Stroke. 2003;34:e92-e94
Published online before print May 29, 2003,
doi: 10.1161/01.STR.0000075768.91709.E4
(Stroke. 2003;34:e92.)
© 2003 American Heart Association, Inc.
Central Retinal Artery Doppler Flow Parameters Reflect the Severity of Cerebral Small-Vessel Disease
Masahiko Hiroki, MD, PhD;
Kotaro Miyashita, MD, PhD;
Hiroshi Yoshida, MD, PhD;
Shunsaku Hirai, MD, PhD
Hidenao Fukuyama, MD, PhD
From the Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan (M.H., H.F.); Cerebrovascular Division, Department of Medicine, National Cardiovascular Center, Suita, Osaka, Japan (K.M.); and Departments of Neurology (S.H.) Neurophthalmology (H.Y), Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan
Correspondence to Masahiko Hiroki, MD, Human Brain Research Center, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail CYI01752{at}nifty.ne.jp
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Abstract
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Background and Purpose— We investigated the usefulness
of central retinal artery (CRA) Doppler flowmetry in patients
with cerebral small-vessel disease (SVD).
Methods— CRA Doppler flowmetry was performed in 103 SVD patients who underwent MRI. Sixty-four adjusted control subjects were also registered. We assessed average CRA flow parameter values for both eyes with the clinical and MRI findings.
Results— Each Doppler flowmetry was performed within 5 minutes. Patients with SVD had significantly lower end-diastolic and mean velocities of the CRA than control subjects; they also had higher pulsatility and resistive indexes. Multivariate analysis showed that the number of small infarcts was an independent predictor of peak systolic and mean velocities. Grade of periventricular hyperintensities was an additional independent predictor of peak systolic and mean velocities, whereas the number of small infarcts was predictive of end-diastolic velocity.
Conclusions— Flow parameters may be useful for the quantitative assessment of SVD severity.
Key Words: retinal artery • small-vessel disease • ultrasonography, Doppler
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Introduction
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Early and quantitative assessment of small-vessel disease (SVD)
is important, but a method has not been established. Recently,
we have focused on the central retinal artery (CRA),
0.15 to
0.20 mm in diameter distally,
1 which corresponds to a small
artery. Because CRA Doppler flowmetry causes minimal discomfort,
requires little time, and has high reproducibility,
2 it seems
useful for the quantitative assessment of SVD. In this study,
we investigated the clinical backgrounds of the CRA flow parameter
in patients with SVD confirmed by MRI.
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Subjects and Methods
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CRA Doppler flowmetry followed carotid ultrasonography in 466
consecutive patients at Tokyo Metropolitan Neurological Hospital
between February 2000 and November 2001. We excluded 92 patients
who had not had MRI within the year and 58 with ophthalmic disease
that affected CRA flow velocity, large-vessel disease, and various
therapies. Using Trial of Org 10172 in Acute Stroke Treatment
(TOAST) criteria,
3 we selected 103 patients with isolated SVD
(mean age, 70.9±9.0 years; 66 men). Furthermore, 64 age-
and sex-adjusted controls were selected the (
Figure). Informed
consent was obtained from all subjects.
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Flow chart showing subject selection. PDF indicates proliferative diabetic retinopathy; CVD, cerebrovascular disease; and LVD, large-vessel disease.
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Hypertension and high blood pressure were defined by World Health Organization criteria.4 All clinical background factors except blood pressure and age were assessed as present or absent. Doppler flowmetry was performed by Powervision 6000 (Toshiba Inc, Tokyo) with 5.0-MHz color and pulsed Doppler transducer set at 12.0-kHz pulse frequency and 50-Hz low-cut filter. A 1.0-mm sample volume was positioned in the CRA 3.5 mm below the optic disc. The average value of each flow parameter of both eyes and the common carotid arteries (CCAs) was determined. MRI (1.5-T, Signa Horizon Hispeed, GE) was performed with a spin-echo pulse sequence to generate T1-weighted (repetition time/echo time, 300/8.0 ms) and T2-weighted (repetition time/echo time, 4000/90.0 ms) axial brain images with 6.0-mm slice thickness. On these MR images, lacunar and small white-matter medullary infarcts were defined as small infarcts (<1.5 cm in greatest diameter).5,6 Periventricular hyperintensities (PVHs) were graded into 3 groups.7
Background factors and CRA flow parameters were compared between SVD and control groups with the Mann-Whitney U test or 
2 test. In the SVD group, multiple linear regression analysis of each CRA flow parameter was done for variables with a significant difference or correlation univariately by the Mann-Whitney U test, Kruskal-Wallis H test, and Spearman’s rank correlation test.
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Results
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Compared with the control group, the SVD group had a significantly
higher prevalence of hypertension, smoking, left ventricular
hypertrophy, and pulsatility and resistive indexes of CCA and
a lower prevalence of end-diastolic and mean velocities of the
CCA (
Table 1). CRA end-diastolic and mean velocities were significantly
lower and CRA pulsatility and resistive indexes were higher
in the SVD group than the control group (
Table 2).
Multiple linear regression analysis showed that the small infarct number was an independent predictor of peak systolic (B=-0.282, P=0.001) and mean (B=-0.164, P<0.001) velocities, and CCA resistivity index was predictive of end-diastolic velocity (B=-2.231, P=0.016) and pulsatility (B=1.830, P<0.001) and resistivity (B=0.438, P<0.001) indexes. PVH was an additional independent predictor of peak systolic and mean velocities; small infarct number, of end-diastolic velocity; and age, of pulsatility and resistivity indexes (Table 3).
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Discussion
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We showed that CRA flow parameters, especially end-diastolic
and mean velocities, related to the severity of SVD. It is thought
that decreases in these velocities reflect increases in small-artery
or arteriolar wall resistance by arteriosclerosis. PVH, lacunar
infarct, and small white-matter medullary infarct are pathologically
known to be caused by small-artery or arteriolar lesions.
6,8,9 Overall, CRA flow parameters can reflect the grade of PVH and
the number of small infarcts. It is reported that carotid atherosclerosis
affects CRA end-diastolic velocity,
10 which was related to the
CCA resistivity index in our study. Therefore, to assess SVD
by ultrasound, both CRA and carotid examinations are necessary.
Patients with vascular risk factors such as hypertension often
show a significant reduction in systolic and diastolic CRA velocities,
11 although we did not find these reductions in our subjects. This
might be due to organic changes in the small arteries or medical
treatment in our subjects.
In conclusion, CRA flow parameters relate to the severity of SVD independently of aging and may be useful as a quantitative indicator. To confirm its clinical application, follow-up study including normal subjects in the community is necessary.
Received August 5, 2002;
revision received December 5, 2002;
accepted December 10, 2002.
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Abstract
Introduction