Jacqueline Chua

Ethnic Differences of Intraocular Pressure and Central Corneal Thickness: The Singapore Epidemiology of Eye Diseases Study

PURPOSE To determine the ethnic differences in the distribution of intraocular pressure (IOP) and central corneal thickness (CCT) in a multi-ethnic Asian population by self-reported ethnicity and genetic ancestry. DESIGN Population-based, cross-sectional study. PARTICIPANTS A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years. METHODS Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The IOP readings were obtained by Goldmann applanation tonometry (Haag-Streit, Konig, Switzerland) before pupil dilation. The CCT was measured with ultrasound pachymetry. Genetic ancestry was derived using principal component (PC) analysis. Regression models were used to investigate the association of IOP and CCT with potential risk factors and genetic ancestry. MAIN OUTCOME MEASURES Intraocular pressure and CCT. RESULTS After excluding participants with a history of glaucoma surgery or medication, refractive surgery, corneal edema, or corneal dystrophy, IOP and CCT readings were available for 3251 Chinese, 3232 Malays, and 3317 Indians. The mean IOP readings in the Chinese, Malay, and Indian participants were 14.3±3.1, 15.3±3.7, and 15.8±2.9 mmHg, respectively (P < 0.001). The prevalence of participants with IOP ≥21 mmHg was 2.6% in Chinese, 6.2% in Malays, and 4% in Indians (P < 0.001). In the multivariate regression analysis, the Malay and Indian participants on average had 0.81 and 1.43 mmHg higher IOP levels, respectively, than Chinese (P < 0.001). The mean CCT reading was 552.3±33.4 μm in Chinese, 540.9±33.6 μm in Malays, and 540.4±33.6 μm in Indians (P < 0.001). The percentage of participants with CCT <555 μm was 52.8% in Chinese, 68.5% in Malays, and 66.2% in Indians (P < 0.001). The IOP and CCT levels are significantly correlated with genetic ancestry in our South East Asian population. CONCLUSIONS Chinese have the thickest CCT but lowest IOP among the 3 major ethnic groups. In addition, there is a higher proportion of Malays with IOP ≥21 mmHg and CCT <555 μm compared with the Chinese or Indians. This disparity across ethnic groups should be taken into account by future studies investigating IOP and CCT as risk factors or diagnostic tests for glaucoma in Asian populations.

Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians The Singapore Epidemiology of Eye Diseases Study

PURPOSE To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population. DESIGN Population-based, cross-sectional study. PARTICIPANTS A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study. METHODS Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry. MAIN OUTCOME MEASURES Age-related cataract. RESULTS A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (P<0.001). The severity of nuclear, cortical, and PSC cataract was significantly correlated with genetic ancestry in our South East Asian population. Less education and lower income were associated with cataract for Chinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged ≥60 years and Malays. CONCLUSIONS We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People of Malay ancestry have a greater severity for all cataract subtypes than people of Chinese ancestry. Education and income were associated with cataract for certain Asian subgroups.

Predicting chemotherapeutic drug combinations through gene network profiling

Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting the most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells to delineate a drug resistance gene network using a synthetic lethality workflow. Using the results of a previous unbiased screen, we assessed the genetic overlap of doxorubicin with six other drugs harboring varied mechanisms of action. Using this fission yeast model, drug-specific ontological sub-classifications were identified through the computation of relative hypersensitivities. We found that human gastric adenocarcinoma cells can be sensitized to doxorubicin by concomitant treatment with cisplatin, an intra-DNA strand crosslinking agent, and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor. Our findings point to the utility of fission yeast as a model and the differential targeting of a conserved gene interaction network when screening for successful chemotherapeutic drug combinations for human cells.

