Effects of losartan on diabetic maculopathy in type 2 diabetic patients: a randomized,double-masked study

OBJECTIVE: Diabetic maculopathy (DMa) is a leading cause of visual loss in the western world. Preliminary studies have suggested that angiotensin converting enzyme inhibitors might be effective in preventing the progression of diabetic retinopathy, but no studies have quantitatively assessed the effect of this treatment on macular oedema in patients with DMa. We evaluated the effect of treatment with the angiotensin II receptor antagonist losartan on macular oedema and hard exudates in patients with an advanced stage of DMa. DESIGN: Randomized, placebo-controlled, double-masked and parallel-group trial. SETTING: Academic medical centre. SUBJECTS: Twenty-four type 2 diabetic patients with DMa. INTERVENTION: Subjects were randomly assigned to a 4-month treatment with either losartan (50 mg o.d.) or placebo. MAIN OUTCOME MEASURES: (i) Degree of macular oedema as estimated by optical coherence tomography scanning of the retina; (ii) fundus photography and flourescein angiography; (iii) 24-h ambulatory blood pressure (BP); (iv) urinary albumin excretion (UAE); and (v) transcapillary escape rate of albumin (TERalb). RESULTS: Central retinal thickness increased from 244 +/- 16 to 256 +/- 31 microm in the losartan group, whilst there was no change in the placebo group (245 +/- 36 microm vs. 242 +/- 30 microm), P = 0.017. Day BP were lowered in the losartan group (from 144/83 +/- 17/10 to 138/78 +/- 20/11 mmHg) compared with the placebo group (140/81 +/- 14/5 to 139/82 +/- 13/9 mmHg), P = 0.27 for systolic and P = 0.009 for diastolic BP. Importantly, there were no changes in night BP in any of the groups. We found no changes in the number of hard exudates, semiquantitative retinopathy grade, visual acuity, UAE, or TERalb in any of the groups. CONCLUSIONS: Type 2 diabetic patients with maculopathy do not seem to benefit from short-term treatment with losartan (50 mg once daily) as far as retinal thickness is concerned, as this dose may increase retinal thickness in the central macular area. Long-term studies are required to assess the clinical implications of these findings.