarding the imaging features, pathophysiological mechanisms, clinical relevance and prognostic implications of the PC in nAMD. The presence of a PC has been variably associated with MNV activity, poor visual outcomes, increased treatment burden and a higher risk of complications, such as retinal pigment epithelium (RPE) tears and submacular haemorrhage (SMH). However, emerging data suggest that the cleft may regress following sustained anti-VEGF therapy, implying a potential role as a marker of therapeutic response and anatomical improvement. Thus, the PC may serve as a dynamic biomarker of disease activity in nAMD patients. Nevertheless, its precise role in disease progression remains unclear, highlighting the need for further longitudinal and histopathological studies.}, }
@article {pmid41773161, year = {2026}, author = {Nakao, G and Hara, C and Nishida, K}, title = {Bilateral Diffuse Uveal Melanocytic Proliferation Masquerading as Refractory Subretinal Fluid Due to Peripapillary Pachychoroid Syndrome.}, journal = {Cureus}, volume = {18}, number = {1}, pages = {e102512}, pmid = {41773161}, issn = {2168-8184}, abstract = {We describe a case of peripapillary pachychoroid syndrome (PPS) that appeared resistant to conventional treatment and was subsequently diagnosed as bilateral diffuse uveal melanocytic proliferation (BDUMP) based on fundus autofluorescence (FAF) images. A 79-year-old man presented with vision loss in both eyes and was initially diagnosed with PPS based on optical coherence tomography, fluorescein angiography, and indocyanine green angiography findings. The patient underwent photodynamic therapy in both eyes, photocoagulation in the left eye, and 2 mg aflibercept injections in both eyes. Although he responded to the initial treatments, the response gradually diminished with subsequent injections. Due to the progression of his cataracts, the patient underwent cataract removal surgery. He was later diagnosed with BDUMP based on subsequent FAF images, which revealed characteristic ocular fundus findings known as giraffe-like patterns. Subsequent systemic evaluation revealed prostate cancer. BDUMP can masquerade as PPS or neovascular age-related macular degeneration (n-AMD), resulting in delayed diagnosis and treatment, and should be considered in the differential diagnosis of cases where PPS or n-AMD is refractory to conventional treatment, even in the absence of a known malignancy.}, }
@article {pmid41773239, year = {2026}, author = {Shiratori, M and Maruyama-Inoue, M and Yanagi, Y and Inoue, T and Kadonosono, K}, title = {Comparison of Short-term Outcomes Between Faricimab and High-Dose Aflibercept in Patients With Neovascular Age-related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261423302}, pmid = {41773239}, issn = {2474-1272}, abstract = {Purpose: To compare functional and morphologic outcomes after loading doses of faricimab and high-dose aflibercept for treatment-naive neovascular age-related macular degeneration (nAMD). Methods: We retrospectively enrolled 62 consecutive patients (64 eyes) with nAMD whose initial visual acuity (VA) was ≤20/25. Patients received 3 consecutive monthly loading doses of intravitreal 6.0 mg/0.05 mL faricimab (IVF) or intravitreal 8.0 mg/0.07 mL high-dose aflibercept (IVHDA). Changes in best-corrected VA (BCVA) and fluid were assessed at 4, 8, and 16 weeks compared with baseline. Results: Two patients were excluded from the final analysis, yielding a total of 60 patients (62 eyes). In the IVF group (n = 31 eyes), the logMAR BCVAs at baseline, 4, 8, and 16 weeks were 0.40, 0.35, 0.33, and 0.30, respectively; significant improvement occurred at 16 weeks only (P = .004 vs baseline). In the IVHDA group (n = 31 eyes), the logMAR BCVAs at the respective timepoints were 0.44, 0.36, 0.30, and 0.32; significant improvements occurred at 8 and 16 weeks (P = .001 and P = .007, respectively, vs baseline). At 16 weeks, 90.3% of patients receiving IVF and 80.6% receiving IVHDA had dry macula (P = .473). Conclusion: Significant BCVA improvements were achieved with both treatments, although improvement was faster with IVHDA. High rates of dry macula were achieved at 16 weeks in more patients in the IVF group than in the IVHDA group.}, }
@article {pmid41774087, year = {2026}, author = {Weatherston, D and Jones, JA and Vargis, E}, title = {Changes in ApoE and TIMP-1 expression correlate with outer blood-retinal barrier disruption in an in vitro model of retinal aging.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {41774087}, issn = {2509-2723}, support = {EY028732/EY/NEI NIH HHS/United States ; M2019109//BrightFocus Foundation/ ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Unfortunately, the early stages of this disease are poorly understood, which has led to limited treatment options. Investigating normal changes in tissues eventually affected by AMD can further elucidate the mechanisms of disease progression and lead to novel therapeutic targets. The primary cell layer affected in AMD is the retinal pigment epithelium (RPE), which forms the outer blood-retinal barrier (oBRB). Beneath the RPE lies Bruch's membrane, a proteinaceous layer that naturally thickens and stiffens with age. These changes to Bruch's membrane are also implicated in RPE dysfunction and AMD progression. To investigate the relationship between normal, age-related changes in Bruch's membrane and AMD development, we engineered a tunable in vitro model of Bruch's membrane to support primary porcine RPE cells. We performed transepithelial electrical resistance (TEER) measurements, viability assays, morphological analysis, immunocytochemistry, and enzyme-linked immunosorbent assays (ELISA) to evaluate monolayer integrity and angiogenic factor expression. Cells cultured on our aged model exhibited changes similar to those seen in AMD, including reduced monolayer integrity, the formation of sub-RPE deposits, and eventual cell death. Notably, apolipoprotein E (ApoE), a known drusen component and Alzheimer's disease marker, was overexpressed prior to deposit accumulation and cell death. Regions of ApoE overexpression corresponded with disrupted expression of zonula occludens-1, a junctional protein. While most angiogenic factors remained unchanged, tissue inhibitor of metalloproteinases-1 (TIMP-1) was transiently overexpressed before cell death. These findings suggest that ApoE and TIMP-1 may play key roles in early AMD pathogenesis and represent potential targets for future therapeutic intervention.}, }
@article {pmid41776295, year = {2026}, author = {Eilon, E and Lishinsky-Fischer, N and Levy, J}, title = {Response to: 'Comment on 'Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study".}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41776295}, issn = {1476-5454}, }
@article {pmid41777091, year = {2026}, author = {Arkhipchenko, AA and Semenov, AN and Chesalin, DD and Sidorenko, SV and Bodunova, DV and Gorokhov, ES and Yakovleva, MA and Feldman, TB and Moysenovich, AM and Senin, II and Shebardina, NG and Tiulina, VV and Ramonova, AA and Andreev, VS and Morozov, PV and Bilan, DS and Ilyinsky, NS and Zernii, EY and Maksimov, EG and Ostrovsky, MA and Kirpichnikov, MP}, title = {Photooxidation Dynamics of Lipofuscin in the Presence of Carotenoid-Binding Protein AstaP: Fluorescence Lifetime Imaging and Pigment Composition Analysis.}, journal = {The journal of physical chemistry. B}, volume = {130}, number = {11}, pages = {2974-2986}, doi = {10.1021/acs.jpcb.5c06621}, pmid = {41777091}, issn = {1520-5207}, mesh = {*Lipofuscin/chemistry/metabolism ; Humans ; Oxidation-Reduction ; Optical Imaging ; Chromatography, High Pressure Liquid ; Retinal Pigment Epithelium/cytology/metabolism ; *Carotenoids/metabolism/chemistry ; Retinoids/chemistry/metabolism ; Cell Line ; Photochemical Processes ; }, abstract = {To introduce noninvasive optical diagnostic methods based on detection of tissue autofluorescence signals into medical practice, it is necessary to correlate the optical response with the functional state of a particular chromophore. Diagnostics of the state of lipofuscin granule chromophores is an important task to assess pathologic changes in the visual system in various diseases, primarily age-related macular degeneration. A key feature of lipofuscin granules (LGs) is the diversity of the chromophores and their susceptibility to oxidation. Here, we used time-resolved emission spectroscopy, confocal fluorescence lifetime imaging microscopy, and high-performance liquid chromatography (HPLC) to follow changes of LG chromophore composition upon photooxidation. In both isolated LGs and LG-loaded retinal pigment epithelium cells (ARPE-19), the distributions of the short lifetime component and its amplitude of LG fluorescence shifted, and the mean lifetime increased upon photooxidation, indicating depletion of population of rapidly relaxing bisretinoids, including A2E, and accumulation of their oxidized species, as confirmed by HPLC data. We applied differential evolution algorithms to decompose LG autofluorescence parameters and identified distinct photooxidation patterns in the presence and absence of antioxidant protection. Delivery of zeaxanthin by water-soluble carotenoprotein ΔNC-AstaP attenuated photooxidation-induced changes in the decay kinetics of both isolated and intracellular LGs, suppressed the accumulation of oxidized bisretinoids, and prevented complete photooxidation. Taken together, our results establish that time-resolved lipofuscin autofluorescence provides a quantitative, label-free readout of chromophore composition and oxidative status that is compatible with functional imaging. We propose that such lifetime-based measurements can be employed for early assessment of retinal pathology and for monitoring antioxidant interventions targeting lipofuscin-induced oxidative stress in emerging clinical techniques such as fluorescence lifetime imaging ophthalmoscopy.}, }
@article {pmid41778671, year = {2026}, author = {Jiménez-Loygorri, JI and Cuervo, AM and Ferrington, DA and Boya, P}, title = {Chaperone-mediated autophagy: the Achilles heel of the retinal pigment epithelium during age-related macular degeneration.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/15548627.2026.2636093}, pmid = {41778671}, issn = {1554-8635}, abstract = {Chaperone-mediated autophagy (CMA) is a selective autophagy pathway that targets specific proteins containing a KFERQ-like motif for lysosomal degradation. It has been shown by us and others that CMA decreases during physiological aging in most tissues, and its impairment is associated with increased incidence of age-related pathologies, such as cardiovascular disease, neurodegenerative disorders or sarcopenia. However, its involvement in age-related macular degeneration (AMD), a prevalent progressive maculopathy that leads to bilateral central vision loss, had not been explored. In the early stages of AMD, the retinal pigment epithelium (RPE), a monolayer of cells that provides trophic support to photoreceptors, already presents major morphological and functional alterations but the cause of this cell type-specific vulnerability is unknown. In our latest work, we analyzed human donor RPE samples and found that CMA is selectively impaired in the RPE of AMD patients compared to healthy donors. These alterations lead to the accumulation of undegraded CMA substrates and untimely recycling of other proteins. Crucially, these findings are conserved in donor-derived iPSC-RPE models. We used this clinically relevant model to assess the consequences of dysfunctional CMA in AMD and found that it caused proteotoxicity, increased oxidative damage, and altered metabolism. Most importantly, using the new-generation CMA activator CA77.1, we restored proteostasis in AMD iPSC-RPE. Our findings shed light on the selective vulnerability of the RPE in AMD and provide evidence in support of CMA as a novel druggable target against AMD.}, }
@article {pmid41779364, year = {2026}, author = {Kitay, AM and Tillmann, A and Pfister, I and Schild, C and Bonanata, M and Heck, K and Spitznagel, T and Gabathuler, F and Bartolomeo, N and Magnin, S and Löliger, J and Munk, MR and Menghini, M and Hatz, K and Somfai, GM and Zweifel, S and Ambresin, A and Eandi, CM and Feltgen, N and Weinberger, A and Garweg, JG and Kurz-Levin, MM}, title = {One-Year Real-World Outcomes of Switching to Aflibercept 8 mg in Eyes with Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41779364}, issn = {2193-8245}, abstract = {INTRODUCTION: This multicenter, longitudinal, observational real-world study evaluated the efficacy and safety of switching to intravitreal aflibercept 8 mg (Afl 8) in pretreated eyes with neovascular age-related macular degeneration (nAMD) within the Swiss Retina Research Network. A total of 283 eyes from 245 patients previously treated with other anti-vascular endothelial growth factor (anti-VEGF) agents (aflibercept 2 mg, faricimab, and ranibizumab) were included, with 1-year efficacy outcomes analyzed in 246 eyes and safety assessed in all treated eyes.<br><br>METHODS: We recorded demographics, baseline functional and anatomical parameters-including spectacle-corrected visual acuity (VA) and optical coherence tomography (OCT) data-treatment history and outcomes over 12&#xa0;months after switching to Afl 8. The main outcome measures were change in VA, central subfield thickness (CST), presence of intra- and subretinal fluid (IRF/SRF) and pigment epithelial detachment (PED), treatment intervals, and adverse events.<br><br>RESULTS: Twelve months after the switch to Afl 8, mean VA remained stable, while mean CST decreased from 329.1 to 302.8&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). The portion of eyes without retinal fluid increased from 29.9% at baseline to 47.5% after 12&#xa0;months. In parallel, the mean treatment interval was extended by 32.3% from 7.1 to 9.4&#xa0;weeks (p&#x2009;<&#x2009;0.001). At 1 year, 35.4% of eyes reached intervals of 8-11&#xa0;weeks, while 20.2% achieved intervals of 12&#xa0;weeks or longer. Intraocular inflammation was reported in 11 cases (3.9%).<br><br>CONCLUSIONS: In pretreated nAMD eyes with high treatment demand, switching to Afl 8 resulted in a significant anatomical improvement and longer treatment intervals in a majority of patients. These real-world results highlight the therapeutic potential of Afl 8, with no new or unexpected safety issues.}, }
@article {pmid41779676, year = {2026}, author = {Maggio, E and Avogaro, F and Casillo, L and Mete, M and Vingolo, EM and Maraone, G and Sanfilippo, L and Guerriero, M and Pertile, G}, title = {Long-term Evolution and Growth Rate Assessment of Non-Exudative Macular Neovascularization: A Multicenter Analysis.}, journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde}, volume = {}, number = {}, pages = {1-17}, doi = {10.1159/000551308}, pmid = {41779676}, issn = {1423-0267}, abstract = {PURPOSE: A population of patients with age-related macular degeneration (AMD) was analyzed to investigate the prevalence of non-exudative macular neovascularizations (neMNV), the conversion rate to exudation, and to discern differences between neMNVs that exhibited exudation versus those that remained non-exudative.<br><br>DESIGN: Retrospective observational case series.<br><br>METHODS: In this retrospective, multicentric, longitudinal study, consecutive patients treated with anti-VEGF between august 2008 and June 2023, presenting exudative AMD in one eye and intermediate AMD in the fellow eye, were analyzed. The presence of neMNVs in the fellow eyes and their conversion rate to exudation were assessed. Clinical and anatomical features were compared between eyes that developed exudation versus those that did not. The correlation between lesion major diameters and areas was examined to evaluate their equivalence as parameters for assessing neMNV growth rate.<br><br>RESULTS: A total of 61 eyes out of 840 (7.3%) exhibited neMNV. Of these, 21 neMNV (34.42%) converted to exudation in a mean time of 24.14 months (min. 7 - max. 113). The remaining 40 eyes did not develop exudation during a mean follow-up of 32.5 months (min. 12 - max. 101). No significant differences were found regarding visual acuity, OCT angiography features, or baseline lesion diameters. NeMNV that developed exudation exhibited a higher lesion growth rate (p-value <0.001). The growth rate evaluated using lesion major diameters was consistent with that obtained through lesion area measurements.<br><br>CONCLUSION: The results highlight lesion growth rate as a marker of conversion risk. Lesion diameter was identified as a reliable parameter for monitoring neMNV progression. Despite a long-term follow-up, many lesions did not develop exudation. These results support the idea that neMNV may represent a spectrum of neovascularizations with different characteristics and clinical courses.}, }
@article {pmid41780904, year = {2026}, author = {Bernal-Morales, C and Burgos Herrera, S and Giralt, L and Alforja, S and Romero-Núñez, B and Catalan-Coronado, S and Bilbao, V and Sala-Puigdollers, A and Pelegrin-Colas, L and Zarranz-Ventura, J and Adan, A and Casaroli-Marano, R and Figueras-Roca, M}, title = {Faricimab for recalcitrant neovascular age-related macular degeneration: a real-life study following aflibercept nonresponse.}, journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjo.2026.02.009}, pmid = {41780904}, issn = {1715-3360}, abstract = {OBJECTIVE: To evaluate anatomical and functional outcomes following a switch to intravitreal faricimab in patients with active, recalcitrant neovascular age-related macular degeneration (nAMD) previously treated with aflibercept in a real-life setting.<br><br>DESIGN: A retrospective, observational, single-centre study.<br><br>METHODS: Demographic data and prior intravitreal treatment (IVT) history were collected. Best-corrected visual acuity (BCVA) and disease activity were assessed using optical coherence tomography (OCT), including fluid compartments: intraretinal fluid, subretinal fluid (SRF), pigment epithelial detachment, and subretinal hyperreflective material.<br><br>RESULTS: A total of 161 eyes from 145 patients (mean age: 80.1&#x202f;&#xb1;&#x202f;7.8 years) were included. Mean prior IVT duration was 2.9&#x202f;&#xb1;&#x202f;2.5 years. All eyes were active at the time of switching, with 82.0% showing persistent SRF. Disease inactivation occurred in 42.9% of eyes after the switch, more frequently in eyes with shorter prior treatment duration. BCVA remained stable throughout the follow-up. SRF resolved in 50.8% of eyes, with 52.2% achieving resolution after a single injection. Mean treatment intervals increased significantly in inactivated eyes (+4.9&#x202f;&#xb1;&#x202f;5 weeks). Disease relapse occurred in 54.6% of the initially inactivated eyes. No adverse events were reported.<br><br>CONCLUSIONS: Switching to faricimab may offer a valuable therapeutic option for recalcitrant nAMD, particularly in eyes with persistent SRF, providing improved anatomical outcomes while maintaining visual acuity in real-life practice. Prospective studies are warranted to better define response profiles and guide personalized treatment strategies.}, }
@article {pmid41782931, year = {2026}, author = {Zhou, Y and Zhan, Z and Wang, Z and Liu, C}, title = {Efficacy and safety of aflibercept biosimilars compared to aflibercept in the treatment of neovascular age-related macular degeneration: a systematic review and meta-analysis.}, journal = {Frontiers in pharmacology}, volume = {17}, number = {}, pages = {1719493}, pmid = {41782931}, issn = {1663-9812}, abstract = {BACKGROUND: This study aimed to evaluate the aflibercept biosimilars compared to the reference product aflibercept (Eylea®) in terms of efficacy, safety, and immunogenicity in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We searched PubMed, Web of Science, Cochrane Library, and Embase from inception to 13 August 2025. We included studies reporting changes in best-corrected visual acuity (BCVA), changes in central subfield thickness (CST), changes in the leakage lesion of choroidal neovascularization (CNV), and adverse events from baseline to endpoint. All statistical analyses were performed using Stata 18.0 software and assessed the certainty of evidence for each outcome using the GRADE approach.<br><br>RESULTS: A total of seven studies involving 2,829 participants were included. There were no statistically significant differences in visual and anatomical outcomes between the aflibercept biosimilars (SB15, P041, SDZ-AFL, AVT06, SCD411, ABP 938, and QL1207) and the reference aflibercept. No significant differences were detected between aflibercept biosimilars and the reference aflibercept with respect to serious ocular and non-ocular adverse events [relative risk (RR) = 1.71, 95% confidence interval (CI): 0.70, 4.19; I [2] = 0.0%, P = 0.913; RR = 1.08, 95% CI: 0.82, 1.42; I [2] = 0.0%, P = 0.936, respectively). Although a slightly higher rate of treatment-emergent adverse events (TEAEs) was noted in the biosimilar group (RR = 1.07, 95% CI: 1.00-1.15; I[2] = 26.1%), the difference was not statistically significant (P = 0.248).<br><br>CONCLUSION: Based on the seven included randomized controlled clinical trials, aflibercept biosimilars demonstrated comparable safety and efficacy to the reference aflibercept. Future research requires more rigorous studies.}, }
@article {pmid41783117, year = {2026}, author = {Zhao, CS and Do, DV and Sanislo, SR and Ludwig, C and Rahimy, E and Mruthyunjaya, P and Wai, KM}, title = {Prevalence of Systemic Comorbidities and Ocular Complications in Patients With Bilateral Retinal Telangiectasia.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261423313}, pmid = {41783117}, issn = {2474-1272}, abstract = {Purpose: To compare systemic comorbidities in bilateral retinal telangiectasia, a proxy for macular telangiectasia (MacTel) type 2, vs matched controls. Methods: We conducted a retrospective cohort study of a large electronic health research network of patients who were older than 45 years at bilateral retinal telangiectasia diagnosis vs controls receiving eye care. Patients with macular edema or exudative age-related macular degeneration were excluded. Propensity score matching was performed on demographics. The prevalence of hypertension, diabetes mellitus, obesity, hyperlipidemia, and death within 5 years of retinal telangiectasia diagnosis or eye care visit were compared. Results: 2320 patients with bilateral retinal telangiectasia and 1 671 600 patients with an eye care visit were included. After matching, no demographic differences persisted. Bilateral retinal telangiectasia (vs control) patients had higher rates of type 2 diabetes mellitus (32.8% vs 20.7%; odds ratio [OR], 1.87; 95% CI, 1.64-2.14; P < .005) and obesity (19.9% vs 16.9%; OR 1.22; 95% CI:1.05-1.42; P = .01) and a lower rate of hyperlipidemia (32.0% vs 39.5%; OR 0.71; 95% CI, 0.63-0.80; P < .005). No differences occurred in hypertension or death. Conclusions: Retinal telangiectasia and MacTel type 2 are uncommon and poorly understood, with high coexisting rates of diabetes and obesity. Systemic disease associations should be investigated to identify disease interactions, the impact of systemic interventions, and leads for potential new treatments.}, }
@article {pmid41783478, year = {2026}, author = {Tsutsumi, N and Sakata, S and Ikari, R and Ebihara, N}, title = {Long-term follow-up of a Tay-Sachs disease patient with cherry-red spot.}, journal = {American journal of ophthalmology case reports}, volume = {42}, number = {}, pages = {102548}, pmid = {41783478}, issn = {2451-9936}, abstract = {PURPOSE: To describe the clinical progression and ophthalmic findings in a Japanese boy with Tay-Sachs disease at ages 5 and 8 months.<br><br>RESULTS: The patient was born at 38 weeks of gestation and developed normally until motor skill delays were identified at age 1 year and 1 month. At that time, brain magnetic resonance imaging revealed diffuse T2 hyperintensity in the bilateral basal ganglia. At age 1 year and 6 months, he was able to fix and follow objects, and the optic discs appeared normal, but bilateral cherry-red spots were observed in the maculae. Based on these findings, together with hypersensitivity to sound and markedly reduced &#x3b2;-hexosaminidase A activity, Tay-Sachs disease was biochemically diagnosed. By age 2 years and 1 month, the patient had lost the ability to fixate on and follow objects. Fundoscopy at age 4 years and 4 months revealed optic atrophy and reduced cherry-red spots, electroretinography (ERG) at age 4 years and 9 months showed a complete loss of retinal responses, and optical coherence tomography at age 5 years and 3 months demonstrated retinal thinning. Long-term observation revealed progressive degeneration, consistent with previous reports. Lipid deposition in all retinal layers was considered to contribute to retinal atrophy.<br><br>CONCLUSIONS: This report highlights progressive retinal degeneration with optic atrophy, retinal thinning, and reduction in cherry-red spots. The flat ERG waveform in this patient suggests more advanced retinal involvement than in previous reports and provides insights into the ocular manifestations of Tay-Sachs disease.}, }
@article {pmid41783692, year = {2026}, author = {Xiao, K and Gao, J and Zhang, Y and Chen, R and Wang, Y and Gu, C and Liu, J and Huang, Y and Li, L}, title = {Healthy Dietary Patterns and Risk of Major Eye Diseases: Evidence From Nationally Population-Based Data and Bibliometric Analysis.}, journal = {Food science &amp; nutrition}, volume = {14}, number = {3}, pages = {e71528}, pmid = {41783692}, issn = {2048-7177}, abstract = {The associations between dietary patterns and major eye diseases remain incompletely understood. This study conducted a cross-sectional analysis of 4241 participants from the 2005-2008 National Health and Nutrition Examination Survey. Eye diseases were assessed using fundus photography and self-reported information, while dietary patterns were evaluated based on two 24-h dietary recalls. Survey-weighted logistic regression and restricted cubic spline models were applied with adjustment for complex sampling design and relevant covariates, alongside subgroup and dietary component-specific analyses. In fully adjusted models, higher HEI-2020 scores were associated with lower odds of retinopathy and composite eye disease outcomes with or without cataract surgery. Similarly, greater adherence to the DASH was inversely associated with retinopathy and composite eye disease outcomes. Mediterranean diet adherence was also associated with reduced odds of retinopathy, and a non-linear association was observed between Mediterranean diet adherence and cataract risk. Subgroup analyses indicated effect modification by age, body mass index, alcohol consumption, and hyperlipidemia status. Whole grains, total vegetables, and nuts emerged as protective dietary components, whereas refined grains were identified as a potential risk factor. In conclusion, higher adherence to HEI-2020, DASH, and Mediterranean dietary patterns was associated with a lower prevalence of selected major eye diseases. These findings reflect associations rather than causation, and prospective studies and randomized trials are needed to clarify temporal and causal relationships.}, }
@article {pmid41783718, year = {2026}, author = {Terao, R and Tsusu, C and Saeki, Y and Yashiro, K and Ota, M and Aoki, S and Kitamoto, K and Azuma, K}, title = {Evaluation of Reticular Pseudodrusen by Polarization-Sensitive Optical Coherence Tomography: Case Report.}, journal = {Case reports in ophthalmology}, volume = {17}, number = {1}, pages = {171-178}, pmid = {41783718}, issn = {1663-2699}, abstract = {INTRODUCTION: Reticular pseudodrusen (RPD) are an important clinical biomarker associated with progression to late age-related macular degeneration (AMD). We report polarization-sensitive optical coherence tomography (PS-OCT) findings in a case of RPD and evaluate the entropy characteristics of these lesions.<br><br>CASE PRESENTATION: A 73-year-old man presented for evaluation of retinal angiomatous proliferation in his right eye. The left eye demonstrated multiple round, white-yellowish macular lesions consistent with RPD. Optical coherence tomography (OCT) angiography showed no macular neovascularization in the left eye. Swept-source (SS-OCT) revealed hyperreflective, spike-like deposits between the photoreceptor outer segments (PROSs) and the retinal pigment epithelium. Corresponding PS-OCT B-scans demonstrated moderately elevated polarimetric entropy values at the same locations. En face images reconstructed from the PROS layer showed circular RPD-like lesions on SS-OCT, which precisely matched high-entropy areas on PS-OCT. Merged en face maps confirmed one-to-one correspondence between RPD and regions of increased entropy.<br><br>CONCLUSION: PS-OCT successfully visualized RPD as moderately high-entropy lesions in the PROS layer, suggesting that these deposits are composed of non-retinal pigment epithelium material, such as lipids or inflammatory cells. These findings indicate that PS-OCT may serve as a useful complementary modality for detecting RPD and may enhance current imaging strategies for assessing RPD and monitoring AMD progression.}, }
@article {pmid41784091, year = {2026}, author = {Devin, F and Kodjikian, L and Fourmaux, E and Deudon-Combe, A and Boulet, JF and Pouriel, M and Marquet, G and Balez, S and Derquenne, F and Savary de Beauregard, V and Souied, E}, title = {Results from a French brolucizumab access program for pretreated patients with neovascular age-related macular degeneration.}, journal = {European journal of ophthalmology}, volume = {}, number = {}, pages = {11206721251414691}, doi = {10.1177/11206721251414691}, pmid = {41784091}, issn = {1724-6016}, abstract = {PurposeFollowing European Medicines Agency (EMA) approval, France implemented a managed access program (MAP) to provide brolucizumab to patients with neovascular age-related macular degeneration (nAMD) who lacked treatment alternatives. The French MAP data analysis evaluated efficacy and safety of brolucizumab in brolucizumab-naïve patients.MethodsOf 599 patients enrolled between February 2022 and January 2024, 360 pretreated with anti-VEGF therapy but brolucizumab-naïve were assessed at baseline for clinical and anatomical benefits of brolucizumab in a close-to-real-world setting.ResultsAfter 18 months, patients received a median of eight injections, maintaining visual acuity and achieving a mean central subfield macular thickness (CSMT) reduction of -92.0 µm among those with baseline CSMT ≥300 µm. Intraretinal fluid, subretinal fluid, and pigment epithelial detachment occurred in 32.8%, 75.3%, and 61.7% patients at baseline, and 16.5%, 47.0%, and 51.3% patients at 18 months. Patients previously requiring Q4 or Q5-Q7 injections successfully extended their intervals to Q8 or longer. Intraocular inflammation rate was 8.0% (n = 29).ConclusionResults demonstrated functional and anatomical benefits of brolucizumab in patients with refractory or suboptimally controlled nAMD, with a manageable safety profile. These findings highlight the potential of brolucizumab to reduce treatment burden in chronic nAMD.}, }
@article {pmid41784336, year = {2026}, author = {Chen, C and Razavi, R and Romano, F and Niessen, H and Sabokrohiyeh, S and Konda, A and Chevrefils, C and Arbour, JD and Rhéaume, MA and Nissan, R and Rojewski, A and Sorya, P and Santucci, L and Campbell, S and Ploumi, I and Zhu, Y and Ding, X and Sylvestre, JP and Miller, JB and Nassar, K}, title = {Hyperspectral Imaging for the Classification and Analysis of Drusen in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {10}, pmid = {41784336}, issn = {1552-5783}, mesh = {Humans ; *Retinal Drusen/classification/diagnosis/etiology ; Cross-Sectional Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Aged ; *Macular Degeneration/complications/diagnosis/classification ; Aged, 80 and over ; *Hyperspectral Imaging/methods ; ROC Curve ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To characterize the spatial-spectral signatures of drusenoid deposits [soft, hard, and reticular pseudodrusen (RPD)] in eyes with non-exudative age-related macular degeneration (AMD).<br><br>METHODS: In this observational, cross-sectional, prospective study, hyperspectral retinal images and corresponding Optical Coherence Tomography (OCT) images were collected from 152 eyes of 100 participants with non-exudative AMD. Drusenoid deposits were manually annotated in 148 eyes (97 participants) by retinal specialists using OCT as the reference standard. Automated drusen identification was then performed using spectral angle mapper (SAM) and random forest classifiers.<br><br>RESULTS: Hyperspectral imaging revealed that RPD was most distinct at 470-500&#xa0;nm, soft drusen at 525-575&#xa0;nm, hard drusen at 620-675&#xa0;nm, and pigmentary abnormalities at 650-725&#xa0;nm. Using the SAM classifier, drusenoid deposits were identified with 97% sensitivity and 70% specificity. The random forest classifier achieved higher overall performance, with 88% sensitivity, 99% specificity, and an area under the receiver operating characteristic curve of 0.96. Pixel-wise SAM mapping delineated drusenoid deposits and healthy retina, extending beyond annotated regions.<br><br>CONCLUSIONS: Distinct spatial-spectral signatures for soft drusen, hard drusen, and RPD were identified using hyperspectral imaging. Both SAM and random forest classifiers demonstrated promising results for automated drusenoid deposit detection. These findings support the role of hyperspectral retinal imaging as a noninvasive tool for automated drusen mapping and patient risk stratification in nonexudative AMD.}, }
