Efficiency, Precision, Validity, and Reliability of GlauCAT-Asian Computerized Adaptive Tests in Measuring Glaucoma-Related Quality of Life.

Purpose: To determine the efficiency, precision, and agreement of GlauCAT-Asian and its corresponding validity and reliability. Methods: In this cross-sectional study, 219 participants (mean ± standard deviation age, 66.59 ± 8.61 years; 34% female) across the spectrum of glaucoma severity and 50 glaucoma suspects were recruited from glaucoma clinics in Singapore. Participants answered seven computerized adaptive testing (CAT) evaluations (Ocular Comfort, Activity Limitation, Lighting, Mobility, Concerns, Psychosocial, Glaucoma Management) and underwent eye examinations. Efficiency (mean number of items required for each CAT and time taken for CAT versus full item banks [IBs]), agreement (concordance between CATs and full IB person measures, henceforth referred to as scores), and precision (standard error of measurement [SE]) were evaluated. Other validity and reliability metrics were also assessed. Results: The mean number of items administered ranged from 9 (Mobility/Glaucoma Management) to 12 (Ocular Comfort). Compared to answering the full IBs, CATs provided an average time saving of 38.3% (range, 10% to 70.6% for Lighting and Activity Limitation, respectively). Agreement between scores obtained by CAT versus full IB was high (intracorrelation coefficient ≥0.75), as was precision of score estimates (mean SE range: 0.35 for Psychosocial to 0.29 for Mobility). Scores from Activity Limitation, Mobility, Lighting, and Concerns decreased significantly as glaucoma severity increased (criterion validity; P-trend <0.05). All tests displayed good convergent/divergent validity and test-retest reliability. Conclusions: GlauCAT-Asian provides efficient, precise, accurate, valid, and reliable measurement of the patient-centered impact of glaucoma. Translational Relevance: GlauCAT-Asian may provide a valuable clinical tool for ophthalmologists to monitor impact of disease progression and the effectiveness of therapies.

Deep Learning Classification of Angle Closure based on Anterior Segment OCT.

PURPOSE: To assess the performance and generalizability of a convolutional neural network (CNN) model for objective and high-throughput identification of primary angle-closure disease (PACD) as well as PACD stage differentiation on anterior segment swept-source OCT (AS-OCT). DESIGN: Cross-sectional. PARTICIPANTS: Patients from 3 different eye centers across China and Singapore were recruited for this study. Eight hundred forty-one eyes from the 2 Chinese centers were divided into 170 control eyes, 488 PACS, and 183 PAC + PACG eyes. An additional 300 eyes were recruited from Singapore National Eye Center as a testing data set, divided into 100 control eyes, 100 PACS, and 100 PAC + PACG eyes. METHODS: Each participant underwent standardized ophthalmic examination and was classified by the presiding physician as either control, primary angle-closure suspect (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG). Deep Learning model was used to train 3 different CNN classifiers: classifier 1 aimed to separate control versus PACS versus PAC + PACG; classifier 2 aimed to separate control versus PACD; and classifier 3 aimed to separate PACS versus PAC + PACG. All classifiers were evaluated on independent validation sets from the same region, China and further tested using data from a different country, Singapore. MAIN OUTCOME MEASURES: Area under receiver operator characteristic curve (AUC), precision, and recall. RESULTS: Classifier 1 achieved an AUC of 0.96 on validation set from the same region, but dropped to an AUC of 0.84 on test set from a different country. Classifier 2 achieved the most generalizable performance with an AUC of 0.96 on validation set and AUC of 0.95 on test set. Classifier 3 showed the poorest performance, with an AUC of 0.83 and 0.64 on test and validation data sets, respectively. CONCLUSIONS: Convolutional neural network classifiers can effectively distinguish PACD from controls on AS-OCT with good generalizability across different patient cohorts. However, their performance is moderate when trying to distinguish PACS versus PAC + PACG. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Examination under anesthesia: Preferred Practice.

