Efficacy and safety of polyhexamethylene biguanide for Acanthamoeba keratitis: Systematic review and proportional meta-analysis

Background Polyhexamethylene biguanide (PHMB) 0.08% has received the orphan drug designation for management of Acanthamoeba keratitis (AK). This review aimed to evaluate the clinical efficacy and safety of PHMB, comparing outcomes across different concentrations (0.08% vs. 0.02%) using a dose-stratified meta-analysis. Methods Online databases were searched until February 2025 for studies on PHMB 0.02% or 0.08% as mono- or combination therapy. The primary outcome was clinical cure and secondary outcomes included conjunctival hyperemia and pain. Subgroup analyses were performed based on PHMB concentration. A random-effects model was applied; sensitivity analyses and publication bias assessments were conducted. Results The pooled proportion of cure across 17 studies (923 eyes) was 75.75% (95% CI: 64.56%–84.27%; p < 0.0001; I² = 85.2%). Subgroup analysis showed the highest cure rate with PHMB 0.08% monotherapy (87.04%; 95% CI: 77.54%–92.88%), followed by 0.02% monotherapy (79.27%; 95% CI: 65.29%–88.60%) and mixed 0.02% regimens (72.59%; 95% CI: 54.86%–85.23%). Conjunctival hyperemia was reported in 15.7%, and subgroup analysis by dose revealed highest prevalence in the 0.08% PHMB group (26.4%; 95% CI: 8.4%–49.2%). Pain was reported in 11.9% ( n = 225), with no significant increase at higher concentrations. The pooled proportion of overall adverse events was 40.2% (95% CI 26.2%–55.0%; p < 0.0001; I² = 81.4%). Findings were robust across sensitivity analyses, with no publication bias detected. Conclusion This dose-stratified meta-analysis found PHMB 0.08% monotherapy to have good efficacy and tolerability, supporting its use as a first-line empirical treatment and underscoring the need for standardized protocols and comparative trials.