@article {pmid41786217, year = {2026}, author = {Chaikitmongkol, V and Somkuna, T and Patikulsila, D and Ruamviboonsuk, P and Jirarattanasopa, P and Srisomboon, T and Narongchai, C and Ratanasukon, M and Bhurayanontachai, P and Kunavisarut, P and Watanachai, N and Choovuthayakorn, J and Chotcomwongse, P and Sangkaew, A and Ingviya, T and Bressler, NM}, title = {Factors predicting fluid-free retina and complete polypoidal regression in polypoidal choroidal vasculopathy eyes receiving 2-mg aflibercept treatments.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100298}, doi = {10.1016/j.apjo.2026.100298}, pmid = {41786217}, issn = {2162-0989}, abstract = {PURPOSE: To determine predictive factors for fluid-free retina and complete polypoidal choroidal vasculopathy (PCV) regression following 1-year aflibercept monotherapy in PCV.<br><br>METHODS: Multicenter, retrospective cohort of treatment-na&#xef;ve PCV eyes receiving 2-mg aflibercept treatments for 1 year from 2015 to 2018 collected demographic data, de-identified fundus photography, optical coherence tomography (OCT), and indocyanine green angiography (ICGA) images at baseline and 1-year of study eyes were graded to identify baseline features and outcomes.<br><br>RESULTS: Of 100 study eyes, mean age [SD] was 63.8 [8] years; 100% were Thai patients. At 1 year, eighty-five eyes (85%) had fluid-free retina; 48 eyes (48%) had complete polypoidal regression. Multivariate analyses showed baseline OCT and ICGA features associated with 1-year outcomes: sharply-peaked PED with/without double-layer sign on OCT and smaller lesion size on ICGA (<1 disc diameter) were associated with fluid-free retina (OR 6.57; 95%CI 1.27-34.10, and OR 7.86; 95%CI 1.33-46.54, respectively). Multilobulated PED on OCT was associated with poor (20/200 or worse) final VA (OR 4.53; 95%CI 1.33-15.36). Smaller number (1-5) of polypoidal lesions on ICGA was associated with complete polypoidal regression (OR 4.87; 95%CI 1.44-16.43) CONCLUSION: Results suggest baseline OCT and ICGA features could predict fluid-free retina and complete polypoidal regression following aflibercept monotherapy.}, }
@article {pmid41786219, year = {2026}, author = {Phan, LT and Chin, J and Broadhead, GK and Hong, TH and Mehta, H and Chang, JH and Fraser-Bell, S and Cheung, CMG and Sun, CZ and Luckie, AP and Wickremasinghe, SS and Liew, G and Gilhotra, JS and Simunovic, MP and Verma, N and Chang, AA}, title = {Faricimab for previously-treated eyes with neovascular age-related macular degeneration with inadequate response - 6-month interim analysis of the FURGGHORN study.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100299}, doi = {10.1016/j.apjo.2026.100299}, pmid = {41786219}, issn = {2162-0989}, abstract = {PURPOSE: To investigate the effect of switching to faricimab therapy patients with neovascular age-related macular degeneration currently treated with anti-VEGF therapy.<br><br>DESIGN: Phase IV, prospective, single-arm, open-label, multi-center, investigator-initiated clinical trial.<br><br>METHODS: Eligible eyes received four initial doses of faricimab 6&#x202f;mg/0.05&#x202f;mL every 4-weeks. From week 12, dosing intervals were increased to eight weeks and then modified according to a treat-and-extend based regimen. This interim analysis reports changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid proportions, and the incidence of adverse events from baseline through to week 24.<br><br>RESULTS: One-hundred-and-two patients of mean age 76.0 years were recruited from 12 sites across Australia and Singapore. Baseline BCVA was 72 Early Treatment Diabetic Retinopathy Study letters and baseline CST was 384&#x202f;&#xb5;m. Seventy-two percent of eyes were being treated with aflibercept 2&#x202f;mg and 28% with ranibizumab. After switching to faricimab, mean BCVA change was +&#x202f;1.9 letters at week 12 (P&#x202f;<&#x202f;0.001), and +&#x202f;1.9 letters at week 24 (P&#x202f;<&#x202f;0.001). Mean CST change was -83.9&#x202f;&#xb5;m at week 12 (P&#x202f;<&#x202f;0.001), and -82.2&#x202f;&#xb5;m at week 24 (P&#x202f;<&#x202f;0.001). The proportion of eyes with fluid resolution was 54% at week 12, and 59% at week 24. The proportion of eyes assigned to 4-weekly, 8-weekly, and 12-weekly treatment intervals were 16%, 35% and 49% respectively at week 24. Anterior chamber inflammation occurred in one eye with no cases of vasculitis or occlusive retinitis.<br><br>CONCLUSIONS: In this pre-specified interim analysis of a prospective study, patients switching to faricimab experienced improved anatomic outcomes and maintained visual function, with a large proportion assigned extended dosing intervals under a flexible treatment regimen.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12623000215628.}, }
@article {pmid41786848, year = {2026}, author = {Chung, DH and Jee, D and Roh, YJ and Ra, H and Lee, MY and Won, JY and Shin, JA and Jung, SH and Park, YH}, title = {Short term real-world effectiveness of faricimab in neovascular age-related macular degeneration patients in the Republic of Korea.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41488-1}, pmid = {41786848}, issn = {2045-2322}, support = {RS-2025-25417985//Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health &amp; Welfare, Republic of Korea/ ; }, abstract = {To analyze visual and anatomic outcomes of faricimab injection in neovascular age-related macular degeneration (nAMD) in a real-world setting in Korea. We collected data from nAMD patients who received faricimab injection from 2024 to 2025. The past injection history, and faricimab injection history was obtained. Visual acuity (VA) and central macular thickness (CMT) outcomes for 1, 3, 6, 12 months after initial faricimab injection were compared to baseline, and also compared between sex, different age-groups, and naïve vs. non-naïve groups. A total of 286 patients, 293 eyes from 8 university hospitals were included in this study. VA improved from baseline 58.9 ± 17.1 letters to 60.7 ± 23.5, 61.0 ± 18.1, 59.9 ± 19.3, 60.5 ± 18.2 letters at 1, 3, 6, 12 months respectively (statistically significant at 3 months, p = 0.009), while CMT improved by -60.6 ± 89.0, -55.9 ± 87.3, -46.5 ± 97.5, -70.7 ± 97.8 μm compared to baseline (p < 0.001 at all timepoints). An age group analysis showed that the youngest age group (< 60 years) had superior VA results, while the naïve group showed superior outcomes compared to the non-naïve group. CMT fluctuation showed inverse correlation with visual acuity at 6 months, with lower CMT fluctuation being associated with the young and naïve. Faricimab injection for nAMD, in a real-world setting in the Republic of Korea, showed significant functional and anatomic improvements with superior results in the younger age group and naïve group, suggesting promising effectiveness of a bispecific blockage of VEGF-A and Ang-2 at the initial phases of nAMD.}, }
@article {pmid41786902, year = {2026}, author = {Judkiewicz, R and Berkowitz, E and Meisel, M and Michaeli, T and Behar, JA}, title = {Shifting the retinal foundation models paradigm from slices to volumes for optical coherence tomography.}, journal = {NPJ digital medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41746-026-02496-7}, pmid = {41786902}, issn = {2398-6352}, abstract = {Optical Coherence Tomography (OCT) is essential in ophthalmology for cross-sectional imaging of the retina. Pretrained foundation models facilitate task-specific model development by enabling fine-tuning with limited labeled data. However, current foundation models rely on a single B-scan (usually the central slice), overlooking volumetric context. This research investigates video foundation models to capture full 3D retinal structure and improve diagnostic performance. V-JEPA, a state-of-the-art video foundation model, was benchmarked against retinal foundation models (RETFound, VisionFM) and a natural image foundation model (DINOv2). All were fine-tuned to detect Age-related Macular Degeneration or Glaucomatous Optic Neuropathy using five OCT datasets. V-JEPA consistently equaled or outperformed image-based models, achieving an average AUROC of 0.94 (0.80-0.99), versus 0.90 (0.76-0.98) for the best image model, a statistically significant improvement (p < 0.001). To our knowledge, this is the first application of transformer-based video models to volumetric OCT, highlighting their promise in 3D medical imaging.}, }
@article {pmid41788302, year = {2026}, author = {Tsiropoulos, GN and Topouzis, F and Amoaku, W and Panos, GD}, title = {Anti-VEGF Agents and the Inner Retina in nAMD: A Narrative Review of RNFL and Ganglion Cell Changes.}, journal = {Drug design, development and therapy}, volume = {20}, number = {}, pages = {591127}, pmid = {41788302}, issn = {1177-8881}, mesh = {Humans ; *Retinal Ganglion Cells/drug effects/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Angiogenesis Inhibitors/pharmacology/administration &amp; dosage ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy ; *Nerve Fibers/drug effects/pathology ; *Retina/drug effects ; }, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapy is the cornerstone of care for neovascular age-related macular degeneration (nAMD), yet its effects on the inner retina are not widely studied. We conducted a narrative review, guided by the SANRA checklist, to map evidence on peripapillary retinal nerve fibre layer (pRNFL), macular RNFL, and ganglion cell-derived metrics (GCL/GCIPL/GCC) during anti-VEGF treatment. Major databases were searched from inception to 10 November 2025 for human studies reporting optical coherence tomography (OCT) measurements of inner-retinal structure during anti-VEGF treatment. Data were charted for study design, OCT device/segmentation, scan protocol, timing relative to injections, treatment regimen, fluid phenotype (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]), follow-up interval, and magnitude of change (µm). Across cohorts and agents, global pRNFL thickness was largely stable over weeks to years, with short-term peri-injection fluctuations typically within device test-retest limits. In contrast, macular ganglion cell layers more often showed modest thinning over time, most consistently in eyes with baseline IRF; SRF-predominant disease showed less consistent inner-retinal change. Apparent between-agent differences were small and inconsistent; evidence specific to faricimab remains limited but generally reassuring for structural stability. Overall, most observed changes were often within OCT test-retest variability. In practice, clinicians should prioritise GCL/GCIPL monitoring where IRF is present, interpret small absolute changes against device repeatability, and avoid attributing trivial sectoral shifts to drug toxicity without corroboration.}, }
@article {pmid41788885, year = {2026}, author = {Wu, W and Guo, H and Wang, L and Yang, M}, title = {SRF and SHRM in nAMD: Retrospective Analysis of Visual Prognosis.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {590001}, pmid = {41788885}, issn = {1177-5467}, abstract = {OBJECTIVE: This study aimed to investigate the correlation between subretinal fluid (SRF) and subretinal hyperreflective material (SHRM) with visual prognosis in neovascular age related macular degeneration (nAMD).<br><br>METHODS: A retrospective analysis was conducted on 60 nAMD patients diagnosed at our ophthalmology department from March 2017 to December 2024. All patients received intravitreal anti-vascular endothelial growth factor (VEGF) injections monthly for the first 3 months, followed by pro re nata (PRN) treatment for the subsequent 9 months. Quantitative measurements&#xa0;of SRF and SHRM (height and width on OCT) were collected, along with patient demographics, best corrected visual acuity (BCVA), and central foveal thickness (CMT).<br><br>RESULTS: After 12 months of treatment, BCVA, CMT, and SRF parameters significantly improved (P < 0.05). The visual improvement group showed superior reductions in SRF and SHRM height compared to the nonimprovement group (P < 0.05). Greater baseline SRF thickness (>180&#xa0;&#x3bc;m) was significantly associated with better final visual acuity&#xa0;(P = 0.034), while&#xa0;baseline SHRM presence correlated with worse final BCVA and CMT&#xa0;(P < 0.05). These findings indicate that SRF serves as a favorable prognostic indicator, whereas SHRM is a key predictor of poor visual outcomes&#xa0;(P = 0.001).<br><br>DISCUSSION: SRF and SHRM morphological features are linked to nAMD treatment response. SRF thickness positively correlates with visual improvement, serving as a prognostic indicator. Persistent SHRM, however, is associated with fibrotic components that may impair retinal function, making it a key parameter for poor outcomes. These findings align with prior studies, highlighting the importance of quantitative SRF and SHRM assessment in predicting treatment response.<br><br>CONCLUSION: SRF and SHRM are clinically significant biomarkers in nAMD treatment, effectively predicting visual prognosis and guiding individualized therapeutic strategies. Their quantitative evaluation may aid in optimizing treatment tolerance strategies and improving real world clinical outcomes.}, }
@article {pmid41788972, year = {2026}, author = {Distefano, A and Calcagno, D and Grasso, G and Monasson, O and Peroni, E and Oliveri, V}, title = {Tolcapone Interferes With Key Pathological Features in Alzheimer's Disease.}, journal = {Bioinorganic chemistry and applications}, volume = {2026}, number = {}, pages = {1036276}, pmid = {41788972}, issn = {1565-3633}, abstract = {Tolcapone, a clinically approved drug for the treatment of Parkinson's disease as an adjunct therapy, has recently emerged as a potential modulator of amyloid-β aggregation and toxicity, which are hallmark features of Alzheimer's disease and are also involved in ocular neurodegenerative disorders, including glaucoma and age-related macular degeneration. Despite these noteworthy findings, the molecular basis of the interaction between amyloid-β and tolcapone remains poorly understood, and the mechanisms by which tolcapone affects metal-amyloid-β species have yet to be explored. In this work, we investigate the binding interactions of tolcapone with both copper-free amyloid-β and copper-associated amyloid-β complexes, using a combination of techniques including UV-vis spectroscopy, circular dichroism, mass spectrometry, and surface plasmon resonance. The results reveal that tolcapone binds directly to amyloid-β monomers. Furthermore, in vitro assays confirm the capacity of tolcapone to act as a radical scavenger and to compete with amyloid-β for the binding of copper ions. Altogether, our findings suggest that tolcapone exerts a multifaceted protective effect, potentially inhibiting toxic metal-free and metal aggregation pathways by preventing metal coordination to amyloid-β or disrupting preformed amyloid-β-metal complexes, thus offering new perspectives to explore and develop its analogs for the treatment of neurodegenerative disorders.}, }
@article {pmid41789719, year = {2026}, author = {Heloterä, H and Sund, R and Rikkonen, T and Kaarniranta, K}, title = {The impact of systemic long-term medications for the development of age-related macular degeneration.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70113}, pmid = {41789719}, issn = {1755-3768}, support = {//the Aarne Koskelo Foundation/ ; //the P&#xe4;ivikki and Sakari Sohlberg Foundation/ ; //the Mary and Georg C. Ehrnrooth Foundation/ ; //the Finnish Eye and Tissue Bank Foundation/ ; //the Finnish Eye Foundation/ ; //Sokeain Yst&#xe4;v&#xe4;t ry-De Blindas V&#xe4;nner sr/ ; 5503770//Kuopio University Hospital VTR grant/ ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of central vision loss in the elderly; however, the systemic factors that modulate its incidence and progression remain unclear. We sought to determine whether long-term use of systemic medications, including diabetes and antithrombotic medications, corticosteroids and immunosuppressants, is associated with the development of AMD.<br><br>METHODS: The data included a pooled cohort of two follow-up studies: the Kuopio Osteoporosis Risk Factor and Prevention Study and the Kuopio Fall Prevention Study. A total of 16&#x2009;518 women born between 1932 and 1946 living in eastern Finland were followed up between 1993 and 2021. The long-term medication use was indicated as &#x2265;5&#x2009;years of regular purchase of drugs. Incidence for AMD was analysed per long-term medication group, but also during the 5&#x2009;years period in age matched groups.<br><br>RESULTS: We observed increased odds for AMD among long-term users of systemic corticosteroids (HR 1.348, p&#x2009;<&#x2009;0.001), immunosuppressants (HR 1.623, p&#x2009;=&#x2009;0.004) and antithrombotic (HR 1.145, p&#x2009;=&#x2009;0.042) medication. However, results with antithrombotic medications were not as consistent as with corticosteroids and immunosuppressants. Interestingly, the mean age at diagnosis of AMD was later among antithrombotic medication users compared to the control group (77.9 vs. 76.1, respectively, p&#x2009;<&#x2009;0.001) and earlier among patients using other diabetes medications than metformin (75.3 vs. 77.1, p&#x2009;=&#x2009;0.026).<br><br>CONCLUSIONS: People with long-term corticosteroid and immunosuppressant use are at greater risk for developing AMD. Further research on systemic components behind corticosteroid and immunosuppressant use, modulating AMD progression, is warranted.}, }
@article {pmid41790302, year = {2026}, author = {Giannuzzi, F and Hu, L and Cusato, M and Cestrone, V and De Vico, U and Caputo, CG and Rizzo, C and Di Fede, L and Carlà, MM and Crincoli, E and Rizzo, S}, title = {Management of submacular hemorrhage: from a case report to a comprehensive review of current treatment strategies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41790302}, issn = {1573-2630}, mesh = {Humans ; *Retinal Hemorrhage/therapy/diagnosis/etiology ; *Vitrectomy/methods ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Visual Acuity ; Intravitreal Injections ; Tissue Plasminogen Activator/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Disease Management ; }, abstract = {PURPOSE: To evaluate current pharmacological and surgical strategies for managing submacular hemorrhage (SMH), a vision-threatening complication which primarily occurs with macular neovascularization in age-related macular degeneration (AMD).<br><br>METHODS: The research involved a literature review of recent studies about SMH treatment methods including anti-vascular endothelial growth factor (VEGF) therapy, tissue plasminogen activator (tPA), pneumatic displacement and pars plana vitrectomy techniques through meta-analyses, comparative studies and case series.<br><br>RESULTS: SMH treatment is guided by hemorrhage size: small (&#x2265;&#xa0;1 to&#xa0;<&#x2009;4 disc diameters), medium (&#x2265;&#xa0;4 disc diameters within the temporal arcade), massive (exceeding temporal arcades). Pharmacological management includes anti-VEGF monotherapy, which demonstrates efficacy comparable to surgical interventions for smaller hemorrhages, while offering a superior safety profile. Combined of tPA and anti-VEGF therapy achieves an 86% displacement success rate, with comparable efficacy between subretinal and intravitreal delivery methods. Surgical methods include pneumatic displacement, which achieves 85-100% efficacy in displacement and 45-80% rates of visual improvement, whereas pars plana vitrectomy is preferred for cases involving dense, organized hemorrhages. Retrospective studies indicate that outcomes are primarily influenced by patient-specific factors, such as hemorrhage size and baseline visual acuity, rather than the treatment modality employed. Intervention within 7 to 14&#xa0;days has been shown to enhance outcomes, particularly when using a stepwise protocol that begins with less invasive techniques and escalates only as necessary.<br><br>CONCLUSIONS: Modern SMH management emphasizes individualized, time-sensitive treatment based on hemorrhage characteristics. A stepwise approach, beginning with pharmacological therapy and moving to surgery only when necessary, tends to offer the best balance between visual recovery and safety. Timely diagnosis and intervention are essential factors for success due to the rapid damage&#xa0;of photoreceptors occurring within 24-72&#xa0;h of onset.}, }
@article {pmid41790421, year = {2026}, author = {Baljoon, A and Diaby, V and Suther, S and Dutton, M and Ali, A and Eljilany, I}, title = {Cost-Utility Analysis of Faricimab Versus Aflibercept in Treating Neovascular Age-Related Macular Degeneration (nAMD) in the United States.}, journal = {PharmacoEconomics - open}, volume = {}, number = {}, pages = {}, pmid = {41790421}, issn = {2509-4254}, abstract = {BACKGROUND/OBJECTIVE: Neovascular age-related macular degeneration (nAMD) imposes a substantial clinical and economic burden in the United States (US). Faricimab offers the potential for longer dosing intervals than aflibercept, but its economic value in the US setting has not been established. This study evaluated the cost utility of faricimab versus aflibercept for treating nAMD from the US payer perspective.<br><br>METHODS: A Markov model of five health states defined by best-corrected visual acuity (BCVA) simulated disease progression over 5 years. Clinical inputs were drawn from pooled 1-year data of the TENAYA and LUCERNE phase III trials (n&#xa0;=&#xa0;1329), which compared faricimab with aflibercept for treating nAMD patients. Direct medical costs encompassed drug acquisition, intravitreal administration, monitoring, office visits, and management of endophthalmitis. Outcomes included total costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB) at a willingness-to-pay (WTP) threshold of US$100,000/QALY. Scenario, deterministic, and probabilistic sensitivity analyses (10,000 iterations) were conducted.<br><br>RESULTS: In the base case, faricimab yielded 2.80 QALYs for US$52,797, whereas aflibercept produced 2.72 QALYs at US$62,367. Faricimab was therefore dominant (-&#x2009;US$9570; +&#x2009;0.08 QALY), with an incremental NMB of US$17,981. Faricimab required markedly fewer injections over 5 years (22.6 vs 34). Scenario analyses did not materially change the directionality of the base-case results, with faricimab being dominant or cost effective. The model was most sensitive to drug acquisition prices and BCVA-state utilities, yet faricimab remained below the WTP threshold across all plausible ranges. Probabilistic analysis showed a 97% probability of faricimab being cost effective at US$100,000/QALY.<br><br>CONCLUSIONS: Faricimab is estimated to be a cost-effective treatment option compared with aflibercept for nAMD from a US payer perspective. This finding may support its inclusion in treatment guidelines and formulary decisions, pending confirmation in real-world practice.}, }
@article {pmid41790486, year = {2026}, author = {Ruuth, J and Tamminen, T and Toropainen, E and Tanila, H and Hyttinen, JMT and Malm, T and Kaarniranta, K and Koskela, A}, title = {Overproduction of 42 Amino Acids Long Amyloid Beta Leads to Activation of Secretory Autophagy and Development of Drusen-Like Structures Originating From Retinal Pigment Epithelium.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {40}, number = {5}, pages = {e71608}, pmid = {41790486}, issn = {1530-6860}, support = {333302//Academy of Finland/ ; //GeneCellNano/ ; //Paivikki ja Sakari Sohlberg Foundation/ ; 5503770//Kuopio University Hospital district/ ; //Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6; (Sigrid Jus&#xe9;lius Stiftelse)/ ; //Silm&#xe4;s&#xe4;&#xe4;ti&#xf6; (Finnish Eye Foundation)/ ; //De Blindas V&#xe4;nner (DBV)/ ; //Finnish eye and Tissue Bank Foundation/ ; //Mary and Georg C. Ehrnrooths Foundation/ ; //Finnish Cultural Foundation-North-Savo/ ; }, mesh = {Animals ; *Autophagy/physiology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Amyloid beta-Peptides/metabolism/genetics ; Mice ; *Retinal Drusen/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; Mice, Transgenic ; Humans ; Disease Models, Animal ; Sequestosome-1 Protein/metabolism ; Alzheimer Disease/metabolism/pathology ; }, abstract = {Age-related macular degeneration (AMD) is a global vision threatening disease affecting the macular region of the retina. AMD is classified into two forms: dry and wet AMD. There are no effective treatment options available for dry AMD (80% of cases). The cellular pathology includes oxidative stress and dysfunctional autophagy challenging the homeostasis of the retinal pigment epithelial (RPE) cells. Clinical findings include the formation of drusen deposits beneath the RPE cells consisting of 42 amino acids long amyloid beta (Aβ) among other components. However, the origin of drusen remains elusive. The 5xFAD (familiar Alzheimer's disease) mouse model of Alzheimer's disease produces abundant levels of Aβ making it an interesting model to study the possible relationship of Aβ to the formation of extracellular deposits and AMD-like pathology. An immunohistology analysis of the 5xFAD mouse model showed accumulation of autophagic markers SQSTM1 (sequestosome 1) and ubiquitin in the RPE. Concurrently, the markers of secretory autophagy enabling the delivery of the intracellular material to the extracellular lumen were upregulated. Aβ, SQSTM1, ubiquitin, catalase, and TRIM16 (tripartite motif containing 16) shifted age-dependently from intracellular origin to drusen-like deposits beneath the RPE cells. Additionally, classical proteins secreted via secretory autophagy, IL-1β (interleukin 1β), HMGB1 (high mobility group box-1), and ferritin showed similar accumulation which became visible in fundus age-dependently. These findings suggest a role for Aβ in the cellular pathogenesis of AMD. Furthermore, this model showed activated secretory autophagy pathway suggesting a role for Aβ in drusen-like deposition formation.}, }
@article {pmid41790719, year = {2026}, author = {Iby, J and Coulibaly, L and Hollaus, M and Yeghiazaryan, L and Schmidt-Erfurth, U and Bühl, W and Sacu, S}, title = {Efficacy of a single dose switch from aflibercept to ranibizumab in the treatment of neovascular age-related macular degeneration.}, journal = {PloS one}, volume = {21}, number = {3}, pages = {e0342927}, pmid = {41790719}, issn = {1932-6203}, mesh = {Humans ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Female ; Aged ; Retrospective Studies ; Aged, 80 and over ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Visual Acuity/drug effects ; *Macular Degeneration/drug therapy/pathology ; Treatment Outcome ; Tomography, Optical Coherence ; }, abstract = {PURPOSE: To analyze morphological and functional response after administration of a single dose of ranibizumab in eyes under treat&amp;extend aflibercept in neovascular age related macular degeneration (nAMD). Additionally, we aimed to identify predictive factors in anti-vascular endothelial growth factor (VEGF) treatment.<br><br>METHODS: A total of 115 patients (133 eyes; 34 male, 81 female, m:f&#x2009;=&#x2009;1:2.4) with a mean age of 79.9&#x2009;&#xb1;&#x2009;8.3 years at baseline (BSL) were included in this retrospective analysis. All eyes had received aflibercept treatment for nAMD before BSL and were subsequently administered a single dose of intravitreal ranibizumab. Data of two visits pre and two visits after BSL were evaluated and compared. Primary outcome measure was the mean change in central macular thickness (CMT, &#xb5;m). CMT-changes between BSL and the next follow-up visit (V4) were roughly divided into decrease (<-10&#xb5;m), equal (-10 to +10 &#xb5;m) or increase (> +10&#xb5;m). We also assessed changes in best-corrected visual acuity (BCVA) and identified influencing factors on CMT and BCVA using linear mixed models (LMM).<br><br>RESULTS: No significant differences in CMT and BCVA were observed over the visits (p&#x2009;>&#x2009;0.05). Factors influencing CMT included prior anti-VEGF injections (p&#x2009;<&#x2009;0.001), the time interval between BSL and visit 4 (p&#x2009;<&#x2009;0.001), and patient age (p&#x2009;=&#x2009;0.032). The number of prior anti-VEGF injections significantly influenced BCVA (p&#x2009;=&#x2009;0.003). After a single administration of ranibizumab, in 19.5% (n&#x2009;=&#x2009;26) of eyes CMT decreased, in 21.8% of eyes (n&#x2009;=&#x2009;29) CMT increased and in 36.8% of eyes (n&#x2009;=&#x2009;49) it remained equal.<br><br>CONCLUSION: Our study indicates that changes in CMT are affected by age, the number of previous injections, and the time interval between visits. These biomarkers may offer valuable insights for future research on switching anti-VEGF drugs to optimize treatment strategies for nAMD. A single dose treatment switch to ranibizumab yielded non-inferior outcomes.}, }
@article {pmid41791029, year = {2026}, author = {Jaffe, GJ and Boyer, D and Hu, A and Warrow, D and Xavier, S and Gonzalez, V and Lad, E and Rosen, RB and Do, DV and Schneiderman, T and Ho, AC and Munk, MR and Tedford, SE and Croissant, CL and Rückert, R and Lavin, P and Tedford, CE}, title = {Long-term Efficacy and Safety of Photobiomodulation in Dry Age-Related Macular Degeneration (LIGHTSITE III: 24-Month Analysis).}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004822}, pmid = {41791029}, issn = {1539-2864}, abstract = {PURPOSE: To evaluate the safety and efficacy of multiwavelength photobiomodulation (PBM) in nonexudative (dry) age-related macular degeneration (AMD).<br><br>METHODS: LIGHTSITE III employed a double-masked, randomized, sham-controlled, parallel-group, prospective study design. Subjects were enrolled with a diagnosis of dry AMD and treated with multiwavelength PBM (Valeda&#xae; Light Delivery System; 590, 660 and 850 nm) or Sham treatment. A treatment series included 9 PBM or Sham treatments delivered 3x/week over 3-5 weeks every 4 months (M) for 24M.<br><br>RESULTS: A total of 148 eyes (100 subjects) with dry AMD were randomized into the study. LIGHTSITE III met the prespecified primary BCVA efficacy endpoint at M21 with a significant difference between treatment groups (p = 0.0036) and a +6.2 letter gain following PBM. At M21, 61.5% of PBM-treated eyes showed &#x2265;5, 23.1% showed &#x2265;10, and 4.4% showed &#x2265;15 letter gains. A favorable safety profile was observed with no signs of phototoxicity. Disease progression to Geographic Atrophy (GA) showed a significant decrease in incidence (Sham, 24.0% vs. PBM, 6.8%; p = 0.007) following PBM treatment at M24. Significant benefit in vision QoL was observed.<br><br>CONCLUSIONS: Multiwavelength PBM represents an interventional therapy that restores visual function and has potential disease-modifying effects in intermediate dry AMD.}, }
@article {pmid41791476, year = {2026}, author = {Hurst, J and Alber, J and Bredehorst, J and Schnichels, S}, title = {A porcine ex vivo angiogenesis model for retinal neovascular diseases.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110958}, doi = {10.1016/j.exer.2026.110958}, pmid = {41791476}, issn = {1096-0007}, abstract = {Retinal and choroidal vascular diseases are the leading causes of vision loss, with diabetic retinopathy and neovascular age-related macular degeneration as prominent examples. Current treatments such as laser photocoagulation and anti-VEGF injections have limitations and side effects. Therefore, there is a need for novel therapies to improve our understanding of underlying disease mechanisms. Animal welfare regulations also mandate a reduction in the use of animals. This study aimed to develop an ex vivo angiogenesis model using porcine retinal explants to study retinal neovascular diseases without using living animals. Porcine retina shares similarities with the human retina, making it a suitable model for studying retinal diseases. Porcine retinas were obtained from a local abattoir and retinal explants were cultured with pro-angiogenic factors to induce neovascularization. Vessel formation was observed using bright-field microscopy and the presence of endothelial cells was confirmed by CD31 immunostaining. qRT-PCR analysis revealed increased expression of angiogenesis-related genes in the treated explants compared to that in the controls. However, this model has limitations such as a lack of blood flow and limited cultivation time. Strategies to address these challenges include optimizing the tissue extraction time, exploring alternative coating materials, and maintaining the retinal tissue-retinal pigment epithelium interface. Nevertheless, this ex vivo porcine retinal angiogenesis model provides a valuable tool for investigating innovative treatment approaches for retinal neovascular diseases while reducing the use of living animals in research.}, }
@article {pmid41791650, year = {2026}, author = {Wu, S and Jeong, H and Reed, HA and Abbass, NJ and Kaelber, DC and Talcott, KE and Singh, RP}, title = {Associations Between Systemic Tyrosine Kinase Inhibitors and Development of Age-Related Macular Degeneration in Patients with Cancer.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.018}, pmid = {41791650}, issn = {2468-6530}, abstract = {PURPOSE: To evaluate the association between systemic tyrosine kinase inhibitor (TKI) therapy and the risk of age-related macular degeneration (AMD) onset, and whether this relationship varies by anti-VEGF activity of TKIs.<br><br>DESIGN: Retrospective cohort study using a large de-identified electronic health records research platform.<br><br>PARTICIPANTS: Patients &#x2265;50 years old with cancer encounter diagnoses were divided into groups with (treatment) and without (control) systemic TKI prescription codes and followed for incident AMD diagnosis.<br><br>METHODS: Landmarked time-to-event analyses were performed at 1, 3, and 5 years post-cancer diagnosis. Treatment and control groups were propensity score matched, followed from landmark date until incident ICD-10 AMD encounter diagnosis, death, or last recorded clinical encounter, and compared using hazard ratios for incident AMD. A three-arm sub-analysis was also performed by stratifying TKIs by anti-VEGF activity, comparing the TKI-with-anti-VEGF and TKI-without-anti-VEGF subgroups to the control group, and to each other.<br><br>MAIN OUTCOME MEASURES: Hazard ratios (HRs) for an incident ICD-10 AMD encounter diagnosis code after the landmark date. Significance was defined as 95% confidence interval (CI) <0.9 and >1.1.<br><br>RESULTS: Across landmark analyses, TKI prescriptions were not consistently associated with the hazard of receiving a new ICD-10 AMD encounter diagnosis code compared with matched controls: 1 year (HR=0.97; 95% CI=0.85, 1.12), 3 years (HR=0.90; 95% CI=0.78, 1.05), and 5 years (HR=0.81; 95% CI=0.69, 0.96). In the subanalysis, the TKI with-anti-VEGF subgroup showed significant reduction only at the 5-year landmark, HR=0.60; 95% CI=0.40, 0.89). The TKI-without-anti-VEGF subgroup demonstrated no significant association between systemic TKI exposure and the hazard of receiving a new ICD-10 AMD encounter diagnosis code at any time point: 1 year (HR=0.98; 95% CI=0.84, 1.15), 3 years (HR=0.97; 95% CI=0.82, 1.15), and 5 years (HR=0.87; 95% CI=0.73, 1.05). In contrast, across analyses, TKI prescriptions were consistently associated with increased hazards of mortality and fewer ophthalmology encounters.<br><br>CONCLUSIONS: This explorative study found that TKI prescriptions are not associated with incident AMD diagnosis. These findings do not support a population-level protective effect of systemic TKIs on AMD risk.}, }
