Shi 2020.

Study characteristics
Patient Sampling	Prospective, single‐centre, case‐control study. People with keratoconus and subclinical keratoconus were recruited from Affiliated Eye Hospital of Wenzhou Medical University. Normal subjects were recruited from the hospital's working staff and students.
Patient characteristics and setting	Normal eyes had to meet the following criteria. No clinical signs or suspected subclinical keratoconus or keratoconus patterns from corneal topography images Central average keratometry < 45.0 D I‐S values < 1.4 D of the vertical power gradient across the 6‐mm region Myopia < −6.0 and astigmatism < −2.0 D No history of contact lens wear, ocular surgery, or trauma Keratoconus eyes had to meet ≥ 1 of the following criteria. Vogt's striae Stromal thinning Fleischer's ring > 2 mm arc Central average keratometry > 47.0 D Asymmetric topographical features with I‐S values ≥ 2.0 D of the vertical power gradient across the 6‐mm region No history of contact lens use, ocular surgery, or extensive scarring Subclinical keratoconus eyes were identified from the other eyes of people with unilateral keratoconus. They had to meet all the following criteria. No clinical signs of keratoconus during slit‐lamp biomicroscope examination, retinoscopy, and ophthalmoscopy Diagnosis of keratoconus in the contralateral eye Central average keratometry < 45.0 D Corneal topographical features with I‐S values < 1.4 D of the vertical power gradient across the 6‐mm region Myopia < –6.0 D with astigmatism < −2.0 D No history of contact lens wear or ocular surgery
Index tests	An automated classification system using a machine learning classifier to distinguish clinically unaffected eyes in people with keratoconus from a normal control population based on a combination of Scheimpflug camera images and ultra‐high‐resolution optical coherence tomography (UHR‐OCT) imaging data. A neural network was used.
Target condition and reference standard(s)	2 experienced doctors (YY and JJ) performed a comprehensive ocular exam, including a review of family and medical history, corrected‐distance visual acuity, slit‐lamp biomicroscope examination, fundus examination, and corneal topography.
Flow and timing	All participants received the same reference standard and were included in the analysis.
Comparative	Not applicable
Notes	This study was supported by research grants from Key R&D Program Projects in Zhejiang Province (2019C03045), the National Major Equipment Program of China (2012YQ12008004), the National Key Research and Development Program of China (2016YFE0107000, the National Nature Science Foundation of China (Grant No. 81570880).
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?	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?	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