Twa 2005.

Study characteristics
Patient Sampling	Retrospective, single‐centre, case‐control study that included eyes diagnosed with keratoconus and a reference group of normal eyes of corneal refractive surgery candidates
Patient characteristics and setting	Normal group included both eyes of people who had myopia with or without astigmatism who were examined for the surgical correction of refractive error and had videokeratography examination data. Exclusion criteria: no other documented ocular disease. The normal participants were sequentially selected from all people who were examined for the surgical correction of refractive error. Keratoconus: keratoconus diagnosis in 1 or both eyes by International Classification of Diseases, 9th Revision diagnosis codes between August 1998 and January 2000. Their diagnostic classification was confirmed by chart review, applying criteria established by the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Exclusion criteria: lack of full videokeratography data over the region of study (central 7 mm), or obvious artifacts in videokeratography data resulting from obstruction of the corneal surface by the eyelids.
Index tests	An automated decision tree analysis that analyses videokeratography and classifies the cases into normal or keratoconus.
Target condition and reference standard(s)	Unclear if the diagnoses were made by the same person(s). All participants were included in the analyses.
Flow and timing	Participants were divided into 2 groups, but it was unclear who made the diagnosis. The diagnoses were made before the analysis with the classification tree.
Comparative	Not applicable
Notes	This study was supported by National Institutes of Health grants EY16225 and EY13359 (MDT), American Optometric Foundation Ocular Sciences Ezell Fellowship, Ameritech faculty fellowship (SP), and NIH‐EY12952 (MAB).
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient selection
Was a consecutive or random sample of patients enrolled?	No
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)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Unclear
Was the model designed in an appropriate manner?	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 standard likely to correctly classify the target condition?	Unclear
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?		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
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk
DOMAIN 5: Comparative