@article {pmid41794975, year = {2026}, author = {Moghul, I and Pontikos, N and Sharma, A and Liu, T and Soomro, T and Wagner, SK and Silva, AS and Zhang, G and Naik, G and Bagga, P and Chan, YW and Keane, PA and Cipriani, V and Sivaprasad, S and Webster, AR and Balaskas, K}, title = {Integrating genetics, age and imaging to predict treatment outcomes in neovascular age-related macular degeneration: a proof-of-concept study.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41931-3}, pmid = {41794975}, issn = {2045-2322}, support = {R190001//Moorfields Eye Charity/ ; }, }
@article {pmid41795704, year = {2026}, author = {Valmaggia, P and Ansari, G and Inglin, N and Schärer, N and Zuche, H and Gabrani, C and Yahya, F and Cattaneo, M and Pfau, K and Giani, A and Esmaeelpour, M and Yamaguchi, TC and Prünte, C and Scholl, HPN and Feltgen, N and Schmetterer, L and Pfau, M and Maloca, PM}, title = {The optical coherence tomography and microperimetry biomarker evaluation in patients with geographic atrophy (OMEGA) study: Geographic atrophy progression in fundus autofluorescence - OMEGA report 3.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.70119}, pmid = {41795704}, issn = {1755-3768}, support = {YTCR 43/23//Schweizerische Akademie der Medizinischen Wissenschaften/ ; 323530_199395//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; //Boehringer Ingelheim Pharma GmbH &amp; Co. KG/ ; }, abstract = {PURPOSE: To measure the progression of geographic atrophy (GA) in subjects with age-related macular degeneration (AMD) in a natural history study.<br><br>METHODS: We analysed fundus autofluorescence (FAF) images using a semiautomatic method (RegionFinder) to quantify the GA area in a monocentric study. Three independent graders analysed each eye. Patient visits were scheduled at baseline, 12, 24 and 48&#x2009;weeks. The primary endpoint was the progression of GA area per eye. Potential correlations with clinical and imaging-based parameters were analysed.<br><br>RESULTS: The annual GA progression rate was 1.16&#x2009;mm[2]/year (95% CI: 0.76-1.56; p&#x2009;<&#x2009;0.001), with faster growth in eyes with larger baseline lesions (R[2]&#x2009;=&#x2009;0.74). After square root transformation, the progression rate was 0.34&#x2009;mm/year (95% CI: 0.26-0.43; p&#x2009;<&#x2009;0.001), and the size dependency was reduced (adjusted R[2]&#x2009;=&#x2009;0.16). Multivariable mixed-effects models identified a significant association between larger GA lesion sizes per eye and the number of smoking pack-years (p&#x2009;=&#x2009;0.017), the presence of perilesional hyperautofluorescence (p&#x2009;=&#x2009;0.044) and a multifocal configuration of the GA lesions (p&#x2009;=&#x2009;0.038). Intermediate AMD in the fellow eye was significantly associated with faster GA progression (p&#x2009;=&#x2009;0.041).<br><br>CONCLUSION: GA progression in AMD is significantly influenced by baseline lesion size and a larger number of smoking pack-years is associated with larger GA lesions. The marked variability between individuals underscores the multifactorial nature of GA dynamics. Quantitative FAF analysis is a reliable method for assessing lesion progression and may inform risk-based monitoring strategies.}, }
@article {pmid41796178, year = {2026}, author = {Tapia-Aguayo, A and Cisneros-Pardo, A and De Los Santos-González, BE and Hernández-Pérez, J and González-Valdez, J and Ramos-Parra, PA}, title = {Carrot extracellular nanovesicles as carotenoid carriers in an in vitro macular degeneration model.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-41792-w}, pmid = {41796178}, issn = {2045-2322}, }
@article {pmid41796922, year = {2026}, author = {Li, J and Peng, J and Liu, J and Cao, Y and Ju, Y and Li, D}, title = {Choroid blood flow analysis in the contralateral eye of neovascular age-related macular degeneration patients with subretinal fibrosis using OCTA.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {}, number = {}, pages = {105429}, doi = {10.1016/j.pdpdt.2026.105429}, pmid = {41796922}, issn = {1873-1597}, abstract = {PURPOSE: To evaluate choroidal vascular alterations in the contralateral eyes of patients with neovascular age-related macular degeneration (N-AMD) and subretinal fibrosis (SRFi) using optical coherence tomography angiography (OCTA).<br><br>METHODS: This retrospective study included 57 patients (57 eyes) with unilateral N-AMD and a normal fellow eye. Patients were classified by multimodal imaging into SRFi (24 eyes) and non-SRFi (32 eyes) groups. Best-corrected visual acuity (BCVA, logMAR), subfoveal choroidal thickness (SFCT), and OCTA-derived choriocapillaris and choroidal vessel density (VD, %) were measured. Group differences were assessed using binarized OCTA scans, and correlation and logistic regression analyses were performed.<br><br>RESULTS: SFCT was significantly reduced in the SRFi group compared with controls (P<0.05) and was positively correlated with choroidal VD (r=0.414, P=0.045). Multivariate logistic regression identified SFCT (OR=0.98, 95% CI: 0.96-0.99, P=0.006) and choroidal VD (OR=0.85, 95% CI: 0.72-1.00, P=0.047) as independent risk factors for SRFi.<br><br>CONCLUSION: Decreased SFCT and choroidal VD in the contralateral eyes of N-AMD patients with SRFi suggest a potential role in disease pathogenesis and progression. These parameters may serve as early biomarkers for the onset of SRFi in N-AMD.}, }
@article {pmid41798214, year = {2026}, author = {Hashimoto, Y and Barthelmes, D and Gillies, M}, title = {The Fight Retinal Blindness! registry: An international treatment outcomes registry for retinal diseases.}, journal = {Annals of clinical epidemiology}, volume = {8}, number = {1}, pages = {28-35}, pmid = {41798214}, issn = {2434-4338}, abstract = {The Fight Retinal Blindness! Registry is a prospectively-designed registry developed in 2009 that collects international data on treatment outcomes for eye diseases including neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion. The validated and high-quality data have generated significant real-world evidence regarding clinically relevant issues, such as long-term visual outcomes, dosing regimens and practitioner variation. This paper outlines the Fight Retinal Blindness! Registry, highlighting its pros and cons, and introduces some findings from the registry.}, }
@article {pmid41799763, year = {2026}, author = {Zhou, Y and Wang, Z and Huang, C and Yu, X and Chen, J and Jiang, X and Dong, J and Peng, Q and Li, L and Song, X and Lu, X}, title = {Gut Microbiota Signatures and Potential Mediators in the Trajectory of Age-related Macular Degeneration: A Phased Atlas by Genetic Inference.}, journal = {International journal of medical sciences}, volume = {23}, number = {3}, pages = {950-962}, pmid = {41799763}, issn = {1449-1907}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics/immunology ; *Macular Degeneration/genetics/microbiology/immunology/pathology ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Disease Progression ; Polymorphism, Single Nucleotide ; }, abstract = {PURPOSE: To depict an atlas of stage-stratified gut microbiota (GM) signatures and intermediatory metabolites, inflammatory proteins, and immune cell traits, governing the AMD trajectory.<br><br>METHODS: We deployed bidirectional two-sample Mendelian randomization (TSMR) integrating GWAS data of 207 GM taxa from the Dutch Microbiome Project (N = 7,738), and multiple AMD stages/subtypes, including 'Macular degeneration (senile) of retina', 'Early AMD', 'Disease progression to GA/CNV', 'Dry AMD includes GA', and 'Wet AMD', encapsulating the disease trajectory (N > 410,000), complemented by multivariable MR (MVMR) mediation analysis of 1,400 circulating metabolites, 731 immune cell traits, and 91 inflammatory proteins.<br><br>RESULTS: We identified 12/8/5/2/9/8 genetically predicted causal GM taxa of various AMD stages/subtypes as a stage-stratified GM signature across the AMD trajectory, among which g.Ruminococcaceae and s.Ruminococcaceae_bacterium_D16 were the sole shared GM taxa in triple AMD stages, while s.Bacteroides eggerthii, c.Gammaproteobacteria, s.Dorea and s.Ruminococcus_obeum influence dual AMD stages. Bidirectional analysis revealed that f.Streptococcaceae, g.Erysipelotrichaceae_noname, g.Streptococcus, s.Streptococcus_thermophilus, g.Ruminococcaceae_noname, and s.Ruminococcaceae_bacterium_D16 exhibited genetically reciprocal causation with AMD. We also proposed that Firmicutes may exhibit stage-specific duality depending on their constituent members and AMD stages. Several understudied GM from p.Actinobacteria and p.Verrucomicrobia have been implicated as AMD-associated taxa for the first time. Key metabolites, immune cell traits, and inflammatory proteins were established as significant mediators of GM-AMD links.<br><br>CONCLUSIONS: This first phased atlas uncovers GM effects over the AMD course, identifying potential microbial and biochemical targets for intervening in disease development.}, }
@article {pmid41799797, year = {2026}, author = {Addo, EK and Lucci, L and Nilson, J and Pasaye, M and Pappas, C and Spoth, E and Ord, L and Jridi, A and Brintz, BJ and Hageman, GS and Hartnett, ME and Bernstein, PS}, title = {Carotenoid Status and Psychological Impact of Presymptomatic Macular Degeneration Genetic Risk Assessment: The MAGENTA Randomized Trial.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101083}, pmid = {41799797}, issn = {2666-9145}, abstract = {PURPOSE: Genetic testing for age-related macular degeneration (AMD) risk reliably offers insight into an individual's susceptibility for future visual loss; however, an American Academy of Ophthalmology expert panel in 2012 discouraged routine AMD genetic risk testing because there was no evidence that such knowledge would alter an individual's clinical course. To address this knowledge gap, we investigated whether disclosure of AMD genetic risk to presymptomatic individuals would encourage healthier lifestyle adoption that could reduce the incidence of AMD later in life.<br><br>DESIGN: The Moran AMD Genetic Testing Assessment (MAGENTA) trial is a single-site, prospective, controlled clinical study (NCT05265624) that randomized 80 presymptomatic subjects in a 3:1 ratio to immediate or 1-year deferred disclosure groups. We stratified participants into high-, intermediate-, and low-risk groups by Mendelian randomization.<br><br>SUBJECTS: We enrolled Whites aged 18 to 64 years with no clinical signs of AMD.<br><br>METHODS: As a biomarker of healthy nutritional status, participants' skin, plasma, and macular carotenoid concentrations were measured using resonance Raman and reflectance spectroscopies, high-performance liquid chromatography, and autofluorescence imaging, respectively. Nutritional and emotional status were assessed with validated surveys.<br><br>MAIN OUTCOME MEASURES: We looked for changes in skin, plasma, and macular carotenoids as biomarkers of healthier lifestyle adoption and for the impact of AMD genetic risk disclosure on participants' psychological well-being.<br><br>RESULTS: Of the 80 participants, 94% had a family history of AMD, and the AMD genetic risk distribution was 36% high, 24% intermediate, and 40% low. We found no statistically significant difference in skin, plasma, and macular carotenoids between study groups at 12 months relative to baseline (P > 0.05 for all comparisons). Participants' interest and compliance were high, as shown by the 95% subject study completion rate, and there was no evidence of worsening stress following AMD genetic risk disclosure to the participants.<br><br>CONCLUSIONS: While AMD genetic risk disclosure did not significantly impact nutritional biomarker levels over 12 months, there were no adverse psychological effects, and the subjects generally felt knowledge of their AMD risk was valuable. Our findings could guide future presymptomatic AMD genetic testing trials with extended biomarker assessments in larger and more diverse populations.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41799798, year = {2026}, author = {Gee, EE and Guymer, RH and Blodi, BA and Holz, FG and Jaffe, GJ and Liakopoulos, S and Sadda, SR and Schmitz-Valckenberg, S and Bjelopera, E and Brown, T and Choong, J and Clifton, B and Hadoux, X and He, Y and Heathcote, J and Jannaud, M and Lentzsch, AM and Mahmoudi, A and Pak, JW and Saßmannshausen, M and Skalak, C and von der Emde, L and Wu, Z}, title = {Geographic Atrophy on Fundus Autofluorescence and Color Fundus Photographs: Association with Deep Visual Sensitivity Losses.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101096}, pmid = {41799798}, issn = {2666-9145}, abstract = {PURPOSE: To determine the functional characteristics of color fundus photograph (CFP)- and fundus autofluorescence (FAF)-defined geographic atrophy (GA) lesions by evaluating the prevalence of repeatable deep visual sensitivity defects.<br><br>DESIGN: Reader study.<br><br>PARTICIPANTS: One hundred seventy-one pairs of CFP and FAF images from 60 eyes of 53 individuals.<br><br>METHODS: High-density, targeted microperimetry testing (with Goldmann Size III stimuli) was performed twice per visit in a 3.5&#xb0; (approximately 1000 &#x3bc;m) diameter region of interest with retinal pigment epithelium and outer retinal atrophy on OCT imaging. Twelve readers from 6 established reading centers assessed CFP and FAF images within these regions sampled on microperimetry for GA, and performed annotations where GA was deemed to be present. Geographic atrophy on CFP was defined as a well-demarcated, roughly round or oval region of hypopigmentation, separately with and without requiring increased visibility of the underlying choroidal vessels (referred to as CFP-defined GA1 and GA2, respectively). GA on FAF was defined as a region of definite decreased autofluorescence.<br><br>MAIN OUTCOME MEASURES: Prevalence of a repeatable &#x2264;10 dB defect for CFP- and FAF-defined GA &#x2265;175 &#x3bc;m, and the minimum lesion size showing a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect (deemed characteristic of regions with a truly nonresponding test location on microperimetry).<br><br>RESULTS: Color fundus photograph-defined GA1 and GA2 and FAF-defined GA &#x2265;175 &#x3bc;m were graded as present in 13%, 31%, and 41% of images, respectively, and 77%, 67%, and 62% lesions, respectively, had a repeatable &#x2264;10 dB defect. Only CFP-defined GA1 &#x2265;625 &#x3bc;m, CFP-defined GA2 &#x2265;650 &#x3bc;m, and FAF-defined &#x2265;675 &#x3bc;m had a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect.<br><br>CONCLUSIONS: Color fundus photograph and FAF-defined GA lesions &#x2265;175 &#x3bc;m do not show the same functional characteristics as regions with a truly nonresponding test location, and only much larger lesions (approximately &#x2265;650 &#x3bc;m) showed such similar functional characteristics. These findings provide crucial insights when considering CFP- and FAF-defined atrophic endpoints for clinical studies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41801974, year = {2026}, author = {Pompös, IM and Polenz, D and Kociok, N and Winkler, S and Strauß, O}, title = {Evaluation of risk promoting effects for age-related macular degeneration by estradiol.}, journal = {PloS one}, volume = {21}, number = {3}, pages = {e0340477}, pmid = {41801974}, issn = {1932-6203}, mesh = {Animals ; *Macular Degeneration/etiology/pathology/blood/metabolism ; Female ; *Estradiol/deficiency/blood ; Rats ; Ovariectomy ; Estrogen Receptor beta/metabolism ; Retina/pathology/metabolism ; Disease Models, Animal ; Aging ; Risk Factors ; }, abstract = {Early menopause increases the risk for age-related macular degeneration (AMD), the most common cause of vision loss in industrialized countries. The supplementation with estradiol reduces the risk in these cases and suggesting that estradiol deficiency is a mediator of the risk association. We investigated rat models of estradiol deficiency mimicking either biological ageing (22 months of age) or early menopause by ovariectomy and age of 22 months. Serum analysis of gonadal hormones in both models showed the expected reduction in estradiol levels compared to 6 months old controls but also increases in progesterone, corticosterone and dehydroepiandrosterone sulfate (DHEA-S). Comparing the two estradiol deficiency models, we found no differences except for DHEA-S that were reduced in ovariectomized rats. The hormone status was associated with degenerative changes in the retina with higher activity of mononuclear phagocytes and p16/p21-dependent senescence. Mainly the estrogen receptor beta (ERβ) expressing cells were affected by estradiol deficiency: ganglion cells, cells of the inner nuclear layer (INL) and retinal pigment epithelial cells. An exception are photoreceptors that were ERβ negative, showed stronger degeneration in ovariectomized rats compared to sham treated animals. We conclude that either biological or ovariectomy induced estradiol deficiency might not cause but rather promote mechanisms that lead to AMD. The phenotype depends on a broader spectrum of altered hormones than on estradiol alone. Photoreceptor degeneration and cellular senescence that were ERβ independent in ovariectomized rats suggest non-estradiol effects to increase AMD risk by early menopause.}, }
@article {pmid41803521, year = {2026}, author = {Ahmed, F}, title = {HOG-CNN: Integrating Histogram of Oriented Gradients with Convolutional Neural Networks for Retinal Image Classification.}, journal = {Journal of imaging informatics in medicine}, volume = {}, number = {}, pages = {}, pmid = {41803521}, issn = {2948-2933}, abstract = {The analysis of fundus images is critical for the early detection and diagnosis of retinal diseases such as diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). Traditional diagnostic workflows, however, often depend on manual interpretation and are both time- and resource-intensive. To address these limitations, we propose an automated and interpretable clinical decision support framework based on a hybrid feature extraction model called HOG-CNN. Our key contribution lies in effectively integrating handcrafted Histogram of Oriented Gradients (HOG) features with representations learned by the pretrained deep convolutional neural network EfficientNetB3. This fusion enables our model to capture both local texture patterns and high-level semantic features from retinal fundus images. We evaluated our model on three public benchmark datasets: APTOS 2019 (for binary and multiclass DR classification), ORIGA (for Glaucoma detection), and IC-AMD (for AMD diagnosis); HOG-CNN demonstrates consistently high performance. It achieves 98.5% accuracy and 99.2 AUC for binary DR classification, and 94.2 AUC for five-class DR classification. On the IC-AMD dataset, it attains 92.8% accuracy, 94.8% precision and 94.5 AUC, outperforming several state-of-the-art models. For Glaucoma detection on ORIGA, our model achieves 83.9% accuracy and 87.2 AUC, showing competitive performance despite dataset limitations. We show, through comprehensive appendix studies, the complementary strength of combining HOG and CNN backbone (EfficientNetB3) features. The model's lightweight and interpretable design makes it particularly suitable for deployment in resource-constrained clinical environments. These results position HOG-CNN as a robust and scalable tool for automated retinal disease screening.}, }
@article {pmid41804429, year = {2026}, author = {Matsuno, T and Tomita, R and Takeuchi, J and Nishiguchi, KM and Yuki, K}, title = {Giant Retinal Pigment Epithelium Tear Secondary to Hypotony After Trabeculectomy for Open-Angle Glaucoma With Preoperative Untreated Choroidal Neovascularization: A Case Report.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103122}, pmid = {41804429}, issn = {2168-8184}, abstract = {Retinal pigment epithelium (RPE) tears are frequently observed following anti-vascular endothelial growth factor therapy for age-related macular degeneration. While rare, giant RPE tears have also been reported secondary to choroidal detachment (CD) induced by postoperative hypotony after trabeculectomy (TLE). Although mechanical stress on the RPE is considered a common underlying factor in both scenarios, the exact mechanisms remain unclear. This report describes a case of a giant RPE tear originating from the site of a previously untreated choroidal neovascularization (CNV) following TLE. A 65-year-old male underwent TLE for intraocular pressure (IOP) control in his left eye with primary open-angle glaucoma. Preoperative IOP was 39 mmHg, and fundus examination revealed untreated CNV and sub-RPE hemorrhage. The scleral flap sutures were sequentially laser lysed on postoperative days two and four, as the postoperative IOP remained stable between 12 and 14 mmHg. On postoperative day seven, IOP decreased to 4 mmHg, and CD was observed. Following observation, the IOP increased to 7 mmHg on postoperative day 10, revealing a giant RPE tear and serous retinal detachment (SRD). An additional scleral flap suture was performed on the same day, and the IOP subsequently stabilized around 10 mmHg. During follow-up, the SRD spontaneously resolved by postoperative day 41, while the RPE tear persisted. Visual field testing revealed worsening of visual field defects compared to preoperative findings, with defects corresponding to the location of the RPE tear. The rapid IOP reduction following TLE may have induced mechanical stress on a vulnerable RPE region affected by CNV, leading to the RPE tear. A rapid IOP reduction may increase the risk of an RPE tear when vulnerable RPE areas exist due to CNV or other factors; therefore, careful preoperative evaluation for vulnerable RPE regions and cautious perioperative IOP management should be considered.}, }
@article {pmid41805144, year = {2026}, author = {Zhou, B and Mokhashi, N and Skondra, D}, title = {Emerging strategies in drug repurposing for decreasing the risk of age-related macular degeneration.}, journal = {Expert opinion on drug discovery}, volume = {21}, number = {3}, pages = {339-354}, doi = {10.1080/17460441.2026.2635492}, pmid = {41805144}, issn = {1746-045X}, mesh = {Humans ; *Macular Degeneration/prevention &amp; control/physiopathology/drug therapy ; *Drug Repositioning/methods ; Animals ; Hypoglycemic Agents/pharmacology/administration &amp; dosage/adverse effects ; Oxidative Stress/drug effects ; Metformin/pharmacology/administration &amp; dosage ; }, abstract = {INTRODUCTION: Vision loss in older adults is largely driven by age-related macular degeneration (AMD), characterized by progressive central visual field damage and functional decline. While current options for wet and dry AMD are limited and expensive, drug repurposing represents a promising strategy to accelerate the discovery of effective, accessible treatment by leveraging medications with established safety profiles. Notably, anti-diabetic agents including metformin, sulfonylureas, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and insulin have emerged as modulators of the retinal pigment epithelium (RPE) function, photoreceptors, and retinal vascular integrity.<br><br>AREAS COVERED: This review highlights the roles of oxidative stress, inflammation, and complement-mediated immune dysregulation in AMD pathogenesis, alongside preclinical data demonstrating metformin's protective effects via AMP-activated protein kinase (AMPK) activation. Population-based studies and meta-analyses further suggest a modest reduction in AMD risk associated with metformin use in both diabetic and non-diabetic cohorts. Additional pharmacological agents include statins, glyburide, L-DOPA, fluoxetine, dimethyl fumarate, and nutraceuticals such as curcumin, melatonin, and N-acetylcysteine.<br><br>EXPERT OPINION: Early AMD prevention through repurposed therapeutics, guided by AI-driven design and systems biology, may enable personalized care via multimodal risk stratification incorporating genetic, metabolomic, and microbiome data. Rigorous, stratified clinical trials integrating bioinformatics and precision medicine are essential to validate the most effective candidates.}, }
@article {pmid41805146, year = {2026}, author = {Gan, Y and Pu, J and Yang, S and Chen, X and Zhang, X and Su, Y and Li, M and Wen, F}, title = {Novel Quantitative OCTA Biomarkers of Choroidal Neovascularization and Associations With Disease Activity and Etiology.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {10}, pmid = {41805146}, issn = {2164-2591}, mesh = {Humans ; *Choroidal Neovascularization/diagnostic imaging/etiology/diagnosis ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; Middle Aged ; Biomarkers ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Wet Macular Degeneration/diagnostic imaging ; }, abstract = {PURPOSE: The purpose of this study was to develop a semi-automated optical coherence tomography angiography (OCTA) framework for quantitative morphological assessment of choroidal neovascularization (CNV) to examine associations between quantitative metrics and CNV etiology, activity, and lesion patterns.<br><br>METHODS: This retrospective study analyzed treatment-na&#xef;ve eyes with neovascular age-related macular degeneration (nAMD), myopic CNV (mCNV), or inflammatory CNV (iCNV). OCTA images were processed with a standardized pipeline combining AngioTool, ImageJ, and custom Python algorithms to extract vascular-network and contour-heterogeneity metrics.<br><br>RESULTS: Sixty&#x2011;six eyes were analyzed (21 with nAMD, 23 with mCNV, and 22 with iCNV). The nAMD lesions were largest and most branched, showing the greatest median vessel area (1.24 mm2), perimeter (8.369 mm), MaxFeret (2.603 mm), MinFeret (1.598 mm), and total vessel length (14.583 mm)-all significantly greater than mCNV (all P < 0.017). The mCNV lesions were compact and regular. The iCNV lesions exhibited pronounced contour irregularity with lowest circularity (0.621) and vertex index (0.843), and highest maximum (0.243 mm) and mean (0.137 mm) depression depths. For activity assessment, a five-parameter model (vessel area, vessel density, total junctions, average depression, and circularity) discriminated active versus inactive CNV with excellent accuracy (area under the curve [AUC] = 0.901).<br><br>CONCLUSIONS: Quantitative OCTA biomarkers distinguish CNV etiologies and activity, providing a noninvasive, objective basis for clinical assessment and individualized treatment planning.<br><br>TRANSLATIONAL RELEVANCE: This study bridges the gap between image processing and clinical practice by validating a quantitative OCTA pipeline sensitive to etiology-specific morphological variations. The resulting multivariate model provides an objective, noninvasive tool for assessing CNV activity. Ultimately, these OCTA biomarkers offer a reproducible method to optimize disease monitoring and guide personalized management of CNV.}, }
@article {pmid41805150, year = {2026}, author = {McLeod, DS and Bhutto, IA and Messinger, JD and Berlin, A and Grebe, R and Bijon, J and Freund, KB and Curcio, CA and Edwards, MM}, title = {Choroidal Vascular Findings in a Case of Multifocal Geographic Atrophy: A Clinicopathologic Correlation.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {19}, pmid = {41805150}, issn = {1552-5783}, mesh = {Humans ; Female ; *Geographic Atrophy/pathology/diagnosis ; *Choroid/blood supply ; Aged, 80 and over ; *Choroidal Neovascularization/pathology/diagnosis/etiology ; Fluorescein Angiography ; Microscopy, Confocal ; Tomography, Optical Coherence ; Retinal Pigment Epithelium/pathology ; Immunohistochemistry ; }, abstract = {PURPOSE: We examined the choroid in both eyes from a donor with multifocal geographic atrophy (GA), enlarged choroidal vessels, and choroidal neovascularization (CNV) secondary to age-related macular degeneration, using histology and immunohistochemistry, and we correlated the findings with multimodal clinical imaging.<br><br>METHODS: A Caucasian woman with bilateral GA was followed clinically for 5 years, until 6 years prior to her death at age 93. To correlate clinical and histologic features, the right eyecup was photographed before dissecting the posterior pole. Choroidal blood vessels were labeled with Ulex europaeus agglutinin-1 (UEA-1) lectin following retinal pigment epithelium removal and imaged by confocal microscopy. Selected regions were embedded and sectioned for histologic staining. The left eye was used for ultrastructure analysis.<br><br>RESULTS: The posterior pole exhibited areas of atrophy surrounded by mottled retinal pigment epithelium overlying calcified drusen. Confocal imaging of the UEA-1 lectin-labeled choroidal flatmounts showed limited visualization of the submacular vasculature, consistent with masking by basal laminar and lipid-rich deposits seen in histologic sections. In well-labeled regions of the posterior pole, the choriocapillaris was attenuated and widely separated by markedly thickened, hyalinized intercapillary pillars. Venules and veins appeared dilated, and arteries exhibited arteriosclerotic changes. A choroidal neovascular complex was observed superior to the optic nerve head near the atrophic border; the adjacent choriocapillaris was attenuated.<br><br>CONCLUSIONS: In this single case of multifocal GA, choroidal thickening and large-caliber outer choroidal vessels coexisted with marked choriocapillaris degeneration and adjacent neovascularization. These observations suggest that structural choroidal enlargement does not preclude choriocapillaris failure and may be associated with ischemic and neovascular phenotypes.}, }
@article {pmid41805864, year = {2026}, author = {Hüsken, D and Webster, E and Künzel, SE and Knecht, V and Strauß, O and Joussen, AM and Zeitz, O}, title = {[Plasma proteomics in age-related macular degeneration].}, journal = {Die Ophthalmologie}, volume = {123}, number = {3}, pages = {184-191}, pmid = {41805864}, issn = {2731-7218}, mesh = {Humans ; *Proteomics/methods ; Biomarkers/blood ; *Proteome/analysis/metabolism ; *Macular Degeneration/blood ; *Blood Proteins/metabolism/analysis ; Aged ; Male ; Female ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) shows a heterogeneous treatment response to anti-vascular endothelial growth factor (VEGF), but the underlying mechanisms remain poorly understood. Classical approaches focus on single biomarkers, whereas the multifactorial and systemic nature of the disease has received less attention.<br><br>METHOD: In the BIOMAC cohort blood proteomes of patients with nAMD were systematically analyzed. Mass spectrometry, dimensionality reduction and pattern-based classifiers were applied to capture systemic proteomic signatures and link them to clinical phenotypes. As a supplement metabolomic analyses were carried out including a&#xa0;focus on xenobiotics.<br><br>RESULTS: The findings demonstrate a&#xa0;distinct yet complex influence of systemic signals: a&#xa0;subset of patients was characterized by oxidative stress and respiratory patterns independent of the ocular morphology. Individual proteins such as aldolase C were associated with disease control but lacked predictive power when considered alone. Only high-dimensional patterns of many proteins enabled a significant, although not yet perfect separation between effectively controlled and chronically active courses of choroidal neovascularization (CNV). Metabolomic profiling further identified unexpected candidates, such as the sweetener saccharin, which consistently showed protective effects in both patients and experimental models.<br><br>CONCLUSION: Systemic plasma proteome and metabolome signatures reflect the clinical phenotype of nAMD. Modern statistical methods supported by artificial intelligence are the key to unravelling these complex datasets. Although no valid single biomarker has yet emerged, the pattern-based approach provides novel translational insights and can potentially broaden the therapeutic target space for nAMD.}, }
