Case of the Month

Edited by Robert N. Johnson, MD

Case #122

August, 2019

Presented by:

Caleb Ng,  MD

A 48-year-old Caucasian man referred for evaluation of retinal lesion in the right eye

Figure 1: Color photo of the right macula, disc and inferior retina. Note the faint gray-white lesion along the inferotemporal arcade. Subtle exudates noted as well.

Case History

A 48-year-old Caucasian man without known medical history presents with a chief complaint of mild blurry vision in both eyes for 1-2 months. On examination, visual acuity was 20/20-1 and 20/13-2 in the right eye and left eye, respectively.  The anterior segment examination was unremarkable. Dilated examination in both eyes revealed an isolated cotton wool spot along the inferotemporal arcade in the right eye (Figure 1). No other abnormalities in the right or left eye (not shown) were present.

What is your Diagnosis?

Differential Diagnosis of Diseases Associated with Cotton Wool Spot(s)1,2

  • Ischemic
    • Diabetes Mellitus
    • Hypertension
    • Retinal vein occlusion
    • Ocular ischemic syndrome
    • Severe anemia
    • Hyperviscosity/hypercoagulable state/dysproteinemia
    • Radiation
    • Acute blood loss
  • Embolic
    • Carotid emboli
    • Cardiac emboli
      • Cardiac valvular disease
      • Endocarditis
      •  Rheumatic heart disease
    • Deep venous emboli
    • Purtscher and Purtsher-like retinopathy
    • Foreign-body emboli
  • Collagen Vascular Disease
    • Systemic lupus erythematosus
    • Dermatomyositis
    • Scleroderma
    • Polyarteritis nodosa
    • Giant cell arteritis
  • Infectious
    • HIV retinopathy
    • Fungemia
    • Bacteremia
    • Rocky Mountain Spotted fever
    • Cat-Scratch disease
    • Leptospirosis
    • Onchocerciasis
  • Infectious
    • HIV retinopathy
    • Fungemia
    • Bacteremia
    • Rocky Mountain Spotted fever
    • Cat-Scratch disease
    • Leptospirosis
    • Onchocerciasis
  • Neoplastic
    • Leukemia
    • Lymphoma
    • Metastatic carcinoma
  • Miscellaneous
    • Traumatic
    • Tractional (epiretinal membrane)
    • High-altitude retinopathy
    • Papilledema/papillitis
  • Idiopathic

Additional History and Diagnosis

The patient has no prior surgeries and does not take systemic medications. He has a family history of glaucoma in his parents. Patient is a prior smoker and consumes alcohol socially. Serum work up was initiated. CBC with differential was unremarkable. Fasting plasma glucose, erythrocyte sedimentation rate (ESR), and anti-nuclear Antibody were all normal. He was HIV negavitve and VDRL and FTA-Abs negative. In our patient, evaluation determined no etiology for the cotton wool spot.


Cotton-wool spots (CWS) appear as small, slightly elevated, yellow-white or gray-white lesions with feathery borders in the superficial retina. They are rarely larger than 500 micrometers (or approximately ⅓ the area of the optic nerve head) and are restricted to the posterior pole. CWS only become symptomatic if they involve the fovea, and typically resolve within 6-12 weeks.3

CWS are hypothesized to be the consequence of retinal arteriolar obstruction with resultant ischemia and infarction of the nerve fiber layer. Hypoxia halts axoplasmic flow within the nerve fiber layer and causes accumulation of intra-axonal organelles, which can be seen on spectral coherence tomography as focal thickening and elevation of the nerve fiber layer.4 Analysis with light microscopy shows the presence of cystoid bodies, which are largely composed of mitochondria, in the swollen nerve fiber layer.5

Brown et al analyzed 24 consecutive patients with incidental findings of cotton wool spot and uncovered the following: undiagnosed diabetes mellitus (21%), systemic hypertension (21%), cardiac valvular disease (8%), radiation retinopathy (8%), severe carotid artery obstruction (8%), and Dermatomyositis, systemic lupus erythematosis, polyarteritis nodosa, leukemia, AIDS, Purtsher’s retinopathy, metastatic carcinoma, intravenous drug use, partial central retinal artery obstruction, and giant cell arteritis (4% each, respectively). The presence of a cotton wool spot commonly portends the diagnosis of a systemic etiology.

Take Home Points

  •  The presence of even one cotton wool spot in an otherwise normal fundus requires a work up for systemic etiologies.

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  1. Brown GC, Brown MM, Hiller T, et al. Cotton wool spots. Retina. 1985 Fall-Winter;5(4):206-14.
  2. Ryan S. Cotton-Wool spots. In: Retina. Fifth ed. Volume II Elsevier: 1022-23.
  3. Cotton-wool spots. Br Med J 1966;2:1474
  4. McLeod D, Marshall J, Kohner EM, et al. The role of axoplasmic transport in the pathogenesis of retinal cotton-wool spots. Br J Ophthalmol 1977;61:177-91
  5. Ashton N. Pathophysiology of retinal cotton-wool spots. Br Med Bull 1970;26:143-50

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