[show abstract][hide abstract] ABSTRACT: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
[show abstract][hide abstract] ABSTRACT: Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17×10-9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45×10-9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
[show abstract][hide abstract] ABSTRACT: To evaluate the contribution of nonsynonymous coding variants of known familial and GWAS-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare nonsynonymous coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 nonsynonymous coding variants of these genes in 710 late-onset PD cases and 9,046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (OR=1.58; 95% CI=1.29-1.93; P=8.05x10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss-of-function of these genes were present in healthy controls. Overall, nonsynonymous coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.
Human Molecular Genetics 02/2014; · 7.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract Purpose: To examine the association of reproductive factors and major eye diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy and cataract, in Asian women. Methods: The Singapore Malay Eye Study is a population-based cross-sectional epidemiological study which examined 3280 persons (78.7% response) of Malay ethnicity aged 40-80 years; 1704 were female. Information on reproductive factors and use of hormone replacement therapy (HRT) was collected using an interviewer-administered questionnaire. Glaucoma was defined according to the International Society for Geographical and Epidemiological Ophthalmology criteria. Retinal photographs were graded for AMD following the Wisconsin grading system, and diabetic retinopathy according to the modified Airlie House classification system. Cataract was graded according to the Lens Opacity Classification System III. Results: A total of 1176 women reported having experienced menopause by the time of the study with 1073 (91%) having a natural menopause, 88 (7.5%) a hysterectomy and 9 (0.8%) due to other reasons; HRT was used by 70 (6%) women. Women whose age at menopause was ≤52 years were 3.5 times more likely to have glaucoma (95% confidence interval, CI, 1.23-9.98, p value = 0.02) than those whose age at menopause was ≥53 years. Age of menopause was not associated with AMD (age-adjusted odds ratio, OR, 1.22, 95% CI 0.65-2.31), diabetic retinopathy (age-adjusted OR 1.01, 95% CI 0.66-1.54) or cataract (age-adjusted OR 1.38, 95% CI 0.95-2.00). Use of HRT was not associated with any of these eye diseases. Conclusion: Women who had menopause at a younger age were more likely to have glaucoma. This association needs to be confirmed in other studies.
[show abstract][hide abstract] ABSTRACT: Purpose:Recently, three genetic susceptibility loci for primary angle closure glaucoma (PACG) were identified: COL11A1 rs3753841, PCMTD1-ST18 rs1015213, and PLEKHA7 rs11024102. The purpose of this study was to investigate whether these single nucleotide polymorphisms (SNPs) affect the phenotype of PACG patients. Methods:: A retrospective analysis was performed for 700 Singaporean Chinese PACG patients who had been genotyped. The associations between the three SNPs and clinical features related to severity of glaucoma were studied. For a subgroup of patients who had ≥5 years of follow-up and ≥5 reliable visual field (VF) tests, differences in glaucoma progression, as measured by the proportion of VF progression and blindness, were compared amongst groups with different genotypes. Results:The minor allele frequency at COL11A1 rs3753841, PCMTD1-ST18 rs1015213, and PLEKHA7 rs11024102 were 36%, 2.1% and 41.5%, respectively. There were no significant differences in gender, diagnosis (acute primary angle closure [APAC] versus non-APAC), age at diagnosis, laterality of glaucoma or need for filtration surgery amongst patients with different genotypes (all P>0.05). We also found no significant difference between genotypes and the intraocular pressure at presentation and other clinical characteristics at DNA collection (vertical cup-to-disc ratio, best corrected visual acuity, baseline VF mean deviation or pattern standard deviation). For the subgroup analysis, we did not observe significant associations between VF progression and the proportion of blindness with any of the PACG susceptibility loci. Conclusions:The three genetic susceptibility loci for PACG did not underlie any major phenotypic diversity in terms of disease severity or progression.
[show abstract][hide abstract] ABSTRACT: To assess iris surface features in Asian eyes and examine their associations with iris thickness measured by anterior segment optical coherence tomography (AS OCT).
We recruited 250 subjects from the Singapore Malay Eye Study.
