Corticosteroid delivered via iontophoresis offers novel treatment

Patients with noninfectious anterior uveitis were more successfully treated with the lowest of four doses of electrical current when dexamethasone phosphate was administered via iontophoresis using the EyeGate II delivery system, according to a prospective clinical trial.

Compared with dosing groups of 4.8 mA/min, 10 mA/min and 14 mA/min, the group with 1.6 mA/min dosing achieved the best results.

“Iontophoresis is an innovative technique that enables you to take a substance, not necessarily limited to a drug, and cause that substance to cross tissue barriers without puncturing them with needles or knives or trocars. Iontophoresis only uses electricity to drive the actual chemical through intact tissue,” Michael S. Korenfeld, MD,

a co-author of the study, said in an interview with OSN Retina.

With the EyeGate II delivery system (EyeGate Pharmaceuticals), dexamethasone phosphate “is made into a charged species,” Dr. Korenfeld said. “The activation of the current causes the plus-charged cathode of the device to generate minus-charged hydroxide ions that then repel the minus-charged drug and drive it across the conjunctiva and sclera.”

Dr. Korenfeld was first introduced to iontophoresis while in medical school in the early 1980s, and he had hoped that a company would expand on the concept.

“However, for the longest time, none of the companies gave it any credibility,” he said. “When I found out that EyeGate Pharmaceuticals had proprietary technology to use iontophoresis to deliver drugs, I contacted the company to let them know about my knowledge of iontophoresis and expressed an interest in participating because I believed in the concept.”

The study

The phase 1/2 study, which was published in Ophthalmology, involved 40 patients who were randomized into one of four dosing groups to receive a single treatment of EGP-437 (dexamethasone phosphate formulated for iontophoresis). The amount of current used to drive the drug into the eye varied, but the concentration of the drug in the solution did not.

In the group receiving the lowest dose of current, the median number of days before the anterior chamber cell score reached zero was 11.5, compared with 31 days for the highest-dose group.

“This came as a surprise,” Dr. Korenfeld said. “You would think that the more current used, the more the drug would be driven into the eye. However, this inverse dose response to the current may be related to how deeply the drug is driven into the eye — at higher currents, more deeply — rather than how much drug is delivered in total.”

Dr. Korenfeld said he does not know why the lower dose of current provided the best outcomes.

“It is possible this is due to chance. The patients in the lower current group may have had a more responsive kind of uveitis than those patients treated with the higher concentration of current,” he said.

Noninvasive treatment

The noninvasive procedure lasts 4 minutes, and patient discomfort is minimal, according to Dr. Korenfeld.

“You don’t feel the electric current at all at this amperage,” he said.

An anesthetic eye drop is administered because the delivery device touches the eye surface near the limbus.

Dr. Korenfeld is participating in a phase 3 follow-up study of the EyeGate II system that is now enrolling patients. Unlike the phase 1/2 study, the phase 3 trial will compare the iontophoretic delivery of dexamethasone to prednisolone acetate eye drops, the standard eye drop treatment for noninfectious anterior uveitis.

“I like that EyeGate is noninvasive, the drug gets into the eye at higher concentrations and more quickly than with an eye drop, and you take patient compliance out of the picture,” Dr. Korenfeld said. “This device could very well eventually become the treatment of choice. In most study patients, a single treatment was sufficient to make the disease go away.” – by Bob Kronemyer

Reference:

Cohen AE, Assang C, Patane MA, From S, Korenfeld M; Avion Study Investigators. Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis. Ophthalmology. 2012;119(1):66-73.

Michael S. Korenfeld, MD, can be reached at Comprehensive Eye Care, 901 E. 3rd St., Washington, MO 63090-3010; 636-390-3999; email: michaelkorenfeld@hotmail.com.

Disclosure: Dr. Korenfeld is a paid consultant to EyeGate Pharmaceuticals.