Steroid implant effective, tolerable at 12 months

Study shows nearly one-third of implanted eyes gained at least 15 letters of best corrected visual acuity at 60 days.

Julia A. Haller

Intravitreal delivery of dexamethasone improved vision in patients with macular edema resulting from retinal vein occlusion, according to clinical trial results.

Twelve-month data came from two trials of Ozurdex (dexamethasone intravitreal implant, Allergan) administered to patients with macular edema resulting from branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). The treatment also decreased retinal thickness and was well-tolerated by patients with both types of retinal vein occlusion.

Julia A. Haller, MD, and colleagues presented their findings in scientific posters at the Association for Research in Vision and Ophthalmology meeting in Fort Lauderdale, Fla.

Dr. Haller said that the trials were the first devoted to macular edema resulting from retinal vein occlusion.

“For the first time, these and other RVO studies are giving us a signal that it may be worth being more aggressive about treating this problem than we had previously thought,” Dr. Haller told Ocular Surgery News in a subsequent interview. “In the past, there was a tendency to let some months go by and just see how patients would do. This is a real sea change in terms of how we look at treating macular edema due to vein occlusions.”

The U.S. Food and Drug Administration approved Ozurdex in June 2009.

Implant for BRVO

Investigators separated trial data into two subgroups: patients with CRVO and patients with BRVO. Dexamethasone was administered in 0.35 mg and 0.7 mg doses.

The BRVO group included 291 eyes randomized to receive the 0.7-mg dose and 279 eyes to undergo sham treatment at baseline; 241 eyes receiving the implant and 235 eyes in the sham group had BRVO for more than 90 days.

At 180 days, 227 eyes from the 0.7-mg dexamethasone group and 210 eyes from the sham treatment group commenced open-label treatment with the 0.7-mg implant.

At 60 days after initial implantation, 30% of eyes gained at least 15 letters of best corrected visual acuity; 34% gained 15 or more letters at 60 days after the second implant. In the sham treatment group that received an initial 0.7-mg implant at 180 days, 29% of eyes gained 15 letters or more by 240 days, the authors reported.

Of 61 eyes that received only a single baseline 0.7-mg implant, 30% gained 15 or more letters at 60 days. At 180 days, 46% gained 15 letters or more; at 360 days, 43% gained 15 letters or more.

CRVO treatment

The CRVO group included 136 patients randomized to receive the 0.7-mg dexamethasone implant and 147 patients to undergo sham treatment.

At 180 days, 114 patients in the 0.7-mg group and 117 patients in the sham treatment group started open-label treatment with the 0.7-mg implant.

At 60 days after initial 0.7-mg implantation, 31% of eyes gained at least 15 letters of BCVA; 27% of eyes gained 15 or more letters at 60 days after the second implant; 21% of eyes in the sham treatment group that received an initial 0.7-mg implant at 180 days gained 15 or more letters at 240 days, the authors said.

Of 19 eyes that received only a single implant at baseline, 53% completed the study; 21% gained 15 or more letters at 60 days, 42% at 180 days and 26% at 360 days, the authors said.

Safety and tolerability

A short-term, transient increase in IOP was seen after implantation in both groups, the authors said.

“The pressure rises were not a problem,” Dr. Haller said. “There were some, but they were transient and very manageable with drops or observation. The IOP peak was at 60 days and resolved at about 2 months.”

In addition, dexamethasone treatment produced no discernable change in cataract progression. This contrasted with some other widely prescribed steroids that are known to spur cataract progression and raise IOP, Dr. Haller said.

A smaller percentage of patients required only one dexamethasone injection in 1 year, she said. Anti-VEGF treatment such as Lucentis (ranibizumab, Genentech), recently approved for macular edema resulting from retinal vein occlusion, requires monthly injections, a clear contrast to dexamethasone, Dr. Haller said.

“So, if you look at 11 or 12 injections over a year vs. one injection, at least in this small group of patients, that is a substantial difference,” she said. “It’s an intriguing finding and it suggests there is probably a role for this, either in selected patients or possibly in combination with other drugs, but that remains to be worked out.”

With ranibizumab approved for macular edema due to retinal vein occlusion, future research may focus on developing optimal customized treatments combining steroids and anti-VEGFs, she said.

“There may be better ways of testing down the road on a molecular basis in terms of what’s going on in the individual patient,” she said. “We know that VEGF is certainly a key player, so anti-VEGF drugs make sense. But it’s a multifactorial process too, and inflammation is very basic to the pathophysiology of vein occlusion. So, anti-inflammatory drugs also seem to make sense.” – by Matt Hasson

• Julia A. Haller, MD, can be reached at Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107; 215-928-3073; fax: 215-928-3853; e-mail: jhaller@willseye.org.