Pediatric ocular examinations are often a challenge in the outpatient setting due to limited cooperation of the child. Hence an evaluation under anesthesia (EUA) or sedation is important for a holistic ophthalmic examination. It can be combined with short procedures, such as suture removal and corneal scrappings, both for diagnosis and for the management of several ophthalmic disorders. It can also be performed before planning a surgical intervention to record the baseline characters and formulate or refine a surgical plan. Every EUA must be used as a chance to perform a complete ophthalmic examination rather than perform a single task such as recording the intraocular pressure. This article aims to provide a protocol that can be followed for a complete EUA.

Handheld chromatic pupillometry can reliably detect functional glaucomatous damage in eyes with high myopia.

BACKGROUND/AIMS: To assess pupillary light responses (PLRs) in eyes with high myopia (HM) and evaluate the ability of handheld chromatic pupillometry (HCP) to identify glaucomatous functional loss in eyes with HM. METHODS: This prospective, cross-sectional study included 28 emmetropes (EM), 24 high myopes without glaucoma (HM) and 17 high myopes with confirmed glaucoma (HMG), recruited at the Singapore National Eye Center. Monocular PLRs were evaluated using a custom-built handheld pupillometer that recorded changes in horizontal pupil radius in response to 9 s of exponentially increasing blue (469.1 nm) and red (640.1 nm) lights. Fifteen pupillometric features were compared between groups. A logistic regression model (LRM) was used to distinguish HMG eyes from non-glaucomatous eyes (EM and HM). RESULTS: All pupillometric features were similar between EM and HM groups. Phasic constriction to blue (p<0.001) and red (p=0.006) lights, and maximum constriction to blue light (p<0.001) were reduced in HMG compared with EM and HM. Pupillometric features of melanopsin function (postillumination pupillary response, PIPR area under the curve (AUC) 0-12 s (p<0.001) and PIPR 6 s (p=0.01) to blue light) were reduced in HMG. Using only three pupillometric features, the LRM could classify glaucomatous from non-glaucomatous eyes with an AUC of 0.89 (95% CI 0.77 to 1.00), sensitivity 94.1% (95% CI 82.4% to 100.0%) and specificity 78.8% (95% CI 67.3% to 90.4%). CONCLUSION: PLRs to ramping-up light stimuli are unaltered in highly myopic eyes without other diagnosed ocular conditions. Conversely, HCP can distinguish glaucomatous functional loss in eyes with HM and can be a useful tool to detect/confirm the presence of glaucoma in patients with HM.

Clinical utility, feasibility of home tonometry using iCare HOME by glaucoma patients.

Purpose: To determine agreement between diurnal variation testing (DVT) of intraocular pressure (IOP) with Goldmann applanation tonometer (GAT) and iCare HOME (IH) by an optometrist (OP) and home monitoring by participants (PT). Methods: Patients (18-80 years) with glaucoma and suspects were enrolled. IH IOP and GAT were taken by an OP at 2 h intervals from 8 AM to 4 PM on Day 1 and PT between 6 AM and 9 PM, for the next 2 days. IOP, date, and time were viewed via iCare LINK software. Results: In total,: 72.9. (: 51/70) PT trained were able to take reliable readings. One hundred two eyes (51 patients, age 53 ± 16 yrs) were analyzed. Correlation between optometrist (OP) and participants (PT) was strong and positive {IH OP-IH PT- r = 0.90, p-0.0001;IH PT-GAT- r = 0.79, p-0.0001}. Agreement by Bland Altman plots was limited {IH OP-IH PT mean 0.1 mmHg (95% LOA -5.3 to 5.5), IH PT-GAT 2.2 mmHg (-5.7 to 10.1)}. Intraclass correlation coefficient for IH OP-IH PT was 1.18 (95% CI 1.37-1.09). Intradevice {0.95 (95% CI 0.94-0.97)} and interrater repeatability {0.91 (0.79-0.96)} were good. 37% of eyes had a synchronous peak on GAT and IH during the day DVT. Conclusion: Home tonometry by iCare HOME is easy, feasible, but due to limited agreement cannot substitute GAT DVT.