Prevalence, Risk Factors, and Visual Features of Undiagnosed Glaucoma: The Singapore Epidemiology of Eye Diseases Study

IMPORTANCE Glaucoma can remain asymptomatic until a severe stage, resulting in a high prevalence of undiagnosed glaucoma worldwide. Asia accounts for 60% of the worlds total glaucoma cases. To our knowledge, no epidemiological studies have assessed ethnic differences in undiagnosed glaucoma among various Asian subgroups. OBJECTIVE To determine the prevalence of, risk factors for, and visual features of undiagnosed primary glaucoma in a multiethnic Asian population. DESIGN, SETTING, AND PARTICIPANTS The Singapore Epidemiology of Eye Diseases Study is a population-based trial in which 3353 Chinese (2009-2011), 3280 Malays (2004-2006), and 3400 Indians (2007-2009) aged 40 to 80 years were invited for an eye examination, including visual field assessment, to establish glaucoma diagnosis. Participants with undiagnosed glaucoma (ie, answering no to whether they previously had been told by a physician that they had glaucoma, not using glaucoma medication, or not having undergone glaucoma surgery) were identified. MAIN OUTCOMES AND MEASURES Prevalence of, risk factors for, and visual features of undiagnosed glaucoma. RESULTS Of 272 participants with primary glaucoma, 196 (72.1%) were previously undiagnosed. The overall prevalence of undiagnosed primary glaucoma was highest among Malays (2.65%; 95% CI, 2.10%-3.31%), followed by Chinese (1.51%; 95% CI, 1.13%-2.01%) and Indians (0.97%; 95% CI, 0.64%-1.43%). In multivariable analysis, variables associated with higher risk of undiagnosed glaucoma were younger age (odds ratio [OR], 1.04; 95% CI, 1.00-1.09; P = .04), Malay ethnicity (OR, 3.65; 95% CI, 1.31-10.13; P = .01), presence of primary open-angle glaucoma (OR, 3.82; 95% CI, 1.60-9.14; P = .003), absence of yearly eyeglass checks (OR, 9.29; 95% CI, 3.43-25.21; P < .001), and lack of cataract surgery (OR, 4.19; 95% CI, 1.68-10.48; P < .001). No patients were blind in both eyes. A mean (SD) of 4.1% (2.8%) (n = 8) of the newly diagnosed patients were blind in 1 eye, and a mean (SD) of 56.0% (7.2%) (n = 102) had noteworthy visual field damage (mean deviation worse than -6 dB) in at least 1 eye. CONCLUSIONS AND RELEVANCE The prevalence of undiagnosed primary glaucoma varied among ethnic populations in whom a mean (SD) of 49.0% (14.0%) (n = 24) of affected individuals 50 to 59 years old already had clinically significant visual field loss. Such data may assist policymakers in implementing cost-effective public health interventions to reduce the effect of blindness associated with undiagnosed glaucoma.

Anterior segment optical coherence tomography

ABSTRACT Optical coherence tomography (OCT) provides non‐contact, rapid in vivo imaging of ocular structures, and has become a key part of evaluating the anterior segment of the eye. Over the years, improvements to technology have increased the speed of capture and resolution of images, leading to the increasing impact of anterior segment OCT imaging on clinical practice. In this review, we summarize the historical development of anterior segment OCT, and provide an update on the research and clinical applications of imaging the ocular surface, cornea, anterior chamber structures, aqueous outflow system, and most recently anterior segment vessels. We also describe advancements in anterior segment OCT technology that have improved understanding with greater detail, such as tear film in dry eye disease evaluation, intra‐operative real‐time imaging for anterior segment surgery, and aqueous outflow with angle assessment for glaucoma. Improvements to image processing and software have also improved the ease and utility of interpreting anterior segment OCT images in everyday clinical practice. Future developments include refinement of assessing vascular networks for the anterior segment, in vivo ultra‐high resolution anterior segment optical coherence tomography with histology‐like detail, en‐face image with 3‐dimensional reconstruction as well as functional extensions of the technique. HighlightsOptical coherence tomography (OCT) technology has increased clinical applications in cornea and anterior segment imaging.Ultra‐high resolution anterior segment OCT may provide in vivo ‘histology’ images of the cornea with greater detail.OCT enables better understanding of glaucoma mechanisms via imaging of the aqueous outflow system and angles.OCT of the tear film and corneal layers has improved understanding and treatment of dry eye disease.Non‐invasive angiography of the anterior segment is now possible with novel OCT algorithms.

