Search

Xian Hui Lim,1 Monisha Esther Nongpiur,1– 3 Raymond P Najjar,2,3 Quan V Hoang,1– 4 Dan Milea,1– 3 Chee Wai Wong,1– 3 Rahat Husain,1,3 Hla Myint Htoon,2,3 Tin Aung,1– 3,5 Shamira Perera,1– 3 Tina Tzee Ling Wong1– 3,5 1Singapore National Eye Centre, Singapore; 2Singapore Eye Research Institute, Singapore; 3Duke-NUS Medical School, Singapore; 4Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeCorrespondence: Tina Tzee Ling WongSingapore National Eye Centre, 11 Third Hospital Avenue, 168751, SingaporeEmail tina.wong.t.l@singhealth.com.sgPurpose: To investigate features of the steady-state pattern electroretinogram (ssPERG) in subjects with glaucoma (G), high myopia (HM; spherical equivalent ≤-6D) and glaucoma with high myopia (GHM).Patients and Methods: Our study included 48 participants divided into 3 groups (G, HM, and GHM) who each underwent monocular ssPERG testing with Diopsys NOVA PERG protocols. The ConStim protocol detects distinct topographic patterns of dysfunction 16° and 24° around the central macula. MagD is the amplitude of the average signal and MagD/Mag ratio indicates the consistency of the response. ssPERG indices were compared between groups and correlated with functional (ie, visual field mean deviation (VFMD)) and structural (ie, average retinal nerve fibre layer (RNFL) thickness; Cirrus optical coherence tomography) features.Results: Participants had an average age of 59.4± 7.6 years. Mean Humphrey VFMD was − 14.22 ± 2.88dB, − 2.62 ± 1.18dB and − 12.80 ± 2.60dB for G, HM and GHM groups, respectively. Mean RNFL thickness was 63.0 ± 8.20μm, 69.5 ± 15.7μm and 60.6 ± 5.0μm for G, HM and GHM groups, respectively. For the 24° setting, no significant differences were noted for any of the parameters. For the 16° setting, MagD was lower in the GHM group compared to the HM group (0.29μV vs 0.52μV; p = 0.02). Significant differences were noted for the MagD/Mag ratio between HM and G groups (0.58 vs 0.40; p = 0.02) and between HM and GHM groups (0.58 vs 0.35; p = 0.002). There were positive correlations between both MagD 16° and MagD/Mag ratio 16° with VFMD (correlation coefficient [r]=0.37, p = 0.009; and r = 0.44, p = 0.002, respectively) and RNFL (r = 0.43, p = 0.002; and r = 0.48, p = 0.001, respectively).Conclusion: MagD/Mag ratio at 16° was significantly lower in glaucomatous eyes (with or without high myopia) compared to those with high myopia without glaucoma, suggesting that glaucoma has a distinct impact on MagD/Mag ratio at 16° irrespective of the presence of myopia.Keywords: pattern electroretinogram, visual field mean deviation, optical coherence tomography, retinal nerve fibre layer

Jin Rong Low,1– 3 Chee Wai Wong,1,3– 6 Jing Liang Loo,1,3,5– 8 Dan Milea,3,5,7,8 Shamira A Perera,1– 3,5 Yi Fang Lee,3,9 Si Rui Ng,1– 3 Mani Baskaran,2,3,5 Monisha Esther Nongpiur,2,3,5 Sharon Lee Choon Tow1,3,5– 8 1Department of Cataract and Comprehensive Ophthalmology, Singapore National Eye Centre, Singapore; 2Department of Glaucoma, Singapore National Eye Centre, Singapore; 3Singapore Eye Research Institute, Singapore; 4Department of Surgical Retina, Singapore National Eye Centre, Singapore; 5Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore; 6Department of Ophthalmology, National University of Singapore, Singapore; 7Department of Neuro-Ophthalmology, Singapore National Eye Centre, Singapore; 8Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School, Singapore; 9Department of Training and Education, Singapore National Eye Centre, SingaporeCorrespondence: Sharon Lee Choon Tow Tel +65 6322 7443Fax +65 6333 8339Email sharon.tow.l.c@singhealth.com.sgPurpose: 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.Keywords: glaucoma, hemifacial spasm, intraocular pressure, water drinking test

Zhu Li Yap,1,2 You Chuen Chin,1 Judy Yu-Fen Ku,1 Tat Keong Chan,1,2 Gillian Teh,1,2 Monisha Esther Nongpiur,2,3 Tin Aung,1,2 Shamira A Perera1–3 1Singapore National Eye Centre, Singapore; 2Singapore Eye Research Institute, Singapore; 3Duke NUS Graduate Medical School, Singapore Purpose: Comparison of the demographic, ocular, systemic and microbiological characteristics of eyes with bleb related infection (BRI) and bleb related endophthalmitis (BRE). Methods: Retrospective chart review of patients with BRI from January 1996–July 2013. Identification done via the center’s longstanding endophthalmitis audit, BRI audit and laboratory database identifying all conjunctival swabs from blebs. Blebitis was defined as anterior segment inflammation with mucopurulent material in or around the bleb, with anterior chamber cells but no hypopyon. BRE was defined by the presence of hypopyon or vitreous inflammation. Results: Twenty-nine patients with blebitis and 10 with BRE were identified. Mean age of subjects (n=39) was 68.4 (±13.3) with a preponderance of men (74.4%) and Chinese ethnicity (74.4%). BRE patients were 10.7 years older than blebitis patients (P=0.026). 28 (71.8%) subjects had primary open angle glaucoma. The presenting intraocular pressure (IOP) dropped in blebitis but almost doubled in BRE (P=0.011) compared to average preinfective IOP. Two weeks after treatment, IOPs in both groups returned to close to preinfective levels. Subjects with blebitis more often had an avascular bleb (88.0%) while those with BRE trended toward a moderately vascular bleb (50%). The distribution of causative microorganisms between the groups was similar. Conclusion: Our study indicates that risk factors are similar in both groups even though the visual outcome and clinical course, in the form of IOP findings and bleb vascularity, can diverge significantly. The decreased IOP in blebitis subjects represents objective evidence of subclinical leaks or bleb sweating. Keywords: bleb related endophthalmitis, blebitis, post-trabeculectomy