We obtained standardized slit-lamp photographs and developed a grading system assessing iris crypts (by number and size), furrows (by number and circumferential extent), and color (higher grade denoting darker iris). Vertical and horizontal cross-sections of the anterior chamber were imaged using AS OCT. Intragrader and intergrader agreements in the grading of iris surface were assessed by weighted κ (κw) statistic. Associations of the average iris thickness with the grade of iris features were assessed using linear regression analysis.
Frequency and size of iris crypts, furrows, and color; iris thickness at 750 μm (IT750) and 2000 μm (IT2000) from the scleral spur; and maximum iris thickness (ITM) averaged from the 4 quarters.
Three hundred sixty-four eyes had complete and gradable data for crypts and color; 330 eyes were graded for furrows. The grading scheme showed good intragrader (crypt κw = 0.919, furrow κw =0.901, color κw = 0.925) and intergrader (crypt κw = 0.775, furrow κw = 0.836, color κw = 0.718) agreements. Higher crypt grade was associated independently with thinner IT750 (β [change in iris thickness per grade higher] = -0.007; P = 0.029), IT2000 (β = -0.018; P < 0.001), and ITM (β = -0.012; P < 0.001). More extensive furrows were associated with thicker IT750 (β = 0.022; P < 0.001). Darker iris was also associated with thicker IT750 (β = 0.014; P = 0.001).
Iris surface features, assessed and measured from slit-lamp photographs, correlate well with iris thickness. Irises with more crypts are thinner; irises with more extensive furrows and darker color are thicker peripherally. These findings may provide another means to assess angle closure risk based on iris features.
[show abstract][hide abstract] ABSTRACT: Measurement error of a phenotypic trait reduces the power to detect genetic associations. We examined the impact of sample size, allele frequency and effect size in presence of measurement error for quantitative traits. The statistical power to detect genetic association with phenotype mean and variability was investigated analytically. The non-centrality parameter for a non-central F distribution was derived and verified using computer simulations. We obtained equivalent formulas for the cost of phenotype measurement error. Effects of differences in measurements were examined in a genome-wide association study (GWAS) of two grading scales for cataract and a replication study of genetic variants influencing blood pressure. The mean absolute difference between the analytic power and simulation power for comparison of phenotypic means and variances was less than 0.005, and the absolute difference did not exceed 0.02. To maintain the same power, a one standard deviation (SD) in measurement error of a standard normal distributed trait required a one-fold increase in sample size for comparison of means, and a three-fold increase in sample size for comparison of variances. GWAS results revealed almost no overlap in the significant SNPs (p<10(-5)) for the two cataract grading scales while replication results in genetic variants of blood pressure displayed no significant differences between averaged blood pressure measurements and single blood pressure measurements. We have developed a framework for researchers to quantify power in the presence of measurement error, which will be applicable to studies of phenotypes in which the measurement is highly variable.
PLoS ONE 01/2014; 9(1):e87044. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Purpose:To determine ocular and systemic factors influencing macular thickness measured by SD-OCT in a population-based sample of healthy eyes. Methods:490 Chinese adults aged 40 to 80 years were recruited from the Singapore Chinese Eye Study. All participants underwent a comprehensive eye examination and a standardized interview. SD-OCT (Cirrus HD-OCT, software version 6.0, Carl Zeiss Meditec, Dublin, CA) measured a range of macular thickness parameters (central foveal subfield thickness, average inner macular thickness, average outer macular thickness, overall average macular thickness and overall macular cube volume). Linear regression analyses were performed to examine the effects of various ocular and systemic factors on macular thickness. Results:The mean (standard deviation) age of the subjects was 53.17 (6.14) years and 50.0% were male. The mean central foveal subfield, average inner and average outer macular thicknesses were 250.38 (20.58) µm, 319.33 (14.40) µm and 276.67 (11.94) µm, respectively. The overall average macular thickness was 280.25 (11.42) µm and overall macular cube volume was 10.09 (0.41) mm3. Age was inversely correlated with macular thicknesses (except central foveal subfield thickness), after adjusting for gender, diastolic blood pressure, axial length (AL) and nuclear opalescence. Increased AL was associated with thicker central foveal subfield thickness (3.33 mm increase per mm increase in AL, p <0.001) but thinner overall average macular thickness (2.34 mm decrease per mm increase in AL, p <0.001). Conclusions:Older age, female gender and longer AL were independently associated with thinner average inner, average outer and overall average macular thicknesses (except AL for average inner macular thickness).
