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Purpose: We hypothesized that the effect of blood lipid-related metabolites on primary open-angle glaucoma (POAG) would differ according to specific lipoprotein particles and lipid sub-fractions. We investigated the associations of blood levels of lipoprotein particles and lipid sub-fractions with POAG., Design: Cross-sectional study., Participants: Individuals recruited for the baseline visit of the population-based Singapore Epidemiology of Eye Disease study (n = 8503)., Methods: All participants underwent detailed standardized ocular and systemic examinations. A total of 130 blood lipid-related metabolites were quantified using a nuclear magnetic resonance metabolomics platform. The analyses were conducted in 2 stages. First, we investigated whether and which lipid-related metabolites were directly associated with POAG using regression analyses followed by Bayesian network modeling. Second, we investigated if any causal relationship exists between the identified lipid-related metabolites, if any, and POAG using 2-sample Mendelian randomization (MR) analysis. We performed genome-wide association studies (GWAS) on high-density lipoprotein (HDL) 3 cholesterol (after inverse normal transformation) and used the top variants associated with HLD3 cholesterol as instrumental variables (IVs) in the MR analysis., Main Outcome Measure: Primary open-angle glaucoma., Results: Of the participants, 175 (2.1%) had POAG. First, a logistic regression model showed that total HDL3 cholesterol (negatively) and phospholipids in very large HDL (positively) were associated with POAG. Further analyses using a Bayesian network analysis showed that only total HDL3 cholesterol was directly associated with POAG (odds ratio [OR], 0.72 per 1 standard deviation increase in HDL3 cholesterol; 95% confidence interval [CI], 0.61-0.84), independently of age, gender, intraocular pressure (IOP), body mass index (BMI), education level, systolic blood pressure, axial length, and statin medication. Using 5 IVs identified from the GWAS and with the inverse variance weighted MR method, we found that higher levels of HDL3 cholesterol were associated with a decreased odds of POAG (OR, 0.91; 95% CI, 0.84-0.99, P = 0.021). Other MR methods, including weighted median, mode-based estimator, and contamination mixture methods, derived consistent OR estimates. None of the routine lipids (blood total, HDL, or low-density lipoprotein [LDL] cholesterol) were associated with POAG., Conclusions: Overall, these results suggest that the relationship between HDL3 cholesterol and POAG might be causal and specific, and that dysregulation of cholesterol transport may play a role in the pathogenesis of POAG., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease., Design: Cross-sectional study., Participants: Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry., Methods: Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography., Main Outcome Measures: Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis., Results: Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm 2 /s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG., Conclusions: Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether newly identified genetic loci for primary angle-closure glaucoma (PACG) are associated with early stage angle-closure disease defined as primary angle closure suspect (PACS)., Design: Case-control study., Participants: A total of 1397 PACS patients and 943 controls of Chinese ethnicity from Singapore and 604 PACS patients and 287 controls of Indian ethnicity., Methods: The 8 PACG single nucleotide polymorphisms (SNPs; rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 son chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were genotyped by Taqman assays. The association between SNP genotypes and PACS status was measured using logistic regression. A P value of 0.006 was set to account for the testing of 8 genetic loci using a Bonferroni correction. A meta-analysis was conducted to calculate the overall P value and accompanying per-allele odds ratios for each SNP analyzed., Main Outcome Measures: Association of PACG loci with PACS status., Results: The PACS patients were significantly older in both cohorts (Chinese, P < 0.001; Indian, P = 0.002), and there were also more women (P < 0.001, both Chinese and Indian cohorts). In the Chinese cohort, significant evidence of association was noted at 3 SNPs: rs1015213 [A] in PCMTD1-ST18 (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.36-4.11; P = 0.002), rs3816415 [A] in EPDR1 (OR, 1.49; 95% CI, 1.19-1.85; P < 0.001), and rs3739821 [G] in DPM2-FAM102A (OR, 1.40; 95% CI, 1.18-1.65; P < 0.001). Only PCMTD1-ST-18 was replicated modestly in the Indian population (P = 0.056). Meta-analysis showed significant evidence of association for PCMTD1-ST-18 (OR, 1.55; 95% CI, 1.18-2.04; P = 0.002) and DPM2-FAM102A (OR, 1.27; 95% CI, 1.12-1.45; P = 0.0002)., Conclusions: In this study, 2 of 8 PACG-associated loci were associated significantly with PACS status, the earliest stage in the angle-closure glaucoma disease course. The association of these PACG loci with PACS status suggests that these loci may confer susceptibility to a narrow angle configuration., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 American Academy of Ophthalmology. All rights reserved.)

