Tin Aung

Duke-NUS Graduate Medical School Singapore, Tumasik, Singapore

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Publications (501)2365.19 Total impact

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    ABSTRACT: Purpose: Primary congenital glaucoma (PCG, OMIM 231300), the most common glaucoma in infancy, is caused by developmental defects in the anterior chamber angle. The 3 implicated genes are cytochrome P450 family I subfamily B polypeptide 1 (CYP1B1), latent transforming growth factor β-binding protein 2 (LTBP2), and myocilin (MYOC). In this study, we sought to determine CYP1B1 and MYOC sequence variations in a Vietnamese cohort of index cases with PCG and their families. Methods: Thirty Vietnamese subjects with PCG and 120 normal Vietnamese subjects were recruited. PCG was defined by the presence of at least 2 of the following clinical manifestations: increased corneal diameter (>10 mm at birth), corneal edema, Haab's striae, optic disc changes, and absence of other ocular or systemic diseases associated with childhood glaucoma. The coding exons, intron and exon boundaries, and untranslated regions of CYP1B1 and MYOC genes were PCR amplified and subjected to bidirectional sequencing in all subjects. Results: We identified 2 homozygous and 3 heterozygous CYP1B1 sequence alterations in our study subjects. Among the 5 mutations identified, 2 (p.H279L and p.L283F) were novel mutations, whereas 3 (p.A121_S122insDRPAFA, p.L107V, and p.V320L) had been previously reported in PCG cases. None of these mutations was observed in any of the 120 controls. Haplotypes generated with 6 non-disease-causing intragenic single nucleotide polymorphisms detected in CYP1B1 indicated that the most common haplotype in Vietnamese population is similar to that found in Chinese and Japanese. The genotype-phenotype correlation showed no significant difference between mutation and no-mutation groups for quantitative clinical features (presenting intraocular pressure, corneal diameter, number of surgeries performed, the cup-to-disc ratio) as well as for qualitative factors (bilateral cases, phenotype severity, and the prognosis) (P>0.05). Conclusions: Five out of 30 families with PCG (16.7%) had disease attributable to CYP1B1 alterations suggesting that CYP1B1 is not the major gene causing PCG in Vietnamese unlike in the case of Arab or Romany patients. This percentage is similar to that detected in studies of Japanese and Chinese patients with sporadic PCG. PCG has proven to be an ocular disease of genetic heterogeneity, calling for further studies to identify novel genes causing this disease.
    Journal of glaucoma 11/2015; DOI:10.1097/IJG.0000000000000331 · 2.11 Impact Factor

  • Clinical Ophthalmology 11/2015; DOI:10.2147/OPTH.S72380 · 0.76 Impact Factor
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    ABSTRACT: We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40–80 years between 2004–2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better-seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional-hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25–1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24–2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all-cause (HR 1.70; 95% CI, 1.25–2.36) and CVD mortality (HR 1.57; 95% CI, 1.05–2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26–7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality.
    Scientific Reports 11/2015; 5:16304. DOI:10.1038/srep16304 · 5.58 Impact Factor

  • Investigative ophthalmology & visual science 10/2015; 56(11):6879. DOI:10.1167/iovs.15-17930 · 3.40 Impact Factor
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    ABSTRACT: Background: To investigate the changes in anterior segment parameters, as assessed by anterior segment optical coherence tomography (ASOCT) in Japanese subjects after laser peripheral iridotomy (LPI). Design: Prospective observational study PARTICIPANTS: 72 subjects with angle closure including primary angle closure suspect (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG). Methods: Customized software was used to measure ASOCT parameters. Complete data of 51 subjects were available for final analysis. Main outcome measures: Angle opening distance (AOD), trabecular-iris space area (TISA), anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness, curvature, and area, and lens vault (LV). Results: A total of 25 PACS, 17 PAC and 9 PACG were included. Mean age was 74.7 ± 6.7 years and majority were females (80.4%). Following LPI, there was a significant increase in mean gonioscopic angle width (1.16 vs. 1.93, p < 0.001) and a corresponding increase in AOD, TISA, and angle recess area (ARA) (all p < 0.001). The ACA (p < 0.001), ACV (p < 0.001), and ACD (p = 0.003) increased significantly; and iris curvature (p < 0.001) was significantly reduced. There were no significant changes in ACW, LV, iris thickness and area. Age- and gender-adjusted analysis for predictors of percentage change in AOD750 showed significant association with greater baseline LV (β = 0.32, p = 0.03). No significant differences were noted in the mean percentage change in parameters between the PACS and PAC-PACG. Conclusions: Japanese eyes with angle closure demonstrated an increase in anterior chamber dimensions, angle widening and iris flattening; with a constant LV, iris thickness and iris area after LPI. This article is protected by copyright. All rights reserved.
