Intraocular steroid delivery system begins FDA phase 3 trials

Issue: February 1998

ST. LOUIS - An intraocular drug delivery system (DDS) containing dexamethasone may be an effective, efficient and patient-friendly way to suppress inflammation following cataract surgery. The system, which has begun Food and Drug Administration (FDA) phase 3 clinical trials, is designed to gradually release dexamethasone directly into the anterior segment.

Therapeutic efficacy may be improved by eliminating the problems of compliance and corneal penetration, according to David F. Chang, MD, a cataract surgeon in private practice in Los Altos, Calif., and associate clinical professor of ophthalmology at the University of California, San Francisco. Dr. Chang was one of four clinical investigators for the FDA phase 2 clinical trials of the device that recently have been completed.

He said traditional perioperative drug delivery methods - eye drops, subconjunctival injection, collagen shields and placement in the infusion bottle - all fail to maintain a high level of drug within the eye for a long enough period of time. Drawbacks to using postoperative eye drops, he continued, include the need for patient education and compliance.

"The ideal perioperative drug delivery system would achieve a high and sustained intraocular drug level, would be compatible with topical anesthesia and immediate vision and would eliminate patient involvement by making postop drops unnecessary," Dr. Chang said.

The dexamethasone DDS was developed by Oculex Pharmaceuticals Inc. of Sunnyvale, Calif., and is to be marketed by Storz Ophthalmics of St. Louis. The implant consists of a tiny, free-floating biodegradable polymer, which is delivered into the anterior chamber with forceps at the end of surgery. "Oculex is able to bind a variety of drugs to biodegradable polymers that can be formulated to dissolve and release the drug over a programmed period of time. This delivery period can range from several days up to a year," Dr. Chang said.

Therapeutic advantages

As formulated currently for cataract surgery, the DDS contains 60 µg of dexamethasone, which is gradually released within the anterior segment over a 1-week period. This is approximately the same amount of dexamethasone as a single drop of dexamethasone eye drops.

"Conventional q.i.d. topical regimens deliver about a 250 µg daily dose of dexamethasone topically," Dr. Chang said. "However, rabbit studies have shown that by bypassing the cornea, the 60 µg intraocular delivery system can achieve higher continuous levels of dexamethasone within the eye than is possible with eye drops alone."

In the FDA phase 1 clinical trial, six patients were followed for 3 months following insertion of dexamethasone DDS after cataract surgery. No complications or side effects were observed. Five of the six patients had
no cell or flare at 1 week postop, and the sixth was clinically quiet by the second week. "A separate randomized double blind study from Singapore showed the product to be clinically superior to dexamethasone drops at suppressing post-cataract inflammation, as judged by anterior chamber flare," Dr. Chang said.

Patient, physician advantages

"It was fairly easy to recruit patients for the phase 2 study because of the potential that they wouldn't have to use drops," Dr. Chang said. "We often underestimate how difficult this responsibility is for some patients, most of whom consider taking drops to be more difficult than pills.

"With an intraocular delivery system, we may be able to avoid all of the problems of patient compliance with eye drops," he continued. "Patients must fill and refill their prescriptions, keep their bottles sterile, remember which medication to use when, adequately shake suspensions and get each drop into the cul-de-sac with enough contact time to penetrate the cornea. Some patients require another person to assist them.

"Meanwhile, we and our staffs spend significant time postop on prescriptions and patient questions and education regarding medications. Indeed, one function of postop visits is to assess anti-inflammatory drug compliance and response," Dr. Chang said.

"This is a win-win concept. If this drug delivery method proves to be therapeutically superior and minimizes the need for patient drug compliance and education, it will be a system that is more patient-friendly, more physician-friendly and more cost effective to the health care delivery system," he said.

For Your Information:

David F. Chang, MD, associate clinical professor of ophthalmology at the University of California, San Francisco, can be reached at his private practice specializing in cataract surgery, 762 Altos Oaks Dr., Ste. 1, Los Altos, CA 94024. Dr. Chang has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Storz Ophthalmics can be reached at 3365 Tree Court Industrial Blvd., St. Louis, MO 63122; (800) 325-9500; fax: (314) 225-1308.