Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy

• Published in: Journal of ocular pharmacology and therapeutics Vol. 38; no. 10; p. 657
• Main Authors: Lindstrom, Richard L, Lewis, Amber E, Holland, Edward J, Sheppard, John D, Hovanesian, John A, Senchyna, Michelle, Hollander, David A
• Format: Journal Article
• Language: English
• Published: United States 01.12.2022
• Subjects: Corneal Edema - drug therapy; Fuchs' Endothelial Dystrophy; Humans; netarsudil; Rho kinase inhibitor; corneal edema; V-FUCHS questionnaire; central corneal thickness; Fuchs corneal dystrophy
• ISSN: 1557-7732
• DOI: 10.1089/jop.2022.0069

This phase 2 study evaluated the therapeutic potential of netarsudil to reduce corneal edema and to improve vision in patients with Fuchs corneal dystrophy (FCD). Patients (  = 40) with baseline central corneal thickness (CCT) of ≥600 μm and best-corrected visual acuity (BCVA) of 70-20 letters (20/40-20/400 Snellen equivalent) were randomized 1:1 to receive netarsudil once a day (QD) or twice a day (BID) for 8 weeks. Primary endpoint was mean CCT change from baseline at week 4. Netarsudil QD and BID significantly reduced CCT at week 4 [mean change (standard error of mean), 28.4 (7.99) μm,  = 0.0021; and 20.1 (8.75) μm,  = 0.0335, respectively]. Five (12.5%) patients achieved complete resolution of corneal edema at week 4. BCVA improved by 3.2 (2.76) letters with QD and 1.5 (2.84) letters with BID, and 10 (25%) patients [5 with QD (  = 0.0078) and 5 with BID (  = 0.0096)] gained ≥10 letters at week 4. Improvements in CCT and vision were observed at week 2 and persisted at week 8, without significant differences between the 2 doses at any time point. Netarsudil QD significantly improved visual acuity and glare factor scores on the Visual Function and Corneal Health Status (V-FUCHS) questionnaire at weeks 4 and 8 (mean change, -0.4 to -0.3;  ≤ 0.0200). Netarsudil was well tolerated. Reticular edema developed in one (2.5%) patient with BID, which resolved with treatment discontinuation. Netarsudil QD led to significant reductions in corneal edema as well as improvements in vision and patient-reported symptoms of glare and visual impairment in patients with FCD. Clinical Trial Registration Number: NCT04498169.