Tin Aung

Genome Institute of Singapore, Tumasik, Singapore

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Publications (512)2414.6 Total impact

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    ABSTRACT: Background To investigate the determinants of pupil diameter (PD), amplitude of pupil diameter change (PD-change) and speed of pupil constriction (SPC) using video anterior segment optical coherence tomography (AS-OCT) in a population-based sample of Chinese adults. Methods Chinese adults aged 40 to 80 years who were free from glaucoma were consecutively recruited from the population-based Singapore Chinese Eye Study. The SPC was measured by AS-OCT videography. Univariate and multivariate analyses were performed to examine the effects of demographic and ocular biometric factors (e.g., axial length [AL], anterior chamber depth [ACD], baseline PD, iris thickness at the area of the dilator muscle [ITDMR], iris area [IA], and iris bowing [IB]) on SPC, PD, and PD-change. Results A total of 266/302 (89.5 %) AS-OCT videos of eligible eyes were available for analysis. Among these subjects, 64.3 % were women, and the mean age (± standard deviation [SD]) was 56 ± 8.3 years. SPC was not associated with sex. In multiple regression analyses, SPC was independently associated with baseline PD (β = 0.116, p = 0.006). Baseline PD was independently associated with ACD (β = 0.341, p < 0.001), TISA 500 (β = −4.513, p < 0.001), IA (β = −2.796, p < 0.001), and ITDMR (β = 6.573, p < 0.001). PD-change was independently associated with ACD (β = 0.256, p < 0.001), IA (β = −1.507, p < 0.001), IB (β = 0.630, p = 0.011), and ITDMR (β = 3.124, p < 0.001). Conclusions Among normal eyes in an adult Chinese population, SPC was associated with larger baseline PD. Larger baseline PD and greater PD change form dark to light were associated with greater ACD, with smaller IA and thicker ITDMR.
    Full-text · Article · Jan 2016 · Albrecht von Graæes Archiv für Ophthalmologie
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    ABSTRACT: We examined the joint effects of intraocular pressure (IOP) and myopia on the risk of primary open angle glaucoma (POAG) in a multi-ethnic Asian population. A total of 9,422 participants (18,469 eyes) in the Singapore Epidemiology of Eye Diseases Study were included. Of them, 213 subjects (273 eyes) had POAG. All participants underwent standardised examinations. The independent and joint effects of IOP and myopia on POAG were examined using logistic regression models. Generalised estimating equation models were used to account for correlation between eyes. Higher IOP, longer axial length, and more negative spherical equivalent were independently associated with POAG, after adjusting for relevant covariates (all P ≤ 0.005). Significant interaction between IOP and myopia on POAG was observed (P interaction = 0.025). Eyes with moderate-to-high myopia (<−3.0 dioptres) with high IOP (≥20 mmHg) were 4.27 times (95% CI, 2.10–8.69) likely to have POAG, compared to eyes without myopia (>−0.5 dioptres) and with IOP <20 mmHg. Eyes with AL of ≥25.5 mm and high IOP (≥20 mmHg) were 16.22 times (95% CI, 7.73 to 34.03) likely to have POAG, compared to eyes with shorter AL (<23.5 mm) and lower IOP (<20 mmHg). These findings may provide additional insights into the pathophysiology of POAG and are particularly relevant for Asian populations.
    Preview · Article · Jan 2016 · Scientific Reports
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    ABSTRACT: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.
    Full-text · Article · Jan 2016 · Nature Genetics
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    ABSTRACT: Background: Genome-wide association studies have identified several loci associated with Parkinson's disease (PD). Whole-exome sequencing detects rare coding variants, but their links with PD genome-wide association study loci are unknown. Our objective was to investigate whether nonsynonymous variants in LRRK2 can explain associations at the PD-associated locus tagged by rs1994090. Methods: We sequenced all coding exons of LRRK2 in 453 East Asian samples and evaluated linkage disequilibrium between each nonsynonymous variant and rs1994090. We then tested selected variants and haplotypes for association with PD in 13,581 East Asian samples. Results: Of all the nonsynonymous variants, only p.Gly2385Arg was in moderate linkage disequilibrium with rs1994090 and was observed on haplotypes tagged by the rs1994090-C risk allele. Conditional analyses showed that associations at these 2 variants are not independent. Conclusions: LRRK2 p.Gly2385Arg can explain most if not all of the PD association at rs1994090 in East Asians, but other nonsynonymous variants are independent. © 2015 International Parkinson and Movement Disorder Society.
    No preview · Article · Dec 2015 · Movement Disorders
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    ABSTRACT: Purpose: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). Design: Randomized controlled trial. Participants: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. Methods: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. Main outcome measures: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. Results: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. Conclusions: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.
    No preview · Article · Dec 2015 · Ophthalmology

