Rho-Kinase Inhibitors in Glaucoma Management: A Systematic Review of Current Evidence and Emerging Ophthalmic Applications

Background: Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive optic neuropathy associated with retinal ganglion cell loss. Elevated intraocular pressure remains the most important modifiable risk factor for disease progression. Objective: To systematically review the mechanism of action, clinical efficacy, and safety profile of Rho-kinase (ROCK) inhibitors in glaucoma management while also highlighting their emerging investigational roles in corneal and retinal diseases. Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 Statement. Studies evaluating the use of ROCK inhibitors in glaucoma and their emerging applications in corneal and retinal disorders were included. Randomized controlled trials, observational studies, and experimental studies were analysed. Risk of bias for randomized controlled trials was assessed using the Cochrane Risk of Bias Tool, while observational studies were evaluated qualitatively. Results: Twenty-eight studies fulfilled the inclusion criteria. ROCK inhibitors, such as netarsudil and ripasudil, significantly lower intraocular pressure by enhancing the trabecular meshwork (TM) outflow and reducing episcleral venous pressure. Randomized trials, including the ROCKET and MERCURY studies, demonstrated efficacy comparable to established glaucoma medications. Experimental and early clinical studies suggest potential therapeutic roles in corneal endothelial regeneration, while evidence supporting retinal neuroprotection remains largely preclinical. Conclusion: ROCK inhibitors represent an important addition to glaucoma pharmacotherapy due to their novel mechanism targeting the TM outflow. Their emerging investigational applications in corneal endothelial disorders and retinal diseases highlight their broader investigational therapeutic potential in ophthalmology, although further clinical studies are required to establish their role beyond glaucoma management.