## Pathophysiology of Cotton-Wool Spots in Hypertensive Retinopathy **Key Point:** Cotton-wool spots represent **nerve fiber layer infarcts** caused by occlusion of precapillary arterioles due to severe hypertensive vasculopathy. ### Mechanism of Formation 1. **Arteriolar Narrowing & Occlusion**: Severe hypertension causes acute arteriolar constriction and endothelial damage, leading to precapillary arteriole occlusion. 2. **Ischemia of Nerve Fiber Layer**: The retinal nerve fiber layer (RNFL), which is highly metabolically active, becomes ischemic distal to the occluded vessel. 3. **Microinfarction**: Ischemic necrosis of nerve fiber bundles results in accumulation of axoplasmic material and cellular debris. 4. **Clinical Appearance**: The white, fluffy appearance on fundoscopy corresponds to the accumulated axoplasmic material within the infarcted nerve fibers. **High-Yield:** Cotton-wool spots are **not hemorrhages** — they are microinfarcts. They appear white and fluffy because of axoplasmic accumulation, not blood. **Clinical Pearl:** Cotton-wool spots are transient findings in hypertensive retinopathy; they typically resolve within 4–6 weeks as the axoplasm is cleared, leaving no permanent scarring. This distinguishes them from hard exudates, which persist. **Mnemonic:** **RNFL Infarct** = **R**etinal **N**erve **F**iber **L**ayer microinfarction → white, fluffy, transient appearance. 
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