Measuring glaucoma quality of life in an Asian population using item banking: psychometric evaluation and computerized adaptive testing simulations.

PURPOSE: To assess the psychometric properties of glaucoma-specific health-related quality of life (HRQoL) item banks (IBs), and explore their efficiency using computerized adaptive testing (CAT) simulations. METHODS: In this cross-sectional, clinical study, 300 Asian glaucoma patients answered 221 items within seven IBs: Ocular Comfort Symptoms (OS); Activity Limitation (AL); Lighting (LT); Mobility (MB); Glaucoma Management (GM); Psychosocial (PSY); and Work (WK). Rasch analysis was conducted to assess each IB's psychometric properties (e.g., item "fit" to the construct; unidimensionality) and a set of analytic performance criteria guiding decision making relating to retaining or dropping domains and items was employed. CAT simulations determined the mean number of items for 'high' and 'moderate' measurement precision (stopping rule: SEM 0.3 and 0.387, respectively). RESULTS: Participants' mean age was 67.2 ± 9.2 years (62% male; 87% Chinese). LT, MB, and GM displayed good psychometric properties overall. To optimize AL's psychometric properties, 16 items were deleted due to poor "fit", high missing data, item bias, low discrimination and/or a low clinical/patient importance rating. To resolve multidimensionality in PSY, we rehomed 16 items into a "Concern (CN)" domain. PSY and CN required further amendment, including collapsing of response categories, and removal of poorly functioning items (N = 7). Due to poor measurement precision, low applicability and high ceiling effect, low test information indices, and low item separation index the WK IB was not considered further. In CAT simulations on the final seven IBs (n = 182 items total), an average of 12.1 and 15.7 items per IB were required for moderate and high precision measurement, respectively. CONCLUSIONS: After reengineering our seven IBs, they displayed robust psychometric properties and good efficiency in CAT simulations. Once finalized, GlauCAT™-Asian may enable comprehensive assessment of the HRQoL impact of glaucoma and associated treatments.

Angle closure extent, anterior segment dimensions and intraocular pressure.

AIM: To investigate the association between the extent of iridotrabecular contact and other quantitative anterior segment dimensions measured by swept-source optical coherence tomography (SS-OCT; CASIA SS-1000, Tomey, Nagoya, Japan) with intraocular pressure (IOP). METHODS: Cross-sectional study. All subjects who were ≥50 years with no history of glaucoma, ocular surgery or trauma, underwent SS-OCT imaging (eight equally spaced radial scans), Goldman applanation tonometry and gonioscopy on the same day. We measured iridotrabecular contact (ITC) index and area, total volume of trabeculo-iris space area and angle opening distance at 500 and 750 from the scleral spur (TISA 500 and 750, AOD 500 and 750, respectively), anterior chamber depth (ACD), volume, area and width, pupil diameter, lens vault and iris volume.Their relationship with IOP (dependent variable) was assessed by locally weighted scatterplot smoothing (Lowess) regression with change-point analysis and generalised additive models adjusted for confounders. RESULTS: 2027 right eyes of mostly Chinese Singaporeans (90%) were analysed. ITC index above a threshold of ~60% (95% CI 34% to 92%) was significantly associated with higher IOP. Independent of the extent of ITC, ACD was also significantly associated with higher IOP below a threshold of 2.5 mm (95% CI 2.33 mm to 2.71 mm). Greater ITC index and shallower ACD had a joint association with IOP. A model including ACD and ITC index was more predictive of IOP than a model considering these variables separately, particularly for women with gonioscopically closed angles (R2 52.7%, p<0.05). CONCLUSIONS: The extent of angle closure and the ACD below a certain threshold had a significant joint association with IOP. These parameters, as biometrical surrogates of mechanical obstruction of the aqueous outflow, may jointly contribute to elevated IOP, particularly in women with gonioscopic angle closure.

