Six-Year Incidence and Risk Factors for Primary Open-Angle Glaucoma and Ocular Hypertension: The Singapore Epidemiology of Eye Diseases Study.

OBJECTIVE: To determine the incidence and risk factors for primary open-angle glaucoma (POAG) and ocular hypertension (OHT) in a multiethnic Asian population. DESIGN: Population-based cohort study. PARTICIPANTS: The Singapore Epidemiology of Eye Diseases study included 10 033 participants in the baseline examination between 2004 and 2011. Of those, 6762 (response rate = 78.8%) participated in the 6-year follow-up visit between 2011 and 2017. METHODS: Standardized examination and investigations were performed, including slit lamp biomicroscopy, intraocular pressure (IOP) measurement, pachymetry, gonioscopy, optic disc examination and static automated perimetry. Glaucoma was defined according to a combination of clinical evaluation, ocular imaging (fundus photo, visual field, and OCT) and criteria given by International Society of Geographical and Epidemiological Ophthalmology. OHT was defined on the basis of elevated IOP over the upper limit of normal; i.e., 20.4 mmHg, 21.5 mmHg, and 22.6 mmHg for the Chinese, Indian, and Malay cohort respectively, without glaucomatous optic disc change. MAIN OUTCOME MEASURES: Incidence of POAG, OHT, and OHT progression. RESULTS: The overall 6-year age-adjusted incidences of POAG and OHT were 1.31% (95% confidence interval [CI], 1.04-1.62) and 0.47% (95% CI, 0.30-0.70). The rate of progression of baseline OHT to POAG at 6 years was 5.32%. Primary open-angle glaucoma incidence was similar (1.37%) in Chinese and Indians and lower (0.80%) in Malays. Malays had higher incidence (0.79%) of OHT than Indians (0.38%) and Chinese (0.37%). Baseline parameters associated with higher risk of POAG were older age (per decade: odds ratio [OR], 1.90; 95% CI, 1.54-2.35; P < 0.001), higher baseline IOP (per mmHg: OR, 1.20; 95% CI, 1.12-1.29; P < 0.001) and longer axial length (per mm: OR, 1.22; 95% CI, 1.07-1.40, P = 0.004). CONCLUSION: Six-year incidence of POAG was 1.31% in a multiethnic Asian population. Older age, higher IOP, and longer axial length were associated with higher risk of POAG. These findings can help in future projections and guide public healthcare policy decisions for screening at-risk individuals. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Use of artificial intelligence in forecasting glaucoma progression.

Artificial intelligence (AI) has been widely used in ophthalmology for disease detection and monitoring progression. For glaucoma research, AI has been used to understand progression patterns and forecast disease trajectory based on analysis of clinical and imaging data. Techniques such as machine learning, natural language processing, and deep learning have been employed for this purpose. The results from studies using AI for forecasting glaucoma progression however vary considerably due to dataset constraints, lack of a standard progression definition and differences in methodology and approach. While glaucoma detection and screening have been the focus of most research that has been published in the last few years, in this narrative review we focus on studies that specifically address glaucoma progression. We also summarize the current evidence, highlight studies that have translational potential, and provide suggestions on how future research that addresses glaucoma progression can be improved.

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial.

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.

Referenced scans improve the repeatability of optical coherence tomography angiography measurements in normal and glaucoma eyes.