@article {pmid41806579, year = {2026}, author = {Song, Y and Xu, T and Zhang, H and Hu, S and Wei, S and Cao, M and Wang, H and Yin, D}, title = {Emerging organophosphate flame retardant CDP causes neovascular macular degeneration-like alterations of outer blood-retinal barrier via paracrine VEGFA signaling.}, journal = {Journal of hazardous materials}, volume = {507}, number = {}, pages = {141669}, doi = {10.1016/j.jhazmat.2026.141669}, pmid = {41806579}, issn = {1873-3336}, abstract = {Visual impairment is an urgent public health concern. Increasing epidemiological research has demonstrated a strong correlation between environmental contaminant exposure and retinal diseases, but the underlying mechanism remains unclear. The disruption of the outer blood-retinal barrier (oBRB) is closely implicated in the pathogenesis of multiple vision-threatening disorders. Given its critical physiological role and anatomical position, we systematically investigated the effects of cresyl diphenyl phosphate (CDP, one emerging organophosphate flame retardant) on the oBRB, applying both zebrafish larvae and an in vitro human oBRB model consisting of ARPE-19 and HUVECs. The downregulation of tight junction expression and retinal neovascularization were observed in the zebrafish larvae under CDP treatment. The establishment of the oBRB model further discovered that CDP exposure caused barrier dysfunction and increased VEGFA secretion of ARPE-19. Through the paracrine signaling, VEGFA promoted the angiogenesis of HUVECs, eliciting pathological feature similar to neovascular macular degeneration. This study was the first to reveal an association between eOPFR exposure and retinal-related diseases, highlighting the significance of paracrine signaling in the pathological process.}, }
@article {pmid41807615, year = {2026}, author = {Talks, J and de Salvo, G and Patel, PJ and de Silva, SR and Gale, RP and McKibbin, M and Varma, D and Pearce, I and Peto, T and Reynolds, R and Bailey, C and Downey, L and Kiire, CA and Sivaprasad, S and Downey, AK and James, N and Chi, GC and Dodds, M and Dayal, P}, title = {Real-world treatment patterns and visual outcomes of faricimab in patients with neovascular age-related macular degeneration in the UK at 12 months: the FARWIDE-nAMD study.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41807615}, issn = {1476-5454}, abstract = {BACKGROUND: The Faricimab Real-World Evidence (FARWIDE) studies are evaluating real-world outcomes of eyes with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) treated with faricimab in the UK. Here, we present results from FARWIDE-nAMD for eyes with 12 months of follow-up after faricimab initiation.<br><br>METHODS: nAMD patient-eyes that received &#x2265;1 faricimab injection after May 2022 at one of 35 participating UK National Health Service retinal clinics with &#x2265;12 months of follow-up after faricimab initiation as of July 2024 were included. Treatment-na&#xef;ve (TN) eyes had no prior anti-VEGF treatment. Previously treated (PT) eyes switched from an anti-VEGF to faricimab. Baseline characteristics, VA, and injection frequency were assessed. Intraocular inflammation (IOI) and presumed infectious endophthalmitis (PIE) rates were pooled for nAMD and DMO eyes with any follow-up duration on faricimab. Analyses are descriptive.<br><br>RESULTS: 5854 nAMD patients (6991 eyes; 26.5% TN, 73.5% PT) were included. 83.3% of PT eyes switched from aflibercept 2.0&#x2009;mg. TN eyes received a mean (SD) of 4.7 (0.7) faricimab injections in months 1-6 and 2.2 (1.1) injections in months 7-12. PT eyes received 4.5 (1.0) injections in months 1-6 and 3.0 (1.2) in months 7-12. In TN eyes, mean (SD) VA increased from 56.4 (16.3) Early Treatment Diabetic Retinopathy Study letters at baseline to 60.1 (19.4) at 12 months (mean [SD] change 3.6 [14.7] letters). PT eyes had stable VA. IOI and PIE rates were consistent with faricimab phase 3 trials.<br><br>CONCLUSIONS: These 1-year data support real-world faricimab effectiveness, durability, and safety in nAMD.}, }
@article {pmid41807617, year = {2026}, author = {Ibrahim, FN and Fan, KR and Chan, HH and Ong, C and Sun, C and Sim, S and Tan, AC and Tan, TE and Teo, KY and Mathur, R and Chan, CM and Cheung, CMG and Fenner, BJ}, title = {Clinical characteristics and progression rates of geographic atrophy in an Asian population from Singapore.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41807617}, issn = {1476-5454}, abstract = {PURPOSE: To characterise geographic atrophy (GA) associated with age-related macular degeneration (AMD) and its progression rates in an Asian cohort.<br><br>METHODS: Retrospective study of 170 eyes characterising GA lesions using near infrared (NIR) and spectral domain optical coherence tomography (SD-OCT).<br><br>RESULTS: The majority of patients were Chinese (88.2%), followed by Malay (4.7%), Indian (3.5%) and Others (3.5%). Mean age at baseline was 78.4 (SD 8.2) years, with 42.9% males. Mean baseline GA area was 4.25mm[2] (SD 4.25), best-corrected visual acuity 0.71logMAR units (SD 0.52) and subfoveal choroidal thickness (SFCT) 168.3&#x2009; &#x3bc;m (SD 77.4). Multifocal GA was present in 97 (57.1%) of eyes, foveal involvement in 114 (67%) and bilateral in 42 (24.7%). Macular neovascularisation was present in the fellow eye of 48 (28.2%) patients. Mean follow-up was 4.12 (SD 2.95) years, with a mean GA progression rate of 0.98 (SD 1.26)mm[2]/yr (SQRT 0.22&#x2009;mm/yr SQRT, SD 0.21). Bilateral disease (p&#x2009;=&#x2009;0.005), reticular pseudodrusen (p&#x2009;=&#x2009;0.02), larger baseline GA area (p&#x2009;<&#x2009;0.001) and multifocal disease (p&#x2009;=&#x2009;0.01) were independently associated with greater odds of rapid GA progression.<br><br>CONCLUSION: We evaluated AMD-associated GA in Asian patients, predominantly of Chinese descent, using NIR and SD-OCT. These findings are valuable to identify high-risk patients and guide future GA therapies in Asian populations.}, }
@article {pmid41807973, year = {2026}, author = {Mi, Y and Zong, J and Wang, S and Zhu, Q and Lin, S and Zheng, X and Hong, Y and Zhou, J and Ye, L}, title = {Accelerometer-derived "weekend warrior" physical activity pattern and risk of age-related eye diseases: a prospective cohort study.}, journal = {Eye and vision (London, England)}, volume = {13}, number = {1}, pages = {}, pmid = {41807973}, issn = {2326-0254}, support = {2023YFC3604104//Key Technologies Research and Development Program/ ; 2023-PT320-04//Special Funds for the Basic Research and Development Program in the Central Non-profit Research Institutesof China/ ; }, abstract = {BACKGROUND: International guidelines recommend at least 150 min of weekly moderate-to-vigorous physical activity (MVPA), but whether concentrated versus distributed activity patterns differ in their associations with age-related eye diseases remains unclear.<br><br>METHODS: This prospective cohort study included 86,271 UK Biobank participants free of age-related eye diseases at baseline. Physical activity was assessed using wrist-mounted triaxial accelerometers (Axivity AX3) over seven consecutive days. Two MVPA thresholds were examined:&#x2009;&#x2265;&#x2009;150&#xa0;min/week (primary) and&#x2009;&#x2265;&#x2009;300&#xa0;min/week (secondary). Participants were categorized as: inactive (below threshold), weekend warriors (WW; meeting threshold with&#x2009;&#x2265;&#x2009;50% MVPA concentrated within 1-2&#xa0;days), or regularly active (meeting threshold without WW criteria). Cox proportional hazards regression models were used to assess associations over a median follow-up of 7.9&#xa0;years.<br><br>RESULTS: At the&#x2009;&#x2265;&#x2009;150&#xa0;min/week threshold, both WW (hazard ratio [HR]&#x2009;=&#x2009;0.89, 95% confidence interval [CI]: 0.84-0.94, P&#x2009;<&#x2009;0.001) and regularly active patterns (HR&#x2009;=&#x2009;0.93, 95% CI: 0.87-0.99, P&#x2009;=&#x2009;0.028) were associated with a reduced risk of cataract compared to inactivity. The WW pattern was also associated with a reduced risk of diabetic retinopathy (DR, HR&#xa0;= 0.74, 95% CI: 0.55-0.99, P&#x2009;=&#x2009;0.043) and age-related macular degeneration (AMD, HR&#x2009;=&#x2009;0.85, 95% CI: 0.75-0.97, P&#x2009;=&#x2009;0.016). Direct comparisons between the WW and regularly active patterns showed no significant differences for these conditions (all P&#x2009;>&#x2009;0.05), except for a nominal difference in glaucoma (P&#x2009;=&#x2009;0.036). At the&#x2009;&#x2265;&#x2009;300&#xa0;min/week threshold, only the WW pattern remained significantly associated with reduced risk of cataract (HR&#x2009;=&#x2009;0.91, 95% CI: 0.86-0.97, P&#x2009;=&#x2009;0.002) and glaucoma (HR&#x2009;=&#x2009;0.86, 95% CI: 0.75-0.97, P&#x2009;=&#x2009;0.019).<br><br>CONCLUSION: Both the WW and regularly active patterns demonstrate protective associations with age-related eye diseases compared to inactivity, with no statistically significant differences between the two active groups for most outcomes. These findings suggest that the WW approach is a viable and flexible alternative for individuals who find it difficult to maintain daily physical activity.}, }
@article {pmid41808823, year = {2026}, author = {Uppal, M and Hosseini, A and Bilal, K and Tan, N and Ai, Z and Khan, W and Samad, I and Gill, G and Yoo, HS and Chakravarthy, H and Kuo, CH and Xi, J and Granville, DJ and Matsubara, JA}, title = {Granzyme B from mast cells contributes to choroidal neovascularization in a model of wet age-related macular degeneration.}, journal = {Frontiers in immunology}, volume = {17}, number = {}, pages = {1710965}, pmid = {41808823}, issn = {1664-3224}, mesh = {*Mast Cells/metabolism/immunology ; Animals ; *Granzymes/metabolism/genetics ; *Choroidal Neovascularization/pathology/metabolism/etiology ; Humans ; Mice ; Mice, Knockout ; Disease Models, Animal ; *Wet Macular Degeneration/pathology/metabolism/etiology ; Cell Degranulation ; Choroid/pathology/metabolism ; Mice, Inbred C57BL ; Male ; Female ; }, abstract = {PURPOSE: Wet age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), yet current anti-VEGF therapies are ineffective in many patients. This study investigates the role of mast cell-derived granzyme B (GzmB), a serine protease responsible for the abnormal cleavage of the extracellular matrix in the outer retina.<br><br>METHODS: Human and mouse choroidal tissues were analyzed for mast cell distribution, GzmB expression, and age-related changes. An ex vivo choroidal sprouting assay (CSA) was used to evaluate the effects of mast cell degranulation and/or stabilization, and the pharmacologic inhibition of GzmB, using tissues from wild-type and GzmB knockout (KO) mice.<br><br>RESULTS: Aging increased mast cell accumulation and degranulation in both the human and mouse choroid, leading to elevated GzmB. GzmB KO mice exhibited reduced choroidal sprouting, and exogenous GzmB promoted angiogenesis. Both GzmB inhibition and mast cell stabilization suppressed angiogenic events, confirming GzmB's role in mast cell-driven angiogenesis.<br><br>CONCLUSIONS: GzmB is a key mediator of mast cell-induced CNV. Targeting GzmB, either directly or through mast cell stabilization, offers a promising strategy for reducing angiogenesis in a condition such as wet AMD.}, }
@article {pmid41809655, year = {2026}, author = {Zhou, B and Parekh, Z and Phung, C and Rodriguez, SH and Skondra, D}, title = {The gut-retina axis in age-related macular degeneration: immune crosstalk and metabolite production.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10847}, pmid = {41809655}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology/physiology ; Animals ; Dysbiosis/immunology ; *Retina/immunology/metabolism/pathology ; }, abstract = {Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbiome as a potential critical modulator in AMD pathogenesis through the gut-retina axis. Dysbiosis, characterized by imbalanced microbial diversity, composition and function, can exacerbate systemic and retinal inflammation through microglial priming, inflammasome activation, and secretion of pro-angiogenic cytokines (IL-6, IL-1β, TNF-α, VEGF). Additionally, microbiome-derived metabolites such as short-chain fatty acids and bile acids may exert modulatory roles in host immunity and homeostasis. Their depletion in conjunction with enrichment of specific microbial taxa have been linked to progression of advanced AMD. Together, these complex systems of immune crosstalk in relation to dysbiosis highlight the gut-retina axis as a promising therapeutic target. Dietary modifications, particularly Mediterranean and high-fiber diets, enhance production of protective metabolites and are associated with decreased AMD progression risk compared to Western dietary patterns. Experimental strategies such as fecal microbiota transplantation in animal models and drug repurposing strategies show promise in modulating disease severity. This review synthesizes current mechanistic insights into microbial-immune crosstalk in AMD, emphasizing the interplay of dysbiosis, immune activation, and metabolite signaling.}, }
@article {pmid41810055, year = {2026}, author = {El Mollayess, G and Jaroudi, M and Tlaiss, Y and Itaoui, R and Abiad, B}, title = {Surgical management of acute choroidal neovascularization related submacular hemorrhage: Three case reports.}, journal = {World journal of clinical cases}, volume = {14}, number = {6}, pages = {118545}, pmid = {41810055}, issn = {2307-8960}, abstract = {BACKGROUND: Acute submacular hemorrhage (SMH) secondary to choroidal neovascularization (CNV), most commonly in neovascular age-related macular degeneration, is a vision-threatening emergency. Thick, fovea-involving SMH can cause rapid photoreceptor injury, and timely intervention aimed at clot lysis and displacement, while continuing CNV suppression with anti-vascular endothelial growth factor (anti-VEGF) therapy, may improve anatomic outcomes.<br><br>CASE SUMMARY: We report a retrospective case series of three eyes with acute, fovea-involving CNV-related SMH treated with pars plana vitrectomy (PPV), subretinal tissue plasminogen activator (tPA), and expansile gas tamponade, with intravitreal anti-VEGF administered at the end of the procedure and continued postoperatively. Two cases had early intraocular pressure-related events (transient hypotony in one patient and transient ocular hypertension in another) requiring close postoperative monitoring and medical management. Follow-up color fundus photography and optical coherence tomography documented postoperative evolution of the hemorrhage compared with baseline, with ongoing anti-VEGF therapy planned to control the underlying CNV.<br><br>CONCLUSION: PPV with subretinal tPA and gas tamponade is a practical surgical strategy for acute, thick, fovea-involving SMH secondary to CNV, particularly when rapid displacement is desired. Careful documentation of operative parameters, strict postoperative monitoring for pressure-related complications, and continued anti-VEGF therapy are essential components of care.}, }
@article {pmid41811401, year = {2026}, author = {Aslam, TM and Ziemssen, F and Loewenstein, A and Nair, R and Thurston, M and Hawkins, A and Daly, A}, title = {Post-Visual Diagnosis Distress: The Weight of Threatened Sight.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41811401}, issn = {2193-8245}, abstract = {Receiving a diagnosis of a vision-threatening eye condition is a psychologically salient event for many patients. Across ophthalmology, fear, uncertainty, and emotional distress are commonly observed at the time of diagnosis, often before substantial functional vision loss occurs. Although depression and anxiety are well documented in chronic eye disease, diagnosis-linked distress remains inconsistently recognised and is rarely addressed systematically within routine ophthalmic care. This article introduces post-visual diagnosis distress (PVDD) as a descriptive, nondiagnostic framework to characterise the predictable, loss-related emotional responses that may arise following the diagnosis of a vision-threatening or irreversible eye condition. PVDD is not proposed as a psychiatric disorder, but as a clinically meaningful construct that helps legitimise patient experience, supports empathetic communication, and facilitates timely recognition and appropriate signposting when distress is significant. Drawing on evidence from age-related macular degeneration, glaucoma, and other chronic eye diseases, and informed by multidisciplinary perspectives spanning ophthalmology, psychiatry, counselling, patient advocacy, and public health, the article argues that recognising PVDD may improve patient engagement, quality of life, and psychological outcomes.}, }
@article {pmid41814099, year = {2026}, author = {Di Criscio, A and Rosso, P and Fico, E and Iannetta, D and Marenco, M and Lambiase, A and Tirassa, P}, title = {VEGF and Neurotrophins Interaction in the Retinal Neurovascular Unit Homeostasis: A Target for Ocular Disease Treatment and Management.}, journal = {Pharmaceutical research}, volume = {}, number = {}, pages = {}, pmid = {41814099}, issn = {1573-904X}, abstract = {Emerging evidence underscores the central role of the retinal neurovascular unit (RNVU) in the pathogenesis of major retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Traditionally considered as primarily vascular diseases, these conditions are now increasingly recognized to involve early neurodegenerative processes that may precede vascular dysfunction. Although anti-VEGF therapies have revolutionized the treatment of neovascular retinal diseases, long-term VEGF inhibition has been associated with adverse effects, including retinal atrophy and diminished neuroprotection, underscoring the need for more targeted strategies. Recent studies have highlighted the differential roles of VEGF-A splice isoforms, particularly the pro-angiogenic VEGF-Axxxa and the anti-angiogenic VEGF-Axxxb, in maintaining RNVU homeostasis and contributing to disease progression. In parallel, neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have demonstrated the ability to exert neuroprotective, anti-inflammatory, and vasomodulatory effects, partly through modulation of VEGF-A signaling. Notably, we have recently demonstrated that NGF modulates VEGF-A isoform expression and VEGFR-2 levels in diabetic retinas, further supporting the hypothesis of a functional cross-talk between neurotrophins and angiogenic pathways. Based on this evidence, a new model is proposed, in which NGF and BDNF interact bidirectionally with VEGF-A to preserve RNVU integrity. This integrated therapeutic perspective, combining neurotrophic support with selective modulation of VEGF-A isoforms, may enhance treatment efficacy, reduce long-term side effects, and minimize the burden of care in chronic retinal neurodegenerative diseases.}, }
@article {pmid41814222, year = {2026}, author = {Aune, D and Jayedi, A and Kazemi, A and Soltani, S and Rezaei, F and Leitzmann, MF}, title = {Physical activity and the risk of cataract and age-related macular degeneration: a systematic review and meta-analysis of cohort studies.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04721-z}, pmid = {41814222}, issn = {1471-2415}, }
@article {pmid41814235, year = {2026}, author = {Han, HY and Park, SM and Lee, JH and Kim, CG and Kim, JH}, title = {Twelve-month lesion reactivation after initial loading injections of faricimab in neovascular AMD: a comparison between three and four loading injections.}, journal = {BMC ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12886-026-04707-x}, pmid = {41814235}, issn = {1471-2415}, }
@article {pmid41814654, year = {2026}, author = {Andres-Mateos, E and Kozlowski, C and Zhang, H and Fajardo, D and Xu, E and Enamorado, IN and Calabro, KR and Rayaprolu, S and Havlik, LP and Handy, TE and Plummer, CE and Stevenson, V and Rind, H and Leahy, M and Boyd, RF and Coleman, KE and Boye, SL and Boye, SE}, title = {Laterally spreading AAV.SPR enables safe and efficient RS1 delivery to the macula after peripheral subretinal injection.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2026.03.014}, pmid = {41814654}, issn = {1525-0024}, abstract = {Mutations in RS1 are associated with X-linked retinoschisis (XLRS), a common cause of juvenile macular degeneration in males. Schisis cavities in the central retina of these patients have hampered submacular delivery with conventional adeno-associated viruses (AAVs). Clinical trials employing intravitreally injected AAVs showed a lack of efficacy and inflammation. Here, we demonstrate, in non-human primate (NHP) retina, that AAV.SPR, a laterally spreading capsid, transduced photoreceptors in the macula/fovea without the need for central retinal detachment, enabling transgene expression multiple millimeters beyond the subretinal injection (SRI) bleb margins. Peripheral SRI of AAV.SPR-hGRK1-RS1 resulted in robust and properly localized RS1 expression in NHP fovea. Despite being a secreted protein, biodistribution of RS1 remains confined to the area of AAV-RS1 transduction. Having established feasibility for the approach, we performed preclinical proof-of-concept, safety, and efficacy studies in support of "ATSN-201" (NCT05878860). In RS1KO mice, a "hybrid" efficacy/safety study demonstrated dose-dependent improvements in retinal function and structure and proper localization of RS1 following treatment with ATSN-201. A good laboratory practice (GLP) toxicology study in NHPs established safety at the highest dose evaluated. The enhanced transduction and lateral spreading ability of AAV.SPR make it an attractive option for treating inherited retinal diseases including, but not limited to, XLRS.}, }
@article {pmid41815438, year = {2026}, author = {Spooner, KL and Fraser-Bell, S and Fu, DJ and Faes, L and Romano, F and Cozzi, M and Chang, AA and Sivaprasad, S}, title = {Imaging and functional correlates of fibrosis in neovascular age-related macular degeneration: a systematic review.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1786309}, pmid = {41815438}, issn = {2674-0826}, abstract = {BACKGROUND: Despite intravitreal anti-vascular endothelial growth factor (VEGF) therapy being the standard of care for neovascular age-related macular degeneration (nAMD), long-term visual decline remains common, with subretinal fibrosis representing a major cause of irreversible vision loss. Objective: To systematically evaluate how imaging-defined fibrosis in nAMD is defined and quantified, its incidence under anti-VEGF therapy, associated baseline associations, and its impact on visual outcomes.<br><br>METHODS: We systematically searched MEDLINE, Embase, CENTRAL, and Scopus through September 2025 for studies reporting imaging-defined fibrosis in anti-VEGF-treated nAMD. Eligible studies included randomized controlled trial secondary analyses, prospective and retrospective cohorts, and registries. Two reviewers independently extracted data on fibrosis definitions, imaging modalities, associations, and functional outcomes. Random-effects meta-analyses pooled the best-corrected visual acuity (BCVA) difference (ETDRS letters) and the odds ratio for incident fibrosis. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool, and the certainty of evidence was evaluated using the GRADE approach.<br><br>RESULTS: Fifty-eight studies were included (12 randomized trial secondary analyses, 18 prospective studies, and 28 retrospective studies). Across studies, subretinal fibrosis developed in approximately 10-15% of eyes within 2 years and 40-50% by 5 years of anti-VEGF therapy, with a lower incidence under fixed or treat-and-extend regimens compared with pro re nata dosing. Eyes with fibrosis had consistently worse visual outcomes (pooled BCVA difference -29 ETDRS letters; 95% CI -47 to -12). Key associations included type 2 macular neovascularisation (OR 5.7), subretinal hyperreflective material (OR 2.7), intraretinal fluid (OR 3.6), and large haemorrhage (OR 2.3), while subretinal fluid appeared protective (OR 0.6). Definitions and quantification approaches varied widely across imaging modalities.<br><br>CONCLUSIONS: Fibrosis remains a frequent and vision-limiting sequela of treated nAMD, with substantial heterogeneity in imaging definitions and grading methods limiting cross-study comparability. Standardised OCT-anchored definitions, reproducible quantitative measures, and functional endpoints beyond BCVA are needed to advance anti-fibrotic therapeutic development and improve long-term visual outcomes.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD420231132016.}, }
@article {pmid41817413, year = {2026}, author = {Shen, Y and Yin, W and Xiao, X and Lu, Y and Feng, Y and Yang, P}, title = {Cigarette Smoking and Eye Diseases: A Comprehensive Review.}, journal = {Ocular immunology and inflammation}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/09273948.2026.2633446}, pmid = {41817413}, issn = {1744-5078}, abstract = {PURPOSE: Cigarette smoking remains a major global public health challenge, with the eye being particularly vulnerable due to its direct exposure to environmental insults. This review aims to synthesize epidemiological and mechanistic evidence linking traditional combustible cigarette smoking to a broad spectrum of ocular diseases.<br><br>METHODS: A comprehensive literature search was conducted to identify studies examining the association between smoking and various ocular conditions, with a focus on epidemiological data and underlying pathological mechanisms.<br><br>RESULTS: Smoking is established as the strongest modifiable risk factor for age-related macular degeneration and is associated with a 10.8-fold increased risk of cataract development. It strongly predicts retinopathy onset after 9 years of diabetes duration. The reviewed evidence links diverse ocular diseases-from common conditions like dry eye and cataracts to less frequently discussed associations such as strabismus and amblyopia-to a unified set of pathological mechanisms centered on cigarette smoke-induced oxidative stress, chronic inflammation, neovascularization, and immune imbalance.<br><br>CONCLUSIONS: This review provides a comprehensive disease-to-mechanism panorama of smoking-related ocular damage. The findings underscore the critical importance of smoking cessation as a primary preventive strategy to mitigate the burden of avoidable vision loss.}, }
@article {pmid41818339, year = {2026}, author = {Guo, G and Wang, R and Zhang, S and Zhang, Y and Li, L and Liu, M and Yin, L and Wei, C and Gong, Y and Jiao, L and Li, D and Zhou, J and Liu, M and Ran, J}, title = {Preserving the UFMylation-cilium axis mitigates blue light-induced retinal degeneration.}, journal = {Journal of molecular cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jmcb/mjag007}, pmid = {41818339}, issn = {1759-4685}, abstract = {Blue light damage (BLD) is a complex process implicated in a variety of ocular diseases, including age-related macular degeneration and dry eye diseases. However, the molecular mechanisms underlying the BLD process remain largely unknown. In this study, using a mouse model, we identify photoreceptor cilium disruption as a key event in BLD and show that the UFMylation of kinesin family member 11 (KIF11) is decreased under BLD conditions. We further reveal that ubiquitin-fold modifier 1-specific ligase 1 (UFL1), the sole ligase for UFMylation, localizes to the basal body and is required for maintaining photoreceptor cilia. Strikingly, exposure to blue light disrupts the basal body localization of UFL1, leading to ciliary defects and subsequent photoreceptor dysfunction. Ufl1 knockout mice exhibit similar ciliary donlefects and retinal impairments. Importantly, intravitreal injection of agents that enhance UFMylation or ciliogenesis can mitigate the pathological changes induced by blue light exposure. These findings establish that UFL1-mediated ciliary integrity contributes to retinal deficits associated with BLD and demonstrate that targeting the UFMylation-cilium axis represents a promising therapeutic strategy for BLD-associated retinal diseases.}, }
@article {pmid41818422, year = {2026}, author = {Lin, CC and Cheng, CK and Peng, PH and Cheng, SF}, title = {Real world practice of Artificial intelligence Diagnostic System for Diabetic Retinopathy in Taiwan.}, journal = {Retina (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/IAE.0000000000004826}, pmid = {41818422}, issn = {1539-2864}, abstract = {PURPOSE: We evaluated the alterations of applying artificial intelligence (AI) diagnostic system for diabetic retinopathy (DR) screening in real-world practice.<br><br>METHODS: This retrospective study included 11,713 diabetic patients from the government-led Diabetes Shared Care Network. The AI system Verisee was integrated into the clinical workflow to identify referable diabetic retinopathy (RDR). Its performance was compared with ophthalmologist grading at the patient level using sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Subgroup analysis was performed by age and gender, with additional referral diseases identified by ophthalmologists.<br><br>RESULTS: Verisee achieved a sensitivity of 0.88, specificity of 0.86, accuracy of 0.86, PPV of 0.58, NPV of 0.97, and AUC of 0.87 in detecting RDR. Performance declined with increasing age, whereas sex distribution remained consistent across age groups. The AI system identified a higher proportion of RDR than ophthalmologists (27.45% vs. 18.15%). In addition to 1,818 patients with RDR, ophthalmologists identified other referral-warranted ocular conditions in 4.5% of cases. The AI system referred age-related macular degeneration (grades 2-4), whereas referral decisions for macular hole and macular edema (grades 1-2) varied; however, glaucoma (grades 0-1) identified by clinicians was not consistently referred.<br><br>CONCLUSION: Verisee demonstrated high accuracy in detecting RDR but exhibited reduced performance in older patients. It had a higher referral rate than ophthalmologists yet missed certain conditions such as glaucoma. Despite effectiveness in DR screening, further refinement is required to support broader ophthalmic disease detection.}, }
@article {pmid41818449, year = {2026}, author = {Maltsev, DS and Kulikov, AN and Kalinicheva, YA}, title = {Possible Association Between Retinal Arterial Occlusions and Subretinal Drusenoid Deposits: A Missing Link.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {3}, pages = {168-173}, doi = {10.3928/23258160-20251202-01}, pmid = {41818449}, issn = {2325-8179}, mesh = {Humans ; Female ; Male ; Tomography, Optical Coherence ; *Retinal Drusen/diagnosis/physiopathology/etiology ; Aged ; Fluorescein Angiography ; *Choroid/blood supply ; *Retinal Artery Occlusion/diagnosis/physiopathology/complications ; Middle Aged ; Visual Acuity ; Aged, 80 and over ; Microcirculation/physiology ; }, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the association between retinal artery occlusion (RAO), subretinal drusenoid deposits (SDD), and choroidal circulation.<br><br>PATIENTS AND METHODS: Patients with RAO and healthy age-matched volunteers were included in this study. The presence of SDD, choriocapillaris perfusion area, and subfoveal choroidal thickness were analyzed using optical coherence tomography (OCT) and OCT angiography.<br><br>RESULTS: In total, 25 patients with RAO (14 women and 11 men, 71.5 &#xb1; 8.9 years) and 19 healthy individuals (10 women and 9 men, 69.0 &#xb1; 5.2 years) were included. SDD were found in seven RAO patients (28.0%), among whom four (18.2%) had no age-related macular degeneration. Patients with RAO had a statistically significantly lower choriocapillaris perfusion area and subfoveal choroidal thickness than healthy controls (P < .05).<br><br>CONCLUSION: RAO may have an association with the presence of SDD that agrees with common systemic risk factors and changes of posterior eye segment microcirculation for both conditions.}, }
@article {pmid41818453, year = {2026}, author = {Prenner, S and Fine, HF and Do, DV}, title = {Photobiomodulation for Dry Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {57}, number = {3}, pages = {146-148}, doi = {10.3928/23258160-20251125-02}, pmid = {41818453}, issn = {2325-8179}, }
@article {pmid41819515, year = {2026}, author = {Abboud, I and Fam, A and Almobayed, A and Guillaume, GI and ElSheikh, RH and Lee, RK and Elhusseiny, AM}, title = {Association Between Pseudoexfoliation Glaucoma and Central Serous Chorioretinopathy.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2026.03.009}, pmid = {41819515}, issn = {1879-1891}, abstract = {PURPOSE: To evaluate whether pseudoexfoliation glaucoma (PXG) is associated with an increased hazard of developing central serous chorioretinopathy (CSCR) compared with primary open-angle glaucoma (POAG).<br><br>DESIGN: Retrospective cohort study using a multicenter, real-world electronic health record database.<br><br>SUBJECTS: Adults aged &#x2265;18 years diagnosed with PXG (study group) or POAG (control group).<br><br>METHODS: We obtained deidentified patient data from the TriNetX U.S. Collaborative Network. Patients with a history of age-related macular degeneration (AMD) or prior anti-vascular endothelial growth factor (anti-VEGF) therapy were excluded. We performed multivariable Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for baseline demographics; ocular and systemic comorbidities; psychiatric conditions; medication exposures (including corticosteroids); and prior ocular surgeries.<br><br>MAIN OUTCOME MEASURES: The primary outcome was the development of CSCR within 1- and 5-year follow-up periods following the glaucoma diagnoses.<br><br>RESULTS: A total of 10,347 patients with PXG and 205,065 with POAG were included. In the Cox proportional hazards model, PXG was significantly associated with a higher hazard of developing CSCR compared with POAG. The aHR for CSCR was 1.807 (95% CI, 1.041-3.136; p&#x202f;=&#x202f;0.036) at the 1-year follow-up and 1.631 (95% CI, 1.014-2.622; p&#x202f;=&#x202f;0.044) at 5 years.<br><br>CONCLUSIONS: PXG is associated with an increased hazard of developing CSCR compared with POAG. These findings suggest that PXG may be associated with an increased susceptibility to posterior segment vascular pathology. Prospective studies incorporating longitudinal imaging are warranted to further elucidate shared choroidal mechanisms underlying this association.}, }
@article {pmid41821033, year = {2026}, author = {Felfeli, T and Lane, NM and Mandelcorn, ED}, title = {Guiding syringe selection for intravitreal injections: injectability and stability analysis of compounded pegcetacoplan (SYFOVRE) and the broader implications for high-viscosity ophthalmic therapies.}, journal = {International journal of retina and vitreous}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40942-026-00832-3}, pmid = {41821033}, issn = {2056-9920}, }
