Surgeon explains options for sustained intraocular drug delivery

VIENNA, Austria — Intravitreal injections are a long-established, effective form of drug delivery into the eye. However, the need for frequent injections is a concern. Longer-term drug delivery systems may represent a better, less invasive approach to the treatment of macular edema, according to Baruch Kuppermann, MD, at the Euretina Congress here.

The Bausch & Lomb Retisert reservoir-style implant for sustained delivery of fluocinolone has obtained U.S. Food and Drug Administration approval for the treatment of uveitis. Dr. Kuppermann said the benefits of the implant are remarkable.

The implant requires a surgical procedure with a 3.5-mm pars plana incision. The device is designed to last for about 1,000 days, delivering a total of 0.5 mg of the substance.

The same implant was also tested for diabetic macular edema, but although benefits were shown, safety concerns were raised by a high rate of increased IOP and cataract.

"The low 0.5-mg dose used against placebo surprised us for how potent the effect was, which confirms the efficacy of this way of delivering anti-inflammatory agents. However, glaucoma occurred in almost 50% of the cases, and cataract was practically ubiquitous. The company therefore decided to limit the indications to uveitis," Dr. Kuppermann said.

The Alimera Medidur implant also releases fluocinolone but has the advantage of being delivered through a 25-gauge injection. This allows implantation in an office setting.

"Once injected, the implant floats freely into the vitreous cavity," Dr. Kuppermann explained.

Two release rates — 0.5 mg and 0.2 mg — are available. Duration in both cases is 1 year. "Phase 3 trials on DME are currently ongoing. Up to now, the safety and efficacy profile seems promising," he noted.

The Posurdex biodegradable dexamethasone implant (Allergan) is a different concept. It is not a reservoir but a biodegradable implant in which the drug is incorporated into a polymer matrix. As the polymer degrades, the drug is released. The first model required surgical implantation in the operating room, but a new version, which is currently used in phase 3 trials, uses an injection process with no surgical incision and can be used in an office setting. Once inserted, the implant floats into the eye.

"Data from a large study on patients with persistent macular edema that failed all other therapies showed a remarkable gain of three or more [visual acuity] lines at 3 and 6 months," Dr. Kuppermann said.

The SurModics I-vation implant is a helical coil containing triamcinolone within a polymer coating.

It is implanted through a 25-gauge needle, and it is self-anchoring within the sclera, so it may be able to be implanted in a nonsurgical setting. Duration is around 18 months. A multicenter trial on this implant is under way in patients with DME.

"In conclusion, we have two fundamental approaches and philosophies with regard to ocular drug delivery. On one hand, we have the longer-acting reservoir implants, which have good long-term control of the disease but a potential for side effects. Even low levels of chronic bathing of the eye with steroids may be associated with increased risk for developing cataract and glaucoma," Dr. Kuppermann said.

"The other approach, particularly that of the new Allergan-Oculex Posurdex model, provides shorter-acting biodegradable inserts that potentially expose the eye to a lower risk of complications and may provide a sufficiently good control of the disease. Potential recrudescence can be re-treated, thus minimizing unnecessary drug exposure."

"It is possible that each approach might have preferential uses in different diseases with different drugs," he said.