Search

Summary: Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a “five-safes” framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

Objective: To assess the association between the continuum of care of mothers and the immunization status of their 12–23 months old children. Study design: A secondary data analysis using the Myanmar Demographic and Health Survey (2015–16) data, a cross-sectional, household-based, nationally representative survey conducted during 2015–2016. Methods: We included 1669 pairs of mothers and their children in this analysis. We categorized the children into fully immunized and no/not fully immunized children and define a continuum of care (CoC) of the mother if women received antenatal care ≥ four times, delivered with skilled birth attendances, and received postnatal care within 48 h after delivery. We used the multivariable binary logistics regression using STATA version 15.1 with the survey command (svy) and reported the results by adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: The mother's CoC prevalence was 42.5%, and that of fully immunized children was 33.5%. However, only one-fifth of mothers and their children received the continuum of care services altogether. The children of mothers who received CoC were more likely to be fully vaccinated than those who did not (aOR = 1.60, 95%CI: 1.21, 2.13, P

Objective: To assess the safety of replacing the postoperative week 1 (POW1) clinic visit with a nurse-conducted telephone call., Design: Retrospective observational study that included cases from January 2019 to June 2021., Participants: Patients who had undergone uncomplicated phacoemulsification surgery with an unremarkable postoperative day 1 (POD1) examination., Methods: All patients were seen in clinic on POD1 by an ophthalmologist. They then had a telephone conversation with a nurse at POW1 and subsequently an in-person postoperative month 1 (POM1) clinic consultation with an ophthalmologist. Main outcome measure was the incidence of unexpected management changes related to cataract surgery within POM1. Data also were collected on the reasons for unscheduled patient-initiated visits, additional procedures or medications, and postoperative visual acuity worse than 6/12 at POM1., Results: Of the 20,475 patients, 541 patients (2.64%) had an unexpected management change within POM1. There were 565 patients (2.76%) who had self-initiated unscheduled visits between POD1 to POM1. There were 23 patients (0.11%) who required additional surgery within POM1 and 1 patient (0.005%) with endophthalmitis. The most common indication for additional surgical procedures was retained lens material (7 patients, 30.43%). Visual acuity was worse than 6/12 in 1,199 patients (6.22%), with the most common causes attributed to preexisting ocular conditions., Conclusions: These results suggest that replacing the POW1 visit with a nurse-conducted telephone consult for patients who have undergone uncomplicated phacoemulsification surgery and had a normal POD1 consultation is safe., Competing Interests: Footnotes and Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG)., Design: Cross-sectional multicenter study., Participants: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included., Methods: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database., Main Outcomes Measures: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG., Results: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all)., Conclusions: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

Background: Sarbecoviruses are a subgenus of Coronaviridae that mostly infect bats with known potential to infect humans (SARS-CoV and SARS-CoV-2). Populations in Southeast Asia, where these viruses are most likely to emerge, have been undersurveyed to date., Methods: We surveyed communities engaged in extractive industries and bat guano harvesting from rural areas in Myanmar. Participants were screened for exposure to sarbecoviruses, and their interactions with wildlife were evaluated to determine the factors associated with exposure to sarbecoviruses., Results: Of 693 people screened between July 2017 and February 2020, 12.1% were seropositive for sarbecoviruses. Individuals were significantly more likely to have been exposed to sarbecoviruses if their main livelihood involved working in extractive industries (logging, hunting, or harvesting of forest products; odds ratio [OR] = 2.71, P = 0.019) or had been hunting/slaughtering bats (OR = 6.09, P = 0.020). Exposure to a range of bat and pangolin sarbecoviruses was identified., Conclusion: Exposure to diverse sarbecoviruses among high-risk human communities provides epidemiologic and immunologic evidence that zoonotic spillover is occurring. These findings inform risk mitigation efforts needed to decrease disease transmission at the bat-human interface, as well as future surveillance efforts warranted to monitor isolated populations for viruses with pandemic potential., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in patients with glaucoma., Design: Clinic-based cross-sectional study., Participants: Two hundred twenty-nine patients with primary open-angle glaucoma (subdivided into 115 patients with high-tension glaucoma [HTG] and 114 patients with normal-tension glaucoma [NTG])., Methods: For 1 eye of each patient, we imaged the ONH using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 35 mmHg) achieved through ophthalmodynamometry. A 3-dimensional strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e., deformation) in each ONH. Strains in the prelaminar tissue (PLT), the retina, the choroid, the sclera, and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec). This was performed globally, then locally according to a previously published regionalization scheme., Main Outcome Measures: Associations between ONH strains and values of retinal sensitivity from visual field testing., Results: For patients with HTG, we found (1) significant