DRCRnet Protocol S results provide evidence for retinopathy advance

By Cheryl Guttman Krader

Las Vegas-Results from the Diabetic Retinopathy Clinical Research Network Protocol S provide evidence for the first major advance in the treatment of proliferative diabetic retinopathy (PDR) in more than 40 years, said Jeffrey Gross, MD.

The results were reported for the first time at Retina 2015 and simultaneously published in the Journal of the American Medical Association, noted Dr. Gross, at the annual meeting of the American Academy of Ophthalmology.

“Panretinal photocoagulation (PRP) is a time-tested treatment for PDR over the last four decades, and it remains effective today,” said Dr. Gross, founder and managing partner, Carolina Retina Center, Columbia, SC. “PRP substantially reduces the risk of severe vision loss, but it is inherently destructive, has other side effects, and it is not perfect because 5% of eyes have severe vision loss despite PRP.”

Ranibizumab (Lucentis, Genentech) for treatment of PDR is at least as good as PRP for visual acuity at 2 years, and it is an effective treatment alternative to PRP, he noted.

“Ranibizumab was associated with no substantial safety concerns for at least 2 years, and it may be the preferred initial treatment approach for some patients, for example those with PDR and diabetic macular edema (DME),” Dr. Gross said. “Longer follow-up should determine whether the effects of ranibizumab are sustained for 5 years.”

Protocol S was undertaken knowing the benefit and limitations of PRP and that anti-VEGF therapy for DME decreases the risk of DR worsening and increases the chance of improving the retinopathy level.

The study enrolled 305 patients at 55 sites; eyes with and without central-involved DME were eligible. At baseline fewer than 25% of eyes in the PRP and ranibizumab treatment groups had central-involved DME with visual loss, and almost 50% of eyes in both groups had very good vision of 20/25 or better.

Eyes randomly assigned to PRP underwent prompt treatment at 1 to 3 sittings completed within 8 weeks. Ranibizumab was required for PRP group eyes with central-involved DME and vision loss at baseline, and if the size or amount of neovascularization increased following initial PRP, additional PRP could be given.

“About 45% of eyes had additional PRP at a median of 7 months, 35% had ranibizumab at baseline, and 18% had ranibizumab during follow-up,” Dr. Gross said.

The ranibizumab group received a mandatory four injections every 4 weeks. Injections could be withheld at the 4 or 5 month visit or any future visit if neovascularization resolved. The injections were continued if neovascularization improved from the previous injection visit and withheld if neovascularization was stable over 3 injection visits. Injections resumed if neovascularization worsened, and PRP was permitted based on specific criteria.

“Essentially almost everyone received injections at every visit within the first 6 months,” Dr. Gross said.

“The median number of injections during the second year, however, was about 50% of the number in the first year,” he said.

The primary endpoint analysis showed ranibizumab injection for PDR was no worse than (not inferior to) PRP for visual acuity at 2 years.

“Visual acuity was stable in the PRP group during the 2 years of follow-up, whereas there was improvement in vision in the ranibizumab group that peaked between 32 and 52 weeks and resulted in a mean gain of 0.2 letters at 2 years,” Dr. Gross said.

Secondary outcomes analyses showed that compared with PRP, ranibizumab injection was associated with superior vision over the course of 2 years, reduced the incidence of central-involved DME (9% versus 28%), and was associated with less peripheral visual field loss, fewer vitrectomies (4% versus 15%), and no major ocular or systemic safety differences compared with PRP except for one case of endophthalmitis.