A comparison of intraocular pressure measurement using SUOER SW-500 rebound tonometer and conventional reusable Goldmann prisms.

Introduction: To determine the agreement between intraocular pressure (IOP) measurements using conventional Goldmann applanation tonometry (GA1,2T) and SUOER SW-500 Rebound Tonometer. Methods: This was a retrospective observational study where 205 eyes of 106 glaucoma patients had their IOPs measured by 2 fellowship trained ophthalmologists. Data were analyzed using the Bland-Altman method of differences. Correlation was measured using the Pearson coefficient. Results: Most of our patients were Chinese (88.7%) and female (51.9%). The average age was 66.9 years. The range of IOPs as measured by GAT was 2 to 58 mm Hg. Using the Bland-Altman method to compare GAT and SUOER SW-500 Rebound Tonometer. The tonometer overestimated the IOP by 0.5 mm Hg in the right eye and underestimated it by 0.1 mm Hg in the left eye. Overall, the tonometer overestimated the IOP by 0.2 mmHg. The Tonometer IOP correlated well with GAT, with a Pearson coefficient of correlation(r) of 0.89 (p < 0.001) for the right eye and 0.86 (p < 0.001) for the left eye, respectively. In patients with GAT IOP ≥ 21 mm Hg (n = 25), the Tonometer underestimated the IOP by 2.96 mm Hg. Discussion: The IOP measurements from the SUOER SW-500 Rebound Tonometer correlates well with the conventional GAT in measuring the IOP within normal ranges of IOP. SUOER SW-500 Rebound Tonometer may be of use, especially if the risk of transmission of infection is high considering that the probes are disposable. It is easy to use and its small size and portability makes it useful in situations where the patient is unable to be examined at the slit lamp.

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.

Does Bevacizumab Improve Outcomes After Ahmed Glaucoma Valve Implantation for Refractory Glaucoma?: A Meta-Analysis.

PRCIS: Mean intraocular pressure (IOP), complete and overall success, mean IOP-lowering medications, incidence of hypertensive phase, and complications were found to be comparable between patients undergoing Ahmed glaucoma valve implantation (AGVI) with adjunctive bevacizumab versus AGVI alone. OBJECTIVE: This meta-analysis aims to assess how adjunctive bevacizumab impacts the surgical outcomes of AGVI compared with AGVI alone in all subtypes of refractory glaucoma. METHODS: A systematic search of databases for relevant randomized controlled trials (RCTs) was performed in March 2023. Primary outcomes included mean IOP and success rates. Secondary outcomes were mean IOP-lowering medications, incidence of hypertensive phase, and complications. Qualitative assessment, meta-analysis, subgroup analyses, and sensitivity analysis were performed. RESULTS: Five RCTs comprising 203 eyes were included in the quantitative analysis. Initial meta-analysis showed a strong yet nonsignificant trend (all P > 0.05) favoring adjunctive bevacizumab in all outcomes of interest. Significant heterogeneity was observed for mean IOP and success outcomes at all time points (all I2 > 50%). Subgroup analysis of the administration route revealed a reduced incidence of hyphaema in the intravitreal bevacizumab subgroup (odds ratio: 0.10; 95% CI: 0.02 to 0.59; P = 0.01) with significant heterogeneity persisting in the intravitreal bevacizumab subgroup for all measures (all I2 > 50%). Post hoc sensitivity analysis of studies without concurrent pan-retinal photocoagulation for mean IOP and success outcomes demonstrated more conservative effect sizes with a corresponding decrease in heterogeneity for all measures (all I2 < 30%). CONCLUSION: Published studies investigating the role of adjunctive bevacizumab show a strong trend to improve outcomes but contain a relatively small number of participants. This analysis underpins the need for an adequately powered RCT to explore the role of anti-vascular endothelial growth factor agents in AGVI surgery.

AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing.

