This randomized pilot study is an important first step in planning a large multi-center clinical trial to evaluate medical and laser approaches that could improve the visual outcome for patients with diabetic retinopathy, specifically diabetic macular edema. This study will provide preliminary safety data on these therapies as well as allow for assessment of the performance of ocular outcomes and study design for use in subsequent trials. If there are no safety concerns, the results of this pilot will be helpful in the design of a large multicenter clinical trial by providing data on estimates of expected treatment effects. A larger trial will proceed regardless of whether or not this study identifies statistically significant main effects. Using a factorial design, this study will compare (1) diode (micropulse) laser photocoagulation to mild ETDRS style focal photocoagulation and, (2) treatment with a COX-2 inhibitor (celecoxib) or vitamin E, or placebo prior to and following laser photocoagulation. The primary safety outcome is a visual acuity drop of 15 letters or more from baseline one year following initial laser treatment. The primary efficacy outcome will be the change in visual acuity and the reduction of the retinal thickening defined as an improvement by at least two steps (on standard fundus photos) combined with a 50% reduction in the area of fluorescein leakage one year after the initial laser compared to baseline. A secondary outcome will be the change in macular height as measured (OCT). These outcomes will be assessed for potential use in future trials. Additioinal objectives of this study will be to investigate whether Vitamin E or the COX-2 inhibitor may affect the ability of either photocoagulation method to reduce retinal thickening, as well as to examine the effects of dramatically reducing low-density lipoproteins cholesterol in patients with diabetic macular edema and elevated serum lipid levels . Change vision and retinal thickness will be compared across three groups; (1) patients without elevated serum lipids at baseline, (2) patients with elevated lipid levels at baseline and receive standard of care treatment, and (3) patients with elevated lipid levels at baseline and are aggressively treated pharmacologically. This study is currently obtaining all the necessary regulatory documentation from the Food and Drug Administration for the study to start recruitment. It is anticipated that recruitment of participants with diabetic macular edema will begin shortly.
