Arterial hypertension is a major risk factor for stroke, and retinal vessels can be regarded as a mirror of the cerebral vasculature. Whether vascular remodeling of retinal arterioles with ageing and hypertension plays a role in cerebrovascular risk stratification has not yet been adequately addressed. In study 1, retinal arteriolar structure was assessed in 182 normotensive volunteers and 117 patients with essential hypertension. In study 2, we compared retinal arteriolar structure among 74 normotensive volunteers, 47 patients with treated essential hypertension, and 18 subjects with a history of a cerebrovascular event. Retinal arteriolar structure was assessed using scanning laser Doppler flowmetry and automatic full-field perfusion imaging analysis. In study 1, wall:lumen ratio of retinal arterioles revealed a significant correlation with age ( r =0.198; P =0.001). In study 2, wall:lumen ratio was highest in patients with a history of a cerebrovascular event compared with treated hypertensive and normotensive subjects (0.46±0.08, 0.36±0.14, and 0.35±0.12; P =0.007). When the treated group with hypertension was divided into 2 subgroups according to the quality of blood pressure control, patients with poor blood pressure control showed higher wall:lumen ratio than subjects with good blood pressure control (0.40±0.13 versus 0.31±0.13; P =0.025). Thus, assessment of wall:lumen ratio of retinal arterioles emerged as an attractive tool to identify treated patients with hypertension with increased cerebrovascular risk.

Background and Purpose— Arterial hypertension constitutes a central factor in the pathogenesis of stroke. We examined endothelial function of the retinal vasculature as a model of the cerebral circulation. Methods— Thirty-eight young subjects (19 hypertensive and 19 normotensive) were treated with the AT ₁ -receptor blocker candesartan cilexetil and placebo, each over 7 days. Retinal capillary flow and blood flow velocity in the central retinal artery were assessed with scanning laser Doppler flowmetry and pulsed Doppler ultrasound, respectively. N ^G -monomethyl- l -arginine ( l -NMMA) was infused to inhibit nitric oxide (NO) synthesis. Diffuse luminance flicker was applied to stimulate NO release. Results— In normotensive subjects, l -NMMA decreased retinal capillary flow by 8.2%±13% ( P <0.05) and flickering light increased mean blood flow velocity in the central retinal artery by 19%±29% ( P <0.01). In contrast, no significant change to these provocative tests was seen in hypertensive subjects. Treatment with candesartan cilexetil restored a normal pattern of reactivity in retinal capillaries ( l -NMMA: decrease in perfusion by 10%±17%, P <0.05) and the central retinal artery (flicker: increase in mean blood flow velocity by 42%±31%, P <0.001) in hypertensive patients. Conclusions— Endothelial function of the retinal vasculature is impaired in early essential hypertension but can be improved by AT ₁ -receptor blockade.

BACKGROUND Scanning laser Doppler flowmetry (SLDF) enables the measurement of the laser Doppler frequency shift in retinal tissue. This process allows the quantification of retinal and optic nerve head perfusion in an area of 2.7 mm × 0.7 mm within 2 seconds and with a spatial resolution of 10 μm × 10 μm. Owing to the local heterogeneity of the retinal microcirculation itself and to heart associated pulsation the capillary retinal blood flow depends on location and time. Because of technical limitations measurements of flow are only valid in retinal points with adequate brightness and focus, and away from big vessels. To include the heart beat associated pulsation and the spatial heterogeneity of retinal blood flow into the evaluation of blood flow an algorithm was developed examining automatically the whole SLDF perfusion image. AIM To report intraobserver reliability and interobserver reliability of a new method for analysing automatically full field perfusion images. METHOD The base of blood flow calculation by the automatic full field perfusion image analyser (AFFPIA) was 16 384 intensity time curves of all pixels of the whole perfusion image gained by the SLDF. AFFPIA calculates the Doppler frequency shift and the haemodynamic variables flow, volume, and velocity of each pixel. The resulting perfusion image was processed with respect to (1) underexposed and overexposed pixels, (2) saccades, and (3) the retinal vessel tree. The rim area and the saccades were marked interactively by the operator. The capillaries and vessels of the retinal vessel tree were identified automatically by pattern analysis. Retinal vessels with a diameter greater than 30 μm, underexposed or overexposed areas, and saccades were excluded automatically. Based on the whole perfusion image total mean flow, total mean volume, total mean velocity, standard deviation, cumulative distribution curve of flow, and the capillary pulsation index were calculated automatically. Heart beat associated pulsation of capillary blood flow was estimated by plotting the mean capillary flow of each horizontal line against time. Intraobserver reliability was estimated by measuring 10 eyes of 10 subjects on five different days by one observer. Interobserver reliability of AFFPIA was evaluated by analysing 10 perfusion maps by five different operators. To find a baseline of retinal blood flow, perfusion maps of 67 eyes of normal subjects with a mean age of 40.4 (SD 15) years were evaluated by AFFPIA. RESULTS The coefficient of reliability of the intraobserver reproducibility of flow was 0.74. The coefficient of reliability of the interobserver reproducibility was 0.95. The juxtapapillary retinal capillary flow was temporally 484 (SD 125), nasally 450 (117); the rim area capillary flow was 443 (110). The mean capillary pulsation index of retinal flow was 0.56 (0.14). CONCLUSION Retinal blood flow evaluation by the AFFPIA increases significantly the interobserver reliability compared with conventional evaluation of 100 μm × 100 μm areas in SLDF images with the original Heidelberg retina flowmeter software. The intraobserver reliability of AFFPIA was in the same range as conventional evaluation.

Increased wall-to-lumen ratio of small arteries is a predictor of adverse cardiovascular prognosis. We aimed to analyze retinal arteriolar structure in never-treated patients with essential hypertension and to test whether elevated blood pressure is associated with an increased wall-to-lumen ratio of retinal arterioles. The study cohort comprised 21 untreated male patients with essential hypertension (mean age 39.1 ± 5.4 years) and 29 untreated normotensive men (mean age 36.7 ± 5.9 years). Wall-to-lumen ratio of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. Patients with essential hypertension had a higher wall-to-lumen ratio of retinal arterioles than normotensive individuals (0.36 ± 0.1 vs. 0.28 ± 0.1, P = 0.028). Wall cross-sectional area of retinal arterioles did not differ between the study groups. The growth index, indicating the percentage of difference in average wall cross-sectional area of retinal arterioles between both groups, was 18%. Both systolic (r = 0.360, P = 0.010) and diastolic (r = 0.536, P < 0.001) blood pressures were related to wall-to-lumen ratio of retinal arterioles. Multiple regression analysis including a variety of known cardiovascular risk factors revealed that blood pressure is independently associated with an increased wall-to-lumen ratio of retinal arterioles (systolic blood pressure: β = 0.417, P = 0.012; diastolic blood pressure: β = 0.548, P = 0.001). The changes in arteriolar structure of retinal vessels in our study cohort revealed a similar pattern to that observed previously by other investigators in subcutaneous small arteries in essential hypertension. Blood pressure emerged as an important and independent determinant of wall-to-lumen ratio of retinal arterioles.