Ophthalmologic Manifestations of Leukemias 

Updated: Feb 11, 2019
Author: Lihteh Wu, MD; Chief Editor: C Stephen Foster, MD, FACS, FACR, FAAO, FARVO 

Overview

Background

Leukemias are a group of heterogeneous neoplastic disorders of white blood cells. Based on their origin, myeloid or lymphoid, they can be divided into two types. Leukemias traditionally have been designated as acute or chronic, based on their untreated course. Acute leukemias usually present as hemorrhage, anemia, infection, or infiltration of organs.

Many patients with chronic leukemias are asymptomatic. Other patients present with splenomegaly, fever, weight loss, malaise, frequent infections, bleeding, thrombosis, or lymphadenopathy. The image below depicts an impending retinal vein obstruction and intraretinal hemorrhage in a patient with chronic myelogenous leukemia. Some chronic leukemias enter a blast phase where the clinical manifestations are similar to the acute leukemias.

An impending bilateral central retinal vein obstru An impending bilateral central retinal vein obstruction was discovered during a routine examination of a 76-year-old man. Further workup revealed a WBC count of 709,000, a hemoglobin count of 12 mg/dL, and a platelet count of 104,000. The man was eventually diagnosed with CML. This image is a red-free photograph of the right fundus. Notice the intraretinal hemorrhages.

See Chronic Leukemias: 4 Cancers to Differentiate, a Critical Images slideshow, to help detect chronic leukemias and determine the specific type present.

Chronic myelogenous leukemia (CML) is characterized by an uncontrolled proliferation of granulocytes. An accompanying proliferation of erythroid cells and megakaryocytes is usually present. Many patients are asymptomatic but may present with splenomegaly, weight loss, malaise, bleeding, or thrombosis.

Chronic lymphocytic leukemia (CLL) represents a monoclonal expansion of lymphocytes. In 95% of cases, CLL is a predominantly malignant clonal disorder of B lymphocytes. The remainder is secondary to a T-cell clone. The neoplastic cell is a hypoproliferative, immunologically incompetent small lymphocyte. There is primary involvement of the bone marrow and secondary release into the peripheral blood. The recirculating lymphocytes selectively infiltrate the lymph nodes, the spleen, and the liver. Most patients are asymptomatic at diagnosis. As the disease progresses, lymphadenopathy, splenomegaly, and hepatomegaly develop. A secondary immune deficiency with hypogammaglobulinemia exists. A study by Wang et al found that when they studied the landscape of somatic mutations in chronic lymphocytic leukemia, pre-mRNA splicing was an important cellular process.[1]

Acute lymphocytic leukemia (ALL) is a malignant clonal disorder of the bone marrow lymphopoietic precursor cells. In ALL, progressive medullary and extramedullary accumulations of lymphoblasts are present that lack the potential for differentiation and maturation. An inhibition of the normal development of hematopoietic cell elements occurs. The clinical presentation is dominated by progressive weakness and fatigue secondary to anemia, infection secondary to leukopenia, and bleeding secondary to thrombocytopenia. When 50% of the bone marrow is replaced, then peripheral blood cytopenias are observed.

Acute myelogenous leukemia (AML) is a group of neoplastic disorders of the hematopoietic precursor cells of the bone marrow. AML is subdivided by the French-American-British system into 6 categories depending on the morphology. AML is not a disorder of rapidly proliferating neoplastic cells. The time for one cell division is prolonged with respect to that of normal bone marrow blast cells. A failure of maturation of the neoplastic cell clone exists. The bone marrow is gradually replaced by blast cells. Therefore, the most important complications are progressive anemia, leukopenia, and thrombocytopenia.

Pathophysiology

In leukemias, a clone of malignant cells may arise at any stage of maturation, that is, in the lymphoid, myeloid, or pluripotential stage. The cause for this clonal expansion is poorly understood in most cases, but it appears to involve some rearrangement of the DNA. External factors, such as alkylating drugs, ionizing radiation, and chemicals, and internal factors, such as chromosomal abnormalities, lead to DNA changes.