negative linear associations between ONH strains and retinal sensitivity (P < 0.001; on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 decibels [dB]), (2) that high-strain regions colocalized with anatomically mapped regions of high visual field loss, and (3) that the strongest negative associations were observed in the superior region and in the PLT. In contrast, for patients with NTG, no significant associations between strains and retinal sensitivity were observed except in the superotemporal region of the LC., Conclusions: We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, patients with HTG who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend in general was less pronounced in patients with NTG, which could suggest a distinct pathophysiologic relationship between the two glaucoma subtypes., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure., Design: Multicenter, prospective study., Participants: A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included., Methods: One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500 = 0 mm and (2) TISA500 = 0 mm 2 . The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis., Main Outcome Measures: Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG., Results: The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500 = 0 mm) to 84.7% (TISA500 = 0 mm 2 ), and the specificity was 85.7% (for both AOD500 = 0 mm and TISA500 = 0 mm 2 ). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500 = 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500 = 0 mm 2 ). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574)., Conclusions: A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop a classification system of visual field (VF) abnormalities in highly myopic eyes with and without glaucoma., Design: Secondary analysis of VF data from a longitudinal cohort study., Participants: One thousand eight hundred ninety-three VF tests from 1302 eyes (825 individuals)., Methods: All participants underwent VF testing (Humphrey 24-2 Swedish interactive threshold algorithm standard program; Carl Zeiss Meditec) and detailed ophthalmic examination. A comprehensive set of VF defect patterns was defined via observation of the 1893 VF reports, literature review, and consensus meetings. The classification system comprised 4 major types of VF patterns, including normal type, glaucoma-like defects (paracentral defect, nasal step, partial arcuate defect, arcuate defect), high myopia-related defects (enlarged blind spot, vertical step, partial peripheral rim, nonspecific defect), and combined defects (nasal step with enlarged blind spot). A subset (n = 1000) of the VFs was used to evaluate the interobserver and intraobserver agreement and weighted κ values of the classification system by 2 trained readers. The prevalence of various VF patterns and their associated factors were determined., Main Outcome Measures: The classification of VF in highly myopic eyes and its associated risk factors., Results: We found that normal type, glaucoma-like defects, high myopia-related defects, and combined defects accounted for 74.1%, 10.8%, 15.0%, and 0.1% of all unique VF tests, respectively. The interobserver and intraobserver agreements were > 89%, and the corresponding κ values were 0.86 or more between readers. Both glaucoma-like and high myopia-related VF defects were associated with older age (odds ratios [ORs], 1.07 [95% confidence interval (CI), 1.04-1.10; P < 0.001] and 1.06 [95% CI, 1.04-1.10; P < 0.001]) and longer axial length (ORs, 1.65 [95% CI, 1.32-2.07; P < 0.001] and 1.37 [95% CI, 1.11-1.68; P = 0.003]). Longer axial length showed a stronger effect on the prevalence of glaucoma-like VF defects than on the prevalence of high myopia-related VF defects (P = 0.036)., Conclusions: We propose a new and reproducible classification system of VF abnormalities for nonpathologic high myopia. Applying a comprehensive classification system will facilitate communication and comparison of findings among studies., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the incidence and risk factors of primary angle-closure disease (PACD) over 6 years in a multi-ethnic Asian population., Design: Population-based, longitudinal study., Participants: The Singapore Epidemiology of Eye Diseases study is a population-based cohort study conducted among adults aged 40 years or more. The baseline examination was conducted between 2004 and 2010, and the 6-year follow-up visit was conducted between 2011 and 2017. Of 6762 participants who attended the follow-up examination, 5298 at risk for primary angle-closure glaucoma (PACG) and 5060 at risk for PACD were included for analyses., Methods: Standardized examinations including slit-lamp biomicroscopy, indentation gonioscopy, intraocular pressure (IOP) measurement, and static automated perimetry were performed. In this study, PACD includes primary angle-closure suspect (PACS), primary angle-closure (PAC), and PACG., Main Outcome Measures: The 6-year PACD incidence was evaluated among an at-risk population excluding adults with baseline glaucoma, PACS, PAC, pseudophakia at baseline or follow-up, or laser peripheral iridotomy or iridectomy at baseline visit. Logistic regression analysis adjusting for age, gender, and ethnicity was performed to evaluate associations between PACD development and demographic or ocular characteristics. Forward selection based on the Quasi-likelihood Information Criterion was used in multivariable analysis to reduce potential multicollinearity., Results: The 6-year age-adjusted PACD incidence was 3.50% (95% confidence interval [CI], 2.94-4.16). In multivariable analysis, increasing age per decade (odds ratio [OR], 1.35; 95% CI, 1.15-1.59), higher IOP (OR, 1.04; 95% CI, 1.00-1.08), and shallower anterior chamber depth (OR, 1.11; 95% CI, 1.08-1.14) at baseline were associated with higher odds of PACD, whereas late posterior subcapsular cataract (PSC) (OR, 0.60; 95% CI, 0.48-0.76) was associated with