Effects of Netarsudil on the Corneal Endothelium: 3-Month Findings From a Phase 3 Trial

Abstract Purpose To describe the changes in endothelial cell density (ECD), the coefficient of variation (CV), and the percent of hexagonal cells (%HEX) following 3 months of therapy with netarsudil (Rhopressa) 0.02% dosed once or twice daily and to compare these changes to those seen with timolol 0.5% twice daily in eyes with ocular hypertension or open-angle glaucoma. Design Post hoc analysis of data from a Phase 3 evaluation of the IOP-lowering efficacy and safety of netarsudil 0.02% versus timolol 0.5%. Subjects A subset of study subjects underwent corneal endothelial cell imaging by specular microscopy at baseline and following 3 months of therapy. Methods Images were evaluated in a masked fashion at an independent reading center. ECD, CV, and %HEX were determined using a standardized protocol for image analysis. Main Outcome Measures Changes in ECD, CV, and %HEX from baseline to 3 months were compared between treatment groups using two-sample t-tests. Results Data from 386 subjects from whom analyzable specular microscopy images were obtained at both baseline and Month 3 were included in this analysis. Mean ECD, CV, and %HEX values were comparable between groups at baseline. There were no statistically significant between-group differences in changes from baseline to Month 3 in ECD, CV, or %HEX between either of the netarsudil groups and the timolol group. Within groups, CV declined in a statistically significant fashion from baseline to Month 3 in all three groups by 1.4-2.1% (P Conclusions Netarsudil 0.02% showed no clinically significant effects on ECD, CV, or %HEX when dosed once or twice daily for 3 months in eyes with ocular hypertension or open-angle glaucoma.