Emerging Role of Rho-kinase Inhibitors in Ophthalmology: A Narrative Review

Abstract

Rho-kinase (ROCK) inhibitors entered clinical practice as intraocular pressure (IOP)-lowering agents, yet emerging evidence suggests they may represent the first ophthalmic drug class capable of simultaneously modulating fibrosis, cellular regeneration, vascular dysfunction, and neurodegeneration across multiple ocular tissues. We reviewed the evidence supporting this expanding therapeutic paradigm. Published evidence spanning basic science, translational research, and clinical investigation was critically synthesized to evaluate the evolving role of ROCK inhibitors across glaucoma, corneal disease, and retinal pathology, with emphasis on clinical readiness, evidence gaps, and future therapeutic opportunities. Evidence maturity differed substantially across ocular subsystems. In glaucoma, multiple phase 2–3 randomized trials establish ROCK inhibitors as effective IOP-lowering agents with favorable long-term safety. In corneal disease, accumulating clinical evidence suggests a potential shift from replacement strategies toward endothelial regeneration, particularly in Fuchs endothelial dystrophy and post-Descemet stripping only procedures. In retinal disease, preclinical and early clinical studies indicate antifibrotic, antiangiogenic, and vasomodulatory effects, but translational development remains limited despite compelling biological rationale. ROCK inhibitors have evolved from IOP-lowering agents into multifunctional therapeutic candidates with potential applications across glaucoma, corneal endothelial disease, and retinal pathology. While clinical evidence is established in glaucoma and increasingly encouraging in corneal disease, retinal applications remain largely translational. Future progress will depend on adequately powered clinical trials capable of determining whether mechanistic promise translates into meaningful patient benefit.