Risk factors and classification

Risk factors

Among the most consistent risk factors, duration of diabetes is probably the strongest predictor for development and progression of the retinopathy. Among patients with younger-onset diabetes, the prevalence is estimated at approximately 8% at 3 years, 25% at 5 years, 60% at 10 years, and 80% at 15 years. Hyperglycemia, hypertension, hyperlipidemia, and renal disease are considerable risk factors. Male sex, higher severity of diabetes (indicated by use of insulin and oral diabetes treatments versus pills alone or use of pills alone versus no treatment), higher average systolic blood pressure, and higher hemoglobin A1c are additional factors to be considered. Obesity, smoking, alcohol consumption, and physical inactivity are also important risk factors, though considered less consistent. Pregnant women with diabetes are a higher risk for developing DR. If gestational diabetes develops, the patient may be at higher risk of developing diabetes with age.

Classification

DR can be classified into 2 stages: nonproliferative (early) and proliferative (advanced).

• Nonproliferative DR is the most common type of RD that can be described as mild-to-moderate. The most common characteristics include signs of retinal ischemia (microaneurysms, hemorrhages, intraretinal microvascular abnormalities, venous beading, and cotton wool spots). However, patients may be asymptomatic and unaware of vision loss. The earliest ophthalmologically visible signs are microaneurysms and retinal hemorrhages. Microaneurysms are visible as round intraretinal lesions ranging from 1 to 100 µm, red or occasionally white, which may be associated with intraretinal hemorrhage or retinal thickening. They occur most frequently at the posterior pole, especially in the area temporal to the macula. Cotton-wool spots appear as localized whitish elevations of the retinal nerve fibre layer. With large areas of microvascular infarction the retina appears diffusely gray ("cloudy swelling"). Increased severity of cotton-wool spots and presence of more spots may be associated with an increased risk of progression. Intraretinal microvascular abnormalities represent either new vessel growth or remodeling of preexisting vessels (which branch with a frequency, number and angulation different from that of normal retinal vessels) through endothelial cell proliferation within the retinal tissues. They may be seen throughout the fundus as flame-shaped, punctuate dot- or larger blot hemorrhages with irregular margins. Venous beading describes veins with irregular increase in caliber.

• Proliferative DR occurs with further retinal ischemia. The most common characteristics includes the formation of new blood vessels (neovascularization) elsewhere and on the optic nerve, fibrous proliferation elsewhere and on the optic nerve, preretinal and vitreous hemorrhage, and retinal detachment due to scar tissue formation. As the abnormal vessels of novascularization are fragile, vitreous hemorrhaging potentially leading to severe loss of vision is frequent. Glaucoma is frequent. The increased eye pressure may damage the optic nerve. DR usually affects both eyes and has a few visual or ophthalmic symptoms until visual loss develops. The main symptoms of DR are predominantly associated with proliferative retinopathy and may include poor night vision, blurred vision, floating spots, black spots or flashing lights in the vision field, and sudden, severe painless vision loss (Figure 2). Some of these symptoms may be caused by vitreous hemorrhage (that usually does not cause permanent vision loss) or traction retinal detachment (that may be associated with a severe vision loss). Signs in later stages are macular edema seen on slit-lamp biomicroscopy as elevation and blurring of retinal layers, and venous dilation and intraretinal microvascular abnormalities. DR progresses from mild nonproliferative abnormalities to moderate and severe nonproliferative stage, and proliferative DR. Proliferative DR may occur in up to 50% of the patients with type 1 diabetes and in about 10% of patients with type 2 diabetes who have had the disease for 15 years. It has been noted that prevalence of proliferative retinopathy is somewhat higher among type 2 diabetes patients who require insulin to control the disease. Pregnancy, puberty, poor blood glucose control, hypertension, and cataract surgery can accelerate these changes. If left untreated, proliferative DR can lead to severe vision loss and blindness.

Diabetic macular edema

Diabetic macular edema (DME) is a common complication associated with DR that seems more frequent in type 2 than type 1 diabetes. It can occur at any stage of DR and is characterized by the breakdown of the blood-retinal barrier with leakage of plasma from small blood vessels in the macula (Figure 3). This causes swelling of the central retina that severely compromises the macular function. Resorption of the fluid elements from plasma leads to the deposition of its lipid and lipoprotein components and the formation of hard exudates. DME is considered one of the principal causes of vision loss in persons with diabetes. Loss of vision may occur suddenly and treatment is not as successful. Macular edema, retinal and vitreous hemorrhages from new vessels, retinal detachment, or neovascular glaucoma are the primary causes of blindness in patients with DR.

Ocular associations of diabetes other than DR

A range of ocular diseases that may lead to vision loss is associated with diabetes. Anterior ischemic optic neuropathy (AION) is an acute vascular condition of the optic nerve. Studies suggest that up to 25% of patients with AION have a history of diabetes. Diabetic papillopathy is an uncommon optic nerve condition characterized by acute disc edema and mild vision loss. It is a risk factor for the progression of DR and, occasionally, it can precede the development of AION. Extraocular motility disorders may occur in patients with diabetes, secondary to diabetic neuropathy mostly involving the third, fourth, or sixth cranial nerve.

Condition for which diabetes is a known risk factor includes glaucoma. The risk of glaucoma has been reported to be 2-5 times higher in individuals with diabetes than in nondiabetic individuals. Between 32 and 43% of neovascular glaucoma cases are caused by proliferative DR. Ocular ischemic syndrome (OIS) is an uncommon vascular problem that typically presents with vision loss and dull ocular pain. The prevalence of diabetes in patients with OIS is higher than in the general population, with one study reporting that more than 50% of patients with OIS have diabetes.

Ocular conditions where diabetes is a possible risk factor include retinal vein and artery occlusion, retinal arteriolar emboli, corneal diseases (corneal erosion, persistent epithelial defect, or corneal ulcers).

The risk of cataract (and associated vision impairment) is believed to increase with increasing diabetes duration and severity of hyperglycemia.