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14 pages, 2596 KB  
Article
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
by Veronika Eggarter, Ludovico Ruscitti, Niccolò Ascioti, Matteo Bonanata, Arianna Peyla, Filippo Simona, Moreno Menghini and Gabriela Grimaldi
J. Clin. Med. 2026, 15(16), 6478; https://doi.org/10.3390/jcm15166478 - 21 Aug 2026
Viewed by 153
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 [...] Read more.
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 mm2, 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. Full article
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14 pages, 3300 KB  
Article
Diabetic Retinopathy Grading and Concurrent Cardiorenal Biomarker Abnormalities in Type 2 Diabetes: Albuminuria and Elevated NT-proBNP—A Retrospective Cross-Sectional Study
by İrfan Alisan, Ahmet Gazi Mustan, Bektas Isik, Fatih Necip Arıcı, Cahit Dinçer, Çisem Yılmaz, Mehmet Erdevir, Ahmet Altıntaş, Çiğdem Erhan, Merve Saracoglu Sumbul, Huseyin Ali Ozturk, Erdinc Gülümsek, Begüm Seyda Avcı and Hilmi Erdem Sumbul
J. Clin. Med. 2026, 15(15), 6106; https://doi.org/10.3390/jcm15156106 - 6 Aug 2026
Viewed by 275
Abstract
Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of type 2 diabetes mellitus (T2DM) and a recognised marker of systemic vascular injury. Whether DR—graded independently by two experienced ophthalmologists as part of routine institutional care—is independently associated with concurrent nephropathy (urine [...] Read more.
Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of type 2 diabetes mellitus (T2DM) and a recognised marker of systemic vascular injury. Whether DR—graded independently by two experienced ophthalmologists as part of routine institutional care—is independently associated with concurrent nephropathy (urine albumin-to-creatinine ratio [UACR] ≥ 30 mg/g) and subclinical cardiac stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥ 125 pg/mL) remains insufficiently examined. Methods: Retrospective cross-sectional study of 401 T2DM adults who underwent dilated fundus examination independently graded by two board-certified ophthalmologists (each ≥ 10 years’ experience in diabetic eye disease) using ETDRS-based classification. Inter-physician agreement was quantified by Cohen’s weighted kappa. The primary composite outcome was concurrent nephropathy and subclinical cardiac stress. Multivariable logistic regression adjusted for age, sex, HbA1c, diabetes duration, eGFR, hypertension, and pharmacological treatments. Results: The composite outcome was present in 120 (64.2%) DR-positive vs. 14 (6.5%) DR-negative patients (crude OR: 25.59 (13.78–47.51); p < 0.001; fully adjusted OR: 21.49 (11.02–41.81); p < 0.001). Inter-physician agreement was high (Cohen’s weighted κ = 0.88; 95% CI: 0.83–0.93). Nephropathy alone was found in 164 (87.7%) vs. 76 (35.5%) patients (OR: 12.95 (7.71–21.75); p < 0.001), and elevated NT-proBNP in 137 (73.3%) vs. 39 (18.2%) patients (OR: 12.29 (7.65–19.76); p < 0.001). A significant trend across DR severity grades was observed (p for trend < 0.001), although the gradient was not strictly monotonic. ROC AUC = 0.837 (95% CI: 0.784–0.860). Conclusions: Ophthalmologist-graded DR was independently associated with the concurrent presence of albuminuria and elevated NT-proBNP in T2DM. Because the design is cross-sectional, these findings describe association rather than prediction or causation. They generate the hypothesis that retinal grading may help flag patients in whom cardiorenal biomarker assessment is worth considering, but prospective validation is required before any screening application. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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11 pages, 1631 KB  
Article
Comparing Patient Experiences in Ophthalmic Workflows with Virtual Reality Versus In-Office Standard Testing: A Preliminary Survey Study
by Margarita Labkovich, Randal A. Serafini, Andrew J. Warburton, Christopher Cheng, Oluwafeyikemi O. Okome, Vicente N. Navarro, Harsha Reddy and James G. Chelnis
J. Clin. Transl. Ophthalmol. 2026, 4(3), 20; https://doi.org/10.3390/jcto4030020 - 29 Jul 2026
Viewed by 243
Abstract
Background/Aims: This study set out to compare patient experiences and attitudes toward virtual reality (VR) versus in-office ophthalmic functional testing, as well as their eye exam visit preferences. Methods: A total of 64 patients undergoing a comparative clinical trial including VR and in-office [...] Read more.