lower odds of PACD. The 6-year age-adjusted incidences of PACG, PAC, and PACS were 0.29% (95% CI, 0.14-0.55), 0.46% (95% CI, 0.29-0.75), and 2.54% (95% CI, 2.07-3.12), respectively., Conclusions: Our study showed that the 6-year incidence of PACD was 3.50%. Increasing age, higher IOP, and shallower anterior chamber were associated with a higher risk of incident PACD, whereas late PSC was associated with a lower odds of PACD. These findings can aid in future projections and formulation of health care policies for screening of at-risk individuals for timely intervention., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies., Design: Cross-sectional pooled analysis., Participants: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium., Methods: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model., Main Outcome Measures: Average RNFL thickness (in micrometers) and rim area (in square millimeters)., Results: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (β values range, 7.31-12.76 μm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 μm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 μm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 μm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, β = -2.70), diabetes (β = -0.72), higher IOP (per 1 mmHg, β = -0.07), more myopic SE (per diopter, β = -1.13), cardiovascular disease (β = -0.94), and hypertension (β = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (β = -0.019), higher IOP (β = -0.010), and more myopic SE (β = -0.025) were associated with smaller rim area (all P < 0.001)., Conclusions: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation., Design: Retrospective case study., Participants: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort., Methods: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account., Main Outcome Measures: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation., Results: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001)., Conclusions: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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 assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC)., Design: Prospective, observational study., Participants: Six hundred forty-three mainland Chinese with untreated PACS., Methods: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression., Main Outcome Measures: Six-year progression from PACS to PAC or AAC., Results: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 μm from the scleral spur (AOD 500 ; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD 500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD 500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72)., Conclusions: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON)., Design: Cross-sectional study., Subjects: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients., Methods: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects., Main Outcome Measures: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input)., Results: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set., Conclusions: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON., (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 develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans., Design: International, cross-sectional, multicenter study., Participants: A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively)., Methods: For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference., Main Outcome Measures: The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated., Results: In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level., Conclusions: The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Topic: Glaucoma is the leading cause of irreversible blindness, despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis., Clinical Relevance: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socioeconomic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions., Methods: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990, and June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (OpenGrey), and nongovernment organization reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the original studies and may include primary open-angle glaucoma (POAG), primary angle-closure-glaucoma, secondary glaucoma, or a combination thereof. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion of undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines in our study., Results: We identified 61 articles from 55 population-based studies (n = 189 359 participants; n = 6949 manifest glaucoma). Globally, more than half of all glaucoma cases were undetected previously on average in each geographical region. Africa (odds ratio [OR], 12.70; 95% confidence interval [CI], 4.91-32.86) and Asia (OR, 3.41; 95% CI, 1.63-7.16) showed higher odds of undetected glaucoma as compared with Europe. Countries with low Human Development Index (HDI; <0.55) showed a higher proportion of undetected manifest glaucoma as compared with countries of medium to very high HDI (≥0.55; all P < 0.001). In 2020, 43.78 million POAG cases were projected to be undetected, of which 76.7% were in Africa and Asia., Discussion: Undetected glaucoma is highly prevalent across diverse communities worldwide and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness resulting from glaucoma., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy., Design: Prospective observational study., Participants: Primary angle-closure suspects (PACSs) 50 to 70 years of age., Methods: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD 750 ); poor angle widening, defined as the lowest quintile of change in mean AOD 750 ; and poor angle opening, defined as residual PACS after LPI based on gonioscopy., Main Outcome Measures: Anatomic changes and predictors of angle widening and opening after LPI., Results: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD 750 (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD 