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

Eur J Ophthalmol. 2012 Jan-Feb;22(1):5-18. doi: 10.5301/ejo.5000009.


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.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Amides / adverse effects
  • Amides / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Bimatoprost
  • Circadian Rhythm
  • Cloprostenol / adverse effects
  • Cloprostenol / analogs & derivatives*
  • Cloprostenol / therapeutic use
  • Drug Combinations
  • Glaucoma / drug therapy
  • Humans
  • Hyperemia / chemically induced
  • Intraocular Pressure / drug effects*
  • Latanoprost
  • Prostaglandins F, Synthetic / adverse effects
  • Prostaglandins F, Synthetic / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Timolol / adverse effects
  • Timolol / therapeutic use*
  • Travoprost
  • Treatment Outcome


  • Amides
  • Antihypertensive Agents
  • Drug Combinations
  • Prostaglandins F, Synthetic
  • Cloprostenol
  • Latanoprost
  • Timolol
  • Bimatoprost
  • Travoprost