  • No preview · Chapter · Dec 2015
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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.
    No preview · Article · Nov 2015 · Journal of glaucoma
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    ABSTRACT: The main first-line treatment strategy for glaucoma is to reduce intraocular pressure (IOP) by topical ocular hypotensive medications, but many patients require multiple medications for adequate IOP control. Fixed-combination therapies provide several benefits, including simplified treatment regimens, theoretical improved treatment adherence, elimination of the potential for washout of the first drug by the second, and the reduction in ocular exposure to preservatives. β-Adrenoceptor antagonists (particularly 0.5% timolol) are the most commonly used agents in combination with other classes of drugs as fixed-combination eyedrops, but they are contraindicated in many patients, owing to local allergy or systemic side effects. A fixed-combination preparation without a β-blocker is therefore warranted. This paper reviews the clinical effectiveness of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) for use in patients with primary open-angle glaucoma and ocular hypertension. We searched PubMed and the ClinicalTrials.gov registry, and identified three randomized controlled trials comparing BBFC vs its constituents (brimonidine vs brinzolamide), and one comparing BBFC with unfixed brimonidine and brinzolamide. All of the studies demonstrated mean diurnal IOP to be statistically significantly lower in the BBFC group compared with constituent groups and noninferior to that with the concomitant group using two separate bottles. The safety profile of BBFC was consistent with that of its individual components, the most common ocular adverse events being ocular hyperemia, visual disturbances, and ocular allergic reactions. Common systemic adverse effects included altered taste sensation, oral dryness, fatigue, somnolence, and decreased alertness. BBFC seems to be a promising new fixed combination for use in glaucoma patients. However, long-term effects of BBFC on IOP, treatment adherence, and safety need to be determined.
    Preview · Article · Nov 2015 · Clinical Ophthalmology
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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.
    Preview · Article · Nov 2015 · Scientific Reports
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    ABSTRACT: PURPOSE. We investigated the association between corneal hysteresis (CH) and corneal resistance factor (CRF) with glaucoma severity in primary angle closure glaucoma (PACG). METHODS. We recruited 204 subjects with PACG. Each subject underwent CH and CRF measurements using the Ocular Response Analyzer (ORA), optic nerve head topography measurement using scanning laser ophthalmoscopy, and visual field assessment. Glaucoma severity was based on the visual field mean deviation (MD) and classified as mild (71), moderate (55), and severe (78). RESULTS. The mean age ± SD of study subjects was 68.7 ± 8.9 years, with most being Chinese (n = 186; 91.2%). Corneal hysteresis and CRF were lowest in the severe PACG group (9.32 ± 1.86 and 9.50 ± 1.67 mm Hg) followed by moderate PACG (9.38 ± 1.88 and 9.73 ± 1.88 mm Hg) and mild PACG (9.47 ± 1.90 and 9.85 ± 1.75 mm Hg) respectively, but the differences were not significant (P = 0.89 and P = 0.46, respectively). There was a significant positive correlation between CH and central corneal thickness (CCT; correlation coefficient [r] = 0.26, P < 0.001), CRF and CCT (r = 0.43, P < 0.001), and negative correlation between CRF and vertical cup-disc ratio (VCDR; r = -0.20, P = 0.004), and CRF with cup-disc area (r = -0.14, P = 0.04). Corneal hysteresis and CRF were not correlated with MD (r = 0.01 for CH, r = 0.1 for CRF). After multivariate analyses, adjusting for age, sex, CCT, axial length, intraocular pressure, and number of glaucoma medication, no significant associations were noted between CH and CRF with MD, VCDR, disc area, rim area, or cup area. CONCLUSIONS. Corneal biomechanical parameters measured by the ORA are not associated with severity of glaucoma in PACG. © 2015 The Association for Research in Vision and Ophthalmology, Inc.
    No preview · Article · Oct 2015 · Investigative ophthalmology & visual science
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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.
    No preview · Article · Oct 2015 · Clinical and Experimental Ophthalmology
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    ABSTRACT: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
    Full-text · Article · Sep 2015 · Nature Genetics
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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.
    No preview · Article · Sep 2015 · American Journal of Ophthalmology
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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.
    No preview · Article · Sep 2015 · Ophthalmology
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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.
    No preview · Article · Sep 2015 · Ophthalmology
  • Dan Milea · Tin Aung

