Non-contact tests for identifying people at risk of primary angle closure glaucoma

Background: Primary angle closure glaucoma (PACG) accounts for 50% of glaucoma blindness worldwide. More than three-quarters of individuals with PACG reside in Asia. In these populations, PACG often develops insidiously leading to chronically raised intraocular pressure and optic nerve damage, which is often asymptomatic. Non-contact tests to identify people at risk of angle closure are relatively quick and can be carried out by appropriately trained healthcare professionals or technicians as a triage test. If the test is positive, the person will be referred for further specialist assessment. Objectives: To determine the diagnostic accuracy of non-contact tests (limbal anterior chamber depth (LACD) (van Herick test); oblique flashlight test; scanning peripheral anterior chamber depth analyser (SPAC), Scheimpflug photography; anterior segment optical coherence tomography (AS-OCT), for identifying people with an occludable angle. Search methods: We searched the following bibliographic databases 3 October 2019: CENTRAL; MEDLINE; Embase; BIOSIS; OpenGrey; ARIF and clinical trials registries. The searches were limited to remove case reports. There were no date or language restrictions in the searches. Selection criteria: We included prospective and retrospective cross-sectional, cohort and case-control studies conducted in any setting that evaluated the accuracy of one or more index tests for identifying people with an occludable angle compared to a gonioscopic reference standard. Data collection and analysis: Two review authors independently performed data extraction and quality assessment using QUADAS2 for each study. For each test, 2 x 2 tables were constructed and sensitivity and specificity were calculated. When four or more studies provided data at fixed thresholds for each test, we fitted a bivariate model using the METADAS macro in SAS to calculate pooled point estimates for sensitivity and specificity. For comparisons between index tests and subgroups, we performed a likelihood ratio test comparing the model with and without the covariate. Main results: We included 47 studies involving 26,151 participants and analysing data from 23,440. Most studies were conducted in Asia (36, 76.6%). Twenty-seven studies assessed AS-OCT (analysing 15,580 participants), 17 studies LACD (7385 participants), nine studies Scheimpflug photography (1616 participants), six studies SPAC (5239 participants) and five studies evaluated the oblique flashlight test (998 participants). Regarding study quality, 36 of the included studies (76.6%) were judged to have a high risk of bias in at least one domain.The use of a case-control design (13 studies) or inappropriate exclusions (6 studies) raised patient selection concerns in 40.4% of studies and concerns in the index test domain in 59.6% of studies were due to lack of masking or post-hoc determination of optimal thresholds. Among studies that did not use a case-control design, 16 studies (20,599 participants) were conducted in a primary care/community setting and 18 studies (2590 participants) in secondary care settings, of which 15 investigated LACD. Summary estimates were calculated for commonly reported parameters and thresholds for each test; LACD ≤ 25% (16 studies, 7540 eyes): sensitivity 0.83 (95% confidence interval (CI) 0.74, 0.90), specificity 0.88 (95% CI 0.84, 0.92) (moderate-certainty); flashlight (grade1) (5 studies, 1188 eyes): sensitivity 0.51 (95% CI 0.25, 0.76), specificity 0.92 (95% CI 0.70, 0.98) (low-certainty); SPAC (≤ 5 and/or S or P) (4 studies, 4677 eyes): sensitivity 0.83 (95% CI 0.70, 0.91), specificity 0.78 (95% CI 0.70, 0.83) (moderate-certainty); Scheimpflug photography (central ACD) (9 studies, 1698 eyes): sensitivity 0.92 (95% CI 0.84, 0.96), specificity 0.86 (95% CI 0.76, 0.93) (moderate-certainty); AS-OCT (subjective opinion of occludability) (13 studies, 9242 eyes): sensitivity 0.85 (95% CI 0.76, 0.91); specificity 0.71 (95% CI 0.62, 0.78) (moderate-certainty). For comparisons of sensitivity and specificity between index tests we used LACD (≤ 25%) as the reference category. The flashlight test (grade 1 threshold) showed a statistically significant lower sensitivity than LACD (≤ 25%), whereas AS-OCT (subjective judgement) had a statistically significant lower specificity. There were no statistically significant differences for the other index test comparisons. A subgroup analysis was conducted for LACD (≤ 25%), comparing community (7 studies, 14.4% prevalence) vs secondary care (7 studies, 42% prevalence) settings. We found no evidence of a statistically significant difference in test performance according to setting. Performing LACD on 1000 people at risk of angle closure with a prevalence of occludable angles of 10%, LACD would miss about 17 cases out of the 100 with occludable angles and incorrectly classify 108 out of 900 without angle closure. Authors' conclusions: The finding that LACD performed as well as index tests that use sophisticated imaging technologies, confirms the potential for this test for case-detection of occludable angles in high-risk populations. However, methodological issues across studies may have led to our estimates of test accuracy being higher than would be expected in standard clinical practice. There is still a need for high-quality studies to evaluate the performance of non-invasive tests for angle assessment in both community-based and secondary care settings