Wittig‐Silva 2008.

Methods	Parallel group RCT If both eyes of a participant were eligible, each eye was randomised independently.
Participants	Country: Australia Number of people randomised: Not stated. 100 eyes Average age: 26 years % women: 43 Inclusion criteria: age 16 to 50 years unequivocal clinical and videokeratographic diagnosis of keratoconus clinically significant progression of the ectasia over the preceding 6 to 12 months. Progression was considered to be confirmed if at least 1 or more of the following criteria were met: an increase of at least 1.00 D in the steepest simulated Kmax derived from computerized videokeratography or in the steepest meridian measured by manual keratometry; an increase in astigmatism as determined by manifest subjective refraction of at least 1.00 D; an increase of 0.50 D in MRSE; or a 0.1 mm or more decrease in back optic zone radius of the best‐fitting contact lens. Exclusion criteria: minimum corneal thickness 400 μm axial corneal scarring previous refractive surgery or other corneal surgery history of chemical burns, severe infections, or other corneal or ocular surface disease pregnant or breastfeeding at the time of the treatment
Interventions	CXL, following epithelial removal, with riboflavin 0.1% and UVA (370 nm at 3 mW/cm2) (n = 47 eyes) Observation (n = 49 eyes) Eyes randomised to control were offered compassionate CXL (no earlier than 6 months after randomisation) during the course of study if continuing and significant progression was noted.
Outcomes	As reported on clinical trials register entry: Primary outcome: Maximum simulated keratometry value measured using computerised videokeratography (Orbscan II; Bausch and Lomb Surgical, Utah). Participants recruited after November 2007 were also imaged with Scheimpflug imaging (Pentacam HR, Oculus, Germany). Secondary outcomes: Uncorrected visual acuity expressed as logMAR BSCVA expressed as logMAR Subjective refraction (sphere and cylinder) performed by trained orthoptists Minimum simulated keratometry value measured using computerised videokeratography (Orbscan II; Bausch and Lomb Surgical, Utah). Participants recruited after November 2007 were also imaged with Scheimpflug imaging (Pentacam HR, Oculus, Germany). Corneal thickness at the thinnest point using ultrasound pachymetry (Pachymeter SP‐3000; Tomey, Nagoya, Japan), computerised videokeratography (Orbscan II; Bausch and Lomb Surgical, Utah) and Scheimpflug imaging (Pentacam HR, Oculus, Germany) Endothelial cell density using the SP‐2000 Specular Microscope (Topcon Corp, Tokyo, Japan) Intraocular pressure using the Tono‐Pen XL (Medtronic, Jacksonville, Florida) and Goldmann applanation tonometer (Haag‐Streit, Koeniz, Switzerland) Follow‐up: 5 years (on clinical trial register). Outcomes reported to date: BSCVA and maximum and average keratometry values at 3, 6, 12, 24, and 36 months. At 12 months, results from 46 treated and 48 control eyes reported using LOCF.
Notes	Date study conducted: June 2006 to June 2009 (as reported on trials register entry) Funding: Royal Victorian Eye and Ear Hospital Research Fund, Eye Research Australia Foundation, Scholarship for Postgraduate Studies (Faculty of Medicine and University of Melbourne), and Contact Lens Society of Australia Conflict of interest: reported "The authors have no financial interest in the materials presented herein." Trial registration: ACTRN12613000143729 Paper was published in 2011. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363630
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Enrolled eyes were randomized separately to either the treatment or control groups using a computer generated randomization plan with blocks of 10. If both eyes of 1 patient qualified for participation in the study, each eye was randomized independently" Page 813, Wittig‐Silva 2014
Allocation concealment (selection bias)	Low risk	"The randomisation plan was maintained in a secure location by a staff member in another hospital department not involved with the recruitment or conduct of the study" Page 813, Wittig‐Silva 2014
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study was described as open label (masking not used) on clinical trials registry entry.
Blinding of outcome assessment (detection bias) All outcomes	High risk	The study was described as open label (masking not used) on clinical trials registry entry. "All images were acquired and analyzed in an unmasked manner". Page 813, Wittig‐Silva 2014
Incomplete outcome data (attrition bias) All outcomes	High risk	Differential follow‐up: At one year 46 (92%) treated and 41 (82%) control eyes followed up to 12 months. Using LOCF, data for 46 treated and 48 control eyes were reported. Over 3 years, 21 eyes in the control group left the trial, of which 12 were treated with CXL, 5 had corneal transplants, and 4 withdrew for personal reasons. In the treatment group, five people (eyes) withdrew for personal reasons. This unequal loss to follow‐up meant that the control group was followed up, on average, for less time than the treatment group.
Selective reporting (reporting bias)	High risk	Different cut‐points used at different time periods: 1.5D or more reported at one year and 2D or more reported at 36 months.

BSCVA: best spectacle‐corrected visual acuity
 CXL: Collagen cross‐linkage
 D: dioptre
 Kmax: maximal keratometry
 LOCF: last observation carried forward
 logMAR: logarithm of the minimum angle of resolution
 MRSE: manifest refraction spherical equivalent
 RCT: randomised controlled trial
 UVA: ultraviolet A