AIM: To compare the repeatability of peripapillary perfusion density and flux index measurements on referenced and non-referenced optical microangiography (OMAG) scans in normal, glaucoma suspect and glaucoma eyes. METHODS: In a cross-sectional study, 48 eyes (33 subjects) underwent three repeat, non-referenced peripapillary OMAG scans in the same session and 43 eyes (25 subjects) underwent three referenced peripapillary OMAG scans. In the referenced scan group, repeat scans (second and the third scan) were acquired exactly on the baseline (first) scan using the 'track to prior scan' option on the device. Repeatability estimates of the mean and four-sector (temporal, superior, nasal and inferior) OMAG measurements on the non-referenced and referenced scans were assessed using within-subject coefficient of repeatability (CRw) and variation (CVw). RESULTS: CRw (%) of peripapillary perfusion density measurements (range: 2.0-4.1) on non-referenced scans were significantly higher than that on referenced scans (range: 1.4-2.7). CVw (%) on non-referenced and referenced scans ranged from 1.7 to 3.1 and from 1.2 to 2.1, respectively . CRw of flux index on non-referenced and referenced scans ranged from 4.4 to 5.8 and from 3.6 to 4.8, respectively. CVw on non-referenced and referenced scans ranged from 4.1 to 5.2 and from 3.3 to 4.5, respectively. CONCLUSIONS: Repeatability estimates of OMAG measurements were better on referenced scans compared with non-referenced scans. Perfusion density measurements had lower variability than flux index. OCTA-measured perfusion density of referenced scans is preferable for monitoring vascular change in glaucoma.

A Comparison of the Visual Field Parameters of SITA Faster and SITA Standard Strategies in Glaucoma.

PURPOSE: To compare the visual field (VF) parameters of the new Swedish Interactive Thresholding Algorithm (SITA), SITA Faster (SFR) with that of SITA Standard (SS) on the Humphrey Field Analyzer. METHODS: Ninety-seven eyes of 97 subjects (63 glaucoma, 26 glaucoma suspects, and 8 normal eyes) underwent VF examination with SFR and SS strategies on the same day in random order. Agreement in VF parameters between SFR and SS strategies was assessed by Bland and Altman plots. In addition, some subjects underwent a second VF examination with SFR strategy to evaluate its test-retest variability. RESULTS: The median test duration of SS strategy was 6 minutes 14 seconds, whereas SFR was 2 minutes 49 seconds (55% shorter, P<0.001). Median mean deviation (-7.3 vs. -7.6 dB, P=0.73) and VF index (88 vs. 88%, P=0.32) were similar between the 2 strategies, whereas pattern standard deviation was significantly higher (4.8 vs. 4.7 dB, P=0.01) with SS strategy. Overall average threshold sensitivity and Garway-Heath sector-wise threshold sensitivities were similar between the 2 strategies except for the nasal sector where SFR strategy had higher sensitivity (26 vs. 25 dB, P=0.02). Bland-Altman plots showed the mean difference in all VF parameters between the SS and SFR strategies were small (ranging from -1.0 dB for the nasal sector to -0.01 dB for superotemporal sector sensitivity). The test-retest variability of VF parameters with SFR strategy was low. CONCLUSIONS: VF parameters with SFR showed good agreement with that of SS strategy. This, combined with low test-retest variability, suggests that SFR can be considered for diagnosis and monitoring of glaucoma.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

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.

The prevalence and types of glaucoma in an urban Indian population: the Singapore Indian Eye Study.

PURPOSE: To determine the prevalence and types of glaucoma in an urban Singaporean Indian population. METHODS: The Singapore Indian Eye Study (SINDI) was a population-based, cross-sectional survey that examined 3400 (75.6% response) persons aged 40 to 80 years. Participants underwent a standardized examination including slit-lamp biomicroscopy, Goldmann applanation tonometry, and dilated optic disc assessment. Participants suspected to have glaucoma also underwent visual field examination (24-2 SITA standard, Humphrey Visual Field Analyzer II), gonioscopy, and repeat applanation tonometry. Glaucoma was defined according to International Society for Geographical and Epidemiologic Ophthalmology criteria. RESULTS: Of the 3400 participants, 78 (2.29%) had diagnosed glaucoma, giving an age-standardized prevalence of 1.95% (95% confidence interval [CI], 1.5%-2.5%). The age-standardized prevalence of primary open-angle glaucoma (POAG) was 1.25% (95% CI, 0.89%-1.73%), primary angle-closure glaucoma (PACG) 0.12% (95% CI, 0.04%-0.33%), and secondary glaucoma 0.55% (95% CI, 0.35%-0.86%). The mean IOP among the participants in the normal group in the study population was 15.6 ± 2.6 mm Hg and 17.7 ± 6.1 mm Hg in subjects with glaucoma (P = 0.003). The mean central corneal thickness (CCT) in the normal study population was 540.31 ± 33.79; the mean CCT in subjects with POAG (529.8 ± 30.8 µm) was statistically different from the normal study group (P = 0.003). CONCLUSIONS: The prevalence of glaucoma among Singaporean Indians 40 years of age and older in Singapore was 1.95%, approximately half that of the Chinese and the Malay persons in Singapore. As in other Asian studies, POAG was the main form of glaucoma accounting for nearly 60% of cases.

