Tien Yin Wong
Email Address
ophwty@nus.edu.sg
895 results
Publication Search Results
Now showing 1 - 10 of 895
Publication Does diet influence the retinal microvasculature in children?(2009) Lim, L.S.; Saw, S.M.; Wong, T.Y.; Cheung, N.; Yap, M.; CHEMICAL & ENVIRONMENTAL ENGINEERING; EPIDEMIOLOGY & PUBLIC HEALTH; OPHTHALMOLOGYPublication Retinal microvascular abnormalities and incident stroke: The Atherosclerosis Risk in Communities Study(2001) Wong, T.Y.; Klein, R.; Hubbard, L.D.; Couper, D.J.; Cooper, L.S.; Sharrett, A.R.; Shahar, E.; Wofford, M.R.; OPHTHALMOLOGYBackground: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. Methods: A cohort of 10 358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. Findings: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. Interpretation: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.Publication Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?(2013-07-02) Dorajoo, R.; Li, R.; Ikram, M.K.; Liu, J.; Froguel, P.; Lee, J.; Sim, X.; Ong, R.T.-H.; Tay, W.T.; Peng, C.; Young, T.L.; Blakemore, A.I.F.; Cheng, C.Y.; Aung, T.; Mitchell, P.; Wang, J.J.; Klaver, C.C.; Boerwinkle, E.; Klein, R.; Siscovick, D.S.; Jensen, R.A.; Gudnason, V.; Smith, A.V.; Teo, Y.Y.; Wong, T.Y.; Tai, E.-S.; Heng, C.-K.; Friedlander, Y.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE; LIFE SCIENCES INSTITUTE; SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH; OPHTHALMOLOGYIntroduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease. © 2013 Dorajoo et al.Publication Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality(2001) Wong, T.Y.; Klein, R.; Klein, B.E.K.; Hubbard, L.; Tielsch, J.M.; Nieto, F.J.; OPHTHALMOLOGYRetinal microvascular abnormalities, such as generalized and focal arteriolar narrowing, arteriovenous nicking and retinopathy, reflect cumulative vascular damage from hypertension, aging, and other processes. Epidemiological studies indicate that these abnormalities can be observed in 2-15% of the nondiabetic general population and are strongly and consistently associated with elevated blood pressure. Generalized arteriolar narrowing and arteriovenous nicking also appear to be irreversible long-term markers of hypertension, related not only to current but past blood pressure levels as well. There are data supporting an association between retinal microvascular abnormalities and stroke, but there is no convincing evidence of an independent or direct association with atherosclerosis, ischemic heart disease, or cardiovascular mortality. New computer-related imaging methods are currently being developed to detect the presence and severity of retinal arteriolar narrowing and other microvascular characteristics. When reliably quantified, retinal microvascular abnormalities may be useful as risk indicators for cerebrovascular diseases. © 2001 by Elsevier Science Inc. All rights reserved.Publication Retinal Vessel Caliber and Lifelong Neuropsychological Functioning: Retinal Imaging as an Investigative Tool for Cognitive Epidemiology(2013-07) Shalev, I.; Moffitt, T.E.; Wong, T.Y.; Meier, M.H.; Houts, R.M.; Ding, J.; Cheung, C.Y.; Ikram, M.K.; Caspi, A.; Poulton, R.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE; OPHTHALMOLOGYWhy do more intelligent people live healthier and longer lives? One possibility is that intelligence tests assess health of the brain, but psychological science has lacked technology to evaluate this hypothesis. Digital retinal imaging, a new, noninvasive method to visualize microcirculation in the eye, may reflect vascular conditions in the brain. We studied the association between retinal vessel caliber and neuropsychological functioning in the representative Dunedin birth cohort. Wider venular caliber was associated with poorer neuropsychological functioning at midlife, independently of potentially confounding factors. This association was not limited to any specific test domain and extended to informants' reports of cohort members' cognitive difficulties in everyday life. Moreover, wider venular caliber was associated with lower childhood IQ tested 25 years earlier. The findings indicate that retinal venular caliber may be an indicator of neuropsychological health years before the onset of dementing diseases and suggest that digital retinal imaging may be a useful investigative tool for psychological science. © The Author(s) 2013.Publication Retinal arteriolar narrowing and incidence of knee replacement for osteoarthritis: A prospective cohort study(W.B. Saunders, 2015) Hussain S.M.; Wang Y.; Shaw J.E.; Magliano D.J.; Wong T.Y.; Wluka A.E.; Graves S.; Tapp R.J.; Cicuttini F.M.