A 68-year-old woman is evaluated for vision impairment. The patient has a decrease in both distant and near vision and has had occasional floaters. She has had no pain or redness in her eyes, headache, focal weakness, or sensory loss. Medical history is notable for type 2 diabetes mellitus, hypertension, and chronic kidney disease. Blood pressure is 138/84 mm Hg and pulse is 76/min. The pupils are equal and reactive to light bilaterally. Anterior chambers are clear, and there are no opacities of the cornea or lens. Funduscopic examination reveals scattered retinal microaneurysms, dot-and-blot hemorrhages, and cotton-wool spots, as well as new blood vessel formation. Which of the following contributed most to the pathogenesis of this patient's current ocular condition?
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This patient, with painless vision loss and retinal neovascularization, has proliferative diabetic retinopathy (DR). DR is a result of chronic hyperglycemic injury to the small retinal vessels and is considered a microangiopathic complication of diabetes (along with neuropathy and nephropathy). The prevalence of DR is proportionate to the duration of diabetes and severity of hyperglycemia over time; tight control of diabetes is associated with a lower long-term risk of DR.
DR is categorized as follows:
Nonproliferative (early disease): The earliest morphologic changes include thickening of the basement membrane and failure of the blood-retinal barrier. Increased permeability allows leakage of fluid into the retina (macular edema), which can distort vision and leave behind lipid-rich deposits (hard exudates). Arteriolar obstruction causes ischemic injury to the retina, which manifests as cotton-wool spots. Other findings include microaneurysms and dot-blot hemorrhages (due to microaneurysm rupture).
Proliferative (advanced disease): Progressive retinal ischemia stimulates production of angiogenic factors (eg, vascular endothelial growth factor), leading to formation of new retinal vessels (neovascularization). The new vessels are fragile and often extend into the adjacent vitreous. Traction from the vitreous can cause detachment of the retina or laceration of the vessels, leading to acute hemorrhage and vision loss.
(Choice A) Age-related macular degeneration presents with slowly progressive central vision loss. It is due to oxidative damage to the pigment epithelium and choriocapillaris with abnormal extracellular matrix formation (drusen). In late-stage disease, patients may develop neovascularization ("wet" macular degeneration), but associated findings include subretinal drusen and pigment abnormalities.
(Choice C) Open-angle glaucoma is a form of optic neuropathy, characterized by ganglion cell death in association with elevated intraocular pressure. It causes insidious loss of peripheral vision; examination findings include enlargement of the retinal cup and a pale optic disc with thinning of the rim.
(Choice D) Atheroembolic retinal artery occlusion presents with acute monocular vision loss. Examination findings include retinal pallor and a cherry red spot at the macula.
(Choice E) Hypertensive retinopathy can manifest with retinal hemorrhages, cotton-wool spots, and hard exudates. However, the thickened and stiffened arterial walls are typically visible as arteriolar narrowing and impingement on the veins where they are crossed by arteries (arteriovenous nicking).
Educational objective:
Chronic hyperglycemia in patients with diabetes can lead to increased permeability and arteriolar obstruction in retinal vessels. The resulting ischemia stimulates production of vascular endothelial growth factor and other angiogenic factors, leading to neovascularization (proliferative diabetic retinopathy). Complications include retinal hemorrhage, retinal detachment, and vision loss.