title: Efficacy and tolerability of prostaglandin-timolol fixed combinations: an updated systematic review and meta-analysis.
abstract: BACKGROUND
  Prostaglandin-timolol fixed combinations (PG-timolol FCs) are now widely used to reduce intraocular pressure in patients with glaucoma. The efficacy and tolerability of these drugs are worthy of further exploration. An updated systematic review and meta-analysis was performed to assess the clinical efficacy and tolerability of the three PG-timolol FCs.
  
  
  METHODS
  Pertinent randomized, controlled trials were identified through systematic searches of PubMed, Embase, the Cochrane central register of controlled trials and the Chinese Biomedicine Database. The main efficacy measures were the weighted mean differences (WMDs) for the reduction from baseline to end of treatment in IOP at 9 am, 12 pm and 4 pm and diurnal curve. The main tolerability measures were the odds ratios (ORs) for the incidence of conjunctival hyperemia.
  
  
  RESULTS
  Nine studies involving 991 patients were included in the meta-analysis. Latanoprost-timolol FC (LTFC) and travoprost-timolol FC (TTFC) were not significantly different in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm. Bimatoprost-timolol FC (BTFC) provided significantly greater efficacy in lowering IOP at the three measurement time points and over the mean diurnal curve than LTFC (diurnal curve: WMD = 0.88 mmHg [95% CI, 0.42 to 1.33]; 9 am: WMD = 1.27 mmHg [0.68 to 1.86]; 12 pm: WMD = 1.16 mmHg [0.85 to 1.46]; 4 pm: WMD = 0.61 mmHg [0.51 to 0.70]) and TTFC (diurnal curve: WMD = 1.94 mmHg [0.19 to 3.68]; 9 am: WMD = 0.68 mmHg [0.15 to 1.21]; 12 pm: WMD = 0.90 mmHg [0.41 to 1.39]; 4 pm: WMD = 1.06 mmHg [0.61 to 1.51]). The incidence of hyperemia was significantly higher with BTFC than LTFC (pooled ORs: 1.85 [1.09 to 3.13]). The incidence of hyperemia was not significantly higher with TTFC than LTFC (pooled ORs: 2.52 [0.85 to 7.46]), and was not significantly higher with BTFC than TTFC (pooled OR: 1.65 [0.48 to 5.70]).
  
  
  CONCLUSIONS
  BTFC provided significantly greater efficacy in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm than LTFC and TTFC. LTFC was as effective as TTFC in lowering IOP at the four measurement time points and BTFC caused conjunctival hyperemia in more patients than LTFC. Further clinical trials are needed because of the limited number of studies.
authors: Department of Ophthalmology, Shanghai Changzheng Hospital, Second Military Medical University , Shanghai , China.
authors: Heng
authors: H
authors: Lou
authors: Hao
authors: H
authors: Wang
authors: Ying
authors: Y
authors: Zong
authors: Jin-Wei
authors: JW
authors: Cheng
authors: Rui-Li
authors: RL
authors: Wei
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069580:Bimatoprost / Q000008:administration & dosage / Q000009:adverse effects; 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 / Q000008:administration & dosage / Q000009:adverse effects; D013999:Timolol / Q000008:administration & dosage* / Q000009:adverse effects; D000069557:Travoprost / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol; D000069580:Bimatoprost; D000069557:Travoprost
keywords: Fixed combination; Glaucoma; Intraocular pressure; Meta-analysis; Prostaglandin; timolol