Session Title: Vascular Diseases and Diabetic Retinopathy III
Session Date/Time: Saturday 19/09/2015 | 16:30-18:00
Paper Time: 17:26
First Author: : P.Schlottmann ARGENTINA
Co Author(s): : P. Wang A. Fung
PURPOSE:To determine whether improvements in diabetic retinopathy (DR) achieved with ranibizumab treatment are maintained after conversion from monthly to PRN therapy during the RIDE/RISE open-label extension (OLE).
In the 2 identically designed, randomized, phase 3 RIDE and RISE trials, patients (N=759) received monthly 0.3 mg ranibizumab, 0.5 mg ranibizumab, or sham injection with rescue laser for diabetic macular edema (DME).
At month 24, patients in the sham arm crossed over to receive monthly 0.5 mg ranibizumab. At month 36, 500 patients entered an open-label extension and were eligible to receive 0.5 mg ranibizumab PRN based on predetermined criteria of worsening vision and evidence of DME on OCT. Seven-field color fundus photographs were taken at baseline and throughout the study. DR severity was graded on the ETDRS DR severity scale (DRSS) by the University of Wisconsin Reading Center. A new composite proliferative DR (PDR) event was defined by the first occurrence of (1) progression from nonproliferative DR (DRSS less than 60) at baseline to PDR (DRSS ≥60) at a later time point, (2) use of pan-retinal photocoagulation (PRP) laser, (3) vitreous hemorrhage (adverse event [AE] or slitlamp grade 0 at baseline to greater than 0 at a later time point), (4) cases identified by ophthalmoscopy, (5) use of vitrectomy for reasons related to DR or its complications, (6) iris neovascularization AE, or (7) retinal neovascularization AE.
Improvements in DR were rapid and sustained in patients treated with ranibizumab. At month 12, rates of ≥2-step improvement were 34.2%, 30.8%, and 2.5% for 0.3 mg ranibizumab, 0.5 mg ranibizumab, and sham, respectively. Respective rates for ≥3-step improvement were 7.3%, 8.1%, and 1.3%. At month 36, rates of ≥2-step DR improvement were 38.9%, 39.3%, and 23.8% for 0.3 mg ranibizumab, 0.5 mg ranibizumab, and sham/crossover, respectively, and rates of ≥3-step improvement were 15.0%, 13.2%, and 3.8%, respectively. When patients switched to less frequent therapy in the OLE, 75% of patients receiving some treatment and nearly 60% of patients who did not receive any ranibizumab injections maintained the DR levels achieved at month 36. Cumulative probability of PDR-related events at months 12, 24, 36, and 48, respectively, among patients in the OLE was 4.7%, 11.6%, 14.5%, and 20.2% for 0.3 mg ranibizumab, 5.5%, 9.8%, 15.3%, and 19.9% for 0.5 mg ranibizumab, and 18.2%, 29.7%, 35.2%, and 38.2% for sham.
Monthly ranibizumab injections resulted in rapid improvements in DR that were maintained in the majority of patients with less-than-monthly therapy, despite the fact that retreatment criteria were not based on worsening of DR. Monthly ranibizumab therapy delayed the incidence of PDR-related events with monthly treatment, and switching to PRN treatment did not appear to result in an increased incidence of such events.