Purpose: 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., Design: Cross-sectional study., Participants: 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., Methods: 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., Main Outcome Measures: 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)., Results: 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., Conclusions: 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.)

Purpose: To evaluate the diagnostic performance of the iris-trabecular contact (ITC) index, a measure of the degree of angle-closure, using swept-source optical coherence tomography (SSOCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) in comparison with gonioscopy., Design: Prospective observational study., Participants: A total of 108 normal subjects and 32 subjects with angle-closure., Methods: The SSOCT 3-dimensional angle scans, which obtain radial scans for the entire circumference of the angle, were performed under dark conditions and analyzed using customized software by a single examiner masked to the subjects' clinical details. The ITC index was calculated as a percentage of the angle that was closed on SSOCT images. First-order agreement coefficient (AC1) statistics and area under the receiver operating characteristic curve (AUC) analyses were performed for angle-closure on the basis of the ITC index in comparison with gonioscopy., Main Outcome Measures: Angle-closure on gonioscopy was defined as nonvisibility of posterior trabecular meshwork for at least 2 quadrants. Agreement of the ITC index with gonioscopically defined angle-closure was assessed using the AC1 statistic., Results: Study subjects were predominantly Chinese (95.7%) and female (70.7%), with a mean age of 59.2 (standard deviation, 8.9) years. The median ITC index was 15.24% for gonioscopically open-angle eyes (n = 108) and 48.5% for closed-angle eyes (n = 32) (P = 0.0001). The agreement for angle-closure based on ITC index cutoffs (>35% and ≥50%) and gonioscopic angle-closure was 0.699 and 0.718, respectively. The AUC for angle-closure detection using the ITC index was 0.83 (95% confidence interval, 0.76-0.89), with an ITC index >35% having a sensitivity of 71.9% and specificity of 84.3%., Conclusions: The ITC index is a summary measure of the circumferential extent of angle-closure as imaged with SSOCT. The index had moderate agreement and good diagnostic performance for angle-closure with gonioscopy as the reference standard., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: A recent study found that a combination of 6 anterior segment optical coherence tomography (ASOCT) parameters (anterior chamber area, volume, and width [ACA, ACV, ACW], lens vault [LV], iris thickness at 750 μm from the scleral spur, and iris cross-sectional area) explain >80% of the variability in angle width. The aim of this study was to evaluate classification algorithms based on ASOCT measurements for the detection of gonioscopic angle closure., Design: Cross-sectional study., Participants: We included 2047 subjects aged ≥50 years., Methods: Participants underwent gonioscopy and ASOCT (Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure ASOCT parameters in horizontal ASOCT scans. Six classification algorithms were considered (stepwise logistic regression with Akaike information criterion, Random Forest, multivariate adaptive regression splines, support vector machine, naïve Bayes' classification, and recursive partitioning). The ASOCT-derived parameters were incorporated to generate point and interval estimates of the area under the receiver operating characteristic (AUC) curves for these algorithms using 10-fold cross-validation as well as 50:50 training and validation., Main Outcome Measures: We assessed ASOCT measurements and angle closure., Results: Data on 1368 subjects, including 295 (21.6%) subjects with gonioscopic angle closure were available for analysis. The mean (±standard deviation) age was 62.4±7.5 years and 54.8% were females. Angle closure subjects were older and had smaller ACW, ACA, and ACV; greater LV; and thicker irides (P<0.001 for all). For both, the 10-fold cross-validation and the 50:50 training and validation methods, stepwise logistic regression was the best algorithm for detecting eyes with gonioscopic angle closure with testing set AUC of 0.954 (95% confidence interval [CI], 0.942-0.966) and 0.962 (95% CI, 0.948-0.975) respectively, whereas recursive partitioning had relatively the poorest performance with testing set AUC 0.860 (95% CI, 0.790-0.930) and 0.905 (95% CI, 0.876-0.933), respectively. This algorithm performed similarly well (AUC, 0.957) in a second independent sample of 200 angle closure subjects and 302 normal controls., Conclusions: A classification algorithm based on stepwise logistic regression that used a combination of 6 parameters obtained from a single horizontal ASOCT scan identified subjects with gonioscopic angle closure>95% of the time., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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 (β = 0.286, P = 0.001), mean IT at 2000 μm (IT2000, β = 0.172, P = 0.034), and intraocular pressure (β = 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., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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 β -0.51; standard error 0.19; P=0.01), and predilation IOP level (coefficient β -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., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure., Design: Prospective, comparative study., Participants: One hundred two Chinese subjects with angle closure (consisting of primary angle closure, primary angle-closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study., Methods: All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, 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. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth [ACD] +1/2 LT) and relative LP (RLP; defined as LP/axial length [AL])., Main Outcome Measures: Lens parameters and angle closure., Results: Significant differences between angle-closure and normal eyes were found for LV (901±265 vs. 316±272 μm; P<0.001), LT (4.20±0.92 vs. 3.90±0.73 mm; P = 0.01), LT-to-AL ratio (0.18±0.04 vs. 0.16±0.03; P<0.001), ACD (2.66±0.37 vs. 2.95±0.37 mm; P<0.001), and AL (22.86±0.93 vs. 23.92±1.37 mm; P<0.001), but no significant differences were found for LP (4.76±0.51 vs. 4.90±0.54 mm; P = 0.34) or RLP (0.21±0.02 vs. 0.20±0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio [OR], 48.1; 95% confidence interval [CI], 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearson's correlation coefficient [PCC], 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2)., Conclusions: Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the characteristics of central corneal thickness (CCT) and its association with age, gender, and intraocular pressure in rural and urban South Indian populations., Design: Population-based cross-sectional study., Participants: Seven thousand seven hundred seventy-four subjects (rural-to-urban ratio, 3924:3850) aged 40 years and older were examined at a dedicated facility in the base hospital., Intervention: All subjects underwent a complete ophthalmic examination that included CCT measurements with an ultrasonic pachymeter and applanation tonometry., Main Outcome Measures: Central corneal thickness., Results: Of the 7774 subjects examined, 974 had undergone cataract surgery and were excluded. The remaining 6800 were bilaterally phakic, of which 46 were excluded (17 glaucoma subjects receiving treatment, 12 with corneal pathologic features and 17 with incomplete data) and 6754 subjects data were analyzed. The mean CCT for the population was 511.4+/-33.5 microm, and CCT in males (515.6+/-33.8 microm) was significantly (P = 0.0001) greater than females (508.0+/-32.8 microm). The CCT was significantly greater (by 18 microm) in the urban population and decreased with age in both genders (P<0.0001). The decrease per decade was 4.34 microm (95% confidence interval [CI], 3.24-5.44) in the rural population and 2.41 microm (95% CI, 1.25-3.53) in the urban population. A 100-microm increase in CCT was associated with a 1.96-mmHg increase in intraocular pressure in the rural population, versus 2.45 mmHg for every 100 microm in the urban population., Conclusions: In this population-based study, females and subjects living in a rural area had thinner corneas. A negative association with age and a positive association with intraocular pressure were seen. These findings will have implications in the diagnosis and management of glaucoma in this population., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate diurnal intraocular pressure (IOP) fluctuation in eyes with angle closure in comparison with normal subjects and to look for associated risk factors for IOP fluctuation., Design: Prospective, cross-sectional study., Participants: Ninety-eight eyes of 98 Asian subjects with angle closure (consisting of 32 primary angle-closure suspects [PACS], 34 subjects with primary angle closure [PAC], and 32 subjects with primary angle-closure glaucoma [PACG]) and 21 eyes of 21 normal control subjects., Methods: All angle-closure subjects were enrolled after laser peripheral iridotomy but before commencement of any medical or surgical treatment. Ophthalmic examination, including dynamic gonioscopy and automated perimetry, were performed, and diurnal IOP measurements were obtained using noncontact air-puff tonometry at hourly intervals between 8:00 am and 5:00 pm. Mean diurnal IOP, peak diurnal IOP, trough IOP, and IOP fluctuation (peak IOP-trough IOP) were compared between groups. Multiple linear regression analysis was performed to study the association of IOP fluctuation with clinical variables such as age, extent of peripheral anterior synechiae (PAS), central corneal thickness, vertical cup-to-disc ratio, and pattern standard deviation (PSD) on automated perimetry., Main Outcome Measures: Mean diurnal IOP, peak IOP, and IOP fluctuation., Results: Most subjects were Chinese (89.1%) and female (61.3%). Intraocular pressure fluctuation was significantly higher in PACG (5.4+/-2.4 mmHg) and PAC (4.5+/-2.3 mmHg) subjects compared with PACS subjects (3.7+/-1.2 mmHg) and normal controls (3.8+/-1.1 mmHg; P = 0.005), with highest IOP found in the early morning. The combined PACG and PAC group had more than twice the risk (odds ratio, 2.38; 95% confidence interval, 1.1-5.1; P = 0.025) of having IOP fluctuation of more than 3 mmHg compared with the combined PACS and normal group. Extent of PAS (Pearson's correlation coefficient, r = 0.37; P = 0.0001) and visual field PSD (r = 0.34; P = 0.0002) were found to be associated with greater IOP fluctuation., Conclusions: The PACG and PAC eyes showed diurnal IOP fluctuation of 4 to 5 mmHg, and this fluctuation was higher than in PACS subjects and normal controls. The degree of PAS and visual field loss were associated with IOP fluctuation in PAC and PACG eyes.