Background/Aims: This study set out to compare patient experiences and attitudes toward virtual reality (VR) versus in-office ophthalmic functional testing, as well as their eye exam visit preferences. Methods: A total of 64 patients undergoing a comparative clinical trial including VR and in-office versions of 24-2 visual field perimetry, Pelli–Robson contrast sensitivity, ETDRS visual acuity, Ishihara plates, and Amsler Grid tests were given a survey that included Likert-scaled questions regarding overall experience, speed, and comfort of broad VR testing versus in-office tests, as well as binary modality preference, like or dislike of various exam modality aspects, ease of understanding each test, distance traveled to their appointment, visit frequency, and remote care preferences. Results: In terms of overall experience, 59 (93.7%) participants rated VR as “Liked” or “Very Much Liked” compared to 38 (60.3%) for in-office tests (χ2 p < 0.0001). Regarding comfort, 59 (93.7%) and 38 (60.3%) participants at least “Liked” VR and in-office tests, respectively (χ2 p < 0.0001). For speed, 60 (95.2%) and 36 (57.1%) participants at least “Liked” VR and in-office tests, respectively (χ2 p < 0.0001). Accordingly, 11 (17.5%) patients liked all aspects of in-office tests, while 54 (85.7%) patients said the same for VR (χ2 p < 0.0001). Overall, 33 (52.4%) patients disliked something about in-office tests, while 20 (31.7%) said the same for VR (χ2 p < 0.0001). There were no differences in ability to understand tests between the two modalities. We noted a variable distribution of distance traveled and visits per year in our population, yet there was also a strong preference for implementing more remote eye testing options. Conclusions: Development and implementation of virtual reality analogs to in-office, functional ophthalmic exams can improve patient experience and facilitate remote care delivery. Full article
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21 pages, 1148 KB  
Article
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
by Maja L. J. Živković, Marko Zlatanović, Nevena Zlatanović, Mladen Brzaković and Mihailo Jovanović
Medicina 2026, 62(7), 1307; https://doi.org/10.3390/medicina62071307 - 6 Jul 2026
Viewed by 407
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Retinal and Macular Diseases: From Diagnosis to Therapy)
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14 pages, 2688 KB  
Article
Deep Learning Prediction of Retinal Thickness from Near-Infrared Fundus Photography: Toward Decentralized Quantitative Assessment of Diabetic Macular Edema
by Behrouz Ebrahimi, Albert K. Dadzie, Mansour Abtahi, Masrur A. Sadhin, Daniel Kim, Srishti Kolla, Baoxin Li, R. V. Paul Chan, Michael J. Heiferman and Xincheng Yao
J. Pers. Med. 2026, 16(7), 361; https://doi.org/10.3390/jpm16070361 - 2 Jul 2026
Viewed by 507
Abstract
Objective: To predict pixel-wise retinal thickness maps from near-infrared (NIR) fundus images using deep learning (DL), and to identify image features in NIR fundus photographs serving as surrogate markers of retinal thickness, with implications for decentralized diabetic macular edema (DME) screening, progression monitoring, [...] Read more.
