Optic nerve head and fibre layer imaging for diagnosing glaucoma

Methodological quality of the review: High confidence

Authors: Michelessi M, Lucenteforte E, Oddone F, Brazzelli M, Parravano M, Franchi S, Ng SM, and Virgili G

Region: Asia, Europe, North America, South America and Oceania

Sector: Glaucoma

Sub-sector: Diagnosis

Equity focus: None specified

Review type: Other review

Quantitative synthesis method: Narrative synthesis

Qualitative synthesis method: Not applicable

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 (through a device commercially known as the Heidelberg Retina Tomograph or 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.

Objectives:

To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage.

Main findings:

A total of 106 studies were included in this review, which analyzed 16,260 eyes (8,353 cases, 7,907 controls) in total. Most studies were conducted in Asia (44), followed by Europe (31), North America (24), South America (two) and Oceania (one). Four studies did not report sufficient information to determine study setting.

Forty studies (5,574 participants) assessed GDx, 18 studies (3,550 participants) HRT, and 63 (9,390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, the authors note that 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.

The authors reported that 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 authors found 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 1,000 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%, (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).

Overall, the authors concluded that the accuracy of imaging tests for detecting manifest glaucoma was similar for different devices. They emphasize that accuracy may have been overestimated due to the case-control design. They recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway.

Methodology: 

The authors included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. They excluded population-based screening studies, since it was 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. The authors only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or ECC.

The authors searched the Database of Abstracts of Reviews of Effects, the Health Technology Assessment Database and the NHS Economic Evaluation Database, Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, EMBASE, MEDION and the Aggressive Research Intelligence Facility database. No date or language restrictions were applied in the electronic searches for studies. Searches were last conducted on 19 February 2015. In addition, the authors reviewed the reference lists of the included studies for further relevant studies.

Two authors independently screened studies for inclusion, extracted data and appraised included studies. Methodological assessment was conducted using QUADAS 2.

Applicability/external validity:

The authors note that the main quality issue was the case-control design (103 studies) or unclear design (two studies) of all included studies except one. This led to a high risk of bias for the Patient Selection domain in QUADAS 2, and raised concerns about the applicability of findings to clinical practice, particularly when the purpose is to triage patients to be referred to glaucoma centres.

Geographic focus

Most included studies were conducted in Asia (44), followed by Europe (31), North America (24), South America (two) and Oceania (one). Four studies did not report sufficient information to determine study setting.

Summary of quality assessment:

High confidence was attributed in the conclusions about the effects of this study. The authors conducted thorough searches of the literature avoiding biases, and used appropriate methods to screen studies for inclusion extract data and appraise included studies. In addition, authors acknowledged limitations of the review and did not draw strong policy conclusions.