Mechanisms for monitoring changes in retinal status following therapeutic intervention in diabetic retinopathy.

Trials of new compounds (e.g., protein kinase C inhibitors) for the treatment of diabetic retinopathy and diabetic macular edema historically have used tools such as seven-field stereoscopic fundus photography to grade retinopathy, and endpoints such as the need for retinal photocoagulation to evaluate efficacy. Improvements in diabetes care have led to slower spontaneous progression of retinopathy than anticipated, however. A consequence of this trend is that clinical trials for diabetic retinopathy and diabetic macular edema are expected to last for many years and require large numbers of patients before evidence-based conclusions can be made. Therefore, interest in new assessment tools is growing. This review briefly describes the basic pathophysiologic factors involved in the pathogenesis of diabetic macular edema to provide a basis for the introduction of new quantitative and objective endpoints. Special consideration is given to measuring fluorescein permeability of the blood-retinal barrier. The quantitative measurement of retinal thickness using optical coherence tomography is a promising noninvasive method. Microaneurysm counts, assessment of length and diameter of retinal vessels, and computerized quantification of all pathologic elements may also be useful as diagnostic tools and/or efficacy endpoints.