Association of Systemic Medication Use With Intraocular Pressure in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study

Importance There is limited understanding of the associations between systemic medication use and intraocular pressure (IOP) in the general population. Objective To examine the association between systemic medication use and IOP in a multiethnic Asian population. Design, Setting, and Participants In this post hoc analysis of the Singapore Epidemiology of Eye Diseases study, a population-based study of 10 033 participants (78.7% response rate) from 3 racial/ethnic groups (Chinese [recruited from February 9, 2009, through December 19, 2011], Malays [recruited from August 16, 2004, though July 10, 2006], and Indians [recruited from May 21, 2007, through December 29, 2009]), participants with glaucoma, previous ocular surgery, or trauma and an IOP asymmetry greater than 5 mm Hg between eyes were excluded. Intraocular pressure was measured using Goldmann applanation tonometry. An interviewer-administered questionnaire was conducted to collect data on medication and other variables. Data analysis was performed from August 1 through October 31, 2015. Main Outcomes and Measures Associations between medication and IOP were assessed using linear regression models adjusted for age, sex, body mass index, ethnicity, and the medical condition for which the medication was taken (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], and &bgr;-blockers adjusted for blood pressure, statins adjusted for lipids, and biguanides, sulfonylureas, &agr;-glycosidase inhibitors [AGIs], and insulin adjusted for glycosylated hemoglobin). Medications associated with significant IOP differences were incorporated into regression models adjusted for concomitant use of multiple medications. Generalized estimating equation models were used to account for correlation between eyes. Results Of the 10 033 participants, we analyzed 8063 (mean [SD] age, 57.0 [9.6] years; 4107 female [50.9%]; 2680 Chinese [33.2%], 2757 Malay [34.2%], and 2626 Indian [32.6%] individuals). Systemic &bgr;-blocker use was independently associated with an IOP of 0.45 mm Hg lower (95% CI, −0.65 to −0.25 mm Hg; P < .001). Conversely, higher mean IOP was associated with use of ACEIs (0.33 mm Hg higher; 95% CI, 0.08 to 0.57 mm Hg; P = .008), ARBs (0.40 mm Hg higher; 95% CI, 0.40-0.75 mm Hg; P = .02), statins (0.21 mm Hg higher; 95% CI, 0.02-0.4 mm Hg; P = .03), and sulfonylureas (0.34 mm Hg higher; 95% CI, 0.05-0.63 mm Hg; P = .02). An interaction between medication classes for additive, synergistic, or antagonistic effects on IOP was not identified. Conclusions and Relevance Although systemic &bgr;-blocker use was associated with lower IOP and systemic ACEI, ARB, statin, and sulfonylurea use was associated with higher IOP in this study, the associations were modest at best. Only the associations with systemic hypoglycemic agents were greater than 1 mm Hg, a threshold that has translated to a 14% greater risk of incident glaucoma across 5 years in other studies. At this point, the effect of systemic medication on IOP in eyes with glaucoma is not well elucidated but important. Our findings indicate that patients with glaucoma may potentially be at risk of higher or lower IOP, depending on medication class, and this would in turn affect management of IOP control.

Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning

Importance Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). Objective To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. Design, Setting, and Participants This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Exposures Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Main Outcomes and Measures Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Results Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was associated with a small reduction in VSF (2.9%; &bgr; = −0.12; 95% CI, −0.23 to −0.00; P = .046) in the Chinese group but not in the Indian and Malay groups. Moreover, Chinese participants with late AMD had a clinically significant 19.1% loss of VSF (&bgr; = −0.78; 95% CI, −1.13 to −0.43, P < .001). In the Malay group, those with late AMD had a 13.5% drop in VSF (&bgr; = −0.49; 95% CI, −1.01 to 0.04; P = .07) compared with their counterparts without AMD. Similarly, late AMD was not associated with VSF in the Indian group. Conclusions and Relevance Early and late AMD negatively affected VSF in Chinese but not in Indian and Malay participants. This finding suggests that there is an independent ethnic influence in the association of the disease with VSF in multiethnic Asian populations, thus warranting ethnicity-based strategies to delay the onset or progression of AMD.

