Elsevier

Ophthalmology

Volume 121, Issue 10, October 2014, Pages 1904-1914
Ophthalmology

Original article
Three-Year, Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema

https://doi.org/10.1016/j.ophtha.2014.04.024Get rights and content
Under a Creative Commons license
open access

Purpose

To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).

Design

Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.

Participants

Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.

Methods

Patients were randomized in a 1:1:1 ratio to study 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 ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.

Main Outcome Measures

The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).

Results

Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The 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 DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.

Conclusions

The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

Abbreviations and Acronyms

AE
adverse event
AUC
area under the curve
BCVA
best-corrected visual acuity
CRT
central retinal thickness
DEX
dexamethasone intravitreal implant
DME
diabetic macular edema
DR
diabetic retinopathy
HbA1C
glycosylated hemoglobin
IOP
intraocular pressure
OCT
optical coherence tomography
TA
triamcinolone acetonide
VEGF
vascular endothelial growth factor

Cited by (0)

Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): Sponsored by Allergan, Inc. The sponsor participated in the design of the study, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript.

The authors have made the following disclosures:

David S. Boyer: Consultant—Allergan; Young Hee Yoon: Consultant–Allergan; Rubens Belfort, Jr: Consultant–Allergan; Francesco Bandello: Consultant–Allergan; Raj K. Maturi: Consultant–Allergan; Albert J. Augustin: Research Support, Speaker Fees — Allergan, Inc; Xiao-Yan Li: Employee — Allergan, Inc; Harry Cui: Employee — Allergan, Inc; Yehia Hashad: Employee — Allergan, Inc; Scott M. Whitcup: Employee — Allergan, Inc.

MEAD Study Group members listed online in Appendix 1 (available at www.aaojournal.org).