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Irvine, CA-Intravitreous dexamethasone in a biodegradable, extended-release implant (Posurdex, Allergan) produced significant improvements in visual acuity and was well tolerated in recent studies. Additional investigation comparing applicator versus incisional placement suggests that the applicator approach is quicker, is at least as safe, and results in similar outcomes, according to Baruch D. Kuppermann, MD, PhD.
Earlier studies of dexamethasone have proven that it prevents swelling and reduces inflammation in retinal diseases, including macular edema. However, when used as a single injection, results have been disappointing because of the inability to deliver and maintain adequate quantities of the drug to produce effective results. The implant being investigated was designed to deliver the drug directly to the retina over a more extended period.
Other steroids are also being tested for use in macular edema. For example, triamcinolone has been used off-label, but it is not formulated for the eye, is associated with toxicity and side effects, and is not the most potent steroid, said Dr. Kuppermann, associate professor of ophthalmology and chief of the retina service at the University of California, Irvine.
Multiple implants can be given over time if the disease recurs. It is hoped that this pulsed approach and drug holiday between implantations will decrease the amount of drug exposure and reduce the side effects of steroids, such as cataracts and glaucoma, Dr. Kuppermann said. The drug is released for a period of weeks to a few months, but the therapeutic effects appear to last at least as long as 6 months, according to study results.
Persistent macular edema
To assess the safety and effectiveness of the dexamethasone implant, Dr. Kuppermann and his colleagues conducted two studies. The first was a phase II, multicenter, randomized, single-masked study in 315 patients with persistent macular edema refractory to medical or laser treatment. Patients had to have macular edema diagnosed associated with one of four conditions: diabetes, retinal vein occlusion, uveitis, and post-cataract surgery.
Patients were randomly assigned (105 per group) to treatment with 350 or 700 µg dexamethasone from a surgically implanted drug delivery device or to observation without drug therapy. The formulation of the dexamethasone drug delivery system used in this trial was an older one than is currently used. Efficacy results were based on 90 days of follow-up, and safety results were based on a 180-day period.
"The results we saw were quite impressive," Dr. Kuppermann said. Visual acuity improved by 15 letters in 18.1% of patients in the 700-µg treatment arm versus 5.7% in the observation group at day 90 (p = 0.006). This effect was observed through 180 days.
"Importantly, the drug was presumably gone by then, but its clinical effect was still apparent," he added.
Dexamethasone appears to work by suppressing mast cell-leukocyte cytokine cascades. It may control disease for a more extended period than fluocinolone because it is more potent and can kill rather than suppress the cells responsible for the cytokine cascade, Dr. Kuppermann said.
"This is a hypothesis we are testing that may be an explanation for some of the results we are seeing," he said.
Results also showed that the drug was well tolerated. Reports of cataract were similar among all study groups, and only 2% of patients who received the drug and 1% of the observation patients had an IOP increase of 10 mm Hg or more at day 90. All cases of elevated IOP were managed with observation or topical medication. There were no cases of treatment-related endophthalmitis or retinal detachment.