@article {pmid41822409, year = {2026}, author = {Klufas, MA and Regillo, CD and Mandava, NK and Miller, EG}, title = {Evolution of Anti-Vascular Endothelial Growth Factor Clinical Trial Design for Treating Neovascular Age-Related Macular Degeneration.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261427831}, pmid = {41822409}, issn = {2474-1272}, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) treatment protocols for neovascular age-related macular degeneration (nAMD) have evolved from fixed, monthly, or bimonthly dosing to individualized, extended dosing regimens. Although a PRN (as-needed) injection protocol may reduce the number of injections, it confers a similar treatment burden by requiring regimented follow-up visits, and disease activity may resurface between visits. Various personalized treatment intervals have been implemented in more recent randomized controlled clinical trials (RCTs), reflecting a shifting focus toward individualized, variable, extended treatment intervals rather than the frequent, fixed regimens used in older RCTs. Newer agents, such as faricimab and aflibercept 8.0 mg, have been evaluated in phase 3 RCTs and potentially offer extended durability of dosing in intervals of up to 12-16 weeks or longer. Recently introduced anti-VEGF agents were tested in pivotal trials using individualized, variable, extended treatment intervals, with results showing adequate nAMD control compared to older, fixed dosing regimens, but additional studies are needed to determine the real-world durability of these agents compared to older anti-VEGF agents.}, }
@article {pmid41822529, year = {2026}, author = {Fong, KCS and Wong, WJ and Samsudin, A and Ganasan, DK and Goh, WN and Tai, JY and Fong, SN and Cheong, CYJ and Rajamanickam, G and Shunmugam, M}, title = {PAIR: Evaluating the Limits of Agreement Among Non-Retinal Specialist Using PathFinder Artificial Intelligence Tool for Retinal Disease Referrals: A Prospective Observational Study.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {584717}, pmid = {41822529}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate the diagnostic and referral agreement between non-retina specialists (NRS) using the PathFinder artificial intelligence (AI) assistant and fellowship-trained retina specialists (RS - gold standard) in interpreting macular optical coherence tomography (OCT) scans.<br><br>METHODS: This cross-sectional study included 202 consecutive patients undergoing OCT on the CIRRUS platform with the PathFinder AI module. Three RS independently graded all scans without clinical data, while three NRS interpreted the same scans using PathFinder assistance and full clinical information. The gold standard for both diagnosis and referral was defined by agreement of at least two of the three RS. The NRS recorded diagnostic confidence and time to AI-assisted decision. Agreement was assessed with Cohen's and Fleiss' &#x3ba; and sensitivity, and specificity were computed for four major pathologies.<br><br>RESULTS: Among 202 eyes (mean age 62.7 &#xb1; 12.3 years), RS inter-agreement was moderate for diagnosis (overall &#x3ba; = 0.59) and referral (&#x3ba; = 0.47). NRS showed substantial (NRS1 &#x3ba; = 0.78) to moderate (NRS2 &#x3ba; = 0.64; NRS3 &#x3ba; = 0.54) diagnostic agreement and high specificity (> 90% for all). Sensitivity varied across raters and diagnoses (0.57-0.89), with comparatively lower sensitivity observed for certain vision-threatening conditions such as age-related macular degeneration and macular hole. Referral agreement varied (&#x3ba; = 0.68, 0.24, 0.34) amongst NRS. Visual acuity was the only significant predictor of referral discordance (OR 0.66, 95% CI 0.55-0.80, p < 0.001). Median NRS with PathFinder assistance processing time was < 20s. The most significant false-positive diagnoses made by PathFinder-assisted NRS in eyes deemed normal by RS was ERM (40.0%), followed by PED (20.0%) and AMD (13.3%), observed across a small number of eyes and does not affect the results.<br><br>CONCLUSION: PathFinder is a valuable real-time decision-support tool in resource-limited settings; however, disease-specific refinements and clinical oversight remain important, particularly for vision-threatening conditions.}, }
@article {pmid41824262, year = {2026}, author = {Avery, R and Diack, C and Holekamp, N and Lhor, M and Mar, F and Maass, K}, title = {Ocular Half-Life: What it Does and Does Not Mean for Intravitreal Anti-angiogenic Drug Durability.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41824262}, issn = {2193-8245}, abstract = {Our commentary provides a conceptual foundation for the relationship between ocular half-life and treatment durability with respect to intravitreally administered anti-angiogenic therapies typically used for the treatment of retinal diseases, such as neovascular age-related macular degeneration and diabetic macular edema. Of note, we critically examine claims suggesting that increasing the dose of aflibercept can reduce ocular clearance and, consequently, increase ocular half-life. By reviewing the available data and exploring the underlying pharmacokinetic principles, this commentary seeks to provide an evidence-based understanding of the factors influencing treatment durability in this therapeutic area.}, }
@article {pmid41825596, year = {2026}, author = {Choi, J and Choi, E and Kang, SW and Kim, SJ and Hwang, S and Lee, H}, title = {Impact of intravitreal anti-vascular endothelial growth factor injections on cataract development.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2026.03.009}, pmid = {41825596}, issn = {1549-4713}, abstract = {PURPOSE: To evaluate the association between intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and incident cataract surgery.<br><br>DESIGN: Retrospective, interventional case series SUBJECTS: Patients with phakic lens status in both eyes at baseline who received &#x2265;12 unilateral anti-VEGF injections.<br><br>METHODS: Electronic medical records were analyzed to compare the incidence of cataract surgery between injected eyes (receiving anti-VEGF treatment) and untreated fellow eyes. Cumulative incidence was assessed using the Kaplan-Meier survival analysis. Lens opacity grades at the time of surgery and change in best-corrected visual acuity before and after the surgery were also analyzed.<br><br>MAIN OUTCOME MEASURES: Hazard ratio (HR) and 95% confidence interval (CI) for incident cataract surgery in the injected eye, compared with the fellow eye.<br><br>RESULTS: A total of 603 patients were followed for a median of 74 months. The 10-year cumulative incidence of cataract surgery was 40.7% (95% CI, 35.9-45.1) and 7.2% (95% CI, 4.1-10.3) in the injected and fellow eyes, respectively. The injected eye (HR, 8.174; 95% CI 5.767-11.586) and older age (HR, 1.069; 95% CI 1.052-1.086) were associated with an increased risk of cataract surgery. At the time of surgery, all lens opacity grades, including nuclear, cortical, and posterior subcapsular, were significantly higher in injected eyes (all p < 0.001), with the greatest difference observed in posterior subcapsular opacity.<br><br>CONCLUSION: Long-term intravitreal anti-VEGF treatment was associated with a significantly increased risk of developing cataract for which surgical intervention was performed.}, }
@article {pmid41826177, year = {2026}, author = {Cornejo-Uixeda, S and Borrás-Blasco, J and Valcuende-Rosique, A and Perez Gil, L and Monteagudo-Martinez, N and Merino, V}, title = {Dosing interval optimization and persistence with faricimab in age-related macular degeneration: An observational study in real-world clinical practice.}, journal = {Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.farma.2026.02.009}, pmid = {41826177}, issn = {2171-8695}, abstract = {OBJECTIVE: To evaluate treatment persistence and dosing interval extension with faricimab in neovascular age-related macular degeneration (nAMD) in real-world practice.<br><br>METHODS: Retrospective observational study conducted in a tertiary hospital (March 2024-March 2025). Patients receiving faricimab (treatment-na&#xef;ve or pre-treated with anti-VEGF therapy), with &#x2265;1 post-loading dose, were included. Dosing intervals were analyzed at baseline, 6 and 12&#x202f;months, Adherence was assessed with the medication possession ratio (MPR), with >80% considered adherent. Persistence was defined as the time from treatment initiation to discontinuation or end of follow-up. Persistence was estimated using Kaplan-Meier survival analysis.<br><br>RESULTS: We included 129 patients (148 eyes), mean age 74.5&#x202f;&#xb1;&#x202f;8.85&#x202f;years; 55% were female. A total of 39 patients (30.2%) were treatment-na&#xef;ve and 90 (69.8%) were pretreated. At 12&#x202f;months, 48.8% of na&#xef;ve and 55.5% of pretreated patients achieved 8-12&#x202f;weeks intervals. Mean persistence was 12.2&#x202f;months (SD 0.2; 95% CI: 11.8-12.6). The median was not reached by the end of the study. Persistence rate was 93% at 6 and 12&#x202f;months. Only one patient discontinued due to inefficacy. No serious adverse events or endophthalmitis occurred.<br><br>CONCLUSIONS: Faricimab showed excellent persistence and extended dosing intervals in real-world practice. This is the first study specifically evaluating faricimab real-world persistence in nAMD.}, }
@article {pmid41826348, year = {2026}, author = {Li, S and Ren, J and Wang, F and Wu, J and Li, Y and Wang, X and Zhang, M and Hu, H and Song, Y and Cao, W and Zhou, X and Li, M}, title = {Routine blood tests and machine learning identify complications in high myopia.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-70891-5}, pmid = {41826348}, issn = {2041-1723}, abstract = {High myopia can lead to cataract, glaucoma, retinal detachment, choroidal neovascularisation, and macular degeneration, causing irreversible vision loss. Imaging detects these complications, but population screening is limited by equipment, and specialist availability. Here we show that a machine learning model using routine blood test results identifies people at increased risk of complications related to high myopia during standard health examinations. We develop the model in a multicentre study of 10,661 participants and validate it in two independent cohorts. The model shows high accuracy across centres (area under the receiver operating characteristic curve=0.9010-0.9649) and flags individuals who receive a clinical diagnosis in a hospital-based prospective follow-up study of 5,067 participants. In a community screening study of 311,254 adults, the model increases the yield of detected complications among those referred for ophthalmic assessment (positive predictive value = 74%). This scalable blood-based approach supports opportunistic screening and earlier referral in primary care and community settings.}, }
@article {pmid41827105, year = {2026}, author = {Nashine, S and Kenney, MC}, title = {Characterization of the Effects of a Humanin Fragment Peptide (HNF14) in Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {5}, pages = {}, pmid = {41827105}, issn = {2077-0383}, support = {20/20 Society Pilot Research Grant//20/20 Society Pilot Research Grant/ ; }, abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of vision loss and is strongly associated with mitochondrial dysfunction in retinal pigment epithelial cells. Mitochondrial-derived peptides, including Humanin and its analogs, have demonstrated cytoprotective effects in AMD-related cellular models. However, the effects of shorter Humanin-derived fragments in disease-specific mitochondrial models remain incompletely characterized. Methods: Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF14, a 14-amino acid Humanin fragment peptide. Cellular metabolic activity, cytotoxicity, oxidative stress, apoptotic signaling, inflammatory markers, angiogenic factor expression, and amyloid-β1-42-induced apoptosis were evaluated using biochemical assays, protein analyses, and live-cell imaging approaches. Results: HNF14 treatment was associated with improved metabolic activity and reduced cytotoxicity in AMD cybrids, with minimal effects in normal cybrids. HNF14 significantly reduced intracellular and mitochondrial oxidative stress, suppressed apoptotic and inflammatory markers, and decreased VEGF-A protein expression in AMD cybrids. In addition, HNF14 attenuated amyloid-β1-42-induced apoptotic signaling in AMD cybrids. These effects were selective for cybrids containing AMD-derived mitochondria. Conclusions: This study demonstrates that HNF14 mitigates mitochondrial and cellular stress responses in AMD transmitochondrial cybrid cells. The findings indicate that a short Humanin-derived fragment retains cytoprotective activity in a disease-specific mitochondrial context and support further investigation of mitochondrial-derived peptides as modulators of mitochondrial dysfunction relevant to AMD pathophysiology.}, }
@article {pmid41827447, year = {2026}, author = {Remolí-Sargues, L and Monferrer-Adsuara, C and Castro-Navarro, V and López-Salvador, B and Francés-Muñoz, E and Marín-Payá, E and Marín-Montiel, J and López-Sánchez, E}, title = {Real-World Outcomes and Choroidal Vascular Structural Changes After Switching to Faricimab in Neovascular Age-Related Macular Degeneration.}, journal = {Journal of clinical medicine}, volume = {15}, number = {5}, pages = {}, pmid = {41827447}, issn = {2077-0383}, support = {10Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO)//10Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO)/ ; }, abstract = {Objectives: The objective of this study was to investigate choroidal structural alterations and evaluate the outcomes of switching to faricimab in patients with neovascular age-related macular degeneration (nAMD) previously treated with other anti-vascular endothelial growth factor (anti-VEGF) therapies after 12 months of follow-up. Methods: We performed a retrospective study of 30 eyes from 30 patients with nAMD who were switched to faricimab. The choroidal vascularity index (CVI), best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (CST), and the presence of subretinal fluid, intraretinal fluid, and wet macula were assessed at baseline and after 6 and 12 months. Results: CVI remained stable during follow-up (p > 0.05). BCVA improved significantly after 6 months (p = 0.041), but not at 12 months (p = 0.075). A significant reduction in CMT was observed (p < 0.05). Additionally, wet macula improved after 12 months (p < 0.05). Moreover, treatment intervals increased from 7.53 ± 2.39 to 12.47 ± 4.51 weeks. Conclusions: Switching to faricimab in patients with nAMD previously treated with other anti-VEGF therapies was associated with anatomical improvement, extended treatment intervals, and short-term visual gains, while choroidal vascular structure was maintained. Nonetheless, additional studies are warranted to more comprehensively evaluate the effectiveness of switching to faricimab, as well as the associated changes in choroidal vascular structure.}, }
@article {pmid41827932, year = {2026}, author = {Alizadeh, A and Alenezi, A and Khakestari, N and Amizadeh, Y and Jodeiri, A}, title = {Investigating the Impact of Semi-Supervised Learning Methods to Improve the Quality of Diagnosis of Retinal Diseases from OCT Images.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, pmid = {41827932}, issn = {2075-4418}, support = {72122//Tabriz University of Medical Sciences/ ; }, abstract = {Background: Age-related Macular Degeneration (AMD) is a leading cause of irreversible vision loss, particularly in the elderly. Optical Coherence Tomography (OCT), a noninvasive imaging modality, is widely used for retinal disease detection. However, the limited availability of labeled OCT datasets poses a significant challenge, making semi-supervised learning a promising approach. This study introduces a novel Iterative Teacher-Student (ITS) framework, which refines pseudo-labeling strategies to improve AMD detection accuracy, particularly in low-data scenarios. Methods: Initially, an optimal supervised model based on EfficientNet was developed to classify AMD using a dataset from Noor Eye Hospital, consisting of 16,822 OCT images. The dataset size was then progressively reduced to 70%, 50%, 20%, and 5% to evaluate model performance under data scarcity. Unlike conventional semi-supervised learning approaches, our ITS framework iteratively refines pseudo-labels, ensuring more reliable knowledge transfer from teacher to student models. Results: The optimized supervised model achieved 87.14% accuracy in AMD classification. As dataset size decreased to 20% and 5%, accuracy declined to 77.05% and 54.78%, respectively. Implementing the ITS framework improved accuracy to 88.56% at 20% and 64.15% at 5%, outperforming traditional semi-supervised methods. Conclusions: This study highlights the potential of semi-supervised learning, particularly our iterative teacher-student approach, to enhance AMD detection when labeled OCT data are scarce. The proposed framework introduces a novel iterative refinement strategy, which can serve as a foundation for future research in retinal disease diagnosis with limited labeled datasets.}, }
@article {pmid41828731, year = {2026}, author = {Zong, M and Qiu, Y and Li, C}, title = {Focus on Lactate and Lactylation Modification: The Potential Role in Ophthalmic Disease Treatment.}, journal = {International journal of molecular sciences}, volume = {27}, number = {5}, pages = {}, pmid = {41828731}, issn = {1422-0067}, mesh = {Humans ; *Protein Processing, Post-Translational ; *Eye Diseases/metabolism/therapy ; Animals ; *Lactic Acid/metabolism ; Lysine/metabolism ; Signal Transduction ; }, abstract = {Lysine lactylation represents a novel post-translational modification (PTM) involved in cellular functions including glycolysis and macrophage polarisation. It differs in form and mechanism from other PTMs such as acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation. As a recently discovered modification, lactylation has been implicated in the progression of multiple diseases. Recent studies further indicate lactylation's association with multiple ocular pathologies. This review systematically summarises and discusses lactylation's involvement in prevalent eye diseases, including myopia, retinopathy, ocular melanoma, uveitis, and macular degeneration. We further collate emerging data suggesting lactylation signalling pathways may represent potential therapeutic targets for ocular pathologies. This review aims to provide a comprehensive overview for holistic intervention strategies and multidimensional assessment across various ocular conditions, while offering valuable insights for future research and development from a lactylation perspective.}, }
@article {pmid41830174, year = {2026}, author = {Jafar Hussain, HM and Wang, M and Yang, P and Tasharrofi, B and Li, Y and Clark, RL and Fale-Olsen, E and Waldow, G and Keramatipour, M and Asadollahi, M and Pennesi, ME and Chen, R}, title = {Bi-allelic Variants in AP5Z1 and AP5B1 lead to retinal degeneration.}, journal = {HGG advances}, volume = {}, number = {}, pages = {100584}, doi = {10.1016/j.xhgg.2026.100584}, pmid = {41830174}, issn = {2666-2477}, abstract = {Inherited retinal diseases (IRDs) comprise a diverse group of disorders that frequently lead to progressive vision impairment and blindness. Despite advances in genetic testing, a significant number of IRD cases remain genetically unsolved, often due to unidentified disease-associated genes or variants. This study aims to report additional cases for the newly discovered IRD genes of the AP5-complex. A comprehensive ophthalmological evaluation was performed for all patients, including retinal imaging (multimodal imaging), visual field testing and electroretinogram (ERG) testing. Whole genome and exome sequencing (WGS &amp; WES) were performed for clinically unsolved IRD patients, and data were analyzed to identify underlying causal variants. The identified variants were subsequently validated using Sanger sequencing. Five unrelated patients from Europe and Iran were identified with a distinctive macular degeneration associated with bi- allelic variants in AP5Z1 (HGNC: 22197) and AP5B1 (HGNC: 25104), subunits of the vesicular fifth adaptor protein (AP-5) complex. AP-5 complex is the part of the intracellular trafficking machinery thought to be involved in cellular homeostasis and lysosomal functioning in the retinal pigment epithelium (RPE). The identification of bi-allelic variants in two proteins of AP-5 complex expand the characterization of AP-5 genes in sustaining and preserving normal macular function.}, }
@article {pmid41830184, year = {2026}, author = {Germano-Morrel, CS and Tomishige, KS and Macchione, RM and Ottaiano-Poli, PA and Kasahara, N}, title = {Comparison of the illness perception between age-related macular degeneration and glaucoma patients living in a middle-income country.}, journal = {Journal of health psychology}, volume = {}, number = {}, pages = {13591053261430435}, doi = {10.1177/13591053261430435}, pmid = {41830184}, issn = {1461-7277}, abstract = {The aim of this cross-sectional study was to compare the cognitive and emotional representations of illness in patients with primary open angle glaucoma (POAG) and age-related macular degeneration (AMD) living in a developing country. All subjects answered the Brief Illness Perception Questionnaire (Brief IPQ) to assess mental defeat. The summed scores were compared among the groups with the ANOVA test. The sample comprised 60 patients with AMD, 64 with POAG and 60 controls. Both AMD and POAG patients scored higher than controls (50.4 ± 10.5, 49.5 ± 14.4, and 10.7 ± 17.6, respectively, p < 0.000). The difference between AMD and POAG did not reach statistical significance (Tukey HSD p = 0.978). Despite different diseases, POAG and AMD patients had similar illness perceptions in a cohort of patients living in a developing country. These results can help patients to take actions to regulate their emotions and improve treatment outcomes of their illness.}, }
@article {pmid41830999, year = {2026}, author = {Neri, G and Bacherini, D and Mastropasqua, R and Dolz-Marco, R and Gallego-Pinazo, R and Reiter, GS and Reibaldi, M and Borrelli, E}, title = {OCTA in age-related macular degeneration: consensus on practical guidelines for optimal imaging strategies across different clinical scenarios.}, journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie}, volume = {}, number = {}, pages = {}, pmid = {41830999}, issn = {1435-702X}, }
@article {pmid41832250, year = {2026}, author = {Demarinis, G and Yeung, I and Preston, E and Patel, PJ and Huemer, J and Hamilton, RD and Nicholson, L and Tucker, WR and Montesel, A}, title = {Clinical spectrum of intraocular inflammation following faricimab intravitreal injections: evidence from a large real-life cohort in the United Kingdom.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {41832250}, issn = {1476-5454}, abstract = {OBJECTIVE: To describe the clinical findings and report the incidence of patients developing non-infectious intraocular inflammation (IOI) following intravitreal faricimab injections (IVFs).<br><br>METHODS: A retrospective review of electronic medical records was conducted for patients receiving faricimab intravitreal injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO) at Moorfields Eye Hospital, London, United Kingdom, over a 24-month period.<br><br>RESULTS: 3985 eyes from 3151 patients were included and underwent a total of 28,535 IVFs (20,982 for nAMD, 7553 for DMO). 57 eyes from 46 patients presented at least one episode of IOI. The 2-year estimated incidence of IOI was 0.20% [95% CI 0.15-0.26] per injection, 1.43% [95% CI 1.08-1.85] per eye and 1.46% [95% CI 1.07-1.94] per patient. Mean visual acuity (VA) was significantly different between the day of IVF (0.48&#x2009;&#xb1;&#x2009;0.43 logMAR, range: 0-1.8) and the day of IOI diagnosis (0.67&#x2009;&#xb1;&#x2009;0.52, range: 0-2.3) (p&#x2009;<&#x2009;0.001). VA after IOI resolution showed no significant difference from baseline (p&#x2009;>&#x2009;0.99). Intravitreal injections were resumed in 42 eyes. IVFs re-challenge was attempted in 9 eyes, with 5 developing another episode of IOI.<br><br>CONCLUSIONS: This study describes one of the largest reported cohorts of IOI cases following faricimab treatment. It confirms that the incidence of IOI is rare and aligns with the rates of IVF-related adverse effects reported in clinical trials and in recent real-world studies. Overall, faricimab demonstrated a favourable safety profile with good prognosis in cases of IOI.}, }
@article {pmid41832694, year = {2026}, author = {Krishnaswami, V and Janakiraman, K and Sethuraman, V and Raja, J}, title = {Nanomicelles in Ocular Drug Delivery: Overcoming Barriers and Enhancing Therapeutic Efficacy.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128416157251203061416}, pmid = {41832694}, issn = {1873-4286}, abstract = {This study provides a comprehensive overview of nanomicelle-based drug delivery methods used to treat ocular disorders. A review of current literature was conducted by scanning electronic databases up until December 2024, including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as "Nanomicelles" and specific ocular conditions including "Glaucoma," "Conjunctivitis," "Cataract," and "Retinopathy" were used to identify relevant material. Original research articles, reviews, and clinical trials were given special attention. Administering drugs to the eye remains one of the most challenging tasks among various drug delivery systems. Delivering drugs to the posterior pole or the delicate anatomical layers of the eye poses a substantial challenge for researchers and pharmacologists. Conventional formulations often exhibit inadequate corneal penetration, poor absorption, or noticeable adverse visual effects. Nanotechnology has greatly facilitated the development of novel therapeutic strategies for ocular disorders. Nanomicelle-based formulations benefit significantly from the nano-delivery platform. Nanomicelles can overcome anatomical barriers and clearance processes. Depending on the polymer used, nanomicelles can be engineered and released to meet specific requirements. They are notable for their small size, low toxicity, ability to improve drug penetration through ocular epithelia with minimal irritation, enhancement of hydrophobic drug solubility, achievement of therapeutic concentrations, and prevention or reduction of drug degradation. This study highlights the use of nanomicellar-based delivery systems in treating ocular diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, cataract, conjunctivitis, keratitis, and retinoblastoma.}, }
@article {pmid41835293, year = {2026}, author = {Chakraborty, S and Sheth, JU and Ganguly, S and Reddy, R}, title = {Vitrectomy with Subretinal Tissue Plasminogen Activator for Submacular Hemorrhage: A Multicenter Retrospective Analysis of Functional and Anatomical Outcomes Across Multiple Etiologies.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {589150}, pmid = {41835293}, issn = {1177-5467}, abstract = {PURPOSE: To evaluate visual and anatomical outcomes of pars plana vitrectomy (PPV) with subretinal tissue plasminogen activator (tPA) and gas or air tamponade for large submacular haemorrhage (SMH>4 disc diameters) of varied etiologies and assess postoperative anti-vascular endothelial growth factor (anti-VEGF) requirements in a multicenter real-world cohort.<br><br>PATIENTS AND METHODS: This retrospective, two-center study included 32 eyes undergoing PPV with subretinal tPA (25-50 &#xb5;g/0.1-0.2 mL) and SF6 or air tamponade, followed for &#x2265;6 months. The primary outcome was change in best-corrected visual acuity (BCVA). Secondary outcomes included central macular thickness (CMT), SMH dimensions, subretinal/intraretinal fluid (SRF/IRF) status, intraocular pressure (IOP), and anti-VEGF use.<br><br>RESULTS: Mean patient age was 60.8 &#xb1; 19.1 years; etiologies included polypoidal choroidal vasculopathy (PCV; 53.1%), neovascular age-related macular degeneration (nAMD; 28.1%), trauma (12.5%), and retinal artery macroaneurysm (RAM; 6.3%). BCVA improved significantly from 1.13 &#xb1; 0.30 to 0.56 &#xb1; 0.26 logMAR (P<0.001), with 55.2% gaining &#x2265;3 lines. CMT reduced from 501 &#xb1; 219 to 276 &#xb1; 70&#xa0;&#xb5;m (P<0.001), and SMH size decreased from 5 &#xb1; 2 to 0 disc diameters by 6 months. SRF resolved in 65.65% of eyes (P<0.001), while IRF remained stable (P=0.51). IOP normalized after a transient 1-month rise. Mean anti-VEGF use was 1.2 injections/eye (bevacizumab 88.2%, brolucizumab 11.8%). No major complications occurred; one transient vitreous hemorrhage and three cataract progressions were noted.<br><br>CONCLUSION: PPV with subretinal tPA achieved rapid hemorrhage clearance, significant visual gain, and durable anatomical restoration with minimal complications and limited anti-VEGF need. It offers an effective, safe option for large SMH across etiologies, enabling timely foveal recovery and improved long-term functional outcomes.}, }
@article {pmid41835799, year = {2026}, author = {Shiromani, S and Chhablani, J}, title = {Deep learning in geographic atrophy: rethinking age-related macular degeneration progression and treatment.}, journal = {Annals of translational medicine}, volume = {14}, number = {1}, pages = {7}, pmid = {41835799}, issn = {2305-5839}, }
@article {pmid41837474, year = {2026}, author = {Cho, M and Lee, J and Kim, Y and Kim, YJ and Doguer, C and Kim, M and Ha, JH}, title = {Hot-Air-Dried Eruca sativa Mill. Extracts Prevent Retinal Inflammation and Unfolded Protein Responses in ARPE-19 Cells.}, journal = {Journal of medicinal food}, volume = {29}, number = {2}, pages = {91-101}, doi = {10.1177/1096620X251412888}, pmid = {41837474}, issn = {1557-7600}, mesh = {Humans ; *Plant Extracts/pharmacology ; Endoplasmic Reticulum Stress/drug effects ; *Unfolded Protein Response/drug effects ; Cell Line ; *Retinal Pigment Epithelium/drug effects/immunology/cytology ; NF-kappa B/genetics/immunology ; Vascular Endothelial Growth Factor A/genetics/immunology/metabolism ; Tumor Necrosis Factor-alpha/genetics/immunology ; Apoptosis/drug effects ; *Diabetic Retinopathy/drug therapy/genetics/immunology ; *Macular Degeneration/drug therapy/genetics/immunology ; Inflammation ; Lipopolysaccharides ; }, abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) constitute leading causes of irreversible visual impairment; both are pathologically linked to chronic inflammation and endoplasmic reticulum (ER) stress in retinal pigment epithelial (RPE) cells. This study aimed to investigate the protective effects of hot-air-dried Eruca sativa Mill. extract (ESH) on lipopolysaccharide (LPS)- and thapsigargin (Tg)-induced inflammatory and ER stress responses, respectively, in ARPE-19 cells. ESH pretreatment significantly suppressed LPS-induced phosphorylation of nuclear factor kappa B (NF-κB), inhibitor of kappa B alpha, and c-Jun N-terminal kinase, indicating effective inhibition of inflammatory signaling cascades. At the transcriptional level, ESH markedly attenuated the expression of tumor necrosis factor-α mRNA, suggesting downstream prevention of NF-κB-mitogen-activated protein kinase-mediated inflammatory gene activation. Under ER stress conditions, ESH significantly attenuated the upregulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein and X-box binding protein-1, along with reductions in the expressions of cleaved caspase-3 and -9, indicating mitigation of ER stress-associated retinal apoptosis. Additionally, ESH prevented Tg-inducible vascular endothelial growth factor (VEGF) mRNA expression, VEGF protein secretion, and intracellular calcium level. Strong positive correlations were observed between intracellular calcium and VEGF secretion (r = 0.888), and between VEGF mRNA and protein levels (r = 0.843), supporting a potential mechanistic link. Collectively, these findings demonstrate that ESH modulates inflammatory, ER stress, apoptotic, and angiogenic pathways, suggesting its potential as a functional dietary supplement to mitigate RPE dysfunction in AMD and DR.}, }
@article {pmid41837572, year = {2026}, author = {Pfau, M}, title = {Introducing Christine A. Curcio and Cynthia Owsley, the 2025 Recipients of the Proctor Medal.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {35}, pmid = {41837572}, issn = {1552-5783}, mesh = {*Awards and Prizes ; Humans ; *Ophthalmology/history ; History, 21st Century ; History, 20th Century ; *Macular Degeneration/history ; United States ; }, abstract = {Christine A. Curcio, PhD, and Cynthia Owsley, PhD, MSPH, have been jointly honored with the 2025 Proctor Medal by ARVO. This distinguished award recognizes their 40 years of pioneering contributions to vision science and ophthalmology, especially in uncovering the early stages of age-related macular degeneration (AMD). Their unique collaboration has effectively connected basic neuroscience with clinical psychophysics, greatly transforming scientific and clinical approaches to the early detection and prevention of AMD. In their Proctor Medal Lecture, titled "The Science of Rod-Mediated Dark Adaptation, an Outcome Measure for Age-Related Macular Degeneration," Drs. Curcio and Owsley combined insights from two research careers on retinal biology, visual function, aging, and AMD.}, }
