Efficacy of Topical Timolol in Chronic Unhealed Ulcers: A Systematic Review and Meta-Analysis

Background Topical timolol appears to provide a curative effect in managing chronic ulcers. However, the pooled evidence of its effect hasn’t been established yet. This is the first Meta-analysis to evaluate and assess the efficacy of topical timolol in accelerating wound healing in patients with chronic refractory ulcers. Methods We comprehensively searched different electronic databases; PubMed, Scopus, Web of Science, Cochrane library and ClinicalTrials.gov from their inception to November 2024. The search was conducted without imposing any restrictions on publication date or study design. The ROB-II tool was used to assess the quality of included RCTs. NIH tools were used to evaluate the quality of included cohort and single arm studies. Risk ratios (RR) and mean differences (MD), with 95% confidence intervals (CIs), were used as effect estimates. Results Six studies were included in this systematic review, comprising two single-arm studies and four double-arm studies (3 RCTs and 1 cohort study). Data from the four double-arm studies on venous ulcers were pooled for meta-analysis. The results showed that topical timolol significantly reduced ulcer area compared to control at 2 weeks (−23.63%; 95% CI: −29.26 to −18.00; p < 0.00001), 4 weeks (−41.40%; 95% CI: −49.57 to −33.23; p < 0.00001), and 12 weeks (−23.38%; 95% CI: −39.43 to −7.33; p = 0.004). Complete ulcer healing was observed at 4 weeks (RR: 12.00; 95% CI: 1.68 to 85.84; p = 0.01) and 12 weeks (RR: 3.79; 95% CI: 0.44 to 32.54; p = 0.22). Conclusion Topical timolol has the potential to promote healing in chronic unhealed ulcers. This meta-analysis, focusing on chronic venous ulcers, consistently showed favorable results across different time points. However, the small sample sizes, lack of blinding, and inclusion of only four studies limit the generalizability of the findings.