Meta-analysis of the efficacy and safety of alpha2-adrenergic agonists, beta-adrenergic antagonists, and topical carbonic anhydrase inhibitors with prostaglandin analogs

Arch Ophthalmol. 2010 Jul;128(7):825-33. doi: 10.1001/archophthalmol.2010.131.


Objective: To perform a meta-analysis to estimate the intraocular pressure (IOP)-lowering efficacy and safety of alpha(2)-adrenergic agonists (AAs), beta-adrenergic antagonists (BBs), and topical carbonic anhydrase inhibitors (TCAIs) when used in combination with a prostaglandin analog (PGA).

Methods: MEDLINE, Embase, and the Cochrane Controlled Trials Register were systematically searched for relevant articles in April 2009. Ten observer-masked randomized clinical trials that reported baseline IOP while receiving PGA monotherapy and follow-up IOP while receiving combination therapy were identified. The pooled IOP-lowering efficacy achieved with each class of adjunctive agent was calculated using random-effects models. The frequencies of adverse events were pooled across studies and compared using Fisher exact test.

Results: Mean diurnal IOP reduction achieved in all 3 groups was statistically similar (P = .22). At trough, IOP reduction was greater in the TCAI (P < .001) and BB (P < .001) groups than in the AA group. Peak IOP reduction was similar in the 3 groups (P = .66). Eye or eyelid pain or burning and xerostomia were significantly more common in the AA group. Fatigue, weakness, or dizziness was more common in the AA and BB groups compared with the TCAI group. Taste disturbance was significantly more common in the TCAI group.

Conclusions: All 3 classes are similarly effective in lowering mean diurnal IOP when used in combination with PGAs. The AA class is statistically significantly less effective in reducing IOP at trough compared with BBs and TCAIs. The types of adverse events that were identified varied among the different classes of adjunctive therapies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adrenergic alpha-2 Receptor Agonists*
  • Adrenergic alpha-Agonists / administration & dosage*
  • Adrenergic alpha-Agonists / adverse effects
  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / adverse effects
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Carbonic Anhydrase Inhibitors / administration & dosage*
  • Carbonic Anhydrase Inhibitors / adverse effects
  • Databases, Factual
  • Drug Therapy, Combination
  • Glaucoma / drug therapy
  • Humans
  • Intraocular Pressure / drug effects*
  • Ocular Hypertension / drug therapy
  • Prostaglandins F, Synthetic / administration & dosage*
  • Prostaglandins F, Synthetic / adverse effects
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Carbonic Anhydrase Inhibitors
  • Prostaglandins F, Synthetic