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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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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.
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).
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.
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.
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