Clarissa Shu Ming Cheng,1,2 Yi Fang Lee,2 Charles Ong,3 Zhu Li Yap,2 Andrew Tsai,2 Aditi Mohla,2 Monisha E Nongpiur,4 Tin Aung,2,4 Shamira A Perera2,4 1Department of Ophthalmology, Tan Tock Seng Hospital, 2Department of Ophthalmology, Singapore National Eye Centre, 3Yong Loo Lin School of Medicine, National University of Singapore, 4Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Background: To compare retinal vessel oxygenation and vessel caliber in primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and normal controls, as well as between eyes of asymmetrical glaucoma severity.Methods: This was a prospective, cross-sectional study. The 159 subjects (PACG, n=39; POAG, n=41; NTG, n=41; normal controls, n=38) underwent retinal oxygen saturation measurements using the Oxymap T1 Retinal Oximeter, optical coherence tomography, and Humphrey visual field testing. Retinal oxygen saturation and vessel diameter were compared between the glaucoma groups and normal controls, as well as between eyes of asymmetrical glaucoma severity. Kruskal–Wallis test was performed for comparison among different subtypes of glaucoma. Wilcoxon signed-rank test was used to compare the inter-eye differences.Results: Compared to normal controls, arteriolar oxygen saturation was increased in PACG eyes (P=0.048) but not in POAG or NTG eyes. There were no significant differences in oxygen saturation in venules or arteriovenous (AV) difference in all three glaucoma groups. Venular diameter was significantly reduced in all glaucoma groups compared to normal controls (P

Shamira A Perera,1–3 Daniel SW Ting,1,2 Monisha E Nongpiur,1–3 Paul T Chew,3 Maria Cecilia D Aquino,3 Chelvin CA Sng,3 Sue-Wei Ho,1,2 Tin Aung1–3 1Singapore Eye Research Institute, Singapore; 2Singapore National Eye Centre, Singapore; 3Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Purpose: To investigate the efficacy and safety of a punctum plug-based sustained drug release system for a prostaglandin analog, travoprost (OTX-TP), for intraocular pressure (IOP) ­reduction in an Asian population. Methods: This is an initial feasibility, prospective, single-arm study involving 26 eyes and a bioresorbable punctum plug containing OTX-TP. An OTX-TP was placed in the vertical portion of the superior or inferior canaliculus of patients with primary open-angle glaucoma or ocular hypertension. The main outcome measure was the IOP-lowering efficacy of OTX-TP at 3 (8 am) and 10, 20, and 30 days (8 am, 10 am, and 4 pm), compared to baseline. Results: A total of 26 OTX-TP were inserted for 17 subjects. The mean (standard deviation) age was 57.2 (13.8) years. At 10 days, all plugs were still present, and the IOP reduction from baseline was 6.2 (23%), 5.4 (21%), and 7.5 mmHg (28%) at 8 am, 10 am, and 4 pm, respectively. At 10 days, the mean IOP (standard error of mean) was 21.2 (1.2), 20.4 (0.8), and 19.7 (1.0) at 8 am, 10 am, and 4 pm, respectively, showing no discernible IOP trend during the course of the day. At 30 days, plug retention had declined to 42%, and the overall IOP reduction had decreased to 16%. Conclusion: The sustained-release OTX-TP is able to reduce IOP by 24% (day 10) and 15.6% (day 30), respectively. It is a potentially well-tolerable ocular hypotensive for glaucoma patients with a history of poor compliance. Keywords: ocular hypertension, travoprost, bioresorbable, punctum plug, glaucoma, Asian

Background/ Aims: The lack of context for anterior segment optical coherence tomography (ASOCT) measurements impedes its clinical utility. We established the normative distribution of anterior chamber depth (ACD), area (ACA) and width (ACW) and lens vault (LV), and applied percentile cut-offs to detect primary angle closure disease (PACD; ≥180° posterior trabecular meshwork occluded)., Methods: We included subjects from the Singapore Chinese Eye Study with ASOCT scans. Eyes with ocular surgery or laser procedures, and ocular trauma were excluded. A deep-learning algorithm was used to obtain Visante ASOCT (Carl Zeiss Meditec, USA) measurements. Normative distribution was established using 80% of eyes with open angles. Multivariable logistic regression was performed on 80% open and 80% angle closure eyes. Diagnostic performance was evaluated using 20% open and 20% angle closure eyes., Results: We included 2157 eyes (1853 open angles; 304 angle closure) for analysis. ACD, ACA and ACW decreased with age and were smaller in females, and vice versa for LV (all p<0.022). ACD 20th percentile and LV 85th percentile had a balanced accuracy of 84.4% and 84.2% in detecting PACD, respectively. When combined, ACD 20th and LV 85th percentile had 88.68% sensitivity and 88.85% specificity in detecting PACD as compared with a multivariable regression model (ACA, angle opening distance, LV, iris area) with 88.33% sensitivity and 83.75% specificity., Conclusion: Anterior chamber parameters varied with age and gender. The ACD 20th and LV 85th percentile values may be used in silos or in combination to detect PACD in the absence of more sophisticated classification algorithms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To use finite element (FE) analysis to assess what morphologic and biomechanical factors of the iris and anterior chamber are more likely to influence angle narrowing during pupil dilation., Methods: The study consisted of 1344 FE models comprising the cornea, sclera, lens, and iris to simulate pupil dilation. For each model, we varied the following parameters: anterior chamber depth (ACD = 2-4 mm) and anterior chamber width (ACW = 10-12 mm), iris convexity (IC = 0-0.3 mm), iris thickness (IT = 0.3-0.5 mm), stiffness (E = 4-24 kPa), and Poisson's ratio (v = 0-0.3). We evaluated the change in (△∠) and the final dilated angles (∠f) from baseline to dilation for each parameter., Results: The final dilated angles decreased with a smaller ACD (∠f = 53.4° ± 12.3° to 21.3° ± 14.9°), smaller ACW (∠f = 48.2° ± 13.5° to 26.2° ± 18.2°), larger IT (∠f = 52.6° ± 12.3° to 24.4° ± 15.1°), larger IC (∠f = 45.0° ± 19.2° to 33.9° ± 16.5°), larger E (∠f = 40.3° ± 17.3° to 37.4° ± 19.2°), and larger v (∠f = 42.7° ± 17.7° to 34.2° ± 18.1°). The change in angles increased with larger ACD (△∠ = 9.37° ± 11.1° to 15.4° ± 9.3°), smaller ACW (△∠ = 7.4° ± 6.8° to 16.4° ± 11.5°), larger IT (△∠ = 5.3° ± 7.1° to 19.3° ± 10.2°), smaller IC (△∠ = 5.4° ± 8.2° to 19.5° ± 10.2°), larger E (△∠ = 10.9° ± 12.2° to 13.1° ± 8.8°), and larger v (△∠ = 8.1° ± 9.4° to 16.6° ± 10.4°)., Conclusions: The morphology of the iris (IT and IC) and its innate biomechanical behavior (E and v) were crucial in influencing the way the iris deformed during dilation, and angle closure was further exacerbated by decreased anterior chamber biometry (ACD and ACW).

