June 2013
Volume 54, Issue 15
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ARVO Annual Meeting Abstract  |   June 2013
Evaluation of transcorneal iontophoresis of riboflavin for corneal collagen cross-linking
Alejandro Arboleda; Laura Kowalczuk; Michèle Savoldelli; Christophe Klein; Sophia Ladraa; Jean-Marie Parel; Francine Behar-Cohen
Author Affiliations & Notes
  • Alejandro Arboleda
    Ophthalmic Biophysics Center, Dept. of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
    Dept. of Biomedical Engineering, University of Miami College of Engineering, Coral Gables, FL
  • Laura Kowalczuk
    INSERM UMRS872: Physiopathology of Ocular Diseases: Therapeutic Innovations, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France
  • Michèle Savoldelli
    AP-HP Hôtel-Dieu, Dept. of Ophthalmology, Sorbonne Paris Cité, Paris Descartes University, Faculty of Medicine, Paris, France
  • Christophe Klein
    INSERM UMRS872: Physiopathology of Ocular Diseases: Therapeutic Innovations, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France
  • Sophia Ladraa
    INSERM UMRS872: Physiopathology of Ocular Diseases: Therapeutic Innovations, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France
  • Jean-Marie Parel
    Ophthalmic Biophysics Center, Dept. of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
    AP-HP Hôtel-Dieu, Dept. of Ophthalmology, Sorbonne Paris Cité, Paris Descartes University, Faculty of Medicine, Paris, France
  • Francine Behar-Cohen
    INSERM UMRS872: Physiopathology of Ocular Diseases: Therapeutic Innovations, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France
    AP-HP Hôtel-Dieu, Dept. of Ophthalmology, Sorbonne Paris Cité, Paris Descartes University, Faculty of Medicine, Paris, France
  • Footnotes
    Commercial Relationships Alejandro Arboleda, None; Laura Kowalczuk, None; Michèle Savoldelli, None; Christophe Klein, None; Sophia Ladraa, None; Jean-Marie Parel, CROMA (F), InnFocus (F), Abeamed (F), University of Miami (P); Francine Behar-Cohen, Inserm/Univesrité ParisDescartes (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4072. doi:
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      Alejandro Arboleda, Laura Kowalczuk, Michèle Savoldelli, Christophe Klein, Sophia Ladraa, Jean-Marie Parel, Francine Behar-Cohen; Evaluation of transcorneal iontophoresis of riboflavin for corneal collagen cross-linking. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4072.

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Abstract
 
Purpose
 

To determine whether two riboflavin solutions can be delivered into the cornea through iontophoresis prior to collagen cross-linking. Two conditions, epithelium-on and epithelium-off, were compared to determine which allowed for the most diffusion of riboflavin throughout the cornea.

 
Methods
 

A Coulomb-controlled iontophoresis (CCI) generator and a corneal probe were used to deliver either 0.1% riboflavin-dextranT5000 or 0.1% riboflavin-phosphate into the eyes of 8-week-old Lewis rats under either epithelium-on (epi-on) or epithelium-off (epi-off) conditions. Within 30 minutes of CCI (1.77 mA/cm2 for 4 minutes), corneas were flat-mounted for fluorescence imaging using a confocal microscope (LSM 710, Zeiss). The distribution of riboflavin in the cornea was evaluated by recording the fluorescence intensity. Aqueous humors (Aq.H) were also collected to assay riboflavin concentration by fluorometry using a multilab counter (Wallac Victor 1420, Perkin Elmer).

 
Results
 

Iontophoresis delivered both riboflavin solutions throughout the whole cornea for the epi-off condition. For the epi-on case, only riboflavin-phosphate was successfully delivered to the cornea (Figure 1). Corneal imaging and Aq.H assay both demonstrated that riboflavin-phosphate delivery is more efficient than riboflavin-dextran delivery. The riboflavin concentrations in Aq.H were: epi-on riboflavin-phosphate, 0.92 µg/mL; epi-on riboflavin-dextran, 0.55 µg/mL; epi-off riboflavin-phosphate, 13.6 µg/mL; and epi-off riboflavin-dextran, 4.73 µg/mL.

 
Conclusions
 

Iontophoresis can be used to efficiently deliver riboflavin into the cornea. The epi-off condition enhances diffusion of riboflavin into the stroma and aqueous humor. Transcorneal delivery is only possible with riboflavin-phosphate. The efficiency of CXL through an intact epithelium, which absorbs most UV radiation, remains to be demonstrated.

 
Figure 1: White shows riboflavin fluorescence: the whiter, the higher the riboflavin concentration (A) Riboflavin-dextran diffusion in the cornea for the epi-off condition (B) Riboflavin-dextran diffusion in the cornea for the epi-on condition (C) Riboflavin-phosphate diffusion in the cornea for the epi-off condition (D) Riboflavin-phosphate diffusion in the cornea for the epi-on condition
View OriginalDownload Slide
 
Figure 1: White shows riboflavin fluorescence: the whiter, the higher the riboflavin concentration (A) Riboflavin-dextran diffusion in the cornea for the epi-off condition (B) Riboflavin-dextran diffusion in the cornea for the epi-on condition (C) Riboflavin-phosphate diffusion in the cornea for the epi-off condition (D) Riboflavin-phosphate diffusion in the cornea for the epi-on condition
 
Figure 1: White shows riboflavin fluorescence: the whiter, the higher the riboflavin concentration (A) Riboflavin-dextran diffusion in the cornea for the epi-off condition (B) Riboflavin-dextran diffusion in the cornea for the epi-on condition (C) Riboflavin-phosphate diffusion in the cornea for the epi-off condition (D) Riboflavin-phosphate diffusion in the cornea for the epi-on condition
Figure 1: White shows riboflavin fluorescence: the whiter, the higher the riboflavin concentration (A) Riboflavin-dextran diffusion in the cornea for the epi-off condition (B) Riboflavin-dextran diffusion in the cornea for the epi-on condition (C) Riboflavin-phosphate diffusion in the cornea for the epi-off condition (D) Riboflavin-phosphate diffusion in the cornea for the epi-on condition
View OriginalDownload Slide
 
Keywords: 484 cornea: stroma and keratocytes • 574 keratoconus • 596 microscopy: confocal/tunneling  
© 2013, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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