RetVIC International Projects

Atherosclerosis Risk In Communities Study (ARIC)

Investigators: A/ Prof Tien Wong, Prof Ron Klein, Prof Barbara Klein, Prof Paul Mitchell, Dr Cong Sun.
Timeline: 1 June 2003 - 31 Dec 2008
Study Population: The ARIC study is a prospective population-based cohort study of cardiovascular diseases in four US communities involving approximately 12,000 participants who have retinal microvascular signs assessed via retinal photography in 1993-1995.

Abstract:

This study aims to determine the relationship of retinal microvascular disease to incident cardiovascular disease, including stroke, heart disease, hypertension, diabetes mellitus, and other age-related vascular conditions (cognitive decline, renal dysfunction, and cerebral white matter lesions and atrophy) among participants of the Atherosclerosis Risk In Communities (ARIC) study.

The ARIC study comprises a large, bi-racial population of men and women residing in four United States communities, who were 45-64 years of age at the baseline examination in 1987-89, and were examined every three years thereafter for a total of four visits, with continuing surveillance follow-up. Retinal microvascular characteristics (e.g. focal arteriolar narrowing, arterio-venous nicking and retinopathy) were graded from retinal photographs taken at the third visit, according to a standardized protocol. Furthermore, photographs were digitized and individual arteriolar and venular calibres measured using a new computer-assisted technique to obtain a quantitative estimate of generalized retinal arteriolar narrowing. During the course of the four ARIC study visits and follow-up, detailed information was collected on numerous systemic vascular disorders

Specific aims of the current study are to:

• Determine if retinal microvascular disease is predictive of incident cardiovascular disease, independent of current and previous blood pressure and other risk factors,
• Examine the cross-sectional association of retinal microvascular disease to cognitive impairment and decline; renal dysfunction, and; MRI-defined cerebral white matter lesions and atrophy.

School Cohort Study of Risk Factors for Myopia (SCORM):
(Study Completed)

Investigators: A/Prof Tien Wong, A/Prof Seang Mei Saw, Dr Anoop Shankar, Mrs Sophie Rogers.
Timeline: 1 Oct 2004 - 1 Apr 2006
Study Population: The SCORM study included children aged 7 to 9 years recruited from two schools (Tao Nan School and Yio Chu Kang Primary School) in 1999, and another study (Rulang Primary School) in 2001 (28-29). Children with serious medical or eye disorders were excluded from the study. The overall participation rate was 70.2%. There were 1478 Chinese, 349 Malays and 152 children who were Indian and other races, and 851 children aged 7 years, 630 children aged 8 years and 498 children aged 9 years.

Abstract:

Cardiovascular disease (CVD) is the most common cause of death worldwide. Recently our research has shown that in adult persons, retinal vascular caliber changes are predictive of CVD, independent of traditional risk factors. However, it is unknown if retinal vascular caliber changes can be detected in children, and whether these changes are related to CVD factors in early life.

This proposal describes a study aimed at evaluating the relationship of retinal vascular caliber with birth parameters, blood pressure, and early childhood and maternal factors in the School Cohort Study of Risk Factors for Myopia (SCORM), a prospective investigation of school children aged seven to nine years of age that began in 1999. Retinal vascular calibres in 851 children who had retinal photographs were measured to determine associations of retinal calibres with birth parameters, blood pressure, other cardiovascular markers, and refractive errors.

The study will provide new information on whether retinal vascular changes occur early in childhood, and whether these are related to birth weight, gestational age, blood pressure and other factors. The identification of structural vascular changes in high-risk children will lead to a better understanding of how CVD develops later in life, which may have significant implications for prevention and treatment of stroke, heart disease, diabetes and hypertension.

Multi-Ethnic Study of Atherosclerosis (MESA)

Investigators: A/Prof Tien Wong, Prof Ronald Klein, Prof Barbara Klein, Dr Amirul Islam.
Timeline: 1 June 2003 - 31 Dec 2008
Study Population: MESA is a cohort study of ethnically-diverse, population-based sample of 6,500 persons 45-84 years of age, recruited from six United States communities. Approximately half of the population will be men and half women; 40% of the cohort will be white, 30% African-American, 20% Hispanic, and 10% Asian (predominantly of Chinese descent).

Abstract:

This study aims to determine the relation of retinal microvascular disease to the presence of subclinical cardiovascular disease (CVD) and clinical CVD, among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a 10-year NIH-NHLBI-funded longitudinal study comprising a sample of 6,500 men and women 45-84 years of age, from Caucasian, African-American, Hispanic and Asian-American ethnic groups. It builds upon new knowledge from the Atherosclerosis Risk in Communities (ARIC) study that showed standardized photographic measures of retinal microvascular changes (e.g., arteriolar narrowing, arterio-venous nicking and retinopathy) are markers of vascular damage from hypertension, independent of concurrently-measured blood pressure, and predict incident coronary heart disease in women, and incident stroke in men and women, independent of established CVD risk factors.

