BLOG: How does anemia cause retinopathy?

ByDoug Rett, OD, FAAO

Picture two patients; you see them back-to-back. The first is an 82-year-old man with a lot of vascular diagnoses for which he’s taking a lot of medications.

The second is a 52-year-old woman without many diagnoses who isn’t taking much medication.

The first patient has one or two dot hemorrhages in both his retinae, and the second patient has multiple cotton-wool spots (CWSs) and flame-shaped hemorrhages (FSHs) in both her retinae. What are the etiologies of each?

Both patients deserve a work-up, and chief among the tests you order will be a CBC and HbA1c. Say the A1c tests show no signs of diabetes, but the CBCs show anemia in both patients. Are both conditions caused by anemia? How should they be managed from here? How exactly does anemia cause retinopathy? Why the differences in presentation between these two patients? This month we’ll look a little deeper into anemia.

To review, there are lots of different types of anemia, but they all refer to a decrease in either red blood cells (RBCs) or hemoglobin, the oxygen-binding component of RBCs. This means when a patient is anemic, they aren’t getting enough oxygen to tissues throughout their body. The treatment for anemia depends on the cause – and there are several – but the causes can be thought of as three groups: blood loss, decreased RBC production and destruction of RBCs.

The first group, anemia caused by blood loss, is typically due to things like stomach ulcers, abnormal menstruation or gastrointestinal cancers. The most common causes of the second group are iron, B12 and/or folate deficiencies, and this is because those minerals and vitamins are needed to make RBCs. You can also get this type of anemia from bone marrow or stem cell problems. The final type of anemia (when RBCs are being destroyed) is called hemolytic anemia and is rarer than the first two. It’s caused by conditions such as sickle-cell anemia and advanced liver or kidney disease.

So it stands to reason that if the oxygen content in the tissues of an anemic patient is decreasing, then particularly-peripheral tissue like the retina could be one of the first manifestations of this disease. The hypoxic pathophysiology of anemic retinopathy is similar to – but subtly different from – (but nevertheless intertwined with) ischemia. Ischemia is the interruption of blood flow to tissue, and hypoxia is the decrease of oxygen saturation within tissue. So hypoxic retina could likely be getting a full blood supply, but that blood is deficient in oxygen. Diabetic retinopathy is more caused by ischemic damage, and anemic retinopathy is an example of hypoxic damage; but they can have similar findings and are often confused for one another. Hypoxia affects the superficial retinal nerve fiber layer more than the deeper retinal vasculature, causing CWSs and FSHs or occasionally sub-hyaloid hemorrhages. So when you see a retinopathy consisting mostly of superficial CWSs and FSHs, think about hypoxia and work the patient up for anemia.

An anemia workup always starts with a CBC. The main values to study are the: hemoglobin count (expressed in g/100 mL), hematocrit (HCT, the packed spun volume of blood that consists of RBCs, expressed as a percentage) and RBC count (the number of RBCs, expressed as millions of cells/µL). The CBC will also yield the RBC indices, which describe that size, shape and hemoglobin content of the RBCs. Evaluation of the indices is beyond the scope of this article, but will give the clinician a way to determine the specific cause of anemia once the diagnosis is suspected with decreased hemoglobin or HCT values. In most cases of anemic retinopathy, the best treatment is just to treat the underlying etiology of the anemia, and the retinopathy will typically resolve on its own.

Recalling our two patients at the beginning of this article, the retinopathy that eye care providers often attribute to anemia can be varied, from mild ischemic-like changes to severe hypoxic-like change. But keep in mind that true anemic retinopathy is typically found when hemoglobin values are quite low, not your typical mild anemia found in an elderly vasculopath. The range for normal hemoglobin concentration (for men) is 13.5 g to 17.5 g/dL; the concern for anemic retinopathy increases when that value falls below 6 g/dL.

So when you see an unexplained hemorrhagic retinopathy, by all means work the patient up for anemia. But keep in mind that hypoxic retinopathy is usually in a setting of severe anemia with superficial retinal findings.

References:

Carraro MC, et al. Eur J Haematol. 2001;67(4):238-244.

Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill Medical; 2008:360.

Schrier, SL. Approach to the adult with anemia. . Accessed March 4, 2019.