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Microvascular damage, as reflected by cerebral small- vessel disease (eg, lacunar infarctions and leukoara-

iosis), has been implicated in the pathogenesis of ischemic stroke.1,2 However, it remains difficult to directly observe damage to the cerebral microcirculation in vivo, despite major advances in neuroimaging technologies. The retina provides a unique window to assess cerebral microvascular health directly and noninvasively in vivo, because the retinal blood vessels share many features with the brain, including embryo-logical origin and anatomic and physiological characteristics.

In the past few years, there has been increasing evidence that traditional indicators of retinal microvascular damage (eg, retinopathy signs, such as retinal hemorrhage and

microaneurysms, and retinal vascular caliber changes) are associated with both cerebrovascular (including clinical stroke and subclinical MRI-defined cerebral infarction)3–5; and neurodegenerative diseases (including cognitive decline, dementia, and cerebral atrophy).6–8 These findings further support the concept that microvascular pathology may play an important role in the development of a wide range of age-related brain diseases, such as stroke, dementia, and Alzheimer disease. These retinal microvascular changes not only may represent cerebral small-vessel damage9,10 but also may be the result of downstream effects of proximal large-artery disease.11 Retinopathy signs are, however, relatively late indicators of target organ damage in the eye and probably

Background and Purpose—Microvascular disease has been implicated in the pathogenesis of stroke. The retina provides a window to assess microcirculation noninvasively. We studied the association between quantitatively measured retinal microvascular characteristics and acute ischemic stroke.

Methods—We conducted a case-control study with acute ischemic stroke patients recruited from a tertiary hospital in Singapore and controls from the Singapore Epidemiology of Eye Disease program matched by 10-year age strata, sex, and race. Strokes were classified using modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Retinal vascular parameters were measured from retinal fundus photographs using a computer program. Logistic regression models for stroke were constructed adjusting for age, sex, race, and additionally for smoking, hypertension, diabetes mellitus, and hypercholesterolemia.

Results—We included 557 ischemic stroke cases (261 lacunar, 185 large artery, and 54 cardioembolic stroke) and 557 controls. After adjusting for vascular risk factors, decreased arteriolar fractal dimension (odds ratio [OR] per standard deviation [SD] decrease, 2.28; 95% confidence interval [CI], 1.80–2.87) and venular fractal dimension (OR per SD decrease, 1.80; 95% CI, 1.46–2.23), increased arteriolar tortuosity (OR per SD increase, 1.56; 95% CI, 1.25–1.95), and venular tortuosity (OR per SD increase, 1.49; 95% CI, 1.27–1.76), narrower arteriolar caliber (OR per SD decrease, 2.79; 95% CI, 2.21–3.53), and wider venular caliber (OR per SD increase, 1.57; 95% CI, 1.27–1.95) were associated with stroke. Stratification by stroke subtypes and further adjustment for retinopathy signs revealed similar results.

Conclusions—Patients with ischemic stroke have a sparser and more tortuous microvascular network in the retina. These findings provide insight into the structure and pattern of microcirculation changes in stroke. (Stroke. 2013;44:2121-2127.)

Key Words: imaging ■ ischemic microvascular dysfunction ■ stroke

Microvascular Structure and Network in the Retina of Patients With Ischemic Stroke

Yi-Ting Ong, BSc; Deidre A. De Silva, MBBS, MRCP; Carol Y. Cheung, PhD; Hui-Meng Chang, MBBS, MRCP; Christopher P. Chen, MRCP, FAMS;

Meng Cheong Wong, MBBS, MRCP; Tien Yin Wong, MD, PhD; Mohammad Kamran Ikram, MD, PhD

Received April 8, 2013; accepted April 26, 2013.From the Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore (Y.-T.O., C.Y.C., T.Y.W., M.K.I.); National University

of Singapore Graduate School for Integrative Sciences and Engineering (Y.-T.O.), Department of Ophthalmology, Yong Loo Lin School of Medicine (Y.-T.O., C.Y.C., T.Y.W., M.K.I.), and Department of Pharmacology (C.C.), National University of Singapore, Singapore, Singapore; National Neuroscience Institute, Singapore General Hospital Campus, Singapore, Singapore (D.A.D.S., H.-M.C., M.-C.W.); Centre for Quantitative Medicine, Office of Clinical Sciences, Duke–National University of Singapore Graduate Medical School, Singapore, Singapore (C.Y.C.); Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore (C.C., M.K.I.); and Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands (M.K.I.).

