Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemCognitive Performance Concomitant With Vision Acuity Predicts 13-Year Risk for Mortality(FRONTIERS MEDIA SA, 2019-03-22)Objective: To assess the joint impact of cognitive performance and visual acuity on mortality over 13-year follow-up in a representative US sample. Methods: Data from National Health and Nutrition Examination Survey (NHANES) participants (≥18 years old) were linked with the death record data of the National Death Index (NDI) with mortality follow-up through December 31, 2011. Cognitive performance was evaluated by the Digit Symbol Substitution Test (DSST) and cognitive performance impairment was defined as the DSST score equal to or less than the median value in the study population. Visual impairment (VI) was defined as presenting visual acuity worse than 20/40 in the better-seeing eye. Risks of all-cause and specific-cause mortality were estimated with Cox proportional hazards models after adjusting for confounders. Results: A total of 2,550 participants 60 years and older from two waves of (NHANES, 1999-2000, 2001-2002) were included in the current analysis. Over a median follow-up period of 9.92 years, 952 (35.2%) died of all causes, of whom 239 (23.1%), 224 (24.0%), and 489 (52.9%) died from cardiovascular disease (CVD), cancer, and non-CVD/non-cancer mortality, respectively. Cognitive performance impairment and VI increased the odds for mortality. Co-presence of VI among cognitive impaired elderly persons predicted nearly a threefold increased risk of all-cause mortality [hazard ratios (HRs), 2.74; 95% confidence interval (CI), 2.02-3.70; P < 0.001) and almost a fourfold higher risk of non-CVD/non-cancer mortality (HR, 3.72; 95% CI, 2.30-6.00; P < 0.001) compared to having neither impairment. Conclusion: People aged 60 years and over with poorer cognitive performance were at higher risk of long-term mortality, and were especially vulnerable to further mortality when concomitant with VI. It is informative for clinical implication in terms of early preventive interventions.
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ItemHigh Myopia and Its Associated Factors in JPHC-NEXT Eye Study: A Cross-Sectional Observational Study.(MDPI AG, 2019-10-25)The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤-6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample.
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ItemDeep learning in estimating prevalence and systemic risk factors for diabetic retinopathy: a multi-ethnic study(NATURE PORTFOLIO, 2019-04-10)In any community, the key to understanding the burden of a specific condition is to conduct an epidemiological study. The deep learning system (DLS) recently showed promising diagnostic performance for diabetic retinopathy (DR). This study aims to use DLS as the grading tool, instead of human assessors, to determine the prevalence and the systemic cardiovascular risk factors for DR on fundus photographs, in patients with diabetes. This is a multi-ethnic (5 races), multi-site (8 datasets from Singapore, USA, Hong Kong, China and Australia), cross-sectional study involving 18,912 patients (n = 93,293 images). We compared these results and the time taken for DR assessment by DLS versus 17 human assessors - 10 retinal specialists/ophthalmologists and 7 professional graders). The estimation of DR prevalence between DLS and human assessors is comparable for any DR, referable DR and vision-threatening DR (VTDR) (Human assessors: 15.9, 6.5% and 4.1%; DLS: 16.1%, 6.4%, 3.7%). Both assessment methods identified similar risk factors (with comparable AUCs), including younger age, longer diabetes duration, increased HbA1c and systolic blood pressure, for any DR, referable DR and VTDR (p > 0.05). The total time taken for DLS to evaluate DR from 93,293 fundus photographs was ~1 month compared to 2 years for human assessors. In conclusion, the prevalence and systemic risk factors for DR in multi-ethnic population could be determined accurately using a DLS, in significantly less time than human assessors. This study highlights the potential use of AI for future epidemiology or clinical trials for DR grading in the global communities.
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ItemInter-relationship between ageing, body mass index, diabetes, systemic blood pressure and intraocular pressure in Asians: 6-year longitudinal study.(BMJ, 2019-02)BACKGROUND: To investigate the biological effect of ageing on intraocular pressure (IOP) and risk factors in a population-based cohort study of Malay and Indian adults. METHODS: Participants aged 40-80 years were recruited for baseline and 6-year follow-up visits between 2004-2009 and 2010-2015, respectively. Blood pressure (BP) was measured with an automatic BP monitor and IOP were obtained by Goldmann applanation tonometry. Main outcome was change in IOP, defined as the difference between the 6-year IOP and the baseline IOP. Linear regression models were used to investigate the association of changes in IOP with risk factors. RESULTS: Participants without a history of glaucoma or cataract surgery at baseline were included (n = 3188; mean age: 54±9 years) . Their average IOP was reduced (-0.5±3.1 mm Hg), except for those who developed hypertension at follow-up (0.0±3.1 mm Hg). After adjusting for covariates, changes in IOP were negatively associated with age (β=-0.07, 95% CI -0.13 to -0.01) and positively associated with body mass index, diabetes, hypertension (normotensive as reference group; newly developed hypertensive (β=0.67, 95% CI 0.39 to 0.95) and chronic hypertensive (β=0.46, 95% CI 0.22 to 0.70)), baseline systolic BP (SBP) (β=0.20, 95% CI 0.14 to 0.26) and diastolic BP (DBP) (β=0.33, 95% CI 0.22 to 0.44), as well as with 6-year increases in SBP (β=0.27, 95% CI 0.21 to 0.33) and DBP (β=0.52, 95% CI 0.41 to 0.63). CONCLUSIONS: Normal ageing and reduced systemic BP are associated with reduced IOP in Malay and Indian adults. Given that high IOP is a risk factor for glaucoma, our finding highlights the importance of controlling hypertension in older adults, where hypertension and glaucoma incidences are on a rise.
