Meta-analysis of randomized controlled trials comparing timolol with brimonidine in the treatment of glaucoma

This paper aims to compare the efficacy and tolerability of timolol versus brimonidine in the treatment of glaucoma. Comprehensive searches were performed using Medline, Embase and the Cochrane Controlled Trials Register for randomized controlled trials comparing timolol and brimonidine. Two reviewers independently assessed trials for eligibility and quality and extracted data. A random effects model was used to combine studies. Outcome was defined as the absolute mean intraocular pressure (IOP) reduction from baseline to end-point for efficacy, and relative risk (RR) for adverse events. Subgroup analysis and meta-regression were used to explore heterogeneity according to trial design and quality. Ten publications reporting on eight trials with 2387 participants were included in the meta-analysis. Two further trials were commented on qualitatively. IOP reduction was not significantly different between timolol and brimonidine. Weighted mean difference (WMD) of IOP reduction was 0.24mmHg (favouring brimonidine) with a 95% confidence interval of -0.57 to 1.04 mmHg. There was significant heterogeneity between studies (X²13 = 73.75, P <0.00001, I² =91%). Subgroup analysis showed no significant WMD for studies where data were analysed from end-points ≥6 months or <6months. Meta-regression analysis showed increased WMD IOP reduction in favour of brimonidine with increased trial quality (t₃ =-4.58, P = 0.01), but no significant association with trial duration (t₃ = 0.73, P = 0.51) or size (t₃ =-0.59, P = 0.57). The RR of ocular allergy was much lower with timolol than brimonidine (RR=0.08, 95% confidence interval 0.01 to 0.47). Publication bias was not evident on a funnel plot, although the number of studies was small. The conclusion is that both drugs are equally effective in lowering IOP. Brimonidine is associated with a higher rate of allergy.