高山 卓也

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.

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.

Aflibercept and brolucizumab, two anti-VEGF agents used as intravitreal injections in ophthalmology, differ significantly in molecular weight (aflibercept-115 kDa and brolucizumab-26 kDa). Using aqueous humor samples collected after drug administration, we measured and performed a comparative analysis of pharmacokinetics and half-lives of these drugs in the human eye. Since the quantification of monoclonal antibodies (mAbs) using antigen-antibody reactions, such as ELISA, is influenced by endogenous ligands or anti-drug antibodies, we employed nano-surface and molecular-orientation limited proteolysis (nSMOL), combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), for accurate measurements. Aqueous humor samples were collected from 59 eyes of 59 patients treated with aflibercept and 52 eyes of 52 patients treated with brolucizumab. Samples were obtained with a median post-injection period of 30 (range, 2-49) days for aflibercept and 28 (range, 4-60) days for brolucizumab. A population pharmacokinetic (PPK) analysis revealed that the half-life of aflibercept in human aqueous humor was significantly shorter than that of brolucizumab, 2.88 days versus 9.00 days, respectively (p = 1.16 × 10-7). Using the same mass spectrometry conditions, we calculated the half-lives of the two drugs. These results may be useful for optimizing the efficacy of these drugs in clinical practice.