Session Title: Vascular Diseases and Diabetic Retinopathy I
Session Date/Time: Thursday 11/09/2014 | 08:00-10:00
Paper Time: 09:20
Venue: Boulevard C
First Author: : R.Belfort BRAZIL
Co Author(s): : The Ozurdex MEAD
To evaluate the occurrence, management, and clinical significance of increases in intraocular pressure (IOP) in patients with diabetic macular edema (DME) treated with dexamethasone intravitreal implant (Ozurdex, DEX implant) in the 3-year MEAD (Macular Edema: Assessment of Implantable Dexamethasone in Diabetes) study.
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 prior to 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) and IOP.
The incidence of AEs in the study eye related to IOP increases was 36.0%, 34.1%, and 5.1% in the DEX implant 0.7-mg, DEX implant 0.35-mg, and sham groups, respectively; IOP-lowering medication was used during the study by 41.5%, 37.6%, and 9.1% of patients. Use of IOP-lowering medication remained similar during each study year. The initial IOP increase typically occurred after the first or second injection. Mean IOP peaked at 1.5 or 3 months after each injection; IOP returned to within the normal range by 6 months after injection. Only 1 (0.3%) patient treated with DEX implant 0.7-mg and 1 (0.3%) treated with DEX implant 0.35-mg underwent glaucoma incisional surgery to manage steroid-induced increased IOP; 2 (0.6%) treated with DEX implant 0.7-mg, 2 (0.6%) treated with DEX implant 0.35-mg, and 1 (0.3%) treated with sham had a laser procedure. At study end, ≥15-letter BCVA gain was achieved by 21.9% (21/96) of patients with a ≥10-mm Hg IOP increase versus 22.4% (57/255) with no ≥10-mm Hg IOP increase in the DEX implant 0.7-mg group, and 25.9% (22/85) of patients with a ≥10-mm Hg IOP increase versus 16.0% (42/262) of patients with no ≥10-mm Hg IOP increase in the DEX implant 0.35-mg group.
Increased IOP was a common side effect of DEX implant treatment for DME but was typically managed by IOP-lowering medication or observation. IOP levels returned to baseline by 6 months after each DEX implant injection, and no cumulative effect of repeat injections on IOP was observed. Among patients who had increased IOP, the initial IOP increase was usually after the first or second DEX implant injection, but in up to 25% of cases, the initial IOP rise occurred after the third, fourth, fifth, sixth, or seventh injection. DEX implant demonstrated clear benefit of treatment in patients despite the occurrence of increases in IOP. Visual and anatomic outcomes in patients with a clinically significant IOP increase were at least as favorable as those in patients without an IOP increase.