Specific aims of the current study are to:

• determine the relation of retinal microvascular characteristics to measures of subclinical CVD, including
• Left ventricular function (as defined from cardiac magnetic resonance imaging [MRI]),
• Flow-mediated endothelial vasodilation (as defined from brachial artery ultrasound),
• Peripheral arterial function (as defined from radial artery tonometry),
• Myocardial perfusion (as defined from quantitative myocardial blood flow measurements from cardiac magnetic resonance imaging in the MESA-Myocardial Perfusion ancillary study);
• determine the relation of retinal microvascular characteristics to clinical CVD, including
• Coronary heart disease and congestive cardiac failure
• Stroke;
• determine the relation of retinal microvascular characteristics to CVD risk factors, including
• Development of Type-2 diabetes mellitus and hypertension
• Markers of inflammation, hemostasis, and fibrinolysis;
• determine the relation of retinal microvascular characteristics to structural and functional disorders of the brain (as defined from quantitative cerebral MRI in the MESA-BRAIN Ancillary Study, pending funding);
• describe the prevalence of retinal microvascular characteristics in different racial/ethnic groups; and
• describe the prevalence and risk factors of diabetic retinopathy and age-related maculopathy.

Cardiovascular Health Study (CHS)

Investigators: A/Prof Tien Wong, Profs Ron Klein, David Siscovick, A.Richey Sharrett, Dr Gabriella Tikellis, Dr Cong Sun.
Timeline: 1 Sept 2004 - 31 Aug 2006
Study Population: The CHS is a longitudinal investigation of vascular diseases in adults 65 years of age and older in which 2,500+ participants had retinal photography and retinal microvascular signs assessment

Abstract:

This proposal describe a study to determine the relation of retinal microvascular signs to incident cardiovascular disease (stroke and coronary heart disease [CHD]), prevalent cognitive impairment, prevent depression and apoliprotein E (APOE) gene in older persons participating in the Cardiovascular Health Study (CHS). It builds upon new data that in middle-aged people, retinal microvascular signs, as documented from retinal photographs, are associate with a range of cardiovascular disorders, including stroke, CHD (in women) and cognitive dysfunction, independent of blood pressures and other risk factors.

The CHS is a population-based study of four communities among older people where both retinal microvascular changes and systemic vascular diseases are measured in details according to standard protocols. Participants were first examined at baseline in 1989-90, and followed up yearly. In 1997-98, retinal photography was added to the study examination, when participants had a median age of 77 years (range 69 to 97 years). These photographs have already been graded for presence of retinal microvascular signs (retinopathy, generalized and focal artiolar narrowing, and arterio-venous nicking) according to a standardized protocol. At each examination, detailed information was collected on cardiovascular disease, cognitive function and depression. APOE genotyping is available on all participants. In the current study, we will examine the relationship of retinal vascular signs to incidence of stroke / CHD, prevalence of cognitive impairment and depression, and to the APOE gene.

Results of the proposed series of analyses will provide new information regarding the impact of microvascular disease to the development of common vascular conditions of the heart and brain as people age. This may ultimately lead to improved identification, and preventive and therapeutic strategies for the most common causes of morbidity, disability and mortality effecting elderly people in the United States.

Blue Mountains Eye Study (BMES)

Investigators: Prof Paul Mitchell, A/Prof Tien Wong, Dr Jie Jin Wang.
Timeline: 1 st Jan 2004 - 31 st Dec 2007
Study Population: The BMES is population-based cohort study of 3654 persons who had detailed eye examinations from 1992 to 1994. The BMES population has been seen in the five-year and ten-year examination

Abstract:

Recent U.S. data from two population-based studies have highlighted retinal microvascular signs as being predictive of systemic vascular and other important health outcomes in middle-aged or older individuals. In particular, the presence of retinal microvascular disease may be a useful predictor of cerebrovascular and cardiovascular morbidity and mortality, independent of traditional vascular risk factors. The present application proposes to evaluate the ten-year incidence and progression of retinal microvascular signs and their relationships to incident cerebrovascular disease (CVD) and other systemic health outcomes in the Blue Mountains Eye Study (BMES) cohort.

Two types of retinal signs will be evaluated: qualitative presence of specific focal signs (focal retinal arteriolar narrowing, arteriovenous nicking, arteriolar wall opacity and the presence of retinopathy lesions; and quantitative measures of generalized retinal vessel calibre (narrowing) using the computer-assisted method developed for the U.S. studies.

This project builds upon our current research. Recently, our research has explored many different aspects of the measurement and grading of these signs, has documented their relation to blood pressure and hypertension, and has begun to assess whether these features are predictive of vascular events and other systemic outcomes in an older Australian population. The new project will assess the evolution of retinal microvascular signs over a ten-year period, using data and retinal photographs from the ten-year examinations of the BMES cohort. It will also extend measures from the baseline cohort dataset with a series of new, relevant questions.