750 (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening., Conclusions: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether recently identified genetic loci for primary angle-closure glaucoma (PACG) are associated with disease severity., Design: Case-control study., Participants: Eight hundred four PACG patients and 943 control participants of Chinese ethnicity from Singapore., Methods: The 8 PACG-associated single nucleotide polymorphisms (SNPs; rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) identified from genome-wide association studies were tested for association with disease severity using logistic regression adjusted for age and gender. A P value of 0.006 was set as significant after Bonferroni correction for testing of 8 loci. We also calculated the weighted genetic risk score (GRS) weighted by the estimated individual SNP effect size on PACG calculated as logarithm of the odds ratio (OR). Disease severity was based on the visual field mean deviation (MD) and classified as early to moderate (MD, >-12 dB) and severe (MD, <-20 dB)., Main Outcome Measures: Association of PACG loci with severe disease., Results: Of the 804 PACG patients, genotyping data were available for 768 individuals and included 436 with mild-to-moderate PACG and 206 with severe PACG. The PACG patients were significantly older (mean age, 64.3 ± 9.1 years vs. 56.4 ± 8.9 years; P < 0.001) and there were proportionately more women compared with control participants (58.4% vs. 49.0%; P < 0.001). Of the 8 loci investigated, we observed significant evidence of association with severe PACG at 1 SNP, namely rs3816415 in EPDR1 (OR, 2.03; 95% confidence interval [CI], 1.49-2.78; P = 1 × 10 -5 ). A higher-weighted GRS was associated significantly with severe PACG, with an OR of 3.11 (95% CI, 1.95-4.96) comparing the lowest quartile with the highest quartile., Conclusions: Our results show that EPDR1 is associated significantly with severe PACG, suggesting that it may predispose patients to more aggressive disease development. Individuals with PACG with a higher GRS were associated with a higher risk of severe PACG., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the safety of pupillary dilation in primary angle-closure suspects (PACS) with concurrent visually significant cataract (VSC), to identify risk factors associated with elevated intraocular pressure (IOP), and to describe changes in anterior segment anatomy after pupillary dilation., Design: Prospective study., Participants: Patients with PACS and VSC and no prior laser or intraocular surgery were recruited. Visually significant cataract was defined as best-corrected visual acuity ≤ 20/40 due to cataract., Methods: Subjects' eyes were dilated with 0.5% tropicamide and 0.5% phenylephrine hydrochloride. A standardized eye examination, biometry, and swept-source OCT (SS-OCT) were performed before dilation. Intraocular pressure and SS-OCT were repeated 1, 4, and 6 hours postdilation (PDH1, PDH4, and PDH6, respectively). All parameters were compared between time points before and after dilation using paired t test. Linear regression models were used to determine the risk factors associated with postdilation IOP changes., Main Outcome Measures: Change in IOP and SS-OCT parameters from baseline., Results: Seventy-eight eyes from 78 patients were included, with 78, 66, and 12 patients completing the study at PDH1, PDH4, and PDH6, respectively. Mean IOP increased from 14.8 ± 2.6 mmHg at baseline to 15.5 ± 3.5 mmHg at PDH1 (P = 0.03) and decreased to 14.9 ± 3.1 mmHg at PDH4 (P = 0.09). Four patients (5.13%) and 3 patients (3.85%) had an increase in IOP ≥ 5 mmHg at PDH1 and PDH4, respectively. Two patients (2.56%) and 1 patient (1.28%) had an increase in IOP ≥ 8 mmHg at PDH1 and PDH4, respectively. None developed acute primary angle-closure during the observation period. Almost all anterior chamber parameters showed a significant increase after dilation at PDH1 and PDH4, except lens vault and iris volume, which decreased at PDH1 and PDH4 from baseline. Increase in anterior chamber depth was negatively associated with the level of IOP elevation after dilation (P < 0.01)., Conclusions: Dilation of patients' eyes with PACS and VSC in this cohort appears to have a low risk for IOP spike. This may be associated with relaxation of the ciliary muscle leading to posterior displacement of the lens-iris diaphragm and deepening of the anterior chamber., (Published by Elsevier Inc.)

Purpose: To examine the normative profile and determinants of macular ganglion cell-inner plexiform layer (GCIPL) thickness based on spectral-domain OCT (SD-OCT) in a nonglaucoma, multi-ethnic Asian population., Design: Population-based, cross-sectional study., Participants: Ethnic Chinese, Malay, and Indian adults aged ≥40 years recruited from the Singapore Epidemiology of Eye Diseases Study., Methods: All participants underwent standardized examinations. The GCIPL thickness was measured using Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). Participants with glaucoma or poor-quality scans were excluded. Eye-specific data were used. Associations of ocular and systemic factors with GCIPL thickness parameters were investigated using multivariable linear regression with generalized estimating equation models to account for correlation between both eyes., Main Outcome Measures: GCIPL thickness., Results: A total of 4464 participants (7520 eyes) consisting of 1625 Chinese, 1212 Malay, and 1627 Indian adults contributed to this analysis. Average GCIPL thickness was 82.6±6.1 μm in Chinese, 81.5±6.8 μm in Malays, and 78.0±6.9 μm in Indians (P < 0.001 by analysis of variance). The 5th percentile limit of average GCIPL thickness was 72 μm in Chinese, 70 μm in Malays, and 67 μm in Indians. In multivariable analysis adjusting for age, gender, axial length, presence of cataract, OCT signal strength, disc area, hypertension, diabetes, and hyperlipidemia, eyes of Indians were observed to