A comparative analysis of surgical outcome in uveitic and non-uveitic steroid-induced glaucoma in children.

Purpose: To compare outcomes of surgical management of uveitic glaucoma (UG) and steroid-induced glaucoma (SIG) in children in terms of intraocular pressure (IOP) control, visual acuity, and associations for failure. Methods: This was a retrospective case-control study of consecutive UG (cases) and non-uveitic SIG (controls) in children <18 years of age who underwent surgery between January 2005 and December 2017. Results: Primary trabeculectomy with mitomycin C (MMC) was performed in 12 cases (mean age: 9.2 ± 4.3 years) and 40 controls (mean age: 10.4 ± 3.7 years) (P = 0.33). Primary phaco-trabeculectomy with MMC was performed in 11 cases (mean age: 11.4 ± 4.7 years) and 16 controls (mean age: 10.4 ± 3.4 years) (P = 0.57). IOP control (P = 0.26), visual acuity (P = 0.97), number of glaucoma medications (P = 0.06), and survival rates (49% cases vs. 68% controls at 5 years; P = 0.22) were similar between the two groups following trabeculectomy. Survival rates in the phaco-trabeculectomy group at 5 years were 68% cases vs. 69% controls (P = 0.71). IOP was higher (P = 0.008) and visual acuity was worse (P = 0.02) in cases at the last visit. Associations for failure (univariate analysis) were younger age (OR: 6.29, 95% CL: 1.43, 27.67; P = 0.03) and male gender (OR: 4.79, 95% CL: 1.09, 20.97; P = 0.04). On multivariate analysis, younger age (OR: 11.985, 95% CL: 1.071, 134.153; P = 0.04) remained significant. Preoperative number of uveitic attacks was protective on univariate (OR: 0.75, 95% CL: 0.48, 1.15; P = 0.1) and multivariate analyses (OR: 0.49, 95% CL: 0.24, 0.09; P = 0.04). Conclusion: Outcomes of trabeculectomy between cases and controls were similar in our series. However, phaco-trabeculectomy in pediatric uveitic eye group fared worse than eyes with SIG.

The development of a glaucoma-specific health-related quality of life item bank supporting a novel computerized adaptive testing system in Asia.

BACKGROUND: A glaucoma-specific health-related quality of life (HRQoL) item bank (IB) and computerized adaptive testing (CAT) system relevant to Asian populations is not currently available. We aimed to develop content for an IB focusing on HRQoL domains important to Asian people with glaucoma; and to compare the content coverage of our new instrument with established glaucoma-specific instruments. METHODS: In this qualitative study of glaucoma patients recruited from the Singapore National Eye Centre (November 2018-November 2019), items/domains were generated from: (1) glaucoma-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with glaucoma patients (n = 27); and (4) feedback from glaucoma experts. Data were analyzed using the constant comparative method. Items were systematically refined to a concise set, and pre-tested using cognitive interviews with 27 additional glaucoma patients. RESULTS: Of the 54 patients (mean ± standard deviation [SD] age 66.9 ± 9.8; 53.7% male), 67 (62.0%), 30 (27.8%), and 11 (10.2%) eyes had primary open angle glaucoma, angle closure glaucoma, and no glaucoma respectively. Eighteen (33.3%), 11 (20.4%), 8 (14.8%), 12 (22.2%), and 5 (9.3%) patients had no, mild, moderate, severe, or advanced/end-stage glaucoma (better eye), respectively. Initially, 311 items within nine HRQoL domains were identified: Visual Symptoms, Ocular Comfort Symptoms, Activity Limitation, Driving, Lighting, Mobility, Psychosocial, Glaucoma management, and Work; however, Driving and Visual Symptoms were subsequently removed during the refinement process. During cognitive interviews, 12, 23 and 10 items were added, dropped and modified, respectively. CONCLUSION: Following a rigorous process, we developed a 221-item, 7-domain Asian glaucoma-specific IB. Once operationalised using CAT, this new instrument will enable precise, rapid, and comprehensive assessment of the HRQoL impact of glaucoma and associated treatment efficacy.

