Efficacy and safety of pilocarpine for the treatment of presbyopia: a systematic review and meta‑analysis of randomized controlled trials.

Pilocarpine, the first Food and Drug Administration-approved ophthalmic solution for presbyopia treatment, has garnered substantial attention owing to its therapeutic efficacy and safety profile. This meta-analysis systematically evaluated the effectiveness and safety of pilocarpine in managing presbyopia.Relevant literature published before April 1, 2025 can be retrieved from Web of Science, Embase, PubMed, and Cochrane Library. After screening, extract baseline features and outcome data for inclusion in the study. Finally, a meta-analysis and Trial Sequential Analysis (TSA) were conducted.Five randomized controlled trials (RCTs) were included in this meta-analysis. The meta-analysis demonstrated that pilocarpine significantly increased the number of participants who achieved a mesopic distance-corrected near visual acuity (DCNVA) gain of ≥ 3 lines at 1 h (relative risk [RR]: 1.99, 95% confidence interval [CI] 1.55-2.56), 2 h (RR: 2.08, 95% CI 1.61-2.69), 3 h (RR: 4.30, 95% CI 2.84-6.52), 6 h (RR: 2.02, 95% CI 1.59-2.56), and 8 h (RR: 1.77, 95% CI 1.37-2.28), compared to controls. However, pilocarpine significantly increased the risk of participants experiencing ≥ 1 treatment-emergent adverse events (TEAEs), blurred vision, visual impairment, eye pain, headache, and nausea (P < 0.05) but had no significant effect on conjunctival hyperemia and instillation site pain (P > 0.05). TSA revealed conclusive results for mesopic DCNVA gain of ≥ 3 lines, participants with ≥ 1 TEAEs, blurred vision, visual impairment, and nausea. Except for eye pain (P = 0.010), the remaining outcomes showed no potential publication bias (P > 0.05). The evidence quality for DCNVA gain of ≥ 3 lines was rated as moderate, while that for safety outcomes ranged from very low to moderate.In conclusion, pilocarpine improves visual function in patients with presbyopia; however, it may increase the risk of adverse events. Owing to the limited sample size, these findings warrant further validation through large-scale multicenter RCTs.