have 3.43 μm thinner GCIPL on average compared with Chinese (P < 0.001) and 3.36 μm thinner GCIPL compared with Malays (P < 0.001). In addition, older age (per decade; β = -2.51), female (β = -1.57), longer axial length (per mm; β = -1.54), and presence of chronic kidney disease (β = -1.49) were significantly associated with thinner average GCIPL (all P ≤ 0.008). Larger optic disc area (per mm 2 ; β = 0.78; P < 0.001) was associated with thicker GCIPL. These factors were consistently observed to be significant for superior and inferior hemisphere GCIPL thickness., Conclusions: GCIPL thickness profiles were significantly thinner in Indians compared with Chinese and Malays. Our findings further highlight the need of a more refined, ethnic-specific normative database for GCIPL thickness, which in turn may improve the detection and diagnosis of glaucoma in Asians., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Anterior ethmoid aneurysms are rare with 5 cases of intracranial rupture and 3 cases of life-threatening epistaxis described in recent literature. We present a case of an intracranial ruptured anterior ethmoid aneurysm treated surgically with a favorable outcome., Case Description: A 64-year-old male presenting with a headache was found to have a right frontal intracranial hemorrhage with an associated 1.5 cm length × 1.8 cm maximal width anterior ethmoidal artery aneurysm. No definitive etiology of the aneurysm was identified. The aneurysm was treated using a bifrontal craniotomy with interhemispheric microdissection, clip ligation, and resection of the aneurysm dome for pathologic analysis, which ruled out a mycotic etiology. He recovered uneventfully and returned to work with no identifiable neurologic deficit., Conclusions: Consistent with prior reports, an intracranial, anterior ethmoidal artery aneurysm can occur in isolation without an associated vascular malformation. On the basis of a literature review and this case, surgical ligation is considered effective and possibly superior over endovascular treatment due to the risk of injury to the orbital vascular supply with transarterial treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To describe variations in retinal nerve fiber layer (RNFL) thickness based on spectral-domain (SD) OCT in a multiethnic Asian population., Design: Population-based, cross-sectional study., Participants: Ethnic Chinese, Malay, and Indian adults older than 48 years without glaucoma who were recruited from the Singapore Epidemiology of Eye Diseases Study., Methods: All participants underwent standardized systemic and ocular examinations. Retinal nerve fiber layer thickness was measured using SD OCT. Participants with poor-quality scans were excluded. Linear regression models were used to investigate the associations of ocular and systemic factors with average RNFL thickness. Generalized estimating equation models were used to account for correlation between both eyes., Main Outcome Measure: Average RNFL thickness., Results: Four thousand four hundred seventy-five participants (8178 eyes) consisting of 1371 Chinese, 1303 Malay, and 1801 Indian adults contributed to this analysis. Average RNFL thickness measured was 95.7±9.6 μm in Chinese participants, 94.9±10.6 μm in Malay participants, and 87.3±10.6 μm in Indian participants (P < 0.001). Multivariate analysis adjusted for age, gender, and ethnicity revealed a reduction in RNFL thickness with increased intraocular pressure and axial length (P < 0.001 for both), as well as a diagnosis of diabetes (P = 0.04); greater RNFL thickness was associated with increased disc area (P < 0.001), signal strength (P < 0.001), and low-density lipoprotein cholesterol (P = 0.02). When these significant variables were taken into account, the average RNFL thickness of Indian participants was significantly thinner compared with Chinese participants (7.45 μm thinner on average [95% confidence interval, 6.75-8.15 μm; P < 0.001]), whereas there was no significant difference in average RNFL thickness between Malay and Chinese participants (P = 0.15)., Conclusions: Average and regional RNFL thicknesses were significantly thinner in Indian eyes compared with Chinese and Malay eyes. Results of the study highlight the need to acquire more refined normative data for the comparison of individual patients with others of similar ethnic background while accounting for ocular factors that could influence RNFL thickness. This in turn may improve the sensitivity and specificity of glaucoma detection., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Primary angle-closure glaucoma affects 20 million people worldwide. People classified as primary angle closure suspects have a higher but poorly quantified risk of developing glaucoma. We aimed to assess efficacy and safety of laser peripheral iridotomy prophylaxis against primary angle-closure glaucoma in Chinese people classified as primary angle closure suspects., Methods: In this randomised controlled trial, bilateral primary angle closure suspects aged 50-70 years were enrolled at the Zhongshan Ophthalmic Center, a tertiary specialised hospital in Guangzhou, China. Eligible patients received laser peripheral iridotomy in one randomly selected eye, with the other remaining untreated. The primary outcome was incident primary angle closure disease as a composite endpoint of elevation of intraocular pressure, peripheral anterior synechiae, or acute angle-closure during 72 months of follow-up in an intention-to-treat analysis between treated eyes and contralateral controls. This trial is registered with the ISRCTN registry, number ISRCTN45213099., Findings: Of 11 991 screened individuals, 889 individuals were randomly assigned from June 19, 2008 (889 treated and 889 untreated eyes). Incidence of the primary outcome was 4·19 per 1000 eye-years in treated eyes compared with 7·97 per 1000 eye-years in untreated eyes (hazard ratio 0·53; 95% CI 0·30-0·92; p=0·024). A primary outcome event occurred