title: Efficacy and tolerability of prostaglandin-timolol fixed combinations: a meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Edouard Herriot Hospital, Lyon, France. aptel_florent@hotmail.com
authors.forename: Florent
authors.initials: F
authors.lastname: Aptel
authors.forename: Michel
authors.initials: M
authors.lastname: Cucherat
authors.forename: Philippe
authors.initials: P
authors.lastname: Denis
mesh_terms: D000577:Amides / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069580:Bimatoprost; D002940:Circadian Rhythm; D003008:Cloprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use*; D000069557:Travoprost; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D003008:Cloprostenol; D000077338:Latanoprost; D013999:Timolol; D000069580:Bimatoprost; D000069557:Travoprost