BACKGROUND/AIMS: To use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness (ie, sensitivity of the ONH to changes in intraocular pressure (IOP)) from a single optical coherence tomography (OCT) volume scan of the ONH without the need for biomechanical testing and (3) identify what critical three-dimensional (3D) structural features dictate ONH robustness. METHODS: 316 subjects had their ONHs imaged with OCT before and after acute IOP elevation through ophthalmo-dynamometry. IOP-induced lamina cribrosa (LC) deformations were then mapped in 3D and used to classify ONHs. Those with an average effective LC strain superior to 4% were considered fragile, while those with a strain inferior to 4% robust. Learning from these data, we compared three AI algorithms to predict ONH robustness strictly from a baseline (undeformed) OCT volume: (1) a random forest classifier; (2) an autoencoder and (3) a dynamic graph convolutional neural network (DGCNN). The latter algorithm also allowed us to identify what critical 3D structural features make a given ONH robust. RESULTS: All three methods were able to predict ONH robustness from a single OCT volume scan alone and without the need to perform biomechanical testing. The DGCNN (area under the curve (AUC): 0.76±0.08) outperformed the autoencoder (AUC: 0.72±0.09) and the random forest classifier (AUC: 0.69±0.05). Interestingly, to assess ONH robustness, the DGCNN mainly used information from the scleral canal and the LC insertion sites. CONCLUSIONS: We propose an AI-driven approach that can assess the robustness of a given ONH solely from a single OCT volume scan of the ONH, and without the need to perform biomechanical testing. Longitudinal studies should establish whether ONH robustness could help us identify fast visual field loss progressors. PRECIS: Using geometric deep learning, we can assess optic nerve head robustness (ie, sensitivity to a change in IOP) from a standard OCT scan that might help to identify fast visual field loss progressors.

Adduction induces large optic nerve head deformations in subjects with normal-tension glaucoma.

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.

Three-Dimensional Structural Phenotype of the Optic Nerve Head as a Function of Glaucoma Severity.

Importance: The 3-dimensional (3-D) structural phenotype of glaucoma as a function of severity was thoroughly described and analyzed, enhancing understanding of its intricate pathology beyond current clinical knowledge. Objective: To describe the 3-D structural differences in both connective and neural tissues of the optic nerve head (ONH) between different glaucoma stages using traditional and artificial intelligence-driven approaches. Design, Setting, and Participants: This cross-sectional, clinic-based study recruited 541 Chinese individuals receiving standard clinical care at Singapore National Eye Centre, Singapore, and 112 White participants of a prospective observational study at Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. The study was conducted from May 2022 to January 2023. All participants had their ONH imaged using spectral-domain optical coherence tomography and had their visual field assessed by standard automated perimetry. Main Outcomes and Measures: (1) Clinician-defined 3-D structural parameters of the ONH and (2) 3-D structural landmarks identified by geometric deep learning that differentiated ONHs among 4 groups: no glaucoma, mild glaucoma (mean deviation [MD], ≥-6.00 dB), moderate glaucoma (MD, -6.01 to -12.00 dB), and advanced glaucoma (MD, <-12.00 dB). Results: Study participants included 213 individuals without glaucoma (mean age, 63.4 years; 95% CI, 62.5-64.3 years; 126 females [59.2%]; 213 Chinese [100%] and 0 White individuals), 204 with mild glaucoma (mean age, 66.9 years; 95% CI, 66.0-67.8 years; 91 females [44.6%]; 178 Chinese [87.3%] and 26 White [12.7%] individuals), 118 with moderate glaucoma (mean age, 68.1 years; 95% CI, 66.8-69.4 years; 49 females [41.5%]; 97 Chinese [82.2%] and 21 White [17.8%] individuals), and 118 with advanced glaucoma (mean age, 68.5 years; 95% CI, 67.1-69.9 years; 43 females [36.4%]; 53 Chinese [44.9%] and 65 White [55.1%] individuals). The majority of ONH structural differences occurred in the early glaucoma stage, followed by a plateau effect in the later stages. Using a deep neural network, 3-D ONH structural differences were found to be present in both neural and connective tissues. Specifically, a mean of 57.4% (95% CI, 54.9%-59.9%, for no to mild glaucoma), 38.7% (95% CI, 36.9%-40.5%, for mild to moderate glaucoma), and 53.1 (95% CI, 50.8%-55.4%, for moderate to advanced glaucoma) of ONH landmarks that showed major structural differences were located in neural tissues with the remaining located in connective tissues. Conclusions and Relevance: This study uncovered complex 3-D structural differences of the ONH in both neural and connective tissues as a function of glaucoma severity. Future longitudinal studies should seek to establish a connection between specific 3-D ONH structural changes and fast visual field deterioration and aim to improve the early detection of patients with rapid visual field loss in routine clinical care.

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.

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.

Lens extraction versus laser peripheral iridotomy for acute primary angle closure.

BACKGROUND: Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process.  OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 10 January 2022. SELECTION CRITERIA: We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( ≥ 35 years) with APAC in one or both eyes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures.  Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95% CI -168.91 to -85.69; 1 study, n = 60).  In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP > 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3).  Neither study reported health- or vision-related quality of life measures. AUTHORS' CONCLUSIONS: Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.

