Evaluation of intrastromal riboflavin concentration in human corneas after three corneal cross-linking imbibition procedures: A pilot study

Purpose. to compare stromal riboflavin concentration after three corneal cross-linking (cxl) imbibition procedures: standard (epioff),transepithelial corneal (epion),and iontophoresis-assisted technique (ionto) using 0.1% hypotonic riboflavin phosphate. methods. randomized open-label pilot clinical study. twelve corneas/12 patients with advanced keratoconus were randomly divided into 4 groups for cxl (n = 3). the corneas underwent imbibition with standard riboflavin epioff and with enhanced riboflavin solution (ricrolin+) epioff,epion,and iontophoresis techniques. thereafter,deep anterior lamellar keratectomy procedure was performed and the obtained debrided corneal tissues were frozen. the maximal intrastromal riboflavin concentration was measured by high-performance liquid chromatography/mass spectrometry (mcg/dg). results. the mean stromal concentration of riboflavin was 2.02 ± 0.72 mcg/dg in epioff group,4.33 ± 0.12 mcg/g in epioff-ricrolin+ group,0.63 ± 0.21 mcg/dg in epion-ricrolin+ group,and 1.15 ± 0.27 mcg/dg in iontophoresis ricrolin+ group. a 7-fold decrease in intrastromal riboflavin concentration was observed comparing epion-ricrolin+ and epioff-ricrolin+ groups. conclusion. the present pilot study indicates that both transepithelial cxl techniques in combination with hypotonic enhanced riboflavin formulation (ricrolin+) were still inferior to the standard cxl technique; however,larger clinical studies to further validate the results are needed and in progress. © 2015 antonella franch et al.