Cardiovascular disease and thinning of retinal nerve fiber layer in a multi-ethnic Asian population: the Singapore epidemiology of eye diseases study.

Introduction: Our study aimed to examine the relationship between cardiovascular diseases (CVD) with peripapillary retinal fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thickness profiles in a large multi-ethnic Asian population study. Methods: 6,024 Asian subjects were analyzed in this study. All participants underwent standardized examinations, including spectral domain OCT imaging (Cirrus HD-OCT; Carl Zeiss Meditec). In total, 9,188 eyes were included for peripapillary RNFL analysis (2,417 Malays; 3,240 Indians; 3,531 Chinese), and 9,270 eyes (2,449 Malays, 3,271 Indians, 3,550 Chinese) for GCIPL analysis. History of CVD was defined as a self-reported clinical history of stroke, myocardial infarction, or angina. Multivariable linear regression models with generalized estimating equations were performed, adjusting for age, gender, ethnicity, diabetes, hypertension, hyperlipidaemia, chronic kidney disease, body mass index, current smoking status, and intraocular pressure. Results: We observed a significant association between CVD history and thinner average RNFL (ß = -1.63; 95% CI, -2.70 to -0.56; p = 0.003). This association was consistent for superior (ß = -1.79, 95% CI, -3.48 to -0.10; p = 0.038) and inferior RNFL quadrant (ß = -2.14, 95% CI, -3.96 to -0.32; p = 0.021). Of the CVD types, myocardial infarction particularly showed significant association with average (ß = -1.75, 95% CI, -3.08 to -0.42; p = 0.010), superior (ß = -2.22, 95% CI, -4.36 to -0.09; p = 0.041) and inferior (ß = -2.42, 95% CI, -4.64 to -0.20; p = 0.033) RNFL thinning. Among ethnic groups, the association between CVD and average RNFL was particularly prominent in Indian eyes (ß = -1.92, 95% CI, -3.52 to -0.33; p = 0.018). CVD was not significantly associated with average GCIPL thickness, albeit a consistent negative direction of association was observed (ß = -0.22, 95% CI, -1.15 to 0.71; p = 0.641). Discussion: In this large multi-ethnic Asian population study, we observed significant association between CVD history and RNFL thinning. This finding further validates the impact of impaired systemic circulation on RNFL thickness.

Six-Year Incidence of Visual Impairment in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

Purpose: To examine the 6-year incidence of visual impairment (VI) and identify risk factors associated with VI in a multiethnic Asian population. Design: Prospective, population-based, cohort study. Participants: Adults aged ≥ 40 years were recruited from the Singapore Epidemiology of Eye Diseases cohort study at baseline. Eligible subjects were re-examined after 6 years. Subjects included in the final analysis had a mean age of 56.1 ± 8.9 years, and 2801 (50.5%) were female. Methods: All participants underwent standardized examination and interviewer-administered questionnaire at baseline. Incidences were standardized to the Singapore Population Census 2010. A Poisson binomial regression model was used to evaluate the associations between baseline factors and incident presenting VI. Main Outcome Measures: Incident presenting VI was assessed at the 6-year follow-up visit. Visual impairment (presenting visual acuity < 20/40), low vision (presenting visual acuity < 20/40 but ≥ 20/200), and blindness (presenting visual acuity < 20/200) were defined based on United States definition. Results: A total of 5551 subjects (2188 Chinese, 1837 Indians, and 1526 Malays) were evaluated, of whom 514 developed incident presenting VI over 6 years. Malays had a higher incidence of low vision and blindness (13.0%; 0.6%) than Indians (7.0%; 0.1%) and Chinese (7.7%; 0.2%). Among Malay individuals with VI at baseline, 52.8% remained visually impaired after 6 years, which was considerably higher than Chinese (32.4%) and Indians (37.2%). Older age (per decade; relative risk [RR] = 1.59), a history of cardiovascular disease (RR = 1.38), current smoking (RR = 1.31), smaller housing type (1- to 2-room public flat; RR = 2.01), and no formal education (RR = 1.63) at baseline were associated with a higher risk of incident VI (all P ≤ 0.027). Older age (> 60 years) contributed the highest population attributable risk to incident VI (27.1%), followed by lower monthly income (Singapore dollar < $2000; 26.4%) and smaller housing type (24.7%). Overall, undercorrected refractive error (49.1%) and cataract (82.6%) were leading causes for low vision and blindness, respectively. This was consistently observed across the 3 ethnicities. Conclusions: In this multiethnic Asian population, Malays had a higher VI incidence compared to Indians and Chinese. Leading causes of VI are mostly treatable, suggesting that more efforts are needed to further mitigate preventable visual loss. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Retinal Nerve Fiber Layer Thickness and Rim Area Profiles in Asians: Pooled Analysis from the Asian Eye Epidemiology Consortium.

