Intraocular leukemia is an uncommon ophthalmic disorder, which is due to an accumulation of circulating leukemic cells in the choroid, iris, ciliary body, neural retina, optic nerve, vitreous, and anterior chamber. Leukemia also causes a hemorrhagic retinopathy.
• Acute myelogenous leukemia is the predominant leukemia type in adults. Compared to children, survival rate is significantly lower.
• Chronic leukemias are generally found in older individuals and often appear in an indolent manner.
Acute lymphocytic leukemia is the predominant leukemia type in children and has a 50% cure rate.
• The cumulative lifetime incidence of intraocular leukemia in the United States is about 1 case per 2000–2500 persons.
• Peak incidence of intraocular lesions mirrors that of leukemia in general.
• 1 out of every 6 patients with leukemia develops ophthalmic symptoms that lead to referral to an ophthalmologist.
• Ocular findings are more common in acute leukemia compared to chronic leukemia.
• In a small prospective series, 62% of 120 newly diagnosed acute leukemia patients had some level of retinopathy (1)[A].
• In another series of 288 newly diagnosed acute leukemia patients, 35% had ocular findings but only 10% had symptoms (2)[A].
– Ocular findings are more common in adults than in children.
• 10% of all detected intraocular lesions in leukemic patients are infiltrative.
• Previous cancer treatment (certain chemotherapy and radiation therapy)
• Genetic diseases (i.e., Down syndrome)
• Blood disorders (i.e., myelodysplastic syndromes)
• High levels of radiation
• Certain chemicals (i.e., benzene)
• Family history of leukemia
History of leukemia, which is a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, usually leukocytes
• Decreased vision or asymptomatic
• Signs and symptoms of leukemia:
– Coagulopathy (decreased platelets)
– Frequent infection (dysfunctional leukocytes and a compromised immune system)
– Dyspnea and pallor (anemia)
– Constitutional symptoms, such as fevers, chills, persistent fatigue, and weight loss
– Enlarged lymph nodes
• Leukemic infiltrates:
– Can involve many intraocular structures – choroidal most common, but retinal changes are most recognizable
– Most characteristic clinical intraocular lesions
– Unifocal or multifocal, and one or both eyes
– Typical lesions are fuzzy, flat, white retinal patch often associated with retinal hemorrhages and overlying vitreous cells.
– Other infiltrative lesions include vitreous cells, retinal vessel sheathing, optic disc infiltration, retinal pigment epithelial detachment, exudative retinal detachment, localized or diffuse choroidal infiltration, neoplastic pseudohypopyon, and iris infiltration.
• Leukemic retinopathy:
– Hemorrhages are the most common finding, frequently multifocal and bilateral. May be sub-, intra-, or preretinal with potential breakthrough into vitreous cavity. Cotton wool spots are also seen.
– Significantly more common than true malignant infiltrates
– Usually secondary to associated anemia and thrombocytopenia
– Larger intraretinal hemorrhages may have prominent white centers, known as Roth spots, some of which may represent small leukemic infiltrates.
– Peripheral retinal capillary nonperfusion and microaneurysm formation has been observed in patients with chronic myelogenous leukemia, which rarely leads to neovascularization.
• Hyperviscosity syndrome:
– Pathologic mechanism related to increased blood viscosity
– Results from high white cell count (leukemia), red blood cell count (polycythemia vera), monoclonal gammopathy (i.e., Waldenstroms, multiple myeloma)
– Venous stasis retinopathy can include vascular tortuosity, microaneurysm formation (posterior and peripheral), retinal hemorrhages, peripheral nonperfusion, neovascularization, intra- and subretinal fluid, mild central retinal vein occlusion appearance,
– Suspected with bilateral changes
• Opportunistic infections:
– CMV retinitis is the most common infectious retinitis
– Progressive outer retinal necrosis
– Ocular toxoplasmosis
– Fungal infection
DIAGNOSTIC TESTS & INTERPRETATION
• Evaluation for suspected leukemic intraocular infiltrate includes a complete hematologic workup in conjunction with an internist.
– Complete blood count
– Bone marrow aspiration or biopsy
– Systemic staging evaluation
– Lumbar puncture for cerebrospinal fluid evaluation
– Serum protein electrophoresis for hyperviscosity syndrome
• Magnetic resonance imaging of the orbits and brain if optic nerve infiltration
• Serous macular detachments with hyperviscosity can show a characteristic silent fluorescein angiogram with minimal leakage (3)[B].
• Fine-needle aspiration biopsy or diagnostic pars-plana vitrectomy if diagnosis in doubt:
– Patients with leukemia are often immunosuppressed from their disease and/or chemotherapy treatment, making it difficult to clinically distinguish between leukemic infiltrates and other infectious lesions by opportunistic organisms.
• In an autopsy series, choroidal infiltration is most common.
• At the time of death, 28–80% of patients have ocular involvement on autopsy (4)[B].
• Leukemic infiltration observed in the uvea, optic disc, retina, vitreous, lumen of choroidal and retinal blood vessels.
• Infectious infiltrate:
• Noninfectious infiltrate:
– Sarcoid granuloma
– Pars planitis
• Primary intraocular lymphoma
• Systemic chemotherapy is administered to control underlying problem.
• Intraocular manifestations of leukemia usually are not treated directly.
When leukemic infiltrates fail to respond to systemic chemotherapy, ocular radiation is often recommended.
• Supportive measures (i.e., blood transfusions) are recommended for patients with severe anemia or thrombocytopenia.
• High-dose chemotherapy may increase susceptibility for radiation retinopathy at otherwise safe radiation doses.
Issues for Referral
Treatment of blood dyscrasia, such as leukemia, is always performed by an experienced hematologist/oncologist.
• Hyperviscosity syndrome often improves with treatment of underlying disorder
– In acute setting, leukapheresis (for leukemia) or plasmapheresis (for Waldenström’s and multiple myeloma) can be successfully utilized.
Panretinal photocoagulation is used in the setting of peripheral nonperfusion and retinal neovascularization.
• Full evaluation, staging and treatment by an oncologist/hematologist
• Given the large percentage of leukemia patients with retinopathy, routine ocular examination is recommended for all patients with newly diagnosed acute leukemia.
• More frequent ophthalmic follow-up is recommended in the setting of significant leukemic infiltrates, retinopathy, or hyperviscosity syndrome.
• Leukemic retinopathy has prognostic significance based on multiple studies.
– In 63 patients with childhood leukemia, 5-year survival was lower in those with leukemic retinopathy on presentation than in those without ophthalmic involvement (21% vs 46%) (5)[B].
• If anemia and thrombocytopenia are addressed, hemorrhagic retinopathy can improve.
• Leukemic infiltrates are viewed as a poor prognostic sign.
1. Schachat AP, Markowitz JA, Guyer DR, et al. Ophthalmic manifestations of leukemia. Arch Ophthalmol 1989;107:697–700.
2. Reddy SC, Jackson N, Menon BS. Ocular involvement in leukemia – a study of 288 cases. Ophthalmologica 2003;217:441–445
3. Ho AC, Benson WE, Wong J. Unusual immunogammopathy maculopathy. Ophthalmology 2000;107:1099–1103.
4. Kincaid MC, Green WR. Ocular and orbital involvement in leukemia. Surv Ophthalmol 1983;27:211–232.
5. Ohkoshi K, Tsiaras WG. Prognostic importance of ophthalmic manifestations in childhood leukaemia. Br J Ophthalmol 1992;76:651–655.