title: Microvascular network alterations in retina of subjects with cerebral small vessel disease.
abstract: Novel retinal imaging techniques have enabled the assessment of quantitative vascular parameters, which provide information on the microvasculature before the appearance of retinopathy signs. Advances in neuroimaging have revealed that cerebral microbleeds (CMB) - besides lacunar infarcts and white matter lesions (WML) - may be a novel marker of cerebral small vessel disease. We examine whether quantitative retinal vascular parameters are related to cerebral small vessel disease in a Chinese population. Participants from Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial magnetic resonance imaging and retinal-photography. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from photographs using a semi-automated computer-assisted program. Lacunar infarcts and CMB were visually graded. Total brain and WML volume were obtained using a validated segmentation tool. A total of 261 subjects were included, of whom 36 had lacunar infarcts, 29 had severe WML, and 83 had CMB. In age-sex-adjusted models, narrower retinal arteriolar caliber, wider venular caliber and smaller arteriolar fractal dimension were associated with presence of multiple CMB. In contrast, no association was found with lacunar infarcts and WML volume. After multivariate adjustments, associations of venular caliber, arteriolar fractal dimensions and arteriolar tortuosity with CMB remained statistically significant. In conclusion, subjects with early structural changes in retinal microvasculature were more likely to have CMBs, supporting hypothesis that CMB may be an early manifestation of cerebral small vessel disease.
authors.affiliation: Memory, Aging & Cognition Center, National University Health System, Singapore, Singapore; Department of Pharmacology, National University of Singapore, Singapore, Singapore.
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Ong
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Carol Y
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Chuen Seng
authors.initials: CS
authors.lastname: Tan
authors.affiliation: Neuroscience Clinic, Raffles Hospital, Singapore, Singapore.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.affiliation: Departments of Radiology & Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Departments of Radiology & Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Henri
authors.initials: H
authors.lastname: Vrooman
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
authors.forename: Ainur R
authors.initials: AR
authors.lastname: Anuar
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
authors.forename: Merwyn
authors.initials: M
authors.lastname: Chew
authors.affiliation: Memory, Aging & Cognition Center, National University Health System, Singapore, Singapore; Department of Pharmacology, National University of Singapore, Singapore, Singapore.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Memory, Aging & Cognition Center, National University Health System, Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore; Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. Electronic address: kamran_ikram@nuhs.edu.sg.
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
mesh_terms: D000368:Aged; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D020520:Brain Infarction / Q000453:epidemiology / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D055806:Microvessels / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*; D012307:Risk Factors; D066127:White Matter / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: Cerebral microbleeds; Cerebral small vessel disease; Chinese; Magnetic resonance imaging; Population based; Retinal microvascular changes