Chromosomal rearrangements may alter the structure or regulation of cellular oncogenes. For instance, in the B-cell lymphocytic leukemias, chromosomal translocations may put the genes that normally regulate heavy and light chain immunoglobulin synthesis next to the genes that regulate normal cellular activation and proliferation. This results in proliferation of lymphoblasts. As the population of cells expands, the bone marrow starts to fail. Pancytopenia is typical and results in part from the physical replacement of normal marrow elements by the immature cells. In addition, the abnormal cells may secrete factors that inhibit normal hematopoiesis.

As the bone marrow becomes replaced, the abnormal cells spill into the circulation and infiltrate other organs, such as the liver, the spleen, and the eye. Any of the ocular structures may be affected. Ocular involvement may occur prior to the diagnosis of leukemia, during the disease course, or as a sign of relapse. The ocular manifestations may be secondary to direct infiltration of the leukemic cells, as a result of abnormal systemic hematological parameters, opportunistic infections, or iatrogenic complications arising from chemotherapy.

Epidemiology

Frequency

United States

An estimated 44,790 new cases of leukemia will be diagnosed in the United States. Of the leukemias, 15,490 (35%) will be CLL; 12,810 (27%), AML; 5,760 (13%), ALL; and 5,050 (11%), CML.[2]

Clinical series show variable data regarding prevalence and incidence of ocular involvement in patients with leukemia. These differences arise from the differences in study design. In some studies, patients were examined at different stages of the disease. In others, ophthalmologists examined only symptomatic patients. In most studies, no distinction is made between the different leukemias.

Three prospective studies reveal that 14-53% of patients had ocular manifestations of the disease prior to the start of chemotherapy. Leukemia is responsible for 2-6% of orbital tumors in children. Furthermore, up to 11% of children with proptosis will have some form of acute leukemia.[3, 4]

Autopsy series show the highest frequency of ocular involvement. It is presumed that dying patients have a higher disease burden. In addition, histopathological methods allow detection of lesions that are not clinically detectable. About 28-80% of cases have intraocular manifestations. An autopsy study reports 8-12% have orbital involvement.[5]

Despite changes in treatment and survival over the past decades, ocular involvement, as examined by histopathological methods, has remained fairly constant in the past 70 years.

International

An estimated 300,000 new cases of leukemia (2.8% of all new cancer cases) are diagnosed each year globally.[6] It has been estimated that in Western countries, CLL constitutes the most frequent type of leukemia with 25% of cases, CML represents 20% of cases, and AML represents 20% of cases.

Mortality/Morbidity

When all leukemias are lumped together, the global 5-year survival is 20%. In developed countries, 31% survive for 5 or more years, compared with 15% in developing countries. This underscores the lack of access to high-tech treatment in the developing world. In 2002, 222,506 deaths were reported globally, secondary to all leukemias. It was estimated that, in the United States during 2009, there would be a total of 21,870 deaths secondary to all leukemias.

The breakdown of deaths according to the different subtypes is as follows:[7, 8, 5, 9]

  • Deaths secondary to ALL and AML have been reported at 1,400 and 6,900, respectively.

  • In children with ALL, 90% of patients achieve a complete remission, and up to 80% can remain disease free at 5 years following treatment. In adults with ALL, remissions occur in 60-80%, while 20-35% will maintain a leukemia-free survival.

  • Currently, 65-70% of patients with AML attain remission. The 5-year survival rate during the period 1989-1994 was 43%.

  • In a study from Italy, the presence of specific orbital or ocular lesions in ALL and AML was associated with a higher frequency of bone marrow relapses and CNS involvement, which led to a lower survival rate.[10]

  • Secondary to CLL, 5,100 deaths have occurred; secondary to CML, 2,300 deaths have occurred; and secondary to other leukemias, 6,400 deaths have occurred.

  • In CLL, the natural history is highly variable. The median survival is 6 years, and the natural history is not altered by therapy. Infection is the leading cause of death. The median survival of CML with treatment is 5 years. Granulocytic sarcoma of the orbit, also known as chloroma, represents an extramedullary site of AML or CML. Survival has been reported to range from 1-30 months after the onset of ocular signs and symptoms. Some studies suggest that the presence of intraocular leukemic infiltrates correlates with CNS involvement and with decreased survival.

Race

In the United States, ALL and CLL are more common in whites than in blacks.