Correspondence to M. Kamran Ikram, MD, PhD, Singapore Eye Research Institute, 11 Third Hospital Ave, Singapore 168751, Singapore. E-mail [email protected]

© 2013 American Heart Association, Inc.

Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.113.001741

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2122 Stroke August 2013

reflect advanced stages of structural microvascular damage, including breakdown of the blood–retina barrier.12,13

Advances in digital retinal photography and computer image analysis have now enabled more objective quantita-tive assessment of retinal microvascular structure and pat-tern, which may reflect earlier and subtler changes in the retinal microcirculation, even before retinopathy signs appear. Additionally, such assessments can be performed objectively even in the presence of retinopathy lesions. A range of novel retinal microvascular parameters have been proposed such as fractal dimension and tortuosity, which are global reflections of how optimal the retinal microcirculation is. To further test the hypothesis that microvascular changes may contribute to the pathogenesis of ischemic stroke, we focused our study on these novel retinal parameters.

In the present study, we applied this novel and advanced image analysis technology to measure and summarize the pattern and geometry of the retinal vasculature and examined their associations with ischemic stroke and its major subtypes.

Materials and MethodsStudy PopulationThe Multi-Centre Retinal Stroke (MCRS) study is a cross-sectional observational study of patients with acute stroke, spanning 3 centers in Sydney, Melbourne, and Singapore.14 In the present study, only patients from Singapore were included. Patients presenting to the Singapore General Hospital with first-ever or recurrent stroke within 7 days of onset were recruited from 2005 to 2007. Patients were in-cluded if they were 40 to 80 years of age, of Chinese, Malay, or Indian race, had ischemic stroke pathogenesis, had adequate sitting ability to tolerate retinal photography, and had retinal photographs of grad-able quality. Eligible stroke cases were matched to controls of the same 10-year age group, sex, and race, with no self-reported history of stroke selected from participants of the Singapore Epidemiology of Eye Diseases (SEED) study.15,16 This study is a population-based study of eye disease in an age-stratified random sample of Chinese, Malay, and Indian residents aged 40 to 80 years living in south west-ern Singapore in the region where Singapore General Hospital pro-vides stroke services. Written informed consent was obtained from each participant or next-of-kin, and previous approval for the project was obtained from the Singapore General Hospital’s Institutional Review Board.

Assessment of Retinal Vascular Parameters and RetinopathyRetinal fundus photographs were taken of each eye with a nonmydriat-ic digital camera after dilation of pupils with 1% tropicamide eye drops according to a standardized protocol for participants of the MCRS study14 and the SEED studies.15,16 Optic disc–centered images of a ran-domly selected eye from each participant were masked and collated for centralized grading at the Singapore Eye Research Institute. Trained graders fed the images through a semiautomated computer-assisted program, Singapore I Vessel Assessment (version 3.0.0.0), grading to a standardized protocol, with measured area defined as 0.5 to 2.0 disc diameters away from the disc margin. Measurement of quantitative retinal parameters, which capture the overall structure of the retinal microvessels, was not influenced by the presence of localized retinopa-thy signs. Quantitative measures of the following retinal vascular pa-rameters were extracted and used for analysis: retinal vascular caliber, fractal dimension, tortuosity, and branching angle.

Retinal Vascular CaliberRetinal vascular caliber measurements were based on the revised Knudtson-Parr-Hubbard formula, as described elsewhere,17 with arte-riolar caliber summarized as central retinal arteriolar equivalent and venular caliber summarized as central retinal venular equivalent.

Retinal Vascular Fractal DimensionRetinal vascular fractal dimension was calculated from skeletonized line tracing using the box counting method, a global measure summa-rizing the entire branching pattern of the retinal vascular tree.18 Larger values indicate a more complex branching pattern.

Retinal Vascular TortuosityRetinal vascular tortuosity was defined as the integral of the curvature square along the vessel path, normalized by the total path length.19 Estimates were summarized as retinal arteriolar tortuosity and retinal venular tortuosity. Smaller values indicate straighter vessels.

