Cotton Wool Spots
In otherwise healthy patients, the observance of a cotton wool spot (CWS) is not considered normal. A single cotton wool spot in one eye can be the earliest ophthalmoscopic finding in diabetic or hypertensive retinopathy. In a series of patients who had cotton-wool spots and no known medical history, diastolic blood pressure equal to or greater than 90 mmHg was detected in 50% of patients, and an elevated blood sugar was found in 20% of patients.   
Can be categorized into:
- Ischemic : hypertension, diabetes, ocular ischemic syndrome(CWS is less common), retinal vein occlusion, anemia, hyperviscosity state, hypercoagulable state, radiation, acute blood loss.
- Immune and inflammatory conditions: systemic lupus erythematosus, dermatomyositis, scleroderma, polyarteritis nodosa, giant cell arteritis.
- Infectious: HIV retinopathy, cat-scratch disease, rocky mountain spotted fever, leptospirosis, onchocerciasis, bacteremia, fungemia.
- Embolic: carotid emboli, cardiac emboli, cardiac valvular disease, endocarditis, rheumatic heart disease, deep venous emboli, Purtscher-like retinopathy, foreign-body emboli.
- Neoplastic: lymphoma, leukemia, metastasis.
- Medication induced: interferon retinopathy.
- Miscellaneous: trauma, epiretinal membrane, high-altitude retinopathy, papilledema, papillitis, Purtscher retinopathy.
- Idiopathic.  
Cotton wool spots are believed to occur secondary to ischemia from retinal arteriole obstruction . It is thought to represent nerve fiber layer infarct and pre-capillary arteriolar occlusion. However, factors responsible for focal interruption of axoplasmic flow in the retinal nerve fiber layer may result in similar intra-axonal organelle accumulations .
The histological hallmark of cotton wool spots is considered by many authors to be cytoid bodies. They are named cytoid bodies because they look like cells, however they are eosinophilic segments of ganglion cell axons that are swollen because of defective axoplasmic flow. Cytoid bodies are usually packed with accumulations of mitochondria and other intracellular material  .
On ophthalmic fundus exam, cotton wool spots may appear as small, yellow-white (or grayish-white), slightly elevated lesions, which look like clouds with a fimbriate border in the superficial retina. Usually they are less than 1/3 disc areas in diameter, and are commonly found in the posterior pole of the fundus .
Cotton wool spots in general are visually asymptomatic, however, a patient may present with vision loss if the fovea is involved . Systemic symptoms of the underlying etiology may be present.
Diagnosis is usually achieved by a complete ocular examination, including a detailed dilated fundus exam. However, fluorescein angiography may reveal areas of capillary nonperfusion adjacent to cotton wool spots . On the other hand, additional work up may be needed to detect the underlying etiology.
Differential diagnosis of other yellow-white retinal lesions may include: myelinated nerve fibers, hard exudate, retinal infiltrate, retinitis, retinal drusen, chorioretinal atrophy, intraluminal plaque and early endogenous chorioretinitis .
Initial work-up may include vitals (blood pressure, heart rate, etc.) and metabolic studies including HbA1c, CBC, CMP, and HIV. Directed work-up may include ESR, CRP, EKG, echocardiogram, carotid ultrasound, hypercoaguable labs (protein C, protein S, Leiden, etc), PT/PTT, homocysteine and more.
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