Rho-Kinase Inhibitors In Fuchs Endothelial Corneal Dystrophy: A Systematic Review

To examine the efficacy and safety of Rho-kinase (ROCK) inhibitors in Fuchs endothelial dystrophy (FECD), the most common form of endothelial dystrophy. Although endothelial keratoplasty remains the standard treatment, limited donor availability, heightened risk for infection and graft failure, have necessitated the investigation of alternative therapeutic options.

This systematic review was conducted at the 2^nd Department of Ophthalmology, Aristotle University of Thessaloniki School of Medicine.

A comprehensive literature search was conducted until February 24, 2026 in PubMed, Scopus and the Cochrane Central Register of Controlled Trials. Search terms comprised variants of “Rho-kinase inhibitors,” “ROCK inhibitors,” “Fuchs endothelial dystrophy” and “FECD.” Only clinical studies evaluating at least one ROCK inhibitor and reporting at least one of the selected functional or cellular outcomes—endothelial cell density, central corneal thickness (CCT), visual acuity, or cell migration/ proliferation—were included in this review. Only peer-reviewed articles in English were considered. Title and abstract were screened by two independent reviewers, while any disagreements were resolved by a third reviewer. 

12 clinical studies met the inclusion criteria, including 4 randomized controlled trials, 3 non-randomized trials and 5 case reports. Ripasudil was investigated in 5 studies, netarsudil in 2 and the ROCK inhibitor Y-27632 in 4. Descemet Stripping Only (DSO) with ripasudil compared to DSO alone, showed significant reductions in CCT and improvement in best-corrected visual acuity (BCVA). Netarsudil significantly reduced CCT after 1 month, with once and twice-daily dosing showing similar efficacy (p= 0.0021 and 0.0335). Transplantation of human corneal endothelial cells supplemented with ROCK inhibitors increased endothelial cell density after 24 weeks. Adverse effects of ROCK inhibitors included ocular irritation and honeycomb corneal edema.

FECD is the main indicator for corneal transplantation in developed countries. At present, there is no FDA-approved pharmacological treatment to prevent its progression. There is a critical need for alternatives to delay or prevent surgery. ROCK inhibitors have emerged as a promising therapeutic option for FECD, playing a vital role in endothelial function by promoting cell proliferation, inhibiting apoptosis and boosting endothelial wound healing.