Ocular Surgery News
a SLACK Incorporated newspaper

An Intraocular Drug Delivery System for Cataract Surgery

Dr. Chang is an Associate Clinical Professor of Ophthalmology at the University of California, San Francisco. He is in private practice in Los Altos, California, specializing in cataract surgery

by David F. Chang, MD


The use of antibiotics and anti-inflammatory drugs for cataract surgery, both perioperatively and postoperatively, continues to be the standard of care.

The options for perioperative drug administration include drops, subconjunctival injections, collagen shields and intraocular placement either by direct injection or placement in the infusion bottle. With the widespread emergence of topical anesthesia, some of these options are less desirable. Subconjunctival injections are painful under topical anesthesia and collagen shields can be blinked out if the eye is not patched. The effectiveness of antibiotics in the infusion bottle remains uncertain. There is still the risk of dosing error and the possibility of the emergence of resistant bacteria. All four of these methods fail to sustain a high level of drug within the eye for a long time.

Postoperatively, most of us would still prescribe antibiotics and either steroidal or nonsteroidal anti-inflammatory drops. The disadvantages of postop drops primarily consist of cost, compliance and chair time in instructing patients. In the Third World, the problems of cost and availability may preclude the use of postop medications altogether.

Compliance problems with drops in the cataract population are well known to all of us. Some patients become confused if they receive more than one medication. The patient must keep the bottles sterile, shake a suspension and get the drop into the cul-de-sac with enough contact time to penetrate the cornea. The responsibility for eye drop administration may be a significant burden for certain individuals, either by raising questions and concerns, or requiring assistance from another person.

The ideal perioperative drug delivery system for intraocular surgery would be effective in providing an adequately high and prolonged level of drug at the intraocular site; safe by confining the effect to this target organ and minimizing systemic effect; long-acting enough so that supplemental postop drops become unnecessary; and, yet, short-acting enough in the event of side effects or allergy. We want to minimize patient involvement and the problems of installation, compliance and instruction. The ideal perioperative drug should also be inexpensive and compatible with topical anesthesia and immediate vision.

Surodex (dexamethasone, Oculex Pharmaceuticals) may be an example of just such a product. Oculex Pharmaceuticals is a Silicon Valley biotechnology firm that was cofounded by an academic ophthalmologist from Georgetown, Dr. Vernon Wong. Oculex has developed a sustained release, intraocular drug delivery system. This tiny particle consists of a biodegradable polymer which is placed in the anterior chamber at the conclusion of surgery. Any drug, bound to the polymer, is gradually released at a programmed rate as the polymer dissolves. Depending on the formulation, the drug can be released over as long a period as 1 year or over as short a period as several days to 1 week.

Surodex contains 60 mcg of dexamethasone. This is approximately the same amount of drug contained in a single topical drop of Decadron (dexamethasone sodium phosphate, Merck Sharp & Dohme). But due to poor corneal penetration, only a small percentage of the topically-applied drug ever reaches the anterior chamber. Studies on rabbit models show that the Surodex system achieves a much higher intraocular steriod level than is achieved with drops, and sustains this high, non-fluctuating level for about a week. In contrast, the steriod level achieved by an eyedrop falls significantly after 90 minutes.

Surodex has passed the FDA's Phase 1 clinical study, which looks at safety. Six patients were monitored for 90 days after placement of the Surodex particle following cataract surgery. There were no complications or side effects in this group. As judged by slit lamp exam, 5 out of 6 patients had no cell and flare at 1 week and all 6 were quiet by 2 weeks.

In a related, randomized, double-blind study from Singapore, 60 patients received either the Surodex particle, or 4 weeks of dexamethasone drops after cataract surgery. In this study, the Surodex group showed a statistically significant lower mean flare score at days 4, 8 and 15, as measured with the Kowa flare meter. Slit-lamp assessment of anterior chamber cell and flare also showed lower mean scores, but was not statistically significant.

The product has now completed the FDA's Phase 2 clinical study which looks at efficacy. I was l of 4 clinical investigators nationally. The final results of this study are not yet available for release, but we can anticipate them during the coming year.

In conclusion, by bypassing the cornea with direct intraocular administration, higher and more sustained levels of drug are theoretically achieved than with eye drops. In addition to the therapeutic advantages of such a system, patients may potentially become relieved of a significant postoperative responsibility and concern. Finally, by reducing or elf eliminating the need for prescribing drops and the associated time instructing patients and answering questions - this patient and surgeon-friendly alternative may also prove to be more efficient and cost-effective as well.