Systemic Therapies for Diabetic Retinopathy: The Accord Eye Study

Abstract

*In prespecified subgroup analyses, the simvastatin-plus-fenofibrate group showed a borderline significant (P 1⁄4 0.057 for interaction) benefit in cardiovascular outcomes in subjectswith atherogenic hyperlipidemia, that is, elevated plasma triglycerides and lowered high-density lipoprotein cholesterol. Diabetic retinopathy is an ocular manifestation of a systemic disease, diabetes mellitus. Although largely successful treatments developed over the past nearly 50 years, including focal and pan-retinal laser photocoagulation, vitrectomy surgery, and more recently, intravitreal injections of corticosteroids and biological agents directed at vascular endothelial growth factor, all have been local therapies within the eye itself and it seems reasonable to suppose that systemic treatments, directed at the systemic metabolic disease, also may have beneficial effects on its ocular sequelae. That has been the basis of previous clinical trials investigating the role of blood glucose and blood pressure control to prevent retinopathy and other complications in type 1 and type 2 diabetes. It is also the premise underlying the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study, a component of the much larger ACCORD Study, which focused on systemic therapies to prevent cardiovascular events in subjects with type 2 diabetes who already had experienced one cardiovascular event or who were considered at high risk for one. The major results of the ACCORD Eye Study were published in 2010, and further analyses appear in this issue of Ophthalmology (see article on page XXX). Results of the overall study, dealing with cardiovascular outcomes, appeared in separate publications in 2010 and 2011. Briefly, the ACCORD Study (and its eye substudy) was a randomized controlled clinical trial with 3 components: extremely rigorous reduction of hyperglycemia to a hemoglobin A1c level of less than 6.0% (treatment group) versus 7.0% to 7.9% (control group); reduction of systolic blood pressure to less than 120 mmHg (treatment group) versus 140 mmHg or less (control group); and lipid control with 160 mg/day fenofibrate plus simvastatin versus simvastatin alone. The treatment phase of the blood glucose trial was discontinued after a mean follow-up of 3.7 years because of a significantly higher all-cause (predominantly cardiovascular) mortality in the group that was randomized to extremely tight blood glucose control, a result that has been discussed extensively, but remains unexplained. However, medical and ophthalmic follow-up of subjects in the blood glucose control arm of the study, as well as other arms, continues. Results of the intensive blood glucose arm of the trial showed decreased retinopathy progression (3 steps on the Early Treatment Diabetic Retinopathy Study scale, vitrectomy, or photocoagulation) over 4 years in the treatment group versus the control group. However, because of the increased mortality in this arm of the study, tight blood glucose control to an hemoglobin A1c level of 6.0% is not recommended for individuals with type 2 diabetes and cardiovascular risks similar to subjects in this study.