Issarti 2019.

Study characteristics
Patient Sampling	Retrospective, single‐centre, case‐control study that used a previously collected database containing the Pentacam Scheimpflug measurements of 851 eyes (Pentacam (Oculus GmbH, Wetzlar, Germany)).
Patient characteristics and setting	Normal eyes (n = 312): bilateral normal topography, with no systemic or ocular disease, without any prior ocular surgery, and no slit‐lamp findings suggestive of cornea ectasia, recruited during a previous epidemiology study Keratoconic eyes (n = 539), divided into the following 3 groups Mild keratoconus Moderate keratoconus Keratoconus suspect
Index tests	A CAD (computer‐aided diagnosis) system, which combines a feedforward neural network (FFN) and a Grossberg‐Runge Kutta architecture to detect clinical and suspect keratoconus.
Target condition and reference standard(s)	Mild keratoconus: clear cornea, tomography maps compatible with Keratoconus, a Fleischer's ring at the apex base, slight thinning, and anterior or posterior corneal steepening Moderate keratoconus: corneas with slit‐lamp findings compatible with keratoconus, corneal thinning at the apex, Vogt's striae, a clearly visible Fleischer's ring, and corneal tomography compatible with keratoconus Keratoconus suspect: unilateral keratoconus, 1 eye normal tomography and no biomicroscopic signs. An ophthalmologist and an optometrist performed the classification. Cases were classified before inclusion.
Flow and timing	All cases were included in the reference standard and index test. All data were included in a 2 × 2 table.
Comparative
Notes	This work was supported in part by a research grant from the Flemish government agency for Innovation by Science and Technology (grant no. TBM‐T000416N).
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?	No
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?	No
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?	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
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk
DOMAIN 5: Comparative