Retinal Vascular Branching AngleBranching angle is defined as the first angle subtended between 2 daughter vessels at each vascular bifurcation.20 The average branch-ing angle of the arterioles and venules of the eye were calculated.

Retinopathy SignsQualified graders masked to participant characteristics and clinical status evaluated fundus photographs from both eyes without assump-tion of cause for the presence of the following retinopathy lesions: focal arteriolar narrowing, arteriovenous nicking, microaneurysms, retinal hemorrhages, soft exudates, hard exudates, macular edema, intraretinal microvascular abnormalities, venous beading, new ves-sels at the disc or elsewhere, and disc swelling.

Assessment of Stroke and Stroke SubtypesAll stroke patients were assessed by a standardized questionnaire with an interview conducted by trained medical staff, a neurological exam-ination, and brain imaging (computed tomography or MRI). Stroke was classified at clinical consensus meetings with research staff and clinicians using a modified version of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification.14 Stroke subtypes were defined as large-vessel atheroscelerotic stroke, small-vessel lacunar stroke, cardioembolic stroke, stroke of other pathogenesis, and stroke of undetermined pathogenesis. Because the original TOAST classi-fication would lead to a large proportion of strokes with uncertain classification, a pragmatic modification was adopted from the Greater Metropolitan Clinical Task Force for Stroke in New South Wales. Additionally, references to hypertension and diabetes mellitus as risk factors for lacunar stroke also were removed to avoid risk factor bias in classification, resulting in a clinico-neuroanatomical definition. Further details of classification have been published elsewhere.10,14

Assessment of Cardiovascular Risk FactorsBoth patients with ischemic stroke and control participants from the SEED study (and their caregivers) were administered detailed questionnaires for information on smoking and history of physician-diagnosed or medication use for hypertension, diabetes mellitus, and hypercholesterolemia. Additionally, as part of clinical care for stroke, patients with ischemic stroke underwent standard clinical assessment after the acute phase for stroke to determine cardiovascular risk factors; this included multiple blood pressure measurements and fasting blood samples for glucose, hemoglobin A1C, and lipids. Controls, as part of the SEED study, underwent extensive examination on the day of retinal photography, which included ≥2 blood pressure measurements at the same sitting and random blood samples for glucose, hemoglobin A1C, and cholesterol. Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg at examination, a reported history of physician-diagnosed


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Ong et al Retinal Microvasculature and Ischemic Stroke 2123

hypertension or a self-reported history of antihypertensive medication use, or both. Diabetes mellitus was defined as random blood glucose ≥200 mg/dL (11.1 mmol/L), fasting blood glucose ≥126 mg/dL (7.0 mmol/L), hemoglobin A1C ≥7%, self-reported history of physician-diagnosed diabetes mellitus, or self-reported history of antihyperglycemic medication use. Hypercholesterolemia was defined as total cholesterol ≥6.2 mmol/L, or a self-reported history of physician-diagnosed hypercholesterolemia, or self-reported use of lipid-lowering medication use.

Statistical AnalysisBaseline characteristics, prevalence of cardiovascular risk factors, and retinal geometric parameters were compared between cases and controls using Student t test for continuous variables and Pearson χ2 test for categorical variables. Odds ratios and their 95% confidence intervals for stroke and its subtypes per SD increase or decrease in retinal vascular parameters were calculated. We initially adjusted for age, sex, and race, and additionally for hypertension, diabetes mellitus, hypercholesterolemia, and smoking history. As proposed previously, because of the high correlation between arteriolar and venular caliber values (Pearson correlation coefficient, 0.691; P<0.001), all models testing vessel caliber were additionally adjusted for the companion vessel. Finally, all fully adjusted models were additionally adjusted for the presence of retinopathy signs to examine whether the associations between novel retinal parameters and stroke were independent of reti-nopathy signs. All analyses were performed using SPSS version 17.0.

ResultsAmong the patients recruited into the Singapore component of the MCRS study, a total of 557 patients were eligible for inclusion into this study and 557 controls were subsequently selected from the SEED study cohorts by matching for sex,

10-year age group, and race. Comparisons of baseline charac-teristics between ischemic stroke cases and controls are pre-sented in Table 1. In general, patients with ischemic stroke were more likely to be current smokers and to have hyper-tension, diabetes mellitus, and hypercholesterolemia. The most common stroke subtype was lacunar infarction (n=261; 47.0%), followed by large-artery stroke (n=185; 33.3%) and cardioembolic stroke (n=54; 9.7%), whereas the remaining 56 (10.1%) strokes were of other or undetermined causes.