Cumulative incidence and risk factors of prediabetes and type 2 diabetes in a Singaporean Malay cohort

AIMS The aim of this work was to determine the cumulative incidence and independent risk factors of prediabetes and type 2 diabetes (T2DM) in a well-characterized cohort of Malays in Singapore. METHODS We included 1137 participants (mean age [SD]: 55 (10) years; 53.6% female) without diabetes (DM) at baseline from the Singapore Malay Eye Study, a population-based longitudinal study with baseline (2004-2006), and follow-up (2010-2013) examinations. Prediabetes was defined as an HbA1c between 5.7% and 6.4%, with no self-reported DM history or insulin/DM medication use. T2DM was defined as a random glucose level ≥200mg/dL or HbA1c>6.4% or use of insulin/DM medication. Age-standardized cumulative incidence was calculated as the crude 6-year cumulative incidence standardized to Singapores Malay population census. Multivariable modified poisson regression models were utilized to determine the risk factors of incident prediabetes and T2DM. RESULTS The age-standardized 6-year cumulative incidence was 11.2% (95% CI 9.5, 13.1%) for T2DM, and 20.4% (95% CI 16.4, 25.2%) for prediabetes. Hypertension, higher body mass index (BMI) and higher Hba1c levels were associated with increased risk of T2DM, while older age and higher high density lipoprotein (HDL) cholesterol were protective (all P<0.05). Only higher BMI and HbA1c levels were independently associated with incident prediabetes (all P≤0.001). CONCLUSIONS While only one in ten adult Malays developed T2DM over 6-years, one in five developed prediabetes over the same time period. Our results suggest that evidence-based interventions addressing modifiable risk factors (obesity, prediabetes, hypertension, low HDL cholesterol) are needed to delay or prevent their onset.

Association of iris surface features with iris parameters assessed by swept-source optical coherence tomography in Asian eyes

Background/aims To characterise the association of iris surface features (crypts, furrows and colour) with iris volume and curvature assessed by swept-source optical coherence tomography (SSOCT) in Asian eyes. Methods Iris crypts (by number and size) and furrows (by number and circumferential extent) were graded from iris photographs. Iris colour was measured by a customised algorithm written on MATLAB (MathWorks, Natick, Massachusetts, USA). The iris was imaged by SSOCT (SS-1000, CASIA, Tomey, Nagoya, Japan). The associations of surface features with iris parameters were analysed using a generalised estimating equation. Results A total of 1704 subjects (3297 eyes) were included in the analysis. The majority was Chinese (86.4%), and 63.2% were females, and their mean age (±SD) was 61.4±6.6 years. After adjusting for age, sex, ethnicity, pupil size and corneal arcus, higher iris crypt grade was independently associated with smaller iris volume (β=−0.54, p<0.001), whereas darker irides and higher iris furrow grade were associated with larger iris volume (β=−0.041, p<0.001) and (β=0.233, p<0.001), respectively. Lighter coloured irides with more crypts and/or more furrows were also associated with less convexity (crypts: β=−0.003, p=0.03; furrows: β=−0.004, p=0.007; and colour: β=−0.001, p=0.005). Conclusions Iris surface features were highly correlated with iris volume and curvature. Irides with more crypts have a smaller volume; and darker irides with more furrows have a larger volume. Lighter irides with more crypts and/or furrows have less convexity.

Inter-relationship between ageing, body mass index, diabetes, systemic blood pressure and intraocular pressure in Asians: 6-year longitudinal study

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.