Lacunar stroke accounts for a quarter of cases of acute ischaemic stroke; however, its underlying pathophysiology remains unclear. Our aim was to establish whether there is an association between changes in the retinal microvasculature and lacunar stroke that might provide clues to the pathology of cerebral small vessel disease.
In this cross-sectional study, we recruited patients who presented with acute stroke at three centres in two countries (Sydney and Melbourne, Australia, and Singapore). Each patient had standardised clinical assessments, retinal photography, and CT or MRI of the brain. Changes in the retinal microvasculature were assessed from retinal photographs by graders who were masked to the patients' clinical details. Lacunar stroke was diagnosed according to a modified version of the TOAST criteria (Treatment of Acute Stroke Trial) or the OCSP criteria (Oxfordshire Community Stroke Project) and by MRI findings.
We recruited 1321 patients aged 19 to 94 years with acute ischaemic stroke; 410 (31%) had lacunar stroke. Patients with acute lacunar stroke were no more likely to have hypertension (p=0.12), diabetes (p=0.51), or hypercholesterolaemia (p=0.91) than were patients with other types of ischaemic stroke. However, patients with lacunar stroke were more likely to have retinal microvessel signs, particularly when stroke subtype was confirmed using diffusion-weighted MRI, than were patients with other stroke subtypes. After adjustment for age, sex, study site, smoking history, hypertension, and diabetes, the patients with lacunar stroke were more likely than those with other stroke subtypes to have microvessel signs, and when stroke subtype was confirmed by diffusion-weighted MRI the odds ratios were: 3.55 (95% CI 1.77-7.12) for focal arteriolar narrowing; 1.96 (1.19-3.24) for arteriovenous nipping; 2.32 (1.42-3.79) for enhanced light reflex of the arteriolar wall; 1.33 (0.74-2.41) for generalised retinal arteriolar narrowing; 1.45 (0.84-2.51) for small retinal arteriole:venule ratio; and 1.35 (0.80-2.26) for retinal venular widening.
Our findings suggest that acute lacunar stroke is a manifestation of non-atherothrombotic occlusive small vessel disease, which might have implications for the prevention and treatment of this stroke subtype.
National Health and Medical Research Council of Australia; National Medical Research Council of Singapore; Scottish Funding Council; New South Wales Health.
"The most studied marker is white matter lesions (WML), with both cross-sectional and prospective studies showing that WML and WML progression are associated with retinopathy, focal retinal arteriolar signs, changes in retinal vascular caliber (retinal arteriolar narrowing and venular widening), and suboptimal retinal bifurcation [18, 21, 36, 47–53]. Lacunar infarcts have been linked to different retinal vascular changes both in population-based studies   and in patients with stroke    and atherosclerotic disease , while cerebral microbleeds have been shown to be associated with retinal arteriolar narrowing , retinal venular widening, and decreased retinal arteriolar fractal dimension , and with proliferative diabetic retinopathy in Type 1 diabetes . "
[Show abstract][Hide abstract] ABSTRACT: Although cerebral small vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. As the retina and the brain share similar embryological origin, anatomical features and physiological properties with the cerebral small vessels, the retinal vessels thus offer a unique and easily accessible "window" to study the correlates and consequences of cerebral small vessel diseases in vivo. Retinal microvasculature can now be visualized, quantified and monitored non-invasively using state-of-the-art retinal imaging technology. Recent clinic- and population-based studies have demonstrated a link between retinal vascular changes and dementia, in particular AD, and cerebral small vessel disease. In this review, we summarize the current findings on retinal vascular changes such as retinopathy signs and changes in novel retinal vascular network parameters and retinal vascular caliber with dementia, cognitive dysfunction and cerebral small vessel disease, and discuss possible future research to further evaluate whether retinal vascular imaging might help to elucidate vascular mechanisms contributing to the development of AD and provide additional value in predicting who may be at risk of developing AD.
