Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy. A multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 GyRBE to the optic apparatus were analyzed in this study. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age, arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. An NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. The authors suggested the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning.