蕪城 俊克

PURPOSE: To evaluate the clinical performance of "Direct Strip PCR," a multiplex solid-phase real-time polymerase chain reaction (PCR) kit, for diagnosing infectious uveitis. STUDY DESIGN: Multicenter, prospective, diagnostic accuracy study METHODS: We analyzed 475 ocular-fluid samples (336 aqueous humor and 139 vitreous fluid) from 29 sites in Japan. Direct Strip PCR, an IVD-grade multiplex real-time PCR kit targeting HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HTLV-1, Toxoplasma gondii, and Treponema pallidum requiring no DNA extraction and incorporating internal controls, was compared with quantitative PCR (qPCR) for concordance and DNA copy-number correlation. RESULTS: All 9 of the target pathogens were detected. Direct Strip PCR showed excellent agreement with qPCR, with percent positive agreement (PPA), percent negative agreement (PNA), and percent overall agreement (POA) in aqueous humor of 98.0%, 99.2%, and 98.5%, respectively, and in vitreous fluid of 95.7%, 97.1%, and 96.4%, respectively, indicating high concordance for positive and negative results. All the values exceeded predefined 90% thresholds agreed upon with the Pharmaceuticals and Medical Devices Agency, meeting the required performance criteria. Discordant results were infrequent (10/4275 targets) and involved low-copy samples near the detection limit. The DNA copy numbers correlated strongly between the methods (r = 0.948-0.996). No adverse events were reported. CONCLUSION: Direct Strip PCR demonstrated high concordance with qPCR, reliably detected major pathogens of infectious uveitis, and yielded quantitative results that correlated with the qPCR results, supporting disease monitoring. Its solid-phase, extraction-free, and per-run calibration-free format provides a practical basis for regulatory submissions and global dissemination of multiplex PCR.

Background: This study aims to characterize the clinical features and outcomes of tattoo-associated sarcoid-like uveitis using a multicenter uveitis registry given the limited existing data. Design: This is a retrospective study. Participants: Ten patients (20 eyes) diagnosed with tattoo-associated sarcoid-like uveitis took part in the study. Methods: The data of patients newly evaluated at participating registry centers from January 2000 to June 2025 were reviewed. Demographic data, treatments, visual acuity, recurrence, glaucoma/intraocular pressure (IOP)-lowering therapy, extraocular involvement, and histologic confirmation were extracted when available. Main Outcome Measures: Recurrence, glaucoma/IOP-lowering therapy, extraocular involvement, and change in logarithm of the minimum angle of resolution (logMAR) from presentation to final follow-up were measured. Results: Seven (70%) patients were male, and the patients' mean age was 35.1 ± 7.8 years. All patients exhibited bilateral ocular involvement. Histologic confirmation at the tattoo site was documented in five (50%) patients. The mean logMAR visual acuity was 0.12 ± 0.31 at presentation and 0.16 ± 0.42 at the final follow-up (median follow-up: 20 months). All patients received topical corticosteroids; periocular steroids were administered in seven cases (70%), oral systemic steroids in four (40%), adalimumab in two (20%), and cyclosporin in one (10%). Seven cases (70%) developed uveitis recurrence, and eight received glaucoma/IOP-lowering therapy (80%). Extraocular inflammation affected the skin/tattoo in seven patients (70%) and the axillary lymph nodes in one (10%). This finding is definitive; however, this is also true even when the organ/body part is plural (e.g., lungs). Conclusions: Tattoo-associated sarcoid-like uveitis often follows a chronic course with frequent recurrence and uveitic glaucoma. Thus, close ophthalmic monitoring and coordinated systemic evaluation may be warranted.

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.