Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma

Am J Ophthalmol. 2001 Jun;131(6):729-33. doi: 10.1016/s0002-9394(01)00834-0.


Purpose: To evaluate the efficacy and safety of brimonidine 0.2% two or three times daily versus timolol maleate 0.5% solution twice daily.

Methods: Patients with primary open-angle glaucoma were randomized by Latin square technique to one of the three treatment sequences in this crossover, prospective double-masked trial. Each treatment period consisted of 6 weeks of chronic dosing followed by a diurnal curve for the intraocular pressure measured at 08:00, 10:00, 16:00, 18:00, 20:00, 22:00, and 24:00 hours. Intraocular pressure was measured by applanation tonometry.

Results: Thirty patients completed this trial. The average diurnal intraocular pressures in the trial were measured for timolol maleate (17.7 +/- 2.7 mm Hg), brimonidine given three times daily (18.0 +/- 2.2 mm Hg), and brimonidine given twice daily (19.2 +/- 2.4 mm Hg). There was a statistical difference between groups (P <.005). When groups were compared by pairs, three times daily dosing with brimonidine and timolol maleate both reduced the pressure more than twice daily brimonidine at every time point past 10:00 hours and for the diurnal curve (P <.05). In contrast, three times daily brimonidine and timolol maleate were statistically similar for the diurnal pressure, and each time point, except timolol maleate, decreased the pressure more at 16:00 (P =.042). Safety was similar between groups.

Conclusions: This study demonstrated that both timolol maleate twice daily and brimonidine three times daily provide a similar intraocular pressure reduction to each other. Timolol maleate twice daily and brimonidine three times daily provide a greater decrease in pressure in the late afternoon and nighttime hours, compared with brimonidine twice daily.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / administration & dosage*
  • Adrenergic alpha-Agonists / therapeutic use
  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Brimonidine Tartrate
  • Circadian Rhythm
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Glaucoma, Open-Angle / drug therapy*
  • Glaucoma, Open-Angle / physiopathology
  • Humans
  • Intraocular Pressure / drug effects
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Prospective Studies
  • Quinoxalines / administration & dosage*
  • Quinoxalines / therapeutic use
  • Timolol / administration & dosage*
  • Timolol / therapeutic use


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Antagonists
  • Quinoxalines
  • Brimonidine Tartrate
  • Timolol