    Clinical and Experimental Ophthalmology 10/2015; DOI:10.1111/ceo.12673 · 2.35 Impact Factor
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    ABSTRACT: High blood pressure, which affects more than 1 billion people worldwide , is a major risk factor for myocardial infarction, stroke and chronic kidney disease. Approximately 9 million deaths each year are attributable to high blood pressure, including >50% of deaths from coronary heart disease and stroke 1,2. High blood pressure is more prevalent in people of East Asian and South Asian ancestry and is a major contributor to their increased risk of stroke and coronary heart disease 3,4. Genome-wide association studies (GWAS) have identified over 50 genetic loci influencing blood pressure in predominantly European populations 5–16. A role for epigenetic mechanisms in blood pressure regulation has also been suggested 17–20. We carried out a GWAS in East Asians and South Asians, as well as Europeans, to seek both cosmopolitan and population-specific genetic effects for five blood pressure phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, mean arterial pressure (MAP) and hypertension (Supplementary Fig. 1) (ref. 5). We then sought DNA coding and gene regulatory mechanisms, including DNA methylation and gene transcription, to help explain the relationships we observed between sequence variation and blood pressure. RESULTS Genome-wide association and replication testing We used genome-wide association data from 99,994 individuals of East Asian (n = 31,516), European (n = 35,352) and South Asian (n = 33,126) ancestry. Characteristics of the participants and information on the genotyping arrays and imputation are summarized in Supplementary Tables 1–3. Phenotype-specific meta-analysis was carried out separately for East Asian, European and South Asian samples, followed by a meta-analysis across the three ancestral population groups. The trans-ancestry genome-wide association results identified 4,077 variants with P < 1 × 10 −4 against any blood pressure phenotype, distributed among 630 genetic loci. At each locus, we identified the sentinel SNP (the SNP with the lowest P value against any phenotype) and carried out combined analysis with phenotype-specific results from the International Consortium on Blood Pressure (ICBP) GWAS (maximum n = 87,205) (refs. 8,9). This analysis identified 19 previously unreported loci where the sentinel SNP had suggestive evidence for association with blood pressure (P < 1 × 10 −7
    Nature Genetics 09/2015; DOI:10.1038/ng.3405 · 29.35 Impact Factor
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    ABSTRACT: Purpose: To describe the relationship between peripapillary choroidal thickness and retinal nerve fiber layer (RNFL) thickness in a population-based sample of non-glaucomatous eyes. Design: Population-based, cross-sectional study. Methods: 478 non-glaucomatous subjects aged over 40 years were recruited from the Singapore Malay Eye Study (SiMES-2). All participants underwent a detailed ophthalmic examination, including Cirrus and Spectralis optical coherence tomography (OCT) for the measurements of RNFL thickness and peripapillary choroidal thickness respectively. Associations between peripapillary choroidal thickness and RNFL thickness were assessed using linear regression models with generalized estimating equations. Results: Of the 424 included subjects (843 non-glaucomatous eyes), 39% were men, and the mean (SD) age was 66.7 (10.5) years. The mean peripapillary choroidal thickness was 135.59 ± 56.74 μm and the mean RNFL thickness was 92.92 ± 11.41 μm. In terms of distribution profile, peripapillary choroid was thickest (150.04 ± 59.72 μm) at superior and thinnest (110.71 ± 51.61 μm) at inferior quadrant, whereas RNFL was thickest (118.60 ± 19.83 μm) at inferior and thinnest (67.36 ± 11.36 μm) at temporal quadrant. We found that thinner peripapillary choroidal thickness was independently associated with thinner RNFL thickness globally (regression coefficient [β] = - 1.334 μm for per SD decrease in PPCT, p = 0.003), and in the inferior (β = - 2.565, p = 0.001) and superior (β = - 2.340, p = 0.001) quadrants even after adjusting for potential confounders. Conclusions: Thinner peripapillary choroid was independently associated with thinner RNFL globally and in the inferior and superior regions. This structure-structure relationship may need further exploration in glaucomatous eyes to apply in clinical settings.
