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Diabetic retinopathy: Pathogenesis

David K McCulloch, MD
Section Editors
David M Nathan, MD
Jonathan Trobe, MD
Deputy Editor
Jean E Mulder, MD


Retinopathy is a major cause of morbidity in patients with type 1 and 2 diabetes. The incidence of blindness, for example, is 25 times higher in patients with diabetes than in the general population. Furthermore, diabetic retinopathy (DR) is the most common cause of blindness in middle-aged subjects, accounting for at least 12,000 new cases in the United States each year [1]. Visual loss from DR may be secondary to macular edema (retinal thickening and edema involving the macula), hemorrhage from new vessels, retinal detachment, or neovascular glaucoma.

The pathogenesis of DR is multifactorial but is primarily caused by the metabolic effects of chronic hyperglycemia, which result in vascular changes and subsequent retinal injury and ischemia. More advanced retinal disease, including proliferative vascular changes and neovascularization in the setting of retinal ischemia, may be mediated by other mechanisms such as the action of vasoactive substances released during the inflammatory process.

The pathogenesis of DR is reviewed here. Issues related to screening and treatment are discussed separately. (See "Diabetic retinopathy: Screening" and "Diabetic retinopathy: Classification and clinical features" and "Diabetic retinopathy: Prevention and treatment".)


Chronic hyperglycemia — Chronic hyperglycemia is thought to be the primary cause of DR [2]. Evidence in support for this hypothesis has come from the Diabetes Control and Complications Trial (DCCT), which found that intensive insulin therapy, achieving a mean glycated hemoglobin (A1C) of 7.9 percent, reduced the incidence of new cases of retinopathy by as much as 76 percent compared with conventional therapy. The reduction was directly related to the degree of glycemic control as estimated from A1C values (mean A1C with conventional therapy was approximately 9.9 percent); progressive retinopathy was uncommon in patients with A1C values below 7 percent (figure 1). (See "Glycemic control and vascular complications in type 1 diabetes mellitus".)

The United Kingdom Prospective Diabetes Study (UKPDS) found similar results in patients with type 2 diabetes; each 1 percent point reduction in A1C was associated with a 37 percent reduction in development of retinopathy [3]. (See "Glycemic control and vascular complications in type 2 diabetes mellitus".)

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Literature review current through: Nov 2017. | This topic last updated: Jan 23, 2017.
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