Objective: To predict pixel-wise retinal thickness maps from near-infrared (NIR) fundus images using deep learning (DL), and to identify image features in NIR fundus photographs serving as surrogate markers of retinal thickness, with implications for decentralized diabetic macular edema (DME) screening, progression monitoring, and treatment assessment. Methods: A DL model based on a U-Net architecture was trained on paired NIR fundus and OCT images from 531 eyes across three groups: healthy controls, diabetic retinopathy (DR) without DME, and DME. Model performance was evaluated using mean absolute error (MAE), root mean squared error (RMSE), structural similarity index (SSIM), and center-involved DME (ci-DME) classification at a central subfield thickness threshold of 300 µm. Controlled image manipulation experiments, including spatial disruption of vascular patterns, relocation of hard exudates, and contrast enhancement, were performed to identify image-level features serving as surrogate markers of retinal thickness. Results: The model achieved an MAE of 30.41 ± 18.68 µm, RMSE of 36.14 ± 21.05 µm, and SSIM of 0.87 ± 0.04 across the macula, with consistent performance across ETDRS subfields. For ci-DME classification, it achieved an accuracy of 84.1%, sensitivity of 69.1%, and specificity of 88.7%. Interpretability analyses were performed as qualitative assessments to visualize image regions contributing to model predictions. These analyses highlighted retinal vascular structures, hard exudates, and local contrast variations as visual features observed in relation to model outputs. Conclusions: NIR fundus images contain sufficient structural information to support pixel-wise retinal thickness estimation, with vascular architecture, hard exudates, and local contrast variations identified as image features potentially associated with model predictions. These findings suggest that NIR-based deep learning approaches may have potential applications in the assessment of diabetic macular edema and warrant further prospective and external validation to determine their role in screening, triage support, longitudinal monitoring, and treatment-related assessment, particularly in decentralized and re-source-limited care environments. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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10 pages, 220 KB  
Article
Intermediate Visual Performance of Clareon Versus Eyhance Enhanced Monofocal Intraocular Lenses
by Marlena Cwynar-Ptak, Wiktoria Czuj-Porębska, Aleksandra Prus-Ludwig, Jarosław Piłat, Dariusz Dobrowolski, Edward Wylęgała and Bogumił Wowra
Diagnostics 2026, 16(13), 2011; https://doi.org/10.3390/diagnostics16132011 - 27 Jun 2026
Viewed by 445
Abstract
Background/Objectives: Intermediate vision has become increasingly important after cataract surgery because many daily activities require functional visual performance beyond distance vision alone. Enhanced monofocal intraocular lenses may improve intermediate visual function while maintaining good distance visual acuity. The aim of this study [...] Read more.
Background/Objectives: Intermediate vision has become increasingly important after cataract surgery because many daily activities require functional visual performance beyond distance vision alone. Enhanced monofocal intraocular lenses may improve intermediate visual function while maintaining good distance visual acuity. The aim of this study was to compare binocular distance and intermediate visual outcomes after bilateral implantation of Clareon and TECNIS Eyhance intraocular lenses. Methods: This was a single-center, non-randomized comparative observational study with assessment of postoperative visual outcomes. Eighty-six patients who had previously undergone uncomplicated bilateral age-related cataract surgery with implantation of the same IOL model in both eyes were included. Forty-two patients received Clareon IOLs and forty-four patients received TECNIS Eyhance IOLs. Postoperative assessment was performed at least 12 weeks after surgery of the second eye. Binocular corrected distance visual acuity (CDVA) and distance-corrected intermediate visual acuity (DCIVA) were measured using ETDRS charts at 4 m and 66 cm. Results: Baseline biometric and clinical parameters were comparable between groups. Mean postoperative DCIVA was 0.23 ± 0.09 logMAR in the Clareon group and 0.21 ± 0.08 logMAR in the Eyhance group. The mean between-group difference, calculated