"Cerebral arteriole sizes are below that which can be visualised reliably using current human imaging techniques but the retina can be photographed directly. Retinal vascular abnormalities are associated with both stroke and white matter disease presence and progression (7–10) and retinal venular (11, 12) and arteriolar (12) widths differ between stroke subtypes. Retinal vessel abnormalities may act as markers for cerebral small vessel disease, although retinal vascular geometry has not been studied in ischaemic stroke subtypes. "
[Show abstract][Hide abstract] ABSTRACT: Cerebral small vessel disease (lacunar stroke and cerebral white matter hyperintensities) is caused by vessel abnormalities of unknown aetiology. Retinal vessels show developmental and pathophysiological similarities to cerebral small vessels and microvessel geometry may influence vascular efficiency.
Retinal arteriolar branching angles or coefficients (the ratio of the sum of the cross-sectional areas of the two daughter vessels to the cross-sectional area of the parent vessel at an arteriolar bifurcation) may be associated with cerebral small vessel disease.
We performed a cross-sectional observational study in a UK tertiary referral hospital. An experienced stroke physician recruited consecutive patients presenting with lacunar ischaemic stroke with a control group consisting of patients with minor cortical ischaemic stroke. We performed brain magnetic resonance imaging to assess the recent infarct and periventricular and deep white matter hyperintensities. We subtyped stroke with clinical and radiological findings. We took digital retinal photographs to assess retinal arteriolar branching coefficients and branching angles using a semi-automated technique.
Two hundred and five patients were recruited (104 lacunar stroke, 101 cortical stroke), mean age 68-years (standard deviation 12). With multivariate analysis, increased branching coefficient was associated with periventricular white matter hyperintensities (P=0.006) and ischaemic heart disease (P<0.001), and decreased branching coefficient with deep white matter hyperintensities (P=0.003), but not with lacunar stroke subtype (P=0.96). We found no associations with retinal branching angles.
Retinal arteriolar geometry differs between cerebral small vessel phenotypes. Further research is needed to ascertain the clinical significance of these findings.
International Journal of Stroke 12/2010; 5(6):434-9. DOI:10.1111/j.1747-4949.2010.00483.x · 3.83 Impact Factor
"They are largely confined to the cerebral white matter and subcortical structures, most commonly found in the putamen, caudate nucleus, thalamus, pons, internal capsule and the cerebral white matter. Lacunar infarcts are associated with SVD [17, 74] but not with CAA. Pathogenetically, hypertension, diabetes, previous brain infarcts, an increase of high-density lipoproteins and triglycerides in the blood  were considered risk factors, but a recent review reported that this risk is not greater than that for large infarcts . "
[Show abstract][Hide abstract] ABSTRACT: Cerebral atherosclerosis (AS), small vessel disease (SVD), and cerebral amyloid angiopathy (CAA) are the most prevalent arterial disorders in the aged brain. Pathogenetically, AS and SVD share similar mechanisms: plasma protein leakage into the vessel wall, accumulation of lipid-containing macrophages, and fibrosis of the vessel wall. CAA, on the other hand, is characterized by the deposition of the amyloid beta-protein in the vessel wall. Despite these differences between CAA, AS and SVD, apolipoprotein E (apoE) is involved in all three disorders. Such a pathogenetic link may explain the correlations between AS, SVD, CAA, and Alzheimer's disease in the brains of elderly individuals reported in the literature. In addition, AS, SVD, and CAA can lead to tissue lesions such as hemorrhage and infarction. Moreover, intracerebral SVD leads to plasma protein leakage into the damaged vessel wall and into the perivascular space resulting in a blood-brain barrier (BBB) dysfunction. This SVD-related BBB dysfunction is considered to cause white matter lesions (WMLs) and lacunar infarcts. In this review, we demonstrate the relationship between AS, SVD, and CAA as well as their contribution to the development of vascular tissue lesions and we emphasize an important role for apoE in the pathogenesis of vessel disorders and vascular tissue lesions as well as for BBB dysfunction on WML and lacunar infarct development.
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