Results of a preclinical pilot study demonstrate ocular iontophoresis accelerates transfer of topically applied riboflavin into the cornea.
Orlando, FL-Results of a preclinical pilot study demonstrate ocular iontophoresis accelerates transfer of topically applied riboflavin into the cornea, said George O. Waring IV, MD, during Refractive Surgery Subspecialty Day at the annual meeting of the International Society of Refractive Surgery/American Academy of Ophthalmology.
The efficacy and safety of the iontophoretic technique was investigated in an animal study. In one experiment, 12 New Zealand rabbits were divided into four groups. In two groups riboflavin 0.1% containing a bioenhancer (Ricrolin TE, SOOFT) to loosen the tight junctions was delivered with iontophoresis using application times of 3 or 5 minutes. An active control group received the same riboflavin solution with delivery by passive imbibition, and a negative control group underwent 5 minutes of iontophoresis using saline instead of riboflavin. Current was delivered using a prototype generator that allowed variation in current intensity and time of current application.
Confocal analysis of the cornea showed no irregularities associated with use of current. However, when higher currents were tested to investigate the possibility of shortening iontophoresis duration, opacities were observed when the current was increased, although the changes were reversible.
The basic principle of iontophoresis involves movement of ions through tissue under the influence of an electrical field. The transport of the ions is governed by the Nernst-Planck equation that indicates ion movement can be modified by changing the drug concentration and current intensity, but also depends on the presence of competing ions that are present in the tears, the riboflavin formulation, or other topical drops.
"Iontophoresis is an old concept that has been used clinically in dermatology for the transdermal delivery of analgesics," Dr. Waring said. "There are many published reports relating to use for delivery of ions into the cornea, and there is currently a phase III clinical trial under way investigating iontophoresis for transscleral corticosteroid delivery.
"Riboflavin is actually a perfect candidate for iontophoresis because it has a small molecular weight, high water solubility, and the prodrug is negatively charged at physiological pH," he said.
A system for the iontophoresis treatment is in development. It includes a generator with a preset current intensity and delivery time. The riboflavin solution is placed into a small silicone ring that is held on the eye with low suction.
A new riboflavin solution formulated for enhanced iontophoretic action (Ricrolin +) is also being released.
A European clinical trial enrolling 50 eyes at 10 sites is planned to launch in the beginning of 2012.
George O. Waring IV, MD
Dr. Waring is a clinical investigator for Topcon/SOOFT and is chairman of the scientific advisory board for Topcon Crosslinking Technologies.