Differential associations of myopia with major age-related eye diseases: the Singapore Indian Eye Study.

PURPOSE: To determine the associations of myopia and axial length (AL) with major age-related eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), age-related cataract, and primary open-angle glaucoma (POAG). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 3400 Indians (75.6% response rate) aged 40 to 84 years in Singapore. METHODS: Refractive error was determined by subjective refraction, and AL was determined by noncontact partial coherence laser interferometry. Age-related macular degeneration and DR were defined from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System and Airlie House classification system, respectively. Age-related cataract was diagnosed clinically using the Lens Opacity Classification System (LOCS) III system. Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. MAIN OUTCOME MEASURES: Age-related macular degeneration, DR, age-related cataract, and POAG. RESULTS: Myopic eyes (spherical equivalent [SE] <-0.5 diopter [D]) were less likely to have AMD (early plus late AMD) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.79) or DR (OR, 0.68; 95% CI, 0.46-0.98) compared with emmetropic eyes; each millimeter increase in AL was associated with a lower prevalence of AMD (OR, 0.76; 95% CI, 0.65-0.89) and DR (OR, 0.73; 95% CI, 0.63-0.86). Myopic eyes were more likely to have nuclear (OR, 1.57; 95% CI, 1.13-2.20) and posterior subcapsular (OR, 1.73; 95% CI, 1.10-2.72) cataract, but not cortical cataract (P = 0.64); each millimeter increase in AL was associated with a higher prevalence of posterior subcapsular cataract (PSC) (OR, 1.29; 95% CI, 1.07-1.55), but not nuclear (P = 0.77) or cortical (P = 0.39) cataract. Eyes with high myopia (SE <-6.0 D) were more likely to have POAG (OR, 5.90; 95% CI, 2.68-12.97); each millimeter increase in AL was associated with a higher prevalence of POAG (OR, 1.43; 95% CI, 1.13-1.80). CONCLUSIONS: Myopic eyes are less likely to have AMD and DR but more likely to have nuclear cataract, PSC, and POAG. The associations of myopia with AMD, DR, and POAG are mostly explained by longer AL. However, the association between myopia and nuclear cataract is explained by lens refraction rather than AL.

Effect of prophylactic laser iridotomy on corneal endothelial cell density over 3 years in primary angle closure suspects.

OBJECTIVE: To assess the effect of prophylactic laser peripheral iridotomy (LPI) on corneal endothelial cell density (ECD) and morphology in primary angle closure suspects (PACS) over 3 years. METHODS: In this prospective cohort study, subjects underwent LPI in one eye, while the fellow eye was untreated. Specular microscopy was performed at baseline and after 1 and 3 years. Central corneal ECD and morphology of both eyes were assessed using non-contact specular microscopy (Konan SP-9000LC, Konan Inc, Hyogo, Japan). RESULTS: 230 subjects completed 3-year follow-up. The mean age was 62.5 ± 8.0 years, and the majority of subjects were Chinese (92.3%) and women (75.4%). In eyes that underwent LPI, ECD was significantly lower at year 1 (2462.3, 95% CI 2414.5 to 2510.0, p<0.0001) and year 3 (2510.6, 95% CI 2462.1 to 2559.2, p=0.0006) compared with baseline (2609.1, 95% CI 2551.4 to 2666.7). There was also a significant decrease in ECD in fellow untreated eyes from baseline to year 1 (p<0.0001) and year 3 (p=0.01). The decrease in ECD at 3 years compared with the baseline in treated and untreated eyes was similar (2.1% vs 0.9%, p=0.20). CONCLUSIONS: In PACS eyes, there was decrease in ECD in LPI-treated and control eyes over 3 years, with no significant difference between groups.