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ItemArtificial intelligence and deep learning in ophthalmology.(BMJ, 2019-02)Artificial intelligence (AI) based on deep learning (DL) has sparked tremendous global interest in recent years. DL has been widely adopted in image recognition, speech recognition and natural language processing, but is only beginning to impact on healthcare. In ophthalmology, DL has been applied to fundus photographs, optical coherence tomography and visual fields, achieving robust classification performance in the detection of diabetic retinopathy and retinopathy of prematurity, the glaucoma-like disc, macular oedema and age-related macular degeneration. DL in ocular imaging may be used in conjunction with telemedicine as a possible solution to screen, diagnose and monitor major eye diseases for patients in primary care and community settings. Nonetheless, there are also potential challenges with DL application in ophthalmology, including clinical and technical challenges, explainability of the algorithm results, medicolegal issues, and physician and patient acceptance of the AI 'black-box' algorithms. DL could potentially revolutionise how ophthalmology is practised in the future. This review provides a summary of the state-of-the-art DL systems described for ophthalmic applications, potential challenges in clinical deployment and the path forward.
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ItemImpact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography.(Ovid Technologies (Wolters Kluwer Health), 2019-03)OBJECTIVE: Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography (OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure (BP) and renal parameters. METHODS: This observational cross-sectional study consisted of 153 normal eyes from 77 nondiabetic hypertensive adults [mean (SD) age, 58 (9) years; 49% women; 23% poorly controlled BP]. Data on 24-h ambulatory BP monitoring, serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. Retinal capillary density measured with the OCT-A (AngioVue) at superficial (SVP) and deep vascular plexuses (DVP). Linear regression was used to investigate the association of risk factors with capillary density. RESULTS: Retinal capillary density (percentage) at DVP was reduced in patients with poorly controlled BP (SBP = 148 ± 8 mmHg; 27.2 ± 13.0) compared with those with well controlled BP (SBP = 125 ± 9 mmHg; 34.7 ± 11.3). In the multivariable analysis, poorly controlled BP [β = -6.49, 95% confidence interval (CI), -12.39 to -0.59], higher SBP (β = -0.23, 95% CI -0.44 to -0.02) and lower eGFR (β = 6.42, 95% CI 1.25-11.60) were associated with sparser retinal capillary density. Systemic factors were not associated with capillary density at SVP (all P > 0.05). CONCLUSION: In adults with treated systemic hypertension, retinal capillary density reduced with higher BP and poorer eGFR. These findings highlight the potential role of OCT-A to study early microvascular changes because of systemic hypertension.
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ItemRetinal vascular changes and right ventricular structure and function: the MESA-Right Ventricle and MESA-Eye studies.(Wiley, 2019)Retinal vessel diameters have been associated with left ventricular morphology and function but their relationship with the right ventricle (RV) has not been studied. We hypothesized that wider retinal venules and narrower retinal arterioles are associated with RV morphology and function. RV end-diastolic mass (RVEDM), end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (RVSV), and ejection fraction (RVEF) were assessed using cardiac magnetic resonance imaging (MRI) scans of 4204 participants without clinical cardiovascular disease at the baseline examination; retinal photography was obtained at the second examination. Mean diameters of retinal arterioles and venules were measured and summarized as central retinal vein and artery equivalents ("veins" and "arteries," respectively). After adjusting for covariates, wider veins were associated with greater RVEDM and RVEDV in women (P = 0.04 and P = 0.02, respectively), whereas there was an inverse association with RVEDV in men (P = 0.02). In both sexes, narrower arteries were associated with lower RVEDM (P < 0.001 in women and P = 0.002 in men) and smaller RVEDV (P < 0.001 in women and P = 0.04 in men) in adjusted models. Narrower arteries were also associated with lower RVEF in men but this was of borderline significance after adjusting for the LVEF (P = 0.08). Wider retinal venular diameter was associated with sex-specific changes in RVEDM and RVEDV in adults without clinical cardiovascular disease. Narrower retinal arteriolar diameter was associated with significantly lower RVEDM and smaller RVEDV in both sexes.