as Clareon minus Eyhance, was 0.02 logMAR, with a 95% confidence interval from −0.02 to 0.06 logMAR. Mean binocular CDVA was 0.02 ± 0.02 logMAR in the Clareon group and 0.02 ± 0.03 logMAR in the Eyhance group, with a 95% confidence interval for the between-group difference from −0.01 to 0.01 logMAR. Mean postoperative manifest refraction spherical equivalent was −0.27 ± 0.42 D in the Clareon group and −0.29 ± 0.37 D in the Eyhance group. Conclusions: Both Clareon and TECNIS Eyhance IOLs provided good binocular distance and intermediate visual acuity after bilateral implantation. Intermediate visual performance after Clareon implantation was comparable to that achieved with TECNIS Eyhance, while distance visual acuity remained similarly high in both groups. These findings suggest that both IOL models may represent useful options for patients undergoing cataract surgery who expect good distance vision and functional intermediate visual performance. Full article
(This article belongs to the Special Issue Eye Disease: Diagnosis, Management, and Prognosis—2nd Edition)
14 pages, 1118 KB  
Article
Systemic Immune and miRNA Signatures Associated with Long-Term Ranibizumab Response in Neovascular Age-Related Macular Degeneration
by Laura García-Quintanilla, Pablo Almuiña-Varela, María José Rodríguez-Cid, María Gil-Martinez, Maximino J. Abraldes, Francisco Gomez-Ulla, Miguel González-Barcia, Diana Carolina Castro-Fernández, Antonio Cañizo-Outeiriño, Andrea Cuartero-Martínez, Ana Estany-Gestal, Francisco J. Otero-Espinar, Maribel Fernández-Rodríguez and Anxo Fernández-Ferreiro
Pharmaceuticals 2026, 19(6), 955; https://doi.org/10.3390/ph19060955 - 19 Jun 2026
Viewed by 444
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 [...] Read more.
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. Full article
(This article belongs to the Section Biopharmaceuticals)
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13 pages, 8192 KB  
Article
Deep Learning-Based Automated Segmentation and Quantification of the Ellipsoid Zone and the RPE–Bruch’s Membrane Complex in Healthy Subjects and in Geographic Atrophy
by Nasiq Hasan, Adarsh Gadari, Sharat Chandra Vupparaboina, Elham Sadeghi, Giulia Gregori, Utkarsh Doshi, José-Alain Sahel, Sandeep Chandra Bollepalli, Kiran Kumar Vupparaboina and Jay Chhablani
Diagnostics 2026, 16(12), 1872; https://doi.org/10.3390/diagnostics16121872 - 16 Jun 2026
Viewed by 1499
Abstract
Purpose: This study aimed to validate a deep learning algorithm for automated segmentation and quantitative assessment of the ellipsoid zone (EZ) and the retinal pigment epithelium (RPE)–Bruch’s membrane (BM) complex in healthy eyes and geographic atrophy (GA) eyes. Methods: In this retrospective study, [...] Read more.
Purpose: This study aimed to validate a deep learning algorithm for automated segmentation and quantitative assessment of the ellipsoid zone (EZ) and the retinal pigment epithelium (RPE)–Bruch’s membrane (BM) complex in healthy eyes and geographic atrophy (GA) eyes. Methods: In this retrospective study, spectral-domain optical coherence tomography (SD-OCT) volume scans from 30 healthy eyes and 30 eyes with GA were analyzed. An NMI-Outer Retina Analyzer was used to segment the inner EZ, inner RPE, and outer BM. Average thicknesses of the EZ-RPE, EZ-BM, and RPE-BM were calculated from volumes and across nine ETDRS sectors. Manual segmentations were corrected by two masked expert graders and compared using intraclass correlation coefficients (ICCs). Dice coefficients (DCs), Pearson correlation coefficients, and absolute thickness differences were used to assess agreement between automated and manual segmentation. Heat maps were generated to visualize thickness. Results: Thirty healthy eyes and thirty GA eyes were included in the analysis. Mean EZ-RPE, EZ-BM, and RPE-BM thicknesses were 47.55 ± 6.75 µm, 69.49 ± 6.92 µm, and 21.94 ± 3.46 µm, respectively, in the healthy eyes and 15.65 ± 11.09 µm, 39.18 ± 23.28 µm, and 23.52 ± 16.21 µm, respectively, in GA eyes. The model demonstrated high segmentation accuracy, with a mean DC of 0.998 in healthy eyes and 0.995–0.998 in GA eyes. In healthy eyes, differences between automated and manual measurements were minimal (1.42 ± 3.39 μm (2.98%) for EZ-RPE, 1.31 ± 3.18 μm (1.88%) for EZ-BM, and 0.67 ± 1.71 μm (3.05%) for RPE-BM), all within 1.88–3.05% of the gold standard (manual corrections). In contrast, GA eyes showed greater variability (mean differences of 3.61 ± 8.62 μm (23.06%) for EZ-RPE, 4.28 ± 11.34 μm (10.92%) for EZ-BM, and 4.4 ± 10.45 μm (18.71%) for RPE-BM). Heat maps revealed increased variability in the junctional zone surrounding the atrophy. Automated and manual measurements showed strong correlations across all sectors in GA eyes (r = 0.97 for EZ-BM, 0.96 for EZ-RPE, and 0.89 for RPE-BM). Conclusions: The NMI-ORA enables accurate, automated segmentation and quantification of outer retinal layers, with performance comparable to that of expert graders. Full article
