rho kinase inhibitor for primary open‐angle glaucoma and ocular hypertension ‐ a Cochrane systematic review

Purpose: To compare the efficacy and safety of rho kinase inhibitor (ROKi) with placebo or other glaucoma medication in people diagnosed with open‐angle glaucoma (OAG), primary open‐angle glaucoma (POAG) or ocular hypertension (OHT). Methods: We searched CENTRAL, MEDLINE, Embase, PubMed, LILACS, ClinicalTrials and ICTRP for randomized clinical trials and controlled clinical trials with no restrictions of type, year, and publication status. Two review authors independently screened, extracted data, and evaluated risk of bias. Results: We included 17 trials (4953 participants) evaluating the efficacy and safety of marketed ROKI‐based drugs; netarsudil and ripasudil. Trial duration varied from 24 h to 12 months. The intraocular pressure (IOP) lowering effect of netarsudil may be superior to placebo (mean difference (MD) 3.11 mmHg 95% CI 2.59–3.62; low‐certainty evidence), but inferior to latanoprost (MD 0.97 mmHg 95% CI 0.67–1.27; moderate‐certainty) and timolol (MD 0.66 95% CI 0.41–0.91; low‐certainty). Combining netarsudil and latanoprost probably further reduces IOP compared with either netarsudil (MD 2.66 mmHg 95% CI 2.35–2.98; moderate‐certainty) or latanoprost (MD 1.64 mmHg 95% CI 1.11–2.16; moderate‐certainty). Combining ripasudil and timolol may probably reduce IOP compared with timolol monotherapy (MD 0.75 mmHg 95% CI 0.21–1.29; moderate‐certainty). The certainty of evidence reporting ocular adverse events (AEs) was very low or low. However, compared to timolol, netarsudil (21 additional ocular AEs per 100‐person‐months 95% CI 14–27; moderate‐certainty) and combination therapy with ripasudil/timolol (35 additional ocular AEs per 100 person‐months 95% CI 25–45; moderate‐certainty) probably lead to more ocular AEs. ROKi was not associated with any particular serious AEs. Conclusions: The current evidence suggests that in people diagnosed with OHT or (P)OAG, the hypotensive effect of netarsudil may be inferior to latanoprost and slightly inferior to timolol. Combining netarsudil and latanoprost probably further reduces IOP compared with monotherapy. However, differences are small and may not be clinically significant. Netarsudil as mono‐ or combination therapy may result in more ocular AEs, but the evidence on AEs is limited.