Objective: To determine the frequency and possible origins of calibration errors of the Goldmann applanation tonometer and to investigate intraobserver and interobserver agreement in the measurement of such calibration errors., Design: Evaluation of diagnostic test or technology., Participants: One hundred thirty-two slit-lamp-mounted Haag-Streit Goldmann tonometers (Model AT 900 C/M; Haag-Streit, Bern, Switzerland)., Methods: Calibration error testing was performed using the standard calibration error check weight bar. A single observer tested 25 instruments on 2 consecutive days. Two observers independently measured calibration errors of another 40 instruments. A single observer performed prospective testing of the remaining Haag-Streit Goldmann tonometers, 6 months after their annual calibration by the bioengineering department of the hospital. Four months later, the same observer retested the instruments that were found to be faulty earlier., Main Outcome Measure: Goldmann applanation tonometer calibration error., Results: Only 4% of Goldmann tonometers were found to be within the manufacturer's recommended calibration error tolerance (+/-0.5 mmHg) at 20 mmHg. Twenty-eight percent of instruments had calibration errors of more than +/-2 mmHg at the 20-mmHg testing level. An additional 12.12% had calibration errors of more than +/-2 mmHg at the 0- or 60-mmHg testing levels, or both. Four months after the initial testing and repair of the 53 faulty instruments, 20.75% again were found to have calibration errors of more than +/-2 mmHg at any one or more testing level(s). Intraclass correlation coefficients for intraobserver agreement at 20 mmHg were 0.57 (95% confidence interval [CI], 0.25-0.78) for positive error, 0.82 (95% CI, 0.65-0.92) for negative error, and for interobserver agreement at 20 mmHg, 0.83 (95% CI, 0.70-0.90) for positive error and 0.83 (95% CI, 0.70-0.90) for negative error., Conclusions: The authors found good agreement in measurement of Goldmann applanation tonometer calibration error. A significant number of instruments had clinically unacceptable calibration errors. A more frequent calibration error testing and automation of calibration error check is desirable., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To determine the prevalence of plateau iris in a cohort of primary angle closure suspects (PACSs) using ultrasound biomicroscopy (UBM)., Design: Cross-sectional observational study., Participants: Subjects over the age of 50 years diagnosed as PACSs., Intervention: Subjects were randomized to undergo laser peripheral iridotomy (LPI) in one eye. Ultrasound biomicroscopy was performed before and a week after LPI., Main Outcome Measures: Ultrasound biomicroscopy images were qualitatively assessed using standardized criteria. Plateau iris was defined in a quadrant by the presence of an anteriorly directed ciliary body, an absent ciliary sulcus, a steep iris root from its point of insertion followed by a downward angulation from the corneoscleral wall, presence of a central flat iris plane, and irido-angle contact. At least 2 quadrants had to fulfil the above criteria for an eye to be defined as plateau iris., Results: Two hundred five subjects were enrolled; UBM images of 167 subjects were available for analysis. Plateau iris was found in 54 of 167 (32.3%) PACS eyes after LPI. Quadrantwise analysis showed that 44 of 167 (26.3%) eyes had plateau iris in 1 quadrant, 36 (21.5%) in 2 quadrants, 16 (9.5%) in 3 quadrants, and 2 (1.2%) in all 4 quadrants. Plateau iris was most commonly observed in the superior and inferior quadrants., Conclusions: Using standardized UBM criteria, plateau iris was found in about a third of PACS eyes after LPI. Prospective longitudinal studies are required to determine the clinical significance of this finding for the management of PACSs.