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Prevalence and risk factors of diabetic retinopathy in migrant Indians in an urbanized society in Asia: the Singapore Indian eye study.

PURPOSE: To describe the prevalence of and risk factors for diabetic retinopathy (DR) in Indian persons living in a newly urbanized society in Asia. DESIGN: Population-based study. PARTICIPANTS: Ethnic Indians aged ≥40 years living in Singapore. METHODS: The Singapore Indian Eye Study was conducted between 2007 and 2009. All participants underwent an extensive ophthalmic examination, including retinal photographs obtained after pupil dilation. These images were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetes was defined as hemoglobin A1c level of ≥6.5%, use of diabetic medication, or a physician diagnosis of diabetes. Risk factors were measured using questionnaires, clinical assessments, or laboratory tests. MAIN OUTCOME MEASURES: Any DR, diabetic macular edema (DME), or vision-threatening DR (VTDR). RESULTS: Among the 3400 participants, the age-standardized prevalence was 33.6% (95% confidence interval [CI], 31.4-35.8) for diabetes and 10.5% (95% CI, 9.3-11.8) for DR. Among those with diabetes only, the age-standardized prevalence was 30.4% (95% CI, 26.5-34.8) for any DR, 7.2% (95% CI, 5.3-9.7) for DME, and 7.1% (95% CI, 5.4-9.5) for VTDR. In multivariate analysis, independent risk factors for any DR were younger age (odds ratio [OR], 0.98; 95% CI, 0.96-1.00, per year increase), longer diabetes duration (OR, 1.09; 95% CI, 1.07-1.11 per year increase), higher hemoglobin A1c (OR, 1.23; 95% CI, 1.13-1.34 per percent increase), higher systolic blood pressure (OR, 1.01; 95% CI, 1.00-1.02 per 1-mmHg increase), lower diastolic blood pressure (OR, 0.97; 95% CI, 0.96-0.99 per 1-mmHg increase), history of previous stroke (OR, 2.16; 95% CI, 1.12-4.16), and insulin treatment (OR, 2.99; 95% CI, 1.84-4.87). Similar independent risk factors, except for blood pressure, were found for VTDR. Additionally, persons with lower income and living in smaller houses were associated with VTDR. CONCLUSIONS: One in 3 migrant Indians living in newly urbanized Asian societies have diabetes and 1 in 10 has DR. This is similar to rates reported in Western populations and significantly higher than those reported in India.

Variation in prevalence of myopia between generations of migrant indians living in Singapore.