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREPublication ABCC5, a Gene That Influences the Anterior Chamber Depth, Is Associated with Primary Angle Closure Glaucoma(Public Library of Science, 2014) Nongpiur M.E.; Khor C.C.; Jia H.; Cornes B.K.; Chen L.-J.; Qiao C.; Nair K.S.; Cheng C.-Y.; Xu L.; George R.; Tan D.; Abu-Amero K.; Perera S.A.; Ozaki M.; Mizoguchi T.; Kurimoto Y.; Low S.; Tajudin L.-S.A.; Ho C.-L.; Tham C.C.Y.; Soto I.; Chew P.T.K.; Wong H.-T.; Shantha B.; Kuroda M.; Osman E.A.; Tang G.; Fan S.; Meng H.; Wang H.; Feng B.; Yong V.H.K.; Ting S.M.L.; Li Y.; Wang Y.-X.; Li Z.; Lavanya R.; Wu R.-Y.; Zheng Y.-F.; Su D.H.; Loon S.-C.; Allingham R.R.; Hauser M.A.; Soumittra N.; Ramprasad V.L.; Waseem N.; Yaakub A.; Chia K.-S.; Kumaramanickavel G.; Wong T.T.; How A.C.; Chau T.N.B.; Simmons C.P.; Bei J.-X.; Zeng Y.-X.; Bhattacharya S.S.; Zhang M.; Tan D.T.; Teo Y.-Y.; Al-Obeidan S.A.; Hon D.N.; Tai E.-S.; Saw S.-M.; Foster P.J.; Vijaya L.; Jonas J.B.; Wong T.-Y.; John S.W.M.; Pang C.-P.; Vithana E.N.; Wang N.; Aung T.; MEDICINE; SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH; DUKE-NUS MEDICAL SCHOOL; BIOCHEMISTRY; OPHTHALMOLOGYPublication Apratoxin S4 Inspired by a Marine Natural Product, a New Treatment Option for Ocular Angiogenic Diseases(NLM (Medline), 2019) Qiu, B.; Tan, A.; Veluchamy, A.B.; Li, Y.; Murray, H.; Cheng, W.; Liu, C.; Busoy, J.M.; Chen, Q.-Y.; Sistla, S.; Hunziker, W.; Cheung, C.M.G.; Wong, T.Y.; Hong, W.; Luesch, H.; Wang, X.; DUKE-NUS MEDICAL SCHOOL; OPHTHALMOLOGYPurpose: Abnormal blood vessel formation is a defining feature of many blinding eye diseases. Targeting abnormal angiogenesis by inhibiting VEGF has revolutionized the treatment of many ocular angiogenic diseases over the last decade. However, a substantial number of patients are refractory to anti-VEGF treatment or may develop resistance over time. The objective of this study was to determine the efficacy and the mechanism of action of Apratoxin S4 in ocular angiogenesis. Methods: Retinal vascular cell proliferation, migration, and the ability to form tube-like structure were studied in vitro. Ex vivo aortic ring, choroid, and metatarsal assays were used to study Apratoxin S4's impact on vessel outgrowth in a multicellular environment. Apratoxin S4 was also tested in mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), and in a rabbit model of persistent retinal neovascularization (PRNV). Western blot and ELISA were used to determine the expression of key angiogenic regulators after Apratoxin S4 treatment. Results: Apratoxin S4 strongly inhibits retinal vascular cell activation by suppressing multiple angiogenic pathways. VEGF-activated vascular cells and angiogenic vessels are more susceptible to Apratoxin S4 treatment than quiescent vascular cells and vessels. Both intraperitoneal and intravitreal delivery of Apratoxin S4 are able to impede ocular neovascularization in vivo. Apratoxin S4 specifically attenuates pathological ocular angiogenesis and exhibits a combinatorial inhibitory effect with standard-of-care VEGF inhibitor drug (aflibercept). Conclusions: Apratoxin S4 is a potent antiangiogenic drug that inhibits the activation of retinal endothelial cells and pericytes through mediating multiple angiogenic pathways.Publication Prevalence and Risk Factors for Diabetic Retinopathy. The Singapore Malay Eye Study(2008) Wong, T.Y.; Cheung, N.; Wang, J.J.; Tay, W.T.; Aung, T.; Saw, S.M.; Mitchell, P.; Lim, S.C.; Tai, E.S.; OPHTHALMOLOGY; COMMUNITY,OCCUPATIONAL & FAMILY MEDICINEPurpose: To describe the prevalence and risk factors of diabetic retinopathy in Asian Malays. Design: Population-based cross-sectional study. Participants: Persons with diabetes of Malay ethnicity aged 40 to 80 years in Singapore. Methods: Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more, use of diabetic medication, or a physician diagnosis of diabetes. Retinal photographs taken from both eyes were graded for diabetic retinopathy using the modified Airlie House classification system. Main Outcome Measures: Any diabetic retinopathy, retinopathy