Ferreras 2008b.

Study characteristics
Patient Sampling	From April, 2006, through December, 2006, 2 samples (one population for obtaining the LDF and a second independent population for testing the LDF) of consecutive healthy control participants and glaucoma patients were pre‐enrolled prospectively. Normal eyes were recruited from among patients referred for refraction who underwent routine examination without abnormal ocular findings, from among hospital staff, and from among relatives of patients in the hospital. Patients with glaucoma were recruited from an ongoing longitudinal follow‐up study. One eye per person was randomly selected.
Patient characteristics and setting	Sample size: 2 samples were enrolled. A first sample of 166 eyes (85 glaucoma/ 81 controls) to calculate a discriminant analysis. A second sample of 435 eyes: 225 controls and 210 glaucomatous eyes (163 POAG, 34 PEX and 13 pigmentary glaucoma). Age: glaucoma mean ± SD, 61.10 ± 10.07 years; controls 57.46 ± 9.84 years, for the first sample. Glaucoma mean ± SD, 61.37 ± 10.4 years; controls 57.67 ± 10.19 years, for the second sample. Ethnicity: white. Country: Spain. Ocular comorbidities: BCVA < 20/40, SE > ± 5 D, no previous intraocular surgery, lens opacity, diabetes, or other ocular or neurologic disease. Setting: Department of Ophthalmology of Miguel Servet University Hospital. Spectrum of glaucoma severity: mean ± SD MD and PSD on the VF test were ‐5.79 ± 5.74 dB and 4.93 ± 3.78 dB for the first sample, ‐5.34 ± 4.87 dB and 4.87 ± 3.95 dB for the second sample. Control participants: IOP < 21 mmHg (on at least 3 readings on different days), and a normal SAP test result.
Index tests	Confocal scanning laser tomography: HRT 3 (Heidelberg Engineering, Heidelberg, Germany). Topographic images were obtained through dilated pupils and were analysed using the Advanced Glaucoma Analysis 3.0 software. All scans had to have an interscan SD of < 30 µm. The margin of the optic disc was traced manually by the same glaucoma specialist who was masked to the patients’ identity and clinical history. No author had conflict of interest.
Target condition and reference standard(s)	Manifest glaucoma: IOP > 21 mmHg and typical SAP defects (defined as a PSD with a P < 5% and/or a GHT outside normal limits). Visual field testing: Humphrey Field Analyzer, model 745, 24‐2 SITA‐standard strategy (Zeiss Humphrey Systems, Dublin, CA, USA). VF reliability criteria included fixation losses and false‐positive and false‐negative rates of < 20%. The participants completed the perimetry tests before undergoing any clinical examination or structural test. Optic disc appearance was not part of the reference standard.
Flow and timing	Reference standard and index test were performed within 1 month. 21 participants (< 10%) were excluded from the analysis: 3 participants did not provide informed consent, 11 participants did not complete all of the required tests, and 7 participants were unable to perform at least 1 of the tests expected.
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?	Yes
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?	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?	Yes
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?		Low risk