PURPOSE: To assess the influence of factors related to migration and acculturation on myopia in migrant Indians in Singapore. DESIGN: Population-based cross-sectional study. METHODS: A total of 3400 Singaporean Indians (75.6% response rate) aged over 40 years participated in this study. Information regarding country of birth, migration age, and language of interview were collected from interviews. Indians born outside of Singapore were defined as "first-generation" immigrants, while Indians born in Singapore were defined as "second-generation (or higher)" immigrants. Refraction was determined by autorefraction and refined by subjective refraction. Ocular biometry including axial length (AL), anterior chamber depth (ACD), and corneal radius (CR) were measured by partial coherence interferometry. Myopia and high myopia were defined as spherical equivalents (SE) of less than -0.5 diopter (D) for myopia, and < -5 D for high myopia, respectively. RESULTS: The prevalence of myopia (30.2% vs 23.4 %) and high myopia (4.8% vs 2.5%) were higher in second-generation immigrants compared with first-generation immigrants. Second-generation immigrants had longer AL (23.50 mm vs 23.37 mm, P = .004) than first-generation immigrants after multivariate adjustment. The excess prevalence of myopia was reduced by 37.5% but remained statistically significant (P = .02) after further controlling for educational level. Among first-generation immigrants, those migrating to Singapore before the age of 21 had significantly higher prevalence of myopia (odds ratio [OR]: 1.85; 95% confidence interval [CI]: 1.32, 2.59) and longer AL (regression coefficient: 0.27; 95% CI: 0.11, 0.43) than those migrating after 21 years of age. Also, first-generation immigrants interviewed in English had higher prevalence of myopia (OR: 1.46; 95% CI: 1.00, 2.17) than their non-English-interviewed counterparts. CONCLUSIONS: The prevalence of myopia among second-generation (or higher) Indian immigrants in Singapore is higher than first-generation immigrants. Country-specific environmental factors may be important for the increasing prevalence of myopia in Asia.

The impact of cataract, cataract types, and cataract grades on vision-specific functioning using Rasch analysis.

PURPOSE: To determine the impact of cataracts and their types and grades on vision-specific functioning. DESIGN: Prospective population-based cross-sectional study. METHODS: The Singapore Indian Eye Study examined 3400 of 4497 (75.6% response rate) ethnic Indians 40 years of age and older living in Singapore. Three thousand one hundred sixty-eight (93.2%) fulfilled inclusion criteria with complete information for final analysis. Cataracts were assessed on slit-lamp examination and were graded according to the Lens Opacity Classification System III. Vision-specific functioning scores were explored with the Visual Function scale, validated using Rasch analysis. RESULTS: Two hundred sixty-nine (8.5%) and 740 (23.4%) of the study participants had unilateral and bilateral cataracts, respectively, and 329 (10.4%), 800 (25.2%), and 128 (4.1%) participants had nuclear, cortical, and posterior subcapsular (PSC) cataracts, respectively. In multivariate linear regression models, the presence of bilateral rather than unilateral cataract (ß = -0.12; 95% confidence interval, -0.20 to 0.00) was associated independently with poorer vision-specific functioning, even after adjusting for undercorrected refractive error (ß = -0.11; 95% confidence interval, -0.21 to 0.00). Bilateral nuclear, cortical, and PSC cataracts also were associated with poorer vision-specific functioning (ß = -0.31, -0.15, and -1.15, respectively), with combinations of them having even greater impact. Significantly poorer vision-specific functioning occurred at Lens Opacity Classification System grades 4 (nuclear opalescence), 5 (nuclear color), 3 (cortical), and 1 (PSC) or higher. CONCLUSIONS: People with bilateral but not unilateral cataracts experience difficulty with performing vision-specific daily activities independent of refractive error, with PSC cataracts and cataract combinations having the greatest impact. Cataract types cause poorer vision-specific functioning beginning at different severity grades.

Determinants of lens vault and association with narrow angles in patients from Singapore.