    American Journal of Ophthalmology 09/2015; DOI:10.1016/j.ajo.2015.09.018 · 3.87 Impact Factor
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    ABSTRACT: Purpose: To investigate whether known genetic loci for primary open-angle glaucoma (POAG) are associated with visual field (VF) progression in patients from a Singaporean Chinese population. Design: Retrospective study. Participants: Patients with 5 or more reliable VF measurements who were being followed up at a Singapore hospital. Methods: Visual field progression was identified using Progressor software version 3.7 (Medisoft, Leeds, United Kingdom) and defined by pointwise linear regression (PLR) criteria as follows: any 2 contiguous points in the same hemifield progressing (≤-1.00 dB/year for inner points and ≤-2.00 dB/year for edge points; P < 0.01). Single nucleotide polymorphisms (SNPs) and their proxies from 10 POAG-associated loci (CAV1-CAV2, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS, PMM2, and TGFBR3-CDC7) identified from genome-wide association studies were tested for association with VF progression using logistic regression with an additive genetic model adjusting for age, gender, average intraocular pressure (IOP), central corneal thickness (CCT), and baseline vertical cup-to-disc ratio (VCDR). Main outcome measure: Visual field progression. Results: Of the 1334 patients included in the study, 469 subjects (35.1%) completed 5 or more reliable VF measurements (mean follow-up, 9.01 years; standard deviation, 5.00 years). The mean age of patients was 59.6 years (standard deviation, 9.0 years); 305 patients were men and all were Chinese. The average IOP in eyes fulfilling PLR progression was 16.5 mmHg versus 17.7 mmHg in those who did not (P = 0.52). Univariate analysis revealed that increased VCDR (P = 0.003), reduced CCT (P = 0.045), and reduced superior and inferior retinal nerve fiber layer thickness (P = 0.01, respectively) were associated with VF progression. No clinical or structural features were associated significantly with VF progression on multivariate analysis. The rs1192415 index SNP in TGFBR3-CDC7 (P = 0.002; odds ratio, 6.71 per risk allele) was the only SNP associated with VF progression. Conclusions: The presence of the index SNP rs1192415 (TGFBR3-CDC7) was associated with VF progression in POAG patients. These findings warrant further investigation in independent cohorts.