(This article belongs to the Special Issue Artificial Intelligence for Health and Medicine—2nd Edition)
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21 pages, 3019 KB  
Systematic Review
Real-World Outcomes of Switching to Aflibercept 8 mg in Previously Treated Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis
by Abdullah Bousamri, Mohammad Kana’an, Faisal Alharbi and Noor Alqudah
J. Clin. Med. 2026, 15(12), 4599; https://doi.org/10.3390/jcm15124599 - 13 Jun 2026
Viewed by 593
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 [...] Read more.
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; I2 = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I2 = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I2 = 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. Full article
(This article belongs to the Section Ophthalmology)
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13 pages, 577 KB  
Article
Functional and Structural Outcomes of Photobiomodulation Therapy in Dry Age-Related Macular Degeneration: A Single-Center Experience
by Sefik Can Ipek, Ceren Durmaz Engin, Ezgi Karatas, Cem Yildirim and Andrzej Grzybowski
J. Clin. Med. 2026, 15(11), 4007; https://doi.org/10.3390/jcm15114007 - 22 May 2026
Viewed by 784
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 [...] Read more.
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 mm3; GEE estimate: +0.0006 mm3; 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. Full article
(This article belongs to the Section Ophthalmology)
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13 pages, 1369 KB  
Article
Real-World Experience with Brolucizumab in Treatment-Naïve nAMD with Low Baseline Visual Acuity: Short-Term Outcomes from a Prospective Single-Institution Study
by Arsim Hajdari and Valdet Uka
Life 2026, 16(5), 754; https://doi.org/10.3390/life16050754 - 1 May 2026
Viewed by 574
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 [...] Read more.
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. Methods: This is a prospective non-randomized study that included 154 treatment-naïve eyes with low baseline visual acuity. We measured visual outcomes (BCVA, logMAR) and structural outcomes (CST, μm). 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. 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 μm after the first injection, 78.5 μm after the second, 117.8 μm after the third, and 143.6 μm at the final timepoint, indicating a pronounced anatomical response to intravitreal brolucizumab therapy. Conclusions: In conclusion, this study demonstrates that brolucizumab therapy provides significant short-term anatomical and functional improvements in treatment-naïve patients with nAMD and poor baseline visual acuity. Baseline visual acuity, treatment-naïve status, and patient age appear to be key determinants of visual gain. Full article
(This article belongs to the Section Medical Research)
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16 pages, 2211 KB  
Article
Subtenon Autologous Platelet-Rich Plasma in Degenerative Retinal Diseases: A Prospective Pilot Study of Safety and Exploratory Functional Signals in Retinitis Pigmentosa and EMAP
by Rubens Camargo Siqueira, Cinara Cássia Brandão, Andreia Conceição de Jesus Souza, Juliana Rodrigues Seixas, Marisa Aparecida Balbino, Luma Moreira Antunes, Charles Muniz de Oliveira, Tainara Souza Pinho and Patrícia Fischer Cruz
Biomedicines 2026, 14(5), 1029; https://doi.org/10.3390/biomedicines14051029 - 30 Apr 2026
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Abstract
Purpose: To evaluate the safety and feasibility of repeated subtenon administration of autologous platelet-rich plasma (PRP) in patients with degenerative retinal diseases and to explore preliminary, hypothesis-generating functional observations in retinitis pigmentosa (RP) and extensive macular atrophy with pseudodrusen-like appearance (EMAP). Methods: This [...] Read more.
