蕪城 俊克

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-28911-9.

PURPOSE: To evaluate real-world adherence to anti-vascular endothelial growth factor (VEGF) therapy among Japanese patients with diabetic macular edema (DME) and identify demographic, clinical, and socioeconomic factors associated with treatment discontinuation. STUDY DESIGN: Retrospective, observational cohort study. METHODS: This study included 380 treatment-naïve patients with center-involved DME. Patients were categorized into continuation (those who maintained therapy) and self-discontinuation (those who discontinued therapy after at least one follow-up visit) groups. All patients were treated under a treat-and-extend regimen with one of five anti-VEGF agents (ranibizumab, aflibercept, brolucizumab, faricimab, or ranibizumab biosimilar) between January 2017 and December 2023. Univariate and multivariate logistic regression analyses identified independent predictors of treatment discontinuation. Pre- and post-treatment visual acuity and anatomic outcomes were assessed. RESULTS: Among 380 patients, 55 (14.5%) self-discontinued therapy. Younger age and poorer baseline best-corrected visual acuity were significantly associated with treatment discontinuation in both univariate and multivariate analyses. Furthermore, faricimab use increased the risk of discontinuation, whereas aflibercept use was associated with better adherence. CONCLUSION: The findings of this study underscore the importance of individualized patient management strategies to enhance long-term adherence to anti-VEGF therapy among patients with DME.

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 (R2) 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 R2 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).

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. 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. 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 = 0.0032), while no significant difference was observed with aflibercept (6.9 vs. 6.7 pc/ms, P = 0.55). Flare values increased significantly with age in the brolucizumab group (P = 0.0076) but not in the aflibercept group (P = 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® (brolucizumab) and 161.8 (31) pc/ms for Eylea® (aflibercept). 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.

Retinal breaks are critical lesions that can cause retinal detachment and vision loss if not detected and treated early. Automated, accurate delineation of retinal breaks in ultra-widefield fundus (UWF) images remains challenging. In this study, we developed and validated a deep learning segmentation model based on the PraNet architecture to localize retinal breaks in break-positive cases. We trained and evaluated the model using a dataset comprising 34,867 UWF images of 8083 cases. Performance was assessed using image-level segmentation metrics, including accuracy, precision, recall, Intersection over Union (IoU), dice score, and centroid distance score. The model achieved an accuracy of 0.996, precision of 0.635, recall of 0.756, IoU of 0.539, dice score of 0.652, and centroid distance score of 0.081. To our knowledge, this is the first study to present pixel-level segmentation of retinal breaks in UWF images using deep learning. The proposed PraNet-based model showed high accuracy and robust segmentation performance, highlighting its potential for clinical application.