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ItemU-Shaped Relationship between Serum Leptin Concentration and Cognitive Performance in Older Asian Adults(MDPI, 2019-03-19)The role of leptin (a hormone related to fat mass) in cognition remains equivocal. Our objective was to investigate the relationship between circulating leptin concentration and cognition in older adults, accounting for potential confounders. We categorized 1061 community-dwelling older participants ≥60 years (mean ± SD, 70.6 ± 6.4 years; 41.6% female) from the Singapore Kidney Eye Study according to quintiles of leptin concentration (≤2.64; 2.64⁻5.1; 5.2⁻8.6; 8.7⁻17.96; ≥18 ng/mL). Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Age, gender, body mass index, mean arterial pressure, smoking, alcohol, education, memory complaint, anxiodepressive disorders, circulating concentrations of 25-hydroxyvitamin D, glycosylated hemoglobin, low-density lipoprotein cholesterol, and estimated glomerular filtration rate were used as potential confounders. Participants within the lowest (Q1) and highest (Q5) leptin quintiles exhibited lower (i.e., worse) mean total AMT scores compared to those within the intermediate quintiles (Q2, Q3, and Q4). Compared to Q3 as the reference, Q1 and Q5 were associated with decreased total AMT score (respectively, β = -0.53 p = 0.018; β = -0.60 p = 0.036). Compared to Q3, Q5 was also associated with decreased subscores on anterograde (β = -0.19 p = 0.020) and retrograde episodic memories (β = -0.18 p = 0.039). We found a non-linear U-shaped relationship between circulating leptin and cognition, with both lower and higher concentrations of leptin being associated with more severe cognitive impairment in community-dwelling older Asians.
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ItemSimplified end stage renal failure risk prediction model for the low-risk general population with chronic kidney disease.(Public Library of Science (PLoS), 2019)BACKGROUND: Chronic kidney disease (CKD) contributes significant morbidity and mortality among Asians; hence interventions should focus on those most at-risk of progression. However, current end stage renal failure (ESRF) risk stratification tools are complex and not validated in multi-ethnic Asians. We hence aimed to develop an ESRF risk prediction model by taking into account ethnic differences within a fairly homogenous socioeconomic setting and using parameters readily accessible to primary care clinicians managing the vast majority of patients with CKD. METHODS: We performed a prospective cohort study of 1970 adults with CKD estimated glomerular filtration rate <60 ml/min/1.73m2 or albuminuria >30 mg/g from the population-based Singapore Epidemiology of Eye Diseases study (n = 10,033). Outcome was incident ESRF, ascertained by linkage to the Singapore Renal Registry until 2015. RESULTS: Mean follow up was 8.5 ± 1.8 years and ESRF occurred in 32 individuals (1.6%). ESRF incidence rates were 2.8, 0.8 and 2.6 per 1000 patient years in Malays, Indians and Chinese respectively. The best ESRF prediction model included age, gender, eGFR and albuminuria (calibration χ2 = 0.45, P = 0.93; C-statistic 0.933, 95% confidence interval (CI) 0.889-0.978, p = 0.01; AIC 356). Addition of ethnicity improved discrimination marginally (C statistic 0.942, 95% CI 0.903-0.981, p = 0.21). Addition of clinical variables such as diabetes and hyperlipidemia did not improve model performance significantly. CONCLUSION: We affirmed the utility of commonly available clinical information (age, gender, eGFR and UACR) in prognosticating ESRF for multi-ethnic Asians with CKD.
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ItemImpact of systemic vascular risk factors on the choriocapillaris using optical coherence tomography angiography in patients with systemic hypertension.(Springer Science and Business Media LLC, 2019-04-09)We investigated the characteristics of the choriocapillaris flow voids using optical coherence tomography angiography (OCTA) in 85 patients (164 eyes) with hypertension (mean ± SD age, 56 ± 11 years; 45% women; 20% poorly controlled BP; 16% diabetes) who are without ocular diseases and determined possible correlations with systemic vascular risk factors. Data on 24-hour ambulatory blood pressure (BP), serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. OCTA imaging (6 × 6 mm scans; AngioVue) with quantitative microvascular analysis of the choriocapillaris was performed. Linear regression was used to investigate the association of systemic risk factors with area (percentage), size (pixels) and number of choriocapillaris flow voids. Diabetes (β = 0.33; 95% CI, 0.02 to 0.63) and daytime systolic BP (β = -0.13; 95% CI, -0.24 to -0.02) were associated with areas of flow voids. Age (β = 0.21; 95% CI, 0.06 to 0.36) and daytime diastolic BP (β = -0.18; 95% CI, -0.34 to -0.02) were associated with size of flow voids. Age (β = -21.21; 95% CI, -31.79 to -10.63) and nighttime diastolic BP (β = 13.89; 95% CI, 0.61 to 27.17) were associated with number of flow voids. Kidney parameters were not associated with any features of flow voids. In patients with hypertension, a higher BP appeared to increase blood flow in the choriocapillaris which needs to be considered when using the OCTA to study eye diseases in hypertensives.