Know the link between cotton wool spot and anemia

Optometry Times JournalOptometry Times Vol. 10 No. 11
Volume 10
Issue 11

A cotton wool spot found during an annual comprehensive exam on an otherwise healthy 54-year-old female may have lead to a life-saving diagnosis

Figure 1. Cotton wool spot inferior arcade.

Figure 2. Normal fundus OD.

Figure 3. Resolving cotton wool spot inferior arcade.

Figure 4. Resolved cotton wool spot.

This case report is part of a series by members of Intrepid Eye Society.

The most common differential diagnoses for cotton wool spot (CWS) are diabetes, hypertension, or even hepatitis C.1,2

What if I told you a cotton wool spot found during an annual comprehensive exam on an otherwise healthy 54-year-old female may have lead to a life-saving diagnosis?

This case study will review the pathophysiology of a CWS and what an optometrist should consider to diagnose and manage these patients in their clinic.

Case presentation
On April 3, 2017, R.M., a 54-year-old female, presented for her annual exam.

Entering unaided visual acuity was 20/20 in both eyes.

A careful review of systems indicated no health concerns, and the patient was on a holistic medication regimen of calcium and fish oil supplements. Furthermore, extraocular muscles were full in all fields without pain, and pupils were equal and normal with no afferent pupil defect noted.

Intraocular pressures (IOPs) were 13 mm Hg and 10 mm Hg via Icare handheld tonometer.

Anterior segment was remarkable for mild signs of meibomian gland dysfunction and mild nuclear sclerotic cataracts in both eyes.

A dilated fundus examination indicated a large optic nerve head with a cup-to-disc ratio of 0.5 in both eyes.

Interestingly, a small CWS was discovered along the inferior arcade below the macula in the right eye (see Figure 1).

A chart review of her fundus photography records from the previous year did not show evidence of a CWS (see Figure 2).

Per our practice protocol, a complete blood count (CBC) with differential was ordered, and a letter was sent to the primary-care physician (PCP) to inform this new finding. The patient was referred to her PCP and was scheduled to follow up in one month with our office.

On May 15, 2017, R.M. returned for her follow-up exam during which she indicated she had undergone abdominal surgery on May 1, 2017, to repair a bleeding stomach ulcer.

The requested blood work performed on April 12, 2017, indicated severe blood loss and anemia from the bleeding ulcer. Her hematocrit level, a measurement of the amount of red blood cells (RBCs) in the blood, was 25.4 percent. Normal hematocrit ranges are 36 to 46 percent in women.3

Additionally, her hemoglobin (Hb), an iron-binding, oxygen-carrying protein within RBCs, count was low (7.2 g/dL; normal 12-15 g/dL).3

The mean corpuscular volume (MCV), a measure of the average volume of red blood cells, was 70.6 fL. Normal female MCV ranges 76 to 96 fL.3

Contextually, a lower number for each of these diagnostics may be indicative of anemia.

Retinal evaluation at this visit revealed a smaller-sized, faintly resolving CWS (see Figure 3).

Repeat blood work conducted on June 16, 2017, with a hematocrit level raised to 45.5 percent, a hemoglobin count of 14.1 g/dL, and a MCV normalized to 87.3 fL. 

On July 7, 2017, R.M. returned for a follow-up visit where the CWS had spontaneously resolved (see Figure 4).

In eye care, CWS is used to describe a retinal nerve fiber layer infarct caused by focal interruption of axoplasmic flow.

Cotton wool spots can be a sign of a number of systemic ailments, including anemia. Anemia occurs when the level of RBCs or Hb is too low. Iron deficiency is the most common type of anemia. Other causes of anemia include blood loss, inadequate production of red blood cells (aplastic anemia,) or increased destruction of red blood cells (hemolytic anemia) that may present lifelong health problems.

Type 2 diabetes mellitus (T2DM) should be considered as a potential etiology for anemia.4 The condition was identified as an independent risk factor of diabetic retinopathy, and more severe retinopathy was found in anemic patients than in non-anemic patients.5,6

Other interrelated health conditions such as rheumatoid arthritis (RA), pernicious anemia causing vitamin B12 deficiency, and malaria can be connected to anemia. Of note, leukemia, lymphoma, and myeloma all downregulate white blood and plasma cell function that can also lead to this disease state.7

Anemia causes retinopathy in 28 percent of patients, especially when there is coexisting thrombocytopenia (38 percent). As the severity of anemia increases, the risk of retinopathy increases, particularly when the Hb level is below 6 g/dL.8

Moreover, sickle cell disease constitutes a group of autosomal recessive genetic disorders characterized by the variant, Hb S.9

The exact pathophysiology of anemic retinopathy is not completely understood. However, it seems to be related to retinal hypoxia, venous stasis, angiospasm, or increased capillary permeability.11

When anemia causes retinal hypoxia, it can lead to infarction of the nerve fiber layer and clinically manifest as cotton wool spots. The ocular changes found in anemic retinopathy are nonspecific and may closely resemble diabetic or hypertensive retinopathy, such as retinal hemorrhages and macular edema.12

As alluded to in the discussion, this disease state may also be a secondary manifestation of other systemic diseases such as cancer or autoimmune disorders. Therefore, in addition to ordering a complete blood count, other appropriate medical testing may be necessary.

With a timely diagnosis, anemic retinopathy can be stabilized and aggressively treated to prevent long-term damage to your patient’s vision.


1. Hammond S, Wells JR, Marcus DM, Prisant LM. Ophthalmoscopic findings in malignant hypertension. J Clin Hypertens (Greenwich). 2006 Mar;8(3):221-3.
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3. Last page of Deepak A. Rao; Le, Tao; Bhushan, Vikas (2007). First Aid for the USMLE Step 1 2008 (First Aid for the Usmle Step 1). McGraw-Hill Medical. ISBN 0-07-149868-0.
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5 He BB, Wei L, Gu YJ, Han JF, Li M, Liu YX, Bao YQ, Jia WP. Factors associated with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:157940.
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8. Carraro MC, Rossetti L, Gerli GC. Prevalence of retinopathy in patients with anemia or thrombocytopenia. Eur J Haematol. 2001 Oct;67(4):238-44.
9. Hooper CY, Fraser-Bell S, Farinelli A, Grigg JR. Complicated hyphaema: think sickle. Clin Exp Ophthalmol. 2006 May-Jun;34(4):377-8.
10. Bansal S, Gunasekeran DV, Ang B, Lee J, Khandelwal R, Sullivan P, Agrawal R. Controversies in the pathophysiology and management of hyphema. Surv Ophthalmol. 2016 May-Jun;61(3):297-308.
11. Loewenstein JI. Retinopathy associated with blood anomalies. In: Jakobieck F (ed). Clinical Ophthalmology. Revised ed. Philadelphia: J.B. Lippincott Company, 1995;3(85): 995-1000.
12. Weiss LM. Anemic Retinopathy. Pa Med 1966 Jun;69(6):35-6.

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