Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study)

TLDR

VEGF is elevated in diabetic macular edema, and ranibizumab binds and inhibits multiple VEGF variants. The study aimed to evaluate the safety and efficacy of ranibizumab in foveal‑center diabetic macular edema over 12 months, with future trials needed to confirm long‑term outcomes. Patients received three monthly ranibizumab injections followed by a pro‑re‑treatment regimen with optional dose doubling and rescue laser photocoagulation per protocol. Ranibizumab produced significant gains in visual acuity (mean +10.3 letters) and central retinal thickness reduction (194.2 µm) versus sham, with 60.8% achieving ≥10‑letter improvement and a safety profile consistent with prior studies.

Abstract

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection).At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.