Retinal microvasculature in acute lacunar stroke: a cross-sectional study.
ABSTRACT 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.
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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.Journal of Alzheimer's disease: JAD 01/2014; 42:S339-52. DOI:10.3233/JAD-141596 · 3.61 Impact Factor
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ABSTRACT: The presence of a native collateral circulation in tissues lessens injury in occlusive vascular diseases. However, differences in genetic background cause wide variation in collateral number and diameter in mice, resulting in large variation in protection. Indirect estimates of collateral perfusion suggest that wide variation also exists in humans. Unfortunately, methods used to obtain these estimates are invasive and not widely available. We sought to determine whether differences in genetic background in mice result in variation in branch patterning of the retinal arterial circulation, and whether these differences predict strain-dependent differences in pial collateral extent and severity of ischemic stroke. Retinal patterning metrics, collateral extent, and infarct volume were obtained for 10 strains known to differ widely in collateral extent. Multivariate regression was conducted, and model performance was assessed using K-fold cross-validation. Twenty-one metrics varied with strain (p < 0.01). Ten metrics (e.g., bifurcation angle, lacunarity, optimality) predicted collateral number and diameter across seven regression models, with the best model closely predicting (p < 0.0001) number (±1.2-3.4 collaterals, K-fold R (2) = 0.83-0.98), diameter (±1.2-1.9 μm, R (2) = 0.73-0.88), and infarct volume (±5.1 mm(3), R (2) = 0.85-0.87). An analogous set of the most predictive metrics, obtained for the middle cerebral artery (MCA) tree in a subset of the above strains, also predicted (p < 0.0001) collateral number (±3.3 collaterals, K-fold R (2) = 0.78) and diameter (±1.6 μm, R(2) = 0.86). Thus, differences in arterial branch patterning in the retina and the MCA trees are specified by genetic background and predict variation in collateral extent and stroke severity. If also true in human, and since genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar "retinal predictor index" could serve as a non- or minimally invasive biomarker for collateral extent in brain and other tissues. This could aid prediction of severity of tissue injury in the event of an occlusive event or development of obstructive disease and in patient stratification for treatment options and clinical studies.Angiogenesis 11/2014; DOI:10.1007/s10456-014-9449-y · 4.41 Impact Factor
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ABSTRACT: PurposeTo investigate the association between visual changes and retinal vessel attenuation in patients with retinitis pigmentosa (RP).DesignA retrospective, longitudinal, observational cohort study.MethodsWe analyzed 45 eyes from 45 subjects who were followed-up for ≥3 years at our clinic. Using the computer-based Interactive Vessel Analysis program, central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were determined. Age- and sex-matched controls from normal subjects were selected from our archived fundus photograph library. Visual acuity, visual field area (Goldmann perimetry, V4e white test light), mean deviation (Humphrey perimetry, central 10-2 program), and central macular thickness (optical coherence tomography) were analyzed for correlations with CRAE and CRVE.ResultsBoth CRAE and CRVE were significantly decreased in RP eyes (94.9±13.5 μm and 155.6±20.0 μm, respectively) compared with control eyes (138.1±14.7 μm and 215.0±20.4 μm, respectively, both P<0.001). After 3 years of follow-up, visual field area was associated with both CRAE (r=0.584, P<0.01) and CRVE (r=0.500, P=0.008). A significant association was also observed between mean deviation and CRAE (r=0.298, P=0.047). In eyes with RP, a narrower vessel caliber at baseline was associated with a larger decline in visual acuity over the 3-year follow-up interval (CRAE: r=−0.344, P=0.021; CRVE: r=−0.314, P=0.035).ConclusionRetinal vessel caliber is associated with some visual functions in patients with RP.Clinical ophthalmology (Auckland, N.Z.) 08/2014; 8:1487-93. DOI:10.2147/OPTH.S66326