Acar 2014.

Study characteristics
Methods	Study design: parallel‐group, randomized controlled trial Number randomized (total and per group): 13 eyes of 13 participants in total; 6 to transepithelial CXL, and 7 to epithelium‐off Unit of randomization (individual or eye): individual (1 eye per participant was included) Number analyzed (total and per group): 13 eyes of 13 participants in total; 6 in transepithelial CXL, and 7 in epithelium‐off Unit of analysis (individual or eye): individual (1 eye per participant) Exclusions and losses to follow‐up (total and per group): none How were missing data handled?: not applicable Length of follow‐up: 6 months Reported power calculation (Y/N), if yes, sample size and power: not reported
Participants	Country: Turkey Setting: Haydarpasa Numune Education and Research Hospital Baseline characteristics 1. Epithelium‐off CXL, n = 7 Age (mean ± SD, range): 22.71 ± 10.14 years Gender: 3 men and 4 women 2. Transepithelial CXL, n = 6 Age (mean ± SD, range): 24.50 ± 8.11 years Gender: 4 men and 2 women Overall, n = 13 Age (mean ± SD, range): 23.5 ± 9.3 years Gender: 7 men and 6 women Inclusion criteria: progressive keratoconus defined as an increase in the steepest keratometry of 1.00 D or more in a 1‐year period, >= 0.50 D increase in manifest refraction spherical equivalent, >= 1.00 D increase in manifest cylinder, or need for new contact lens fitting more than once in 2 years Exclusion criteria: a corneal thickness of less than 400 mm, central/paracentral scars in epithelial or stromal layers, history of herpetic keratitis, active ophthalmic infection or inflammation, pregnancy, lactation, and dry eye Baseline equivalence: "no significant difference with respect to age" in the 2 groups; the mean endothelial cell counts, polymegathism, pleomorphism, and central corneal thickness values of the 2 groups were compared and P > 0.05; "confocal microscopy showed no significant differences between the two groups in stromal morphology."
Interventions	1 drop of proparacaine HCl 0.5% (Alcain; Alcon Inc., Fort Worth, TX) was instilled 4 times every 5 min, starting 20 min before the intervention. To reduce the risk of UVA exposure, miosis was induced with pilocarpine 1.0% 30 min before the procedure. 1. Transepithelial CXL UVA was applied in the presence of intact epithelium using Ricrolin TE (Sooft Italia SpA), which consists of riboflavin‐5‐phosphate 0.1%, dextran T500 20%, and enhancers (i.e. tris hydroxymethyl aminomethane (trometamol) and sodium ethylenediaminetetraacetic acid (EDTA)) to facilitate penetration of the solution trough intact corneal epithelium in 6, 5‐minute steps, with 1 drop of Ricrolin TE at the start of each step (every 5 minutes). 1 drop of Ricrolin TE was applied every 10 min for 2 hours before the procedure. Crosslinking was performed with irradiation for 30 min in conjunction with 1 drop of Ricrolin TE at the start of each of 6, 5‐minute steps. 2. Epithelium‐off CXL Central corneal epithelium removed from a 7.0‐ to 9.0‐millimeter diameter area using a blunt spatula. After de‐epithelialization, the photosensitizer solution containing riboflavin‐5‐phosphate 0.1% (G. Streuli & Co. AG) with dextran T‐500 20% (Roth AG) was applied every 5 min for 30 min. Corneal pachymetry guidance was performed in all participants before the operation by a Galilei dual Scheimpflug analyzer to ascertain a minimal corneal thickness greater than 400 mm throughout the cornea and to define the area with minimal thickness. Intraoperatively, ultrasonic pachymetry readings (Accupach V; Accutome Ultrasound, Inc., Malvern, PA) were used to identify the area that approximately corresponded to the area of minimum thickness and to ensure that minimum thickness exceeds 400 mm. During UVA irradiation for 30 min, iso‐osmolar riboflavin 0.1% solution was administered during 6, 5‐minute steps.
Outcomes	Primary outcome: in vivo confocal microscopy (the mean endothelial cell counts, morphology of endothelial cells (polymegathism and pleomorphism), and depth of CXL effect in the stroma), and central corneal thickness values Secondary outcomes: none Adverse outcomes: No clinically significant corneal decompensation Measurement time points: examined 1, 4, 7 days after surgery; outcomes were assessed 1 and 6 months after surgery Other issues with outcome assessment (e.g. quality control for outcomes, if any): none
Notes	Study period: not reported Publication language: English Trial registration: not found Conflicts of interest: "The authors have no funding or conflicts of interest to disclose." Funding source: "The authors have no funding or conflicts of interest to disclose."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of random sequence generation was not reported: "Patients were randomized into two groups: CXL after total epithelial debridement (standard CXL group) and CXL with intact epithelium (transepithelial CXL group)."
Allocation concealment (selection bias)	Unclear risk	Allocation concealment before assignment was not reported.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Masking of participants and personnel was not reported.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The analyses were performed by the same investigator (C.A.U.) blinded to intervention modality."
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no missing outcome data.
Selective reporting (reporting bias)	Unclear risk	Neither protocol nor trial registry was available.
Other bias	Unclear risk	None identified.