title: Corneal cross-linking: intrastromal riboflavin concentration in iontophoresis-assisted imbibition versus traditional and transepithelial techniques.
abstract: OBJECTIVE
  To determine differences in riboflavin concentration in the anterior, intermediate, and posterior stroma after 3 corneal cross-linking imbibition techniques (standard epithelial [epi]-off, epi-on, and iontophoresis-assisted administration) of 0.1% riboflavin.
  
  
  METHODS
  Experimental laboratory investigation of human cadaver corneas not suitable for transplantation.
  
  
  METHODS
  Ten corneas underwent imbibition with epi-on (n = 3), epi-off (n = 3), iontophoresis (n = 3), and saline exposure (control; n = 1). Femtosecond laser was used to produce 3 8-mm discs of the superficial (0-150 μm), intermediate (150-300 μm), and deep stroma (>300 μm). Riboflavin concentration was measured with high-performance liquid chromatography. The main outcome measure was riboflavin concentration at the 3 evaluated depths.
  
  
  RESULTS
  The overall stromal concentration of riboflavin was 34.1 ± 7.1 μg/g in epi-off, 7.2 ± 3.7 μg/g in epi-on, and 15.0 ± 5.1 μg/g in iontophoresis. The mean riboflavin content in the superficial slice in the epi-off group was about 2-fold greater than that of the iontophoresis group (50.5 ± 5.3 μg/g and 23.6 ± 2.5 μg/g, respectively) and 4-fold greater than that of the epi-on group (11.7 ± 3.3 μg/g). Similar differences among the 3 groups were observed for the intermediate and posterior stromal slices, presenting an evident reduction of riboflavin concentration with increasing depth in all groups. Slice depth-dependent decrease in riboflavin concentration was statistically significant (general linear model (GLM); F1,6 = 62.265, P < .001), as was the group-dependent variation (GLM; F2,6 = 20.268, P = .002) and the slice depth group interaction (GLM; F2,6 = 18.004, P = .002).
  
  
  CONCLUSIONS
  Corneal cross-linking transepithelial iontophoresis imbibition yielded greater and deeper riboflavin saturation with respect to conventional epi-on, while maintaining the advantages of avoiding epithelial removal and shorter procedure time, but did not reach concentrations obtained with standard epi-off.
authors: Department of Medicine and Ageing Sciences, Ophthalmology Clinic, University "G. d'Annunzio" of Chieti and Pescara, Chieti, Italy.
authors: Leonardo
authors: L
authors: Mastropasqua
authors: Department of Medicine and Ageing Sciences, Ophthalmology Clinic, University "G. d'Annunzio" of Chieti and Pescara, Chieti, Italy. Electronic address: m.nubile@unich.it.
authors: Mario
authors: M
authors: Nubile
authors: Department of Medicine and Ageing Sciences, Ophthalmology Clinic, University "G. d'Annunzio" of Chieti and Pescara, Chieti, Italy.
authors: Roberta
authors: R
authors: Calienno
authors: Department of Medicine and Ageing Sciences, Ophthalmology Clinic, University "G. d'Annunzio" of Chieti and Pescara, Chieti, Italy.
authors: Peter A
authors: PA
authors: Mattei
authors: Ophthalmology Clinic, University of Verona, Verona, Italy.
authors: Emilio
authors: E
authors: Pedrotti
authors: Department of Medicine and Ageing Sciences, Ophthalmology Clinic, University "G. d'Annunzio" of Chieti and Pescara, Chieti, Italy.
authors: Niccolò
authors: N
authors: Salgari
authors: Ophthalmology Clinic, University of Verona, Verona, Italy.
authors: Rodolfo
authors: R
authors: Mastropasqua
authors: Department of Medicine and Ageing Sciences, Ophthalmology Clinic, University "G. d'Annunzio" of Chieti and Pescara, Chieti, Italy.
authors: Manuela
authors: M
authors: Lanzini
mesh_terms: D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003319:Corneal Stroma / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics*; D019573:Epithelium, Corneal / Q000378:metabolism; D006801:Humans; D007478:Iontophoresis; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D012256:Riboflavin / Q000493:pharmacokinetics*
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D012256:Riboflavin