As shown in Table 1 and in Figures 1 and 2, patients with ischemic stroke had relatively smaller fractal dimensions (total, arteriolar, and venular), higher arteriolar and venular tortuosity, and narrower arteriolar calibers. After adjustment for age, sex, race, and for the cardiovascular risk factors of hypertension, diabetes mellitus, hypercholesterolemia, and smoking history (Table 2), decreasing arteriolar and venular fractal dimension, increasing arteriolar and venular tortuosity, narrower arteriolar caliber, and wider venular caliber were associated with isch-emic stroke, whereas associations with other branching param-eters such as branching angle were not significant.

Associations of these parameters were similar with stroke subtypes of lacunar, large artery, and cardioembolic stroke, with no observable differences in effect sizes between different stroke pathogeneses (Table 2). Furthermore, when fully adjusted models were additionally adjusted for presence of clinically visible reti-nopathy signs, decreasing arteriolar and venular fractal dimen-sion, increasing arteriolar and venular tortuosity, and narrower arteriolar caliber remained significantly associated with stroke.

Table 1. Comparison of Baseline Characteristics and Retinal Geometric Parameters in Stroke Cases and Controls

Cases (n=557) Controls (n=557) P Value

Demographics and cardiovascular risk factors

Male, n (%) 356 (63.9) 356 (63.9) 1.000

Age (years), mean (SD) 61.9 (9.4) 61.9 (9.1) 0.988

Chinese race, n (%) 451 (81.0) 451 (81.0) 1.000

Malay race, n (%) 63 (11.3) 63 (11.3)

Indian race, n (%) 43 (7.7) 43 (7.7)

Never smoker, n (%) 274 (50.9) 396 (71.1) <0.001

Ex-smoker, n (%) 92 (17.1) 112 (20.1)

Current smoker, n (%) 163 (30.3) 49 (8.8)

Hypertension, n (%) 377 (67.8) 235 (42.2) <0.001

Diabetes mellitus, n (%) 226 (40.6) 60 (10.9) <0.001

Hypercholesterolemia, n (%) 259 (46.5) 219 (39.7) 0.025

Retinal vessel parameters, mean (95% confidence interval)

Total fractal dimension 1.379 (1.373–1.385) 1.421 (1.416–1.425) <0.001

Arteriolar fractal dimension 1.153 (1.147–1.159) 1.198 (1.193–1.203) <0.001

Venular fractal dimension 1.185 (1.179–1.190) 1.208 (1.204–1.213) <0.001

Arteriolar curvature tortuosity (×104) 0.646 (0.622–0.670) 0.605 (0.592–0.618) 0.003

Venular curvature tortuosity (×104) 0.852 (0.835–0.869) 0.785 (0.769–0.802) <0.001

Arteriolar caliber 127.8 (126.7–128.8) 134.5 (133.1–135.9) <0.001

Venular caliber 198.6 (197.0–200.2) 199.4 (197.4–201.4) 0.564

Arteriolar branching angle (°) 75.2 (74.1–76.3) 75.7 (74.8–76.6) 0.511

Venular branching angle (°) 77.5 (76.4–78.6) 77.8 (76.8–78.7) 0.720

Presence of retinopathy signs, n (%) 416 (74.7) 56 (10.1) <0.001


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DiscussionIn this study, we demonstrate for the first time to our knowledge that the structure and pattern of quantitatively measured micro-vasculature in the retina are different in patients with ischemic stroke compared with healthy control subjects. Novel retinal measures indicative of a sparser and more tortuous vascular network, in addition to narrower arteriolar caliber and wider venular caliber, were associated with ischemic stroke and with its major etiologic subtypes, independent of traditional cardio-vascular risk factors and clinically visible retinopathy signs.