Prcis: The microvasculature of the optic disc and macula in eyes with acute primary angle closure and primary angle closure glaucoma was lower across the disease spectrum, but the significant difference was only observed in primary angle closure glaucoma., Purpose: To assess the microvasculature in the optic nerve head (ONH) and macula across primary angle-closure disease (PACD) spectrum using optical coherence tomography angiography (OCTA)., Methods: OCTA (AngioVue, Fremont, CA) imaging was performed on 122 PACD subjects. Flow area (FA) and vessel density (VD) in the ONH, radial peripapillary capillary (RPC) network, and superficial and deep capillary plexuses of the macula were calculated and compared across the PACD spectrum using linear regression models with generalized estimating equations adjusted for inter-eye correlation., Results: A total of 234 eyes including 44 primary angle-closure suspects (PACS), 93 primary angle-closure (PAC), 79 primary angle-closure glaucoma (PACG) and 18 PAC with history of previous acute primary angle-closure (APAC) were included in the analysis. Compared to other groups, PACG eyes showed smaller FA in the ONH (1.35±0.02 mm2), RPC (0.78±0.03 mm2), and the superficial retinal layer (1.08±0.03 mm2) (all P<0.05). Lower VD was also observed in the "whole image", "inside disc", and "peripapillary" regions of the ONH and RPC, and the "whole image" and "parafoveal" regions of the retinal layer in the PACG group when compared with other groups (all P<0.05). No significant differences were found for the other groups (all P>0.05). Lower VD in the ONH, RPC, and superficial retinal layer significantly correlated with worse visual field loss in PACG eyes (all P<0.05)., Conclusions: Significant reduction in the microvasculature of the optic disc and macula in PACG suggests that glaucoma development may contribute to lower VD in these regions., Competing Interests: Conflict of Interest: No conflicting relationship exists for any author., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: To identify ocular determinants of iridolenticular contact area (ILCA), a recently introduced swept-source optical coherence tomography (SSOCT) derived parameter, and assess the association between ILCA and angle closure., Methods: In this population-based cross-sectional study, right eyes of 464 subjects underwent SSOCT (SS-1000, CASIA, Tomey Corporation, Nagoya, Japan) imaging in the dark. Eight out of 128 cross-sectional images (evenly spaced 22.5° apart) were selected for analysis. Matlab (Matworks, Massachusetts, USA) was used to measure ILCA, defined as the circumferential extent of contact area between the pigmented iris epithelium and anterior lens surface. Gonioscopic angle closure (GAC) was defined as non-visibility of the posterior trabecular meshwork in two or more angle quadrants., Results: The mean age of subjects was 62±6.6 years, with the majority being female (65.5%). 143/464 subjects (28.6%) had GAC. In multivariable linear regression analysis, ILCA was significantly associated with anterior chamber width (β=1.03, p=0.003), pupillary diameter (β=-1.9, p<0.001) and iris curvature (β=-17.35, p<0.001). ILCA was smaller in eyes with GAC compared with those with open angles (4.28±1.6 mm 2 vs 6.02±2.71 mm 2 , p<0.001). ILCA was independently associated with GAC (β=-0.03, p<0.001), iridotrabecular contact index (β=-6.82, p<0.001) or angle opening distance (β=0.02, p<0.001) after adjusting for covariates. The diagnostic performance of ILCA for detecting GAC was acceptable (AUC=0.69)., Conclusions: ILCA is a significant predictor of angle closure independent of other biometric factors and may reflect unique anatomical information associated with pupillary block. ILCA represents a novel biometric risk factor in eyes with angle closure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: RPN, DM and TA have a patent application based on the handheld pupillometer used in this study (PCT/SG2018/050204): Handheld ophthalmic and neurological screening device. The rest of the authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma., Methods: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity., Results: The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR., Conclusions: RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice., Translational Relevance: We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Purpose: To assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG)., Design: Clinic-based cross-sectional study., Methods: The ONH from one eye of 228 subjects (114 subjects with HTG (pre-treatment IOP≥21 mm Hg) and 114 with NTG (pre-treatment IOP<21 mm Hg)) was imaged with optical coherence tomography (OCT) under the following conditions: (1) OCT primary gaze, (2) 20° adduction from OCT primary gaze, (3) 20° abduction from OCT primary gaze and (4) OCT primary gaze with acute IOP elevation (to approximately 33 mm Hg). We then performed digital volume correlation analysis to quantify IOP-induced and gaze-induced ONH tissue deformations and strains., Results: Across all subjects, adduction generated high effective strain (4.4%±2.3%) in the LC tissue with no significant difference (p>0.05) with those induced by IOP elevation (4.5%±2.4%); while abduction generated significantly lower (p=0.01) effective strain (3.1%±1.9%). The lamina cribrosa (LC) of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG: 4.6%±1.7% vs NTG: 4.1%±1.5%, p<0.05). Conversely, the LC of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9%±1.9% vs HTG: 4.0%±1.4%, p<0.05)., Conclusion: We found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects-and that these differences were most pronounced in the LC tissue., Competing Interests: Competing interests: MJAG is the co-founder of the AI start-up company Abyss Processing Pte Ltd., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the incidence and risk factors for primary open-angle glaucoma (POAG) and ocular hypertension (OHT) in a multiethnic Asian population., Design: Population-based cohort study., Participants: The Singapore Epidemiology of Eye Diseases study included 10 033 participants in the baseline examination between 2004 and 2011. Of those, 6762 (response rate = 78.8%) participated in the 6-year follow-up visit between 2011 and 2017., Methods: Standardized examination and investigations were performed, including slit lamp biomicroscopy, intraocular pressure (IOP) measurement, pachymetry, gonioscopy, optic disc examination and static automated perimetry. Glaucoma was defined according to a combination of clinical evaluation, ocular imaging (fundus photo, visual field, and OCT) and criteria given by International Society of Geographical and Epidemiological Ophthalmology. OHT was defined on the basis of elevated IOP over the upper limit of normal; i.e., 20.4 mmHg, 21.5 mmHg, and 22.6 mmHg for the Chinese, Indian, and Malay cohort respectively, without glaucomatous optic disc change., Main Outcome Measures: Incidence of POAG, OHT, and OHT progression., Results: The overall 6-year age-adjusted incidences of POAG and OHT were 1.31% (95% confidence interval [CI], 1.04-1.62) and 0.47% (95% CI, 0.30-0.70). The rate of progression of baseline OHT to POAG at 6 years was 5.32%. Primary open-angle glaucoma incidence was similar (1.37%) in Chinese and Indians and lower (0.80%) in Malays. Malays had higher incidence (0.79%) of OHT than Indians (0.38%) and Chinese (0.37%). Baseline parameters associated with higher risk of POAG were older age (per decade: odds ratio [OR], 1.90; 95% CI, 1.54-2.35; P < 0.001), higher baseline IOP (per mmHg: OR, 1.20; 95% CI, 1.12-1.29; P < 0.001) and longer axial length (per mm: OR, 1.22; 95% CI, 1.07-1.40, P = 0.004)., Conclusion: Six-year incidence of POAG was 1.31% in a multiethnic Asian population. Older age, higher IOP, and longer axial length were associated with higher risk of POAG. These findings can help in future projections and guide public healthcare policy decisions for screening at-risk individuals., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Primary angle closure glaucoma is a visually debilitating disease that is under-detected worldwide. Many of the challenges in managing primary angle closure disease (PACD) are related to the lack of convenient and precise tools for clinic-based disease assessment and monitoring. Artificial intelligence (AI)- assisted tools to detect and assess PACD have proliferated in recent years with encouraging results. Machine learning (ML) algorithms that utilize clinical data have been developed to categorize angle closure eyes by disease mechanism. Other ML algorithms that utilize image data have demonstrated good performance in detecting angle closure. Nonetheless, deep learning (DL) algorithms trained directly on image data generally outperformed traditional ML algorithms in detecting PACD, were able to accurately differentiate between angle status (open, narrow, closed), and automated the measurement of quantitative parameters. However, more work is required to expand the capabilities of these AI algorithms and for deployment into real-world practice settings. This includes the need for real-world evaluation, establishing the use case for different algorithms, and evaluating the feasibility of deployment while considering other clinical, economic, social, and policy-related factors., (Copyright © 2023. Published by Elsevier Ltd.)

