ROCK inhibitors in ophthalmology: A critical review of the existing clinical evidence

Abstract

Rho kinase (ROCK) inhibitors have emerged as a key therapeutic class of interest in ophthalmology over the last decade. Promising in vitro studies laid the foundations for the development of novel therapeutic agents that target the ROCK signalling pathway in ocular disease, with subsequent clinical trials supporting their use. Corneal endothelial disease, glaucoma, and vitreoretinal disease are the major pathologies in which ROCK inhibitors have been investigated to date. Ripasudil and netarsudil represent the current leaders in this pharmaceutical group, having been extensively validated and approved for use in glaucoma in some countries. Less substantial evidence exists for fasudil in ophthalmic use. ROCK inhibitors are also increasingly used in cultured endothelial cell grafting and as an adjunct to aid in endothelial cell migration and replication in Descemet's stripping procedures or Descemet's membrane injuries. This review has synthesised both established and emerging research to provide a practical guide to prescribing in this drug class. Drug efficacies, side effect profiles, and the demographic and clinical characteristics of appropriate drug candidates are discussed.

Evaluating the efficacy of Rho kinase inhibitor eye drops in the management of corneal edema: A single-center retrospective cohort study

“…Approved in the US in 2017 and Europe in 2019 for reducing elevated IOP in primary open-angle glaucoma or ocular hypertension, it is administered once daily. [ 19 20 ] The drug has demonstrated consistent IOP reduction throughout the day and night and has been well-tolerated in multiple studies. [ 18 21 22 ]…”

“…[ 23 ] Other ROCK inhibitors such as SNJ-1656 and Y-27632 are in various stages of clinical trials but are not yet commercially available. [ 18 19 21 22 ]…”

The Role of Rho Kinase Inhibitors in Corneal Diseases

“…Several mechanisms have been proposed for the activation of the ROCK pathway in corneal endothelial cells which cause increased cellular contractility, decreased cell proliferation, and reduced cell migration, ultimately leading to endothelial cell dysfunction. 7 , 37–39 …”

“…It has been approved in the United States since 2017, with subsequent authorization in the European Union in 2021. 7 , 39 …”

Rho-Kinase Inhibitors as Emerging Targets for Glaucoma Therapy

“…The use of ripasudil for treating different subtypes of glaucoma, its long-term effects and adverse reactions, and maximum therapy tolerance, and the criteria for selecting target patients have been reported. Although ripasudil has been suggested as an effective monotherapy for uveitic glaucoma, most studies have indicated ripasudil as an adjuvant therapy to the first-line drugs for glaucoma [ 51 ]. So far, randomized controlled clinical trials of ripasudil monotherapy or existing standard therapy are lacking.…”