Purpose: To evaluate the safety and feasibility of repeated subtenon administration of autologous platelet-rich plasma (PRP) in patients with degenerative retinal diseases and to explore preliminary, hypothesis-generating functional observations in retinitis pigmentosa (RP) and extensive macular atrophy with pseudodrusen-like appearance (EMAP). Methods: This prospective, open-label, uncontrolled pilot study included 13 patients (6 RP, 7 EMAP) who received three subtenon PRP injections (1.5 mL each) at baseline, Month 2, and Month 4, with follow-up through Month 6. The study was designed primarily to assess safety and feasibility and was not powered or intended to evaluate efficacy. The primary outcome was safety, including adverse events and intraocular pressure changes. Exploratory secondary outcomes included best-corrected visual acuity (BCVA, logMAR), visual field mean deviation (MD), and structural optical coherence tomography (OCT) parameters. Electrophysiological outcomes were analyzed descriptively due to incomplete paired data. Analyses were conducted within diagnostic groups, and no between-group comparisons were performed. Results: All 13 patients completed the study. No serious adverse events or permanent ocular morbidity were observed. Two transient and self-limited adverse events occurred (anterior uveitis and intraocular pressure elevation), both resolving without sequelae. In the overall cohort, BCVA remained stable without statistically significant change. In the RP subgroup, a small exploratory change in BCVA was observed (mean ΔlogMAR −0.09; nominal p = 0.048), corresponding to approximately 4–5 ETDRS letters; however, this finding was associated with wide confidence intervals and limited statistical power and should be interpreted cautiously. In the EMAP subgroup, functional stability was observed without evidence of consistent improvement. Visual field mean deviation and OCT findings were consistent with absence of short-term deterioration across available paired data. Electrophysiological outcomes showed no consistent directional change. Conclusions: Repeated subtenon PRP administration appeared feasible and well tolerated in this small, uncontrolled pilot cohort. Any observed functional changes are preliminary and hypothesis-generating only and do not establish efficacy. Larger, adequately powered controlled studies with standardized endpoints are required to determine the potential role of PRP in degenerative retinal diseases. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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13 pages, 2059 KB  
Article
Five-Year Changes in Pachydrusen with Late-Phase Hyperfluorescence on Indocyanine Green Angiography
by Hiroyuki Kamao, Katsutoshi Goto, Kenichi Mizukawa, Ryutaro Hiraki, Atsushi Miki and Shuhei Kimura
J. Clin. Med. 2026, 15(8), 2836; https://doi.org/10.3390/jcm15082836 - 9 Apr 2026
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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 [...] Read more.
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. Full article
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16 pages, 1810 KB  
Article
Local Versus Global Binarization Techniques After Frangi Filtering for Optical Coherence Tomography Angiography Based Retinal Vessel Density Assessment in Diabetic Retinopathy
by Andrada-Elena Mirescu, Ioana Teodora Tofolean, Sanda Jurja, Florian Balta, Alina Popa-Cherecheanu, Ruxandra Angela Pirvulescu, Gerhard Garhofer, George Balta, Irina-Elena Cristescu and Dan George Deleanu
Diagnostics 2026, 16(6), 934; https://doi.org/10.3390/diagnostics16060934 - 21 Mar 2026
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Abstract
Background/Objectives: Optical coherence tomography angiography (OCTA) enables noninvasive quantitative assessment of the retinal microvasculature and is widely used in diabetic retinopathy (DR). However, OCTA-derived metrics are highly dependent on post-processing techniques, particularly vessel binarization. This study aimed to compare local and global binarization [...] Read more.