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., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The purpose of this study was to isolate the structural components of the ex vivo porcine iris tissue and to determine their biomechanical properties., Methods: The porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n = 32) to evaluate for permeability using Darcy's Law (ΔP = 2000 Pa, A = 0.0391 mm2), and both tissues underwent stress relaxation experiments (ε = 0.5 with initial ramp of δε = 0.1) to evaluate for their viscoelastic behaviours (n = 28). Viscoelasticity was characterized by the parameters β (half width of the Gaussian distribution), τm (mean relaxation time constant), E0 (instantaneous modulus), and E∞ (equilibrium modulus)., Results: For the stroma, the hydraulic permeability was 9.49 ± 3.05 × 10-6 mm2/Pa · s, and the viscoelastic parameters were β = 2.50 ± 1.40, and τm = 7.43 ± 4.96 s, with the 2 moduli calculated to be E0 = 14.14 ± 6.44 kPa and E∞ = 6.08 ± 2.74 kPa. For the dilator tissue, the viscoelastic parameters were β = 2.06 ± 1.33 and τm = 1.28 ± 1.27 seconds, with the 2 moduli calculated to be E0 = 9.16 ± 3.03 kPa and E∞ = 5.54 ± 1.98 kPa., Conclusions: We have established a new protocol to evaluate the biomechanical properties of the structural layers of the iris. Overall, the stroma was permeable and exhibited smaller moduli than those of the dilator muscle. An improved characterization of iris biomechanics may form the basis to further our understanding of angle closure glaucoma.

