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Gilbert T. Feke, Douglas J. Rhee, Angela V. Turalba, Louis R. Pasquale; Effect of Timolol 0.5%-Dorzolamide 2% versus Timolol 0.5%-Brimonidine 0.2% on Retinal Vascular Autoregulation and Ocular Perfusion Pressure in Patients with Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2839.
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To assess the impact of timolol 0.5%-dorzolamide 2% (Cosopt™) and timolol 0.5%-brimonidine 0.2% (Combigan™) on retinal vascular autoregulation (RVA) and ocular perfusion pressure (OPP) in primary open angle glaucoma (POAG) patients who demonstrate retinal vascular dysregulation (RVD) on timolol 0.5% (Timoptic™) alone.
This was a prospective, observer-masked two-period crossover study of POAG patients with a history of untreated IOP > 21 mmHg and reproducible Humphrey 24-2 full threshold visual field loss. Prior to initial testing, subjects were run in for 6 weeks on Timoptic BID OU. At each visit, a Canon CLBF 100 Laser Blood Flowmeter was used to measure arterial blood column diameter, centerline blood speed, and blood flow in a temporal retinal artery in the left eye with the subject seated, while reclining for 30 minutes, and again while seated. IOP was measured while seated using both Goldmann and Perkins applanation tonometry (PAT) and while reclining using PAT. Seated OPP was calculated as 2/3 MAP (mean brachial artery blood pressure) minus IOP. Subjects with a change in retinal blood flow induced by posture change outside of the range previously found in healthy subjects were randomized to either Cosopt or Combigan BID OU for 6 weeks and re-tested. This was followed by treatment with the opposite medication for another 6 weeks and final re-testing.
21 subjects were studied (mean age 63.2 ± 8.5 years). 7 subjects had RVD in response to posture change following Timoptic with blood flow increases ranging from 70% to 102% (n=3) or blood flow decreases ranging from -23% to -33% (n=4) while reclining versus seated. After randomization, all 7 showed a normalization of RVA following Cosopt (p=0.016) with blood flow changes induced by posture change ranging from +3% to + 28%. Measurements were not obtained in one subject following Combigan; 4 of the remaining 6 subjects showed a normalization of RVA following Combigan (p=0.69). There were no significant differences in baseline retinal blood flow (p = 0.73) following each of the 3 treatments. Seated IOP was 17.1 ± 3.1 mmHg post Timoptic, 15.6 ± 2.1 mmHg post Cosopt, and 13.7 ±1.9 mmHg post Combigan (Timolol vs Combigan, p=0.016) . However, seated MAP was significantly higher (p = 0.011) following Cosopt than following Combigan. As a result, mid-morning seated OPP was 41.1 ± 5.5 mmHg post Timoptic, 46.3 ± 6.5 mmHg post Cosopt, and 38.6 ± 6.0 mmHg post Combigan (Cosopt vs Combigan, p=0.026).
Treatment with Cosopt normalized RVA in POAG patients who exhibited RVD while on Timoptic alone. Cosopt had the desired additional effect of increasing the OPP compared to Combigan.
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