Several studies previously have suggested that cerebral small-vessel disease is implicated in ischemic stroke and is considered to be highly related to, but not restricted to, lacu-nar infarction.21 Pathological processes in the brain such as atherosclerosis, lipohyalinosis, and arteriosclerosis lead to the destruction and occlusion of small perforating vessels21,22 and cause vessel wall remodeling, resulting in elongated and tortu-ous vessels associated with increased vascular leakage.21 These changes affect the ability of cerebral arterioles to maintain control of local blood flow, predisposing areas served by these dysfunctional vessels to ischemic damage. In the retina, vessel rarefaction and collapse, leading to reduction in vascular frac-tal dimension, is associated with hypoxia23; whereas increased vessel tortuosity is indicative of vessel wall dysfunction and blood–retina barrier damage.24,25 Our findings suggest that simi-lar pathological changes in the small vessels of the brain and retina may adversely affect perfusion and vessel wall function. Our study provides direct in vivo data that show a difference in the pattern and structure of the microvascular network between patients with stroke compared with healthy controls.

To our knowledge, this is the first study of a comprehensive assessment of quantitatively measured retinal microvascular parameters in stroke cases. Previous studies have identified individual associations with specific parameters. For example, the link between retinal fractal dimension and stroke has been reported.26,27 Our study shows that reduced retinal fractal dimen-sion and increased retinal vessel tortuosity is associated with ischemic stroke, suggesting that the retinal vascular network can reflect corresponding microvascular abnormalities indica-tive of reduced vascular perfusion and barrier damage leading to ischemic damage in the cerebral vasculature.28 Furthermore, because these morphological changes in the retinal microvas-culature are similarly associated with both large-artery stroke and lacunar infarcts in our study, it is suggested that structural changes to retinal microvessels not only reflect small-vessel pathology but also may result from downstream effects of large-artery pathology in the retinal and cerebral circulations.9,11

Importantly, it has been demonstrated that similar changes in retinal pattern and geometry are also implicated in cognitive dysfunction29 and dementia (Alzheimer disease; Carol Yim Cheung, PhD, unpublished data, 2013), suggesting that similar cerebral microvascular pathologies—as reflected by alterations in the retinal microvasculature—may underlie both stroke and dementia.

The most studied parameter is retinal vascular caliber, and our study is consistent with previous population-based stud-ies that show narrower arteriolar caliber and wider venular caliber are associated with ischemic stroke. However, because of pulse period variation in vessel calibers,30 measurements from a single time point may not be as useful in stroke risk

Figure 1. Retinal fundus photo grading by semiautomated computer software (SIVA) showing vessel path tracing of images from a stroke patient (A) and a healthy control sub-ject (B), with fundus image on the left and vessel path tracing for fractals on the right. Stroke patient (A) has a sparser retinal network and reduced fractal dimension compared with the healthy control (B).


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stratification, and less time-variable novel structural retinal parameters may be more informative in evaluating cerebral microvascular damage. Fractals and tortuosity measures are attractive because they are relatively static and reflect blood distribution optimality and efficiency; in our study, we found that subtle changes measured by these parameters remain associated with stroke even after adjustment for visible reti-nopathy signs. Hence, these novel structural parameters have

potential advantages beyond that of qualitative signs. These definitely should be further validated and studied in prospec-tive studies.

Several limitations need to be discussed. First, because we had no data on hemorrhagic strokes, we could only focus on ischemic stroke. Second, because patients were required to sit upright for retinal photography, we were limited to patients with relatively mild strokes. Third, the definition of

Figure 2. Retinal fundus photo grading by semiautomated computer software (SIVA) showing vessel path tracing of images from a stroke patient (A) and a healthy control sub-ject (B), with fundus image on the left and magnified image of vessel path tracing for arte-rioles (red) and venules (blue) on the right. Stroke patient (A) has more tortuous venules compared with the healthy control (B).

Table 2. Age, Sex, Race, and Multivariable-Adjusted ORs of Retinal Vascular Parameters for Stroke and its Subtypes

Retinal Vessel Parameters Stroke* (n=557) Stroke† (n=557) Stroke‡ (n=557)

Subtypes by TOAST Classification†

Lacunar (n=261) Large Artery (n=185) Cardioembolic (n=54)

Fractal dimension

Arteriolar per SD decrease 2.44 (2.09–2.87) 2.28 (1.80–2.87) 1.92 (1.47–2.51) 2.28 (1.80–2.87) 2.27 (1.62–3.18) 2.47 (2.01–3.03)

