Differences in retinal vessels support a distinct vasculopathy causing lacunar stroke

Doubal, Fergus; MacGillivray, Tom; Hokke, Petra; Dhillon, Baljean; Dennis, Martin; Wardlaw, Joanna M.

doi:10.1212/wnl.0b013e3181a60a71

Cited by 55 publications

(57 citation statements)

References 33 publications

(45 reference statements)

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“…The exact cause of lacunar stroke is unclear but it may be the focal manifestation of a widespread nonatheromatous small vessel vasculopathy perhaps resulting from increased bloodbrain barrier permeability associated with endothelial dysfunction. 24 We have shown that although the presence of retinopathy (hemorrhages and exudates) does not differ, 8 retinal venules are wider in lacunar compared to cortical stroke, 6 which has been confirmed by others. 7 The presence of these small yet important differences in the retinal vessels points toward a distinct vasculopathy causing lacunar stroke, which is likely to be systemic and also affect other major organs.…”

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confidence: 76%

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Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke

Doubal¹,

MacGillivray²,

Patton³

et al. 2010

Neurology

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152

133

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Objectives: Lacunar strokes account for 25% of all ischemic strokes and may represent the cerebral manifestation of a systemic small vessel vasculopathy of unknown etiology. Altered retinal vessel fractal dimensions may act as a surrogate marker for diseased cerebral vessels. We used a cross-sectional study to investigate fractal properties of retinal vessels in lacunar stroke. Methods:We recruited patients presenting with lacunar stroke and patients with minor cortical stroke as controls. All patients were examined by a stroke expert and had MRI at presentation. Digital retinal photographs were taken of both eyes. Monofractal and multifractal analyses were performed with custom-written semiautomated software. Results:We recruited 183 patients. Seventeen were excluded owing to poor photographic quality, leaving 166 patients (86 with lacunar and 80 with cortical stroke). The mean age was 67.3 years (SD 11.5 years). The patients with lacunar stroke were younger but the prevalence of diabetes, hypertension, and white matter hyperintensities did not differ between the groups. The mean Dbox (monofractal dimension) was 1.42 (SD 0.02), the mean D0 (multifractal dimension) 1.67 (SD 0.03). With multivariate analysis, decreased Dbox and D0 (both representing decreased branching complexity) were associated with increasing age and lacunar stroke subtype after correcting for hypertension, diabetes, stroke severity, and white matter hyperintensity scores. Conclusions:Lacunar stroke subtype and increasing age are associated with decreased fractal dimensions, suggesting a loss of branching complexity. Further studies should concentrate on longitudinal associations with other manifestations of cerebral small vessel disease.

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confidence: 76%

“…Previous studies have focused on retinopathy, 8 vessel widths, 6,7 or simple geometric abnormalities 9,10 in cerebral small vessel disease, but have only found small differences, perhaps reflecting a low sensitivity for identification of subtle changes.…”

mentioning

confidence: 99%

Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke

Doubal¹,

MacGillivray²,

Patton³

et al. 2010

Neurology

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152

133

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“…32 Retinal vessels share ontogeny, size and physiological characteristics with cerebral small vessels, suggesting potential for using retinal imaging in studying small-vessel disease. 9,33 Retinal venules are wider in patients with lacunar strokes than those in patients with cortical strokes (which are commonly caused by embolism from the heart or large arteries), 34 while analysis of the microvascular network visible in fundus images showed lacunar stroke and increasing age are associated with a loss of branching complexity. 35 Thus, parameters demonstrating a suboptimal retinal vascular network act as a surrogate marker for diseased cerebral vessels.…”

Section: Strokementioning

confidence: 99%

Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions

MacGillivray¹,

Trucco²,

Cameron³

et al. 2014

BJR

119

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imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions. Br J Radiol 2014;87:20130832. REVIEW ARTICLERetinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions 1,2 T J MACGILLIVRAY, MSc ABSTRACTThe black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions.Currently about 20 million people in the UK suffer from at least 1 long-term condition (a health problem that cannot be cured but can be controlled by medication or other therapies), and this is set to increase 3-fold over the next decade placing an enormous economic and humanresource strain on the National Health Service.1-3 The retina is unique in the body in allowing easy observation of blood vessels with simple, non-invasive instruments. It is also the only accessible site for studying the central nervous system (CNS) in vivo.4 This makes it a ripe environment for the study of systemic and neurological disease, in a patient-acceptable way. Changes to the retina can occur in some chronic diseases years before other signs become apparent. [5][6][7][8][9] Thus, studying the retina may provide an additional means for clinicians to stratify risk and help identify people who would benefit from early lifestyle changes and preventative therapies, as well as assessing the efficacy of new treatments. In addition, there is some early evidence that certain retinal measures may correlate with disease characterization and also prognosis, which not only provides clinicians with a useful assessment tool but also offers research scientists new avenues to explore in the understanding of the p...

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“…2 Recent studies, however, have challenged this assumption and suggested an alternative hypothesis that lacunar infarction is related to nonatherothrombotic small vessel pathology. 3 We recently reported that among 1321 patients with acute ischemic stroke, those with lacunar infarction were more likely to have focal retinal arteriolar narrowing, enhanced arteriolar light reflex, arteriovenous nicking, and widening of retinal venules than patients with nonlacunar infarction, and that both lacunar and nonlacunar infarction had similar proportions with hypertension, diabetes, or hypercholesterolemia. 4 Because deep ICH and lacunar infarcts occur within the same vascular structural level (ie, small vessel disease), 5 we hypothesized they may share similar retinal microvascular signs with those seen in lacunar infarction, but that this pattern would differ from the retinal microvascular signs seen in patients with nonlacunar infarction (eg, resulting from atherothromboembolism and cardiac embolism).…”

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confidence: 97%

Retinal Microvascular Signs May Provide Clues to the Underlying Vasculopathy in Patients With Deep Intracerebral Hemorrhage

Baker

Hand²,

Liew³

et al. 2010

Stroke

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Background and Purpose-Deep intracerebral hemorrhage (ICH) and lacunar infarcts are the result of small vessel disease, whereas nonlacunar infarcts are often caused by large artery atherosclerosis or cardiac embolism. We hypothesized that patients with deep ICH and lacunar infarcts have similar retinal microvascular signs and that these differ from those seen in patients with nonlacunar infarcts. Methods-We studied patients with acute stroke and classified their stroke as deep ICH, lacunar infarction, or nonlacunar infarction. In a masked fashion we assessed retinal photographs for quantitative and qualitative evidence of microvascular damage. Results-We recruited 630 patients (51 had deep ICH, 93 had lacunar infarction, and 486 had nonlacunar infarction).Patients with deep ICH were more likely than those with nonlacunar infarcts to have severe focal narrowing of the retinal arterioles (OR, 3.7), severe arteriovenous nicking (OR, 2.6), and quantitatively narrower retinal arterioles and wider retinal venules. Retinal microvascular signs were similar in patients with deep ICH and lacunar infarction. Conclusions-Patients

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Differences in retinal vessels support a distinct vasculopathy causing lacunar stroke

Abstract: Retinal venules are wider and arteriovenous ratios are smaller in patients with lacunar strokes compared with those in patients with cortical strokes.

Cited by 55 publications

References 33 publications

Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke

Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke

Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions

Retinal Microvascular Signs May Provide Clues to the Underlying Vasculopathy in Patients With Deep Intracerebral Hemorrhage

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