[show abstract][hide abstract] ABSTRACT: To develop a score along with an estimated probability of disease for detecting angle closure based on anterior segment optical coherence tomography (AS OCT) imaging.
A total of 2047 subjects 50 years of age and older were recruited from a community polyclinic in Singapore. All subjects underwent standardized ocular examination including gonioscopy and imaging by AS OCT (Carl Zeiss Meditec). Customized software (Zhongshan Angle Assessment Program) was used to measure AS OCT parameters. Complete data were available for 1368 subjects. Data from the right eyes were used for analysis. A stepwise logistic regression model with Akaike information criterion was used to generate a score that then was converted to an estimated probability of the presence of gonioscopic angle closure, defined as the inability to visualize the posterior trabecular meshwork for at least 180 degrees on nonindentation gonioscopy.
Of the 1368 subjects, 295 (21.6%) had gonioscopic angle closure. The angle closure score was calculated from the shifted linear combination of the AS OCT parameters. The score can be converted to an estimated probability of having angle closure using the relationship: estimated probability = e(score)/(1 + e(score)), where e is the natural exponential. The score performed well in a second independent sample of 178 angle-closure subjects and 301 normal controls, with an area under the receiver operating characteristic curve of 0.94.
A score derived from a single AS OCT image, coupled with an estimated probability, provides an objective platform for detection of angle closure.
American journal of ophthalmology 11/2013; · 3.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Purpose:To examine the relationship between retinal vascular geometric parameters with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) parameters in non-glaucomatous subjects. Methods:Study subjects were identified from the Singapore Chinese Eye Study (SCES), a population-based survey of Singaporean Chinese aged 40 to 80 years. All subjects underwent standardized systemic and ocular examinations. Non-glaucomatous eyes were defined as eyes with normal, reliable visual field results. Retinal vascular parameters (retinal vascular fractal dimension, tortuosity and caliber) were measured from retinal photographs by using a computer-assisted program, according to a standardized protocol. Spectral-domain optical coherence tomography (SD-OCT) was used to measure RNFL and macular GC-IPL thicknesses. Results:352 non-glaucomatous subjects with gradable retinal photographs and OCT images were included for the final analyses. In multiple regression analyses, after adjusting for age, gender, hypertension, diabetes, axial length, disc area and OCT signal strength; decreased retinal vascular fractal dimension (β = -1.60, p=0.002), narrower retinal arteriolar caliber (β = -1.60, p=0.001) and venular caliber (β = -1.97, p<0.001) were independently associated with thinner average RNFL thickness. In addition, decreased retinal vascular fractal dimension (β = -0.77, p=0.017) and decreased retinal venular tortuosity (β = -0.63, p=0.042) were independently associated with thinner average GC-IPL thickness after adjusting for age, gender, hypertension, diabetes, axial length and OCT signal strength. Conclusions: Rarefaction, vasoconstriction and straightening of the retinal vasculature are associated with thinner RNFL and GC-IPL thickness. This information may potentially provide further insights on the role of vascular processes in glaucoma development and progression.
[show abstract][hide abstract] ABSTRACT: The Moorfields Motion Displacement Test (MMDT; Enhanced Standard Threshold Algorithm [ESTA] version 1, London, UK) is a new 31-point suprathreshold test for visual field assessment using moving line stimuli displayed on a standard laptop computer. This study evaluated the diagnostic performance of the MMDT for discriminating between healthy eyes and eyes with glaucoma.
Evaluation of diagnostic technology.
Seventy-eight subjects with glaucoma and 348 healthy subjects.
All participants underwent a standardized ophthalmologic examination, including the MMDT and Heidelberg Retina Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany) scanning of the optic disc. The diagnosis of glaucoma was based on clinical examination with glaucomatous optic neuropathy defined by the presence of neuroretinal rim thinning, notching or excavation of the cup, cup-to-disc asymmetry between eyes of 0.25 or more, nerve fiber layer thinning (focal or diffuse), or a combination thereof; and HRT-based Moorfields Regression Analysis (MRA) results of outside normal limits in any sector. Normal eyes were defined as clinically having healthy neuroretinal rims and an MRA analysis of within normal limits in all sectors. The MMDT used a Pandora response version of the ESTA without optical correction. Subjects with a false-positive response of 15% or more in MMDT were excluded.
