title: Optic nerve head and fibre layer imaging for diagnosing glaucoma.
abstract: BACKGROUND
  The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma.
  
  
  OBJECTIVE
  To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage.
  
  
  METHODS
  We searched several databases for this review. The most recent searches were on 19 February 2015.
  
  
  METHODS
  We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or ECC.
  
  
  METHODS
  We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level.
  
  
  RESULTS
  We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear.Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study.The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio.Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people.Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD < -6 db versus 0.64 (0.60 to 0.69) for MD ≥ -6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P < 0.0001 for the difference in relative DOR).
  
  
  CONCLUSIONS
  The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base.We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data.
authors.affiliation: Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Via Livenza n 3, Rome, Italy, 00198.
authors.forename: Manuele
authors.initials: M
authors.lastname: Michelessi
authors.forename: Ersilia
authors.initials: E
authors.lastname: Lucenteforte
authors.forename: Francesco
authors.initials: F
authors.lastname: Oddone
authors.forename: Miriam
authors.initials: M
authors.lastname: Brazzelli
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Parravano
authors.forename: Sara
authors.initials: S
authors.lastname: Franchi
authors.forename: Sueko M
authors.initials: SM
authors.lastname: Ng
authors.forename: Gianni
authors.initials: G
authors.lastname: Virgili
mesh_terms: D003951:Diagnostic Errors / Q000706:statistics & numerical data; D005901:Glaucoma / Q000175:diagnosis*; D006801:Humans; D009412:Nerve Fibers / Q000473:pathology*; D016017:Odds Ratio; D009887:Ophthalmoscopy / Q000592:standards*; D009898:Optic Disk / Q000473:pathology*; D011446:Prospective Studies; D012189:Retrospective Studies; D057109:Scanning Laser Polarimetry / Q000592:standards*; D012680:Sensitivity and Specificity; D041623:Tomography, Optical Coherence / Q000592:standards*; D058609:Visual Field Tests