Effects of dorzolamide-timolol and brimonidine-timolol on retinal vascular autoregulation and ocular perfusion pressure in primary open angle glaucoma

J Ocul Pharmacol Ther. 2013 Sep;29(7):639-45. doi: 10.1089/jop.2012.0271. Epub 2013 Mar 26.

Abstract

Purpose: To assess whether dorzolamide 2%-timolol 0.5% (D/T) and/or brimonidine 0.2%-timolol 0.5% (B/T) alters retinal vascular autoregulation (RVA) and seated ocular perfusion pressure (sOPP) in primary open angle glaucoma (POAG) patients who demonstrate retinal vascular dysregulation (RVD) on timolol 0.5% alone.

Methods: In this prospective, observer-masked, crossover study, 21 POAG patients with untreated intraocular pressure (IOP) >21 mmHg were treated for 6 weeks with timolol 0.5%. Subsequently, we measured inferior temporal retinal artery blood flow in the left eye with subjects seated and then while reclined for 30 min using the Canon Laser Blood Flowmeter. Subjects with a change in retinal blood flow in response to posture change outside of the range previously found in healthy subjects were designated as having RVD and randomized to either D/T or B/T for 6 weeks and re-tested. This was followed by treatment with the opposite medication.

Results: Seven of the 21 subjects demonstrated RVD in response to posture change following timolol 0.5%. Multiple linear regression analysis indicated that lower sOPP was the main determinant of RVD (P=0.033). After treatment with D/T, all 7 converted from RVD to normal RVA status (P=0.001). Four of 6 subjects showed a similar return to normal RVA following B/T (P=0.066). Mid-morning sOPP was 41.1±5.5 mmHg post-timolol, 46.3±6.5 mmHg post-D/T, and 38.6±6.0 mmHg post-B/T (D/T vs. B/T, P=0.026).

Conclusions: D/T significantly improved RVA in POAG patients exhibiting RVD while on timolol 0.5% alone. D/T also increased sOPP compared to B/T. There was no significant difference (P=0.37) between D/T and B/T in improving RVA.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / pharmacology
  • Brimonidine Tartrate
  • Cross-Over Studies
  • Drug Combinations
  • Eye / blood supply
  • Eye / drug effects
  • Female
  • Glaucoma, Open-Angle / drug therapy*
  • Glaucoma, Open-Angle / pathology
  • Homeostasis / drug effects*
  • Humans
  • Intraocular Pressure / drug effects*
  • Male
  • Middle Aged
  • Prospective Studies
  • Quinoxalines / pharmacology*
  • Regional Blood Flow / drug effects*
  • Sulfonamides / pharmacology*
  • Thiophenes / pharmacology*
  • Timolol / pharmacology*

Substances

  • Antihypertensive Agents
  • Drug Combinations
  • Quinoxalines
  • Sulfonamides
  • Thiophenes
  • dorzolamide-timolol combination
  • Brimonidine Tartrate
  • Timolol