Purpose: To compare the performance of the scanning peripheral anterior chamber depth analyzer (SPAC) and the modified van Herick grading system in the assessment of angle closure, using gonioscopy as the reference standard., Design: Prospective comparative study., Participants: One hundred twenty phakic subjects (53 with primary angle closure and 67 with open angles) with no history of laser or intraocular surgery., Methods: The modified van Herick grading system was used to grade the peripheral anterior chamber depth (ACD) clinically. The SPAC was used to assess ACD, and this was graded categorically as S (suspect angle closure), P (potential angle closure), or N (normal) and numerically from 1 to 12. One randomly selected eye of each subject underwent examination with the modified van Herick grading, SPAC, Goldmann applanation tonometry, optic disc examination, and gonioscopy. The SPAC measurements, modified van Herick grades (0%, 5%, 15%, 25%, 40%, 75%, and > or =100% of corneal thickness), and gonioscopy (graded as narrow or open) were correlated using the Spearman correlation coefficient. The receiver operating characteristics of the 2 methods to detect angle closure also were compared., Main Outcome Measures: Grading of ACD by the SPAC, the modified van Herick system, and gonioscopic grading of the angle., Results: The SPAC results correlated well with the modified van Herick grading system (categorical grade, r = 0.527; numerical grade, r = 0.542; P<0.0001). For eyes graded as having narrow angles by gonioscopy, the area under the curve (AUC) for SPAC categorical grade S or P was 0.790; sensitivity and specificity were 84.9% and 73.1%, respectively. For the modified van Herick grading system, using a cutoff of peripheral ACD < or = 25% corneal thickness, the AUC was 0.872 and sensitivity and specificity were 84.9% and 89.6%. Compared with gonioscopy that found 53 of 120 cases of narrow angles, the SPAC graded more eyes as having narrow angles (63/120) than the modified van Herick system (52/120)., Conclusions: The SPAC correlated well with the modified van Herick system in grading peripheral ACD. However, the SPAC appeared to overestimate the proportion of eyes with narrow angles relative to gonioscopy and the modified van Herick grading system.

Purpose: To study the intraocular pressure (IOP) changes in Sirsasana (headstand posture) done by experienced yoga practitioners and correlate the ocular biometric parameters with the IOP changes, and to screen for the prevalence of ocular hypertension in this group of subjects., Design: Prospective case observational series., Participants: Seventy-five subjects (50 Asian Indians and 25 Caucasians) from a yoga training institute volunteered for the study., Methods: All participants underwent a detailed ophthalmic examination along with ocular biometry and corneal pachymetry. Intraocular pressure was recorded using a Tonopen before, during, and after the Sirsasana. Changes were compared using the paired t test. Age, axial length, anterior chamber depth, lens thickness, corneal curvature, corneal thickness, race, and the length of time for which the practitioner was performing yoga were correlated with the induced IOP difference in a randomly selected eye using Pearson's correlation coefficient with Bonferroni correction for multiple comparisons., Main Outcome Measures: Ocular biometry and induced IOP difference., Results: The mean increase in IOP at baseline and immediately after assuming Sirsasana was 15.1+/-4.1 mmHg (R = 0.07; P = 0.999) and after 5 minutes was 15.8+/-4.6 mmHg (R = -0.25; P = 0.357). The induced increase in IOP during the posture was twice the baseline IOP. There was no correlation between age, ocular biometry, and ultrasound pachymetry when compared with the induced IOP difference. One subject (1.33%) was found to have baseline IOP of more than 21 mmHg., Conclusion: There was a uniform 2-fold increase in the IOP during Sirsasana, which was maintained during the posture in all age groups irrespective of the ocular biometry and ultrasound pachymetry. We did not demonstrate a higher prevalence of ocular hypertensives in this cohort of yoga practitioners nor did the risk factors contributing to glaucoma show any correlation with magnitude of IOP raise during the posture.

Purpose: To evaluate the changes in optic disc morphology in the first 4 months after an episode of acute primary angle closure (APAC) using stereoscopic optic disc photography and computer-assisted planimetry., Design: Prospective observational case series., Participants: Forty-seven Asian subjects with unilateral APAC who were successfully treated with laser peripheral iridotomy (LPI)., Main Outcome Measures: Cup-to-disc ratio (CDR) and optic cup and neuroretinal rim areas., Methods: Stereoscopic optic disc photographs were taken 2 and 16 weeks after LPI, and the images were analyzed by computer-assisted planimetry. The overall, quadrantic, and 30 degrees sector areas of the optic disc, CDR, and neuroretinal rim area were analyzed by 2 independent masked graders, and the mean of the readings was used to calculate changes in optic disc parameters., Results: The majority of the subjects were female (66%) and Chinese (90%), and the mean age was 67.6+/-11.2 years (range, 40-94). In APAC eyes from week 2 to week 16, the mean CDR increased from 0.56+/-0.05 to 0.59+/-0.03 (P<0.001), and the mean neuroretinal rim area decreased from 1.74+/-0.31 mm2 to 1.59+/-0.27 mm2 (P<0.001). Quadrantic and sector analysis showed preferential loss of neuroretinal rim area at the superotemporal and inferotemporal areas. There was no significant change in optic disc parameters in the fellow eyes over the study period., Conclusions: This study demonstrated changes in optic disc morphology from week 2 to week 16 after an episode of APAC. The pattern of optic nerve damage demonstrated in our study was comparable with that seen in primary open-angle glaucoma and experimental glaucoma models.