The imaging data of one eye from 154 healthy and 143 glaucoma participants were acquired to evaluate the contributions of the neuronal and vascular components within the retinal nerve fiber layer (RNFL) for detecting glaucoma and modeling visual field loss through the use of optical coherence tomography (OCT) and OCT angiography. The neuronal and vascular components within the circumpapillary RNFL were independently evaluated. In healthy eyes, the neuronal component showed a stronger association with age (r = -0.52, p < 0.001) compared to measured RNFL thickness (r = -0.46, p < 0.001). Using the neuronal component alone improved detection of glaucoma (AUC: 0.890 ± 0.020) compared to measured RNFL thickness (AUC: 0.877 ± 0.021; χ 2 = 5.54, p = 0.019). Inclusion of the capillary components with the sectoral neuronal component resulted in a significant improvement in glaucoma detection (AUC: 0.927 ± 0.015; χ 2 = 15.34, p < 0.001). After adjusting for potential confounders, AUC increased to 0.952 ± 0.011. Results from modeling visual field loss in glaucoma eyes suggest that visual field losses associated with neuronal thinning were moderated in eyes with a larger capillary component. These findings suggest that segregation of the neurovascular components could help improve understanding of disease pathophysiology and affect disease management in glaucoma., (© 2023 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Objective: To develop and validate a deep learning algorithm that could automate the annotation of scleral spur (SS) and segmentation of anterior chamber (AC) structures for measurements of AC, iris, and angle width parameters in anterior segment OCT (ASOCT) scans., Design: Cross-sectional study., Subjects: Data from 2 population-based studies (i.e., the Singapore Chinese Eye Study and Singapore Malay Eye Study) and 1 clinical study on angle-closure disease were included in algorithm development. A separate clinical study on angle-closure disease was used for external validation., Method: Image contrast of ASOCT scans were first enhanced with CycleGAN. We utilized a heat map regression approach with coarse-to-fine framework for SS annotation. Then, an ensemble network of U-Net, full resolution residual network, and full resolution U-Net was used for structure segmentation. Measurements obtained from predicted SSs and structure segmentation were measured and compared with measurements obtained from manual SS annotation and structure segmentation (i.e., ground truth)., Main Outcome Measures: We measured Euclidean distance and intraclass correlation coefficients (ICC) to evaluate SS annotation and Dice similarity coefficient for structure segmentation. The ICC, Bland-Altman plot, and repeatability coefficient were used to evaluate agreement and precision of measurements., Results: For SS annotation, our algorithm achieved a Euclidean distance of 124.7 μm, ICC ≥ 0.95, and a 3.3% error rate. For structure segmentation, we obtained Dice similarity coefficient ≥ 0.91 for cornea, iris, and AC segmentation. For angle width measurements, ≥ 95% of data points were within the 95% limits-of-agreement in Bland-Altman plot with insignificant systematic bias (all P > 0.12). The ICC ranged from 0.71-0.87 for angle width measurements, 0.54 for IT750, 0.83-0.85 for other iris measurements, and 0.89-0.99 for AC measurements. Using the same SS coordinates from a human expert, measurements obtained from our algorithm were generally less variable than measurements obtained from a semiautomated angle assessment program., Conclusion: We developed a deep learning algorithm that could automate SS annotation and structure segmentation in ASOCT scans like human experts, in both open-angle and angle-closure eyes. This algorithm reduces the time needed and subjectivity in obtaining ASOCT measurements., Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article., (© 2023 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Background/aims: Early detection and treatment of glaucoma can delay vision loss. In this study, we evaluate the performance of handheld chromatic pupillometry (HCP) for the objective and rapid detection of functional loss in glaucoma., Methods: In this clinic-based, prospective study, we enrolled 149 patients (median (IQR) years: 68.5 (13.6) years) with confirmed glaucoma and 173 healthy controls (55.2 (26.7) years). Changes in pupil size in response to 9 s of exponentially increasing blue (469 nm) and red (640 nm) light-stimuli were assessed monocularly using a custom-built handheld pupillometer. Pupillometric features were extracted from individual traces and compared between groups. Features with the highest classification potential, selected using a gradient boosting machine technique, were incorporated into a generalised linear model for glaucoma classification. Receiver operating characteristic curve analyses (ROC) were used to compare the performance of HCP, optical coherence tomography (OCT) and Humphrey Visual Field (HVF)., Results: Pupillary light responses were altered in glaucoma compared with controls. For glaucoma classification, HCP yielded an area under the ROC curve (AUC) of 0.94 (95% CI 0.91 to 0.96), a sensitivity of 87.9% and specificity of 88.4%. The classification performance of HCP in early-moderate glaucoma (visual field mean deviation (VFMD) > -12 dB; AUC=0.91 (95% CI 0.87 to 0.95)) was similar to HVF (AUC=0.91) and reduced compared with OCT (AUC=0.97; p=0.01). For severe glaucoma (VFMD ≤ -12 dB), HCP had an excellent classification performance (AUC=0.98, 95% CI 0.97 to 1) that was similar to HVF and OCT., Conclusion: HCP allows for an accurate, objective and rapid detection of functional loss in glaucomatous eyes of different severities., Competing Interests: Competing interests: DM has a patent application based on the pupillometry protocol used in the present study (PCT/SG2015/050494): A method and system for monitoring and/or assessing pupillary responses. RPN, TA and DM have a patent application based on the handheld pupillometer used in this study (PCT/SG2018/050204): Handheld ophthalmic and neurological screening device. The rest of the authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Observational studies suggest that myopic eyes carry a greater risk of primary open-angle glaucoma (POAG); however, the evidence for this association is inconsistent. This may be the result of confounding factors that arise from myopia that complicate clinical tests for glaucoma. This study used Mendelian randomization (MR) analysis to determine genetic causal associations among myopia, glaucoma, and glaucoma-related traits that overcome the effects of external confounders., Design: Bidirectional genetic associations between myopia and refractive spherical equivalent (RSE), POAG, and POAG endophenotypes were investigated., Participants: Data from the largest publicly available genetic banks (n = 216,257-542,934) were analyzed., Methods: Multiple MR models and multivariate genomic structural modeling to identify significant mediators for the relationship between myopia and POAG., Main Outcome Measures: Genetic causal associations between myopia and POAG and POAG endophenotypes., Results: We found consistent bidirectional genetic associations between myopia and POAG and between myopia and intraocular pressure (IOP) using multiple MR models at Bonferroni-corrected levels of significance. Intraocular pressure showed the most significant mediation effect on RSE and POAG (Sobel test, 0.13; 95% confidence interval, 0.09-0.17; P = 1.37 × 10 -8 )., Conclusions: A strong bidirectional genetic causal link exists between myopia and POAG that is mediated mainly by IOP. Our findings suggest that IOP-lowering treatment for glaucoma may be beneficial in myopic eyes, despite the challenges of establishing a clear clinical diagnosis., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the performance of swept source optical coherence tomography (SS-OCT) to detect gonioscopic angle closure using different classification algorithms., Methods: This was a cross-sectional study of 2028 subjects without ophthalmic symptoms recruited from a community-based clinic. All subjects underwent gonioscopy and SS-OCT (Casia, Tomey Corporation, Nagoya, Japan) under dark room conditions. For each eye, 8 out of 128 frames (22.5° interval) were selected to measure anterior chamber parameters namely anterior chamber width, depth, area and volume (ACW, ACD, ACA, and ACV), lens vault (LV), iris curvature (IC), iris thickness (IT) from 750 µm and 2000 µm from the scleral spur, iris area and iris volume. Five diagnostic algorithms-stepwise logistic regression, random forest, multivariate adaptive regression splines, recursive partitioning and Naïve Bayes were evaluated for detection of gonioscopic angle closure (defined as ≥2 closed quadrants). The performance of the horizontal frame was compared with that of other meridians., Results: Data from 1988 subjects, including 143 (7.2%) with gonioscopic angle closure, were available for analysis. They were divided into two groups: training (1391, 70%) and validation (597, 30%). The best algorithm for detecting gonioscopic angle closure was stepwise logistic regression with an area under the curve of 0.91 (95% CI 0.88 to 0.93) using all parameters, and 0.88 (95% CI 0.82 to 0.93) using only ACA, LV and IC of the horizontal meridian scan., Conclusions: A stepwise logistic regression model incorporating SS-OCT measurements has a high diagnostic ability to detect gonioscopic angle closure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022. The Author(s).)