Towards 'automated gonioscopy': a deep learning algorithm for 360° angle assessment by swept-source optical coherence tomography.

AIMS: To validate a deep learning (DL) algorithm (DLA) for 360° angle assessment on swept-source optical coherence tomography (SS-OCT) (CASIA SS-1000, Tomey Corporation, Nagoya, Japan). METHODS: This was a reliability analysis from a cross-sectional study. An independent test set of 39 936 SS-OCT scans from 312 phakic subjects (128 SS-OCT meridional scans per eye) was analysed. Participants above 50 years with no previous history of intraocular surgery were consecutively recruited from glaucoma clinics. Indentation gonioscopy and dark room SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle. For each subject, all images were analysed by a DL-based network based on the VGG-16 architecture, for gonioscopic angle-closure detection. Area under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators were calculated for the DLA (index test) against gonioscopy (reference standard). RESULTS: Approximately 80% of the participants were Chinese, and more than half were women (57.4%). The prevalence of gonioscopic angle closure in this hospital-based sample was 20.2%. After analysing a total of 39 936 SS-OCT scans, the AUC of the DLA was 0.85 (95% CI:0.80 to 0.90, with sensitivity of 83% and a specificity of 87%) to classify gonioscopic angle closure with the optimal cut-off value of >35% of circumferential angle closure. CONCLUSIONS: The DLA exhibited good diagnostic performance for detection of gonioscopic angle closure on 360° SS-OCT scans in a glaucoma clinic setting. Such an algorithm, independent of the identification of the scleral spur, may be the foundation for a non-contact, fast and reproducible 'automated gonioscopy' in future.

High-Density Lipoprotein 3 Cholesterol and Primary Open-Angle Glaucoma: Metabolomics and Mendelian Randomization Analyses.

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.

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

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

Changes in Iris Stiffness and Permeability in Primary Angle Closure Glaucoma.

Purpose: To evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects. Methods: A total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris. Results: For all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm2/kPa s vs. 0.55 ± 0.2 mm2/kPa s; p = 0.142). Conclusions: This study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.

Development and Validation of a Preference-Based Glaucoma Utility Instrument Using Discrete Choice Experiment.

IMPORTANCE: A glaucoma-specific instrument for estimating utilities across the spectrum of glaucoma severity is currently lacking, hindering the assessment of the cost-effectiveness of glaucoma treatments. OBJECTIVE: To develop and validate the preference-based Glaucoma Utility Instrument (Glau-U) and to ascertain the association between Glau-U utilities and severity of glaucoma and vision impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted in 2 stages at the Singapore National Eye Centre glaucoma clinics. Stage 1 focused on the identification and pretesting of the Glau-U attributes and was carried out between June 2009 and May 2016. Stage 2 involved the development and administration of the discrete choice experiment (DCE) survey and tasks and was conducted between May 7, 2018, and December 11, 2019. Stage 2 participants were English- or Mandarin-speaking Singaporean citizens or permanent residents of Chinese, Malay, or Indian ethnicity who were 40 years or older and had a clinical diagnosis of glaucoma in at least 1 eye. EXPOSURES: Glau-U comprised 6 quality-of-life attributes: activities of daily living, lighting and glare, movement, eye discomfort, other effects of glaucoma, and social and emotional effects. The descriptions or response options for these attributes were no difficulty or never, some difficulty or sometimes, or severe difficulty or often. MAIN OUTCOMES AND MEASURES: Utility weights for Glau-U were developed using a DCE questionnaire, which was interviewer administered to participants. Mixed logit regression determined utility weights for each health state. Glau-U utility weights across better- or worse-eye glaucoma and vision impairment severity were calculated using 1-way analysis of variance. Correlations between Glau-U utilities and better- or worse-eye visual fields and EuroQol 5-Dimension utilities were ascertained to assess convergent and divergent validity. RESULTS: Of the 304 participants (mean [SD] age, 68.3 [8.7] years; 182 men [59.9%]), 281 (92.4%) had no vision impairment in the better eye, 13 (4.3%) had mild impairment, and 10 (3.3%) had moderate to severe vision impairment. Mean (SD) Glau-U utilities decreased as better-eye glaucoma severity increased (none: 0.73 [0.21]; mild: 0.66 [0.21]; moderate: 0.66 [0.20]; severe: 0.60 [0.28]; and advanced or end-stage: 0.22 [0.38]; P < .001), representing reductions of 20.7% to 76.1% in quality-adjusted life-years compared with a health state that included preperimetric glaucoma. Mean (SD) Glau-U utilities also decreased as better-eye vision impairment worsened from 0.67 (0.23) for none to 0.58 (0.32) for mild to 0.46 (0.29) for moderate to severe vision impairment. Glau-U utilities demonstrated moderate correlations with better-eye (r = 0.34; P < .001) and worse-eye (r = 0.33; P < .001) mean deviation scores and low correlations with EuroQol 5-Dimension utilities (r = 0.22; P < .001), supporting convergent and divergent validity. CONCLUSIONS AND RELEVANCE: Use of Glau-U revealed large decrements in utility that were associated with late-stage glaucoma, suggesting that this new instrument may be useful for cost-effectiveness analyses of interventions and informing resource allocation policies for glaucoma and vision loss.

