OBJECTIVE: Preservation of visual acuity remains a challenging issue after globe sparing therapy of large uveal melanoma. The aim of our study was analyzing the functional outcome after brachytherapy with bi-nuclide plaques (BBNP), maintaining prognostic factors for legal blindness (LB). METHODS: We have analyzed all consecutive patients with large uveal melanoma treated with BBNP at our institution between 01/1999 and 12/2020. The post-treatment follow-up data were screened up to 06/2023. Univariate and multivariate Cox regression analysis was performed to identify predictive factors for development of LB following BBNP. RESULTS: Overall, 570 patients with median age of 65.6 years (interquartile range [IQR]: 54.5-74.0) underwent BBNP. During the median post-treatment follow-up of 30.8 months (IQR: 12.9-57.3), LB was diagnosed in 287 (50.4%) patients. Patients' age (>
67 years, adjusted hazard ratio [aHR] = 1.58, 95%-confidence interval [CI] = 1.24-2.00, p <
0.0001), tumor thickness (>
8.5 mm, aHR = 1.43, 95%-CI = 1.12-1.82, p = 0.004), VA (>
0.5 LogMAR, aHR = 1.59, 95%-CI = 1.25-2.02, p <
0.0001), and ciliary body involvement (aHR = 0.77, 95%-CI = 0.60-0.97, p = 0.029) were confirmed as independent predictors of LB in the final multivariable Cox regression analysis. CONCLUSIONS: Approximately a half of patients with large uveal melanoma develop LB around 2.5 years after brachytherapy. Further optimization of treatment strategies, including both therapeutic and preventive measures, has the potential to enhance the functional outcome after episcleral plaque therapy for large UMs.