Medeiros 2005.

Study characteristics
Patient Sampling	Patients' data were selected from a research database, containing patients included in a prospective, longitudinal study designed to evaluate optic nerve structure and visual function in glaucoma. Normal participants were recruited from the staff and employees of the University of California, as well as from the general population. One eye per person was randomly selected.
Patient characteristics and setting	Sample size: 136 patients (41 perimetric glaucoma, 30 preperimetric glaucoma, 65 healthy controls). Age: perimetric glaucoma patients mean ± SD, 65 ± 9 years, preperimetric glaucoma 70 ± 11 years, controls 66 ± 11 years. Ethnicity: not specified. Country: USA. Ocular comorbidities: no co‐existing retinal disease, uveitis, or non‐glaucomatous optic neuropathy. BCVA ≥ 20/40, spherical refraction within ±5.0 D, cylinder correction within ±3.0 D. Setting: Hamilton Glaucoma Center, University of California. Spectrum of glaucoma severity: mean ± SD MD and PSD on the VF test were ‐7.53 ± 6.58 dB and 7.13 ± 3.60 dB for perimetric glaucoma, ‐2.07 ± 1.65 dB and 1.65 ± 0.3 dB for preperimetric glaucoma, ‐0.59 ± 1.13 dB and 1.59 ± 0.38 dB for control group, respectively. Control participants: IOP ≤ 22 mmHg,with no history of increased IOP, a normal VF result and a normal clinical examination.
Index tests	Scanning laser polarimetry: GDx VCC, software version 5.0.1 (Laser Diagnostic Technologies Inc, San Diego, CA, USA). To be acceptable each image required a focused and evenly‐illuminated reflectance image with a centred optic disc, residual anterior segment retardation ≤ 15 nm and an atypical scan score > 25. Quality assessment was performed by an experienced examiner masked to the participant’s identity and results of the other tests. No details about conflict of interest were reported.
Target condition and reference standard(s)	Manifest perimetric glaucoma: evidence of progressive glaucomatous change in the appearance of the optic disc (as assessed by simultaneous stereoscopic optic disc photographs and defined by focal or diffuse thinning of the neuroretinal rim, increased excavation, or enlargement of RNFL defects) and abnormal VF result (GHT outside normal limits or a PSD with P < 5%). Manifest preperimetric glaucoma: evidence of progressive glaucomatous change in the appearance of the optic disc (as assessed by simultaneous stereoscopic optic disc photographs and defined by focal or diffuse thinning of the neuroretinal rim, increased excavation, or enlargement of RNFL defects) and normal VF result. Optic disc evaluation: stereoscopic optic disc photographs were acquired with TRC‐SS (Topcon, Paramus, New Jersey, USA) and included only if had a good quality. For each participant, the most recent stereophotograph was compared with the oldest available (at least 1 year time interval) by 2 experienced graders masked to the participant’s identity and to the temporal sequence of the photographs. Visual field testing: Humphrey Field Analyzer,24‐2 SITA standard (Zeiss‐Humphrey, Dublin, CA, USA).
Flow and timing	No patients were reported by the authors as excluded from the analysis. The GDx VCC imaging date was always after the date of the optic disk stereophotograph that showed progression.
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	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear 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?	Yes
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?	Yes
Did all patients receive a reference standard	Yes
Could the patient flow have introduced bias?		Unclear risk