Determinants of lamina cribrosa depth in healthy Asian eyes: the Singapore Epidemiology Eye Study.

AIM: To investigate the determinants of lamina cribrosa depth (LCD) in healthy eyes of Chinese and Indian Singaporean adults. METHODS: The optic nerve head (ONH) of the right eye of 1396 subjects (628 Chinese and 768 Indian subjects) was imaged with optical coherence tomography (OCT, Spectralis, Heidelberg, Germany). LCD was defined as the distance from the Bruch's membrane opening (LCD-BMO) or the peripapillary sclera (LCD-PPS) reference plane to the laminar surface. A linear regression model was used to evaluate the relationship between the LCD and its determinants. RESULTS: Both LCDs were significantly different between the two races (LCD-BMO: 421.95 (95% CI 365.32 to 491.79) µm in Chinese vs 430.39 (367.46-509.81) µm in Indians, p=0.021; and LCD-PPS: 353.34 (300.98-421.45) µm in Chinese vs 376.76 (313.39-459.78) µm in Indians, p<0.001). In the multivariable regression analysis, the LCD-PPS of the whole cohort was independently associated with females (ß=-31.93, p<0.001), Indians subjects (ß=21.39, p=0.004) (Chinese as the reference), axial length (Axl) (ß=-6.68, p=0.032), retinal nerve fibre layer thickness (RNFL) (ß=0.71, p=0.019), choroidal thickness (ChT) (ß=0.41, p<0.001), vertical cup disc ratio (VCDR) (ß=24.42, p<0.001) and disc size (ß=-60.75, p=0.001). For every 1 year older in age, the LCD-PPS was deeper on average by 1.95 µm in Chinese subjects (p=0.01) but there was no association in Indians subjects (p=0.851). CONCLUSIONS: The LCD was influenced by age, gender, race, Axl, RNFL, ChT, VCDR and disc size. This normative LCD database may facilitate a more accurate assessment of ONH cupping using OCT in Asian populations.

Factors affecting the diagnostic performance of circumpapillary retinal nerve fibre layer measurement in glaucoma.