grades, macular edema, or vision-threatening retinopathy. Results: Of the 3261 persons who participated in this study, 757 (23.1%) had diabetes and gradable retinal photographs. In persons with diabetes, the overall prevalence of any retinopathy was 35.0% (95% confidence interval [CI], 28.2-43.4), the overall prevalence of macular edema was 5.7% (95% CI, 3.2-9.9), and the overall prevalence of vision-threatening retinopathy was 9.0% (95% CI, 5.8-13.8). Compared with men, women had significantly higher proportions with more severe diabetic retinopathy, moderate (12% vs. 4%) and severe (3% vs. 0.2%) nonproliferative retinopathy, proliferative retinopathy (7% vs. 2%), and vision-threatening retinopathy (13% vs. 3%). In multiple logistic regression, independent risk factors for any retinopathy were longer diabetes duration (odds ratio [OR], 1.07; 95% CI, 1.04-1.09, per year increase), higher hemoglobin A1c (OR, 1.21; 95% CI, 1.10-1.33, per % increase), hypertension (OR, 1.85; 95% CI, 1.04-3.30), and higher pulse pressure (OR, 1.34, 95% CI, 1.19-1.51, per 10-mmHg increase); older age (OR, 0.73; 95% CI, 0.57-0.93, per decade increase) and higher total cholesterol levels (OR, 0.75; 95% CI, 0.63-0.89, per 1-mmol/l increase) were protective of any retinopathy. Vision-threatening retinopathy additionally was associated with previous stroke (OR, 3.74; 95% CI, 1.24-11.26), cardiovascular disease (OR, 2.23; 95% CI, 1.08-4.62), and chronic kidney disease (OR, 4.45; 95% CI, 2.18-9.07). Female gender was not an independent risk factor for diabetic retinopathy after adjusting for metabolic and socioeconomic risk factors. Conclusions: One in 10 Malay adults with diabetes in Singapore has vision-threatening diabetic retinopathy. Risk factors for retinopathy in this population are largely similar to white populations elsewhere, suggesting that control of these risk factors may reduce both the prevalence and impact of retinopathy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. © 2008 American Academy of Ophthalmology.Publication Relationship between glycated haemoglobin and microvascular complications: Is there a natural cut-off point for the diagnosis of diabetes?(Springer Verlag, 2009-07-01) CHARUMATHI SABANAYAGAM; Liew, G; TAI E SHYONG; Shankar, A; Lim, SC; Subramaniam, T; Wong Tien Yin; Assoc Prof Charumathi Sabanayagam; DUKE-NUS MEDICAL SCHOOLAims/hypothesis: This study was designed to determine whether the relationship of glycated haemoglobin to diabetic microvascular complications shows any natural thresholds that could be useful in diagnosing diabetes. Methods: We examined a population-based sample of 3,190 Malay adults aged 40-80 years in Singapore. The microvascular outcomes of interest were: (1) any retinopathy, defined from fundus photographs; (2) mild retinopathy, defined as in (1); (3) moderate retinopathy, defined as in (1); (4) chronic kidney disease, defined from estimated glomerular filtration rate; (5) micro- or macroalbuminuria, defined from urinary albumin to creatinine ratio; and (6) peripheral neuropathy, defined from neurothesiometer or monofilament sensory testing. Results: Increasing HbA1c was associated with all microvascular complications. The optimal cut-off points for detecting mild and moderate retinopathy were 6.6% (87.0% sensitivity, 77.1% specificity and area under the receiver operating characteristics [ROC] curve 0.899) and 7.0% (82.9% sensitivity, 82.3% specificity and area under ROC curve 0.904). The prevalences of mild and moderate retinopathy were <1% below the optimal cut-off points. For other complications, the association with HbA1c was linear without evidence of a distinct threshold. Although ROC analysis for these other complications also suggested optimal cut-off points between 6.6% and 7.0%, the sensitivity at these cut-off points was considerably lower than for mild and moderate retinopathy, ranging from 31.8% to 66.5%. Conclusions/interpretation: Higher levels of HbA1c were associated with microvascular complications. Our data support use of an HbA1c cut-off point of between 6.6 and 7.0% in diagnosing diabetes. Cut-off points in this range were best for the identification of individuals with mild and moderate retinopathy. Any retinopathy, chronic kidney disease, albuminuria and peripheral neuropathy are less well detected at these cut-off points. © 2009 Springer-Verlag.