Session Title: Vascular Diseases and Diabetic Retinopathy I
Session Date/Time: Thursday 11/09/2014 | 08:00-10:00
Paper Time: 08:08
Venue: Boulevard C
First Author: : U.Chakravarthy UK
Co Author(s): :
DME is now commonly treated with monthly injections of the vascular endothelial growth factor (VEGF) inhibitor ranibizumab. Despite the success of this targeted therapy, not all patients achieve vision benefits. A recent analysis of the READ-2 trial of ranibizumab for DME found that poor baseline best corrected visual acuity (BCVA) predicted poor visual outcome after 2 years of treatment (Channa R, et al. Eye. 2013). The purpose of this analysis was to determine whether lower levels of baseline acuity influenced outcomes in patients with chronic DME in the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) studies.
Two randomized, multicenter, 36-month, phase 3 trials run under identical protocols, which resulted in the marketing authorizations in 6 European countries of ILUVIEN® (intraocular, nonbioerodible, 0.2 μg/d FAc implant) for the treatment of chronic DME considered insufficiently responsive to available therapies.
Patients were randomized 2:2:1 to receive ILUVIEN (0.2 μg/d FAc implant; n = 376), 0.5 μg/d FAc implant (n = 395), or sham control (n = 185). Patients were eligible for rescue laser 6 weeks after randomization at the discretion of the masked investigator and retreatment with randomized therapy after 12 months by meeting prespecified retreatment criteria of either loss of ≥ 5 letters of BCVA or an increase in center point thickness ≥ 50 µm from best reading in previous 12 months by time-domain optical coherence tomography. The trial results indicated that the greatest benefit was seen in patients with chronic DME (≥ 3 years at baseline). A subsequent exploratory analysis was performed to examine outcome by baseline VA (≤ 20/64, ≤ 20/80 and ≤ 20/100).
Approximately 78% of patients with chronic DME had baseline BCVA ≤ 20/64 (80.4% of control and 77.0% of 0.2 μg/d FAc-treated patients); ≈58% had BCVA ≤ 20/80 (56.3% and 59.3%, respectively) and ≈43% had BCVA ≤ 20/100 (42.9% and 43.1%, respectively). Among all patients with chronic DME, the proportion with ≥ 15-letter improvement at month 36 was 13.4% for control and 34.0% for 0.2 μg/d FAc-treated patients, a treatment difference of 20.6%. Among patients with chronic DME with baseline BCVA ≤ 20/64, 14.4% of control and 38.5% of 0.2 μg/d FAc-treated patients experienced ≥ 15-letter improvement at month 36 (treatment difference, 24.1%). For those with ≤ 20/80 baseline BCVA, these values were 12.7% vs 42.7% (treatment difference, 30%), and those with ≤ 20/100 experienced the greatest benefit, 12.5% vs 46.7% (treatment difference, 34.2%). At 36 months, mean change from baseline in BCVA among those with ≤ 20/80 baseline vision was +2.1 letters for control vs +10.7 letters for 0.2 μg/d FAc (P = .002), and among those with ≤ 20/100 baseline vision, mean change was +1.5 letters for control vs +12.2 letters for 0.2 μg/d FAc (P < .001).
The treatment difference from sham control increased as baseline visual acuity decreased. These findings suggest that steroid therapy provides better benefit relative to control treatment (including intermittent laser and off-protocol therapies) in patients with chronic DME in the worse baseline visual function strata. These results also support the use corticosteroid therapy in patients with DME that are insufficiently responsive to anti VEGF agents.