PURPOSE: To describe the distribution and determinants of lens vault and to investigate the association of lens vault with narrow angles. DESIGN: Prospective cross-sectional study. METHODS: Phakic subjects 50 years and older were evaluated at a primary healthcare clinic with gonioscopy, partial laser interferometry, and anterior segment optical coherence tomography (AS-OCT). Narrow angles were defined as posterior trabecular meshwork not visible for ≥2 quadrants on non-indentation gonioscopy. Lens vault was defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs on horizontal AS-OCT scans. Analysis of covariance, multivariate logistic regression, and area under the receiver operating characteristic curves (AUC) were performed. RESULTS: Of the 2047 subjects recruited, 582 were excluded because of poor image quality or inability to locate scleral spurs, leaving 1465 subjects for analysis. Eyes with narrow angles had greater lens vault compared to eyes with open angles (775.6 µm vs 386.5 µm, P < .0001). Women had significantly greater lens vault than men (497.28 µm vs 438.56 µm, P < .001), and lens vault increased significantly with age (P for trend <.001). Adjusted for age and sex, significant associations with greater lens vault were shorter axial length, shallower anterior chamber depth(ACD), higher intraocular pressure, and more hyperopic spherical equivalent (all P < .001). On multivariate analysis, subjects with lens vault >667.6 µm were more likely to have narrow angles (OR 2.201, 95% CI: 1.070-4.526) compared to those with lens vault ≤462.7 µm. The AUC for lens vault (0.816) and ACD (0.822) for detecting narrow angles were similar (P = .582). CONCLUSIONS: Lens vault was independently associated with narrow angles and may be useful in screening to detect eyes with narrow angles.

Changes in anterior segment morphology after laser peripheral iridotomy: an anterior segment optical coherence tomography study.

PURPOSE: Novel anterior segment optical coherence tomography (ASOCT) parameters associated with angle closure include anterior chamber area (ACA), anterior chamber volume (ACV), anterior chamber width (ACW), lens vault (LV), iris thickness (IT), iris area (I-area), and iris curvature (I-curv). We aimed to investigate changes in these parameters after laser peripheral iridotomy (LPI) in a cohort of primary angle-closure suspects (PACS). DESIGN: Prospective observational study. PARTICIPANTS AND CONTROLS: A total of 176 PACS aged ≥ 50 years who underwent LPI in 1 eye. METHODS: We analyzed ASOCT images (Visante, Carl Zeiss Meditec, Dublin, CA) from all subjects using customized software before and 1 week after LPI. Multivariate linear regression analysis was performed for predictors of percentage change in mean angle opening distance (AOD750). MAIN OUTCOME MEASURES: Change in ASOCT parameters after LPI. RESULTS: The mean age of participants was 63 ± 7.3 years. The majority of subjects were Chinese (95.5%) and women (76.7%). Mean angle width (modified Shaffer grade) changed from 0.68 ± 0.54 at baseline to 1.76±0.69 after LPI (P<0.001) with a corresponding increase in mean AOD500 (0.12 vs. 0.19 mm, P<0.001), trabecular iris surface area (TISA500, 0.06 vs. 0.08 mm(2), P<0.001), and angle recess area (ARA, 0.13 vs. 0.17 mm(2), P<0.001). Mean ACA (15.0 vs. 16.0 mm(2), P<0.001) and ACV (91.6 vs. 103.0 mm(3), P<0.001) increased significantly after LPI, but there was no change in ACW, anterior chamber depth (ACD), or LV. Mean I-curv was reduced (0.375 vs. 0.18 mm, P<0.001) after LPI, but there was no significant change in IT or I-area. After multivariate analysis, mean LV (ß = 0.286, P = 0.001), mean IT at 2000 µm (IT2000, ß = 0.172, P = 0.034), and intraocular pressure (ß = 0.159, P = 0.042) at baseline were found to be associated with ΔAOD750. CONCLUSIONS: This study confirms that LPI results in a significant increase in the angle width in PACS. The ACA and ACV increased after LPI, but there was no change in ACD, ACW, LV, IT, or I-area. The increase in ACA/ACV was mainly due to decreased I-curv after LPI.

Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations.

Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent. We have followed up on all suggestive signals of association with CCT (P < 10(-4)) from the previously reported meta-analysis comprising Indians and Malays in a sample of Chinese individuals (n= 2681). In the combined sample (n= 7711), strong evidence of association was observed at four novel loci: IBTK on chromosome 6q14.1; CHSY1 on chromosome 15q26.3; and intergenic regions on chromosomes 7q11.2 and 9p23 (8.01 × 10(-11) < λ(GC) corrected P(meta) < 8.72 × 10(-8)). These four new loci explain an additional 4.3% of the total CCT variance across the sample cohorts over and above that of previously identified loci. We also extend on a previous finding at a fifth locus (AKAP13) where a new single-nucleotide polymorphism (rs1821481, P(meta) = 9.99 × 10(-9)) was found to be significantly more informative compared with the previously reported rs6496932 (P(meta) = 3.64 × 10(-5)). Performing association analysis in Asians may lead to the discovery of ethnic-specific genes that control CCT, offering further mechanistic insights into the regulation of CCT. In addition, it may also provide several candidate genes for interrogation for POAG, keratoconus and possible racial/ethnic variations.

Risk of acute angle closure and changes in intraocular pressure after pupillary dilation in Asian subjects with narrow angles.

OBJECTIVE: To evaluate the risk of primary acute angle closure (AAC), changes in intraocular pressure (IOP), and associated risk factors after pupil dilation in Asian subjects with narrow angles (primary angle-closure suspects [PACS]). DESIGN: Prospective clinical study. PARTICIPANTS: A total of 471 subjects aged more than 50 years with narrow angles in Singapore. METHODS: This study was part of a prospective trial of PACS. Subjects underwent a detailed ophthalmic evaluation including gonioscopy, biometry, pachymetry, and ultrasound biomicroscopy. All subjects underwent pupil dilation with 1% tropicamide eye drops at the baseline visit, before any laser or medical intervention. Intraocular pressure was measured using Goldmann applanation tonometry by the same observer before and 1 hour after pupil dilation. A dose of oral acetazolamide was given before the patient left the clinic. MAIN OUTCOME MEASURES: Intraocular pressure before and after dilation, and an AAC event. RESULTS: The mean age of the 471 subjects was 63.0 ± 6.9 years (mean ± standard deviation); 75.4% were women, and 92.8% were Chinese. Of the 471 participants, 3 (0.64%; 95% confidence interval [CI], 0.13-1.85) developed AAC within 6 hours of dilation despite pretreatment with oral acetazolamide. Twenty-two subjects (4.67%; 95% CI, 2.95-6.99) showed a postdilation increase in IOP of ≥ 5 mmHg in either eye, 6 subjects (1.27%; 95% CI, 0.47-2.75) had an IOP increase of ≥ 8 mmHg in either eye, and 4 subjects (0.85%; 95% CI, 0.23-2.16) had a postdilation IOP of >25 mmHg in either eye. Narrower gonioscopic angle width, that is, having a lower mean gonioscopic modified Shaffer grading (coefficient ß -0.51; standard error 0.19; P=0.01), and predilation IOP level (coefficient ß -0.17; standard error 0.04; P < 0.001) were significant risk factors for IOP increase after dilation in multivariate linear regression analysis. CONCLUSIONS: The risk of AAC among Asian subjects with narrow angles was low after pupillary dilation with tropicamide and oral acetazolamide prophylaxis. The presence of narrower angle width by gonioscopy was the only clinical parameter identified for a significant IOP increase after pupil dilation.

Independent impact of area-level socioeconomic measures on visual impairment.

PURPOSE: It is known that a person's socioeconomic status (SES; individual-level SES) is closely correlated with his or her degree of visual impairment. Whether there is an independent relationship between area-level measures of SES (e.g., living in a lower SES environment) and visual impairment is unclear. This study describes the associations of area-level SES with visual impairment. METHODS: The authors conducted two population-based cross-sectional studies of 3280 adult Malays and 3400 adult Indians living in Singapore. Visual impairment was defined as LogMAR visual acuity >0.30 in the better-seeing eye. Area-level SES measures (e.g., proportion of people not speaking English, proportion of people with low income) were derived from the Singapore's 2000 population census. RESULTS: Increasing age and individual-level SES measures (including lower education level, lower income level, and lower occupational status) were significantly associated with increased odds of visual impairment. In analyses adjusting for age and individual-level SES measures, many area-level SES measures (e.g., higher proportion of people not using English, higher proportion of people with low income) were also significantly associated with increased odds of visual impairment. These associations were consistently observed in both Malays and Indians. CONCLUSIONS: These data suggest that not only is a person's SES, but the SES of his or her immediate community, is associated with visual impairment. Further research is needed to investigate the underlying causes of visual health disparities and to improve the eye health of communities with lower SES.