Aims: To characterise the association between visual field (VF) defects and myopic macular degeneration (MMD) in highly myopic adults without glaucoma., Methods: Participants (n=106; 181 eyes) with high myopia (HM; spherical equivalent ≤-5.0 D or axial length (AL) ≥26 mm), after excluding glaucoma and glaucoma suspects, from the Singapore Epidemiology of Eye Diseases-HM study were included in this cross-sectional study. Humphrey VF (central 24-2 threshold), cup-disc ratio (CDR) and intraocular pressure (IOP) measurements were performed. Mean deviation (MD) and pattern SD (PSD), VF defects (normal or abnormal; p<0.05 in ≥3 non-edge contiguous locations) and pattern (eg, generalised sensitivity loss) were analysed. MMD presence was diagnosed from fundus photographs. Generalised estimating equations were used for analysing factors (MD, PSD, VF defects, CDR and IOP) associated with MMD., Results: Mean age was 55.4±9.9 years and 51.9% were women (AL=26.7±1.1 mm). MMD eyes had lower MD (-3.8±2.9 dB vs -1.1±1.4 dB) and higher PSD (2.8±1.7 dB vs 1.7±0.6 dB). A higher percentage of MMD eyes (n=48) had abnormal VF (62.5% vs 28.6%; p<0.001) compared with no MMD (n=133 eyes). VF pattern in MMD eyes was significantly different from eyes without MMD (p=0.001) with greater generalised sensitivity loss (53.3% vs 10.5%) and arcuate defects (16.7% vs 10.5%). In multivariate analyses, MD (OR=1.52) and PSD (OR=1.67) were significantly (p=0.003) associated with MMD, but VF defects were not associated with MMD., Conclusion: Highly myopic adults with MMD may have VF loss when compared with highly myopic patients without MMD even in adults without glaucoma., Competing Interests: Competing interests: YLW is an employee of Essilor International, Singapore., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

To evaluate machine learning (ML) approaches for structure-function modeling to estimate visual field (VF) loss in glaucoma, models from different ML approaches were trained on optical coherence tomography thickness measurements to estimate global VF mean deviation (VF MD) and focal VF loss from 24-2 standard automated perimetry. The models were compared using mean absolute errors (MAEs). Baseline MAEs were obtained from the VF values and their means. Data of 832 eyes from 569 participants were included, with 537 Asian eyes for training, and 148 Asian and 111 Caucasian eyes set aside as the respective test sets. All ML models performed significantly better than baseline. Gradient-boosted trees (XGB) achieved the lowest MAE of 3.01 (95% CI: 2.57, 3.48) dB and 3.04 (95% CI: 2.59, 3.99) dB for VF MD estimation in the Asian and Caucasian test sets, although difference between models was not significant. In focal VF estimation, XGB achieved median MAEs of 4.44 [IQR 3.45-5.17] dB and 3.87 [IQR 3.64-4.22] dB across the 24-2 VF for the Asian and Caucasian test sets and was comparable to VF estimates from support vector regression (SVR) models. VF estimates from both XGB and SVR were significantly better than the other models. These results show that XGB and SVR could potentially be used for both global and focal structure-function modeling in glaucoma., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

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.)