PURPOSE: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies. DESIGN: Cross-sectional pooled analysis. PARTICIPANTS: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium. METHODS: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model. MAIN OUTCOME MEASURES: Average RNFL thickness (in micrometers) and rim area (in square millimeters). RESULTS: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (ß values range, 7.31-12.76 µm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 µm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 µm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 µm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, ß = -2.70), diabetes (ß = -0.72), higher IOP (per 1 mmHg, ß = -0.07), more myopic SE (per diopter, ß = -1.13), cardiovascular disease (ß = -0.94), and hypertension (ß = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (ß = -0.019), higher IOP (ß = -0.010), and more myopic SE (ß = -0.025) were associated with smaller rim area (all P < 0.001). CONCLUSIONS: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.

Normative profiles of neuroretinal rim area in a multiethnic Asian population: the Singapore Epidemiology of Eye Diseases study.

AIMS: To evaluate the normative profiles for neuroretinal rim area (RA) in a multiethnic Asian population. METHODS: Subjects were recruited from the Singapore Epidemiology of Eye Diseases (2009-2015) study and underwent standardised examinations. RA measurements were performed using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec). Multivariable linear regression with generalised estimating equation model was used to evaluate the associations between demographic, systemic and ocular factors with RA. RESULTS: A total of 9394 eyes from 5116 subjects (1724 Chinese, 1463 Malay, 1929 Indian) were included in the final analysis. The mean (±SD) of RA was 1.28 (±0.23) mm2 for Chinese, 1.33 (±0.26) mm2 for Malays, and 1.23 (±0.23) mm2 for Indians. The 5th percentile value for RA was 0.94 mm2 for Chinese, 0.96 mm2 for Malay, and 0.89 mm2 for Indian. In multivariable analysis, following adjustment for age, gender, body mass index, diabetes mellitus, hyperlipidaemia, history of cataract surgery, axial length, intraocular pressure (IOP) and disc area, Indian eyes have smaller RA when compared with Malays (ß=-0.074; 95% CI -0.090 to -0.058; p<0.001) and Chinese (ß=-0.035; 95% CI -0.051 to -0.019; p<0.001), respectively. Additionally, older age (per decade, ß=-0.022), male gender (ß=-0.031), longer axial length (per mm, ß=-0.025), spherical equivalent (per negative dioptre, ß=-0.005), higher IOP (per mm Hg, ß=-0.009) were associated with smaller RA (all p≤0.004). CONCLUSION: In this multiethnic population-based study, we observed significantly smaller RA in Indian eyes, compared with Chinese and Malays. This indicates the need of a more refined ethnic-specific RA normative databases among Asians.

Ethnic differences in the incidence of pterygium in a multi-ethnic Asian population: the Singapore Epidemiology of Eye Diseases Study.

