Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review

Abstract

Worsening of diabetic retinopathy (DR) is associated with the initiation of effective treatment of glycaemia in some patients with diabetes. It has been associated with risk factors such as poor blood-glucose control and hypertension, and it manifests prior to the long-term benefits of optimizing glycaemic control. The majority of evidence supports an association of large and rapid reductions in blood-glucose levels with early worsening of DR. Despite a general awareness of early worsening within the diabetes community, mechanisms to explain the phenomenon remain speculative. We provide an overview of early worsening of DR and its pathophysiology based on current data. We describe the phenomenon in various settings, including in patients receiving insulin- or non-insulin-based treatments, in those undergoing bariatric surgery, and in pregnant women. We discuss various mechanisms and theories that have been suggested to explain this paradoxical phenomenon, and we summarize the implications of these in clinical practice.

Keywords: GLP-1 analogue; diabetic retinopathy; glycaemic control; insulin therapy; type 1 diabetes; type 2 diabetes.

Figure 1

Cumulative incidence of DR progression (three‐step or greater by ETDRS criteria) in the Diabetic Control and Complications Trial (DCCT) primary prevention cohort. There was little difference in percentage of patients with retinopathy progression between the Intensive and Conventional groups over the first 3 years; however, there was a 76% reduction in risk of DR progression evident at the conclusion of the DCCT after mean follow‐up of 6.5 years.28 ©2014 by the American Diabetes Association Diabetes Care 2014;37:17‐23. Reprinted with permission from the American Diabetes Association