De Leon‐Ortega 2006.

Study characteristics
Patient Sampling	Data were obtained from patients who had undergone optic disc imaging and visual functional testing between January 2003 and February 2005 as part of ongoing longitudinal glaucoma studies. Controls were obtained primarily from referrals and University of Alabama employees. One eye per person was randomly selected.
Patient characteristics and setting	Sample size: 228 eyes of 228 participants (79 glaucoma and 149 healthy controls). Age: glaucoma patients mean ± SD, 56.0 ± 13.9 years; controls 40.3 ± 11.3 years. Sex: 63 men (25 glaucoma and 38 controls) and 165 women (54 glaucoma and 111 controls). Ethnicity: 42 of 79 in the glaucoma group and 82 of 149 in the controls were African‐American. Country: USA. Ocular comorbidities: no BCVA < 20/40, SE > ± 5 D, comorbid ophthalmic, or neurologic surgery/disease. Setting: University of Alabama at Birmingham. Spectrum of glaucoma severity: mean ± SD MD  on the VF test was ‐3.8 ± 3.6 dB. According to Hodapp et al. grading scale, 44 eyes had an early glaucoma, 31 moderate, and 4 severe. Control participants: IOP < 22 mmHg, bilateral normal eye examination findings and bilateral normal VF results (defined as PSD within the 95% normal limits and a GHT result within 99% limits).
Index tests	Scanning laser polarimetry: GDx VCC (Carl Zeiss Meditec, Inc., Dublin, CA, USA). The mean of 3 images was calculated. Images were considered of good quality if there was good fixation, minimal eye movement, and good illumination on the reflectance image, with no artefacts on the retardance image. No author had conflict of interest.
Target condition and reference standard(s)	Manifest glaucoma: glaucomatous VF loss (defined as PSD outside 95% normal limits or GHT outside 99% normal limits) confirmed with a second VF test. Visual field testing: no details about how it was conducted and which instrument was used. VF reliability criteria included fixation losses and false‐positive and false‐negative rates of < 30%. Optic disc appearance was not part of the reference standard.
Flow and timing	Reference standard and index tests were completed within 1 to 8 weeks. 45 glaucoma patients (> 10%) were excluded due to poor‐quality images.
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?		Unclear 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?	No
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Did all patients receive a reference standard	Yes
Could the patient flow have introduced bias?		High risk