Addressing diabetic retinopathy by treating underlying disease

Clinical trials and observational studies have found that proper management of blood glucose levels and, to a lesser extent, blood pressure, can delay or even halt the progression of diabetic retinopathy (DR).

A physician can monitor blood glucose control by measuring the patient's glycosylated hemoglobin (HbA_1c) levels. Within red blood cells, glucose molecules bind with hemoglobin to form HbA_1c, levels of which indicate the average level of glucose to which the cell has been exposed over its life cycle. HbA_1c levels typically are around 4% to 5.9% in healthy individuals, but they can be much higher in patients with diabetes, because of prolonged periods of hyperglycemia.

The American College of Physicians sets blood glucose targets for patients with type 2 diabetes at HbA_1c at 6% to 7%. Values within this range indicate that a patient has been adequately controlling his or her blood glucose level. Likewise, the American Diabetes Association recommends that patients maintain a blood pressure below 130/80 mm Hg and LDL cholesterol level below 100 mg/dl to avoid complications and sustain glycemic control.¹

Seemingly minute differences in disease management can have a drastic effect on the microvascular complications of patients with diabetes, and patients in whom blood glucose levels are adequately controlled have a substantially reduced risk of developing DR.⁴ Results of the Diabetes Control and Complications Trial showed that patients aged 13 to 39 years with either no retinopathy or mild to moderate nonproliferative DR (NPDR) who received intensive insulin treatment were much less likely to experience a worsening of ocular complications than those who received conventional insulin treatment. At the 3.5-year follow-up, those in the conventional treatment group, who received one or two daily insulin injections, had more than a five-fold greater risk of disease progression than those who received intensive treatment with shots of insulin at least three times a day based on self blood-glucose monitoring.⁵ Likewise, in the Wisconsin Epidemiologic Study of Diabetic Retinopathy, researchers found that elevated glycosylated hemoglobin levels were associated with more severe retinopathy in patients with younger-onset or older-onset disease.^6,7

Management of blood pressure also may have a direct effect on the course of ocular complications in those with diabetes. In a study of adolescents with type 1 diabetes, researchers found that a 10-mm Hg increase in systolic blood pressure was associated with a 3% to 20% higher risk of retinopathy, and a 10-mm Hg increase in diastolic blood pressure was associated with a 2% to 30% higher risk of retinopathy.⁸

The Wisconsin Epidemiologic Study of Diabetic Retinopathy also found a link between higher blood pressure and increased risk of DR progression, but the difference was only marginally significant and may have been due to increased morbidity (myocardial infarction, stroke, and nephropathy) as well as morbidity.⁹ Evidence of nephropathy, in the form of proteinuria, also was associated with an increased risk for DR progression, likely because of the shared role of microvascular damage among the two conditions.