Do retinal microvascular abnormalities shed light on the pathophysiology of lacunar stroke?
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Doubal2011.doc (4.653Mb)
Date
05/07/2011Author
Doubal, Fergus Neil
Metadata
Abstract
Background. Lacunar strokes account for 25% of all ischaemic stroke but the exact
nature of the causative cerebral small vessel abnormality remains unknown.
Pathological studies are technically difficult and brain imaging cannot adequately
characterise the cerebral small vessels. The retinal blood vessels are of similar size
and physiology to the cerebral small vessels and may act as a surrogate marker for
these cerebral small vessels. We therefore investigated retinal microvascular
abnormalities in lacunar stroke.
Methods. We performed a systematic review of retinal microvascular abnormalities
in lacunar stroke to clarify associations and identify where further research was
required. We then established a cohort of patients presenting with lacunar stroke
with cortical stroke controls to investigate differences in retinal microvascular
abnormalities between stroke subtypes. All patients had MRI brain at presentation
and digital retinal photography of both eyes. We investigated the prevalence of
retinopathy (hard and soft exudates or haemorrhages/microaneurysms), focal
arteriolar narrowing and arteriovenous nicking . We developed, validated and used
novel semi-automated techniques for measuring retinal arteriolar and venular widths,
retinal arteriolar geometry (branching co-efficients (change in arteriolar cross
sectional area across a bifurcation) and branching angles) and fractal dimensions
(reflecting branching complexity) of the vasculature. We also assessed MRI
parameters in lacunar stroke. We used multivariable analysis to correct for baseline
imbalances in vascular risk factors.
Results. From the systematic review we demonstrated that retinal microvascular
abnormalities are associated with incident and prevalent stroke but that in general,
strokes were inadequately characterised and there were no data regarding retinal
microvascular abnormalities in ischaemic stroke subtypes. We recruited 253
patients, 129 lacunar strokes and 124 cortical strokes, mean age 68 years. We found
no difference in the prevalence of retinopathy, arteriovenous nicking, focal arteriolar
narrowing or arteriolar widths between lacunar and cortical stroke subtypes. We
found that venules were wider in lacunar stroke. We found no differences in
arteriolar branching co-efficients or arteriolar branching angles between lacunar and
cortical strokes but found that deep white matter white matter hyperintensities on
MRI were associated with increased branching co-efficients and periventricular
white matter hyperintensities associated with decreased branching co-efficients. We
found that the fractal dimension of the vascular tree was decreased in lacunar stroke.
Furthermore we found that enlarged perivascular spaces on MRI are associated with
lacunar stroke and white matter disease.
Conclusions. We have clearly demonstrated that retinal microvascular abnormalities
differ between lacunar and cortical stroke suggesting that a distinct small vessel
vasculopathy may cause lacunar stroke. We have also identified MR markers of
lacunar stroke. These results suggest that venular disease (a hitherto underresearched
area) may play a role in the pathophysiology of lacunar stroke. Retinal
microvascular abnormalities can act as markers for cerebral small vessel disease. We
plan collaborative analyses with colleagues who have performed similar studies to
further assess retinal abnormalities in lacunar stroke.
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