Role of dexamethasone implant in DME characterized in study

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A prospective, randomized trial of treatment for diabetic macular edema finds similar vision improvement with intravitreal bevacizumab (Avastin, Genentech) and an intravitreal dexamethasone implant (Ozurdex, Allergan), but differences in other endpoints.

By Cheryl Guttman Krader; Reviewed by Mark A. Gillies, MD

Sydney, Australia-Results from 1 year of follow-up in a prospective, randomized controlled clinical trial comparing the sustained-release, biodegradable dexamethasone intravitreal implant (Ozurdex, Allergan) and intravitreal bevacizumab (Avastin, Genentech) do not indicate a clear efficacy advantage of one modality versus the other.

However, taking into account treatment burden and safety, the data would support considering the dexamethasone implant over bevacizumab in pseudophakic eyes, said Mark C. Gillies, MD.

“Both intravitreal bevacizumab and the dexamethasone implant have been shown to be efficacious for center-involving DME,” said Dr. Gillies, professor of clinical ophthalmology & eye health, The University of Sydney, Australia. “However, this is the first head-to-head randomized clinical trial directly comparing them.

“The results so far show the proportion of eyes with a BCVA improvement of at least 10 letters at 1 year was similar in the two groups,” Dr. Gillies said. “The dexamethasone implant group had more eyes that lost vision, but that was mostly due to unoperated cataract, and the dexamethasone group also had a better anatomical outcome and needed fewer injections.”

However, with those benefits, there were also risks of significant IOP elevation and need for IOP-lowering medication, he noted.

On June 30, 2014, the FDA approved the dexamethasone implant for the treatment of DME in pseudophakic eyes or those scheduled for cataract surgery.

The 2-year multicenter trial is under way at four sites in Australia. It enrolled 88 eyes of 61 patients meeting eligibility criteria of having center-involving DME, VA of 6/9 or worse, and central macular thickness (CMT) >300 µm.

Patients were randomly assigned 1:1 to intravitreal bevacizumab every 4 weeks or dexamethasone implant every 4 months as needed. Re-treatment was considered if CMT exceeded 300 µm.

The 12-month analysis used an intent-to-treat population with last observation carried forward for 4 bevacizumab eyes and 3 dexamethasone eyes of patients who withdrew from the study on their own accord.

The two groups were well matched at baseline in all demographic and disease characteristics. Mean logMAR BCVA was about 56 letters (around 20/80). Mean CMT was 503 µm in the bevacizumab eyes and 474 µm for the dexamethasone group.

Proportion of eyes with a BCVA improvement of 10 or more letters, which was analyzed as the primary outcome, was the same at 1 year in the bevacizumab and dexamethasone groups (40% versus 43%, respectively). There was also no statistically significant difference between groups in the analysis of mean BCVA changed from baseline at 1 year (bevacizumab 8.9 letters, dexamethasone 5.6 letters), although there was greater fluctuation in BCVA levels over time in the dexamethasone group.

“Sensitivity analyses were also conducted for the primary endpoint assuming either that all eyes lost to follow-up improved by at least 10 letters or that all eyes lost to follow-up did not reach that threshold. In each scenario, there was still no significant difference between treatment groups indicating that results from the primary analysis were robust from the presence of missing data,” Dr. Gillies said.

No bevacizumab-treated eyes lost 10 or more letters from baseline VA compared with 5 (11%) eyes in the dexamethasome group, of which 3 were due to cataract.

Mean change in CMT at 1 year was significantly greater in the dexamethasone eyes compared to the bevacizumab group (189 versus 122 µm).

Mean number of treatments received calculated using data only for the 81 eyes reaching the 12-month visit was 8.6 for the bevacizumab group and 2.7 for the dexamethasone implant

A between-group comparison for the proportion of phakic eyes that experienced cataract progression of 2 or more grades showed no statistical significance difference between groups, although these events were more common in the dexamethasone eyes than in the bevacizumab group (20% versus 9.3%). During the first year of the study, cataract surgery was performed in one bevacizumab-treated eye and three eyes with the dexamethasone implant.

“The 2-year analysis will include the effect of steroid-induced cataract and its removal,” Dr. Gillies said.

No eyes treated with bevaciuzmab experienced an IOP reading >25 mm Hg above baseline compared with 12 eyes in the dexamethasone group. IOP-lowering medication was initiated in 7 dexamethasone-treated eyes, but in no eyes in the bevacizumab group.

Mark A. Gillies, MD

E: mark.gillies@sydney.edu.au

This article was adapted from Dr. Gillies’ presentation at the 2014 meeting of the Association for Research in Vision and Ophthalmology. Dr. Gillies is a consultant, advisory board member, and receives research support from Allergan, Bayer, and Novartis.