Hersh 2011.

Methods	Parallel group RCT Results reported by eye, but more eyes enrolled than people and unclear whether there was also within‐person randomisation. Study recruited participants with ectasia due to keratoconus and iatrogenic (after surgery for myopia). Only the keratoconus participants were included in this review.
Participants	Country: USA Number of people randomised: not reported, (77 eyes) Average age: Not reported % women: Not reported Inclusion criteria: 14 years of age or older axial topography pattern consistent with keratoconus an inferior–superior ratio greater than 1.5 on topography mapping corrected distance visual acuity worse than 20/20 diagnosis of progressive keratoconus, which was defined as 1 or more of the following changes over a period of 24 months: an increase of 1.00 D or more in the steepest keratometry measurement, an increase of 1.00 D or more in manifest cylinder, an increase of 0.50 D or more in MRSE. Exclusion criteria: history of corneal surgery corneal pachymetry less than 300 mm history of chemical injury or delayed epithelial healing, pregnancy or lactation during the course of the study
Interventions	CXL, following epithelial removal, with riboflavin 0.1% and UVA (370 nm at 3 mW/cm2) (n = 49 eyes) Sham treatment (n = 28 eyes) "The sham control group received riboflavin 0.1% ophthalmic solution alone. In this group, the epithelium was not removed. Riboflavin was administered topically every 2 minutes for 30 minutes. Next, the cornea was exposed to a sham treatment in which the UVA light was not turned on, during which time riboflavin was administered topically every 2 minutes for an additional 30 minutes. The sham control patients were followed for 3 months postoperatively, at which point the study eye crossed over to the treatment group and received full CXL treatment." Hersh 2011 page 150
Outcomes	From clinical trials registry entry: Primary outcome: Change in keratometry at 3 and 12 months No secondary outcomes listed. The following outcomes were reported in various publications: Change in maximum keratometry values (Hersh 2011) Change in average keratometry values (Hersh 2011) Change in BSCVA (Hersh 2011) Refractive sphere, astigmatism, MRSE (Hersh 2011, reported not statistically significant only, no data) Adverse effects (Hersh 2011) Patient questionnaire on visual functioning including driving, reading, double vision, glare, halos, dryness, pain, foreign body sensation (Brooks 2012, intervention group only) Corneal thickness (Greenstein 2011) Higher‐order aberrations (Greenstein 2011, intervention group only) Biomechanical changes (Greenstein 2011a) Follow‐up: 1, 3, 6, and 12 months Note: As the sham control group was treated at 3 months, comparisons are valid up to 3 months only.
Notes	Date study conducted: December 2007 to April 2011 (from trials register), but main publication accepted for publication in 2010. Funding: "Supported in part by Peschke Meditrade GmbH, Zurich, Switzerland, and an unrestricted grant to the Department of Ophthalmology, UMDNJ–New Jersey Medical School from Research to Prevent Blindness, Inc., New York, New York, USA" Conflict of interest: "No author has a financial or proprietary interest in any material or method mentioned." "Dr. Hersh is a paid medical consultant to Avedro, Inc." Trial registration: NCT00647699
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was computer generated ..." Hersh 2011 page 150
Allocation concealment (selection bias)	Low risk	"... on the procedure day, a sealed envelope was opened revealing whether the eye would be in the sham or treatment group" Hersh 2011 page 150
Blinding of participants and personnel (performance bias) All outcomes	High risk	"Patients were aware of their randomly assigned group." Hersh 2011 page 150 but the control group was given a sham procedure, it is not clear why if participants were told which group they were in.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Control group was given a sham procedure, but participants were aware of their status (see above).
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Follow‐up not reported.
Selective reporting (reporting bias)	Unclear risk	We did not have access to the study protocol and could not accurately judge the extent of selective reporting.