Efficacy and tolerability of prostaglandin-timolol fixed combinations: a meta-analysis of randomized clinical trials.

PURPOSE To evaluate the intraocular pressure (IOP)-lowering effects and tolerability of the 3 prostaglandin-timolol fixed combinations (PG-timolol FCs). METHODS Clinical trials comparing directly the PG-timolol FCs or comparing the PG-timolol FCs to their individual components were thoroughly searched. The main outcome measures were efficacy assessed by IOP (taken at 9 am, noon, 4 pm, and over the mean diurnal curve) change at 3 months (or after 1 to 6 months of treatment if no data were available at month 3) from baseline and tolerability assessed by the incidence of conjunctival hyperemia. RESULTS Twenty trials were identified (n = 4684 patients). Intraocular pressure reduction was usually greater with the 3 PG-timolol FCs than the individual PG (mean difference [MD] 0.00 mmHg to 2.59 mmHg; p>0.1 to p<0.001). The incidence of hyperemia was significantly less with latanoprost- and bimatoprost-timolol FCs than with the individual PG (relative risk = 0.66 and 0.61; p = 0.05 and p<0.001). From direct comparisons, IOP reduction was significantly greatest with bimatoprost-timolol FC, at 9 am, 4 pm, and over the mean diurnal curve compared to latanoprost-timolol FC (MD = 0.90 mmHg to 1.48 mmHg; p<0.001) and at all time points compared to travoprost-timolol FC (MD = 0.66 mmHg to 0.90 mmHg; p<0.001). The incidence of hyperemia was not significantly less with latanoprost-timolol FC than with bimatoprost-timolol FC (relative risk = 1.32; p>0.1). CONCLUSIONS The 3 PG-timolol FCs provide a greater IOP reduction and lower incidence of hyperemia than the 3 PGs alone. The direct comparisons suggest a greater efficacy of the bimatoprost-timolol FC compared with latanoprost- and travoprost-timolol FCs.