Because a retinal exam can identify abnormalities of the blood before they manifest as signs or symptoms elsewhere in the body, eyecare practitioners should be vigilant for signs that could point to a blood dyscrasia.
Originally used to indicate an abnormal mixture of bodily fluids or humors (from the Greek dys- + krasis, meaning “mixture”), the word “dyscrasia” today refers to a host of disorders affecting the cellular elements of the blood. Blood dyscrasias can include an increase or decrease in the total number of red blood cells (polycythemia or anemia), abnormal or neoplastic white blood cells (leukemias), or abnormal or insufficient platelets (coagulopathy or thrombocytopenia). Many blood dyscrasias are overlapping conditions; a patient with leukemia might also have thrombocytopenia and coagulopathy.
Besides the skin and mucous membranes, where blood dyscrasias can sometimes produce visible symptoms, the retina presents our best early diagnostic opportunity. Indeed, significant ocular manifestations are not uncommon in these disorders, and vision-related issues may be the presenting symptom. However, since patients may often present without symptoms, a review of retinal signs associated with blood dyscrasias is warranted.
Signs to Look For
There are no pathognomonic retinal signs or symptoms of any blood dyscrasia: many of the retinopathies we see in patients with high blood pressure or diabetes also show up in patients with cellular abnormalities of the blood. In some cases, abnormal blood cells lead to vascular changes which result in hemorrhages or aneurysms. For example, in a patient with thrombocytopenia and anemia, retinal blood vessels can leak and then clot, resulting in hemorrhages visible on funduscopic exam. In other cases, a direct infiltration of abnormal cells (such as leukemic cells) in the choroid, retina, or optic nerve becomes apparent. As these are nonspecific signs, it is necessary to carefully evaluate each patient’s systemic health and history to determine what further testing and/or referral is required.
The most obvious signs of blood dyscrasia are retinal hemorrhages, including dot-blot hemorrhages found in the plexiform and nuclear layers, flame-shaped hemorrhages in the nerve fiber layer, and white-centered hemorrhages, which can be indicative of infiltrative leukemic cells or platelet fibrin infiltrates. White-centered hemorrhages may often be seen in patients with a combination of anemia and thrombocytopenia (Figure 1).
Macular aneurysms are another finding that may be associated with blood dyscrasias, caused by increased blood viscosity, venous pressure, or decreased oxygen levels. These microaneurysms differ slightly from those associated with diabetic retinopathy. Histologically, diabetic microaneurysms result from a loss of pericytes, which function to maintain the integrity of the capillary endothelial cells. In blood dyscrasias—particularly leukemias and plasma cell abnormalities—pericytes are typically preserved. Interestingly, microaneurysms in diabetic retinopathy tend to occur more often around the posterior pole, whereas in blood dyscrasias, they are typically found in the peripheral retina.
Cotton wool spots, the result of arteriole occlusions in the nerve fiber layer, are also commonly found in patients with blood dyscrasias. Vascular leakage from hyperviscosity or venous congestion can lead to hard exudates, yellowish deposits of lipid and protein from the blood, and to retinal edema.
Less frequent ocular manifestations of blood dyscrasias include disc edemas, neovascularization of the disc or peripheral retina, or central vein occlusion, in which vascular tortuosity is part of the picture. Vitreous hemorrhage is an extreme manifestation of blood dyscrasia, in which a decrease in vision and the presence of floaters are presenting symptoms.
As a retina specialist, most of the patients I see with blood-dyscrasia associated retinopathies are referred to me by comprehensive ophthalmologists or optometrists, who have noted a retinal hemorrhage or cotton wool spot and want further evaluation. Far less frequently do patients present of their own accord with ocular symptoms related to a blood dyscrasia. But because we have a robust leukemia and liquid cancer service at my institution, already-diagnosed patients are sometimes referred to me because of floaters or decreased vision.
Patients without a diagnosis who have cotton wool spots, hemorrhages, or vascular congestion, should be screened for diabetes and hypertension. In the absence of either condition, we must begin to look for other causes of these symptoms, including cellular abnormalities in the blood. In such cases, and in younger patients, a complete blood count—looking at the platelets, red blood cells, and white blood cells—is essential for the workup.
A careful patient history is critical when any abnormal retinal sign is detected. Even a distant history of a blood abnormality is significant, as the sign could indicate a possible recurrence manifesting initially in the eye. In a young and apparently healthy patient with no history or diagnoses, referral to an internist or hematologist for a complete physical exam, blood glucose testing, and a complete blood count is warranted.
At this point, identifying and treating the underlying disorder is most important, both to stop the progression of the noted retinopathy and to preserve the patient’s overall health. By treating the underlying disorder, the retinal signs and symptoms often resolve.
In certain cases, it is necessary to intervene directly or refer to a retina specialist to address visually-significant retinopathies, such as cystoid macular edema (CME) or non-clearing vitreous hemorrhage. CME secondary to blood dyscrasia will often respond to typical treatment, including topical anti-inflammatory medications and oral acetazolamide.
THE BOTTOM LINE
Abnormal retinal signs—hemorrhages, cotton wool spots, or micro-aneurysms—can be early signs of blood cellular abnormalities. A careful patient history and referral to a primary care physician, hematologist, or retina specialist are keys to timely diagnosis, underlying disease management, and, if necessary, treatment of associated retinopathy. While these conditions are rare, comprehensive ophthalmologists and optometrists are often the first ones to pick up signs of what turns out to be a blood dyscrasia.
Szilárd Kiss, MD, is a vitreoretinal surgeon and assistant professor of ophthalmology at Weill Cornell Medical College. Refractive Eyecare managing editor Jennifer Zweibel assisted in the preparation of this manuscript.