Rao 2012b.

Study characteristics
Patient Sampling	Consecutive early glaucoma patients and healthy controls were enrolled at a tertiary eye‐care facility between August 2008 and June 2009. The normal participants were recruited from among those who came for a routine eye examination, patients’ relatives and hospital staff. Both eyes were included for some participants.
Patient characteristics and setting	Sample size: 216 (91 early glaucoma, 125 control) eyes of 123 participants (59 early glaucoma, 64 control) were enrolled and included in the analysis. Age: glaucoma eyes mean ± SD 51.8 ± 13.4 years; controls 47.7 ± 13.4 years. Sex: not reported. Ethnicity: Indian. Country: India. Setting: glaucoma Center L. V. Prasad Eye Institute, Banjara Hills, Hyderabad. Ocular comorbidities: patients with any media opacities, intraocular surgery within the previous 6 months, and any retinal or neurologic diseases other than glaucoma that could confound the results of VF examination and structural measurements with SD‐OCT were excluded. All eyes had to have BCVA ≥ 20/40, refractive error within ±5.0 D sphere and ±3 D cylinder. Spectrum of glaucoma severity: the mean ± SD MD and PSD on the VF test were ‐2.6 ± 1.8 dB and 2.4 ± 1.5 dB, respectively for glaucoma. All glaucoma eyes had early stage of disease according to Hodapp et al. classification. Control participants: IOP < 22 mmHg with no history of increased IOP, no family history of glaucoma, no optic disc morphology suspicious for glaucoma (focal or diffuse neuroretinal rim thinning, localised notching or nerve fibre layer defects) and normal VF result.
Index tests	Optical coherence tomography: RTVue (software version 4.0.5.39; Optovue Inc., Fremont, CA, USA). The ONH and GCC scanning protocols were used to acquire the images. Only well‐centred images with a signal strength index of ≥ 30 were included in the analysis. One author had conflict of interest.
Target condition and reference standard(s)	Manifest glaucoma: glaucomatous optic disc changes (defined as focal or diffuse neuroretinal rim thinning, localised notching or nerve fibre layer defects) and corresponding VF defects (defined by 2 of the following criteria: the presence of a cluster of 3 points on a pattern deviation probability plot with P < 5%, one of which had P < 1% or a PSD with P < %5 or a GHT result outside normal limits). Visual field testing: Humphrey Field Analzyer, model 750 (24‐2 SITA standard programme (Carl Zeiss Meditec). Reliability criteria were fixation losses, false‐positive and false‐negative rates < 20%. Optic disc evaluation: dilated fundus examination by 2 glaucoma specialists.
Flow and timing	The index test and reference standard were performed on the same day. No participants were reported by the authors as excluded from the analysis.
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	No
Could the conduct or interpretation of the index test have introduced bias?		High 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?	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