Edward D. Gilmore

Retinal Arteriolar Hemodynamic Response to a Combined Isocapnic Hyperoxia and Glucose Provocation in Early Sight-Threatening Diabetic Retinopathy

PURPOSE To quantify the magnitude of change of retinal arteriolar hemodynamics induced by a combined isocapnic hyperoxia and glucose provocation in diabetic patients with early sight-threatening diabetic retinopathy (DR) and in age-matched control subjects and to compare the response to that of an isocapnic hyperoxia provocation alone. The study hypothesis was that hyperglycemia reduces the retinal vascular reactivity response to a hyperoxic stimulus. METHODS The sample comprised 17 control subjects (group 1), 15 patients with no clinically visible DR (group 2), 16 patients with mild-to-moderate nonproliferative DR (group 3), and 15 patients with diabetic macular edema (group 4). Retinal hemodynamic measurements were acquired in the subjects, at baseline and 1 hour after consuming a standardized oral glucose load drink while breathing oxygen isocapnic with baseline. RESULTS Retinal blood velocity and flow significantly decreased in all groups (P < or = 0.001 and P < or = 0.0002, respectively) in response to a combined isocapnic hyperoxia and glucose provocation. The maximum-to-minimum velocity ratio significantly increased (P < or = 0.005), and wall shear rate (WSR) significantly decreased (P < or = 0.0002), in groups 1, 2, and 3, but not in group 4. The vascular reactivity response was not significantly different across the groups. The control group demonstrated a reduced change in flow (P = 0.009) and WSR (P = 0.010) to the combined isocapnic hyperoxia and glucose provocation compared with that of hyperoxia alone. CONCLUSIONS The vascular reactivity response to a combined isocapnic hyperoxia and glucose provocation produced a pronounced reduction in blood flow. Unlike the response to hyperoxia alone, the vascular reactivity response was not significantly different across the groups. Hyperglycemia reduced the retinal vascular reactivity response to hyperoxia in age-matched control subjects.

The relationship between retinal vascular reactivity and arteriolar diameter in response to metabolic provocation.

PURPOSE To compare the magnitude of vascular reactivity in response to metabolic provocation in retinal arterioles of varying diameter in healthy young subjects. METHODS Ten healthy young subjects (26.2 +/- 3.5 years [mean +/- SD]) attended for three sessions. Session 1 was used to select two discrete hemodynamic measurement sites along the superior temporal arteriole. Retinal arteriolar blood flow was assessed at relatively narrow and wide sites. At sessions 2 and 3, CO(2) and O(2) were sequentially administered (and alternated across sessions) using manual gas flow control via a modified sequential rebreathing circuit to achieve target hypercapnia and hyperoxia. Blood flow was assessed for each gas phase. Total vascular reactivity capacity (TVRC) was taken as the difference in flow between hypercapnia and hyperoxia. RESULTS The baseline diameter for the narrow and wide measurement sites was 92.4 microm (+/-13.6) and 116.7 microm (+/-12.7), respectively (ReANOVA; P < 0.0001). Hyperoxia induced a decrease in blood flow, whereas hypercapnia increased flow (P < 0.0001). TVRC was greater for the wide than for the narrow measurement sites (Delta flow narrow = 3.0 microL/min versus Delta flow wide = 6.6 microL/min; P < 0.0001). In terms of percentage change in flow relative to baseline, TVRC was the same between the wide and narrow sites (Delta narrow = 67% versus Delta wide = 61%; P > 0.05). CONCLUSIONS In response to metabolic provocation, absolute TVRC was greater for retinal arteriolar measurement sites with wider baseline vessel diameters. However, percentage change in retinal blood flow was the same irrespective of initial arteriolar diameter.