Abstract

This systematic review evaluated the efficacy and safety of netarsudil compared to traditional prostaglandin analogs (PGAs) for intraocular pressure (IOP) control in open-angle glaucoma, synthesizing evidence from randomized clinical trials published between 2020 and 2025. A comprehensive literature search of PubMed, Web of Science, and Google Scholar yielded 10 randomized controlled trials meeting the inclusion criteria. The findings demonstrated that netarsudil effectively reduces IOP, though PGA monotherapy generally achieves greater mean reductions. The fixed-dose combination of netarsudil and latanoprost consistently provided superior IOP lowering compared to either agent alone, suggesting an additive or synergistic effect. Regarding safety, netarsudil was associated with a higher incidence of ocular adverse events, predominantly mild-to-moderate conjunctival hyperemia, subconjunctival hemorrhage, and corneal verticillata, while PGAs demonstrated their known profile of hyperemia, iris pigmentation changes, and eyelash growth. No serious treatment-related adverse events were reported across the included trials. Risk of bias assessment using the Cochrane Risk of Bias 2 tool identified four studies with low risk, two with some concerns, and four with high risk, primarily due to missing outcome data or limitations in randomization. In conclusion, while prostaglandin analogs remain more potent as monotherapy, netarsudil represents a valuable adjunctive option, particularly for patients requiring additional IOP lowering or those with suboptimal response or intolerance to first-line PGA therapy. Careful patient counseling regarding the higher likelihood of conjunctival hyperemia is warranted to optimize adherence and treatment success.

Key words: Open-angle glaucoma, netarsudil, prostaglandin analogs, intraocular pressure, Rho kinase inhibitors