Analysis of GENEVA data suggests early treatment with corticosteroid implant

Eyes with macular edema for a shorter time gained up to 3.4 more letters than those with longer disease duration, physician says.

Julia A. Haller

Early treatment may enhance visual outcomes for patients who receive a dexamethasone implant for macular edema due to branch retinal vein occlusion, a physician said.

At the American Society of Retina Specialists meeting in Boston, Julia A. Haller, MD, OSN Retina/Vitreous Board Member, discussed a post hoc analysis of data from the phase 3 GENEVA trials, which compared Ozurdex (dexamethasone intravitreal implant 0.7 mg, Allergan) with sham treatment.

“I think there are larger clinical and research implications that we need to be thinking about if we look at this data,” Dr. Haller said. “From a public health standpoint, maybe we should be diagnosing retinal venous occlusive disease earlier. We’d see more of a push to get these patients in. In terms of clinical care, maybe we should be considering treating these patients earlier. In terms of our practice of evidence-based medicine and trial interpretation, it may be important to start looking at duration of disease and its impact on the results of different trials.”

Historically, retina specialists were advised to wait at least 3 months before starting to treat branch retinal vein occlusion (BRVO), Dr. Haller said.

“The delay in treatment was not thought to be any way detrimental to outcomes,” she said. “And, as a practical matter, if there were hemorrhages in the macula, the person had to wait before you could treat with grid laser, which was the only available treatment. This idea, that treatment delay had no significant impact, actually held until very recently.”

Study design and analysis

The GENEVA study was a 6-month prospective, randomized controlled trial with an additional 6-month follow-up conducted at 167 sites in North America, Latin America, Europe, Israel, South Africa and the Asia-Pacific region.

All subjects were 18 years of age or older. Snellen visual acuity ranged from 20/50 to 20/200. Patients had retinal thickness greater than 300 µm. Duration of macular edema ranged from 6 weeks to 12 months.

Patients were randomized to undergo treatment with a 0.7 mg dose of dexamethasone or sham treatment.

The post hoc analysis compared visual outcomes of patients with macular edema for up to 90 days with outcomes of patients who had the disease longer than 90 days.

The analysis suggested an association, not a causal relationship, between disease duration and patient outcomes and was limited by potential recall bias regarding edema duration, Dr. Haller said.

“It’s important to remember that the GENEVA trials were not specifically designed to assess a causal relationship between macular edema duration and outcomes. The results here indicate an association but, of course, we can’t confirm a causal relationship,” Dr. Haller said.

The analysis included 50 patients who had BRVO for up to 90 days and 241 patients who had the disease longer than 90 days.

Disease duration, outcomes

Results of the analysis were reliable despite the difficulty of accurately determining disease duration, Dr. Haller said.

“The findings are robust for a number of reasons,” she said. “One is the large number of patients enrolled and evaluated. The dropout rate was low, less than 6%, in these trials. None of the patients received rescue medication in this particular protocol. … And the results were consistent when they were analyzed in a number of different ways. Again, that gives more confidence in this analysis.”

Data showed that shorter disease duration translated to a 3.4-letter gain in best corrected visual acuity in eyes treated with dexamethasone and a 1.3 letter gain in eyes that underwent sham treatment, Dr. Haller said.

“Macular edema duration is a significant predictor for best corrected visual acuity improvement in vein occlusion eyes. Subjects with less than or equal to 90 days duration exhibited greater improvement, and the results suggest that earlier treatment … may provide greater clinical benefit,” Dr. Haller said.

Eyes with shorter disease duration had superior visual outcomes at all follow-up intervals, Dr. Haller said.

“When you look at the proportion of BRVO subjects with a greater than or equal to 15-letter improvement in visual acuity from baseline stratified by macular edema duration,” she said, “we’ll see at every time point shorter duration eyes do better and significantly so, particularly at day 60, where the maximum effect of the drug has peaked.” – by Matt Hasson and Michelle Pagnani

• Julia A. Haller, MD, can be reached at Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107; 215-928-3073; fax: 215-928-3853; email: jhaller@willseye.org.
• Disclosure: Dr. Haller is a consultant for Allergan and Genentech.