Glaucoma
Conditions
Keywords
Retinal Vascular Autoregulation
Brief summary
We have completed a study in which we examined the response of the retinal circulation to changes in posture from sitting to lying down in patients with primary open angle glaucoma (POAG). 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 POAG, this often does not occur. As a result, there are large fluctuations in blood flow which may produce the retinal neuronal damage associated with glaucoma. The purpose of this study is to demonstrate that topical anti-glaucoma treatments with agents that have vasoactive as well as IOP-lowering effects can have a beneficial effect on maintaining a steady retinal blood flow rate even when there are changes in local blood pressure.
Interventions
DRUGDorzolamide 2%-timolol 0.5%
BID OU for 6 weeks
DRUGBrimonidine 0.2%-0.5% timolol 0.5
BID OU for 6 weeks
Sponsors
Massachusetts Eye and Ear Infirmary
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* POAG * Age 40 to 80 years * Untreated IOP greater than 21 mm Hg
Exclusion criteria
* More than two IOP lowering medications * Exfoliation or pigment dispersion syndrome * Diabetic retinopathy * History of ocular surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Retinal Vascular Dysregulation (RVD) | 6 weeks post treatment | We determined whether RVD was present in the following way. The difference between the retinal blood flow measured while reclining for 30 minutes and the baseline retinal blood flow measured while seated was calculated. In a previous study, we found that among healthy subjects the change in the blood flow while reclining compared to baseline was +6.5% ± 12%. For this study, we defined the normal range of blood flow autoregulation as ± 2 standard deviations about the mean percentage change found in the control group in the initial study (6.5% ± 24.0%); that is, as -17.5% to +30.5%. Participants with a change in retinal blood flow induced by posture change outside this range were randomized to either dorzolamide-timolol fixed combination BID OU or brimonidine-timolol fixed combination BID OU for 6 weeks. |
Countries
United States
Participant flow
Recruitment details
A total of 21 primary open angle glaucoma patients were recruited for the study from the practices of Douglas J. Rhee, Angela V. Turalba, and Louis R. Pasquale at Massachusetts Eye and Ear Infirmary, Boston. Recruitment took place between February 13, 2009 and December 21, 2011.
Pre-assignment details
Prior to the initial testing visit, subjects ceased using their current IOP-lowering medications and were run in for 6 weeks on timolol 0.5% BID OU. After this 6 week period baseline measurements were taken and 7 were identified with retinal vascular dysregulation. These 7 patients were then randomized into one of two treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Primary Open Angle Glaucoma Subjects of either gender with age range 40 to 80 years old with POAG were eligible for the study. Eligible subjects had a history of an untreated IOP \> 21 mmHg in the left eye and a CPSD ≥ 1.0 in this eye. Patients being treated with more than two IOP lowering medications concurrently were excluded. All eligible subjects had open angles on gonioscopy with the filtering portion of the trabecular meshwork visible for 360° in both eyes. All subjects also had at least two reliable Humphrey 24-2 full threshold visual fields that showed reproducible loss in the left eye on tests with fixation loss ≤33%, false positives ≤ 20% and false negatives ≤ 20%. Patients with evidence of exfoliation or pigment dispersion syndrome in either eye were excluded. Subjects with diabetic retinopathy or a history of ocular laser or incisional surgery in either eye were also excluded. | 14 |
| POAG With RVD 7 subjects with POAG were identified to have retinal vascular dysregulation (RVD). We determined whether RVD was present in the following way. The percentage change between the retinal blood flow measured while reclining for 30 min and the baseline retinal blood flow measured while seated was calculated. In a previous study, we found that among healthy subjects the change in the retinal blood flow while reclining compared to sitting was +6.5% ± 12%. For this study, we defined the normal range of blood flow autoregulation as ±2 standard deviations about the mean percentage change found in the control group in our previous study. Subjects with a change in retinal blood flow induced by posture change outside of -17.5% to +35.5% where considered to have RVD. | 7 |
| Total | 21 |
Baseline characteristics
| Characteristic | Primary Open Angle Glaucoma | Total | POAG With RVD |
|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 8.2 | 63 years STANDARD_DEVIATION 8.3 | 60.0 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 20 Participants | 7 Participants |
| Region of Enrollment United States | 14 participants | 21 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 16 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
Presence of Retinal Vascular Dysregulation (RVD)
We determined whether RVD was present in the following way. The difference between the retinal blood flow measured while reclining for 30 minutes and the baseline retinal blood flow measured while seated was calculated. In a previous study, we found that among healthy subjects the change in the blood flow while reclining compared to baseline was +6.5% ± 12%. For this study, we defined the normal range of blood flow autoregulation as ± 2 standard deviations about the mean percentage change found in the control group in the initial study (6.5% ± 24.0%); that is, as -17.5% to +30.5%. Participants with a change in retinal blood flow induced by posture change outside this range were randomized to either dorzolamide-timolol fixed combination BID OU or brimonidine-timolol fixed combination BID OU for 6 weeks.
Time frame: 6 weeks post treatment
Population: 21 participants were tested for RVD after 6 weeks of timolol treatment. Of the 21 participants who were tested, 7 had RVD and were randomized to Dorzolamide-Timolol and Brimonidine-Timolol; 14 had normal autoregulation. One participant was removed from the analysis in the Brimonidine-Timolol arm due to technical difficulties with equipment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dorzolamide-Timolol | Presence of Retinal Vascular Dysregulation (RVD) | 7 Participants |
| Brimonidine-Timolol | Presence of Retinal Vascular Dysregulation (RVD) | 4 Participants |