Effect of Alphagan on Retinal Blood Flow Autoregulation and Motion Detection in Patients With Normal Pressure Glaucoma
Condition: Glaucoma
MeSH terms: Glaucoma
Study type: Interventional

Summary: 
      The investigators have completed a study in which the investigators examined the response of
      the retinal circulation to changes in posture from sitting to lying down in patients with
      Normal Tension Glaucoma (NTG). This alteration in position produces changes in the local
      blood pressure at the entrance to the retinal vasculature. In a healthy retina, the
      vasculature adapts by dilating and constricting in order to maintain a steady blood flow
      rate. In an eye with NTG, this often does not occur. Upon analysis at the completion of the
      study , the investigators found that the patients who had been taking Alphagan (brimonidine)
      during the study did not exhibit the blood flow increases typical of NTG while lying down;
      instead, they maintained a steady blood flow rate as did the group of healthy control
      subjects. The investigators primary objective is to now demonstrate in a prospective study
      that Alphagan can restore retinal vascular autoregulatory function in patients with NTG who
      do not autoregulate. The investigators will also determine the effect of Alphagan treatment
      on the patients' ability to detect motion.
    

Detailed description: 
      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%.
    

Intervention name(s): brimonidine 0.15%
Intervention type(s): Drug
Intervention description(s): One drop in each eye three times a day for 8 weeks.
Other intervention name(s): Alphagan
Intervention MeSH terms: Brimonidine Tartrate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Normal Pressure Glaucoma