Angiotensin-converting enzyme inhibition for the treatment of moderate to severe diabetic retinopathy in normotensive Type 2 diabetic patients. A pilot study.

A few reports have suggested that angiotensin-converting enzyme inhibitors (ACE-I) have a beneficial effect on mild diabetic retinopathy (DR). This pilot study was carried out to determine if a small dose of an ACE-I would retard the progression of moderate to severe DR in normotensive Type 2 diabetic patients. Normotensive patients were selected to isolate the effect on the ocular RAS independent of any lowering of blood pressure. Thirty-five normotensive Type 2 diabetic patients with <1+ dipstick proteinuria and with moderate to severe DR by modified Arlie House Classification criteria on seven field stereoscopic photographs through dilated pupils were randomized to an ACE-I (5 mg of enalapril) (n=18) or to a multivitamin (MVI) placebo (n=17). They were evaluated by an ophthalmologist every 3 months for a planned duration of 2 years. Endpoints of the study were progression to proliferative DR (PDR) or macular edema (ME) for which laser therapy was necessary or for the development of >/=1+ dipstick proteinuria times two (sustained proteinuria) for which an ACE-I was indicated. There were no differences in baseline age, gender, duration of diabetes, body mass indices, blood pressure, treatment of hyperglycemia or Hb A1C levels between the two groups. Blood pressure and Hb A1C levels did not change in either group during the study. The study was stopped prematurely after a mean duration of 7.2 months after an interim analysis revealed that it was very unlikely that a beneficial effect of ACE-I could be shown. At that time in the ACE-I group, four patients had progressed to PDR, three to ME and one had developed sustained proteinuria. In the MVI group, three patients had progressed to PDR, one to ME and one had developed sustained proteinuria. Small doses of an ACE-I did not exert a beneficial effect on the progression of moderate to severe DR over a short period of follow-up. An analysis of previously published clinical information on the effects of ACE-I, most of which evaluated patients with milder DR, supports only a limited (if any) beneficial effect of this class of drugs on the early stages of this microvascular complication.

RCT Entities:   Population Interventions Outcomes