Dexamethasone for DME delivers long-term visual benefits

Take-Home

A dexamethasone implant provides long-term visual improvements in patients with diabetic macular edema treated with two doses of the drug.

By Lynda Charters; Reviewed by David S. Boyer, MD

Los Angeles-Use of a dexamethasone intravitreal implant (Ozurdex, Allergan) provided long-term, rapid, sustained clinically relevant visual improvements in patients with diabetic macular edema (DME) treated with two doses of the drug.

“[The dexamethasone implant] fulfills an unmet need in the treatment of inflammation in DME,” said David S. Boyer, MD, clinical professor of ophthalmology, University of Southern California Keck School of Medicine, Los Angeles.

“It is a potent steroid in a novel, long-acting delivery system [Novadur, Allergan] that provides sustained, localized release of dexamethasone-which inhibits a variety of inflammatory mediators involved in macular edema,” he said.

Two drug groups versus sham

Dr. Boyer-on behalf of the Macular Edema Assessment of Implantable Dexamethasone in Diabetes Study Group-presented the results of phase III multicenter, masked, randomized, sham-controlled trials to assess the safety and efficacy of the dexamethasone implant for treating DME with 700 or 350 µg of the drug in a posterior segment drug-delivery system.

The phase III studies-010 and 011-were parallel studies in which one eye of each patient was treated.

A total of 347 patients were randomly assigned to the 700-µg dose, 343 patients to the 350-µg dose, and 350 patients to sham treatment. Patients-all of whom had diabetes and a central retinal thickness of 300 µm or more-were assessed for re-treatment every 3 months after the month 6 evaluation; re-treatments could not be performed earlier than every 6 months.

The primary end point was 3 years and a gain in best-corrected visual acuity (BCVA) of 15 or more ETDRS letters.

Secondary end points were the percentage of patients with a gain of 20 or more letters, mean BCVA change from baseline, mean BCVA change in a subset of pseudophakic patients (25% of study population), and changes in retinal anatomy seen on optical coherence tomography, Dr. Boyer noted.

The three groups were well matched demographically at baseline:

• Most patients (90%) had type 2 diabetes.

• The mean diabetes duration was more than 16 years.

• The mean duration of DME was about 15 months.

Patients could receive up to 7 treatments. Over the 3-year study period, in the 700-µg group, the mean number of treatments was 4.1; in the 350-µg group, 4.4 treatments; and in the sham group, 3.3 treatments.

“Use of the dexamethasone implant led to a clinically meaningful improvement in vision, that is, 3 lines or more (15 letters or more), in the high-dose group in 22.2% of patients, and in the low-dose group in 18.4% of patients compared with 12% in the sham group,” Dr. Boyer said. “The results were significant at p < 0.05.”

Some patients achieved 4 or more lines of vision (20 or more letters): 8.5% in the high-dose group, 11% in the low-dose group, and 4.6% in the sham group. These results were also significant (p < 0.05) compared with the sham group.

Patient subset

In the subset of pseudophakic patients, “the early increase in vision following treatment was maintained throughout the course of the study” compared with phakic patients who lost some of the gain in vision as the result of cataract development, Dr. Boyer noted.

The lens status at baseline was irrelevant, because “in all groups the patients’ vision improved,” he said.

The mean average deceases in central retinal thickness compared with baseline were significantly greater in the two drug groups compared with the sham group. In the high-dose group, the average decrease was 111.6 µm and in the low-dose group 107.9 µm compared with 41.9 µm in the sham group, differences that also reached significance (p < 0.05).

Development of cataract and increase in IOP were the two main adverse events. Cataracts developed in about 70% of patients, whereas IOP increased following each treatment and then decreased without an added effect.

“Only 0.3% of patients required a trabeculectomy in the two drug groups-one patient in each group-to control IOP,” Dr. Boyer noted.

Review of study results

“Long-acting dexamethasone provided long-term visual improvement in patients with DME,” Dr. Boyer concluded.

The percentage of patients with 3 lines or more gains in visual acuity was significantly higher in the treated groups compared with the sham group, he noted.

Despite development of cataracts in most patients, the visual benefit of the drug treatment was restored after cataract surgery and the vision did not worsen.

DME improved rapidly after treatment, with an average treatment of 4.1 injections.

The drug’s safety profile was good as or better than that of steroids used routinely in clinical practice. IOP elevations rarely required treatment. There was no evidence of arterial thrombotic events, Dr. Boyer summarized.

David S. Boyer, MD

E: vitdoc@aol.com

Dr. Boyer is a consultant to Allergan.

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