@article {pmid41837573, year = {2026}, author = {Curcio, CA and Owsley, C}, title = {The Science of Rod-Mediated Dark Adaptation, an Outcome Measure for Age-Related Macular Degeneration: The 2025 Proctor Medal Lecture.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {34}, pmid = {41837573}, issn = {1552-5783}, mesh = {Humans ; *Macular Degeneration/physiopathology/diagnosis ; *Dark Adaptation/physiology ; *Retinal Rod Photoreceptor Cells/physiology ; Retinal Pigment Epithelium/pathology ; Awards and Prizes ; Tomography, Optical Coherence ; }, abstract = {Age-related macular degeneration (AMD) degrades central vision in older adults worldwide. To enable precision prevention and early intervention, the longitudinal Alabama Study of Age-related Macular Degeneration 2 (ALSTAR2) seeks functional and imaging outcomes at the aging-AMD interface. ALSTAR2 relies on accurate two-dimensional maps of photoreceptor and retinal pigment epithelium (RPE) distributions and a histology-informed, deposit-driven progression sequence involving dysregulated bi-directional transport between photoreceptors and circulation. This transport is globally assessed by rod-mediated dark adaptation (RMDA), a dynamic measure of rod sensitivity recovery after exposure to a bright light. RMDA measured at the rim of the high-risk macula lutea is affected earlier and is more predictive of AMD onset and progression than steady-state functional measures of rods, cones, and neural circuitry, in both tested and fellow eyes. Delayed RMDA incorporates the Oil Spill hypothesis of drusen formation, which posits that lipoprotein particles constitutively released by RPE are trapped by aged Bruch's membrane and choriocapillaris. Subretinal drusenoid deposit, associated with poor RMDA and risk for advanced AMD, may represent a late-appearing barrier to transport at the level of the RPE. Although RMDA slowing is already underway before routinely visible AMD pathology, some structural and metabolic imaging technologies may assist early detection.}, }
@article {pmid41837574, year = {2026}, author = {Sharma, A and Kizy, S and Singh, NK}, title = {Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {33}, pmid = {41837574}, issn = {1552-5783}, mesh = {Humans ; *Retinal Neovascularization/metabolism/genetics ; *RNA, Untranslated/physiology ; Animals ; *Lipid Metabolism/physiology ; Signal Transduction ; *Lipids/physiology ; Vascular Endothelial Growth Factor A/metabolism ; Retinal Pigment Epithelium/metabolism ; Angiogenesis ; }, abstract = {Pathological retinal neovascularization is a prevalent cause of blindness, impacting millions of individuals across all age groups, from infants to older adults. It is a key clinical feature of several retinal diseases, such as diabetic retinopathy (DR), retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and Coats disease. Researchers have extensively investigated the involvement of vascular endothelial growth factor (VEGF) signaling, hypoxia inducible factor (HIF) signaling, and inflammation in the regulation of pathological retinal neovascularization. Recent breakthroughs have demonstrated the influence of several substances and cells in the retina on the regulation of pathological retinal neovascularization. This review emphasizes the rising significance of substances such as lipid mediators, non-coding ribonucleic acids, as well as the involvement of several retinal cell types, including endothelial cells (ECs), pericytes, glial cells, and the retinal pigment epithelium (RPE) in the regulation of pathological neovascularization. Here, we emphasize the interactions among these cell types in maintaining retinal homeostasis and their role in abnormal neovascularization in diseases like DR, AMD, ROP, etc. This review aims to highlight the importance of molecules and cells that go beyond the VEGF-centric therapeutic focus to treat pathological neovascularization.}, }
@article {pmid41838271, year = {2026}, author = {Das, T and Jalali, S and Jonas, J and Kawasaki, R and Saw, SM and Sivaprasad, S and Tan, ACS and Ruamviboonsuk, P}, title = {From Science and Technology to Eye-Health Policy: A Review on Global and Asia-Pacific Strategies on the Prevention of Blindness from Retinal Diseases.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41838271}, issn = {2193-8245}, abstract = {The World Health Organization (WHO) is making a concerted effort to enhance health, including eye health and overall well-being. This global effort has resulted in a reduced age-standardized prevalence of avoidable blindness and no increase in avoidable moderate and severe vision impairment. However, the absolute number of cases has increased for both avoidable blindness and moderate-to-severe vision impairment. Globally, the leading causes of visual impairment include uncorrected refractive errors and cataract, though many retinal conditions equally contribute. All causes of blindness and moderate-to-severe visual impairment are higher in low- and middle-income countries, including many in the Asia-Pacific region. This inequality could be reduced by harmonizing science and technology and translating them into regulatory policy to close the care loop.This review aimed to provide a perspective on the disease burden of common retinal conditions such as diabetic retinopathy, age-related macular degeneration, myopia, and retinopathy of prematurity; the latest science and technology for diagnosing and treating these conditions; and recommendations to translate them into national policy. We also reviewed the WHO's global policy and targets related to the United Nations Sustainable Development Goals, recommended to prevent global blindness by the year 2030. The national health and eye care systems, from primary to tertiary care, in an Asia-Pacific country, which align with "Integrated People-Centered Eye Care" proposed by WHO, are also reviewed.}, }
@article {pmid41840324, year = {2026}, author = {Sharma, A and Sheth, JU and Kuppermann, BD}, title = {Anti-Vascular Endothelial Growth Factor Biosimilars for Use in the Aging Eye.}, journal = {Drugs &amp; aging}, volume = {}, number = {}, pages = {}, pmid = {41840324}, issn = {1179-1969}, abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapies have revolutionized the treatment of neovascular age-related macular degeneration (nAMD), a leading cause of vision loss, in addition to other retinal vascular diseases such as diabetic macular edema (DME), retinal vein occlusions (RVO). Biosimilars, which are nearly identical versions of original biologic drugs, offer a promising alternative to these costly treatments. Several biosimilars for anti-VEGF drugs including bevacizumab, ranibizumab, and aflibercept are in various stages of development and approval (e.g. Afilivu, Yesafili, Enzeevu, Ahzantive, AVT-06, ABP 938, and ALT L9). These biosimilars have shown comparable results in improving visual acuity and reducing retinal fluid in patients with nAMD but their adoption in clinical practice faces challenges, including regulatory hurdles, physician and patient acceptance, and the need for extensive post-marketing surveillance to monitor long-term safety and efficacy. However, as more data becomes available and biosimilars gain approval, they are expected to become an integral component in the management of nAMD. This review explores the current landscape of anti-VEGF biosimilars, their clinical efficacy, safety profiles, and the economic implications for treating the aging eye. It also addresses the challenges and future directions in the integration of biosimilars into routine ophthalmic practice.}, }
@article {pmid41840936, year = {2026}, author = {Cho, YJ and Kook, KY and Park, DH and Ji, YS}, title = {Effectiveness Of Ultrathin 40-Gauge Needles for Intravitreal Injections.}, journal = {Korean journal of ophthalmology : KJO}, volume = {}, number = {}, pages = {}, doi = {10.3341/kjo.2025.0134}, pmid = {41840936}, issn = {2092-9382}, abstract = {PURPOSE: To compare pain perception and immediate post‑procedural complications of intravitreal injections (IVIs) performed with conventional 30‑gauge (30 G) needles versus ultrathin 40‑gauge (40 G) needles.<br><br>METHODS: &#x2003;This single center, retrospective crossover study reviewed consecutive patients who underwent serial IVIs for neovascular age related macular degeneration, diabetic macular edema, retinal vein occlusion, myopic choroidal neovascularization, or other indications between April and October 2020. Each patient received one injection with a 30&#x202f;G needle and one with a 40&#x202f;G needle-either to the fellow eye on the same day or to the same eye one month apart. Injections (0.05&#x202f;mL bevacizumab, ranibizumab, or aflibercept) were administered in an operating room by a single surgeon following Avery et&#x202f;al. guidelines. Pain was recorded immediately post injection on a visual analogue scale (VAS). Subconjunctival hemorrhage (SCH) and vitreous reflux (VR) were graded 0-4.<br><br>RESULTS: &#x2003;Mean age was 69.3&#x202f;&#xb1;&#x202f;11.5&#x202f;years; 69&#x202f;% were men. VAS pain scores were significantly lower with 40&#x202f;G needles than with 30&#x202f;G needles (2.33&#x202f;&#xb1;&#x202f;1.26 vs&#x202f;4.02&#x202f;&#xb1;&#x202f;1.73; mean paired difference -1.69&#x202f;&#xb1;&#x202f;0.33; p&#x202f;<&#x202f;0.001). Median VR grade declined from&#x202f;2 (IQR&#x202f;2-3) to&#x202f;0 (IQR&#x202f;0-1) with 40&#x202f;G needles (p&#x202f;<&#x202f;0.001). SCH grade did not differ between gauges (median&#x202f;0, IQR&#x202f;0-1; p&#x202f;=&#x202f;0.93). No injection related adverse events occurred.<br><br>CONCLUSIONS: &#x2003;Using an ultrathin 40&#x202f;G needle for IVIs significantly reduces patient&#x2011;reported pain and vitreous reflux without increasing subconjunctival hemorrhage. These findings support the integration of 40 G needles into routine IVI practice to enhance long-term patient adherence and treatment efficacy.}, }
@article {pmid41841063, year = {2026}, author = {Pagán-Melvin, C and Izquierdo, N and Alejandro, KC}, title = {Clinical Validation of a CRX Variant Leading to a Cone-Rod Dystrophy.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103528}, pmid = {41841063}, issn = {2168-8184}, abstract = {Patients with cone-rod dystrophy (CORD) due to CRX mutations have progressive visual impairment characterized by central vision loss, photophobia, and color vision defects. On ophthalmic examination, patients with CRX-associated CORD may have macular abnormalities, changes in the retinal pigment epithelium, and progressive macular degeneration, affecting central visual function. Variants in the CRX gene located on chromosome 19q13 lead to photoreceptor dysfunction and retinal degeneration. Variant classification in CRX presents unique challenges, as approximately half of heterozygous missense variants may be benign, requiring careful phenotype-genotype correlation for accurate pathogenicity determination. Our patient had progressive vision loss, bilateral macular abnormalities, and visual symptoms compatible with CORD. The patient's clinical findings included central visual field defects, reduced multifocal electroretinography responses, and preserved full-field electroretinography consistent with macular-restricted disease. Next-generation sequencing showed a heterozygous, likely pathogenic variant c.166G>A (p.Ala56Thr) located within the homeodomain at residue 56. Comprehensive ophthalmic examination, electrophysiological testing, and genetic studies may all help reach a CORD diagnosis. This case highlights the importance of phenotype-driven variant interpretation for reclassifying CRX variants from "likely pathogenic" to "pathogenic" and raises clinical awareness for the critical role of genotype-phenotype concordance in inherited retinal dystrophies.}, }
@article {pmid41841116, year = {2026}, author = {Kaganovski, A and Bhuiyan, A and Kasi, A and Kamyab, D and Grinberg, A and Chen, S and Thomson, R and Bhuiyan, T and Govindaiah, A and Deobhakta, A and Lema, G and Tai, K and Weissman, MA and Amoruso, L and Smith, RT}, title = {Elevated prevalence of age-related macular degeneration in a low-income urban primary care setting.}, journal = {Discover public health}, volume = {23}, number = {1}, pages = {321}, pmid = {41841116}, issn = {3005-0774}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss among adults over 50. Early detection enables interventions such as Age-Related Eye Disease Study (AREDS) supplementation to slow disease progression, yet AMD remains underdiagnosed in primary care, particularly in underserved populations. This study assessed AMD sample prevalence and its association with social determinants of health in a diverse, urban primary care cohort.<br><br>METHODS: We performed a post hoc analysis of a cross-sectional study conducted from June 2020 to May 2023 at a hospital-based primary care clinic in New York City (NYC). Patients aged 50-89 underwent nonmydriatic color fundus photography graded independently by two physicians using Beckman Initiative criteria. Median household income by ZIP code served as a proxy for socioeconomic position. Multivariable logistic regression examined associations between AMD and demographic or social determinants of health variables.<br><br>RESULTS: Of 393 patients enrolled, 312 were included in the final analysis. Referable AMD was present in 48.4% of participants based on the Beckman classification, representing the sample prevalence within this clinic cohort and exceeding national population-based estimates. Only 4 of 151 AMD cases had been previously diagnosed. Referable AMD prevalence was higher in males than females (56.2% vs. 44.4%) and increased with age. Median household income was significantly lower among patients with referable AMD compared with those without ($72,000 vs. $151,000; p&#x2009;<&#x2009;0.0001). In adjusted models, male sex (OR&#x2009;=&#x2009;2.00, 95% CI 1.02-4.00) and lower income were strongly associated with referable AMD prevalence; race and age were not.<br><br>CONCLUSION: Undiagnosed referable AMD was highly prevalent within this primary care clinic sample of low-income, urban patients. Integrating affordable retinal screening, potentially aided by artificial intelligence, into primary care may help address vision health disparities driven by social determinants of health.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12982-026-01672-0.}, }
@article {pmid41841652, year = {2026}, author = {Chen, CH and Lin, CW and Wu, SH and Yang, ZW and Lin, CW and Shen, YC and Cheng, YW and Su, MW and Tang, SC}, title = {NOTCH3 Pathogenic Variant and Risk of Age-Related Macular Degeneration: Findings From the Taiwan Biobank and Small Vessel Disease Registry.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {37}, pmid = {41841652}, issn = {1552-5783}, mesh = {Humans ; *Receptor, Notch3/genetics/metabolism ; Female ; Male ; Taiwan/epidemiology ; *Macular Degeneration/genetics/epidemiology ; Middle Aged ; Aged ; Registries ; Risk Factors ; Biological Specimen Banks ; Prevalence ; *Mutation ; }, abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of central vision loss involving retinal microvascular dysfunction. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary small vessel disease caused by NOTCH3 mutations, primarily affects the cerebral vasculature but may also involve the retinal microvasculature. This study investigated the association between the NOTCH3 R544C variant and AMD using the Taiwan Biobank and validated the findings in a hospital-based cohort.<br><br>METHODS: In the Taiwan Biobank, individuals carrying the NOTCH3 R544C variant were matched with noncarriers (1:10) by demographic and cardiovascular factors. Odds ratios (ORs) for self-reported AMD and other eye diseases were calculated. Validation was performed in the Taiwan-Associated Genetic and Non-Genetic Small Vessel Disease (TAG-SVD) cohort, including 64 NOTCH3 R544C carriers and 84 age-matched controls who underwent ophthalmic evaluation.<br><br>RESULTS: In the Taiwan Biobank, NOTCH3 R544C carriers (n = 1134) had higher prevalence rates of stroke (OR = 2.23; 95% confidence interval [CI], 1.30-3.84), family history of stroke (OR = 2.05; 95% CI, 1.78-2.35), and AMD (OR = 2.26; 95% CI, 1.38-3.71) compared with matched controls (n = 11,340), but not of other eye diseases. Individuals with AMD were older and more likely to have diabetes, higher fasting glucose, HbA1c, total cholesterol, and low-density lipoprotein levels. Multivariate analysis identified age (OR = 1.06; 95% CI, 1.01-1.11) and diabetes (OR = 5.51; 95% CI, 1.84-14.79) as independent correlates. In the TAG-SVD cohort, AMD prevalence was higher in carriers (23.4%) than in controls (13.1%), although not statistically significant (P = 0.10).<br><br>CONCLUSIONS: The NOTCH3 R544C variant may be associated with an increased risk of AMD, warranting further studies to clarify the underlying mechanisms.}, }
@article {pmid41841653, year = {2026}, author = {Nodecker, KN and Romano, F and Stettler, I and Shah, S and Ploumi, I and Cort, T and Ding, X and Chen, C and Zhu, Y and Nigalye, A and Choi, H and Gumustop, S and Bannerman, A and Vingopoulos, F and Laíns, I and Miller, JW and Vavvas, DG and Husain, D and Miller, JB}, title = {Reduced Macular Pigment Optical Volume Is Linked to High-Risk OCT Biomarkers and Lower Contrast Sensitivity Function in iAMD.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {36}, pmid = {41841653}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Macular Pigment/metabolism ; Biomarkers/metabolism ; *Contrast Sensitivity/physiology ; Visual Acuity/physiology ; *Retinal Pigment Epithelium/pathology ; Middle Aged ; Aged, 80 and over ; *Macular Degeneration/physiopathology ; Macula Lutea ; }, abstract = {PURPOSE: To investigate relationships among macular pigment optical volume (MPOV), optical coherence tomography (OCT) biomarkers, and contrast sensitivity (CS) measured by the quantitative contrast sensitivity function (qCSF) test in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: Sixty-five eyes from 34 patients with OCT-confirmed iAMD, visual acuity (VA) >20/100, and no confounding comorbidities underwent same-day qCSF testing (area under the logarithmic CS function [AULCSF], contrast acuity [CA], and CS at 1-18 cycles per degree [cpd]), MPOV imaging, and macular OCT. OCT features evaluated within the central 3-mm circle included outer nuclear layer (ONL) thickness, retinal pigment epithelium (RPE) volume, subretinal drusenoid deposits, hyporeflective drusen cores (hDCs), intraretinal hyperreflective foci, and incomplete RPE and outer retinal atrophy (iRORA). MPOV was quantified at 1&#xb0;, 2&#xb0;, and 9&#xb0; eccentricities (plateau set at 9&#xb0;). Generalized linear mixed-effects models assessed associations of MPOV with OCT biomarkers and qCSF metrics.<br><br>RESULTS: Lower MPOV values were associated with reduced ONL thickness (&#x3b2;*, 0.343-0.424; all P < 0.01), presence of hDCs (&#x3b2;*, -0.80 to -0.60; all P < 0.01), and iRORA at 1&#xb0; (&#x3b2;*, -0.43; P = 0.03). MPOV at all eccentricities was associated with lower AULCSF (&#x3b2;*, 0.32-0.45), CA (&#x3b2;*, 0.38-0.48), and CS at 3 cpd and 6 cpd (&#x3b2;*, 0.39-0.69; all P < 0.05), but not with VA (&#x3b2;*, 0.10-0.28; all P > 0.05).<br><br>CONCLUSIONS: MPOV was significantly associated with high-risk OCT biomarkers and qCSF-derived CS metrics in iAMD, highlighting its potential role as a biomarker of structural integrity and functional impairment not captured by standard VA testing.}, }
@article {pmid41841662, year = {2026}, author = {Janetos, TM and Gill, MK and French, DD}, title = {Associations Between Social Determinants of Health and Treatment of Exudative Age-Related Macular Degeneration: A Retrospective Cohort Analysis.}, journal = {Ophthalmic epidemiology}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/09286586.2026.2645106}, pmid = {41841662}, issn = {1744-5086}, support = {K12 TR005104/TR/NCATS NIH HHS/United States ; }, abstract = {PURPOSE: To evaluate associations between social determinants of health (SDOH) and treatment rates among patients with exudative age-related macular degeneration (exAMD).<br><br>METHODS: Retrospective cohort study of patients with exAMD utilizing data from the NIH All of Us Research Program. The primary outcome was annual rate of intravitreal injections abstracted from the EHR. Negative binomial regression was used to assess associations between the treatment rate and individual SDOH constructs developed from survey responses among other sociodemographic factors, adjusting for bilateral disease status and follow-up duration. An exploratory factor analysis (EFA) of all SDOH constructs was performed to identify potential latent constructs associated with the primary outcome.<br><br>RESULTS: Among sociodemographic factors, Black individuals had significantly lower injection rates (IRR: 0.32, 95% CI: 0.13-0.79) compared to White individuals. When correcting for multiple comparisons, among the SDOH constructs, there were none that were significantly associated with treatment rate. Within the exploratory factor analysis, a factor identified by poor English proficiency, transportation difficulty, rural care access issues, worse health literacy, and provider concordance issues was associated with a significantly decreased rate of treatment (IRR: 0.73, 95% CI: 0.55-0.96), as well as a factor identified by high neighborhood disorder, high loneliness, high perceived health care and everyday discrimination, and high stress (IRR: 0.74, 95% CI: 0.60-0.92).<br><br>CONCLUSIONS: This study identifies significant racial disparities and SDOH constructs associated with exAMD treatment rates. These findings underscore the complexity of sociodemographic influences on treatment and suggest potential inequities which warrant additional study.}, }
@article {pmid41842764, year = {2026}, author = {Whang, K and Garg, I and Harel, ID and Katz, R and Cui, Y and Zeng, R and Duich, M and Wescott, HE and Koch, T and Bannerman, A and Baldwin, G and Nigalye, A and Lains, I and Eliott, D and Patel, NA and Kim, LA and Vavvas, DG and Miller, JW and Hussain, D and Miller, JB}, title = {Comparative Study of Swept-source Optical Coherence Tomography Angiography Metrics Between Eyes With Adult Onset Vitelliform Dystrophy, Age-related Macular Degeneration, and Healthy Controls.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-8}, doi = {10.3928/23258160-20260122-02}, pmid = {41842764}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to investigate swept-source OCT angiography (SS-OCTA) metrics in adult-onset foveovitelliform dystrophy (AOFVD), intermediate age-related macular degeneration (iAMD), and healthy control eyes.<br><br>PATIENTS AND METHODS: A cross-sectional study analyzing SS-OCTA foveal avascular zone (FAZ), vessel skeletonized density (VSD), and vessel density (VD) using the ARI network was conducted. A mixed-effects multiple regression model adjusting for age was used for statistical analyses.<br><br>RESULTS: The cohort included 204 eyes of 125 patients (control, n = 63; iAMD, n = 93; AOFVD, n = 48). Compared to iAMD, AOFVD eyes had significantly reduced VD, VSD, and FAZ circularity on 3 &#xd7; 3-mm and 6 &#xd7; 6-mm angiograms, and significantly increased FAZ area and FAZ perimeter on 6 &#xd7; 6-mm angiograms. There was no difference on 12 &#xd7; 12-mm angiograms. Compared to controls, AOFVD eyes had significantly reduced FAZ circularity on 3 &#xd7; 3-mm angiograms.<br><br>CONCLUSION: SS-OCTA metrics may help in distinguishing AOFVD from iAMD.}, }
@article {pmid41842765, year = {2026}, author = {Mohan, N and Schulgit, MJ and Bellanda, V and Barbosa, GCS and Szigiato, A and Talcott, KE and Mammo, DA and Babiuch, AS and Kaiser, PK and Ehlers, JP and Rachitskaya, A and Yuan, A and Srivastava, SK and Sharma, S}, title = {Long-term Outcomes of Faricimab in Previously Treated Neovascular Age-related Macular Degeneration.}, journal = {Ophthalmic surgery, lasers &amp; imaging retina}, volume = {}, number = {}, pages = {1-7}, doi = {10.3928/23258160-20260127-02}, pmid = {41842765}, issn = {2325-8179}, abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate long-term outcomes of intravitreal faricimab injections (IFIs) in previously treated neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This retrospective cohort included 204 eyes from 178 patients with nAMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Clinical and imaging data were collected at baseline, after three injections, 1 year, 2 years, and final follow-up.<br><br>RESULTS: Patients were followed for 2.5 &#xb1; 0.3 years. Central subfield thickness decreased from 267.6 &#xb1; 61.0 &#xb5;m to 225.8 &#xb1; 42.1 &#xb5;m (P < .001), and treatment intervals extended from 6.5 &#xb1; 2.4 to 11.5 &#xb1; 8.0 weeks (P < .001). Intraretinal fluid declined from 44.5% to 29.5% (P = .048) and subretinal fluid from 67.5% to 36.8% (P < .001), while vision and pigment epithelial detachment height remained stable. Switching from faricimab to another agent provided no added benefit.<br><br>CONCLUSION: Faricimab demonstrated sustained anatomical improvement and treatment durability over 2.5 years, with a subset of patients showing lasting benefit.}, }
@article {pmid41844139, year = {2026}, author = {Kim, Y and Kim, YT and Kong, M and Kim, JH}, title = {Risk Factors and Quality of Life in Patients With Geographic Atrophy, a Late Stage of Age-Related Macular Degeneration: Findings From the Korea National Health and Nutrition Examination Survey.}, journal = {Journal of Korean medical science}, volume = {41}, number = {10}, pages = {e63}, pmid = {41844139}, issn = {1598-6357}, mesh = {Humans ; *Quality of Life ; Male ; Republic of Korea/epidemiology ; Female ; Aged ; Cross-Sectional Studies ; Risk Factors ; Nutrition Surveys ; *Geographic Atrophy/epidemiology/pathology/diagnosis/complications ; Middle Aged ; *Macular Degeneration/pathology/epidemiology ; Aged, 80 and over ; Smoking ; Diabetes Mellitus/epidemiology ; Adult ; }, abstract = {BACKGROUND: To evaluate the risk factors and quality of life (QoL) in geographic atrophy (GA) in a Korean population.<br><br>METHODS: This cross-sectional study, based on data from the Korea National Health and Nutrition Examination Survey (2017-2021), included 15,030 subjects aged &#x2265; 40 years. Participants were classified into four categories: early age-related macular degeneration (AMD) (n = 2,068), wet AMD (n = 94), GA (n = 36), and no AMD (n = 12,832). Demographics and activity limitations were compared across these groups. Additionally, the subjects' QoL was assessed using the EuroQoL-5 Dimension (EQ-5D) and Health-Related Quality of Life Instrument with 8 Items (HINT-8) methods.<br><br>RESULTS: Among the four groups, the GA group showed highest mean age (72.47 &#xb1; 7.45 years), prevalence of current smokers (61.11%), and prevalence of diabetes (41.67%). GA group reported activity limitations (16.67%) and vision problems (5.56%) at relatively higher rates compared to other groups. In the QoL assessment, the EQ-5D evaluation showed that the GA group experienced a similar decline in QoL as the wet AMD group (0.93 &#xb1; 0.02 vs. 0.93 &#xb1; 0.01; P = 0.971), while the HINT-8 evaluation indicated a relatively more severe QoL decline in GA group compared to wet AMD group (22.74 &#xb1; 3.70 vs. 20.35 &#xb1; 3.33; P = 0.007). GA group frequently reported difficulties with mobility (27.27%), usual activities (15.15%), and climbing stairs (61.54%), which were comparable to the frequencies observed in patients with wet AMD.<br><br>CONCLUSION: In South Korea, patients with GA tended to have relatively higher rates of current smoking and diabetes compared to individuals without GA. A decline in QoL in these patients was primarily associated with activity limitations. To improve patients' QoL, social support is needed to help overcome these activity limitations. Furthermore, it will be necessary to introduce therapeutic interventions to slow the progression of GA.}, }
@article {pmid41844146, year = {2026}, author = {Chotikavanich, S and Phisalprapa, P and Kositamongkol, C and Choopong, P and Eiamsamarng, A and Muneesri, P and Yingyong, R and Nujoi, W and Dongngam, S and Jai-Ai, J and Sarinak, N and Eksupapan, E and Sagan, S}, title = {Socioeconomic impact assessment of low vision and blindness on patients and households in Thailand.}, journal = {Clinical &amp; experimental optometry}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/08164622.2026.2641537}, pmid = {41844146}, issn = {1444-0938}, abstract = {CLINICAL RELEVANCE: Services for patients with low vision and blindness aim to improve their well-being. This can be achieved by understanding the effects of vision loss on all aspects of life, thereby enabling clinicians to design appropriate rehabilitation models.<br><br>BACKGROUND: This study explored the socioeconomic impact of low vision and blindness, mainly due to untreatable bilateral eye diseases, on individuals and their households.<br><br>METHODS: A cross-sectional study conducted at a low-vision clinic, in which participants were interviewed regarding socioeconomic changes following visual impairment. Multivariable logistic regression was used to identify predictors of income reduction.<br><br>RESULTS: A total of 110 patients (mean age 51.4&#x2009;&#xb1;&#x2009;14.6&#x2009;years) were enrolled. Retinitis pigmentosa was the leading cause of visual impairment (35.4%), followed by optic atrophy, glaucoma, and age-related macular degeneration. Following vision loss, 41.8% of patients became unemployed. A significant occupational shift occurred, with many transitioning from professionals to having no occupation (p&#x2009;<&#x2009;0.001). The primary monthly income of patients decreased significantly (p&#x2009;<&#x2009;0.001), and the proportion of patients with no income increased (7.3-50.9%). Multivariable analysis showed significant associations between primary income reduction and age groups of 31-40&#x2009;years (adjusted odds ratio [AOR] 10.7, 95% CI: 1.2-96.0, p&#x2009;=&#x2009;0.035), 51-60&#x2009;years (AOR 8.4, 95% CI: 1.2-59.9, p&#x2009;=&#x2009;0.034), and over 60&#x2009;years (AOR 46.5, 95% CI: 4.8-445.6, p&#x2009;<&#x2009;0.001). Although not significant, the income decline was greater in patients with poor visual acuity or large peripheral field loss than in those with central scotoma. Most patients had family caregivers who remained employed.<br><br>CONCLUSION: Low vision and blindness due to incurable bilateral eye disease were associated with substantial income loss and transition out of paid employment, underscoring the need for integrated rehabilitation and social protection policies to address functional and socioeconomic needs.}, }
@article {pmid41844666, year = {2026}, author = {Shen, J and Zhao, H and Fang, Y and Lv, X and Chen, L and Miao, Y and Wu, Z and Liu, N and Zhang, Q and Yang, Y and Chen, Q}, title = {Permeable nanoreactor eye drop for enzymatic cascade-mediated treatment for acute retinal injury model mimicking geographic atrophy.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-70761-0}, pmid = {41844666}, issn = {2041-1723}, abstract = {Geographic atrophy (GA), the most prevalent form of age-related macular degeneration (AMD), remains clinically challenging due to its complex pathogenesis. Using an acute retinal injury model that mimics GA pathology (oxidative stress-induced retinal apoptosis), we identify enzymatic cascade restoration as a promising therapeutic strategy. To overcome ocular delivery barriers, we engineer zwitterionic nanocages for co-delivering catalase (CAT) and superoxide dismutase (SOD) (Z(CAT&amp;SOD)). These optimized nanocages achieve a remarkable 9.32% ocular penetration rate, which significantly outperforms free peroxidase (0.54%), through conjunctival-sclera-retina and conjunctival-blood-retina penetration pathways, and achieve therapeutic efficacy comparable to intravitreal injection. In the chronic management of GA, the non-invasive Z(CAT&amp;SOD) eye drops show superior therapeutic effects to the current gold standard clinical antioxidants and lutein supplement. Therefore, this work reveals the possible association between retinal peroxidase deficiency and GA progression, and proposes a non-invasive, highly effective zwitterionic nanocage for AMD treatment.}, }
@article {pmid41844873, year = {2026}, author = {Cebatoriene, D and Vilkeviciute, A and Duseikaite-Vidike, M and Pileckaite, E and Bruzaite, A and Kriauciuniene, L and Zaliuniene, D and Liutkeviciene, R}, title = {Genetic variants and serum biomarkers of CXCL8, MAP3K7, LTA/TNF, EXOC3L1, PROCR, and TRAF2 in Age-Related macular degeneration: associations with disease risk and therapeutic response.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-42838-9}, pmid = {41844873}, issn = {2045-2322}, abstract = {Since age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in the aging population, it is a significant global health concern. Although anti-vascular endothelial growth factor (anti-VEGF) treatments are effective, not all patients respond to them fully. This study focuses on key single-nucleotide variants in the CXCL8 (rs2227306), MAP3K7 (rs157432), LTA/TNF (rs2229094), EXOC3L1 (rs868213), PROCR (rs867186), TRAF2 (rs10781522), and serum levels of these genes in AMD development and treatment response. It examines the genetic factors associated with susceptibility to AMD and how they influence response to therapy. The study investigates the relationships between specific genetic variations, serum protein levels, and both exudative and early AMD, as well as responses to anti-VEGF treatment. These findings may help guide risk assessment and personalized AMD therapies.}, }
@article {pmid41846907, year = {2026}, author = {Loya, A and Chen, V and Siddiqui, T and Rao, P and Chang, EY}, title = {Morphologic Changes of Macular Choroidal Neovascularization on OCT Angiography Following Faricimab Therapy in Patients With AMD.}, journal = {Journal of vitreoretinal diseases}, volume = {}, number = {}, pages = {24741264261427833}, pmid = {41846907}, issn = {2474-1272}, abstract = {Purpose: To describe morphologic changes on optical coherence tomography angiography (OCTA) in 4 eyes with exudative neovascular age-related macular degeneration (nAMD) after a switch in treatment from aflibercept to faricimab. Methods: A total of 4 eyes from 3 patients were evaluated. Results: Three patients (4 eyes) with nAMD were included. Treatment was switched to faricimab due to inadequate control of exudation or limited treatment interval extension with other antivascular endothelial growth factor (anti-VEGF) therapies. All eyes showed morphologic changes in macular neovascularization (MNV) on OCTA after the switch from aflibercept to faricimab. The MNV trunk persisted in all eyes, with regression of the lacy vasculature after treatment. Despite residual MNV, exudation was well controlled in all eyes at 9- to 11-week treatment intervals. Notably, morphologic changes were seen on OCTA even when structural findings remained largely unchanged. Conclusions: Long-term faricimab therapy is associated with distinct morphologic changes in MNV seen on OCTA that were not observed with other anti-VEGF therapies, highlighting the added value of OCTA for assessing treatment response.}, }