We evaluated the 6-year incidence and risk factors of pterygium in a multi-ethnic Asian population. Participants who attended the baseline visit of the Singapore Epidemiology of Eye Diseases Study (year 2004-2011) and returned six years later, were included in this study. Pterygium was diagnosed based on anterior segment photographs. Incident pterygium was defined as presence of pterygium at 6-year follow-up in either eye, among individuals without pterygium at baseline. Multivariable logistic regression models were used to determine factors associated with incident pterygium, adjusting for baseline age, gender, ethnicity, body mass index, occupation type, educational level, income status, smoking, alcohol consumption, presence of hypertension, diabetes and hyperlipidemia. The overall age-adjusted 6-year incidence of pterygium was 1.2% (95% confidence interval [CI] 1.0-1.6%); with Chinese (1.9%; 95% CI 1.4%-2.5%) having the highest incidence rate followed by Malays (1.4%; 95% CI 0.9%-2.1%) and Indians (0.3%; 95% CI 0.3-0.7%). In multivariable analysis, Chinese (compared with Indians; odds ratio [OR] = 4.21; 95% CI 2.12-9.35) and Malays (OR 3.22; 95% CI 1.52-7.45), male (OR 2.13; 95% CI 1.26-3.63), outdoor occupation (OR 2.33; 95% CI 1.16-4.38), and smoking (OR 0.41; 95% CI 0.16-0.87) were significantly associated with incident pterygium. Findings from this multi-ethnic Asian population provide useful information in identifying at-risk individuals for pterygium.

Albuminuria and Primary Open-Angle Glaucoma: the Singapore Chinese Eye Study (SCES).

AIMS: To determine the association between albuminuria and primary open-angle glaucoma (POAG). METHODS: Participants of the Singapore Chinese Eye study were recruited and underwent standardised ocular and systemic examinations. Albuminuria was determined using urinary albumin-to-creatinine ratio (UACR, mg/g) based on random spot urinary albumin and creatinine measurements. POAG was defined using the International Society of Geographic and Epidemiological Ophthalmology classification. Multivariable logistic regression with generalised estimating equation model was used to evaluate the association between albuminuria and POAG, while accounting for correlation between eyes. RESULTS: A total of 3009 Chinese adults (5963 eyes), aged 40-80 years, were included in this study, of which, 52 subjects (75 eyes) had POAG. Higher UACR (per 50 mg/g increase) was independently associated with POAG (OR=1.04, 95% CI 1.01 to 1.07, p=0.003) following adjustment for age, gender, intraocular pressure, diabetes mellitus, hyperlipidaemia, hypertension, anti-hypertensive medication, history of cardiovascular disease, current smoking status, alcohol intake, body mass index and estimated glomerular filtration rate. Further stratification revealed that individuals with macroalbuminuria were 8.00 times likely to have POAG (95% CI 2.97 to 21.54, p<0.001), compared with those with normoalbuminuria. Microalbuminuria was not significantly associated with POAG (OR=0.49, 95% CI 0.19 to 1.29, p=0.150). The association between macroalbuminuria and POAG remained significant among individuals who were diabetic (OR=9.89, 95% CI 2.49 to 39.30, p=0.001) and hypertensive (OR=8.39, 95% CI 3.07 to 22.94, p<0.001). CONCLUSION: In this population-based study of Chinese adults, albuminuria was independently associated with POAG. Our findings provide further understanding on the pathogenesis of POAG and may potentially help to better identify individuals at risk of POAG.

Big Data in Ophthalmology.

Big data is the fuel of mankind's fourth industrial revolution. Coupled with new technology such as artificial intelligence and deep learning, the potential of big data is poised to be harnessed to its maximal in years to come. In ophthalmology, given the data-intensive nature of this specialty, big data will similarly play an important role. Electronic medical records, administrative and health insurance databases, mega national biobanks, crowd source data from mobile applications and social media, and international epidemiology consortia are emerging forms of "big data" in ophthalmology. In this review, we discuss the characteristics of big data, its potential applications in ophthalmology, and the challenges in leveraging and using these data. Importantly, in the next phase of work, it will be pertinent to further translate "big data" findings into real-world applications, to improve quality of eye care, and cost-effectiveness and efficiency of health services in ophthalmology.

Association of Cataract Surgery With Risk of Diabetic Retinopathy Among Asian Participants in the Singapore Epidemiology of Eye Diseases Study.