The performance of the global probability of true damage (global PTD) for diagnosing glaucoma was assessed by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The global PTD was calculated as a sum of individual PTD values, ranging from 0% to 100% for all 31 visual locations, and was expressed as a quotient of 100.
Seventy-eight subjects with glaucoma (mean age, 66.6±13.1 years; male gender, 55.1%) and 348 healthy subjects (mean age, 55.2±9.2 years; male gender, 35.3%) were analyzed. The AUC for the global PTD was 0.930 (95% confidence interval, 0.893-0.967) for diagnosing glaucoma. At 85% specificity, the MMDT demonstrated a sensitivity of 88.5%. This decreased to 83.3% at 95% specificity. At the global PTD cutoff point value of 2.0, the sensitivity was 85.9% and the specificity was 94.5%.
The suprathreshold MMDT showed good diagnostic performance for diagnosing glaucoma when glaucoma was defined by a structural criterion.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
[show abstract][hide abstract] ABSTRACT: To determine the relationship between macular ganglion cell-inner plexiform layer (GC-IPL) thickness and optic disc/retinal nerve fibre layer (RNFL) parameters in non-glaucomatous eyes measured by spectral-domain optical coherence tomography (SD-OCT).
491 non-glaucomatous Chinese aged 40-80 years were recruited from a population-based study and underwent standardised ophthalmic examination. SD-OCT was used to measure GC-IPL thickness, optic disc parameters and RNFL thickness. Univariate and multiple linear regression analyses were performed to assess the association between GC-IPL and optic disc/RNFL parameters.
In univariate analyses, all RNFL parameters and rim area were significantly correlated with all macular GC-IPL parameters (p<0.001, r=0.12-0.56). In multiple regression analyses, after adjusting for age, gender, disc area, signal strength and axial length, average RNFL thickness (per µm decrease) was most strongly correlated with average GC-IPL thickness (β=-0.30, standardised β=-0.499, p<0.001) compared with other optic disc/RNFL parameters.
Our study demonstrated only fair correlations between macular GC-IPL and optic disc/RNFL parameters measured by SD-OCT. This information is important for further evaluation of macular GC-IPL thickness as an additional marker in detecting glaucomatous damage and progression.
The British journal of ophthalmology 10/2013; · 2.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Refractive error is a complex ocular trait governed by both genetic and environmental factors and possibly their interplay. Thus far, data on the interaction between genetic variants and environmental risk factors for refractive errors are largely lacking. By using findings from recent genome-wide association studies, we investigated whether the main environmental factor, education, modifies the effect of 40 single nucleotide polymorphisms (SNP) on refractive error among 8,461 adults from five studies including ethnic Chinese, Malay and Indian residents of Singapore. Three genetic loci SHISA6-DNAH9, GJD2 and ZMAT4-SFRP1 exhibited a strong association with myopic refractive error in individuals with tertiary or university education (SHISA6-DNAH9: rs2969180 A allele, β=-0.33 diopters (D), P=3.6×10(-6); GJD2: rs524952 A allele, β=-0.31 D, P=1.68×10(-5); ZMAT4-SFRP1: rs2137277 A allele, β=-0.47 D, P=1.68×10(-4)), whereas the association at these loci was non-significant or of borderline significance in those with secondary education or lower (P for interaction: 3.82×10(-3) to 4.78×10(-4)). The evidence for interaction was strengthened when combining the genetic effects of these three loci (P for interaction=4.40×10(-8)), and significant interactions with education were also observed for axial length and myopia. Our study shows that low level of education may attenuate the effect of risk alleles on myopia. These findings further underline the role of gene-environment interactions in the pathophysiology of myopia.