Sex

Of the estimated 44,790 new cases of leukemia to be diagnosed in the United States during 2009, 25,630 cases will be in males and 19,160 cases in females.[2]

The breakdown of new cases of leukemia by gender and category is as follows:

  • CLL: 9,200 cases in males and 6,290 cases in females

  • CML: 2,930 cases in males and 2,120 cases in females

  • ALL: 3,350 cases in males and 2,410 cases in females; childhood ALL demonstrates a notable male predominance.

  • AML: 6,290 cases in males and 5,890 cases in females

  • In other leukemias, 3,230 cases in males and 2,450 cases in females 5680 total cases

Age

Most childhood leukemias are acute.

ALL is the most common malignancy in children, especially affecting those aged 2-10 years. ALL is seen in only 20% of adult acute leukemias and behaves more aggressively than the childhood type.

AML constitutes 15-20% of acute leukemias in children. Incidence of AML increases with age; in persons younger than 65 years, the incidence is 1.3, and in persons older than 65 years, the incidence is 12.2.

CML constitutes less than 5% of childhood leukemias. The incidence of CML increases slowly with age until the middle 40s, when the incidence starts to rise rapidly.

Incidence of CLL is over 10 per 100,000 for persons older than 70 years but is less than 1 per 100,000 for those younger than 50 years. Mean age at diagnosis of CLL is 60 years.

Prognosis

Retinal involvement in patients with leukemia appears to have a prognostic value. Those with retinopathy have more aggressive disease and therefore worse outcomes.[11, 12] The presence of cotton wool spots decreases the mean survival significantly.[13]

 

Presentation

History

In most patients, a diagnosis of leukemia has been made before presenting to an ophthalmologist. However, in some patients, ocular symptoms and examination lead to a diagnosis of leukemia. In other cases, ocular manifestations may occur during systemic relapse or even during a complete remission.[14]

Most patients do not develop symptoms as a result of intraocular involvement.

Physical

Posterior segment manifestations

The posterior segment manifestations are protean in nature and may be secondary to direct invasion of the leukemic cells.

They result from systemic hematological abnormalities, such as anemia, thrombocytopenia, and hyperviscosity or opportunistic infections secondary to the immune dysfunction.

Direct infiltration

Retinal grayish white nodules that may be surrounded by hemorrhage manifest direct infiltration.

Perivascular sheathing may be another manifestation of a leukemic infiltrate.

Roth spots, white-centered retinal hemorrhages, may represent a cluster of leukemic cells. On the other hand, septic emboli or platelet-fibrin material gives a similar funduscopic finding.

Rarely, pale gray swelling of the optic nerve head may indicate optic nerve infiltration.[15]

Leukemic retinopathy

Retinal lesions are the most common ocular manifestation of leukemia. They are found most often in adults and in patients with myeloid leukemia.

Retinal hemorrhages are the most common finding in most series and are thought to be secondary to anemia and thrombocytopenia. These hemorrhages may be dot-shaped, flame-shaped, intraretinal, subretinal, or subhyaloid.

An impending retinal vein obstruction and intraretinal hemorrhage are shown in the images below.

An impending bilateral central retinal vein obstru An impending bilateral central retinal vein obstruction was discovered during a routine examination of a 76-year-old man. Further workup revealed a WBC count of 709,000, a hemoglobin count of 12 mg/dL, and a platelet count of 104,000. The man was eventually diagnosed with CML. This image is a red-free photograph of the right fundus. Notice the intraretinal hemorrhages.
Same patient as in the image above. This image is Same patient as in the image above. This image is a red-free photograph of the left eye showing intraretinal hemorrhages.

Cotton-wool spots are known to represent nerve fiber layer infarcts. However, they are not correlated with hematological parameters of anemia or blood viscosity.

Retinal vein tortuosity and dilation are thought to be secondary to hyperviscosity.

Peripheral retinal microaneurysms and retinal neovascularization may be seen, particularly in patients with CML. They are thought to occur as a result of peripheral nonperfusion and ischemia from hyperviscosity.

Sea fans reminiscent of sickle cell retinopathy may be seen.

Neovascularization of the disc has been reported in a case where no apparent ischemia was present. It was recognized that angiogenic factors secreted from the tumor may play a role in the pathogenesis of retinal and optic nerve head neovascularization.

The vitreous seldom is involved.

The choroid is the most commonly affected ocular structure in pathological studies. Clinically, it often is difficult to detect the subtle choroidal changes.