BACKGROUND/AIMS: To identify factors that influence the diagnostic performance of circumpapillary retinal nerve fibre layer (RNFL) thickness measurements in the detection of primary open-angle glaucoma (POAG). METHODS: 1592 eyes from 1076 healthy controls and 758 eyes from 502 patients with POAG underwent optical coherence tomography (OCT) imaging to assess RNFL parameters. Visual field (VF) mean deviation (MD) from standard automated perimetry was used to indicate severity in subjects with glaucoma. RESULTS: RNFL thickness significantly decreased with age (ρ=-0.10 to -0.16, p<0.001) and increased with spherical equivalent (SE) refractive error (ρ=0.23-0.29, p<0.001) in healthy and glaucoma groups but showed a significant reduction with SE (ρ=-0.20, p<0.001) in the temporal RNFL of healthy subjects. RNFL measurements significantly decreased with VF MD (ρ=0.08-0.53, p<0.05) in subjects with POAG. When healthy subjects and subjects with glaucoma were matched to subgroups within a factor, significant differences in area under the curve (AUC) between subgroups were only found with SE AUCs increased significantly with disease severity, particularly in the global, inferior and superior measurements (p<0.001). Overall, the diagnostic performance of the inferior and global RNFL measurements were found to be more resilient to different factors. CONCLUSION: Diagnostic accuracy in glaucoma was influenced by SE but could be mitigated by using controls with similar refractive characteristics. Increasing disease severity led to significantly better diagnostic accuracy. These factors should be considered when using OCT for glaucoma diagnosis in practice.

Evaluation of meridional scans for angle closure assessment with anterior segment swept-source optical coherence tomography.

BACKGROUND/AIMS: As swept-source optical coherence tomography (SS-OCT) simultaneously obtains 128 meridional scans, it is important to identify which scans are playing the main role in classifying gonioscopic angle closure to simplify the analysis. We aimed to evaluate the diagnostic performance of every meridional scan in its ability to detect gonioscopic angle closure. METHODS: Observational study with 2027 phakic subjects consecutively recruited from a community polyclinic. Gonioscopy and SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle, while SS-OCT was defined as iridotrabecular contact anterior to the scleral spur. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic performance of each single scan, the sequential anticlockwise cumulative effect of those single scans and different combinations of them. RESULTS: The AUCs of each scan ranged from 0.73 to 0.82. The single scan at 80°-260° had the highest AUC (0.82, 95% CI 0.79 to 0.84) and performed significantly better than most of the temporonasal scans (from 0° to 52° and from 153° to 179°). The superoinferior scans achieved higher AUCs compared with the temporonasal ones. When assessing the cumulative effect of adding individual scans consecutively, the peak AUC (0.80) was obtained when considering the superoinferior scans closer to 80°-85°, but no further positive cumulative effect was seen when adding the rest of the temporonasal scans of the circumference. CONCLUSIONS: In conclusion, the single SS-OCT scan at 80°-260° had the highest diagnostic performance. Our study suggests that the 360° evaluation may not translate to better clinical utility for detection of gonioscopic angle closure.

Noninvasive and Noncontact Sequential Imaging of the Iridocorneal Angle and the Cornea of the Eye.

Purpose: High-resolution imaging of the critical anatomic structures of the eye, especially of the anterior chamber, in vivo, remains a challenge, even with currently available state-of-the-art medical imaging techniques. This study aims for the noninvasive and noncontact sequential imaging of the iridocorneal angle, especially the trabecular meshwork (TM) and the cornea of the eye in high-resolution using a newly developed imaging platform. Methods: Bessel beam scanned light sheet fluorescence microscopy is used to attain high-resolution images of the TM. The ability of the Bessel beam to self-reconstruct around obstacles increases the image contrast at the TM region inside eye by reducing scattering and shadow artifacts. With minimal modifications, the excitation arm of the developed imaging system is adapted for noncontact, high-resolution corneal imaging. Results: High-resolution images of the TM structures and cellular-level corneal structures are obtained in ex vivo porcine eyes, and subsequently in New Zealand white rabbit, in vivo. The spatial resolution of the developed system is 2.19 µm and has a noncontact working distance of 20 mm. Conclusions: A high-resolution imaging platform for noncontact sequential imaging of the TM and the cornea of the eye is developed. This imaging system is expected to be of potential interest in the evaluation and diagnosis of glaucoma and corneal diseases. Translational Relevance: The developed prototype offers the plausibility of in vivo, noncontact, and high-resolution imaging of the iridocorneal angle and cornea of the eye that will aid clinicians in diagnosing open-angle glaucoma and corneal diseases better.

