Diabetic Retinopathy

Diabetic retinopathy is development of retinal microaneurysms, hemorrhages, exudates, neovascularization, and macular edema in patients who have had diabetes for at least several years. The cause is unknown but may involve excess glucose in pericytes. Diagnosis is by slit-lamp examination and ophthalmoscopy. Treatment includes control of diabetes and coexisting hypertension and laser coagulation. In advanced cases, vitrectomy may also be indicated.

Diabetic retinopathy is the 3rd leading cause of adult blindness and is the most common cause of blindness in middle-aged patients; it accounts for almost 7% of cases of blindness in the US. Risk increases with duration of diabetes; therefore, as the population ages and as patients with diabetes live longer, the prevalence of diabetic retinopathy will increase.

Diabetic retinopathy may be nonproliferative or proliferative. Nonproliferative diabetic retinopathy typically develops in patients with type 1 or 2 diabetes before proliferative diabetic retinopathy develops. Proliferative diabetic retinopathy involves growth of new retinal blood vessels (neovascularization). Risk factors for this type are the same as those for atherosclerotic cardiovascular disease, and patients are at higher risk of fatal and nonfatal MI, stroke, diabetic nephropathy, and death.

Pathophysiology

Retinal capillaries have 2 cell types: endothelial cells, which line the capillary lumen, and intramural pericytes (mural cells), which are embedded in the basement membrane of the capillary.

Nonproliferative retinopathy: The first observable change is selective loss of pericytes. This loss probably involves aldose reductase, an enzyme that occurs in pericytes but not in endothelial cells. Excess glucose in pericytes is converted by aldose reductase to its sugar alcohol, sorbitol, which is metabolized slowly and diffuses poorly across cell membranes. The sorbitol concentration increases within the pericyte, and water moves down its osmotic gradient into the pericyte, which swells, eventually ruptures, and disappears.

Because pericytes appear to have contractile properties, their loss results in capillary dilation. The dilated capillaries tend to carry more blood because they are wider than adjacent capillaries that still contain a full complement of pericytes. In the dilated capillaries, endothelial cells proliferate and form outpouchings, which become microaneurysms. Eventually, the adjacent capillaries carry no blood and become ghost vessels without cellular components. Thus, the part of the retina next to clusters of microaneurysms is not perfused; shunt vessels appear between adjacent areas of microaneurysms. Microaneurysms with areas of nonperfused retina indicate early diabetic retinopathy. The microaneurysms leak and capillary vessels may bleed, causing exudates and hemorrhages.

The microaneurysms disappear after 3 to 6 mo and are replaced by new microaneurysms. This stage is called minimal background retinopathy. Once this stage is established, the disorder progresses over years, developing into proliferative diabetic retinopathy in about 5% of patients.

Proliferative diabetic retinopathy: Some areas of the retina continue to lose their capillary vessels and become nonperfused. The ischemic retina is believed to liberate angiogenic factors (eg, vascular endothelial growth factor), which stimulate the growth of new, abnormal blood vessels; thus, new blood vessels appear on the disk and elsewhere on the retina. These new blood vessels grow into the vitreous and, because they are friable, bleed easily, leading to preretinal hemorrhages.

In advanced proliferative diabetic retinopathy, a massive vitreous hemorrhage may fill a major portion of the vitreous cavity. In addition, the new vessels are accompanied by fibrous tissue proliferation, which can lead to traction retinal detachment.

Symptoms and Signs

Usually, little or no evidence of diabetic retinopathy appears until about 3 to 5 yr after the onset of diabetes; in many patients, onset is much later. Symptoms may be subtle (eg, early and minimal vision loss due to macular edema, a shower of spots, clouded vision due to a small vitreous hemorrhage).

The first signs of the nonproliferative form are microaneurysms, seen as red spots with sharp margins in the area around the optic nerve and macula. In the next stage, punctate, flame-shaped (linear), or blot-shaped retinal hemorrhages, cotton-wool spots, hard exudates, and intraretinal microvascular abnormalities (seen as small areas of dilated capillaries) develop. Patients may be asymptomatic.

Macula edema may also occur, resulting in macular elevation. Macular edema is a common cause of reduced vision in patients with nonproliferative diabetic retinopathy and, if allowed to persist, can result in irreversible vision loss.

In proliferative retinopathy, an eye may become blind because of dense vitreous hemorrhage, total traction retinal detachment, or secondary glaucoma due to obstruction of outflow channels in the anterior chamber angle by proliferating new vessels (see Table 127-2).

Diagnosis

Diagnosis is by slit-lamp examination. Because onset of type 2 diabetes is often insidious, a patient's eyes should be examined as soon as diabetes is diagnosed. If no evidence of retinopathy is seen and diabetes remains well controlled, patients should be examined every year by a retinal specialist. Patients with nonproliferative retinopathy should be examined every 6 mo. This interval is decreased to every 4 mo when nonproliferative retinopathy is advanced (with increased ischemia, many cotton-wool spots, and other signs of nonperfusion).

Periodic fluorescein angiography can also be done to follow the course of retinopathy. If laser treatment is needed, periodic fluorescein angiography should be done before advanced retinopathy affects vision; angiography can detect when changes are most amenable to treatment.

Treatment

Primary treatment is tight glycemic control and careful control of systemic hypertension. Glycemic control, when instituted early, can significantly slow the development and progression of disease. Controlling hypertension can slow progression of macular edema, retinopathy, and vision loss.

Secondary treatment is management of retinopathy. Focal laser treatment of leaking microaneurysms around the macula reduces vision loss in 50% of patients with clinically significant macular edema. In the proliferative form, panretinal photocoagulation--the creation of several thousand tiny burns throughout the retina (sparing the macular area)--reduces risk of blindness by 60%. Early treatment of macular edema and proliferative diabetic retinopathy prevents blindness for 5 yr in 95% of patients; late treatment prevents blindness in only 50%. Therefore, early diagnosis and treatment plus regular examinations, done at least yearly, are essential. Vitrectomy can be used to preserve useful vision in advanced cases characterized by persistent, dense, or vitreous hemorrhage or by traction retinal detachment.

This topic was last updated May 2006.