Occasionally, serous retinal detachments and retinal pigment epithelium (RPE) changes have been reported. In rare cases, they can be the first sign of relapsing leukemia.[16]

Opportunistic infections include cytomegalovirus retinitis, toxoplasma chorioretinitis, endogenous fungal endophthalmitis, and herpetic retinitis.

Anterior segment manifestations

Anterior segment involvement in leukemia is rare but significant because it often is an extramedullary site of relapse. Anterior segment manifestations occur more commonly in ALL than in all the other types of leukemia.

A change in iris color, iris nodules, hyphema, hypopyon, glaucoma, a sterile corneal ring ulcer, and a pannus all have been described in patients with leukemia.[17] A case report has described a man with AML relapse characterized by iris infiltration and pseudohypopyon.[18]

Corneal involvement is rare. Scleral, episcleral, and conjunctival involvement usually is silent and is limited to perivascular infiltration that can be demonstrated on pathological sections.

Orbital manifestations

Leukemic cells may infiltrate the orbit during the course of acute or chronic leukemia. Unusual orbital involvement with leukemia has been reported to include infiltration of the lacrimal gland and drainage system, rectus muscles, and dermis.

Orbital involvement in children is more common in acute leukemias, whereas orbital involvement in adults is more common in chronic leukemias.

The leukemic infiltrate may range from insignificant, where it is virtually asymptomatic, to a space-occupying lesion with its concomitant symptoms.

The patient may have proptosis, ecchymosis, chemosis, diplopia, visual disturbance, or motility disturbances.

AML may present as gaze palsy.[19]

In children, the orbital involvement is characterized by an acute and rapid process that may be confused with orbital cellulitis. In general, these infiltrates are bilateral and do not destroy bone.

Granulocytic sarcoma of the orbit, also known as chloroma, is an extramedullary form of myelogenous leukemia.

Unilateral, painless proptosis develops over weeks to months prior to a diagnosis of leukemia. Eyelid redness or violaceous discoloration may be present, which turns into ecchymosis that may be confused with rhabdomyosarcoma or metastatic neuroblastoma. If AML or CML is already present, then a rapid and fulminant bilateral proptosis is characteristic.

An example of orbital presentation and outcome of leukemia are shown in the images below.

A 4-year-old boy presented with sudden proptosis o A 4-year-old boy presented with sudden proptosis of his left eye.
Same patient as in the image above. A CBC revealed Same patient as in the image above. A CBC revealed anemia (Hb 8.6 mg/dL), thrombocytopenia (64,000), and leukocytosis (12,900). The peripheral smear revealed the presence of blasts 28%, lymphocytes 44%, segmented 14%, monocytes 6%, bands 2%, metamyelocytes 1%, and myelocytes 1%. The boy was diagnosed with AML type M4-M5 chloroma of the left orbit.
Systemic chemotherapy was instituted, and the prop Systemic chemotherapy was instituted, and the proptosis resolved. Unfortunately, 4.5 months later, the boy passed away secondary to multiorgan failure.

Causes

The etiology of the leukemias appears to be multifactorial. Genetic, viral, and environmental factors, such as ionizing radiation, drugs, and chemicals, have been implicated in the pathogenesis of leukemia.

It is believed that the final common pathway is damage to the DNA. This damage may rearrange the genetic material, thereby allowing previously silent oncogenes to be expressed.

Patients with an abnormal number of chromosomes (eg, trisomy 21) and chromosomal translocations are at an increased risk of developing ALL.

Risk factors implicated in the development of AML include the following:

  • Myelotoxic agents (eg, ionizing radiation, benzene, alkylating agents)
  • Chromosomal abnormalities (eg, Down syndrome, chromosomal instability syndromes)
  • Predisposing hematological disorders (eg, aplastic anemia, chronic myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria)

Chromosomal abnormalities, especially trisomy 12, are common in patients with CLL. Familial case clusters have been reported in CLL. HTLV-1 infection has also been implicated in CLL.

Damage to the bone marrow by agents, such as benzene and ionizing radiation, may cause CML.

Of patients with CML, 90% have an acquired chromosomal abnormality, the Philadelphia chromosome, which is a translocation of half of the long arm of chromosome 22 to another chromosome, usually chromosome 9.

