Dexamethasone for DME shows stronger results compared with sham group

Take-home message: Use of an intravitreal implant for diabetic macular edema was more effective than a sham treatment across a variety of parameters in a subanalysis of the MEAD trial.

By Vanessa Caceres; Reviewed by Anat Lowenstein, MD

Tel Aviv, Israel-The benefits of treatment with a dexamethasone intravitreal implant (Ozurdex, Allergan) for diabetic macular edema (DME) were found in a variety of subgroups.

These groups were defined by demographics, diabetes status, diabetes and DME duration, prior treatment, and severity of diabetes, according to Anat Lowenstein, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Subgroup analysis

Dr. Lowenstein presented the results of a subgroup analysis of the MEAD trial, focused on 3-year results with the dexamethasone implant 0.7 and 0.35 mg in 1,048 patients with DME.

The trial met its primary efficacy endpoint of improvement in best-corrected visual acuity (BCVA) stronger than that of the sham-controlled group and had a safety profile consistent with previous reports, according to the study authors.¹

Dr. Lowenstein described a typical patient from the trial. The patient was a 65-year-old with severe diabetic retinopathy in both eyes. Despite focal laser therapy and three bevacizumab injections, the patient still had severe DME. The patient was treated with the dexamethasone implant, responded nicely for 4 to 5 months, and then had another recurrence. The patient developed a cataract and was treated for it after the third use of the implant.

“At the last follow up, with the seventh injection, the patient had good anatomic results,” Dr. Lowenstein said.

Dr. Lowenstein also described the various parameters under which the implant performed better than the sham-controlled group, including mean change in BCVA from baseline at 3 years, a BCVA improvement of 15 letters or more at 3 years, the time that it took to reach an improvement of 15 letters or more, and the mean average change from baseline in ocular coherence tomography retinal thickness at the center subfield. The numbers were clinically higher in patients in the 0.35-mg group as well as the 0.7-mg group.

The improvements with the implant also spanned a variety of demographic characteristics.

“The higher percentage of at least three lines of improvement was seen with the dexamethasone implant across sex, age, and ethnic group,” Dr. Lowenstein said.

Although statistics seemed to show a strikingly high result in patients under the age of 45, that was likely because of a smaller sample size, Dr. Lowenstein explained.

When analyzing vision improvement based on diabetes and DME characteristics, there was a higher percentage of at least three lines of improvement with the implant versus the sham across diabetes duration (measured as fewer than or greater than 15 years), HbA1C (less than or greater than 8%), and duration of DME (broken down into year-long increments and then 3 years or longer), she said.

“There was a trend toward an increased benefit to dexamethasone in patients with a shorter duration of disease and better control,” she said. “However, the sample size is small.”

When analyzing patients’ prior treatments, those receiving the implant once again saw a benefit regardless of the previous type of therapy or the type of DME they had, Dr. Lowenstein said.

There was also a higher percentage of 15-letter improvement or greater in patients receiving the implant regardless of their baseline ocular BCVA or retinal thickness.

“The differential efficacy here is likely caused by the ceiling effect and less thick retinas at baseline, with less room for improvement possible,” Dr. Lowenstein said.

Other benefits

Study researchers also analyzed the benefit of the implant in phakic versus pseudophakic eyes. Although they observed a treatment benefit consistent at all time points in pseudophakic eyes, this was not initially seen in the phakic eyes.

“When we looked at patients who underwent cataract surgery, they eventually did gain the same acuity benefits as pseudophakic patients,” Dr. Lowenstein said.

Finally, researchers analyzed how effective the implant was in patients based on the severity of their diabetic retinopathy.

“In patients with diabetic retinopathy graded as severe NPDR or worse, the implant was significantly more effective than sham in all visual acuity and retinal thickness parameters,” Dr. Lowenstein said.

Reference

1. Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014;121:1904-1914.

Anat Lowenstein, MD

E: anatl@tlvmc.gov.il

This article was adapted from Dr. Lowenstein’s presentation during Retina Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Lowenstein did not indicate any proprietary interest in the subject matter.