    Ophthalmology 09/2015; DOI:10.1016/j.ophtha.2015.08.016 · 6.14 Impact Factor
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    ABSTRACT: Purpose: To investigate the incidence of gonioscopic angle closure after 4 years in subjects with gonioscopically open angles but varying degrees of angle closure detected on anterior segment optical coherence tomography (AS OCT; Visante; Carl Zeiss Meditec, Dublin, CA) at baseline. Design: Prospective, observational study. Participants: Three hundred forty-two subjects, mostly Chinese, 50 years of age or older, were recruited, of whom 65 were controls with open angles on gonioscopy and AS OCT at baseline, and 277 were cases with baseline open angles on gonioscopy but closed angles (1-4 quadrants) on AS OCT scans. Methods: All subjects underwent gonioscopy and AS OCT at baseline (horizontal and vertical single scans) and after 4 years. The examiner performing gonioscopy was masked to the baseline and AS OCT data. Angle closure in a quadrant was defined as nonvisibility of the posterior trabecular meshwork by gonioscopy and visible iridotrabecular contact beyond the scleral spur in AS OCT scans. Main outcome measures: Gonioscopic angle closure in 2 or 3 quadrants after 4 years. Results: There were no statistically significant differences in age, ethnicity, or gender between cases and controls. None of the control subjects demonstrated gonioscopic angle closure after 4 years. Forty-eight of the 277 subjects (17.3%; 95% confidence interval [CI], 12.8-23; P < 0.0001) with at least 1 quadrant of angle closure on AS OCT at baseline demonstrated gonioscopic angle closure in 2 or more quadrants, whereas 28 subjects (10.1%; 95% CI, 6.7-14.6; P < 0.004) demonstrated gonioscopic angle closure in 3 or more quadrants after 4 years. Individuals with more quadrants of angle closure on baseline AS OCT scans had a greater likelihood of gonioscopic angle closure developing after 4 years (P < 0.0001, chi-square test for trend for both definitions of angle closure). Conclusions: Anterior segment OCT imaging at baseline predicts incident gonioscopic angle closure after 4 years among subjects who have gonioscopically open angles and iridotrabecular contact on AS OCT at baseline.
    Ophthalmology 09/2015; DOI:10.1016/j.ophtha.2015.07.030 · 6.14 Impact Factor
  • Dan Milea · Tin Aung ·

    Albrecht von Graæes Archiv für Ophthalmologie 09/2015; DOI:10.1007/s00417-015-3167-z · 1.91 Impact Factor
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    ABSTRACT: Non-contact imaging techniques are preferred in ophthalmology. Corneal disease is one of the leading causes of blindness worldwide, and a possible way of detection is by analyzing the shape and optical quality of the cornea. Here, a simple and cost-effective, non-contact optical probe system is proposed and illustrated. The probe possesses high spatial resolutions and is non-dependent on coupling medium, which are significant for a clinician and patient friendly investigation. These parameters are crucial, when considering an imaging system for the objective diagnosis and management of corneal diseases. The imaging of the cornea is performed on ex vivo porcine samples and subsequently on small laboratory animals, in vivo. The clinical significance of the proposed study is validated by performing imaging of the New Zealand white rabbit's cornea infected with Pseudomonas.
    Review of Scientific Instruments 09/2015; 86(9). DOI:10.1063/1.4929684 · 1.61 Impact Factor

  • Value in Health 09/2015; DOI:10.1016/j.jval.2015.08.002 · 3.28 Impact Factor
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    ABSTRACT: To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss. Cross-sectional study. One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older. Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system. Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7-14 log photons/cm(2) per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany). The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = -0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters. In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    Ophthalmology 09/2015; 122(9):1777-85. DOI:10.1016/j.ophtha.2015.06.002 · 6.14 Impact Factor
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    ABSTRACT: Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. XFS greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (∼40kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7kb region bounded by the 3 prime end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in U.S. Caucasian (91 cases/1031 controls), German (771 cases/1365 controls), and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that strongly-associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Molecular Genetics 08/2015; DOI:10.1093/hmg/ddv347 · 6.39 Impact Factor
  • Xiulan Zhang · Wei Wang · Tin Aung · Jost B Jonas · Ningli Wang ·
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    ABSTRACT: Primary angle closure disease (PACD), prevalent in Asian countries, is generally associated with a shallower anterior chamber, a shorter axial length, thicker lens, hyperopia, and female sex. Other physiological factors, however may be important, especially with regard to triggering acute primary angle closure (APAC). Thickening of the choroid has been demonstrated in untreated and treated, acute and chronic PACD eyes. Recently, there has been growing interest in studying the role of the choroid in the pathophysiology of PACD. The emergence of new imaging technology such as the enhanced depth imaging (EDI) mode of spectral-domain optical coherence tomography (OCT) and swept source OCT (SS-OCT) has contributed to understanding PACD pathologies. We summarize the functions of the choroid and choroidal changes in the pathogenesis of PACD, and discuss potential future developments. Copyright © 2015 Elsevier Inc. All rights reserved.