in 19 treated eyes and 36 untreated eyes with a statistically significant difference using pair-wise analysis (p=0·0041). No serious adverse events were observed during follow-up., Interpretation: Incidence of angle-closure disease was very low among individuals classified as primary angle closure suspects identified through community-based screening. Laser peripheral iridotomy had a modest, albeit significant, prophylactic effect. In view of the low incidence rate of outcomes that have no immediate threat to vision, the benefit of prophylactic laser peripheral iridotomy is limited; therefore, widespread prophylactic laser peripheral iridotomy for primary angle-closure suspects is not recommended., Funding: Fight for Sight, the Sun Yat-Sen University 5010 Project Fund, Moorfields Eye Charity, and the National Natural Science Foundation of China., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Keyhole craniotomy is a minimally invasive approach for the treatment of middle cerebral artery (MCA) aneurysms. The aim of this study was to compare the clinical outcome between supraorbital keyhole approach and pterional keyhole approach (PKA) in Chinese patients with MCA aneurysm., Methods: Consecutive patients with MCA aneurysms were reviewed between January 2013 and December 2017. Efficacy and safety between PKA and supraorbital keyhole approach were compared. Poor outcome was defined as modified Rankin Scale score of 3-6 at discharge., Results: This study enrolled 260 patients; 222 (85.4%) had ruptured aneurysm, and 183 (70.4%) received PKA. The distribution of PKA in unruptured and ruptured aneurysms showed no significant difference (P > 0.05). In subgroup analyses, PKA was more likely associated with poor outcome at discharge in patients with unruptured aneurysms (odds ratio = 5.500, 95% confidence interval = 1.013-29.850, P = 0.048), whereas approach selection was not an independent factor predicting poor outcome in patients with ruptured aneurysms (P > 0.05)., Conclusions: In a Chinese population, supraorbital keyhole approach was superior to PKA in improving outcome in patients with unruptured MCA aneurysms, but the 2 approaches showed comparable outcomes at discharge in patients with ruptured aneurysms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months., Design: Prospective, multicenter, single-masked, randomized controlled trial., Participants: Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg., Methods: Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months., Main Outcome Measures: The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events., Results: A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95% confidence interval [CI] 11.2%-27.8%, P < 0.001). The mean reduction in 24-month unmedicated MDIOP was -7.6±4.1 mmHg (mean ± standard deviation) in the HMS group and -5.3±3.9 mmHg in the NMS group (difference = -2.3 mmHg; 95% CI, -3.0 to -1.6; P < 0.001). The mean number of medications was reduced from 1.7±0.9 at baseline to 0.3±0.8 at 24 months in the HMS group and from 1.7±0.9 to 0.7±0.9 in the NMS group (difference = -0.4 medications; P < 0.001). There were no serious ocular adverse events related to the microstent, and no significant differences in safety parameters between the 2 groups., Conclusions: This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone., (Copyright © 2018 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 quantitatively determine how the reliability indices in standard automated perimetry (SAP) affect the global indices of visual field (VF) results in nonglaucomatous eyes., Design: Observational, cross-sectional study., Participants: A total of 830 adults aged 40 to 80 years, without visual impairment, glaucoma, significant cataract, and major eye diseases, were selected from the population-based Singapore Chinese Eye Study (SCES)., Methods: Study participants underwent a comprehensive and standardized ocular examination and VF assessment using a Humphrey Field Analyzer II (Carl Zeiss Meditec, Inc., Dublin, CA). The effects of the test reliability, as indicated by the false-negative (FN), false-positive (FP), and fixation loss (FL) rates, on global indices, as indicated by the mean deviation (MD) and pattern standard deviation (PSD), were analyzed with multivariable regression models., Main Outcome Measures: The MD and PSD., Results: A total of 1828 VF results from 1235 normal eyes of 830 study subjects were included in the analyses. The multivariable regression analyses adjusted for age, gender, best-corrected visual acuity, and test duration showed that at lower frequencies of false answers (<15%), FNs decreased the MD (β [change in decibels {dB} per 5% increment in false answers] = -0.71 dB; P < 0.001), whereas FPs increased the MD (β = 0.65 dB; P < 0.001). At higher frequencies (≥15%), the false answers influenced the MD to a greater extent, where the β for the associations with FN and FP rates was -1.15 and 1.26 dB, respectively (both P < 0.001). We also found that when FN rate was <15%, higher FN rate increased the PSD (β = 0.51 dB; P < 0.001), and the effect was slightly larger when FN rate was ≥15% (β = 0.71 dB; P < 0.001). The effect of FPs on PSD was observed only when FP rate was <15% (β = -0.22 dB; P < 0.001). The FL had no associations with the MD, and had minimal effects on the PSD., Conclusions: We quantified the effect of unreliable responses on the MD and PSD in SAP. Our study may allow clinicians to estimate how VF results are affected by varying degrees of unreliability, instead of relying on cutoff values for reliability indices., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1.71 × 10 -9 , odds ratio [OR] = 4.35) and rs149308743 in CARD9 (P = 2.09 × 10 -8 , OR = 4.75); three low-frequency variants: rs76418789 in IL23R (P = 1.03 × 10 -10 , OR = 1.36), rs146466242 in FLG (P = 3.39 × 10 -12 , OR = 1.45), and rs55882956 in TYK2 (P = 1.04 × 10 -6 , OR = 1.30); and two common variants: rs780668 in SLC29A3 (P = 2.17 × 10 -9 , OR = 1.14) and rs181206 in IL27 (P = 1.08 × 10 -7 , OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, showed involvement of skin barrier and endocytosis/phagocytosis/autophagy, in addition to known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein-coding variant studies for complex diseases., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage. It is the most frequent cause of irreversible blindness worldwide. Progression usually stops if the intraocular pressure is lowered by 30-50% from baseline. Its worldwide age-standardised prevalence in the population aged 40 years or older is about 3·5%. Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late. Early detection by ophthalmological examination is mandatory. Risk factors for primary open-angle glaucoma-the most common form of glaucoma-include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia. Older age, hyperopia, and east Asian ethnic origin are the main risk factors for primary angle-closure glaucoma. Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry. Treatment to lower intraocular pressure is based on topical drugs, laser therapy, and surgical intervention if other therapeutic modalities fail to prevent progression., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the difference in corneal hysteresis (CH) and corneal resistance factor (CRF) between Indian and Chinese populations., Design: Population-based cross-sectional study., Participants: Three hundred eighty-two Singaporean Indian persons and 764 Singaporean Chinese 50 years of age or older were included from the Singapore Indian Eye Study and Singapore Chinese Eye Study, respectively., Methods: Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The CH and CRF were measured with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY). Information on genetic ancestry was derived using principal component analysis. Linear regression models were used to investigate the association of CH and CRF with potential risk factors., Main Outcome Measures: Corneal hysteresis and CRF., Results: After excluding participants with a history of intraocular surgery, a diagnosis of glaucoma suspect or glaucoma, refractive surgery, or presence of corneal abnormalities, CH and CRF readings were available for 382 Indian persons. For each Indian participant, 2 Chinese participants were selected and matched for age and gender (n = 764). There were no differences in the clinical measurements of CH (10.6±1.6 mmHg; P = 0.670) or CRF (10.3±1.7 mmHg; P = 0.103) between the ethnic groups. However, after adjusting for covariates, Indian persons had, on average, 0.18-mmHg higher CH levels than in Chinese (95% confidence interval [CI], 0.02-0.38; P = 0.031). Consistently, CH level was correlated significantly with genetic ancestry in the Southeast Asian population. Corneal resistance factor level was not associated independently with self-reported ethnicity (95% CI, -0.10 to 0.29; P = 0.335)., Conclusions: Chinese have lower CH than Indian persons, and this disparity may reflect biomechanical differences of the cornea., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate visual field (VF) progression and rate of glaucomatous VF loss in patients with primary angle-closure glaucoma (PACG) using pointwise linear regression (PLR) trend analysis., Design: Clinic-based retrospective study., Participants: Primary angle-closure glaucoma patients with 5 or more reliable VF tests and with 5 years or more of follow-up., Methods: Visual field progression was assessed by PROGRESSOR software version 3.7 (Medisoft, Leeds, United Kingdom) and was defined by the presence of at least 2 adjacent testing points located within the same hemifield that showed progression with a change of -1 dB/year or more (P < 0.01) for inner points or -2 dB/year or more (P < 0.01) for edge points. We also performed a logistic regression analysis to determine the variables associated with rapid progression (defined as mean slope of progressing points ≥-1.5 dB/year)., Main Outcome Measures: Visual field progression and rate of VF loss., Results: Of the 1296 patients who were assessed, 398 (30.7%) fulfilled the inclusion criteria of 5 or more VFs and 5 years or more of follow-up. Visual field progression was observed in 63 of 398 eyes (15.8%) according to the PLR criteria. The overall mean rate of VF change for these patients was -0.12±0.51 dB/year over a mean follow-up period of 10.4±3.7 years. There were no significant differences in the age, gender distribution, follow-up duration, or number of VFs between those who showed progression and those who did not (all P > 0.05). The most common sector of VF progression was the superior arcuate area (65%). Rapid progression was found in 36 patients (57%). Multiple logistic regression analysis revealed older age and higher vertical cup-to-disc ratio (VCDR) at presentation as predictors of rapid progression (all P < 0.005) in the progressing group (n = 63)., Conclusions: In patients with PACG being managed in a hospital setting, VF progression was noted in 15.8%, and the overall rate of VF loss was -0.12±0.51 dB/year. The superior arcuate was the most common sector of progression. Older age and higher VCDR at presentation were associated with rapid progression., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare anterior segment optical coherence tomography (ASOCT) angle morphology before and after laser peripheral iridotomy (LPI) in a cohort of South Indian subjects with primary angle-closure suspect (PACS) or primary angle-closure/primary angle-closure glaucoma (PAC/PACG) and to examine baseline parameters associated with angle widening., Design: Prospective observational study., Participants: A total of 244 subjects aged ≥30 years with PACS or PAC/PACG in at least 1 eye., Methods: The ASOCT images and angle gonioscopic grades were analyzed for all subjects at baseline and 2 weeks after LPI. Multivariable linear and logistic regression models were used to