Session Title: Vascular Diseases and Diabetic Retinopathy I
Session Date/Time: Thursday 11/09/2014 | 08:00-10:00
Paper Time: 08:00
Venue: Boulevard C
First Author: : F.Bandello ITALY
Co Author(s): : A. Augustin D. Boyer R. Belfort Y.H. Yoon R. Maturi S. Whitcup
To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 mg and 0.35 mg in the treatment of patients with diabetic macular edema (DME).
Clinical practices at 131 sites in 22 countries worldwide.
Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted and the data were pooled for analysis. Patients (n=1048) with DME, 20/50–20/200 best-corrected visual acuity (BCVA), and central retinal thickness (CRT) ≥300 µm by optical coherence tomography were enrolled. Patients were randomized in a 1:1:1 ratio to treatment with DEX implant 0.7-mg, DEX implant 0.35-mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at up to 40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months (maximum of 7 injections). Patients who received escape treatment for DME were exited from the study before receiving the escape treatment. The predefined primary efficacy endpoint was achievement of ≥15-letter improvement in BCVA from baseline at study end with missing values imputed using the last-observation-carried-forward method. Safety measures included adverse events (AEs), cataract, and intraocular pressure (IOP).
Mean number of treatments was 4.1, 4.4, and 3.3 (DEX implant 0.7-mg, 0.35-mg, and sham groups, respectively). Percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7-mg (22.2%) and 0.35-mg (18.4%) than sham (12.0%) (P≤0.018). Mean average reduction in CRT from baseline (area-under-the-curve approach) was greater with DEX implant 0.7-mg (–111.6 µm) and 0.35-mg (–107.9 µm) than sham (–41.9 µm) (P<0.001). Rates of cataract-related AEs in phakic eyes were 67.9%, 64.1%, and 20.4%; rates of cataract surgery were 59.2%, 52.3%, and 7.2%. In phakic eyes, vision loss occurred after cataract AEs; vision improved and treatment benefit was restored following cataract surgery. From cataract surgery to study end, BCVA mean average change from baseline was +4.3, +4.7, and +1.7 letters (+6.7, +7.1, and 2.1 letters when surgery ≥12 months before study end) in the DEX implant 0.7-mg, 0.35-mg, and sham groups, respectively. CRT mean average change from baseline from cataract surgery to study end was –88.8, –84.8, and +77.5 µm (P≤0.003 DEX implant vs sham). IOP increases were usually controlled with medication/no therapy; 1 (0.3%) patient in each DEX implant group required glaucoma incisional surgery for steroid-induced IOP increases.
In this study, an average of only 4–5 injections of DEX implant 0.7-mg or 0.35-mg over 3 years provided long-term improvement in vision and macular edema in patients with DME. DEX implant 0.7-mg and 0.35-mg met the primary efficacy endpoint for improvement in BCVA. Development of cataract decreased the benefit of treatment in phakic eyes during the second year of the study, but treatment benefit was restored follow cataract extraction. The data suggest that DEX implant may protect against increases in retinal edema associated with cataract surgery. By the end of the study, treatment with DEX implant resulted in clinically meaningful improvement in BCVA independent of lens status at baseline. The safety profile of DEX implant was better than the reported safety profile of other intraocular corticosteroids and consistent with previous reports.