Table 1.

Characteristics of the included systematic reviews

	Ahmed et al²⁰	Fallon et al²¹	Kansal et al²²	Michelessi et al²⁸
Clinical pathway discussion	Target condition and the current gold standard for glaucoma diagnosis were described. Five glaucoma technologies compared with the gold standard of white on white perimetry for glaucoma detection. No further info	Target condition defined in term of frequency, severity and prognosis. The authors reported how glaucoma is currently identified and how the imaging devices may play a role in glaucoma diagnosis, with the aim to identify patients with glaucoma early in the disease course. No further info	Target condition defined in terms of frequency and severity. The currently accepted gold standard for glaucoma diagnosis is discussed. Test variations in terms of different manufacturers, which are playing an increasing role in glaucoma diagnosis. No further info	Evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma by using these devices as add-on test, in people who have already been tested by means of clinical examination at primaiy care level, including ONH clinical assessment, IOP measurement and even visual field testing. Target condition, index test and clinical pathway categories, almost completely described
Databases searched and date restrictions	5 (from 1993 to February 2015)	4 (from January 2004 to February 2015)	6 (up to February 2017)	8 (up to February 2015)
Grey literature	Websites of HTA agencies, professional associations. Google search for web based, hand searching the bibliographies and abstracts of key papers and conference proceedings, contacts with appropriate experts and agencies	None	None	Reference lists of the included studies
Tests included and OCT models	OCT (time domain (TD), spectral domain (SD)), confocal scanning laser ophthalmoscopy, scanning laser polarimetiy or frequency doubling technology, blue/yellow perimetry	OCT SD), confocal scanning laser ophthalmoscopy, scanning laser polarimetry	OCT (SD,TD)	OCT (SD), confocal scanning laser ophthalmoscopy, scanning laser polarimetiy
Inclusion/exclusion criteria	Inclusion criteria: any study evaluating testing outcomes for open-angle glaucoma. Any geographical study type (single vs multicentre); any sampling strategy; all ethnic background and studies conducted in any country. Any study bases (population or clinic-based samples). Age >18 years old Exclusion criteria:<20 participants	Inclusion criteria: any study evaluating the ability of image devices (HRT3, GDx, and SD-OCT) to differentiate between normal and glaucoma in which index and reference test were used in the same population. Prospective design. Observational, descriptive (base population, cross sectional), analytical studies (case control, cohort), and experimental studies (clinical trials). >50 participants. Study reporting sensitivity and specificity of the test(s) and quality criteria. Study published in English, Spanish or French. Screening studies were included only in the qualitative analysis Exclusion criteria: study investigating specific subgroups of subjects, such as children, young individuals or subjects with ophtha I mo logical or neurological diseases	Inclusion criteria: study evaluating the diagnostic accuracy of OCT (Stratus OCT, Cirrus OCT, Spectralis OCT, RTVue, and 3D-OCT Topcon) for glaucoma detection. Human, clinical studies published in English-language. Age>18 years. Any patient ethnicity, or countiy. Studies reporting area under the ROC curve. Exclusion criteria: not reporting SE or CIs, duplicate manuscripts, non-diagnostic studies, paediatric patients, no control group	Inclusion criteria: prospective and retrospective cohort studies and case-control studies evaluating the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. Both single studies assessing each imaging method and comparative studies assessing more than one imaging method in the same patient population. Studies providing data to allow calculation of sensitivity and specificity estimates Exclusion criteria: screening study
Reference standard	White on white automated perimetry	The assessment of the structure and/or visual function	White on white automated perimetry and/or optic disc appearance (clinically or by photograph)	Any diagnosis of glaucoma given by the study investigators by using both optic disc and/or visual field damage
No studies (eligible/included)	2474/357	8028/81	2264/150	9332/106
No OCT studies (SD,TD)	84 (17 SD, 67TD)	54(54SD)	150 (113 SD, 42 TD)	63 (63 SD)
Effect measure	Sensitivity, specificity, DOR, AUC	Sensitivity, specificity, DOR	AUC	Sensitivity, specificity, relative DOR
Risk-of-bias assessment	QUADAS	QUADAS-2	QUADAS-2	QUADAS-2
Qualitative conclusions	OCT has the highest glaucoma diagnostic accuracy followed by GDx and then HRT	All three instruments showed good diagnostic accuracy, and OCT obtained the best value of DORs	The currently available OCT devices (Zeiss Cirrus, Zeiss Stratus, Heidelberg Spectralis, Optovue RTVue,Topcon 3D-OCT) demonstrated good diagnostic ability in differentiating normal from glaucoma. This ability increased with the severity of the glaucoma and no device-related differences in diagnostic accuracy emerged	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
Impact on practice and research	Work needs to be done by glaucoma content experts to create a more homogenous consensus regarding how to use the new technologies and to agree on cutoffs	The best performing algorithm/parametes were MRA for HRT, NFI for GDx and RNFL and GCC thickness for OCT	The diagnostic capacity of RNFL is similar to segmented macular regions (GCIPL, GCC), and better than total macular thickness. As OCT technology continues to evolve at a faster pace than functional assessments of optic nerve health, future studies will be needed to fully understand its role in glaucoma management	The findings of this review could be used in an add-on setting which could be a primary care, or a triage setting when somebody has already been referred from primary care to secondary care as suspect glaucoma and needs triage by a non-glaucoma specialist. Further case-control studies are not useful in this research fie Id. There is room for improving diagnostic accuracy studies evaluating OCT devices in glaucoma

AUC, area under the ROC; DOR, diagnostic OR; GCC, ganglion cell complex; GCIPL, ganglion cell layer +inner plexiform layer; GDx, Scanning laser polarimetry; HRT, Heidelberg Retina Tomograph; HTA, health technology assessment; IOP, intraocular pressure; MRA, Moorfield’s regression analysis; NFI, nerve fibre indicator; OCT, optical coherence tomography; ONH, optic nerve head; QUADAS, Quality Assessment of Diagnostic Accuracy Studies; RNFL, retinal nerve fibre layer; ROC, receiver operating characteristic curve.