Evaluation of Intraocular Pressure After Water Drinking Test in Patients with Unilateral Hemifacial Spasm.

PURPOSE: The aim of the study is to examine the baseline intraocular pressure (IOP) and its changes after performing a water drinking test (WDT) in patients with unilateral hemifacial spasm (HFS). PATIENTS AND METHODS: In this prospective observational study, patients aged 21 years and above diagnosed with unilateral HFS were recruited from the Singapore National Eye Centre between January 2015 and August 2016. The unaffected eye of each patient served as a matched control. An interviewer-administered standardized questionnaire on HFS symptoms and ophthalmic examination was performed. Automated perimetry, optical coherence tomography (OCT) of the optic nerve head, color disc stereophotography and water drinking test (WDT) were done. The primary outcome measure was the difference in IOP between eyes affected by HFS and fellow eyes at baseline and at 15, 30 and 45 minutes of the WDT. RESULTS: Fifty-four patients with unilateral HFS were included. Mean age was 59.8±9.9 years (range, 37.0-84.0). Of these, 54% were female and 94% were Chinese. Mean baseline IOP was significantly higher in eyes with HFS (13.9±3.1mmHg) compared to fellow eyes (13.3±2.8mmHg) (p=0.008). There was no significant difference in absolute or percentage change in IOP from baseline between the 2 groups at 15, 30 and 45 minutes of the WDT. Mean vertical cup-disc ratio (VCDR) on clinical examination was significantly higher in eyes with HFS (0.5±0.2) compared to fellow eyes (0.4±0.2) (p=0.02). There was no significant difference between the groups for visual field parameters and mean retinal nerve fiber layer thickness on OCT. CONCLUSION: Hemifacial spasm is associated with a small but significant difference in mean baseline IOP and VCDR between affected and fellow eyes. However, when eyes affected by HFS and fellow eyes were challenged with the WDT, both responded in similar ways.

Association Between Structure-function Characteristics and Visual Field Outcomes in Glaucoma Subjects With Intraocular Pressure Reduction After Trabeculectomy.

PRECIS: Improvements in post-trabeculectomy visual field (VF) outcomes were found to be significantly associated with preoperative nerve fiber layer thickness parameters extracted from the sectorized structure-function relationship, baseline VF, and severity of glaucoma. OBJECTIVE: To determine whether the preoperative structure-function relationship helps to predict visual outcomes at 1-year post-trabeculectomy. PATIENTS AND METHODS: In total, 91 eyes from 87 participants who successfully underwent trabeculectomy were included in our study. All eyes received optical coherence tomography imaging and VF assessment using 30-2 standard automated perimetry preoperatively at baseline and postoperatively 1 year after trabeculectomy. The linear mixed-model analysis was used to assess the association of structure and function at baseline, and multivariate analysis to investigate factors associated with postoperative VF outcomes. RESULTS: Results from multivariate and univariate analysis for VF 1 year after trabeculectomy showed that a positive preoperative retinal nerve fiber layer thickness deviation from the structure-function model was found to be significantly associated with improved postoperative VF outcomes [ß=0.06 dB/µm; 95% confidence interval (CI), 0.03-0.09]. Other significant factors included baseline VF MD (ß=-0.18; 95% CI, -0.23 to -0.13) and the presence of severe glaucoma (ß=-1.69; 95% CI, -2.80 to -0.57). Intraocular pressure was positively associated with improved VF outcomes only in univariate analysis (ß=0.06; 95% CI, 0.01-0.11). CONCLUSIONS AND RELEVANCE: Characteristics derived from the baseline structure-function relationship were found to be strongly associated with postoperative VF outcomes. These findings suggest that the structure-function relationship could potentially have a role in predicting VF progression after trabeculectomy.