Human Molecular Genetics 09/2013; · 7.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although single-SNP analysis has proven to be useful in identifying many disease-associated loci, region-based analysis has several advantages. Empirically, it has been shown that region-based genotype and haplotype approaches may possess much higher power than single-SNP statistical tests. Both high quality haplotypes and genotypes may be available for analysis given the development of next generation sequencing technologies and haplotype assembly algorithms.
As generally it is unknown whether genotypes or haplotypes are more relevant for identifying an association, we propose to use both of them with the purpose of preserving high power under both genotype and haplotype disease scenarios. We suggest two approaches for a combined association test and investigate the performance of these two approaches based on a theoretical model, population genetics simulations and analysis of a real data set.
Based on a theoretical model, population genetics simulations and analysis of a central corneal thickness (CCT) Genome Wide Association Study (GWAS) data set we have shown that combined genotype and haplotype approach has a high potential utility for applications in association studies.
[show abstract][hide abstract] ABSTRACT: Purpose: Three susceptibility loci for primary angle closure glaucoma (PACG) were recently identified; PLEKHA7 rs11024102, COL11A1 rs3753841, and rs1015213 located in the intergenic region between PCMTD1 and ST18. The purpose of this study was to investigate the associations of these loci with the ocular biometric parameters, anterior chamber depth (ACD) and axial-length (AL). Methods: Genotype and ocular biometric data were available for 4 population-based studies including 3 from Singapore (Singapore Chinese Eye Study, Singapore Malay Eye Study, and Singapore Indian Eye Study) and one from China (Beijing Eye study) exceeding 7,000 participants. ACD and AL were measured using the IOLMaster (Carl Zeiss Meditec, Dublin, CA) for the Singapore cohorts; and optical low coherence reflectometry (Lenstar900® Optical Biometer, Haag-Streit, Switzerland) for the Beijing cohort. Five readings were obtained for each participant and the average computed. Analysis was excluded from any eye which was pseudophakic or aphakic. Results: ACD measurements and genotype data of the three loci were available for 7245, 7243 and 7239 subjects respectively. We noted nominal evidence of association between SNP rs1015213 (PCMTD1-ST18) and a shallower ACD when all data were meta-analyzed (β=-0.033, P=0.021). However, when multiple testing was considered, the observation was non-significant. There was no association between ACD and rs11024102 (PLEKHA7) or rs3753841 (COL11A1). We did not observe significant associations between AL and any of the three SNPs. Conclusion: The lack of association between the PACG susceptibility loci with ACD or AL suggests that predilection to PACG may be mediated by factors other than shallow anterior chamber or short eyeball length.
[show abstract][hide abstract] ABSTRACT: To identify subgroups of primary angle-closure suspects (PACS) based on anterior segment optical coherence tomography (AS-OCT) and biometric parameters.
We evaluated 243 PACS subjects in the primary group and 165 subjects in the validation group.
Participants underwent gonioscopy and AS-OCT (Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure AS-OCT parameters. An agglomerative hierarchical clustering method was first used to determine the optimum number of parameters to be included in the determination of subgroups. The best number of subgroups was then determined using Akaike Information Criterion (AIC) and Gaussian Mixture Model (GMM) methods.
Subgroups of PACS.
The mean age of the subjects was 64.8 years, and 65.02% were female. After hierarchical clustering, 1 or 2 parameters from each cluster were chosen to ensure representativeness of the parameters and yet keep a minimum of redundancy. The parameters included were iris area, anterior chamber depth (ACD), anterior chamber width (ACW), and lens vault (LV). With the use of GMM, the optimal number of subgroups as given by AIC was 3. Subgroup 1 was characterized by a large iris area, subgroup 2 was characterized by a large LV and a shallow ACD, and subgroup 3 was characterized by elements of both subgroups 1 and 2. The results were replicated in a second independent group of 165 PACS subjects.
Clustering analysis identified 3 distinct subgroups of PACS subjects based on AS-OCT and biometric parameters. These findings may be relevant for understanding angle-closure pathogenesis and management.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
[show abstract][hide abstract] ABSTRACT: We determined the accuracy of the inferior > superior > nasal > temporal (ISNT) neuroretinal rim area rule and its variants in adult Asian populations, and evaluated whether disc area impacts its performance characteristics.
