Nonproliferative diabetic retinopathy is the initial manifestation of diabetic eye disease and consists of intraretinal vascular damage. Loss of capillary pericytes, thickening of basement membranes, swelling and proliferation of endothelial cells, and intravascular thrombosis occur. These changes result in both dilation of small vessels and vascular closure, leading to ischemia. In addition, there is abnormal endothelial permeability with breakdown of the normal blood-retinal barrier. Retinal capillaries become permeable to water, lipids, and large molecules, which are not adequately removed by the usual cellular pump mechanism of the adjacent retinal pigment epithelium.

Clinically, this process results in microaneurysms, intraretinal hemorrhages, cotton-wool spots, and lipid and serous exudates leading to retinal edema. Microaneurysms are abnormal outpouchings of the capillary wall that may leak fluid and lipid into the retina and sometimes thrombose. They appear as red dots in the retina, similar to the small dot-blot intraretinal hemorrhages that result from bleeding in the deep layers of the retina. Flame-shaped hemorrhages occur in the striated superficial ganglion cell layer. Cotton-wool spots are infarcts in the nerve fiber layer. The swollen, infarcted axons become ophthalmoscopically visible as white, feathery, soft lesions. Hard exudates are deposits of the intravascular lipid in the retina and appear as yellow, glistening, spherical aggregates of lipid, sometimes arranged in a circular pattern or circinate ring around leaking microaneurysms. Accumulation of serous fluid in the intercellular spaces of the retina results in retinal thickening or edema.

Patients with nonproliferative retinopathy are asymptomatic unless retinal edema or ischemia involves the central macula. Macular edema causes blurring or distortion followed by loss of central vision. Macular edema is the leading cause of visual loss in diabetics, especially older, type 2 patients. Hypertension and hyperlipidemia can increase the risk of and severity of macular edema.

Proliferative diabetic retinopathy describes abnormal vascular proliferation (neovascularization) originating in the retina and extending into the vitreous cavity. This form of retinopathy generally occurs at a later stage than does nonproliferative retinopathy and tends to have a worse visual prognosis without prompt treatment. There is a correlation between the duration and degree of hyperglycemia and the progression of retinopathy. Tight control (hemoglobin A1c [HbA1c] <7.0%) slows the onset and severity of retinopathy and other microvascular complications of diabetes (see Chapter 102).

The onset of proliferative disease is often preceded by severe nonproliferative changes, such as a large number of cotton-wool spots and intraretinal hemorrhages, venous beading, and small networks of weblike intraretinal vessels (intraretinal microvascular abnormalities). As increased capillary and arteriolar closure result in widespread retinal ischemia, vasoproliferative factors trigger neovascularization, the hallmark of proliferative disease.

Neovascular fronds appear ophthalmoscopically as a fine network of small vessels proliferating from the optic disk, the major retinal vessels, or areas adjacent to retinal ischemia. As neovascularization progresses, dense, white, fibrotic tissue forms and adheres
to the posterior vitreous. Such fibrosis can cause the vitreous to contract and pull anteriorly, rupturing the fragile network of vessels growing into the vitreous and producing a vitreous hemorrhage inside the eye that compromises vision. When traction is severe enough, it can elevate the retina, resulting in a tractional retinal detachment. If traction results in the formation of a retinal hole, a rhegmatogenous retinal detachment may result. Neovascularization may also occur on the iris, leading to neovascular glaucoma from obstruction of the trabecular meshwork.

A diabetic patient who notices small floating specks or cobwebs in the vision may have a small vitreous hemorrhage. Sudden profound loss of vision occurs most commonly in the setting of a severe vitreous hemorrhage but may also signal a retinal detachment. If the loss of vision is also accompanied by eye pain, neovascular glaucoma may have developed.

The risks of developing retinopathy and its progression are a function of the duration and the severity of the disease. Smoking exacerbates the risk, and retinal pathology can progress with unanticipated speed during pregnancy. Hypertension and renal failure also increase the risk of nonproliferative and proliferative diabetic retinopathy, and hyperlipidemia increases the risk of vision loss from macular edema. The prevalence of retinopathy after 5 years of type 1 disease is 25%, rising to 60% after 10 years and 80% after 15 years. In the absence of “tight” glycemic control (HbA1c <7.0), proliferative changes are found in about 2% of type 2 patients at 5 years, increasing to 25% by 25 years; approximately 25% of type 1 patients manifest proliferative changes by 15 years. As noted, the risk of developing proliferative retinopathy can be reduced significantly by achieving tight glycemic control.

Screening asymptomatic diabetic patients for retinopathy is an essential part of effective diabetic care. Screening methods for detecting diabetic retinopathy include undilated ophthalmoscopy, dilated ophthalmoscopy performed by the ophthalmologist, and stereoscopic fundus photography. Fundus photography has been implemented for some populations for whom access to ophthalmologists is limited; its sensitivity for detecting retinopathy has not been definitively established. The American Academy of Ophthalmology therefore recommends that patients with access to an ophthalmologist have routine (annual) dilated examinations. Dilation allows examination of the more peripheral retina, and stereoscopic biomicroscopy allows evaluation for macular edema. Examination of the nondilated eye with a handheld ophthalmoscope is inadequate for screening because only a small area of the retina is visualized, the lack of stereopsis does not allow for detection of macular edema, and the procedure may not allow for easy detection of early neovascularization. Nonetheless, handheld ophthalmoscopic examination by the primary care physician during routine diabetes follow-up visits might serve as a potentially useful adjunct to formal ophthalmologic screening.