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David Myung, Gail Zaler, Anthony Abbate, Drew DiGiore, Don Eaton, Edward E Manche; Vacuum-mediated transepithelial delivery of riboflavin to the cornea. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3014.
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© ARVO (1962-2015); The Authors (2016-present)
Riboflavin-mediated UV crosslinking has emerged as an effective means to slow the progression of structural corneal disorders such as keratoconus and post-LASIK ectasia. One of its limitations, however, is the need for epithelial debridement to increase riboflavin diffusion into the stroma, which requires a painful recovery period and carries the risk of infection and scarring. Transepithelial delivery through ultrasound or iontophoresis, for example, have been studied as potential ways to overcome this problem. We report here a novel vacuum-based delivery system to facilitate delivery of riboflavin to the stroma without the need for epithelial debridement.
The delivery system includes a fenestrated hand-held unit fabricated via high resolution stereolithography that creates a sealed reservoir over the cornea, and a vacuum pump that induces negative pressure. Riboflavin was delivered to the corneas of both enucleated porcine eyes and rabbit eyes in vivo using this system. Riboflavin 0.1% without dextran was used for all experiments. Fluorescein staining and clinical evaluation of the samples were performed to evaluate for any epithelial defects caused by the procedure. Samples of excised corneal buttons 8.25 mm in diameter were evaluated by mass spectrometry to determine the total riboflavin content as a function of time and vacuum pressure.
The concentration of riboflavin in explanted corneal buttons was measured by liquid chromatography tandem mass spectrometry (LC/MS/MS). Transepithelial diffusion of riboflavin into the cornea was achieved with concentrations increasing as a function of time, ranging between 90 ng/mL and 1200 ng/mL. The maximum riboflavin concentration achieved was found to be greater than six-fold higher than the epithelium-on study control. No epithelial defects were detected after vacuum-mediated riboflavin delivery. Real-time intraocular pressure of the eyes during vacuum application remained within normal limits.
We have developed a novel, vacuum-based transepithelial delivery system for delivering therapeutic doses of riboflavin to the cornea and significantly higher levels of stromal riboflavin than epithelium-on topical administration. The technology has the potential to deliver other drugs non-invasively into the eye as well. In future work, UV irradiation will be used to crosslink corneas imbibed with riboflavin with this delivery system.
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