title: Prostaglandin analogs and timolol-fixed versus unfixed combinations or monotherapy for open-angle glaucoma: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with β-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.
authors.affiliation: Ophthalmology Department, University of Brescia, Brescia, Italy. quaranta@med.unibs.it
authors.forename: Luciano
authors.initials: L
authors.lastname: Quaranta
authors.forename: Elena
authors.initials: E
authors.lastname: Biagioli
authors.forename: Ivano
authors.initials: I
authors.lastname: Riva
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.forename: Davide
authors.initials: D
authors.lastname: Poli
authors.forename: Andreas
authors.initials: A
authors.lastname: Katsanos
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced / Q000453:epidemiology; D007429:Intraocular Pressure / Q000187:drug effects; D009798:Ocular Hypertension / Q000188:drug therapy; D011453:Prostaglandins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D011453:Prostaglandins; D013999:Timolol