Elsevier

Ophthalmology

Volume 120, Issue 9, September 2013, Pages 1843-1851
Ophthalmology

Original article
Dexamethasone Intravitreal Implant in Combination with Laser Photocoagulation for the Treatment of Diffuse Diabetic Macular Edema

Presented in part at: American Academy of Ophthalmology Annual Meeting, October 2011, Orlando, Florida.
https://doi.org/10.1016/j.ophtha.2013.02.018Get rights and content

Purpose

To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME).

Design

Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial.

Participants

Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled.

Intervention

Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed.

Main Outcome Measures

The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP).

Results

The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P≤0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P≤0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required.

Conclusions

There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Methods

This randomized, double-masked, sham-controlled, phase 2 clinical study evaluated the safety and efficacy of the intravitreal DEX implant 0.7 mg in combination with laser photocoagulation therapy in diabetic patients with diffuse DME at 48 sites in the United States and Canada. The study duration was 1 year, with up to 3 months of additional follow-up. Institutional review board/ethics committee approval was obtained at each site, the study complied with the Health Insurance Portability and

Patient Population and Disposition

A total of 253 patients were enrolled in the study and were randomized to combination treatment with the DEX implant plus laser photocoagulation (DEX implant plus laser) or to treatment with sham plus laser photocoagulation (laser alone). Enrollment commenced in May 2007 and the study was completed in February 2010. Of the 253 patients in the ITT population, 200 (79.1%) had diffuse macular capillary bed leakage verified by a central reading center and were included in the mITT population for

Discussion

Patients with diffuse DME who were treated with DEX implant plus laser were not statistically different from the laser alone group at month 12 when looking at a 10-letter or more improvement from baseline (the primary outcome). The DEX implant plus laser group was significantly better than the laser alone group at week 1 and month 1, as well as at month 9 for this variable. Reductions in retinal thickness also favored DEX implant plus laser therapy over laser therapy alone at half of the time

Acknowledgments

Kate Ivins, PhD, a freelance medical writer funded by Allergan, Inc, prepared a manuscript draft under the direction of the authors.

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    Manuscript no. 2012-467.

    A full listing of the Ozurdex PLACID Study Group is available at http://aaojournal.org.

    Financial Disclosure(s): The author(s) have made the following disclosure(s):

    David G. Callanan: Consultant- Alcon, Allergan, Inc., Bausch and Lomb, Lux Biosciences, and Forsight

    Sunil Gupta: Consultant - Allergan, Inc.

    David S. Boyer: Consultant - Alcon, Allegro, Allergan, Inc., Genentech, Novartis, and Regeneron

    Thomas A. Ciulla: Advisory Board - Allergan, Inc.

    Michael A. Singer: Consultant - Allergan Inc., Genentech

    Baruch D. Kuppermann: Consultant - Alimera, Allegro, Allergan, Inc., Fovea, Genentech, Glaukos, Neovista, Novagali, Novartis, Ophthotech, Regeneron, 2C Tech, and Thrombogenics

    Ching-Chi Liu: Employee - Allergan, Inc.

    Xiao-Yan Li: Employee - Allergan, Inc.

    David A. Hollander: Employee - Allergan, Inc.

    Rhett M. Schiffman: Employee - Allergan, Inc.

    Scott M. Whitcup: Employee - Allergan, Inc.

    Sponsored by Allergan, Inc., Irvine, California. The sponsor participated in design of the study, data management, data analysis, interpretation of the data, and the preparation, review, and approval of the manuscript.

    Group members listed online in Appendix 1 (available at http://aaojournal.org).

    View full text