    Survey of Ophthalmology 07/2015; DOI:10.1016/j.survophthal.2015.06.005 · 3.85 Impact Factor
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    ABSTRACT: There has been limited success in identifying causal variants underlying association signals observed in genome-wide association studies (GWAS). The use of 1000 Genomes Project (1KGP) allows the imputation to estimate the genetic information at untyped variants. However, long stretches of high linkage disequilibrium within the genome prevent us from differentiating between causal variants and perfect surrogates, thus limiting our ability to identify causal variants. Transethnic strategies have been proposed as a possible solution to mitigate this. However, these studies generally rely on imputing genotypes from multiple ancestries from 1KGP but not against population-specific reference panels. Here, we perform the first transethnic fine-mapping study across three Asian cohorts from diverse ancestries at the loci implicated with eye and blood lipid traits, using population-specific reference panels that have been generated by whole-genome sequencing samples from the same ancestry groups. Our study outlines several challenges faced in a fine-mapping exercise where one simply aims to meta-analyse existing GWAS that have been imputed against reference haplotypes from the 1KGP.European Journal of Human Genetics advance online publication, 1 July 2015; doi:10.1038/ejhg.2015.150.
    European journal of human genetics: EJHG 07/2015; DOI:10.1038/ejhg.2015.150 · 4.35 Impact Factor
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    ABSTRACT: Purpose To evaluate glaucoma prevalence and disease burden across Asian subregions from 2013 to 2040. Methods We conducted a systematic review and meta-analysis of 23 population-based studies of 1318 primary open angle glaucoma (POAG) cases in 66 800 individuals and 691 primary angle closure glaucoma (PACG) cases in 72 767 individuals in Asia. Regions in Asia were defined based on United Nations’ (UN) classification of macro-geographic regions. PubMed, Medline and Web of Science databases were searched for population-based glaucoma prevalence studies using standardised criteria published to 31 December 2013. Pooled glaucoma prevalence for individuals aged 40–80 years was calculated using hierarchical Bayesian approaches. Prevalence differences by geographic subregion, subtype and habitation were examined with random effects meta-regression models. Estimates of individuals with glaucoma from 2013 to 2040 were based on the UN World Population Prospects. Results In 2013, pooled overall glaucoma prevalence was 3.54% (95% credible interval (CrI) 1.83 to 6.28). POAG (2.34%, 95% CrI 0.96 to 4.55) predominated over PACG (0.73%, 95% CrI 0.18 to 1.96). With age and gender adjustment, PACG prevalence was higher in East than South East Asia (OR 5.55, 95% CrI 1.52 to 14.73), and POAG prevalence was higher in urban than rural populations (OR 2.11, 95% CrI 1.57 to 2.38). From 2013 to 2040, South Central Asia will record the steepest increase in number of glaucoma individuals from 17.06 million to 32.90 million compared with other Asian subregions. In 2040, South-Central Asia is also projected to overtake East Asia for highest overall glaucoma and POAG burden, while PACG burden remains highest in East Asia. Conclusions Across the Asian subregions, there was greater glaucoma burden in South-Central and East Asia. Sustainable public health strategies to combat glaucoma in Asia are needed.