    No preview · Article · Sep 2015 · Albrecht von Graæes Archiv für Ophthalmologie
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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.
    No preview · Article · Sep 2015 · Review of Scientific Instruments
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    ABSTRACT: Background Recently, a vision "bolt-on" EuroQol five-dimensional questionnaire (EQ-5D) was developed and tentative utility values (i.e., a "value set") for this new descriptive system were estimated. Objectives To compare the discriminatory power of this bolt-on and standard utility-based EQ-5D health indices. Methods Cross-sectional data on the (3-level) vision bolt-on EQ-5D were collected through face-to-face interviews with 500 and 336 individuals with and without visual impairment, respectively. To assess the discriminatory power of the vision bolt-on index relative to the standard EQ-5D index developed in the vision bolt-on valuation study, 16 pairs of mutually exclusive subgroups of individuals defined by the individuals' visual acuity and responses to the 14-item visual function questionnaire were compared pairwise. The absolute mean difference in the two index scores and the corresponding F statistic derived from the comparisons were used as measures of discriminatory power. Results The absolute mean difference in the bolt-on index score was larger than that in the standard EQ-5D index score in 14 of the 16 comparisons. The bolt-on index score exhibited a larger F-statistic value than did the standard EQ-5D index score in all known-group comparisons, with the F-statistic ratio ranging from 0.415 to 0.770. Conclusions The vision bolt-on EQ-5D appears to be more discriminative than the standard EQ-5D in measurement of vision problems. Future studies should investigate the extent to which the vision bolt-on item can increase the sensitivity of the EQ-5D to vision change in interventional studies. © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
    No preview · Article · Sep 2015 · Value in Health
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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.
    No preview · Article · Sep 2015 · Ophthalmology
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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.
    Full-text · Article · Aug 2015 · Human Molecular Genetics

Publication Stats

11k Citations
2,414.60 Total Impact Points

Institutions

  • 2015
    • Genome Institute of Singapore
      Tumasik, Singapore
  • 2013-2015
    • Duke-NUS Graduate Medical School Singapore
      • Centre for Quantitative Medicine
      Tumasik, Singapore
    • Narayana Nethralaya
      Bengalūru, Karnataka, India
    • University of Iowa
      • Department of Ophthalmology and Visual Sciences
      Iowa City, Iowa, United States
    • Nanyang Technological University
      • School of Electrical and Electronic Engineering
      Tumasik, Singapore
  • 2011-2015
    • National University Health System
      Singapore
    • University of Aberdeen
      • Health Services Research Unit
      Aberdeen, Scotland, United Kingdom
  • 2006-2015
    • Singapore Eye Research Institute
      Tumasik, Singapore
  • 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
    • 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
  • 2008-2011
    • University of Medicine 1, Yangon
      Yangon, Yangon, Myanmar
    • University of Melbourne
      Melbourne, Victoria, Australia
    • Johns Hopkins Bloomberg School of Public Health
      Baltimore, Maryland, United States
    • Royal Adelaide Hospital
      • Department of Ophthalmology
      Tarndarnya, South Australia, Australia
    • Royal Victorian Eye and Ear Hospital
      Melbourne, Victoria, Australia
  • 2009
    • Capital Medical University
      Peping, Beijing, China
  • 2007
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2002-2006
    • University College London
      • Institute of Ophthalmology
      Londinium, England, United Kingdom
  • 1996-2004
    • Tan Tock Seng Hospital
      • Department of Ophthalmology
      Tumasik, Singapore
  • 1998
    • Changi General Hospital
      • Department of Ophthalmology
      Tumasik, Singapore