New Easy-to-Use Device Enhances Ocular Drug Delivery

Neil Canavan

February 20, 2012

February 20, 2012 (Abu Dhabi, United Arab Emirates) — Iontophoresis, a technique long known but never successfully used for ocular drug delivery, has been shown to be a safe and effective method for the delivery of dexamethasone to the eye using the power of an electric field, according to data presented here at the World Ophthalmology Congress 2012.

In this study, a small electrical charge was used to introduce high concentrations of charged dexamethasone (EGP-347) through the antechamber of the eye in patients with dry eye. Both the delivery device and the drug are manufactured by EyeGate Pharmaceuticals in Waltham, Massachusetts.

"This is a new method for the delivery of an old medication," explained lead investigator John D. Sheppard, MD, associate professor at the Eastern Virginia Medical School in Norfolk.

Using an iontophoresis device to deliver EGP-347, Dr. Sheppard and colleagues were able to demonstrate a marked improvement in the symptoms of dry eye, compared with placebo.

Dr. Sheppard noted that previous research showed a charge/dose response.

In this phase 3 multicenter study, 181 subjects were randomized in a 1:1:1 fashion to 1 of 3 ocular iontophoresis groups: EGP-347 4.0 mA/minute delivered at 1.5 mA (low dose); EGP-347 10.5 mA/minute delivered at 3.5 mA (high dose), and placebo 10.5 mA/minute delivered at 3.5 mA.

To create the conditions of chronic dry eye, all subjects were exposed to a controlled adverse environment. Patients were exposed to this environment 9 times over a period of 63 days, and received active treatment or placebo before (preventive) or after (curative) exposure to the environment.

At the sixth exposure on day 22, subjects were assessed for dry eye symptoms and adverse events.

After active treatment, signs of dry eye (corneal staining, conjunctival staining, conjunctival redness) were significantly improved, compared with placebo, at visits 3 and 5 (P < .05), and dry eye symptoms (burning, stinging, dryness) improved at exposures 6, 7, 8, and 9 (P < .05).

Iontophoresis treatments were safe and well tolerated.

Numerical differences in adverse events (blurred vision, eye irritation, eye pain) between high and low doses of dexamethasone were noted, but showed no dose–intensity correlation. Differences in efficacy between active treatment groups were not reported.

"This device is attached to the forehead," said Dr. Sheppard, describing how the iontophoresis device is used, "and over the course of 3 very benign minutes delivers the medication to the patient." This approach is proven to be efficacious, and has the potential to eliminate the compliance issues seen with chronic topical administration of the drug.

Dr. Sheppard pointed out that with enhanced efficacy, iontophoresis has the potential to mitigate the effects of systemic steroid exposure.

Dry Eye, Uveitis, and Beyond With Iontophoresis

"The advantage of a technique such as this is that you can deliver high amounts of drug rapidly, which potentially spares the patient from having to continually use medication," said Marc D. de Smet, MD, PhD, professor of ophthalmology at the University of Amsterdam, the Netherlands.

Dr. de Smet is particularly interested in the use of this method to treat uveitis, the subject of other EyeGate investigations. "For ocular inflammation, I think that this particular device might be very useful for anterior segment delivery. It may also have very interesting applications for inflammation in the back of the eye, but that's something they've not really explored so far."

Because the technique has the potential to deliver any charged particle, broader applications are sure to be pursued as the development program for the device moves forward.

Dr. Sheppard is a paid consultant for EyeGate Pharmaceuticals. Dr. de Smet has disclosed no relevant financial relationships.

World Ophthalmology Congress (WOC) 2012: Abstract FP-PHA-FR 99 (10). Presented February 18, 2012.