Oral Ibuprofen is Associated With Reduced Likelihood of Early Bleb Failure After Trabeculectomy in High-Risk Glaucoma Patients.

PRCIS: Individuals prescribed ibuprofen after trabeculectomy have better postoperative intraocular pressure (IOP) control and a higher chance of bleb survival despite being at a higher risk of scarring. PURPOSE: To investigate the effects of early adjunctive oral ibuprofen treatment on IOP and bleb failure in eyes at high risk of scarring. METHODS: In these retrospective analyses, 288 eyes of 273 patients (mean ± SD age: 68.56 ± 10.47 y; 32.60% females) with primary glaucoma who underwent trabeculectomy/phacotrabeculectomy at the Singapore National Eye Centre between April 2020 and April 2021 with a follow-up duration ≥1 year were included. Of these, 77 (26.7%) eyes deemed to be at high risk of scarring were administered oral ibuprofen ≥3 months postoperatively (mean ± SD ibuprofen administration duration: 4.08 ± 2.28 wk). Participant's IOPs at baseline and at postoperative weeks 1, 2-3; and months 1, 2, 3, 6, and 12 were recorded. Bleb failure was defined as 2 consecutive IOP readings of >21, >18, and >15 mm Hg, and/or requiring remedial postoperative laser or surgery. RESULTS: The ibuprofen group experienced significantly greater postoperative IOP reductions at week 1 [mean difference, 95%CI: -2.89 (-5.22, -0.56) mm Hg] and month 1 [-2.29 (-4.53, -0.05) mm Hg]; and substantially lower odds of bleb failure at the >18 mm Hg [odds ratio, 95% CI: 0.39 (0.20-0.79)] and >15 mm Hg [0.52 (0.29-0.94)] thresholds, compared with the non-ibuprofen group. No differences in adverse ocular hypotony events were observed. CONCLUSION: Early adjunctive oral ibuprofen administered to individuals at high risk of posttrabeculectomy scarring is associated with greater IOP reductions and reduced likelihood of bleb failure. Our results suggest that oral nonsteroidal anti-inflammatory drugs may be a safe way of improving trabeculectomy survival in high-risk eyes.

A decision-support tool for funding health innovations at a tertiary academic medical center.

OBJECTIVES: To report the processes used to design and implement an assessment tool to inform funding decisions for competing health innovations in a tertiary hospital. METHODS: We designed an assessment tool for health innovation proposals with three components: "value to the institution," "novelty," and "potential for adoption and scaling." The "value to the institution" component consisted of twelve weighted value attributes identified from the host institution's annual report; weights were allocated based on a survey of the hospital's leaders. The second and third components consisted of open-ended questions on "novelty" and "barriers to implementation" to support further dialogue. Purposive literature review was performed independently by two researchers for each assessment. The assessment tool was piloted during an institutional health innovation funding cycle. RESULTS: We used 17 days to evaluate ten proposals. The completed assessments were shared with an independent group of panellists, who selected five projects for funding. Proposals with the lowest scores for "value to the institution" had less perceived impact on the patient-related value attributes of "access," "patient centeredness," "health outcomes," "prevention," and "safety." Similar innovations were reported in literature in seven proposals; potential barriers to implementation were identified in six proposals. We included a worked example to illustrate the assessment process. CONCLUSIONS: We developed an assessment tool that is aligned with local institutional priorities. Our tool can augment the decision-making process when funding health innovation projects. The tool can be adapted by others facing similar challenges of trying to choose the best health innovations to fund.

Handheld chromatic pupillometry can accurately and rapidly reveal functional loss in glaucoma.

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.

Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Patients with Normal- and High-Tension Glaucoma.

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

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.

The three-dimensional structural configuration of the central retinal vessel trunk and branches as a glaucoma biomarker.

