Cotton Wool Spots

From EyeWiki

Cotton Wool Spots

Disease entity


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. [1] [2] [3]


Can be categorized into:


Cotton wool spots are believed to occur secondary to ischemia from retinal arteriole obstruction [5]. 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 [6].

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 [7] [8].



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 [5].


Cotton wool spots in general are visually asymptomatic, however, a patient may present with vision loss if the fovea is involved [5]. Systemic symptoms of the underlying etiology may be present.

Clinical diagnosis

Wide-field color fundus photograph of the right eye shows multiple fluffy, ill-defined white parapapillary lesions consistent with cotton-wool spots. Their superficial location is demonstrated by the obscuration of retinal vessels by some of the larger lesions. © 2023 American Academy of Ophthalmology

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 [1]. On the other hand, additional work up may be needed to detect the underlying etiology. On optical coherence tomography (OCT), cotton wool spots can appear as focal or segmental areas of thickening and hyperreflectivity of the inner retinal layers in the acute phase. This thickening may be mostly confined to the nerve fiber layer with sparing of the outer retinal layers, consistent with the postulation of axoplasmic debris accumulation within the ganglion cell axons that correlate to clinically apparent CWS[9]. During resolution, these lesions can progress to inner retinal thinning or atrophy, or may in some cases result in cystic changes. OCT has been used to monitor the progression, extent, and resolution of cotton wool spots.

OCT through the lesion in B shows hyperreflectivity in the inner retina. © 2023 American Academy of Ophthalmology

Differential diagnosis

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 [10].


Work up and treatment are directed towards the underlying etiology. Cotton wool spots classically disappear in 6–12 weeks, however in diabetic retinopathy they may persist for longer [1][5]. In patients with HIV, cotton wool spots are a hallmark of HIV retinopathy, but the presence of new or large cotton wool spots should be monitored closely if the CD4 count is less than 200, as this may represent an early sign of viral retinitis.[11]

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, hypercoagulable labs (protein C, protein S, Leiden, etc), PT/PTT, homocysteine and more.

Additional Resources


  1. 1.0 1.1 1.2 Adam T. Gerstenblith, Michael P. Rabinowitz. Wills Eye Manual, The: office and emergency room diagnosis and treatment of eye disease, 6th edition. Lippincott Williams & Wilkins, 2012.
  2. 2.0 2.1 Brown GC, Brown MM, Hiller T, Fischer D, Benson WE, Magargal LE. "Cotton-wool spots." Retina. 5, no. 4 (Fall-Winter 1985): 206-14.
  3. 3.0 3.1 Arroyo, Jorge G. "Cotton-Wool Spots May Challenge Diagnosis ." Review of ophthalmology, 2004: 111-114.
  4. Arroyo JG, Irvine AR. "Retinal distortion and cotton-wool spots associated with epiretinal membrane contraction." Ophthalmology 102 (1995): 662-8.
  5. 5.0 5.1 5.2 5.3 5.4 Purnima S. Patel, SriniVas R. Sadda. "Retinal Artery Obstructions." In Retina (Fifth Edition), by Stephen J. Ryan, 1012-1025. Elsevier Inc., 2012.
  6. D. McLeod, D. McLeod, E. M. Kohner and A. C. Bird. "The role of axoplasmic transport in the pathogenesis of retinal cotton-wool spots." Br J Ophthalmol 61 (1977): 177-191.
  7. McLeod, D. "Why cotton wool spots should not be regarded as retinal nerve fibre layer infarcts." Br J Ophthalmol. 89, no. 2 (2 2005): 229–237.
  8. Jr, Ralph C. Eagle. Eye pathology an atlas and text . 2nd edition. Philadelphia: Lippincott Williams & Wilkins, 2011.
  9. Ioannides A, Georgakarakos ND, Elaroud I, Andreou P. Isolated cotton-wool spots of unknown etiology: management and sequential spectral domain optical coherence tomography documentation. Clin Ophthalmol. 2011;5:1431-3.
  10. The Eyes Have It: Yellow-White Things in the Retina. (accessed 11 02, 2014).
  11. Chen C, Guo CG, Meng L, Yu J, Xie LY, Dong HW, Wei WB. Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome. Int J Ophthalmol. 2017 Sep 18;10(9):1396-1401.
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