Arbelaez 2012.

Study characteristics
Patient Sampling	Retrospective case series. Clinical data and corneal examinations were retrieved from clinical records from 2 centres (Oman and Italy). 3502 eyes were enroled.
Patient characteristics and setting	According to the clinical diagnosis, participants were classified into the following 4 groups. Keratoconus Subclinical keratoconus (early keratoconus, forme fruste and suspected) Other conditions (history of refractive surgery, penetrating keratoplasty, or ocular trauma) Normal eyes, enroled among subjects undergoing a routine ophthalmological examination for minor refractive defects. Each group was divided into a training set (including 200 eyes) to be used to develop the keratoconus detection program and a validation set (including the remaining eyes). Participants were excluded if tomography scans had poor quality.
Index tests	Classification algorithm based on support vector machine (SVM), a supervised learning technique that can be used for pattern classification. It analysed symmetry index of front and back corneal curvature, best fit radius of the front corneal surface, Baiocchi Calossi Versaci front index (BCVf) and BCV back index (BCVb), root‐mean‐square of front and back corneal surface higher order aberrations, and thinnest corneal point provided by a Scheimpflug camera combined with Placido corneal topography (Sirius, CSO, Italy).
Target condition and reference standard(s)	Unclear who performed the classification of the eyes, which was done before the analysis with the algorithm.
Flow and timing	It is unclear if all cases received the same reference standard. All data were included in a 2 × 2 table.
Comparative	Not applicable
Notes	No funding source mentioned.
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?	Yes
Was the model designed in an appropriate manner?	No
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