Rho-kinase Inhibitors in Ocular Diseases: A Translational Research Journey.

Abstract

This review summarizes current data on Rho-kinase (ROCK) inhibitors use in ocular diseases, primarily glaucoma. Translational research over the last decade culminating in the development of ROCK inhibitors has provided a much-needed shot in the arm to glaucoma pharmacopeia. ROCK pathway is intricately involved in cytoskeletal modulation with action on cell morphology, cell motility, cell adhesion, cell apoptosis, and smooth muscle contraction. This cytoskeletal modulation property has been utilized to modify trabecular meshwork (TM) resistance, resulting in the discovery of ROCK inhibitors to increase trabecular outflow. Multicentric trials on ROCK inhibitors for antiglaucoma medications are summarized. The focus is on linking pharmacological action to the clinical utility of these drugs. While the Rho Kinase Elevated intraocular Pressure (IOP) Treatment (ROCKET) trials compared monotherapy with ROCK inhibitor netarsudil vs timolol, MERCURY trials compared a fixed dose combination of latanoprost and ROCK inhibitor netarsudil [fixed combination netarsudil-latanoprost (FCNL)] vs monotherapy with either and bimatoprost-timolol combination. While ROCKET trials showed ROCK inhibitors to be non-inferior to timolol, MERCURY trials showed FCNL achieving a much greater IOP reduction than monotherapy with either. Conjunctival hyperemia was the most common side effect reported with ROCK inhibitor use. Moderate efficacy of ROCK inhibitors with a common side effect of conjunctival hyperemia, makes it an adjunctive antiglaucoma drug of choice and not a first-line therapy. ROCK inhibitors' action on diseased TM is more physiological compared to available antiglaucoma medications that either reduce aqueous secretion or enhance uveoscleral outflow. The property of ROCK inhibition to stabilize the endothelium of both retinal vasculature and cornea has opened a new chapter in the treatment of diabetic retinopathy and corneal decompensation. Singh K, Singh A. Rho-kinase Inhibitors in Ocular Diseases: A Translational Research Journey. J Curr Glaucoma Pract 2023;17(1):44-48.