AAO 2017 Retina Subspecialty Day: Protocol U

Kevin Chen, MD
Vitreoretinal Surgery Fellow
University of California San Diego

Dr. Raj Maturi reported on data from the highly anticipated DRCR.net Protocol U. This study is a multicenter randomized clinical trial of a combination of the dexamethasone intravitreal implant (Ozurdex [DEX], Allergan) + ranibizumab 0.3 mg (Lucentis, Genentech) versus ranibizumab alone for persistent central-involved diabetic macular edema (DME).

Persistent DME was defined as being present for more than 6 months, and required at least 3 anti-VEGF injections prior to a run-in-phase that involved an additional 3 monthly ranibizumab injections. Subjects were then randomized to DEX + ranibizumab, or continued ranibizumab.

Treatment was as-needed based on visual acuity and OCT treatment criteria. Subjects received the assigned treatment at baseline, but at 4 weeks and 8 weeks, both groups only received ranibizumab if treatment criteria were met. Subsequently at 12 weeks, they received their assigned treatments if needed. At 16 weeks, combination treatment was given if it was not given at 12 weeks, but ranibizumab only for both groups if treatment was provided at 12 weeks. At 20 weeks, combination treatment was administered if subjects hadn’t undergone a second combination treatment yet, but ranibizumab only if they had.

A total of 129 eyes from 116 patients were randomized. The primary outcome was change in the mean visual acuity letter score at 24 weeks. Combination DEX-ranibizumab injections took place 0-8 days within the first injection, although 95-96% received both injections the same day.

Primary outcome: The investigators found an average of 2.7 letters gained in the combination arm, compared to 3.0 letters gained in the ranibizumab alone arm (P=0.73).

Secondary outcomes: More subjects obtained 15 letters or more improvement in the combination group (11%), compared to the ranibizumab-only group (2%) (P=0.03). Central subfoveal thickness decreased by 110 microns in the combination group compared to 62 microns in the ranibizumab only group (P>0.001). 20% of patients developed ocular hypertension in the combination group (P>0.001).

When looking only at the pseudophakic subjects (25 in the combination group, 32 in the ranibizumab along group), the mean letters gained was 5.1 letters for the combination group, and 2.0 for the ranibizumab alone group (P=0.08).

To conclude, Protocol U showed that based on the protocol’s design, adding DEX to continued as-needed ranibizumab treatment did not improve visual acuity at 24 weeks, but it was more likely to reduce macular thickness.