PURPOSE: To assess whether the 3-dimensional (3D) structural configuration of the central retinal vessel trunk and its branches (CRVT&B) could be used as a diagnostic marker for glaucoma. DESIGN: Retrospective, deep-learning approach diagnosis study. METHODS: We trained a deep learning network to automatically segment the CRVT&B from the B-scans of the optical coherence tomography (OCT) volume of the optic nerve head. Subsequently, 2 different approaches were used for glaucoma diagnosis using the structural configuration of the CRVT&B as extracted from the OCT volumes. In the first approach, we aimed to provide a diagnosis using only 3D convolutional neural networks and the 3D structure of the CRVT&B. For the second approach, we projected the 3D structure of the CRVT&B orthographically onto sagittal, frontal, and transverse planes to obtain 3 two-dimensional (2D) images, and then a 2D convolutional neural network was used for diagnosis. The segmentation accuracy was evaluated using the Dice coefficient, whereas the diagnostic accuracy was assessed using the area under the receiver operating characteristic curves (AUCs). The diagnostic performance of the CRVT&B was also compared with that of retinal nerve fiber layer (RNFL) thickness (calculated in the same cohorts). RESULTS: Our segmentation network was able to efficiently segment retinal blood vessels from OCT scans. On a test set, we achieved a Dice coefficient of 0.81 ± 0.07. The 3D and 2D diagnostic networks were able to differentiate glaucoma from nonglaucoma subjects with accuracies of 82.7% and 83.3%, respectively. The corresponding AUCs for the CRVT&B were 0.89 and 0.90, higher than those obtained with RNFL thickness alone (AUCs ranging from 0.74 to 0.80). CONCLUSIONS: Our work demonstrated that the diagnostic power of the CRVT&B is superior to that of a gold-standard glaucoma parameter, that is, RNFL thickness. Our work also suggested that the major retinal blood vessels form a "skeleton"-the configuration of which may be representative of major optic nerve head structural changes as typically observed with the development and progression of glaucoma.

Outcomes of surgical bleb revision at a tertiary Singapore eye hospital.

PURPOSE: To describe the outcomes of surgical bleb revisions from a tertiary glaucoma service in Singapore. METHODS: One hundred and thirty-one eyes of 129 patients who underwent surgical bleb revisions at the Singapore National Eye Centre between 2007 and 2014 were included in the study. The indications for bleb revision were: bleb-related infection (BRI), early and late bleb leak, early and late overfiltration, and bleb dysesthesia. Regression analysis was applied to elucidate risk factors. RESULTS: The mean age of the patients was 66 years, 62.6% were male, and 88.5% were Chinese. The majority of the eyes had primary glaucoma (79.4%). The mean interval from the initial trabeculectomy or phaco-trabeculectomy to the bleb revision was 58.8 months. The overall success rate was 69.5%. By Kaplan-Meier survival analysis, the overall cumulative success range fell from 78.6% to 49.1% over 10 years. Eyes with early bleb leak had lower surgical success compared to eyes with late bleb leak, early overfiltration and late overfiltration (P = 0.026, log-rank test). The IOP improved significantly post-operatively for eyes with BRI, early bleb leak, late bleb leak, early overfiltration and overfiltration (P < 0.05). Vision improved significantly in eyes with early overfiltration, but deteriorated in eyes with BRI (P < 0.05). CONCLUSION: The overall success rate for surgical bleb revisions was good with complete resolution of the primary problem in the majority of cases. However, eyes with early bleb leak were less likely to have successful outcomes and should be monitored more closely post-operatively.

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.

Describing the Structural Phenotype of the Glaucomatous Optic Nerve Head Using Artificial Intelligence.

PURPOSE: To develop a novel deep-learning approach that can describe the structural phenotype of the glaucomatous optic nerve head (ONH) and can be used as a robust glaucoma diagnosis tool. DESIGN: Retrospective, deep-learning approach diagnosis study. METHOD: We trained a deep-learning network to segment 3 neural-tissue and 4 connective-tissue layers of the ONH. The segmented optical coherence tomography images were then processed by a customized autoencoder network with an additional parallel branch for binary classification. The encoder part of the autoencoder reduced the segmented optical coherence tomography images into a low-dimensional latent space (LS), whereas the decoder and the classification branches reconstructed the images and classified them as glaucoma or nonglaucoma, respectively. We performed principal component analysis on the latent parameters and identified the principal components (PCs). Subsequently, the magnitude of each PC was altered in steps and reported how it impacted the morphology of the ONH. RESULTS: The image reconstruction quality and diagnostic accuracy increased with the size of the LS. With 54 parameters in the LS, the diagnostic accuracy was 92.0 ± 2.3% with a sensitivity of 90.0 ± 2.4% (at 95% specificity), and the corresponding Dice coefficient for the reconstructed images was 0.86 ± 0.04. By changing the magnitudes of PC in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a "nonglaucoma" to a "glaucoma" condition. CONCLUSIONS: Our network was able to identify novel biomarkers of the ONH for glaucoma diagnosis. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma.

Multivariate Normative Comparison, a Novel Method for Improved Use of Retinal Nerve Fiber Layer Thickness to Detect Early Glaucoma.

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.