Network Meta-analysis for Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma

Ann Intern Med. 2016 May 17;164(10):674-82. doi: 10.7326/M15-2367. Epub 2016 Apr 19.


Background: Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines.

Purpose: To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis.

Data sources: MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines.

Study selection: Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person.

Data extraction: One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs.

Data synthesis: Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: β-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24).

Limitation: When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable.

Conclusion: For timely recommendations when multiple treatment options are available, guidelines developers should consider network meta-analysis.

Primary funding source: National Eye Institute, National Institutes of Health.

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / therapeutic use
  • Adrenergic beta-Antagonists / therapeutic use
  • Glaucoma, Open-Angle / drug therapy*
  • Humans
  • Network Meta-Analysis*
  • Practice Guidelines as Topic*
  • Prostaglandins / therapeutic use


  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic beta-Antagonists
  • Prostaglandins