This is a prospective, nonrandomized clinical trial of POAG patients with a history of untreated IOP \<22 mm Hg.

RETINAL VASCULAR AUTOREGULATION TESTING PROTOCOL:

At approximately 10 AM, we allowed subjects to sit for 15 minutes and then measured blood pressure and heart rate using a Keller Vital Signs Monitor (Keller Medical Specialties, Antioch, Illinois, USA). We measured seated IOP in both eyes using Goldmann applanation tonometry (Haag Streit USA, Mason, Ohio, USA) and 1 eye was dilated with tropicamide 1%. Baseline seated ocular perfusion pressure (OPP) was estimated using the standard formula: OPP=2/3 MAP - IOP, where MAP refers to mean arterial pressure. The factor of two-thirds adjusts for the decline in blood pressure between the brachial and ophthalmic artery with the subject sitting. We used the Canon CLBF 100 Laser Blood Flowmeter (Canon Inc, Tokyo, Japan) to measure baseline retinal arterial blood column diameter and centerline blood speed, which allows for automatic calculation of the blood flow rate. We chose a site along either the inferior temporal retinal artery or the superior temporal retinal artery adjacent to the optic disc for baseline measurements. Following the baseline measurements, the subjects assumed a posture typically used for face-on x-rays, reclining on their right side with their head supported by a foam wedge making a 24-degree angle from the horizontal. Subjects reclined for 30 minutes while brachial blood pressure and heart rate were automatically measured at 5-minute intervals. Laser Doppler blood flow measurements were obtained from the same arterial site that was used at baseline after approximately 15 and 30 minutes of reclining. Immediately following the 30-minute laser Doppler measurement, with the subject still reclining, we used the Perkins handheld applanation tonometry (Haag Streit USA) to remeasure IOP in the eye undergoing hemodynamic testing. In the reclined position, OPP was estimated using the following formula: OPPreclining = MAPreclining - IOPreclining, where MAPreclining is the mean brachial artery blood pressure measured in the left arm with the subject reclining on the right side. Subsequently, blood pressure, heart rate, and laser Doppler measurements were repeated after the subjects were reseated for 15 minutes.

Only patients who exhibited retinal vascular dysregulation continued in the study. We defined retinal vascular dysregulation based on the percentage change between the retinal blood flow measured while reclining for 30 minutes and the baseline seated measures. Previously, we found that healthy subjects exhibited a +6.5% +/- 12% blood flow change induced by 30 minutes of reclining. Thus, we defined the normal range of blood flow autoregulation as within 2 standard deviations of the mean percentage change found in this group, or -17.5% to +30.5%. Patients who exhibited retinal vascular dysregulation began an 8-week course of brimonidine 0.15% 3 times a day in both eyes. Subsequently, they returned at 10 AM and repeated the testing protocol described above. We obtained retinal hemodynamic measurements at the same retinal arterial site used during the initial visit. Each patient also underwent visual function testing in the eye that had hemodynamic studies both before and after 8-week treatment with brimonidine 0.15%.