Intravitreous Dexamethasone Effects on Different Patterns of Diabetic Macular Edema

Macular edema (ME) is thought to be caused by abnormal retinal capillary permeability leading to swelling in the central retina.¹ Different patterns of diabetic ME (DME) have distinct clinical appearances and correspond to different pathophysiological manifestations of diabetic retinopathy.² In general, focal ME is characterized by focal fluorescein leakage and hard exudates, and diffuse ME is characterized by geographic areas of leakage with hard exudates being less common. Cystoid ME refers to the clinical and fluorescein angiographic appearance of fluid-filled spaces within the retina and is typically associated with diffuse ME.^3,4 Patients typically have more than 1 pattern.

A phase 2 randomized trial of patients with persistent ME due to a variety of causes found that a single treatment with a dexamethasone drug delivery system (DDS) of 700 μg (Ozurdex; Allergan, Inc, Irvine, California) was superior to observation in improving best-corrected visual acuity (BCVA) by 10 or more letters and in reducing central retinal thickness and fluorescein leakage (90 days after treatment).³ The current analysis focused on those patients from the phase 2 study with ME due to diabetic retinopathy and compared the response to treatment between patients with different patterns of ME at baseline.

The methods for the phase 2 study have been published previously³ and are described briefly here. Adult patients with ME persisting for 90 days or longer after laser treatment or medical therapy were randomized to observation or to a 350-μg or 700-μg dexamethasone DDS implanted surgically. In this analysis, only patients with DME from the 700-μg group or the observation group were included. Efficacy measures included BCVA and central retinal thickness (using optical coherence tomography). Baseline ME was characterized as focal, cystoid, diffuse, or both cystoid and diffuse (cystoid-diffuse) by each investigator using his or her own criteria; all patterns observed were noted. Data were analyzed using the Cochran-Mantel-Haenszel method, Pearson χ² test, or Fisher exact test.

The phase 2 study enrolled 315 patients; of these, 57 in the observation group and 57 in the 700-μg dexamethasone DDS group had DME. At baseline, most patients were described as having 2 or more patterns of ME. The number of patients with each pattern was similar between the 2 study groups (focal ME: observation, 49; dexamethasone DDS, 47; cystoid ME: observation, 33; dexamethasone DDS, 33; diffuse ME: observation, 46; dexamethasone DDS, 48; cystoid-diffuse: observation, 25; dexamethasone DDS, 26). There were no significant differences in mean age, baseline BCVA, baseline retinal thickness, or racial or sex distributions between patients with different patterns of ME.

At day 90 among all patients with DME, a significantly greater proportion of patients in the 700-μg dexamethasone DDS group had achieved improvement of 10 or more letters from baseline BCVA (19 of 57 patients [33.3%]) than did patients in the observation group (7 of 57 patients [12.3%]) (P = .007). This significant difference was maintained within the different ME pattern categories (Figure 1).

The improvements in retinal thickness mirrored those seen for BCVA. Among all patients with DME, the mean decrease in retinal thickness at day 90 was significantly greater in the 700-μg dexamethasone DDS group (mean decrease, 132.2 μm) than in the observation group (mean increase, 30.2 μm) (P < .001). This significant difference was maintained over different ME pattern categories (Figure 2).

An earlier report of the results of the phase 2 study demonstrated that the 700-μg dexamethasone DDS produced statistically significant improvements in BCVA in patients with persistent ME and that these benefits were maintained in the subpopulation of patients with ME due to diabetic retinopathy.⁵ The present analysis showed that a similar degree of efficacy was maintained across patients with DME regardless of the pattern of ME.

Correspondence: Dr Kuppermann, Department of Ophthalmology, University of California, Irvine, 118 Med Surge I, Irvine, CA 92697-4375 (bdkupper@uci.edu).

Published Online: March 8, 2010 (doi:10.1001/archophthalmol.2010.44).

Author Contributions: Dr Kuppermann had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: Drs Kuppermann, Haller, and Blumenkranz have served as consultants for Allergan, Inc. Dr Whitcup is currently employed by Allergan, Inc. Drs Chou and Weinberg are former employees of Allergan, Inc.

Dexamethasone DDS Phase II Study Group Investigators: Carl Awh, MD, Nashville, Tennessee; Brian Berger, MD, PA, Austin, Texas; Paul Bernstein, MD, PhD, Salt Lake City, Utah; Mark S. Blumenkranz, MD, Stanford, California; Herbert Cantrill, MD, Minneapolis, Minnesota; Thomas Chang, MD, Los Angeles, California; Stanley Chang, MD, New York, New York; Connie Chou, PhD, Irvine, California; Robert Diaz-Rohena, MD, McAllen, Texas; Bernard Doft, MD, Pittsburgh, Pennsylvania; Pravin Dugel, MD, Phoenix, Arizona; Kurt Gitter, MD, New Orleans, Louisiana; Bert Glaser, MD, Chevy Chase, Maryland; Stuart Green, MD, New Brunswick, New Jersey; Julia A. Haller, MD, Baltimore, Maryland; Dennis Han, MD, Milwaukee, Wisconsin; Bradley Jost, MD, Dallas, Texas; Baruch D. Kuppermann, MD, PhD, Irvine; Hilel Lewis, MD, Cleveland, Ohio; Helen Li, MD, Galveston, Texas; Peter Liggett, MD, Hamden, Connecticut; Travis Meredith, MD, Chapel Hill, North Carolina; George Novalis, MD, Tucson, Arizona; Steven Sanislo, MD, San Francisco, California; Steven Schwartz, MD, Los Angeles; Lawrence Singerman, MD, Beachwood, Ohio; Alan Wagner, MD, Virginia Beach, Virginia; George A. Williams, MD, Royal Oak, Michigan; David Wilson, MD, Portland, Oregon; Keye Wong, MD, Sarasota, Florida; Lucy Young, MD, PhD, Boston, Massachusetts.

Funding/Support: This study was sponsored by Oculex Pharmaceuticals, Inc.

Trial Registration: clinicaltrials.gov Identifier: NCT00035906

Previous Presentations: This work was presented at the 109th Annual Meeting of the American Academy of Ophthalmology; October 16, 2005; Chicago, Illinois.

Additional Information: This study was conducted in compliance with sponsor and investigator obligations, the Declaration of Helsinki, and the institutional review board and informed consent regulations at each investigational site.

Additional Contributions: Additional data analysis and interpretation was provided by Allergan, Inc, which also supervised the preparation of the manuscript and approved the final version. Allergan, Inc, also supervised a secondary analysis of all of the data by an independent statistician. Amy Lindsay, PhD, Lindsay Biomedical Communications, Inc, provided professional writing assistance in the preparation of the manuscript.