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

Abstract

Purpose: To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with b-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.

24-hour efficacy of the bimatoprost–timolol fixed combination versus latanoprost as first choice therapy in subjects with high-pressure exfoliation syndrome and glaucoma

“…This meta-analysis together with a more recent meta-analysis by Quaranta and coworkers30 confirmed that prostaglandin–timolol fixed combinations can significantly enhance the efficacy of prostaglandin monotherapies and, at the same time, reduce one of their important side effects, conjunctival hyperaemia. There is however limited information available concerning the comparative efficacy of these newer medicines in XFG compared with POAG 7 12 31.…”

“…There is however limited information available concerning the comparative efficacy of these newer medicines in XFG compared with POAG 7 12 31. In a direct comparison between travoprost–timolol and latanoprost–timolol fixed combinations over 24 h the travoprost–timolol fixed combination provided statistically greater 24-h efficacy specifically in XFG 30. In another previous diurnal study8 we compared one ingredient of BTFC, bimatoprost to latanoprost, in a crossover study on XFG eyes.…”

Bimatoprost 0.03%/timolol 0.5% preservative-free ophthalmic solution versus bimatoprost 0.03%/timolol 0.5% ophthalmic solution (Ganfort) for glaucoma or ocular hypertension: a 12-week randomised controlled trial

“…Similarly, in a meta-analysis of 20 clinical trials comparing fixed combinations of prostaglandin analog/timolol with prostaglandin agonist monotherapies, bimatoprost/timolol was found to provide significantly greater IOP reduction than latanoprost-based and travoprost-based combinations, as well as bimatoprost alone (in most studies) 26. A more recent meta-analysis of five trials comparing fixed and unfixed timolol combinations found fixed combinations of the three prostaglandin agonists to be less effective than concurrently administered agents in an unfixed combination (p=0.0007); the studies, however, were characterised by significant quantitative heterogeneity (I 2 =58%),27 suggesting that the observed effect was likely due to inconsistency between studies 28…”

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

“…Prostaglandin analogues have become a popular firstline therapy option for lowering IOP in POAG owing to their superior 24-hour efficacy, [1][2][3][4][5][6] convenient once-a-day administration, 5 and favorable systemic safety profile. 7 Travoprost is a synthetic prostaglandin F2a analogue that exerts its IOP-lowering effect through the prostaglandin FP receptors situated at the ciliary muscle 8 and the trabecular meshwork.…”