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.

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.

Retinal arteriolar hemodynamic response to an acute hyperglycemic provocation in early and sight-threatening diabetic retinopathy.

The aim was to quantify the magnitude of retinal arteriolar vascular reactivity to a hyperglycemic provocation in diabetic patients stratified by severity of retinopathy and in age-matched controls. The sample comprised 20 non-diabetic controls (Group 1), 19 patients with no clinically visible DR (Group 2), 18 patients with mild-to-moderate non-proliferative DR (Group 3) and 18 patients with diabetic macular edema (Group 4). Retinal hemodynamic measurements using the Canon Laser Blood Flowmeter (CLBF-100) were acquired before and 1 h after drinking a standardized oral glucose load drink. The magnitude of the retinal vascular response, as well as max:min velocity ratio and wall shear rate (WSR), was calculated and compared across groups. A significant change in blood glucose level was observed for all groups (p<0.05). The change in blood glucose elevation was significantly less in Group 1 compared to the other groups. No significant change in arteriolar diameter, blood velocity, blood flow, max:min velocity ratio and WSR was found in patients with diabetes and in age-matched subjects without diabetes. The results of this study indicate that retinal arteriolar blood flow is unaffected by acute elevation of blood glucose using an oral glucose load drink in patients with diabetes and in age-matched controls. This lack of a blood flow response to acute hyperglycemia in patients with early sight-threatening DR may be explained by a loss of retinal vascular reactivity.

Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation in early sight-threatening diabetic retinopathy.

PURPOSE: To quantify the magnitude of retinal arteriolar vascular reactivity in diabetic patients stratified by severity of retinopathy and in age-matched control subjects. The sample comprised 21 nondiabetic control subjects (group 1), 19 patients with no clinically visible DR (group 2), 19 patients with mild-to-moderate nonproliferative DR and without clinically evident diabetic macular edema (DME) (group 3), and 17 patients with DME (group 4). methods Subjects initially breathed air, followed by oxygen, while isocapnia was maintained. Retinal arteriolar diameter and blood velocity measurements were acquired simultaneously. RESULTS: Changes in blood velocity and wall shear rate (WSR) were significantly less in groups 3 and 4 (P < 0.0001 and P = 0.0002, respectively) than in groups 1 and 2. Change in blood flow was significantly less in group 4 (P < 0.004) than in groups 1 and 2. The change in maximum-to-minimum (max:min) ratio was significantly less in groups 2 and 4 than in group 1 (P = 0.001). There was a significant relationship between baseline objective edema indices and vascular reactivity. The magnitude of vascular reactivity in response to isocapnic hyperoxia was reduced in those individuals with clinically evident DR relative to subjects without diabetes. CONCLUSIONS: The differences in vascular reactivity occurred in the absence of any difference in baseline hemodynamic values. Vascular reactivity is impaired in early sight-threatening DR, and this impairment is related to the objectively defined magnitude of retinal edema.

Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation.

The aim of this study was to simultaneously quantify the magnitude and response characteristics of retinal arteriolar diameter and blood velocity induced by an isocapnic hyperoxic provocation in a group of clinically normal subjects. The sample comprised 10 subjects (mean age, 25 yr; range, 21-40 yr). Subjects initially breathed air for 5-10 min, then breathed O(2) for 20 min, and then air for a final 10-min period via a sequential rebreathing circuit (Hi-Ox; Viasys) to maintain isocapnia. Retinal arteriolar diameter and blood velocity measurements were simultaneously acquired with a Canon laser blood flowmeter (CLBF-100). The response magnitude, time, and lag of diameter and velocity were calculated. In response to hyperoxic provocation, retinal diameter was reduced from control values of 111.6 (SD 13.1) to 99.8 (SD 10.6; P < 0.001) microm and recovered after withdrawal of hyperoxia. Retinal blood velocity and flow concomitantly declined from control values of 32.2 (SD 6.4) mm/s and 9.4 (SD 2.5) microl/min to 20.7 (SD 3.4) mm/s and 5.1 (SD 1.3) microl/min, respectively (P < 0.001 for both velocity and flow), and recovered after withdrawal of hyperoxia. The response times and response lags were not significantly different for each parameter between effect and recovery or between diameter and velocity. We conclude that arteriolar retinal vascular reactivity to hyperoxic provocation is rapid with a maximal vasoconstrictive effect occurring within a maximum of 4 min. Although there was a trend for diameter to respond before velocity to the isocapnic hyperoxic provocation, the response characteristics were not significantly different between diameter and velocity.

Comparison of different hyperoxic paradigms to induce vasoconstriction: implications for the investigation of retinal vascular reactivity.

PURPOSE: To compare the impact of three different techniques used to induce hyperoxia on end-tidal CO2 (PETCO2). The relationship between change in PETCO2 and retinal hemodynamics was also assessed to determine the clinical research relevance of this parameter. METHODS: The sample comprised 10 normal subjects (mean age, 25 years; range, 21-49 years). Each subject attended for three sessions. At each session, subjects initially breathed air followed by O2 only; O2 plus CO2, using a nonrebreathing circuit (with CO2 flow continually adjusted to negate drift of PETCO2); or air followed by O2, using a sequential rebreathing circuit. In addition, using a separate sample of eight normal subjects (mean age, 26.5 years; range, 24-36 years), a methodology that initially raised PETCO2 and then returned to homeostatic levels was used to determine the impact, if any, of perturbation of PETCO2 on retinal hemodynamics. RESULTS: The difference in group mean PETCO2 between baseline and elevated O2 breathing was significantly different (t-test, P = 0.0038) for O2-only administration with a nonrebreathing system. The sequential rebreathing technique resulted in a significantly lower difference (i.e., before and during hyperoxia) of individual PETCO2 (t-test, P = 0.0317). The PETCO2 perturbation resulted in a significant (P < 0.005) change of retinal arteriolar diameter, blood velocity, and blood flow. CONCLUSIONS: The sequential rebreathing technique resulted in a reduced variability of PETCO2. A relatively modest change in PETCO2 resulted in a significant change in retinal hemodynamics. Rigorous control of PETCO2 is necesssary to attain standardized, reproducible hyperoxic stimuli for the assessment of retinal vascular reactivity.