Background/Objectives: Optical coherence tomography angiography (OCTA) enables noninvasive quantitative assessment of the retinal microvasculature and is widely used in diabetic retinopathy (DR). However, OCTA-derived metrics are highly dependent on post-processing techniques, particularly vessel binarization. This study aimed to compare local and global binarization methods applied after Frangi filtering for vessel enhancement in parafoveal vessel density analysis. Methods: This cross-sectional study included 69 participants: 17 healthy controls and 52 diabetic patients, classified as the following: no DR (n = 14), non-proliferative DR (NPDR, n = 18), or proliferative DR (PDR, n = 20). All subjects underwent comprehensive ophthalmological examination and OCTA imaging of the superficial capillary plexus using a Topcon OCTA system. Images were processed using a custom MATLAB protocol. Following Frangi filtering, five binarization methods were applied: three local (Phansalkar, local Otsu, adaptive mean) and two global (global mean and global Otsu). Parafoveal vessel density was quantified within the four inner quadrants of the ETDRS grid. Results: Statistically significant differences in vessel density were consistently observed between PDR group and both the control and no DR groups across all local binarization methods. Among global methods, only global Otsu thresholding detected a significant difference between PDR and control. The most robust differences were predominantly identified in the nasal and inferior quadrants. Conclusions: Local adaptive binarization methods demonstrated superior sensitivity and structural preservation for parafoveal vessel density analysis in DR. Global methods showed limited discriminative capability. These findings support the preferential use of local adaptive techniques for reliable OCTA-based vascular assessment in diabetic retinopathy. Full article
(This article belongs to the Special Issue Diagnosing, Treating, and Preventing Eye Diseases)
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16 pages, 874 KB  
Article
Assessment of Visual Acuity and Stereopsis in Older Adults: A Comparison Between a Screening Application and Clinical Standards—A Feasibility Study
by Dorottya Wiegand, Eszter Mikó-Baráth, Ildikó Telkes, Balázs Patczai, Adrienne Csutak and Vanda Agnes Nemes
Medicina 2026, 62(3), 517; https://doi.org/10.3390/medicina62030517 - 11 Mar 2026
Viewed by 998
Abstract
Background and Objectives: Visual impairment and reduced stereovision significantly impact the quality of life and increase fall risk in older adults. While standard clinical assessment of visual functions is essential in this population, its use is often limited by the need for specialized [...] Read more.
Background and Objectives: Visual impairment and reduced stereovision significantly impact the quality of life and increase fall risk in older adults. While standard clinical assessment of visual functions is essential in this population, its use is often limited by the need for specialized equipment and trained personnel. Tablet-based screening tools offer a practical alternative but require clinical validation. This study aimed to assess the agreement, reliability, and diagnostic performance of a tablet-based screening application (index methods) compared to established clinical reference methods for assessing visual acuity (VA) and stereovision (SV) in adults over 60 years. Materials and Methods: This prospective, non-blinded, cross-sectional, feasibility study included two cohorts: a test–retest group of 24 older adults assessed twice within 7 days, and a clinical cross-sectional group of 135 participants recruited from primary care practices. VA was measured using tablet-based Landolt C test and compared with an ETDRS-style chart, while stereovision was assessed using tablet-based static and dynamic random dot stereograms and compared with the TNO stereotest. Agreement and reliability were evaluated using Bland–Altman analysis, intraclass correlation coefficients (ICC), and receiver operating characteristic (ROC) curves. Results: The index VA method demonstrated good test–retest reliability (ICC = 0.79) with no significant difference between repeated measurements. In the clinical cross-sectional group, visual acuity measurements showed a small mean bias (0.022 logMAR) between the index and reference methods, which remained within clinically acceptable limits, particularly in the intermediate acuity range. For stereovision, the index SV tests showed high test–retest agreement. Using a TNO cutoff of 480 arcsec, the index SV method demonstrated good diagnostic accuracy (AUC 0.87 for static and 0.85 for dynamic stimuli) with high sensitivity for detecting impaired stereovision. Conclusions: The tablet-based index method provided reliable and clinically comparable results for VA and SV assessments in older adults, supporting its potential use as a screening tool in primary care and community-based settings. Full article
(This article belongs to the Special Issue Personal and Pervasive Health Care for the Elderly)
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