Leukemia is a cancer of the blood-forming tissues, causing the abnormal production and proliferation of white blood cells. These malignant cells circulate throughout the body, often reaching the eyes. Ocular involvement is a known complication, with studies suggesting that up to 69% of patients may show changes in the back of the eye during their illness. Recognizing these changes is important because they may be the first physical manifestation of the disease or a sign of its relapse.
Recognizable Signs and Symptoms
Patients with ocular manifestations may experience subjective symptoms, often starting with decreased visual clarity or blurred vision. Floaters, or dark spots moving within the field of vision, are a common complaint, typically caused by bleeding or cellular debris entering the vitreous humor. Other discomforts include eye pain, persistent redness, and increased sensitivity to light.
A more observable sign is proptosis, or the bulging of the eyeball, which occurs when leukemic cells infiltrate the orbital tissues surrounding the eye. In the anterior segment, inflammation of the uvea (uveitis) can occur, sometimes leading to pseudo-hypopyon—a layer of white cells settling in the lower anterior chamber. These symptoms may develop gradually or appear suddenly, requiring immediate medical attention.
The most frequent sign observed is leukemic retinopathy, which involves visible changes in the retina. This often includes retinal hemorrhages, which are small areas of bleeding that can appear flame-shaped or as dot-blot patterns. Many hemorrhages have a distinct white center, referred to as Roth spots, characteristic of blood disorders. The ophthalmologist may also observe cotton-wool spots, which are fluffy, white patches indicating localized nerve fiber layer damage due to blocked blood flow.
How Leukemia Affects Ocular Structures
Eye problems in leukemia patients stem from two distinct mechanisms: direct infiltration by malignant cells and secondary effects caused by blood abnormalities. Direct infiltration involves the physical invasion of leukemic cells into the delicate tissues of the eye, frequently targeting the retina, choroid, and optic nerve. Infiltration of the optic nerve can cause swelling of the optic disc, known as leukemic optic neuropathy, often signaling disease involvement in the central nervous system.
Secondary ocular changes are caused by systemic hematological issues, such as anemia, low platelet counts (thrombocytopenia), and blood thickening (hyperviscosity). Thrombocytopenia impairs clotting, making retinal vessels fragile and prone to rupturing, which causes many retinal hemorrhages. Anemia (low red blood cell count) also contributes to retinal changes because reduced oxygen-carrying capacity leads to tissue stress.
Hyperviscosity is a damaging effect, common in Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML) where the white blood cell count is extremely high. This increased thickness makes blood flow sluggish, causing retinal veins to become abnormally dilated and tortuous. Slow flow can lead to blockages in small vessels (leukostasis), which starves the surrounding tissue and manifests as cotton-wool spots. Ocular involvement is more frequent in acute forms of the disease, such as Acute Lymphoblastic Leukemia (ALL) and AML, compared to chronic leukemias.
Clinical Approach to Ocular Complications
Since ocular manifestations can be present even without symptoms, a comprehensive ophthalmological examination is suggested for all newly diagnosed leukemia patients. The primary diagnostic tool is a dilated fundus examination (fundoscopy), which allows the specialist to visualize the retina and optic nerve for characteristic signs like hemorrhages and cotton-wool spots. Advanced imaging, such as Optical Coherence Tomography (OCT), provides detailed cross-sectional views of the retina, helping track subtle leukemic infiltrates and fluid accumulation.
Management of these complications is achieved primarily by treating the underlying systemic leukemia, most often through chemotherapy. As the systemic disease burden decreases, secondary hematological effects like hyperviscosity and low platelet counts typically resolve, leading to the improvement of retinal signs. If vision loss is severe due to extreme blood thickening, an immediate procedure like leukapheresis may be performed to rapidly lower the white blood cell count and restore circulation.
If leukemic cells have directly infiltrated ocular structures, such as the optic nerve or orbit, localized treatments may be necessary in addition to systemic therapy. This may involve targeted external beam radiation therapy or the injection of chemotherapy drugs, such as methotrexate, directly into the eye (intravitreal injection) to manage persistent vitreoretinal infiltration. Localized interventions are important for preserving vision, as ocular involvement often indicates a more aggressive systemic disease state.