Bertuzzi 2014.

Study characteristics
Patient Sampling	Case‐control study in which patients attending the glaucoma clinic and healthy volunteers were enrolled between September 2009 and October 2010. One eye per person (randomly selected if both eligible) was considered.
Patient characteristics and setting	Sample size: 205 eyes of 205 participants (70 glaucoma, 65 ocular hypertension, 70 normal controls). Age: perimetric glaucoma mean ± SD, 65.87 ± 11.90 years; controls, 56.80 ± 11.16 years. Sex: 69 men (38 glaucoma, 31 controls) and 71 women (32 glaucoma, 39 controls). Ethnicity: not reported. Setting: Glaucoma Service of Policlinico di Monza Hospital (University of Milan‐Bicocca). Country: Italy. Ocular comorbidities: eyes with significant lens opacity, systemic diseases with ophthalmic involvement, co‐existing retinal disease, uveitis, or non‐glaucomatous optic neuropathy were excluded. Spectrum of glaucoma severity: the mean ± SD mean deviation and PSD on the VF test were ‐6.49 ± 6.46 and 6.39 ± 3.97 respectively, for glaucoma. Control participants: IOP of < 21 mmHg, no history of high IOP, and 2 reliable normal VFs (PSD and GHT within normal limits).
Index tests	Optical coherence tomography: RTVue (Optovue Inc.), software version 4.0.5.39. ONH and GCC scanning protocol were used for the analysis. Only good‐quality images, defined as a signal strength index of Z50 without motion artefacts, were used for the analysis. The authors declare no conflict of interest.
Target condition and reference standard(s)	Manifest perimetric glaucoma: glaucomatous VF damage defined as PSD outside the 95% normal confidence limits or a GHT result outside the 99% normal confidence limits, in at least 2 consecutive and reliable VF examinations. Visual field test: automated perimetry model 750i (Carl Zeiss Meditec Inc.), with 24‐2 SITA‐algorithm. Tests were considered reliable only with fixation loss of < 30%, and false‐positive and false‐negative response rates of < 20%.
Flow and timing	No details were reported about patients exclusion or time interval between index and reference test.
Comparative
Notes	None.
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
If a threshold was used, was it pre‐specified?	Yes
Were imaging test's quality assessed?	Yes
Were any conflict of interest avoided	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Unclear
Did all patients receive a reference standard	Yes
Could the patient flow have introduced bias?		Unclear risk