Intraocular pressure-lowering efficacy and ocular safety of Rho-kinase inhibitor in glaucoma: a meta-analysis and systematic review of prospective randomized trials

Abstract

Purpose: To evaluate the intraocular pressure (IOP)-reducing efficacy and safety of Rho-kinase inhibitor (RKI).

Methods: Published studies in PubMed and EMBASE were searched on March 20, 2021. Study selection and data extraction were performed according to PRISMA. Meta-analysis of the IOP-lowering effect was performed with the bivariate random-effects model, with studies categorized into 2 classes: RKI versus placebo and RKI versus another medication. The main outcome was the difference in IOP reduction between RKI and non-RKI groups. Subgroup analysis of adjunctive RKI efficacy and additional review of its major ocular adverse events (AE) were also performed.

Results: Ten (2.6%) out of 391 studies were retrieved. In the RKI versus placebo class, RKI showed greater IOP reduction after 4-8 weeks (mean difference = - 1.69 mmHg [- 2.22, - 1.16], P < 0.001). In the RKI versus another medication class, IOP reduction by RKI was noninferior to timolol 0.5% twice-daily after 4-8 weeks (mean difference = 0.39 mmHg [0.01, 0.76], P = 0.043) and 12 weeks (mean difference = 0.48 mmHg [0.11, 0.85]; P = 0.011). In the subgroup analysis, the mean difference in IOP reduction by adjunctive RKI and placebo was - 1.42 mmHg (P < 0.001). The most common ocular AE of RKI was conjunctival hyperemia (19-65%), followed by conjunctival hemorrhage (6-20%) and cornea verticillata (13-26%).

Conclusions: With a treatment duration of 1-3 months, RKI showed effective IOP reduction noninferior to timolol as monotherapy and as adjunctive therapy. Our results suggested RKI be a reliable IOP control medication; however, its higher incidence of some ocular complications should be attended to.

Keywords: Efficacy; Glaucoma; Intraocular pressure; Netarsudil; Ocular adverse events; Ocular safety; Rho-kinase inhibitor; Ripasudil.