Anti-VEGF, laser recommended to treat diabetic macular edema

Two treatment regimens may result in superior visual outcomes and fewer office visits.

Neil M. Bressler

Intravitreal injection of ranibizumab with prompt or deferred focal/grid laser may be an efficacious and manageable treatment regimen for patients with diabetic macular edema, a study found.

The multicenter, randomized clinical trial was conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net) and included 854 eyes that received sham treatment with prompt laser, 0.5 mg Lucentis (ranibizumab, Genentech) with prompt laser, 0.5 mg ranibizumab with deferred laser or 4 mg triamcinolone with prompt laser.

To be included in the study, patients were required to have some edema in their macular center, visual impairment ranging from 20/32 to 20/320 and a retinal thickness of at least 250 µm in the central subfield. Median preoperative visual acuity was approximately 20/50, and median retinal thickness was roughly 380 µm to 400 µm.

Participants received four mandatory injections and subsequent treatment as needed until stabilization occurred. For patients whose condition regressed after the injections were stopped, treatment was reinitiated.

“The goal was to avoid substantial vision loss while also avoiding a regimen which requires monthly treatments regardless of the clinical course,” Neil M. Bressler, MD, said in a presentation at Retina 2011.

Ranibizumab with or without laser

On average, patients treated with ranibizumab and prompt or deferred laser received six injections within the first 6 months, two to three in the next 6 months and two to three in the second year.

“Only two to three treatments were needed in the second year, so this is very different from what we discussed with neovascular age-related macular degeneration. In neovascular AMD, we found that if you stop, [macular edema] comes back and you have to repeat and repeat [treatment],” Dr. Bressler said.

The study’s comparison of ranibizumab with prompt laser and ranibizumab with delayed laser ultimately demonstrated little difference in terms of visual outcomes as well as required number of injections; prompt laser did not reduce the number of injections for patients by any significant degree.

“Even though it was hoped that prompt laser might reduce the number of injections needed, it’s almost the same, whether you initiate with laser or you don’t apply any laser until at least 6 months — and only then if there’s still edema,” Dr. Bressler said.

About 60% of patients in the ranibizumab plus deferred laser treatment group never received laser in the 2-year follow-up period. Of those patients who received prompt laser, 69% had one additional laser treatment in the first year and 43% had another in the second year.

Results

Approximately 50% of eyes treated with ranibizumab and prompt or deferred laser achieved 10 or more letters of visual improvement during the 2-year follow-up. About 30% gained 15 letters, and visual loss of 10 or more letters was rare, occurring in approximately 5% of eyes.

Twenty-five percent of eyes treated with ranibizumab and prompt or deferred laser experienced complete resolution of their edema after the first four mandatory treatments. However, nine of 10 of these cases involved one additional treatment during the follow-up period, suggesting that continued surveillance is necessary but not on a monthly basis, Dr. Bressler said.

Of those treated with triamcinolone and prompt laser, approximately 30% achieved 10 or more lines of visual improvement, but about 10% to 15% experienced substantial vision loss by the 2-year follow-up. Eyes in this group improved initially and then declined, an occurrence that Dr. Bressler attributed to possible cataract formation.

However, improvement in visual acuity was uniform for the subset of eyes that were pseudophakic at baseline, regardless of whether or not they received triamcinolone or ranibizumab with or without prompt laser.

Whereas there was little difference in visual acuity outcomes for eyes treated with triamcinolone or laser alone, eyes in the ranibizumab groups demonstrated greater visual enhancement overall.

“Intravitreal ranibizumab with prompt or deferred focal/grid laser had superior visual acuity and OCT outcomes compared with focal/grid laser treatment alone,” Dr. Bressler said.

He cautioned that the two ranibizumab treatments involve a risk of endophthalmitis over time. However, IOP increases were comparable to those experienced for laser alone, and only one retinal detachment occurred, which Dr. Bressler suggested may have been caused by proliferative retinopathy. The ranibizumab treatments were not associated with an increased risk of death, and cataract surgery occurred far more frequently with triamcinolone, while cardiovascular or cerebrovascular events occurred more frequently with laser alone.

“We think that this should be considered now, recognizing the risk of endophthalmitis, in the management of diabetic macular edema, and it is very different from neovascular age-related macular degeneration,” Dr. Bressler said. – by Cara Hvisdas and Michelle Pagnani

• Neil M. Bressler, MD, can be reached at the Wilmer Eye Institute, 550 N. Broadway, Suite 115, Baltimore, MD 21205; 410-955-8342; email: nmboffice@jhmi.edu.
• Disclosure: Dr. Bressler is the principal investigator of grants at Johns Hopkins University, sponsored by the following entities: Abbott Medical Optics, Allergan, Bausch + Lomb, Carl Zeiss Meditec, EMMES Corporation, ForSight Labs, Genentech, Genzyme Corporation, Lumenis, Notal Vision, Novartis, Ora, QLT, Regeneron and Steba Biotech. Under School of Medicine policy, support for costs of research administered by the institution does not constitute a financial conflict of interest.