Prostaglandin Analogs and Timolol-Fixed Versus Unfixed Combinations or Monotherapy for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

Purpose: To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with beta-blockers. Methods: We searched the Medline and Embase databases for randomized trials comparing topical therapies with PGAs and timolol administered as monotherapy (Mt), or in fixed (FC) or unfixed combinations (UC) to patients with glaucoma or ocular hypertension. The efficacy endpoint was the mean difference (MeD) in the reduction in IOP from baseline; the tolerability endpoint was the incidence of hyperemia. Results: The 18 eligible trials involved 23 comparisons of FC versus Mt, and 5 of FC versus UC. The FCs were less efficacious than UCs (MeD: 0.69, 95% CI: 0.29 to 1.08). In comparison with timolol Mt, the latanoprost/timolol FC led to a greater IOP reduction (MeD: - 2.74, 95% CI: - 3.24 to - 2.23) than the bimatoprost/timolol FC (MeD: - 1.49, 95% CI: - 1.86 to - 1.12) or the travoprost/timolol FC (MeD: - 1.93, 95% CI: - 2.98 to - 0.88). The FCs led to a lower hyperemia risk than UCs [relative risk (RR): 0.70, 95% CI: 0.43 to 1.14] and PGA Mt (RR: 0.61, 95% CI: 0.53 to 0.70). Conclusions: FCs are more efficacious than their individual components, but less efficacious than their respective UCs. FCs lead to a lower hyperemia risk than UCs and their respective PGA Mts.