The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and uveal tissues were historically considered "alymphatic" and thought to be immune privileged. The very fact that the aqueous outflow channels carry a clear fluid (aqueous humor) along the outflow pathway makes it hard to ignore its lymphatic-like characteristics. The development of novel lymphatic lineage markers and expression of these markers in aqueous outflow channels and improved imaging capabilities has sparked a renewed interest in the study of ocular lymphatics. Ophthalmic lymphatic research has had a directional shift over the last decade, offering an exciting new physiological platform that needs further in-depth understanding. The evidence of a presence of distinct lymphatic channels in the human ciliary body is gaining significant traction. The uveolymphatic pathway is an alternative new route for aqueous outflow and adds a new dimension to pathophysiology and management of glaucoma. Developing novel animal models, markers, and non-invasive imaging tools to delineate the core anatomical structure and physiological functions may help pave some crucial pathways to understand disease pathophysiology and help develop novel targeted therapeutic approaches for glaucoma., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). This study assessed whether compensating the RNFL thickness for multiple demographic and anatomic factors improves the detection of glaucoma., Design: Cross-sectional study., Participants: Three hundred eighty-seven patients with glaucoma and 2699 healthy participants., Methods: Two thousand six hundred ninety-nine healthy participants were enrolled to construct and test a multivariate compensation model, which then was applied in 387 healthy participants and 387 patients with glaucoma (early glaucoma, n = 219; moderate glaucoma, n = 97; and advanced glaucoma, n = 71). Participants underwent Cirrus spectral-domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. The RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained., Main Outcome and Measures: Measured and compensated RNFL thickness measurements., Results: After applying the Asian-specific compensation model, the standard deviation of RNFL thickness reduced, where the effect was greatest for Chinese participants (16.9%), followed by Malay participants (13.9%), and Indian participants (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC, 0.90 vs. 0.85; P < 0.001), moderate glaucoma (AUC, 0.94 vs. 0.91; P < 0.001), and advanced glaucoma (AUC, 0.98 vs. 0.96; P < 0.001)., Conclusions: The multivariate normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting that accounting for demographic and anatomic variance in RNFL thickness may have usefulness in improving glaucoma detection., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aims: To compare the shape of the anterior surface of the peripapillary sclera (PPS) between glaucoma and healthy subjects., Methods: 88 primary open angle glaucoma (POAG), 98 primary angle closure glaucoma (PACG) and 372 age-matched and gender-matched healthy controls were recruited in this study. The optic nerve head of one randomly selected eye of each subject was imaged with spectral domain optical coherence tomography. The shape of the PPS was measured through an angle defined between a line parallel to the nasal anterior PPS boundary and one parallel to the temporal side. A negative value indicated that the PPS followed an inverted v-shaped configuration (peak pointing towards the vitreous), whereas a positive value indicated that it followed a v-shaped configuration., Results: The mean PPS angle in normal controls (4.56±5.99°) was significantly smaller than that in POAG (6.60±6.37°, p=0.011) and PACG (7.90±6.87°, p<0.001). The v-shaped PPS was significantly associated with older age (β=1.79, p<0.001), poorer best-corrected visual acuity (β=3.31, p=0.047), central corneal thickness (β=-0.28, p=0.001), peripapillary choroidal thickness (β=-0.21, p<0.001) and presence of POAG (β=1.94, p<0.009) and PACG (β=2.96, p<0.001). The v-shaped configuration of the PPS significantly increased by 1.46° (p=0.001) in healthy controls for every 10-year increase in age, but not in glaucoma groups., Conclusions: The v-shaped configuration of the PPS was more pronounced in glaucoma eyes than in healthy eyes. This posterior bowing of the PPS may have an impact on the biomechanical environment of the optic nerve head., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

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.

To investigate the association of peripheral anterior synechiae (PAS) with intraocular pressure (IOP) and anterior-segment parameters in subjects with primary angle-closure glaucoma (PACG). A total of 267 subjects with PACG were recruited and underwent gonioscopy and anterior-segment optical coherence tomography (ASOCT). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750) and trabecular-iris-space-area (TISA750) at 750 µm from the scleral spur, anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Presenting IOP was defined as the first IOP reading before the initiation of IOP-lowering treatment. The mean age of the 267 subjects was 67.0 ± 8.9 years, 140 (52.4%) were male, and 246 (92.1%) were of Chinese ethnicity. PAS was present in 122 (45.7%) subjects, and was most frequently found in the superior quadrant (79.5%). Subjects with PAS had greater presenting IOP (28.7 ± 12.9 vs 22.4 ± 9.7 mmHg, p < 0.001), narrower AOD750 (p < 0.001), smaller TISA750 (p < 0.001), ACD (p = 0.04), ACA (p = 0.02), ACV (p = 0.01) and larger LV (p = 0.01) compared to PACG eyes without PAS. No significant differences were noted for iris parameters. A multivariate logistic regression analysis showed that higher presenting IOP (β = 0.20, p < 0.001), worse visual field mean deviation (β = - 0.20, p = 0.01) and narrower AOD750 (β = - 0.25, p = 0.03) were the only parameters that significantly correlated with the extent of PAS in clock hours. Almost one-half of the subjects with PACG demonstrated PAS; these eyes were associated with higher presenting IOP, smaller anterior segment dimensions and more severe disease.

