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August 17, 2011

Retinal microvascular changes and subsequent vascular events after ischemic stroke

August 30, 2011 issue
77 (9) 896-903

Abstract

Objectives:

Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007.

Methods:

Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2–4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models.

Results:

Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20–4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14–6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31–5.86) compared to those without FAN.

Conclusions:

Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

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Supplementary Material

File (appendix_e-1.doc)
File (figure_e-1_with_legend.pdf)

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Information & Authors

Information

Published In

Neurology®
Volume 77Number 9August 30, 2011
Pages: 896-903
PubMed: 21849643

Publication History

Received: February 11, 2011
Accepted: May 12, 2011
Published online: August 17, 2011
Published in print: August 30, 2011

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Disclosure

Dr. De Silva, Dr. Manzano, E.Y. Liu, F.-P. Woon, and W.-X. Wong report no disclosures. Dr. Chang receives research support from Boehringer Ingelheim, SERVIER, Singapore BMRC, Singapore NMRC, and University of Nottingham. Dr. Chen serves on scientific advisory boards for Baxter International Inc., Allergan, Inc., and Pfizer Inc; has received funding for travel from Moleac Pte Ltd.; serves on the editorial boards of Stroke, the Journal of Neurology, Neurosurgery and Psychiatry, and the International Journal of Stroke; serves as a consultant for BrainsGate; and receives research support from GlaxoSmithKline, Merck Serono, Wyeth, Eisai Inc., and the National Medical Research Council of Singapore. Dr. Lindley receives research support from the National Health and Medical Research Council of Australia, the NSW Department of Health, and the Moran Foundation for Older Australians (funds University salary). Dr. Wang serves on the editorial boards of Clinical & Experimental Ophthalmology and the Journal of Ophthalmology; receives publishing royalties for Retinal Degenerations, Biology, Diagnostics, and Therapeutics (Humana Press, 2007); and receives research support from NHMRC, the Heart Foundation, and the Health Assistance Foundation. Dr. Mitchell serves on scientific advisory boards for Novartis, Allergan, Inc., Bayer Schering Pharma, and Pfizer Inc; has received funding for travel and speaker honoraria from Novartis, Bayer Schering Pharma, Allergan, Inc., and Abbott; serves on the editorial boards of Eye and the British Journal of Ophthalmology; and receives research support from the Australian National Health and Medical Research Council. Dr. T.-Y. Wong serves on scientific advisory boards and as a consultant for Pfizer Inc, Novartis, Bayer Schering Pharma, and Allergan, Inc.; serves as Executive Editor for the American Journal of Ophthalmology and on editorial advisory boards for Investigative Ophthalmology and Visual Sciences, Diabetes Care, and Ophthalmic Epidemiology; and receives research support from the National Medical Research Council of Singapore and the Singapore Biomedical Research. Dr. M.-C. Wong receives research support from the National Medical Research Council (NMRC) of Singapore.

Authors

Affiliations & Disclosures

D.A. De Silva, MRCP
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
J.J.F. Manzano, MD
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
E.Y. Liu, BSc
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
F.-P. Woon, MSc
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
W.-X. Wong, BSc
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
H.-M. Chang, MRCP
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
C. Chen, FRCP
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
R.I. Lindley, FRACP
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
J.J. Wang, PhD
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
P. Mitchell, MD, PhD
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
T.-Y. Wong, FRCSE, PhD*
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.
M.-C. Wong, FRCP* On behalf of the Multi-Centre Retinal Stroke Study Group
From the National Neuroscience Institute (D.A.D.S., J.J.F.M., H.-M.C.), Singapore General Hospital Campus, Singapore; Singapore Eye Research Institute (E.Y.L., W.-X.W., T.-Y.W.), Singapore National Eye Centre, Singapore; National Heart Centre Singapore (F.-P.W.), Singapore; Department of Pharmacology (C.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Geriatric Medicine (R.I.L.), Discipline of Medicine, Westmead Hospital, and Centre for Vision Research (J.J.W., P.M.), Westmead Millennium Institute and Department of Ophthalmology, Western Clinical School, University of Sydney, Westmead, New South Wales, Australia; and National Medical Research Council (M.-C.W.), Singapore.

Notes

*
These senior authors contributed equally to this work.
Study funding: Supported by grants from the Australian National Health and Medical Research Council (NHMRC 352337) and Singapore National Medical Research Council (NMRC 2004/073, NMRC/0914/2004, and NMRC/0914/S2).
Address correspondence and reprint requests to Dr. D.A. De Silva, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608 [email protected]

Author Contributions

Dr. De Silva conceptualized and designed the study, recruited patients and collected data, analyzed and interpreted the data, and drafted and edited the manuscript. Dr. Manzano analyzed and interpreted the data and drafted and edited the manuscript. E.Y. Liu analyzed the data, edited the manuscript, and conducted the statistical analysis. F.-P. Woon recruited patients and collected data, analyzed and interpreted the data, and edited the manuscript. W.-X. Wong recruited patients and collected data and edited the manuscript. Dr. Chang recruited patients and collected data and edited the manuscript. Dr. Chen recruited patients and collected data and edited the manuscript. Dr. Lindley conceptualized and designed the study, obtained funding, and edited the manuscript. Dr. Wang conceptualized and designed the study, obtained funding, analyzed the data, and edited the manuscript. Dr. Mitchell conceptualized and designed the study, obtained funding, analyzed the data, and edited the manuscript. Dr. T.Y. Wong conceptualized and designed the study, obtained funding, analyzed and interpreted the data, and drafted and edited the manuscript. Dr. M.C. Wong conceptualized and designed the study, obtained funding, recruited patients and collected data, analyzed and interpreted the data, and drafted and edited the manuscript.

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