A Pilot Study Assessing Retinal Blood Flow Dysregulation in Glaucoma Using Erythrocyte Mediated Velocimetry

Abstract

Purpose: The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry.

Methods: This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations.

Results: In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (β = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (β = -21.1%, P = 0.03), and White race (β = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia.

Conclusions: Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia.

Translational relevance: The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

Figure 1.

Study enrollment flowchart. Incomplete EMA imaging was due to equipment malfunction, elevated blood pressure, and vasovagal reaction. Angiograms were graded as poor quality if the minimum requirement of 30 measurements per angiogram could not be met. EMA, erythrocyte mediated angiography.

Figure 2.

Superimposed images demonstrating tracked erythrocytes within the same retinal arteriole in (A) room air and (B) hyperoxia conditions using erythrocyte mediated velocimetry. Consecutive frames at 0.04 seconds, 0.08 seconds, 0.12 seconds, and additional 0.4 second intervals were superimposed to demonstrate the movement of one cell over time.

Figure 3.

Bar graphs illustrating (A) mean absolute change in erythrocyte velocity and (B) percent change from baseline velocity with hyperoxia in arterioles and venules from the subset of paired vessels (n = 46) among the three study groups. Means are shown with standard error of the mean. *Statistical significance at the P < 0.05 level as determined by generalized estimating equation (GEE) to account for multiple vessels per individual.