Differential association of retinal arteriolar and venular caliber with diabetes and retinopathy.

AIMS: To describe the relationship of retinal arteriolar and venular caliber with diabetes, retinopathy and hyperglycemia, in an Asian Indian population. METHODS: This was a population-based cross-sectional study of 3400 (75.6% response rate) Singapore ethnic Indians aged 40-80 years. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were obtained using a validated computer-assisted program. Diabetes mellitus was identified using standardized criteria. Diabetic retinopathy was graded based on the modified Airlie House Classification System. RESULTS: There were 980 (32.2%) participants with diabetes. Of these, 327 (33.4%) had diabetic retinopathy. After multivariate adjustment, diabetic persons had a wider CRAE (145.23µm vs 142.38µm, P<0.001). This relationship was stronger in persons without hyperlipidemia (P-interaction<0.1). Among diabetic participants, wider CRVE was related to increasing severity of retinopathy (P for trend<0.05) and this association may be altered by hypertensive status. Retinal arteriolar caliber widened with increasing glucose (P<0.001) and HbA1C (P<0.001) levels. CONCLUSIONS: In Indian adults, wider retinal arteriolar caliber is associated with diabetes and hyperglycemia, while wider retinal venular caliber is associated with diabetic retinopathy. This is consistent with white populations and confirms the differential systemic association of retinal vascular caliber in Asian Indians.

Corneal arcus is a sign of cardiovascular disease, even in low-risk persons.

PURPOSE: To examine the association of corneal arcus to cardiovascular disease (CVD) in an adult, ethnic Indian population. DESIGN: Population-based cross-sectional study. METHODS: Population-based study of ethnic South Asian Indians 40 to 80 years of age in Singapore from June 2007 through March 2009. We obtained a 75.5% response rate (3397/4497). All participants underwent standardized interview and systemic and ocular examinations, followed by nonfasting blood sampling. Corneal arcus was detected using a standardized slit-lamp examination. The main outcome measure was CVD, defined from a self-reported history of previous myocardial infarction, angina, or stroke. RESULTS: Corneal arcus, found in 1701 (50.1%) of 3397 participants, was associated with older age (odds ratio [OR], 3.07; 95% CI, 2.78 to 3.40; P < .001), male gender (OR, 2.17; 95% CI, 1.81 to 2.62; P < .001), higher levels of total cholesterol (OR, 1.14; 95% CI, 1.05 to 1.24; P = .002), hypertension (OR, 1.14; 95% CI, 1.05 to 1.24; P = .013), and cigarette smoking (OR, 1.59; 95% CI, 1.25 to 2.03; P < .001). Corneal arcus was associated with CVD (OR, 1.31; 95% CI, 1.02 to 1.7; P = .0038) independent of the above-named cardiovascular risk factors. Participants with low-risk Framingham scores were more likely to be associated with CVD if they had corneal arcus (men: OR, 2.02; 95% CI, 1.20 to 3.40; P = .008; women: OR, 2.78; 95% CI, 1.36 to 3.01; P < .001). Corneal arcus was associated with CVD independent of the Framingham score (men: Akaike information criterion, 1524.39 for Framingham Score and corneal arcus vs 1527.38 for Framingham Score alone; women: 1000.14 vs 1003.54, respectively). CONCLUSIONS: Corneal arcus is associated with CVD, independent of risk factors in ethnic Indian adults, even in those at low risk for vascular disease.