Efficacy of antiglaucoma fixed combination therapy versus unfixed components in reducing intraocular pressure: a systematic review

Br J Ophthalmol. 2008 Jun;92(6):729-34. doi: 10.1136/bjo.2008.139329. Epub 2008 May 6.


Aim: To evaluate the efficacy of the fixed combination ocular hypotensive therapies compared with their non-fixed components used concomitantly for lowering intraocular pressure (IOP) in glaucoma and ocular hypertension.

Methods: A systematic review of the literature, up to May 2007, without limits on year or language of publication was performed. Seven randomised controlled trials (n = 2,083 eyes) were identified. Assessment of methodological quality was made using standardised criteria. Results were pooled quantitatively using meta-analysis methods, and statistical analysis was performed using STATA software. The difference in mean intraocular pressure (mm Hg) from baseline between the fixed combination and non-fixed component therapies was compared. Non-inferiority in terms of efficacy was set at an upper confidence limit of < or =1.5 mm Hg for all time points (hour (Hr)0, Hr2 and Hr8) and evaluated at 12 weeks. Safety was evaluated from data on adverse events as reported in the included studies.

Results: Of the 679 abstracts identified, seven randomised controlled trials met the selection criteria. The quality scores of included studies were high (mean of 29.4, maximum score 30). The mean differences (95% CI) and p values at 12 weeks were as follows: 0.200 mm Hg, (CI -0.106 to 0.507), p = 0.20 for Hr0, 0.393 mm Hg (CI 0.038 to 0.747), p = 0.03 for Hr2 and 0.501 mm Hg (CI 0.156 to 0.846), p = 0.004 for Hr8. Although both Hr2 and Hr8 showed statistical significance favouring the non-fixed combinations, the non-inferiority measure < or =1.5 mm Hg upper confidence limit was not exceeded.

Conclusions: Fixed combination therapies are equally safe and effective at lowering IOP as their non-fixed components administered concomitantly.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glaucoma / drug therapy*
  • Humans
  • Intraocular Pressure / drug effects
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Ocular Hypertension / drug therapy*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Antihypertensive Agents