Singapore Prospective Cohort Study (SP2):

Investigators: Dr E Shyong Tai, Prof Tien Wong, Dr Chee Eng Tan, Dr Cong Sun.
Timeline: 1 Jan 2005 - 31 Dec 2007
Study Population: The study population includes two cross-sectional populations; the 1992 and 1998 National Health Study (N=3,568 in 1992 and N=4,723 in 1998) aged 18-69 years were selected by disproportionate stratified sampling followed by systematic sampling. Minority races (Asian Indians and Malays) were over-sampled to ensure adequate sample size for statistical analysis.

Abstract:

Singapore Prospective Study Program (SP2) is a prospective cohort study with the aim of identifying risk factors for cardiovascular disease (CVD i.e. macroangiopathy) and Type 2 diabetes. The current proposal is an ancillary study to SP2 with a different focus of investigating the relationship between the metabolic syndrome and microangiopathy (retinal microvascular abnormalities, albuminuria and peripheral neuropathy). We will also study the relationship between the metabolic syndrome and peripheral arterial disease (PAD) - an under-studied macrovascular disease.

We propose a population based study to investigate the relationship between microangiopathy (i.e. retinal microvascular abnormalities, albuminuria and peripheral neuropathy) and the metabolic syndrome. At the same setting, we will also investigate the relationship between the metabolic syndrome and PAD - a less well-studied macrovascular disease. Our proposal builds upon the Singapore Prospective Study Program (SP2,) which plans to recall approximately 5,000 subjects from our 1992 and 1998 National Health Survey (NHS) for follow up re-examination in 2004-2006. We will digitally capture the retinal photographs of all the participants and grade them according to standard protocol into the presence or absence of retinal microvascular abnormality. Early morning urine sample will also be collected for measurement of albumin over creatinine ratio. Lower extremities peripheral neuropathy and macroangiopathy will be quantitatively assessed using the neurosthesiometer and ultrasound Doppler (i.e. Ankle brachial index, ABI). Subjects are deemed to have microangiopathy if they have any retinal microvascular abnormality and/or significant albuminuria and/or peripheral neuropathy. Lower extremities macroangopathy will be defined as subjects with ABI < 0.9. W e will determine the longitudinal relationship between metabolic syndrome at baseline (1992 or 1998) and the presence of microvascular disease at the 2004-06 follow-up examinations. We hypothesize that subjects who have microangiopathy or PAD are also more likely to have pre-existing metabolic syndrome.

With the growing problem of obesity, the metabolic syndrome and related consequences are major health burdens among Asians. It is expected that the study will provide valuable data on the relationship between pre-existing metabolic syndrome, microangiopathy and PAD. In addition, information collected on retinal microvascular abnormalities, albuminuria status, neuropathy and PAD will also be extremely valuable in correlating with future cardiovascular events (myocardial infarction and stroke), renal impairment, lower extremities amputation and mortality.

Singapore Malay Eye Study (SiMES)

Investigators: A/Prof Tien Wong, A/Prof Seang Mei Saw, Prof Donald Tan, Dr Cong Sun
Timeline: 1 Jan 2004 - 31 Dec 2007

Abstract:

Although there are approximately 300 million people of Malay ethnicity living in Asia, the burden and risk factors of blinding eye diseases in this racial group are unknown. This proposal describes a population-based, cross-sectional, epidemiological study aimed at determining the prevalence and risk factors of visual impairment, blindness and major eye conditions in adult Malay Singaporeans, including refractive errors, glaucoma, age-related cataract, age-related maculopathy, and diabetic retinopathy. It builds upon the experience obtained from the Tanjong Pagar Study, which successfully documented the epidemiology of refractive errors, glaucoma, cataract and pterygium in Chinese Singaporeans aged 40-79 years.

In the proposed study, we will examine 3,200 Malay Singaporeans aged 40-79 years, selected via a stratified, clustered, random sampling strategy. The study will include a detailed ocular assessment of visual acuity, refraction, biometry, tonometry, gonioscopy, visual field, and digital lens and retinal photography. L ens photographs will be graded for cataract and retinal photographs for retinal diseases using standardized protocols.

The proposed study will allow us to: (1) determine the prevalence of visual impairment, refractive errors, glaucoma, cataract, age-related maculopathy, diabetic retinopathy, and other major eye diseases in adult Malay people, and (2) to test new hypotheses that link traditional (e.g., blood pressure) and novel (e.g., retinal arteriolar changes) risk factors to the occurrence of these conditions. The study will provide the first population-based data on the epidemiology of the most important age-related eye conditions effecting adult Malay in Singapore. This will have broad public health implications for the purposes of understanding the burden, risk factors and etiology of eye diseases, and for resource planning and allocation for millions of Malay people in Asia.