Importance: Cataracts and diabetic retinopathy (DR) are the leading causes of acquired blindness worldwide. Although extraction is the standard treatment option for cataracts, it is also reported to increase the risk of developing DR among individuals with diabetes. Nevertheless, the association between cataract surgery and risk of DR is still not well understood, and there have been no prior population-based reports in this area. Objective: To assess the risk of developing DR after cataract surgery among individuals with type 2 diabetes. Design, Setting, and Participants: A population-based prospective cohort study was conducted among participants recruited from the Singapore Epidemiology of Eye Diseases Study. The baseline visit was conducted between June 1, 2004, and March 31, 2009, and the 6-year follow-up visit was conducted between June 1, 2011, and July 31, 2016. Statistical analysis was performed from October 1 to 31, 2019. Exposures: Cataract surgery performed before a follow-up visit, determined based on slitlamp evaluation of lens status at baseline and follow-up visits. Main Outcomes and Measures: Eyes with incidence of DR were defined as those with the presence of any DR (level ≥15 based on the modified Airlie House classification system, graded from retinal photographs) at 6-year follow-up with no DR at baseline. The association between cataract surgery and incidence of DR was evaluated using a multivariable Poisson regression model with a generalized estimating equation to account for correlation between both eyes. Results: A total of 1734 eyes from 972 participants with diabetes (392 Malay individuals and 580 Indian individuals; 495 men; mean [SD] age, 58.7 [9.1] years) were included in the analysis. A total of 163 study eyes had already undergone cataract surgery at baseline, and a total of 187 eyes (originally phakic at baseline) underwent cataract surgery any time during the follow-up period. Of these 350 eyes, 77 (22.0%) developed DR. Among the 1384 eyes that never underwent cataract surgery, 195 (14.1%) developed DR. After adjustments for age, sex, race/ethnicity, baseline hemoglobin A1c level, duration of diabetes, random blood glucose level, antidiabetic medication use, hypertension, body mass index, and smoking status, multivariable regression analysis showed that any prior cataract surgery was associated with incidence of DR (relative risk, 1.70; 95% CI, 1.26-2.30; P = .001). Subgroup analyses by race/ethnicity showed similar associations in both Malay individuals (relative risk, 1.73; 95% CI, 1.13-2.69; P = .02) and Indian individuals (relative risk, 1.93; 95% CI, 1.33-2.80; P < .001). Conclusions and Relevance: The findings of this population-based cohort study suggest that prior cataract surgery was associated with a higher risk of developing DR among individuals with diabetes. Further validation is warranted to confirm this association.

Association Between Visual Impairment and Decline in Cognitive Function in a Multiethnic Asian Population.

Importance: With the rapidly aging population, the burden of visual impairment (VI) and cognitive decline is expected to increase. Previous cross-sectional studies suggest an association between these 2 health outcomes. However, few longitudinal reports have examined this association, and to our knowledge, no studies have been performed in Asian populations. Further investigation on this association may help to better identify individuals at risk of cognitive decline. Objective: To examine the longitudinal association between VI and decline in cognitive function in a multiethnic Asian population. Design, Setting, and Participants: In this longitudinal, population-based, prospective cohort study, Chinese, Indian, and Malay adults 60 years or older at baseline were recruited from the Singapore Epidemiology of Eye Diseases (SEED) study. At baseline, participants from the SEED study were recruited under 3 studies: the Singapore Malay Eye Study (SiMES; 2004-2006), the Singapore Indian Eye Study (SINDI; 2007-2009), and the Singapore Chinese Eye Study (SCES; 2009-2011). Eligible participants were reexamined after 6 years (2011-2013 for SiMES, 2013-2015 for SINDI, and 2015-2017 for SCES). Data analysis was performed from November 1 to 24, 2019. Exposures: Visual impariment was defined as presenting visual acuity worse than 20/40 based on the better-seeing eye. Main Outcomes and Measures: Cognitive function was assessed using a locally validated Abbreviated Mental Test (AMT). The association between baseline VI and change in AMT score was determined using the multivariable linear regression model adjusting for baseline age; sex; race/ethnicity; presence of diabetes, hyperlipidemia, hypertension, and chronic kidney disease; history of cardiovascular disease; smoking status; alcohol intake; body mass index; educational status; and AMT score. Results: A total of 2478 individuals (1256 [50.7%] male; 1073 Chinese, 768 Indian, and 637 Malay adults) with mean (SD) age of 67.6 (5.6) years were evaluated, of whom 489 (19.7%) had reduction in AMT scores over 6 years. Baseline VI was associated with a decrease in AMT score over 6 years (ß = -0.27; 95% CI, -0.37 to -0.17; P < .001). When change in vision over 6 years was evaluated, unchanged or deteriorated VI was associated with a decrease in AMT score over 6 years (ß = -0.29; 95% CI, -0.40 to -0.18; P < .001). Among individuals with baseline VI and a substantial decrease in AMT score of 3 units or more over 6 years, the leading causes of VI were undercorrected refractive error (14 [45.2%]) and cataract (11 [35.5%]). Conclusions and Relevance: In this study, poor vision was independently associated with a decline in cognitive function. Causes of visual loss in these cases were mostly preventable, further suggesting that preserving good vision may be an important interventional strategy for mitigating cognitive decline.

