Early findings in a prospective randomised study on three cross-linking treatment protocols: interruption of the iontophoresis treatment protocol

PURPOSE: To present the outcome of the interrupted iontophoresis-assisted treatment arm in an ongoing randomised clinical trial (NCT04427956). METHODS: A randomised clinical study of corneal cross-linking (CXL) using continuous UV-A irradiation at a rate of 9 mW/cm(2) and three different types of riboflavin and riboflavin delivery mode: (1) iso-osmolar dextran-based riboflavin (epithelium-off), (2) hypo-osmolar dextran-free riboflavin (epithelium-off) and (3) iontophoresis-assisted delivery of riboflavin (epithelium-on) for the treatment of progressive keratoconus. Inclusion criteria were an increase in the maximum keratometry value (Kmax) of 1.0 dioptre over 12 months or 0.5 dioptre over 6 months. The primary outcome in evaluating treatment efficacy was Kmax. Recently presented stratified detection limits were used post hoc to confirm the enrolment of patients with truly progressive keratoconus and in the assessment of the need for re-CXL. RESULTS: Thirteen patients had been randomised to iontophoresis-assisted CXL when the treatment arm was interrupted; two patients dropped out. Of the remaining 11 patients, 7 were deemed as having truly progressive disease according to the more recent stratified detection limits. The disease continued to progress in three patients according to the original definition (increase in Kmax≥1 D), necessitating re-CXL with epithelium-off CXL. This progression was confirmed by post hoc analysis using the stratified detection limits for progression. CONCLUSIONS: The iontophoresis-assisted CXL protocol failed to halt further disease progression in 27% of the patients. The failure rate increased to 38% when considering only the patients deemed to have truly progressive disease using the stratified detection limits.