Protocol V Summary

Written by: Judy Chen, MD

Baker CW, Glassman AR, Beaulieu WT, et al. Effect of Initial Management of Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients with Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA 2019 Apr 29 [Epub ahead of print].

Most major clinical trials demonstrating the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in the treatment of diabetic macular edema (DME) have previously excluded patients with vision better than 20/32. However, various population-based studies of DME have documented 20/25 or better vision in up to 84% of patients with center-involving DME (CI-DME). Therefore, Protocol V was conducted to compare visual acuity results between eyes with CI-DME and with vision of 20/25 or better; these eyes were treated with aflibercept, focal/grid laser photocoagulation or observation.

The aflibercept group received an injection every 4 weeks as needed, with laser photocoagulation rescue allowed after 24 weeks. The laser photocoagulation group received laser treatment at baseline, with retreatment at 13-week intervals as necessary. The observation group was given no treatment initially. Aflibercept injections were initiated in both the laser and observation groups if vision declined, per prespecified criteria.

At 2 years, there was no difference between the three groups in primary outcome, defined as percentage of eyes with greater than 5-letter visual acuity loss. There was also no difference in the mean change in central subfield thickness (CST) from baseline or in the percentage of eyes with a 2-step change in diabetic retinopathy severity level on color fundus photos. Most interestingly, the eyes that started with laser photocoagulation and observation but later received aflibercept when visual acuity declined received a similar median number of injections as the aflibercept group, and had similar visual acuity outcomes. The mean visual acuity in all groups was maintained at 20/20. Therefore, the authors concluded that there is no significant difference in vision loss at 2 years between the three groups and observation with close monitoring is a reasonable strategy in these eyes.