Normative patterns and factors associated with presbyopia progression in a multiethnic Asian population: the Singapore Epidemiology of Eye Diseases Study.

BACKGROUND/AIM: To investigate normative patterns and factors associated with presbyopia progression in a multiethnic Asian population. METHODS: Malay, Indian and Chinese participants aged 40-80 years who had baseline and 6-year follow-up examinations with subjective refraction data were recruited from the Singapore Epidemiology of Eye Diseases Study. Presbyopia progression was defined as an increase in near addition power of ≥+0.50 dioptre (D) from baseline to follow-up visit. Modified Poisson regression analyses were used to determine baseline factors associated with presbyopia progression. RESULTS: From the eligible 3974 eyes, 2608 eyes were included for final analysis after excluding eyes with a history of cataract surgery (929 eyes) and best-corrected distance visual acuity worse than 20/40 (342 eyes). Overall the mean near addition power change over 6 years was +0.25 D; Malays showed greater change (+0.37 D) compared with Indians (+0.23 D) and Chinese (+0.16 D). After adjusting for baseline age, gender, body mass index, hypertension, cataract, refractive error and daily hours of reading and writing, Malays were more likely to have presbyopia progression compared with Chinese (RR (relative risk)=1.67; 95% CI 1.43 to 1.95; p<0.001) and Indians (RR=1.45; 95% CI 1.25 to 1.68; p<0.001). Individuals aged 60-69 years (RR=0.77; p=0.006) and ≥70 years (RR=0.51; p<0.001) were less likely to progress in presbyopia compared with those aged 40-49. CONCLUSION: In this Asian population, the near addition power change over 6 years was lower than the current near addition prescription guidelines (+0.25 D vs +0.60 D). Our findings may help update near addition prescription guidelines that can be more tailored to Asians.

Systemic medications and cortical cataract: the Singapore Epidemiology of Eye Diseases Study.

BACKGROUND/AIMS: To evaluate the association between systemic medications and cortical cataract prevalence in an Asian population. METHODS: The Singapore Epidemiology of Eye Diseases Study recruited 10 033 Chinese, Malay and Indian residents aged 40+ years living in Singapore. Information on medication use was collected at interview using questionnaires. The presence and severity of cortical cataract were assessed from lens photographs using the modified Wisconsin Cataract Grading System. Associations between medications and the presence of cortical cataract were assessed using logistic regression. Associations between medications and greater severity of cortical cataract (none, minimal, early and late) were assessed using ordinal logistic regression. RESULTS: A total of 8965 participants were included, the mean age was 57.6 (SD=9.8) years, and 4555 (50.8%) were women. After adjusting for age, gender, ethnicity, body mass index, smoking status, socioeconomic status, hypertension, hyperlipidaemia, diabetes, duration of diabetes and cardiovascular disease, ACE inhibitors (OR=1.27; 95% CI 1.05 to 1.55), fibrates (OR=1.57; 95% CI 1.05 to 2.35), alpha-glucosidase inhibitors (AGIs) (OR=1.85; 95% CI 1.13 to 3.02) and insulin (OR=1.80; 95% CI 1.11 to 2.93) were significantly associated with the presence of cortical cataract. Further adjusting for concurrent medication use did not alter these associations. Consistently, the four medications were also associated with a greater severity level of cortical cataract. CONCLUSION: ACE inhibitors, fibrates and AGIs were associated with increased prevalence of cortical cataract in this Asian population, independent of the presence of hypertension, hyperlipidaemia and diabetes, respectively. Whether they contribute to the risk of cortical cataract needs confirmation in longitudinal studies.