Participants in the Singapore Malay Eye Study (SiMES) and Singapore Indian Eye Study (SINDI) underwent standardized ocular examinations, including optic disc imaging with the Heidelberg retinal tomograph (HRT). Glaucoma was defined using the ISGEO criteria. HRT rim areas in the superior, inferior, nasal, and temporal quadrants were quantified. We determined sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of violating the ISNT rule and 4 variants (I > S > T, I > S, I > T, and combined I > T and S > T). The influence of disc area was analyzed with multivariate marginal logistic regression.
There were 6112 participants (mean age: 57.6 ± 10.3 years). Glaucoma was present in 194 individuals (3.2%). Among 11,840 eyes, 232 (93.2%) of 249 glaucomatous eyes and 9768 (84.3%) of 11,591 nonglaucomatous eyes, violated the ISNT rule. The ISNT rule had highest sensitivity (93.5%), but lowest specificity (15.7%); I > T had highest specificity (98.2%), but low sensitivity (7.4%). For all variants, PPVs were low (2.1%-8.4%) and NPVs were high (97.9-99.1%). Larger disc area was associated with reduced specificity for the ISNT rule (P < 0.001), and reduced sensitivity (P = 0.01) and increased specificity for I > S > T (P < 0.05). PPV increased (P < 0.05) and NPV decreased (P < 0.001) with increasing disc area.
The ISNT rule based on HRT has high sensitivity, and the I > T, S > T, and combined I > T and S > T variants have high specificity. Disc area influences sensitivity, specificity, PPV, and NPV of the ISNT rule and its variants.
The high sensitivity of the ISNT rule, and high specificities of its variants, may have potential utility when used in combination with other HRT algorithms for glaucoma assessment.
[show abstract][hide abstract] ABSTRACT: Purpose: 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 free from glaucoma, aged between 40 and 80 years 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 effect 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], and iris area [IA], 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. Of these subjects, 64.3% were female, and the mean age of subjects (± 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), trabecular-iris space area (TISA-500, β=-4.513, ρ<0.001), IA (β=-2.796, ρ<0.001), and ITDMR (β=6.573, ρ<0.001). PD-change was independently associated with ACD (β=0.256, ρ<0.001), IA (β=-1.507, ρ<0.001), IB (β=0.630, ρ=0.011) and ITDMR (β=3.124, ρ<0.001).
Conclusions: Among normal adult Chinese eyes, SPC was associated with larger baseline PDs. Larger baseline PDs and greater PD changes form dark to light were observed in deeper ACD with smaller iris cross-sectional areas and thicker irides.
[show abstract][hide abstract] ABSTRACT: Purpose: To compare differences in retinal vascular caliber (RVC) between fellow eyes with glaucoma of asymmetric severity.
Methods: Subjects enrolled had: a) an eye diagnosed with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) or primary angle closure glaucoma (PACG) while the other eye was normal, b) both eyes with POAG, NTG or PACG but difference in vertical cup-disc ratio (VCDR) between eyes was > 0.2, or c) both eyes with POAG, NTG or PACG but difference in Humphrey visual field (HVF) mean deviation (MD) between eyes was > 6.0 dB.
Results: Among 158 subjects arteriolar caliber for glaucoma eyes was 131.5 ± 17.8 µm vs. 141.6 ± 18.8 µm in fellow eyes with milder disease (p<0.001). Eyes with worse disease had > VCDR (0.9 + 0.1 vs. 0.7 + 0.1, p < 0.001), and > HVF MD (-18.5 + 8.6 vs. -6.6 + 5.6, p < 0.001). Venular caliber for eyes with worse disease was 201.0 ± 21.4 µm vs. 211.7 ± 25.3 µm in eyes with mild disease (p<0.001). This relationship held in clustered linear regression models adjusted for age, gender, and vascular risk factors, with RVC narrower in eyes with worse disease vs. mild disease. Arteriolar calibers for worse vs. mild disease were 112.8 µm vs. 122.9 µm respectively (p<0.001) and the venular calibers for worse vs. mild disease were 201.7 µm vs. 212.4 µm respectively (p<0.001).
Conclusions: In glaucoma with asymmetric severity between fellow eyes, retinal vascular narrowing is more pronounced in the eye with more severe glaucoma.