@article {pmid41847520, year = {2026}, author = {Johnson, EJ and Poteet, J and Gioia, N and Maharaj, RRL and Benitez-Del-Castillo, JM and Labetoulle, M}, title = {B Vitamins and Ocular Health.}, journal = {Clinical ophthalmology (Auckland, N.Z.)}, volume = {20}, number = {}, pages = {575752}, pmid = {41847520}, issn = {1177-5467}, abstract = {The B vitamins are a varied family whose members are integral to metabolic pathways and cellular processes throughout the body. Unlike vitamins A, C, and E, the B complex has generally not been considered among the key ingredients of supplements intended to maintain eye health and prevent age-related disease and vision loss. This perspective may be shifting with the emergence of 3 elements: (1) a greater understanding of the pathogenic mechanisms involved in conditions such as age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, dry eye disease, and other ocular surface disorders; (2) observational studies linking B vitamins to risk of eye disease development or progression; and (3) preclinical and clinical evidence supporting supplementation with B vitamins to improve potential ocular outcomes. This review synthesizes the available data on the role of B vitamins in promoting healthy eye structure and function, highlighting connections between individual vitamins and disease, and discussing the clinical considerations for B vitamin supplementation.}, }
@article {pmid41848365, year = {2026}, author = {Wang, CX and Wang, J and Hormel, TT and Hwang, TS and Lujan, BJ and Bailey, ST and Huang, D and Jia, Y}, title = {Volumetric and En Face Hyper-Reflective Henle Fiber Layer in Age-Related Macular Degeneration.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {67}, number = {3}, pages = {41}, pmid = {41848365}, issn = {1552-5783}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis/pathology ; Aged, 80 and over ; Fluorescein Angiography ; Geographic Atrophy ; Retinal Drusen ; Retinal Pigment Epithelium/pathology ; Middle Aged ; }, abstract = {PURPOSE: To analyze Henle fiber layer (HFL) hyper-reflectivity in age-related macular degeneration (AMD) with en face optical coherence tomography (OCT).<br><br>METHODS: A total of 279 eyes affected by AMD were imaged with either an Optovue Avanti or Optovue Solix device. Imaging was conducted within a 3 &#xd7; 3-mm area centered on the foveal avascular zone. Hyper-reflective HFL (hr-HFL) regions were segmented by binarizing en face OCT images generated by projecting a slab 45 to 65 &#xb5;m below the inner nuclear layer and outer plexiform layer boundary. Pathological changes, including drusen, subretinal fluid, pigment epithelial detachments (PEDs), macular neovascularization (MNV), and geographic atrophy (GA) were semi-automatically segmented. We investigated the association of these features with the hr-HFL by measuring the overlap ratios, defined as the proportion of hr-HFL area overlapping with the pathological regions after projection onto the same plane.<br><br>RESULTS: Hyper-reflective HFL regions were distinguished by distinct patterns in AMD eyes. It consistently colocalized with drusen, subretinal fluid, PEDs, MNV, and GA. Quantitatively, hr-HFL area was significantly larger in AMD eyes compared to healthy controls (P < 0.001) but did not differ across AMD severity stages. The hr-HFL area correlated with the size of pathologic features (r = 0.64-0.93; all P < 0.001), suggesting that the hr-HFL marks outer retinal abnormalities in AMD.<br><br>CONCLUSIONS: Hyper-reflective HFL regions are a robust marker of outer retinal pathology in AMD. Structural changes such as drusen, fluid, and atrophy likely alter HFL orientation, leading to hyper-reflectivity. Although not specific to any single pathology, the hr-HFL reliably reflects the presence of AMD-related pathological changes.}, }
@article {pmid41849558, year = {2026}, author = {Li, S and Zhang, E and Pan, J and Xu, Y and Zheng, K and Xu, X and Fang, Q}, title = {Usability Evaluation of a Macular Quantitative Square Grid Self-Examination Application in Patients With Macular Disease: Mixed Methods Study.}, journal = {JMIR human factors}, volume = {13}, number = {}, pages = {e79699}, pmid = {41849558}, issn = {2292-9495}, mesh = {Humans ; Female ; Male ; Aged ; Middle Aged ; *Self-Examination/methods ; *Macular Degeneration/diagnosis ; *Vision Disorders/diagnosis ; Diabetic Retinopathy/diagnosis ; Aged, 80 and over ; *Mobile Applications ; }, abstract = {BACKGROUND: Digital self-monitoring applications could provide individuals with macular disease with a convenient, quantitative method for tracking metamorphopsia at home; yet the usability of such tools remains to be fully established.<br><br>OBJECTIVE: This study evaluated the usability of a macular quantitative square grid self-examination application, a semiquantitative, touch-based self-monitoring application for macular function.<br><br>METHODS: This study used a convergent mixed methods design. The application quantifies (1) distortion severity, (2) distortion area, and (3) temporal trends through a 3-step touch interface. A total of 24 adults with neovascular age-related macular degeneration or diabetic macular edema, accompanied by self-reported metamorphopsia, participated in a single supervised test session. A 10-item System Usability Scale (SUS) was used to assess usability, and semistructured interviews were conducted to gather further insights. Quantitative data were summarized descriptively, and qualitative feedback underwent inductive thematic analysis.<br><br>RESULTS: A total of 24 participants completed the GridMacuScan application self-assessment, the SUS questionnaire, and 11 participants completed the interview when data saturation was achieved. All eyes that showed distortion on the Amsler grid also produced positive distortion maps on the GridMacuScan application, yielding 100% diagnostic concordance. The mean SUS score was 82.1 (SD 8.7), indicating "good-excellent" usability. The inductive thematic analysis yielded four overarching themes: (1) high usability and positive overall experience, (2) perceived functional advantages, (3) shortcomings and optimization suggestions, and (4) strong willingness for continued use.<br><br>CONCLUSIONS: The GridMacuScan application demonstrated diagnostic sensitivity comparable to that of the traditional Amsler grid and received high user ratings for usability. Furthermore, it provided quantitative distortion metrics that could facilitate longitudinal disease surveillance. Future research must be conducted to validate performance in unsupervised home environments and investigate whether sustained use improves time-to-disease-progression detection and treatment outcomes.}, }
@article {pmid41850516, year = {2026}, author = {Datta, M and Bessen, BM and Patel, MJ and Hackam, AS}, title = {Cellular responses of human Muller glia exposed to test dust pollution.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {397}, number = {}, pages = {127968}, doi = {10.1016/j.envpol.2026.127968}, pmid = {41850516}, issn = {1873-6424}, support = {P30 EY014801/EY/NEI NIH HHS/United States ; R21 EY036169/EY/NEI NIH HHS/United States ; }, abstract = {Air pollution is a global environmental hazard and is associated with increased severity and progression of several retinal diseases, including glaucoma and age-related macular degeneration. Muller glia are radial glia in the retina that play essential roles in metabolic support, redox balance and neuroprotection. Despite their importance, the effects of pollution on retinal glial responses are not well characterized. The objectives of this study were to determine the effects of a test dust preparation on viability, injury responses and oxidative stress levels in human Muller glia cell line. Arizona test dust (ATD) contains silica, oxides, particulate matter smaller than 10 μm and other potentially harmful components. Subconfluent cultures of Muller glia MIO-M1 cells were exposed to ATD (0.1 - 50 μg/mL) and cell viability, reactive oxygen species (ROS) production, antioxidant gene expression and transcriptomic analyses were performed. ATD exposure led to increased ROS without reducing viability, and was accompanied by reduced expression of antioxidant genes NRF2 and SOD1. Bulk RNA-seq analysis demonstrated downregulation of numerous mitochondrial genes and alterations in genes regulating migration, inflammation and adhesion. Therefore, these findings indicate that ATD pollution disrupts antioxidant protective mechanisms and mitochondrial gene expression in Muller glia, potentially leading to oxidative imbalance and transcriptional alterations that could contribute to retinal dysfunction.}, }
@article {pmid41850601, year = {2026}, author = {Parashar, AK and Kumar, B}, title = {A framework of hybrid deep learning and nature-inspired algorithms for accurate multi-class fundus disease classification.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110966}, doi = {10.1016/j.exer.2026.110966}, pmid = {41850601}, issn = {1096-0007}, abstract = {Fundus imaging is an essential technique for detecting anatomical changes indicative of various ophthalmological diseases. These alterations-including changes in the macula, optic disc, fovea, and blood vessels-can signal conditions such as diabetic retinopathy, glaucoma, age-related macular degeneration, cataracts, and myopia. In this paper, we propose a novel hybrid framework for classifying multi-class fundus images by combining deep learning feature extraction with nature-inspired algorithms. Pre-trained ResNet-18 and GoogLeNet architectures are employed to extract features, which are subsequently refined using nature-inspired algorithms including Particle Swarm Optimization, Grey Wolf Optimizer, Differential Evolution, Firefly Algorithm, and Genetic Algorithm. Finally, machine learning classifiers, such as K-Nearest Neighbor, Gaussian Naive Bayes, Support Vector Machine, and Logistic Regression, are applied to the optimized feature sets. Our extensive experiments on the ODIR and RFMiD datasets demonstrate that the proposed framework-specifically the combination of the Firefly Algorithm with K-Nearest Neighbor (FAKNN)-achieves state-of-the-art performance, reaching 100% accuracy, recall, precision, Kappa, F1 score, and Area Under the Curve. This approach not only improves diagnostic accuracy but also demonstrates significant potential for clinical application, facilitating early intervention and better patient outcomes.}, }
@article {pmid41851144, year = {2026}, author = {Oh, JY and Chae, JB and Lee, HK and Park, CW and Bae, M and Kim, G and Oh, Y and Yang, G and Kim, S and Ok, HW and Kim, D and Kim, C and Lee, S and Jang, J and Chung, H and Ryu, JH}, title = {Bst2-targeted senotherapy restores visual function by eliminating senescent retinal cells.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-70797-2}, pmid = {41851144}, issn = {2041-1723}, support = {RS-2023-00281553//National Research Foundation of Korea (NRF)/ ; 2020M3A9D8038192//National Research Foundation of Korea (NRF)/ ; RS-2025-00553501//National Research Foundation of Korea (NRF)/ ; RS-2025-16063013//National Research Foundation of Korea (NRF)/ ; RS-2025-25454860//Korea Health Industry Development Institute (KHIDI)/ ; }, abstract = {Senescent cells contribute to degenerative processes in multiple tissues, including the retina. In the retinal pigment epithelium (RPE), their accumulation is closely associated with retinal aging and disease progression. Eliminating senescent RPE cells has shown therapeutic potential, but conventional senolytics often lack the specificity required to spare non-senescent cells, raising safety concerns. To overcome this, we performed integrated transcriptomic analyses of male mouse-derived RPE cells under natural aging and chemically induced senescence conditions. These analyses identified Bst2 as a membrane-localized marker selectively upregulated in senescent RPE cells, with minimal expression in young controls. Based on this discovery, we developed a modular, antibody-pluggable drug delivery platform-B-Z-PON-comprising mesoporous silica nanoparticles functionalized with a recombinant Fc-binding domain and conjugated with anti-Bst2 antibodies. This nanocarrier selectively accumulates in Bst2-expressing senescent RPE cells, enabling targeted drug delivery and sparing healthy retinal cells. In vivo administration of ABT-263-loaded B-Z-PON in aged and senescence-induced retinal degeneration models resulted in the selective ablation of senescent cells, restoration of RPE function, and improved visual outcomes. Together, our study integrates senescence-specific marker discovery with precision nanomedicine, establishing a versatile platform for targeted senotherapy. These findings offer a promising therapeutic approach for retinal aging disorders, such as age-related macular degeneration.}, }
@article {pmid41853443, year = {2026}, author = {Moniruzzaman, M and Azzam, M and Nessa, MS and Ahmed, A and Ahmed, T and Rahman, M}, title = {Intravitreal Brolucizumab Use for Retinal Vascular Diseases in Resource-Constrained Settings: A Retrospective Study From Bangladesh.}, journal = {Cureus}, volume = {18}, number = {2}, pages = {e103620}, pmid = {41853443}, issn = {2168-8184}, abstract = {Background Anti-Vascular Endothelial Growth Factor (VEGF) therapy has been proven effective and safe for retinal vascular diseases, but the use of this agent is scarce in resource-constrained countries, including Bangladesh. Considering the limited literature, we have described 17 cases and their outcome using an anti-VEGF agent (brolucizumab) for retinal vascular diseases. Methods This retrospective case review described patients undergoing intravitreal brolucizumab at a tertiary eye care center in Bangladesh from January 2022 to December 2023. Eighteen eyes of 17 patients with complete best corrected visual acuity (BCVA) data for four follow-ups were included. Outcomes of the treatment over six months were changes in BCVA and optical coherence tomography (OCT) measurements, including foveal center point thickness, central subfield retinal thickness, and macular volume. Results Ten eyes were refractory cases who switched from other anti-VEGF agents, while eight were treatment naïve. The median age of the patients was 56 years (Interquartile range or IQR: 48-68 years). Out of all, 52.9% were female patients (n=9) and 47.1% were male patients (n=8). Diabetic retinopathy (n=10, 55.6%) was the most common indication, followed by age-related macular degeneration (n=6, 33.3%). Average BCVA improved in both naïve and refractory eyes over the course of treatment. Median OCT measurements showed a decrease in both naïve and refractory cases. No adverse events occurred. Conclusion Brolucizumab demonstrated visual gain in the short term with a favorable safety profile in a series of cases in the real-world settings of Bangladesh. Larger studies with extended follow-up can further elucidate its long-term utility.}, }
@article {pmid41853568, year = {2026}, author = {Gayraud, L and Lequy, E and Hucteau, E and de Hoogh, K and Coeuret-Pellicer, M and Schweitzer, C and Korobelnik, JF and Delyfer, MN and Vienneau, D and Goldberg, M and Zins, M and Delcourt, C}, title = {Association of Air Pollution Exposure with Incident Cataract Surgery and Neovascular Age-Related Macular Degeneration in 2 French Nationwide Cohorts.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101099}, pmid = {41853568}, issn = {2666-9145}, abstract = {PURPOSE: Age-related macular degeneration (AMD) and cataracts are part of the leading causes of blindness globally, with oxidative stress being a key factor in their development. Air pollution, known to exacerbate oxidative stress, may contribute to the progression of these diseases. This study aims at investigating the association between ambient air pollution exposure and the incidence of cataract surgery and neovascular AMD (nAMD).<br><br>DESIGN: Two nationwide prospective French cohorts.<br><br>PARTICIPANTS: The study involved 36 140 participants, including 17 911 Electricit&#xe9; de France-Gaz de France employees from the Gazel cohort and 18 229 individuals from the general French population in the Constances cohort, all aged over 53 years at inclusion and followed up for 10 years.<br><br>METHODS: Cataract surgery and nAMD cases were identified using the French National Health Data System (SNDS), which provided medical procedures and prescriptions. Air pollution exposure to nitrogen dioxide (NO2), fine particulate matter, and black carbon (BC) were estimated using land-use regression models. Cox proportional hazards models adjusted for age, sex, and education were used to assess associations. Analyses were stratified by area of residence (urban vs. rural), because of significant interactions.<br><br>MAIN OUTCOME MEASURES: Neovascular AMD was identified through intravitreal anti-VEGF injections, and cataract surgery by the first surgery date, both extracted from SNDS data.<br><br>RESULTS: Among the 36 140 participants included (39% women, mean age 60.2 years), 5543 incident cataract surgery and 266 nAMD cases were identified. In the combined Constances and Gazel populations, urban individuals exposed to more than 34.8 &#x3bc;g/m[3] of NO2 had an 8% higher risk of cataract surgery (HR = 1.08, 95% confidence interval [CI]: 1.01-1.16, P = 0.017), while no significant effect was observed among rural participants. Additionally, in the Constances cohort, participants exposed to the fourth quartile (&#x2265;2.33 10[-5]/m) of BC had an 88% increased risk of nAMD compared to those exposed to the first quartile (HR = 1.88, 95% CI: 1.03-3.45, P = 0.041). No significant association with BC was observed in the combined Constances and Gazel populations.<br><br>CONCLUSIONS: This study provides new insights into the impact of air pollution on ocular aging at a national level, highlighting the distinct effects observed between urban and rural populations.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41853572, year = {2026}, author = {Kaufmann, A and Blair, J and Lasagni Vitar, R and Wykoff, CC and Cao, J and Staurenghi, G and Cozzi, M and Ciller, C and Apostolopoulos, S and De Zanet, S}, title = {Phenotyping of Patients with Age-Related Macular Degeneration Using Artificial Intelligence-Driven Biomarker Patterns in OCT.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101101}, pmid = {41853572}, issn = {2666-9145}, abstract = {PURPOSE: To leverage artificial intelligence-based OCT analysis to classify age-related macular degeneration (AMD) images into distinct subgroups based on retinal layer and fluid biomarkers.<br><br>DESIGN: Retrospective analysis of a data set of retinal OCT images.<br><br>PARTICIPANTS: Anonymized data from 157 patients with AMD and 58 healthy volunteers.<br><br>METHODS: This study analyzed OCT scans from patients with AMD and healthy volunteers to extract retinal layer thickness and fluid biomarkers by artificial intelligence-driven image segmentation. We performed dimensionality reduction using parametric Uniform Manifold Approximation and Projection, followed by k-means clustering to partition the continuous disease space into 9 subphenotypes for analysis. Statistical analyses included linear mixed-effects modeling, analysis of variance, and Fisher exact tests to assess biomarker differences, visual acuity (VA), and lesion size across clusters. We mapped International Classification of Diseases, 10th Revision (ICD-10) codes to validate disease staging.<br><br>MAIN OUTCOME MEASURES: We examined the potential of artificial intelligence-driven biomarker patterns based on the comparison to traditional clinical measures such as VA, lesion size, and ICD-10 codes for different disease stages.<br><br>RESULTS: By dividing the continuous landscape into 9 regions for interpretability, we observed that each cluster was characterized by a distinct biomarker pattern. Clusters exhibited outer retinal thinning of varying degrees and showed significant differences in inner retinal layers, choroidal thickness, subretinal pigment epithelium material, and fluid presence compared with a healthy cohort, suggesting diverse AMD subtypes beyond simple characterization by VA and atrophic lesion size alone. The distribution of ICD-10 codes further supported the interpretation of the AMD landscape as a representation of AMD progression.<br><br>CONCLUSIONS: This study reveals a continuous AMD landscape based on OCT-derived biomarkers, suggesting the existence of subphenotypes beyond traditional staging methods. The findings further highlight the limitations of fundus-based disease classification and support the role of OCT scans in personalized disease management.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41854587, year = {2026}, author = {Liu, TYA and Ko, S and Rosettie, KL and Bonine, NG and Pletcher, A and Burke-Conte, Z and Flaxman, AD and Lei, J and Oron, AP and Borkar, D and Brodie, FL}, title = {Prevalence and Health Care Disparities of Retinal Conditions: A Meta-Analysis.}, journal = {JAMA ophthalmology}, volume = {}, number = {}, pages = {}, pmid = {41854587}, issn = {2168-6173}, abstract = {IMPORTANCE: Age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular edema (DME), and retinal vein occlusion (RVO) are leading causes of vision impairment and can lead to permanent, irreversible blindness.<br><br>OBJECTIVE: To update age-standardized prevalence estimates for AMD, DR, DME, and RVO by gender, race and ethnicity, and US state or county for 2022.<br><br>DATA SOURCES: The National Health and Nutrition Examination Survey (NHANES; 2005-2008 and 2017-March 2020), Medicare fee-for-service claims (2017-2019), IBM MarketScan commercial insurance claims (2016), and eligible population-based studies.<br><br>DATA EXTRACTION AND SYNTHESIS: Bayesian meta-regression analysis of data sources containing prevalence information for AMD, DR, DME, and RVO in the US. Data were analyzed from March to September 2024.<br><br>MAIN OUTCOMES AND MEASURES: AMD prevalence was estimated for ages 40 years and older and reported as total AMD (inclusive of early and late stage). DR (stratified by vision threatening and non-vision threatening) and DME prevalence were estimated across all ages as a proportion of people with diabetes (as defined in NHANES). RVO, defined by the presence of either retinal branch or central vein occlusion, was estimated for ages 18 years and older. Age-standardized estimates were calculated using the 2010 US Census age pyramid.<br><br>RESULTS: For 2022, age-standardized prevalence estimates per 100&#x202f;000 people were 5677 (95% uncertainty interval [UI], 4513-7374) for AMD, 2710 (95% UI, 2112-3647) for DR, 317 (95% UI, 243-505) for DME, and 214 (95% UI, 168-409) for RVO. For all conditions, prevalence was higher in males than females. White individuals had 1.7-fold higher AMD prevalence than Black individuals and 2-fold higher RVO prevalence than Hispanic individuals; Black individuals had more than 2-fold higher DR prevalence and 4.6-fold higher DME prevalence than White individuals, and Hispanic individuals had 1.8-fold higher DR prevalence and 3.7-fold higher DME prevalence than White individuals. State-level prevalence (per 100&#x202f;000 people) ranged from 3497 to 7214 for AMD, 1654 to 3607 for DR, 126 to 504 for DME, and 157 to 273 for RVO.<br><br>CONCLUSIONS AND RELEVANCE: In this meta-analysis, the US prevalence of retinal conditions was substantial, highlighting a considerable health care burden. The updated estimates and sex, race and ethnicity, and regional disparities identified in this study could inform resource allocation across the US and aid in the development of approaches to improve treatment accessibility and patient outcomes for underserved communities.}, }
@article {pmid41854807, year = {2026}, author = {Gil-Rojas, Y and Nicholson, L and Eymere, S and Cox, O and Bagijn, M}, title = {Beyond Cost: Faricimab as a Driver of Service Efficiency and Quality in Neovascular Age-Related Macular Degeneration Care.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {41854807}, issn = {2193-8245}, abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a chronic, vision-threatening condition requiring ongoing anti-vascular endothelial growth factor (anti-VEGF) injections. As the population ages and the demand for eye care rises, capacity-constrained healthcare systems struggle to deliver timely treatment. In the UK, many patients experience delays, increasing the risk of irreversible visual loss. Therapies with extended dosing intervals, such as faricimab, may reduce treatment burden and improve care quality.<br><br>METHODS: A microsimulation model was developed representing a hypothetical UK National Health Service (NHS) retinal clinic over 5 years, comparing service and cost outcomes for two nAMD therapies. The study included a pairwise comparison (base case) of faricimab versus biosimilar aflibercept 2&#xa0;mg, and a future market analysis comparing contrasting payer strategies, 'treatment choice' (75% faricimab market share) versus 'strict biosimilar mandate' (75% biosimilar market share). Outcomes included quality care delivery metrics, service utilisation, NHS provider costs, and litigation costs. Sensitivity analyses were performed to explore uncertainty.<br><br>RESULTS: Across all scenarios, faricimab reduced injection frequency, clinic visits, and treatment delays compared with biosimilar aflibercept 2&#xa0;mg. In the base case, faricimab reduced delayed visits by 97.4% (158 vs 6171) and improved the key quality care delivery metric of loading phase completion by 54.1 percentage points (95.8% vs 43.7%). Faricimab was also associated with lower acquisition costs, with additional savings arising from reduced service and litigation-related costs. In the future market analysis, a treatment choice policy resulted in improved operational and quality-of-care metrics compared with a strict biosimilar mandate, resulting in lower total costs.<br><br>CONCLUSION: In capacity-constrained settings, more durable options like faricimab can unlock operational capacity, enabling health systems to treat more patients, reduce delays, and more effectively achieve quality standards. These improvements not only help preserve vision but also generate economic value, as operational efficiencies can reduce service and litigation costs, complementing potential reductions in acquisition costs.}, }
@article {pmid41855010, year = {2026}, author = {Wang, XC and Hong, GH and Yun, YS and Choi, IW and Yuk, J and Cha, GH}, title = {Ferroptosis modulation by Toxoplasma gondii suppresses sodium iodate-driven age-related macular degeneration.}, journal = {Genes &amp; genomics}, volume = {}, number = {}, pages = {}, pmid = {41855010}, issn = {2092-9293}, support = {RS-2025-16068439//Basic Science Research Program of the National Research Foundation of Korea/ ; }, }
@article {pmid41856306, year = {2026}, author = {Yan, D and Ouyang, W and Li, K and Sun, X}, title = {Targeting the cGAS-STING pathway in ophthalmology: from innate immunity to therapeutic innovation.}, journal = {Experimental eye research}, volume = {267}, number = {}, pages = {110978}, doi = {10.1016/j.exer.2026.110978}, pmid = {41856306}, issn = {1096-0007}, abstract = {The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a key mediator of the innate immune response to cytosolic DNA, with growing implications beyond traditional host defense mechanisms. Recent research has linked the abnormal activation of this pathway to a wide range of ocular diseases, such as age-related macular degeneration, diabetic retinopathy, corneal injuries, glaucoma, and ocular tumors. This review examines the multifaceted roles of cGAS-STING signaling in ocular inflammation, tissue degeneration, fibrosis, angiogenesis, and immune surveillance. We emphasize the mechanistic basis through which the cGAS-STING pathway orchestrates various pathological processes across different ocular compartments, from the ocular surface to the retina. Additionally, we discuss its interactions with autophagy, cellular senescence, and cell death, exploring its potential as a therapeutic target in inflammatory and neoplastic eye conditions. Finally, we identify key unresolved questions and outline future research directions aimed at exploiting cGAS-STING modulation for precision therapies in vision-threatening diseases.}, }
@article {pmid41857480, year = {2026}, author = {Wu, TE and Chen, HS}, title = {Ocular complications from glucagon-like peptide-1 receptor agonists: Clinical evidence, potential mechanisms, and clinical recommendations.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001370}, pmid = {41857480}, issn = {1728-7731}, abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)-central to type 2 diabetes mellitus (T2DM) management owing to their comprehensive benefits (glycemic control, weight reduction, cardiovascular benefits, and renal protection)-exhibit a concerning ocular safety profile. Clinical trial data, notably from SUSTAIN-6, revealed a higher incidence of diabetic retinopathy (DR) complications with semaglutide, particularly in patients with pre-existing DR and rapid HbA1c reduction, reflecting early worsening. Conversely, the REWIND and LEADER trials reported no significant DR, suggesting variability among agents and the potential influence of glycemic trajectory. Observational studies and meta-analyses provide mixed findings: some suggest increased DR progression risk in vulnerable populations, while others indicate a lower risk than insulin therapy. Beyond DR, recent pharmacoepidemiologic studies and pharmacovigilance reports have implicated GLP-1 RAs-especially semaglutide-in nonarteritic anterior ischemic optic neuropathy (NAION), leading the European Medicines Agency to classify NAION as a very rare adverse effect and prompting regulatory scrutiny. Conversely, real-world data suggest possible protective associations with other retinal disorders, including reduced incidence of neovascular age-related macular degeneration and diabetic macular edema, although findings remain inconsistent. The mechanistic pathways involve rapid metabolic shifts, vascular dysregulation, and potentially direct effects on retinal or optic nerve tissue. While GLP-1 RAs confer substantial systemic benefits, their ocular risks appear concentrated in high-risk subgroups. Individualized prescribing, baseline ophthalmic assessment, and interdisciplinary monitoring are essential until ongoing prospective trials clarify their long-term ocular impact.}, }
@article {pmid41858558, year = {2026}, author = {Tran, MH and Pruitt, K and Bryarly, M and Emordi, I and Ali, A and Ma, L and Fei, B}, title = {Development and validation of a high-resolution hyperspectral imaging system for the retina.}, journal = {Journal of biomedical optics}, volume = {31}, number = {3}, pages = {036006}, pmid = {41858558}, issn = {1560-2281}, mesh = {Animals ; *Hyperspectral Imaging/methods/instrumentation ; Mice ; *Retinal Vessels/diagnostic imaging ; Algorithms ; Phantoms, Imaging ; *Retina/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Oxygen/metabolism ; Deep Learning ; Mice, Inbred C57BL ; }, abstract = {SIGNIFICANCE: Early detection of Alzheimer's diseases, diabetic retinopathy, or macular degeneration with advanced retinal imaging technologies can help improve patient care and treatment outcome.<br><br>AIM: We aim to create a high-resolution hyperspectral imaging (HSI) system for the retina. Retinal vessel diameter and oxygenation rate will be extracted simultaneously from HSI data.<br><br>APPROACH: Our hyperspectral retinal imaging system consists of a snapshot hyperspectral camera, a high-resolution RGB camera, a beamsplitter, and an imaging endoscope. Multiple pansharpening algorithms, including deep learning methods, were developed to generate high-resolution hyperspectral images that were further used for the measurement of vessel size and oxygenation rate in mice.<br><br>RESULTS: The hyperspectral retinal imaging system was tested for its spatial resolution and spectral fidelity in retina phantoms. In vivo imaging experiments were performed in mice. The deep learning-based pansharpening algorithm achieved a root mean square error (RMSE) of 2.15 &#xb1; 0.64 , a correlation coefficient (CC) of 0.96 &#xb1; 0.05 , a spectral angle score of 0.06 &#xb1; 0.03 radians, and an error relative global dimensionless synthesis (ERGAS) score of 2.37 &#xb1; 1.71 . Oxygen saturation (sO 2) and lumen diameters of blood vessels were measured in the retina. The average lumen diameter of the venules was 45.7 &#xb1; 13.6 &#x2009;&#x2009; &#x3bc; m , whereas the average lumen diameter of the arterioles was 31.5 &#xb1; 8.7 &#x2009;&#x2009; &#x3bc; m . The average arteriole sO 2 was 98%, whereas the average venule sO 2 was 58%.<br><br>CONCLUSIONS: A high-resolution hyperspectral imaging system was developed and validated for retina imaging and measurement of blood vessels and oxygen saturation.}, }
