The CALDIRET Study: A Phase–3 Randomised Clinical Trial on Medical Prevention of Diabetic Macular Edema

Abstract

Abstract: : Purpose: To investigate a preventive effect of calcium dobesilate on the formation of diabetic macular edema. Methods: A randomised, placebo–controlled multi–centre trial. A total of 639 patients was recruited. Inclusion criteria were such as, mild to moderate NPDR, proteinuria, no signs of macular edema. The period of review was 5 years. Every 6 months ETDRS seven field stereo photographs, HbAlc levels, and blood pressure values were recorded, including a clinical eye examination. Patients were assigned to 1500 mg calcium dobesilate daily or placebo. Formation of CSME was considered as an endpoint. Results: First CSME occurred after 6 months and the incidence continued until the final visit after 5 years (median: 18 CSME per visit ). The relative risk of developing CSME after 5 years was 42%. Metabolic control was worse in patients developing CSME (mean HbA1c 8.4% vs. 7.9%, p <0.001). Retinal neovascularization occurred in 3 eyes only. Overall, patients in the treatment group did not differ from those in the placebo group (p=0.1084). However, subgroup analysis of the high risk group of women with poor metabolic control (HbA1c >9.0%) revealed a significant benefit for the treatment group (p=0.04) Conclusions: Calcium dobesilate can delay the formation of CSME in diabetic women with poor metabolic control. There is no effect in patients with good metabolic control. The design of the CALDIRET study provided a sufficient incidence rate of CSME endpoints. Type II diabetics with NPDR and proteinuria are a viable population to study the formation of CSME.

Keywords: diabetic retinopathy • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled • macula/fovea