Subbasal Nerve Plexus Alterations Following Ocular Proton Therapy in Uveal Melanoma Assessed by Corneal Confocal Microscopy

Purpose To evaluate longitudinal changes in the subbasal nerve plexus (SNP) after ocular proton therapy (OPT) in eyes with uveal melanoma and associated changes in corneal sensitivity, cell density, and patient-reported outcomes. Design Prospective clinical cohort study. Subjects Fifty-eight patients (58 eyes) with uveal melanoma were enrolled; 54 had evaluable baseline corneal confocal microscopy images, and 40 formed the longitudinal analysis cohort. Follow-up data were available for 30 patients at 3 months and 27 patients at 12 months. Methods Corneal confocal microscopy was used to assess SNP parameters and cell density. Corneal sensitivity was measured with a Cochet-Bonnet aesthesiometer. Patient-reported outcomes were assessed using the German Ocular Surface Disease Index (OSDI) and selected domains from the German version of the NEI VFQ-25. Examinations were performed before OPT and at 3 and 12 months after OPT. Main Outcome Measures Primary outcome measures were changes in corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL). Secondary outcome measures included corneal nerve fiber tortuosity (CNFT), cell density, corneal sensitivity, OSDI, and selected NEI VFQ-25 domains. Results CNFD decreased from 18.2 to 11.4 (3 months) and 12.7 no./mm² (12 months) ( P = .002 and .001). CNBD decreased from 23.9 to 13.5 and 15.8 no./mm² ( P = .012 and .040), and CNFL from 11.0 to 6.2 and 7.3 mm/mm² (both P < .001). Nerve loss was associated with treatment-related exposure, particularly the clinical target volume. CNFT decreased at 3 months ( P = .018) and approached baseline at 12 months ( P = .28). Corneal sensitivity did not change significantly. OSDI increased at 12 months ( P = .049). After Benjamini-Hochberg correction, the 3-month CNFT, 12-month OSDI, and 12-month cell density changes were no longer significant. Among NEI VFQ-25 domains, only peripheral vision declined (84 to 68; P = .006). Conclusions OPT was associated with marked reduction of SNP parameters, with only partial recovery by 12 months. Greater nerve loss was associated with larger treatment volumes and greater corneal irradiation. Cell density and corneal sensitivity remained unchanged, whereas patient-reported outcomes did not consistently reflect structural denervation.