@article {pmid41858680, year = {2026}, author = {Prasad, M and Nagarkar, A and Agron, E and Weber, C and Chew, EY and De Silva, T and Mukherjee, S}, title = {A Datasheet for the Age-Related Eye Disease Study (AREDS) on the database of Genotypes and Phenotypes.}, journal = {Ophthalmology science}, volume = {6}, number = {4}, pages = {101115}, pmid = {41858680}, issn = {2666-9145}, abstract = {OBJECTIVE: Over the years, the Age-Related Eye Disease Study (AREDS) has contributed to the natural history and understanding of progression related to age-related macular degeneration (AMD) and cataracts. This paper summarizes AREDS data elements available for research.<br><br>DESIGN: Data set description for data acquired during AREDS.<br><br>PARTICIPANTS: Adults aged 55 to 80 years with no to advanced AMD in 1 eye but visual acuity >20/32 in eye without advanced AMD.<br><br>METHODS: database of Genotypes and Phenotypes archives and distributes data acquired in clinical studies such as AREDS. This article provides a detailed description of the data available under controlled access under the National Institutes of Health genomic data sharing Policy.<br><br>MAIN OUTCOME MEASURES: Age-Related Eye Disease Study evaluated progression to advanced AMD, 15-letter decrease in visual acuity, and progression of lens opacities as primary outcome measures.<br><br>RESULTS: The data set includes 4757 participants enrolled across 11 participating clinical centers representing varying AMD severity categories and lens opacities. The participants' demographics and clinical variables were collected during baseline and follow-up visits, and data elements included ophthalmic images (fundus and lens photographs) with reading center gradings; nutritional estimates captured from food frequency questionnaires; data related to quality of life, hospitalization, morbidity, and mortality; and genetic data (available in a subset of approximately 2400 participants who submitted blood samples).<br><br>CONCLUSIONS: Summary of data available under controlled access acquired as part of AREDS was provided. The AREDS data set offers a valuable resource for advancing our understanding of AMD and cataract progression and for developing novel tools and applications to transform ophthalmic diagnostics and therapeutics.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.}, }
@article {pmid41858838, year = {2026}, author = {Cheng, SY and Giguere, D and Kim, S and Seddon, JM and Caiazzi, J and Gross, K and McHugh, N and Echeverria, D and Alterman, JF and Gray-Edwards, H and Benatti, HR and Renner, L and Woolard, H and Stoddard, J and McGill, TJ and Neuringer, M and Brush, RS and Agbaga, MP and Khvorova, A and Punzo, C}, title = {An siRNA targeting S6k1 identifies photoreceptor phospholipid metabolism as a contributor to lipid buildup in age-related macular degeneration.}, journal = {Molecular therapy. Nucleic acids}, volume = {37}, number = {2}, pages = {102878}, pmid = {41858838}, issn = {2162-2531}, abstract = {Age-related macular degeneration (AMD) remains a leading cause for visual impairment in the elderly. We recently showed that activated mammalian target of rapamycin complex 1 (mTORC1) in photoreceptor cells causes AMD-like pathologies in mouse. Employing mouse genetics, we dissect the mTORC1 pathway and identify ribosomal protein S6 kinase beta-1 (S6k1) as a key component required for disease onset in our mouse model. Using a previously identified fully chemically modified tetravalent small interefing RNA (siRNA) that enriches in photoreceptors, we target S6k1 in mouse, pigs, and non-human primates (NHP) by intravitreal injection. We find that S6k1 silencing in diseased mice reverses phospholipid changes induced by activated mTORC1, restores lysosomal activity of retinal-pigmented epithelium cells, and reduces lipoprotein buildup at Bruch's membrane (BM). In pigs, which do not develop disease, we find a similar shift in phospholipids as in mouse, indicating a conserved role for S6k1 in photoreceptor phospholipid metabolism. In aged NHPs with macular drusen, the lipoprotein-rich BM deposits that are a hallmark of human AMD, S6k1 silencing slows drusen growth over a 6-month period. These findings establish S6k1 as modifier of lipoprotein buildup at the BM and support our siRNA platform as a potential treatment modality for AMD and other retinal diseases.}, }
@article {pmid41860312, year = {2026}, author = {Khan, A and Hormel, TT and Gao, M and Guo, Y and Zang, P and Wang, J and Hwang, TS and Bailey, ST and Jia, Y}, title = {Automated Segmentation and Characterization of Retinal Hyperreflective Foci in Age-Related Macular Degeneration.}, journal = {Translational vision science &amp; technology}, volume = {15}, number = {3}, pages = {20}, doi = {10.1167/tvst.15.3.20}, pmid = {41860312}, issn = {2164-2591}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; *Macular Degeneration/diagnostic imaging/diagnosis ; Aged ; Female ; Male ; Neural Networks, Computer ; *Retina/diagnostic imaging/pathology ; Aged, 80 and over ; ROC Curve ; Middle Aged ; }, abstract = {PURPOSE: Retinal hyperreflective foci (HRF) are associated with higher risk of progression to advanced age-related macular degeneration (AMD). To enable automated detection, we developed Foci-Net, a convolutional neural network for segmenting HRF in optical coherence tomography (OCT) volumes.<br><br>METHODS: This cross-sectional study included eyes clinically diagnosed with intermediate to advanced AMD and healthy controls. We acquired 6 &#xd7; 6-mm macular-centered scans using 2 OCT systems. Foci-Net modifies the U-Net by replacing the bottleneck with a fine-to-coarse feature extraction block to improve segmentation of both small and large foci. HRF volume was quantified as the proportion of total volume within each retinal layer and characterized by anatomic location. Model performance was evaluated at the count, pixel, eye, and B-scan levels using F1-score, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, precision, sensitivity, and specificity.<br><br>RESULTS: Sixty-one volumetric OCT scans (50 AMD and 11 healthy control eyes) obtained from 50 participants, age 77.65 &#xb1; 9.24 years (mean &#xb1; SD), of whom 72% were women. Foci-Net achieved F1-scores of 73.0 &#xb1; 3.8% counts (based on en face analysis) and 71.6 &#xb1; 29.1% pixels (based on cross-sectional analysis) level relative to the ground truth in 3-fold cross-validation. Diagnostic performance was strong, with an AUC of 100 &#xb1; 0.0% (eye) and 92.7 &#xb1; 0.3% (B-scan) level. HRF was least (2.10%) abundant in the ganglion cell complex and most (55.37%) in the outer nuclear layer.<br><br>CONCLUSIONS: A deep learning approach enables fast HRF segmentation, supporting its role as a biomarker for predicting AMD progression.<br><br>TRANSLATIONAL RELEVANCE: The proposed HRF segmentation method could enhance AMD diagnosis and prognosis.}, }
@article {pmid41860622, year = {2026}, author = {Al-Shammari, YM and AlDhafiri, YM and Ahmad, AK and Alkharraz, BB and Al-Awadhi, MA and Alnabhan, RM}, title = {Clinical efficacy and safety of anti-VEGF biosimilars compared to reference anti-VEGF agents for neovascular age-related macular degeneration: a systematic review, meta-analysis, and meta-regression.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {}, pmid = {41860622}, issn = {1573-2630}, mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly. Current treatment options include intravitreal anti-VEGF therapy with ranibizumab and aflibercept. These medications are very effective but expensive. Biosimilars of these expensive intravitreal medications have been proposed as less expensive treatment options. However, their clinical equivalence and safety are of concern.<br><br>PURPOSE: The purpose of this study was to assess the efficacy, safety, and immunogenicity of biosimilars of ranibizumab and aflibercept, and their clinical equivalence with their reference biologics, in the treatment of neovascular AMD.<br><br>METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing biosimilar anti-VEGF agents with reference ranibizumab or aflibercept. A comprehensive search of PubMed, Scopus, and Cochrane Library (inception-September 2025) was performed following PRISMA guidelines. Outcomes included change in best-corrected visual acuity (BCVA) at 12&#xa0;weeks and study endpoint, &#x2265;&#x2009;15-letter responder rates, treatment-emergent anti-drug antibodies (ADAs), and ocular/serious ocular adverse events. Risk of bias was assessed using the Cochrane ROB-2 tool.<br><br>RESULTS: Seventeen phase 3 RCTs including 6694 patients were analyzed. Pooled results showed no clinically meaningful differences in BCVA improvement at 12 weeks (MD&#x2009;=&#x2009;-&#x2009;0.42, p&#x2009;=&#x2009;0.17) or at study endpoint (MD&#x2009;=&#x2009;-&#x2009;0.32, p&#x2009;=&#x2009;0.23) between biosimilars and reference biologics. Responder rates (&#x2265;&#x2009;15-letter gain) were comparable (RR&#x2009;=&#x2009;1.06, p&#x2009;=&#x2009;0.36), as were rates of treatment-emergent ADAs (RR&#x2009;=&#x2009;0.89, p&#x2009;=&#x2009;0.40) and ocular adverse events (RR&#x2009;=&#x2009;0.99, p&#x2009;=&#x2009;0.86). The subgroup analysis did not demonstrate significant results for biosimilars of aflibercept compared with the reference aflibercept; however, biosimilars of ranibizumab had slightly less BCVA improvement at the end point (RR 0.53, p 0.02). Heterogeneity was low to moderate, and no publication bias was noted.<br><br>CONCLUSION: Our analysis has demonstrated that biosimilars of ranibizumab and aflibercept have equivalent efficacy, safety, and immunogenicity profiles compared with the reference biologics. Future studies should focus on long-term outcomes, switching studies, and health economics to help determine the long-term success of biosimilar therapy.}, }
@article {pmid41861216, year = {2026}, author = {Lu, F and Zhang, J and Lu, J and Jiang, W and Fei, Z and Xiao, Q and Wang, Z}, title = {Trends, hotspots, and future directions of inflammation in age-related macular degeneration: A 20-year bibliometric study.}, journal = {Medicine}, volume = {105}, number = {12}, pages = {e46598}, pmid = {41861216}, issn = {1536-5964}, mesh = {*Bibliometrics ; Humans ; *Macular Degeneration ; *Inflammation/complications ; *Biomedical Research/trends ; }, abstract = {BACKGROUND: Inflammation significantly impacts the pathogenesis of age-related macular degeneration (AMD), the primary cause of vision loss in the elderly. With the aging global population and increasing incidence of AMD, understanding the inflammation-related mechanisms and identifying potential therapeutic targets have become paramount. This study aims to offer a bibliometric analysis of global research contributions focused on inflammation in AMD, shedding light on research trends, collaborations, and future directions.<br><br>METHODS: We retrieved publications related to inflammation in AMD from 2003 to 2023 from the Web of Science Core Collection database. A total of 2044 articles were analyzed using VOSviewer, CiteSpace, and R-bibliometrix to examine publication trends, influential countries, institutions, authors, and journals, as well as emerging research topics.<br><br>RESULTS: Our analysis revealed a steady global increase in annual publications. The United States and China emerged as leading contributors, demonstrating substantial collaboration and investment in AMD research. Among institutions, the National Eye Institute in the United States and the University of Eastern Finland stood out for their prolific contributions. Key researchers such as Kaarniranta have been central to advancing the field, offering potential collaboration opportunities. Investigative Ophthalmology and Visual Science and Experimental Eye Research were identified as the top journals publishing significant work on inflammation in AMD. Keywords such as "oxidative stress," "complement" "autophagy," "macrophage," and "microglia" were frequently mentioned, highlighting these as current research hotspots.<br><br>CONCLUSION: This analysis underscores the importance of inflammation in AMD and maps the evolution of research, suggesting future directions that may offer new therapeutic strategies.}, }
@article {pmid41861959, year = {2026}, author = {Gale, RP and Loewenstein, A and Zhang, X and Leal, S and Machewitz, T and Sivaprasad, S and Wong, DT and Zeitz, O and Korobelnik, JF and , }, title = {PULSAR: Clinical Outcomes of Aflibercept 8 mg with Extended Dosing and 2 mg in nAMD in Subgroups Defined by Baseline Characteristics.}, journal = {Ophthalmology. Retina}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oret.2026.02.020}, pmid = {41861959}, issn = {2468-6530}, abstract = {OBJECTIVE: To evaluate the impact of baseline disease severity on clinical outcomes with aflibercept 8 mg with extended dosing intervals versus aflibercept 2 mg in patients with treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Post hoc descriptive subgroup analysis of PULSAR (NCT04423718), a 96-week, double-masked, randomized, active-controlled clinical trial investigating treatment of nAMD with aflibercept 8 mg with extended dosing intervals or aflibercept 2 mg every 8 weeks. Patients were subgrouped according to severity of baseline disease characteristics, namely best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal neovascularization (CNV) lesion type, and CNV area.<br><br>PARTICIPANTS: Patients with nAMD who were randomly assigned to receive aflibercept 8 mg or 2 mg. Overall, 869 patients completed treatment through week 96.<br><br>INTERVENTION: Aflibercept 8 mg was administered every 12 or 16 weeks (8q12 or 8q16) after 3 initial monthly injections. Dosing intervals could be shortened in years 1 and 2 and extended in year 2 based on prespecified disease activity criteria. Aflibercept 2 mg every 8 weeks was administered after 3 initial monthly injections.<br><br>MAIN OUTCOME MEASURES: BCVA and CRT outcomes among subgroups defined by baseline BCVA (&#x2264;54, 55-73, and &#x2265;74 ETDRS letters), CRT (&#x2264;278 &#x3bc;m, 279-343 &#x3bc;m, 344-422 &#x3bc;m, and &#x2265;423 &#x3bc;m), CNV lesion type (minimally classic, occult only, and predominantly classic), and CNV area (<1.3 mm[2], 1.3 to <4 mm[2], 4 to <5 mm[2], and &#x2265;5 mm[2]). Last assigned dosing interval at week 96 for the aflibercept 8q12 and 8q16 treatment arms was also analyzed by disease severity.<br><br>RESULTS: Patients in the aflibercept 8q12 and 8q16 arms achieved visual and anatomic outcomes at week 96 comparable to those in the 2q8 arm within subgroups defined by baseline disease severity. Most patients randomized to the 8q12 and 8q16 arms in each subgroup defined by baseline disease severity had last assigned dosing intervals of &#x2265;12- and &#x2265;16 weeks, respectively, at week 96.<br><br>CONCLUSIONS: Treatment with aflibercept 8 mg can achieve the functional and anatomic benefits observed with aflibercept 2 mg, but with prolonged dosing intervals, regardless of disease severity at initiation.}, }
@article {pmid41862006, year = {2026}, author = {Martyka, A and Bolek, B and Gospodarczyk, N and Czuj, W and Wylęgała, A and Wylęgała, E}, title = {Therapeutic potential of norrin/FZD4/β-catenin signaling in blood-retinal barrier protection.}, journal = {Survey of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.survophthal.2026.03.013}, pmid = {41862006}, issn = {1879-3304}, abstract = {The therapeutic potential of the norrin protein, Frizzled-4 (FZD4) receptor, and the β-catenin signaling pathway is gaining increasing importance in ophthalmology due to their multifaceted effects on the function of the blood-retinal barrier (BRB). Disruption of BRB integrity represents a key mechanism underlying pathological vascular permeability and the progression of diabetic retinopathy and age-related macular degeneration. There remains an unmet need for the development of therapies specifically targeting the protection and regeneration of the BRB, as current treatment strategies primarily focus on symptom alleviation rather than addressing the underlying mechanisms of barrier breakdown. Interest in norrin signaling within the Wnt/β-catenin pathway arises from its crucial role in maintaining BRB integrity through the activation of the Frizzled-4 (FZD4) receptor and LRP5/6 co-receptors, leading to the stabilization of endothelial junctional complexes and the maintenance and restoration of retinal vascular barrier properties, particularly following vascular endothelial growth factor (VEGF)-induced barrier disruptionmodulation of this pthway may represent a novel therapeutic approach aimed at protecting and regenerating the BRB in degenerative retinal diseases. Weidentify current research directions regarding new therapeutic strategies for ophthalmic diseases associated with BRB dysfunction, with particular emphasis on the role of norrin protein, Frizzled-4 (FZD4) receptors, and β-catenin. A comprehensive search was conducted in electronic databases (PubMed, Google Scholar) using the following.}, }
@article {pmid41864469, year = {2026}, author = {Leung, HYE and Zhang, J and Radke, NV and Gan, S and Yao, S and Wang, Z and Li, J and Liu, X and Chong, V and Wang, X and Tan, W and Lam, DSC}, title = {Novel drug development for geographic atrophy.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {}, number = {}, pages = {100305}, doi = {10.1016/j.apjo.2026.100305}, pmid = {41864469}, issn = {2162-0989}, abstract = {Geographic atrophy (GA), the advanced stage of dry age-related macular degeneration, has transitioned from an untreatable condition to a field of active therapeutic development. This review outlines the key molecular pathways driving GA progression, including complement system dysregulation, oxidative stress, and chronic inflammation. A marked important therapeutic milestone with the first FDA approvals of complement inhibitors, Pegcetacoplan and Avacincaptad pegol, demonstrated a modest but statistically significant slowing of lesion growth. However, these anatomic benefits have not consistently translated into meaningful functional visual improvement, underscoring the need for additional therapeutic strategies. Beyond complement, the therapeutic landscape is rapidly expanding to include oral agents, topical therapies, implant-based delivery systems, subcutaneous injections, and device-based approaches targeting oxidative stress, neuroprotection, mitochondrial dysfunction, lipid metabolism and proteostasis. Emerging modalities, including gene therapy, stem cell-based repair, and bioelectronic implants, aim to move beyond disease slowing toward durable retinal restoration. Despite progress, significant unmet needs persist. Key challenges include treatment burden associated with frequent intravitreal injections, safety considerations, and the persistent disconnect between anatomic endpoints and functional outcomes. These underscore the necessity for future treatments that not only alter disease anatomy but also effectively preserve patients' vision and improve their quality of life.}, }
@article {pmid41866494, year = {2026}, author = {Bhargava, M and Mehta, KN and Parikh, BH and Liu, Z and Su, X}, title = {Advances in retinal pigment epithelium transplantation for age-related macular degeneration: bridging biology to therapeutic frontiers.}, journal = {Stem cell research &amp; therapy}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13287-026-04971-0}, pmid = {41866494}, issn = {1757-6512}, }
@article {pmid41867320, year = {2026}, author = {Lin, Z and Huang, L and Li, D and Yi, S and Weng, J}, title = {Case Report: Maculopathy following standard dose intracameral cefuroxime injection during ICL surgery.}, journal = {Frontiers in ophthalmology}, volume = {6}, number = {}, pages = {1778421}, pmid = {41867320}, issn = {2674-0826}, abstract = {PURPOSE: To describe two rare occurrences of acute toxic maculopathy, specifically Intracameral Cefuroxime Ocular Toxic Syndrome (ICOTS), following uncomplicated posterior-chamber toric phakic implantable collamer lens (TICL) surgery despite the administration of a standard dosage of cefuroxime.<br><br>MATERIALS AND METHODS: This case report identified two patients from a clinical volume of 1,590 eyes treated between 2021 and 2024. Inclusion criteria consisted of patients undergoing bilateral TICL implantation with intracameral cefuroxime who presented with unexpected visual disturbances on postoperative day 1. To isolate cefuroxime as the primary toxic factor, exclusion criteria included systemic comorbidities (such as diabetes mellitus), pre-existing ocular pathologies (including uveitis, macular degeneration, or prior retinal detachment), history of prostaglandin analog use, or baseline structural abnormalities on preoperative optical coherence tomography (OCT). Clinical evaluation included UDVA, BCVA, and SD-OCT imaging.<br><br>RESULTS: Two female patients (aged 29 and 32) underwent bilateral TICL surgery with 0.1 mL of 10 g/L intracameral cefuroxime administered at the conclusion of the procedure. On postoperative day 1, both patients presented with unilateral vision loss (BCVA 20/32 and 20/80, respectively) and reported dim or distorted vision. SD-OCT revealed macular edema and subretinal fluid (SRF). Following conventional postoperative treatment with topical steroids and nonsteroidal anti-inflammatory drugs, complete absorption of SRF was achieved within two weeks to one month, and BCVA improved to 20/16 and 20/20, respectively.<br><br>CONCLUSION: While intracameral cefuroxime is a highly effective prophylactic against endophthalmitis, it may cause sporadic toxic maculopathy even at standard doses during ICL surgery. Unlike typical post-cataract inflammatory edema, ICOTS presents acutely on day 1. Surgeons should maintain a high index of suspicion and utilize early OCT imaging for unexpected postoperative visual disturbances.}, }
@article {pmid41867365, year = {2025}, author = {Gregory-Evans, K and Gregory-Evans, CY}, title = {Molecular insights into foveal hypoplasia: development, genetics, mechanisms, and models.}, journal = {Molecular vision}, volume = {31}, number = {}, pages = {319-343}, pmid = {41867365}, issn = {1090-0535}, mesh = {Humans ; *Fovea Centralis/abnormalities/pathology/growth &amp; development/metabolism ; Animals ; Disease Models, Animal ; Eye Diseases, Hereditary ; Nystagmus, Congenital ; }, abstract = {The fovea is an anatomic specialization of the human retina critical for high visual acuity, color vision, and contrast sensitivity. The molecular and cellular pathways directing this focal topography are still to be determined. Abnormalities of the fovea (e.g., foveal hypoplasia in children) are considered a significant contributor to reduced quality of life. In addition, the fovea is often damaged in common retinal diseases, such as age-related macular degeneration and diabetic retinopathy, with a global economic burden of $500 billion USD. Currently, there are no treatments for foveal defects. Most genes contributing to foveal abnormalities have been identified but are yet to be characterized and studied. This is because common laboratory animals do not have a fovea, and only rare human tissue samples are available during the major phase of foveal maturation, from birth to the end of the fourth year of life. We discuss validation of the anole lizard, which has a foveal structure, for research studies into foveal development. Since foveal development continues after birth, it may be possible to stimulate new foveal maturation where there is developmental damage. From this review, we propose an evidence-based cellular mechanism that offers new possibilities for testing future therapies for foveal defects.}, }
@article {pmid41867749, year = {2026}, author = {Wu, Y and Tong, Y and Byrnes, KG and Zhou, Q and Dong, C and Benjamin, C and Parker, E and Bao, D and Ren, Z and Anderson, CA and Ufret-Vincenty, RL and He, YG and Zhang, Z and Hinkle, D and Ma, J and Wang, S}, title = {Myofibroblast lineage mapping and inhibiting subretinal fibrosis by targeting SMAD3 and MRTF pathways via microRNA-24 functional study.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.03.03.709397}, pmid = {41867749}, issn = {2692-8205}, abstract = {Subretinal fibrosis underlies the end-stage pathogenesis of retinal diseases including age- related macular degeneration (AMD). It can disrupt retinal structure and eventually lead to legal blindness by generating contractile force, fibrotic scarring, subretinal hemorrhage, and retinal detachment. Myofibroblasts are the predominant cells critically involved in subretinal fibrosis, however, the cellular contribution to myofibroblasts remains unclear. Here we demonstrate that multiple cell lineages, including macrophages, endothelial cells (EC), retinal pigment epithelial (RPE) cells and pericytes, significantly contribute to myofibroblasts in a laser-induced subretinal fibrosis model. We found microRNA miR-24 is significantly downregulated in the plasma of wet AMD patients. Overexpression of miR-24 represses epithelial-mesenchymal transition (EMT), endothelial-mesenchymal transition (EndMT), and the resulting fibrosis by regulating TGF- β/SMAD3 and PAK4/LIMK2/MRTF pathways. Consistently, a combination of SMAD3 and MRTF inhibitors show superior efficacy to individual inhibitors in repressing fibrosis in vitro and laser-induced subretinal fibrosis in vivo . Together, these suggest the contribution of multiple cell-types in myofibroblast transformation in subretinal fibrosis, and repression of miR-24 -regulated TGF-β/SMAD3 and PAK4/LIMK2/MRTF pathways in multiple cell types holds therapeutic potential for treating subretinal fibrosis in AMD and other fibrotic disorders.}, }
@article {pmid41867838, year = {2026}, author = {Little, DR and Shirinifard, A and Lupo, M and Wu, CH and Chen, H and Clemons, MR and Maclean, M and Marola, OJ and Howell, GR and Li, C and Dyer, MA}, title = {Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2026.02.27.708333}, pmid = {41867838}, issn = {2692-8205}, abstract = {Imageomics uses machine learning to accelerate our understanding of biological traits and human disease processes. Some of the earliest imageomics applications used deep learning to assess human diseases. For example, retinal fundus images were analyzed to diagnose diabetic retinopathy. The imaging modality optical coherence tomography (OCT) is widely used to diagnose and monitor the progression of retinopathy in patients and preclinical models. The standardized instrumentation and image format of OCT lends itself to imageomics, but generalizable, automated pipelines for segmentation and quantitation of large numbers of OCT images are still in early development. Here, we present the automated, end-to-end pipeline Crop-OCT that extracts features from thousands of OCT images, while preserving their location within the eye. We used the Crop-OCT pipeline on a diverse dataset, including 13 genetic models of retinopathy, with more than 20,000 OCT images, which allowed us to analyze nearly 6 million measured features. The pipeline was generalized on an independent dataset that was analyzed in a blinded manner. The pipeline enabled us to monitor ocular changes associated with aging and progression of diseases, such as retinitis pigmentosa, Leber congenital amaurosis, achromatopsia, Stargardt disease, diabetic retinopathy, and age-related macular degeneration. We also characterized heterogeneity across animals and identified regional and focal lesions. Our pipeline will unify feature extraction for preclinical models of retinal disease and serve as a foundation for future multimodal data integration for artificial intelligence applications based on imageomics.}, }
@article {pmid41868207, year = {2026}, author = {Guo, B and Wang, D and Zhao, Z and Liu, W and Hou, J and Liang, R and Zhang, L}, title = {Evaluation of classification performance for six types of fundus diseases in OCT images based on multi-source training strategy.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1775911}, pmid = {41868207}, issn = {2296-858X}, abstract = {OBJECTIVE: Currently, publicly available Optical Coherence Tomography (OCT) datasets are commonly plagued by limited coverage of disease categories, scarce samples and severe class imbalance, which leads to insufficient generalization ability of deep learning models in real-world clinical settings. This study aims to construct a high-quality OCT dataset encompassing six key types of fundus lesions and normal controls, and to systematically evaluate the improvement effect of training strategies for multi-source data fusion on the performance of multi-class classification.<br><br>METHODS: We integrated local clinical data from Shanxi Eye Hospital with the latest public dataset OCTDL to establish a combined dataset. This dataset consists of 6,165 images, covering seven categories: age-related macular degeneration (AMD), diabetic macular edema (DME), retinal artery occlusion (RAO), retinal vein occlusion (RVO), epiretinal membrane (ERM), vitreomacular interface disease (VID), and normal controls (NO). On this basis, six representative deep learning architectures were selected, and two training paradigms were compared under unified experimental settings: (1) Training exclusively on open-source OCTDL data (S1); (2) Joint training using both local data and OCTDL data (S2). All models were evaluated on the identical OCTDL test set. A comprehensive analysis was conducted using multi-dimensional metrics including accuracy, weighted F1-score, class-specific recall, and area under the curve (AUC), with a particular focus on the misdiagnosis rate.<br><br>RESULTS: The S1 strategy exhibited significantly limited model recognition capability due to the extremely small sample sizes of certain categories. In contrast, the S2 strategy markedly improved the overall performance of the models. Confusion matrix analysis demonstrated that ViT-Base achieved the optimal performance under the S2 strategy: the accuracy reached 93.61%, the misdiagnosis rate of RAO was reduced to 0%, the misdiagnosis rate of AMD was controlled at 1.34%, and the misdiagnosis rate of RVO decreased from 14.89 to 8.51%.<br><br>CONCLUSION: Multi-source data fusion serves as an effective approach to enhance the robustness of OCT multi-category classification models, and it can notably strengthen the recognition capability for certain diseases in particular. This study not only verifies the universal benefits of this strategy but also reveals the critical impact of model selection on the transfer learning effect.}, }
@article {pmid41868220, year = {2026}, author = {Kim, MS and Nam, S and Lee, J and Woo, SJ}, title = {Prevalence, incidence and risk factors of visual disability in patients with exudative age-related macular degeneration: a nationwide population-based study in Korea.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1766076}, pmid = {41868220}, issn = {2296-858X}, abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in the elderly. Although anti-vascular endothelial growth factor (VEGF) therapy has improved the visual prognosis of exudative AMD, a considerable proportion of patients still develop severe vision loss. However, real-world data on the prevalence, incidence and risk factors for visual disability among patients with exudative AMD remain limited. This study investigates the prevalence, incidence and risk factors for visual disability among patients with exudative AMD.<br><br>METHODS: This nationwide, population-based retrospective cohort study used Korean National Health Insurance Service data from 2009 to 2023. Patients with newly diagnosed exudative AMD were identified, with a two-year washout period (2009-2010). Prevalence, incidence, hazard ratio (HR) for visual disability were analyzed.<br><br>RESULTS: A total of 147,406 patients with exudative AMD were included. The prevalence of visual disability in 2023 was 4.82% and the overall incidence rate was 12.18 per 1,000 person-years. At 8&#x202f;years, the cumulative incidence probability of monocular visual disability was 4.8% (95% CI, 4.6-5.1), and that of binocular visual disability was 4.4% (95% CI, 4.1-4.7). The mean duration from exudative AMD diagnosis to visual disability was 3.3&#x202f;&#xb1;&#x202f;2.6&#x202f;years. The risk of visual disability increased with older age group (HR, 1.38; 95% CI, 1.35-1.42) and lower income level (HR, 1.06; 95% CI, 1.05-1.08). Female sex (HR, 1.41; 95% CI, 1.35-1.47), diabetic retinopathy (HR, 1.16; 95% CI, 1.08-1.25), glaucoma (HR, 1.10; 95% CI, 1.05-1.15), and severe intraocular hemorrhage requiring vitrectomy (HR, 3.14; 95% CI, 2.63-3.75) were also significant risk factors. A decreasing trend in visual disability incidence was observed among patients who were more recently diagnosed with exudative AMD (-0.25% point per year; p&#x202f;<&#x202f;0.001).<br><br>CONCLUSION: The burden of AMD-related visual disability remains significant, highlighting the need for strategies to improve treatment adherence and ensure equitable access to vision-preserving care. The decreasing trend of visual disability in recent years suggests the practical benefit of improved access to anti-VEGF treatment through lower drug costs and expanded insurance coverage.}, }
@article {pmid41868245, year = {2026}, author = {Xu, W and Zhang, J and Shangguan, Y and Luo, R and Zhu, Y and Bi, Y and Chen, L and Li, B}, title = {Targeting the neurovascular unit in retinal fibrosis: mechanisms and therapeutic perspectives.}, journal = {Frontiers in medicine}, volume = {13}, number = {}, pages = {1776869}, pmid = {41868245}, issn = {2296-858X}, abstract = {Retinal fibrosis, a severe complication observed in conditions like age-related macular degeneration and diabetic retinopathy, characterized by aberrant myofibroblast activation and excessive extracellular matrix (ECM) deposition, which ultimately led to irreversible visual impairment. Currently, the mechanisms underlying retinal fibrosis remain unclear and existing treatments remain incompletely understood. Thus, a comprehensive understanding of disease mechanisms, together with the development of innovative therapeutic approaches, is essential for advancing effective treatment strategies. This review systematically examines the pathogenesis of retinal fibrosis from the perspective of the neurovascular unit (NVU), with a particular focus on the roles of endothelial cells, pericytes, and glial cells in fibrotic processes. It highlights key fibrotic mechanisms