    The British journal of ophthalmology 06/2015; DOI:10.1136/bjophthalmol-2014-306102 · 2.98 Impact Factor
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    ABSTRACT: To assess the visibility of the choroidal-scleral interface (CSI) from spectral domain optical coherence tomography (SD-OCT) and evaluate the ocular and systemic factors influencing the visibility of CSI in healthy eyes from population-based Malay sample. Participants were consecutively recruited from the population-based Singapore Malay Eye Study-2 (SiMES-2). SD-OCT images were obtained by Spectralis OCT with enhanced depth imaging (EDI) mode. Visibility of CSI was assessed by a grading system ranging from 0 to 2 scores. The reliability of choroidal thickness measurement in different grades of CSI visibility was assessed using intraclass correlation coefficient. Ordinal regression analyses were performed to evaluate a range of ocular and systemic factors influencing the visibility of CSI. A total of 176 healthy eyes were analysed, and 59.1% of our subjects had well-defined CSI (score 2), 8.5% had poorly defined CSI (score 0), and 32.4% had CSI between well and poorly defined (score 1). The reliability of subfoveal choroidal thickness measurement decreased with each grade of CSI visibility score. Decreased axial length (AL) (estimate of ordinal regression [OR] = 0.465, p = 0.003), thicker retinal thickness (estimate of OR = -0.030, p = 0.004), younger age (estimate of OR = 0.045, p = 0.030) and diabetes (estimate of OR = -0.746, p = 0.004) were associated with lower CSI visibility score. Only 60% of normal healthy eyes had well-defined CSI from SD-OCT images. Our data suggest that choroidal thickness measurements can be substantially affected by the visibility of CSI. The visibility of CSI varies with AL, retinal thickness, age and diabetes. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
    Acta ophthalmologica 06/2015; DOI:10.1111/aos.12777 · 2.84 Impact Factor
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    ABSTRACT: Glaucoma can remain asymptomatic until a severe stage, resulting in a high prevalence of undiagnosed glaucoma worldwide. Asia accounts for 60% of the world's total glaucoma cases. To our knowledge, no epidemiological studies have assessed ethnic differences in undiagnosed glaucoma among various Asian subgroups. To determine the prevalence of, risk factors for, and visual features of undiagnosed primary glaucoma in a multiethnic Asian population. 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. Prevalence of, risk factors for, and visual features of undiagnosed glaucoma. 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. 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.
    Jama Ophthalmology 06/2015; 133(8). DOI:10.1001/jamaophthalmol.2015.1478 · 3.32 Impact Factor
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    ABSTRACT: IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
    Nature Communications 06/2015; 6:7270. DOI:10.1038/ncomms8270 · 11.47 Impact Factor

Publication Stats

10k Citations
2,365.19 Total Impact Points


  • 2013-2015
    • Duke-NUS Graduate Medical School Singapore
      • Centre for Quantitative Medicine
      Tumasik, Singapore
    • Nanyang Technological University
      • School of Electrical and Electronic Engineering
      Tumasik, Singapore
    • University of Iowa
      • Department of Ophthalmology and Visual Sciences
      Iowa City, Iowa, United States
  • 2011-2015
    • National University Health System
    • University of Aberdeen
      • Health Services Research Unit
      Aberdeen, Scotland, United Kingdom
  • 2004-2015
    • National University of Singapore
      • Department of Ophthalmology
      Tumasik, Singapore
  • 1996-2015
    • Singapore National Eye Centre
      Tumasik, Singapore
  • 2014
    • Prince of Wales Hospital, Hong Kong
      Chiu-lung, Kowloon City, Hong Kong
  • 2006-2014
    • Singapore Eye Research Institute
      Tumasik, Singapore
    • Moorfields Eye Hospital NHS Foundation Trust
      • Department of Glaucoma Services
      Londinium, England, United Kingdom
  • 2012
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2010-2011
    • Institute for Infocomm Research
      • Department of Human Language Technology
      Tumasik, Singapore
    • Singapore Health Services
      Tumasik, Singapore
  • 2008-2011
    • University of Medicine 1, Yangon
      Yangon, Yangon, Myanmar
    • Johns Hopkins Bloomberg School of Public Health
      Baltimore, Maryland, United States
    • University of Melbourne
      Melbourne, Victoria, Australia
    • Royal Victorian Eye and Ear Hospital
      Melbourne, Victoria, Australia
    • Royal Adelaide Hospital
      • Department of Ophthalmology
      Tarndarnya, South Australia, Australia
  • 2009
    • Capital Medical University
      Peping, Beijing, China
  • 1996-2009
    • Tan Tock Seng Hospital
      • Department of Ophthalmology
      Tumasik, Singapore
  • 2007
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2002-2006
    • University College London
      • Institute of Ophthalmology
      Londinium, England, United Kingdom
  • 1998
    • Changi General Hospital
      • Department of Ophthalmology
      Tumasik, Singapore