Prcis: Reduction of intraocular pressure (IOP) by latanoprost in treatment-naive eyes is significantly correlated to an increase in vessel density (VD) at the optic nerve head (ONH)., Purpose: To evaluate the effect of topical latanoprost on ocular microvasculature using optical coherence tomography angiography (OCTA)., Patients and Methods: In this prospective case-control study, 26 eyes from 18 treatment-naive subjects in whom prostaglandin analogue (PGA) latanoprost 0.005% was initiated were included as cases. In 10 out of the 18 subjects, medication was initiated in only 1 eye; their contralateral untreated eyes were used as controls. OCTA (AngioVue, Optovue Inc., Fremont, CA) was performed at baseline and ≥3 weeks after commencing treatment. Main outcome measures were change in flow area and VD at the ONH, radial peripapillary capillaries (RPC), and macula. Comparison between the 2 visits was performed using a linear mixed model adjusted for intereye correlation and mean ocular perfusion pressure., Results: IOP decreased by 26.1%±11.3% (P<0.001) in the cases and 0.18%±12.2% (P=0.63) in controls. Significant correlations between change in IOP and change in ONH VD (correlation coefficient [r]=-0.42, P=0.04), and between change in IOP and change in RPC VD (r=-0.48, P=0.02) were observed in the cases, whereas none were observed in the controls. When multiple testing was considered, no significant changes in flow area and VD were observed in cases and controls., Conclusions: The reduction of IOP by a PGA in treatment-naive eyes was significantly correlated to the increase in ONH VD and RPC VD. This may indicate a mechanism by which IOP reduction modulates the risk of glaucoma progression by improving ocular microperfusion., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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 (β=-31.93, p<0.001), Indians subjects (β=21.39, p=0.004) (Chinese as the reference), axial length (Axl) (β=-6.68, p=0.032), retinal nerve fibre layer thickness (RNFL) (β=0.71, p=0.019), choroidal thickness (ChT) (β=0.41, p<0.001), vertical cup disc ratio (VCDR) (β=24.42, p<0.001) and disc size (β=-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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness., Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function., Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome., Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function., Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses., Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome., Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Glaucoma is a leading cause of irreversible visual impairment, and primary angle closure glaucoma (PACG) affects Asians disproportionately. Whereas advances in ocular imaging have identified several anatomical risk factors, our ability to predict PACG still requires considerable improvement. The iris plays a crucial role in the pathophysiology of angle closure disease, either through a mechanical or vascular mechanism. Irises of closed-angle eyes inhibit vastly different structural constituents as compared with those of open-angle eyes, thereby effecting variations in biomechanical properties and iris fluid conductivity. The clinical consequences include a smaller change in iris volume on pupil dilation in closed-angle eyes, thereby bringing the iris and trabecular meshwork closer in apposition. In this review, we summarise the potential role of the iris in the pathogenesis of angle closure disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Trabeculectomy has been performed since the mid-1960s and remains the gold standard for glaucoma surgery. Newer surgical options have evolved, collectively referred to as minimally invasive glaucoma surgeries. Despite producing large intraocular pressure decreases, full-thickness procedures into the subconjunctival space may be limited by fibrosis. Mitomycin C (MMC) and 5-fluorouracil have been in use with trabeculectomy with good evidence of significantly increased success at the cost, however, of an increased risk of complications. Off-label MMC application can be found in almost all clinical trials, including in combination with minimally invasive glaucoma surgeries. We explore current evidence for MMC use in trabeculectomy and how this may differ for minimally invasive glaucoma surgery devices and analyze the range of agents and doses that are used. Although we found that most studies could not show any correlation between MMC dosage and the surgical outcome, the success rates with the Xen® microshunt seemed to be higher when using 20 mcg of MMC than when using 10 mcg. Certain important methodological considerations make this hard to confirm definitively, and other factors such as placement of the device may play a more substantial role. For the PreserFlo® microshunt, preliminary data suggest higher success rates with higher MMC dosage at the cost of higher device-related adverse events and reoperations. Although the ideal dose still needs to be established, it seems very likely that MMC provides significant improvement in outcomes in bleb-forming minimally invasive glaucoma procedures., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To compare the distribution of plateau iris in eyes across varying severity of primary angle closure glaucoma (PACG) using standardized ultrasound biomicroscopy (UBM) criteria., Design: Cross-sectional study., Methods: UBM was performed on 210 patients with PACG who had previously undergone laser peripheral iridotomy. Plateau iris was defined as the presence of all the following UBM criteria in ≥2 quadrants of the angle: anteriorly directed ciliary body, absent ciliary sulcus, iris angulation, flat iris plane, and iridotrabecular contact. Disease severity was based on the visual field mean deviation (MD) and classified as early-to-moderate (MD ≥ -12 dB), advanced (-12.01 dB to -20 dB), and severe (MD < -20 dB)., Results: Of 210 subjects recruited, 23 were excluded because of poor quality UBM images. The remaining 187 patients were categorized as having early-to-moderate (n = 103), advanced (n = 38), and severe PACG (n = 46). Of these subjects, 48.1% were male, and 90.9% were of Chinese ethnicity. The overall proportion of plateau iris was 36.9%, with 32.0% (33/103) in early-to-moderate, 34.2% (13/38) in advanced, and 50% (23/46) in severe PACG (P = .03, comparing severe PACG with early-to-moderate groups). Among the severe PACG group, those with plateau iris configuration had significantly smaller anterior chamber area (P = .03) and volume (P = .01) compared with those without plateau iris., Conclusion: The higher proportion of plateau iris configuration in eyes with severe PACG compared with early-to-moderate PACG suggest that this may be a contributory factor for disease severity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare the diagnostic ability of macular intraretinal layer thickness with circumpapillary retinal nerve fiber layer (cpRNFL) thickness, either when used individually or in combination with cpRNFL for detecting early, moderate, and advanced glaucoma., Design: Cross-sectional study., Participants: A total of 423 glaucoma participants and 423 age- and gender-matched normal participants., Methods: Participants underwent Cirrus spectral-domain OCT (SD-OCT) imaging (Carl Zeiss Meditec, Dublin, CA) using the optic disc and macular scanning protocols. Iowa Reference Algorithms (version 3.8.0) were used for intraretinal layer segmentation, and mean thickness of intraretinal layers was rescaled with magnification correction using axial length value. Thickness measurements of each layer/sector and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. Glaucoma eyes were subdivided based on of their visual field severity (early, n = 234; moderate, n = 107; advanced, n = 82)., Main Outcome Measures: Intraretinal layers., Results: Some 67% of participants were male, their average ± standard deviation age was 65±9 years. Circumpapillary retinal nerve fiber layer, macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) were significantly thinner in the glaucoma groups (P < 0.0005). The 2 best parameters for detecting normal eyes from early glaucoma was cpRNFL (AUC = 0.861) and mGCL (AUC = 0.842), from moderate glaucoma was mGCL combined with inner plexiform layer (IPL) (AUC = 0.915) and cpRNFL (AUC = 0 .914), and from advanced glaucoma was mGCL-IPL (AUC = 0.984) and cpRNFL (AUC = 0.977). There was no statistical significance between AUCs for the macular parameter and cpRNFL thickness measurement at any of the severities (P > 0.05). Combining macular and cpRNFL parameters improved the diagnostic performance for early glaucoma (AUC = 0.908; P = 0.002) and moderate glaucoma (AUC = 0.944; P = 0.031) but not for advanced glaucoma (AUC = 0.991; P > 0.05)., Conclusions: Single-layer mGCL thickness is comparable to the traditional cpRNFL thickness for the diagnosis of early/moderate glaucoma, whereas cpRNFL thickness remains the most efficient for advanced glaucoma. Combining macular measurements (GCL and GCL-IPL) and cpRNFL improved the discrimination of early/moderate glaucoma but not of advanced glaucoma. For the diagnosis of early glaucoma, both macular and optic disc scans should be used., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)