Kim 2014a.

Study characteristics
Patient Sampling	Case‐control study including participants in an ongoing study of glaucoma and healthy individuals. If both eyes eligible only one eye per person was randomly chosen.
Patient characteristics and setting	Sample size: 184 eyes of 205 participants (92 preperimetric glaucoma, 92 normal controls). Age: preperimetric glaucoma mean ± SD, 57.8 ± 11.4 years; controls, 57.6 ± 11.3 years. Sex: 95 men (45 preperimetric glaucoma, 50 controls) and 89 women (47 preperimetric glaucoma, 42 controls). Ethnicity: Korean Setting: Glaucoma Clinic of Seoul National University Hospital, Seoul. Country: South Korea. Ocular comorbidities: eyes with history of amblyopia, uveitis, intraocular surgery (excepting uncomplicated cataract surgery), diabetes, ocular diseases possibly affecting the peripapillary area (e.g., large peripapillary atrophy), or macular area (e.g., epiretinal membrane), and any other ocular or systemic diseases affecting the VF (e.g., retinal vein occlusion, ischaemic optic neuropathy), were excluded. Spectrum of glaucoma severity: the mean ± SD mean deviation and PSD on the VF test were ‐0.16 ± 1.61 and 1.99 ± 0.86 respectively, for preperimetric glaucoma. Control participants: IOP ≤ 21 mmHg with no history of increased IOP, an absence of glaucomatous disc appearance, no visible RNFL defect on red‐free fundus photography, and a normal VF result.
Index tests	Optical coherence tomography: Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA); software version 6.0. Only images that were well centred on the optic disc or fovea with signal strength of ≥ 6 were included in the analyses. GCA and optic disc cube 200 x 200 scanning protocols were used. The authors declare no conflict of interest.
Target condition and reference standard(s)	Manifest glaucoma: 1+ localised RNFL defects associated with a glaucomatous disc appearance (e.g. notching or thinning of neuroretinal rim), which have documented evidence of progression (e.g. focal or diffuse narrowing of neuroretinal rim, increased excavation, increased width or depth of RNFL defects) through stereoscopic disc photography (SDP) or red‐free fundus photography performed at least 6 months before enrolment, and normal VF result (PSD > 5% and GHT within normal limits). Visual field test: Humphrey Field Analyzer II (Carl Zeiss Meditec, Inc.) with 30‐2 SITA‐algorithm. VF exams were considered reliable when fixation loss < 20%, false‐positive and false negative rates < 33%. RNFL evaluation: red‐free fundus photography (VX‐10; Kowa Optimed, Tokyo, Japan). 2 glaucoma specialists independently evaluated the red‐free fundus photographs without knowledge of the participant’s clinical information.
Flow and timing	209 eyes were initially involved (117 eyes with glaucoma and 92 normal control eyes). After excluding 4 eyes for ambiguous RNFL defects and age‐matching the two groups, 184 eyes of 184 subjects (92 preperimetric glaucoma and 92 age‐matched healthy control participants) were included in the analysis. More than 10% of the enrolled eyes were excluded from the analysis. No details reported about 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?	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?	No
Did all patients receive a reference standard	Yes
Could the patient flow have introduced bias?		High risk