determine predictors of angle widening (change in mean angle opening distance [AOD750]) and angle opening (all 4 quadrants with trabecular meshwork [TM] visible on gonioscopy after LPI)., Main Outcome Measures: Change in ASOCT parameters with LPI and baseline predictors of angle widening., Results: Laser peripheral iridotomy resulted in angle widening on ASOCT with significant increases in AOD750, angle recess area, and trabecular iris surface area (P < 0.05 for all). Gonioscopically, 44.7% of all subjects had open angles in all 4 quadrants after LPI, with a greater percentage of angles open in the PACS group compared with the PAC/PACG group (52.4% vs. 36.4%; P = 0.01). In multivariable regression analyses, greater postoperative angle widening as defined by change in AOD750 was associated with shorter baseline AOD750 and axial length, and greater baseline anterior chamber depth, iris curvature, and lens vault (P ≤ 0.002 for all). Gonioscopic angle opening after LPI was more common with wider baseline angle width (modified Shaffer grade) and lower cup-to-disc ratio (P < 0.001 for both)., Conclusions: In a South Indian population with PACS or PAC/PACG, LPI results in significant anterior chamber angle widening seen on both ASOCT and gonioscopy, although some degree of persistent iridotrabecular contact was present in approximately half of PACS eyes and approximately two thirds of PAC/PACG eyes on gonioscopy. The greatest widening by ASOCT was observed in eyes with features most consistent with greater baseline pupillary block., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Purpose: To determine the association of iris surface features with iris volume change after physiologic pupil dilation in adults., Design: Cross-sectional observational study., Participants: Chinese adults aged ≥ 50 years without ocular diseases., Methods: Digital iris photographs were taken from eyes of each participant and graded for crypts (by number and size) and furrows (by number and circumferential extent) following a standardized grading scheme. Iris color was measured objectively, using the Commission Internationale de l'Eclairage (CIE) L* color parameter (higher value denoting lighter iris). The anterior segment was imaged by swept-source optical coherence tomography (SS-OCT) (Casia; Tomey, Nagoya, Japan) under bright light and dark room conditions. Iris volumes in light and dark conditions were measured with custom semiautomated software, and the change in iris volume was quantified. Associations of the change in iris volume after pupil dilation with underlying iris surface features in right eyes were assessed using linear regression analysis., Main Outcome Measures: Iris volume change after physiologic pupil dilation from light to dark condition., Results: A total of 65 Chinese participants (mean age, 59.8±5.7 years) had gradable data for iris surface features. In light condition, higher iris crypt grade was associated independently with smaller iris volume (β [change in iris volume in millimeters per crypt grade increment] = -1.43, 95% confidence interval [CI], -2.26 to -0.59; P = 0.001) and greater reduction of iris volume on pupil dilation (β [change in iris volume in millimeters per crypt grade increment] = 0.23, 95% CI, 0.06-0.40; P = 0.010), adjusting for age, gender, presence of corneal arcus, and change in pupil size. Iris furrows and iris color were not associated with iris volume in light condition or change in iris volume (all P > 0.05)., Conclusions: Although few Chinese persons have multiple crypts on their irides, irides with more crypts were significantly thinner and lost more volume on pupil dilation. In view that the latter feature is known to be protective for acute angle-closure attack, it is likely that the macroscopic and microscopic composition of the iris is a contributing feature to angle-closure disease., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) across different severity levels and to assess hemifield differences within each severity level., Design: Cross-sectional study., Participants: Three hundred four patients diagnosed with PACG were recruited from glaucoma clinics at a Singapore hospital., Methods: Point-wise total deviation values were recorded from the static automated perimetry (Swedish interactive threshold algorithm standard program 24-2; Humphrey model 750 [Carl Zeiss Meditec, Dublin, CA]) printouts. Patients were excluded if they had unreliable VFs (fixation losses >33% and false-positive responses >15%), had undergone only 10-2 VF testing, had VF defects not typical of glaucoma, or had undergone cataract extraction. Mild, moderate, and severe VF loss were defined by a mean deviation of -6.00 dB or more, -6.01 to -12.00 dB, and -12.01 dB or less, respectively. Each hemifield was divided into regions according to glaucoma hemifield test sectors. The average mean deviation (MD) of each region was obtained using total deviation values., Main Outcome Measures: Between- and within-hemifield differences of the regions across the severity levels., Results: After excluding ineligible cases, 249 patients with PACG were included in the analysis. Mean age of the patients was 65.7±8.6 years, with a 1:1 gender ratio. The number of patients who had mild, moderate, and severe VFs was 72 (28.9%), 78 (31.3%), and 99 (39.8%), respectively. For between-hemifield comparisons, all regions in the superior hemifield had worse MDs compared with their counterparts in the inferior hemifield across the severity spectrum. Likewise, for within-hemifield comparisons, MDs of the regions gradually worsened with increasing distance from the fixation point., Conclusions: In this group of clinic-based PACG patients, the superior hemifield was found to be affected more severely than the inferior hemifield, and the differences between them increased with worsening disease severity. The damage was consistently more pronounced in the nasal area., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)