Venular per SD decrease 1.63 (1.42–1.87) 1.80 (1.46–2.23) 1.79 (1.39–2.31) 1.80 (1.46–2.23) 1.99 (1.45–2.73) 1.70 (1.41–2.05)

Tortuosity

Arteriolar per SD increase 1.29 (1.09–1.53) 1.56 (1.25–1.95) 1.91 (1.32–2.76) 1.45 (1.13–1.86) 1.68 (1.30–2.17) 1.60 (1.12–2.26)

Venular per SD increase 1.50 (1.31–1.73) 1.49 (1.27–1.76) 1.32 (1.02–1.72) 1.45 (1.21–1.75) 1.61 (1.31–1.98) 1.54 (1.14–2.08)

Caliber

Arteriolar§ per SD decrease 2.61 (2.14–3.17) 2.79 (2.21–3.53) 2.35 (1.64–3.35) 2.87 (2.19–3.76) 3.49 (2.55–4.78) 1.72 (1.09–2.72)

Venular§ per SD increase 1.83 (1.53–2.20) 1.57 (1.27–1.95) 1.34 (0.96–1.88) 1.60 (1.25–2.06) 1.89 (1.42–2.52) 0.97 (0.63–1.51)

Branching angle

Arteriolar, per SD increase 0.96 (0.95–1.08) 1.08 (0.94–1.24) 1.24 (0.98–1.58) 1.07 (0.90–1.27) 1.09 (0.89–1.33) 0.97 (0.91–1.31)

Venular, per SD increase 0.98 (0.87–1.10) 1.00 (0.87–1.15) 1.12 (0.91–1.39) 0.98 (0.83–1.15) 0.97 (0.80–1.17) 1.05 (0.79–1.40)

CI indicates confidence interval; OR, odds ratio; SD, standard deviation; and TOAST, Trial of Org 10172 in Acute Stroke Treatment.Data are presented as OR (95% CI).*Adjusted for age, sex, race, and arteriolar and venular caliber.†Adjusted for age, sex, race, smoking status, hypertension status, diabetes mellitus status, and hypercholesterolemia status.‡Adjusted for age, sex, race, smoking status, hypertension status, diabetes mellitus status, hypercholesterolemia status, and retinopathy signs.§Additionally adjusted for other vessel caliber.


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cardiovascular risk factors was not exactly similar in cases (fasting blood samples) and controls (random blood sam-ples), and confounding may not have been fully accounted for. Fourth, although Singapore General Hospital provides stroke services to a region overlapping the SEED catchment area, some stroke cases may be from outside this catchment area. However, because Singapore is a small city state with a homogenously urban environment, the SEED region is not expected to be significantly different from that of the rest of Singapore. Finally, the case-control design of our present study did not allow us to determine the temporal sequence of these associations. Further longitudinal studies are required to establish whether changes in retinal vascular geometry are related to the risk of incident stroke and whether they are indicative of cerebrovascular risk beyond conventional risk indicators. Strengths of our study include the large sample size, population-matched controls, and objective measure-ment of quantitative retinal vascular parameters.

ConclusionsRetinal vascular changes reflective of a sparser and more tortuous network in the microcirculation are seen in patients with ischemic stroke, beyond the effects of age, vascular risk factors, and clinically visible retinopathy signs. These data provide convincing evidence of global alterations in the retinal microvasculature in stroke. More prospective studies are required to confirm these associations before they can be implemented as a screening tool.

AcknowledgmentsThe authors thank all staff and participants of the Multi-Centre Retinal Stroke Study and the Singapore Epidemiology of Eye Disease Study for their important contributions.

Sources of FundingThis study was funded by National Medical Research Council, Singapore (073/2004, 0796⁄2003, StaR/0003/2008, and National Medical Research Council/Clinician Scientist Award/038/2012), Biomedical Research Council, Singapore (501/1/25-5, and 08/1/35/19/550), and National Health and Medical Research Council, Australia (352337). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

DisclosuresNone.

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Meng Cheong Wong, Tien Yin Wong and Mohammad Kamran IkramYi-Ting Ong, Deidre A. De Silva, Carol Y. Cheung, Hui-Meng Chang, Christopher P. Chen,Microvascular Structure and Network in the Retina of Patients With Ischemic Stroke

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