 

DDx

 

Workup

Laboratory Studies

CBC and differential

CBC is the most useful initial laboratory test in patients suspected of having leukemia. Most patients will show some abnormality in the CBC and some blasts will be seen in the peripheral smear in patients with acute leukemias.

To diagnose CLL, a lymphocytosis of greater than 5000/mm3 must be present. The absolute neutrophil count is usually normal (see the Absolute Neutrophil Count calculator) and red blood cell counts and platelet counts are mildly decreased. In addition, the peripheral smear or bone marrow should show normal mature small lymphocytes with less than 55% atypical or blast forms.

CML is defined by its peripheral WBC count. Typically, leukocytosis is in excess of 100,000/mm3. The differential count shows that neutrophil precursors are present. This is accompanied by basophilia and eosinophilia. Unlike those in AML, these cells are mature and functional.

Bone marrow aspiration

Bone marrow aspiration establishes the diagnosis of leukemia. The morphology of blasts usually can differentiate between ALL and AML.

In ALL, a homogeneous infiltrate of lymphoblasts replaces the normal bone marrow elements. Lymphoblasts usually are small and measure approximately 14 µm in diameter. They have scant cytoplasm with no granules. The nucleus has no nucleoli or a small indistinct one.

For the diagnosis of AML, 30% of the nucleated cells in the aspirate must be blast cells of myeloid origin. Multiple large nucleoli, delicate chromatin, gray-blue cytoplasm, and Auer rods characterize myeloblasts. The presence of Auer rods is virtually diagnostic of AML, because these condensed lysosomal cytoplasmic azurophilic rod-shaped structures do not appear in ALL.

In CLL, bone marrow infiltration exceeds 30% lymphocytes. The lymphocytes are mature with less than 55% atypical or blast forms. The nuclei are round, cytoplasm is scant, chromatin is compact, nucleoli are inconspicuous, and mitotic figures are rare.

Immunophenotyping

Immunophenotyping using multiparameter flow cytometry following labeling with monoclonal antibodies to cell-surface antigens identifies the B or T cell origin of the lymphoblasts.

Based on the expression of B lineage-restricted antigens and clonal rearrangements of immunoglobulin heavy and light chain genes, it has been estimated that up to 80% of ALL cases arise from B-cell precursors. The majority possesses a common ALL antigen (CALLA) that is present only on leukemic cells.

T-cell ALL possesses receptors for sheep erythrocytes, and, when these are combined, they form E-rosettes.

A final subset of ALL lacks B- or T-cell characteristics and is referred to as null-cell ALL.

Certain myeloid-specific antigens, such as CD13, CD33, and CD41, have been used to diagnose AML.

The malignant cells in CLL correspond to a minor subpopulation of B cells that express cell surface immunoglobulin M (IgM) and immunoglobulin D (IgD) and the T-cell associated antigen CD5.

Histochemical stains

Histochemical stains for myeloperoxidase (Leder stain) and nonspecific esterase have a strong affinity for myelogenous precursors but fail to stain lymphocytic forerunners.

Demonstration of nuclear DNA polymerizing enzyme terminal deoxynucleotidyl transferase (TdT) is indicative of a lymphoid origin. However, up to 2-5% of patients with AML exhibit this enzyme. Exceptions may occur when a malignant clone arises from multipotent cells that may express both myelogenous characteristics and lymphocytic characteristics.

Chromosomal analysis

Chromosomal analysis also plays an important role. The diagnosis of CML is established by identifying cytogenetically or molecularly a clonal expansion of a hematopoietic stem cell possessing a reciprocal translocation between chromosomes 9 and 22.

Chromosomal analysis of the leukemic cell currently provides the most important pretreatment prognostic information in AML.

Imaging Studies

Fluorescein angiography may reveal myriad diffuse leakage points at the level of the RPE. This pattern also may be seen in Vogt-Koyanagi-Harada disease, diffuse choroidal melanoma, metastatic tumors, and posterior scleritis.

Optical coherence tomography (OCT) can help confirm the diagnosis of macular exudative detachment. OCT can also be useful in monitoring patients following treatment.

Histologic Findings

Histopathological studies have shown the choroid to be the ocular structure most commonly involved by leukemia. The choroid is thickened, especially at the posterior pole. The RPE may be hyperplastic, atrophied, or hypertrophied. Photoreceptor loss, drusen formation, serous detachment, and cystoid retinal edema may be present.

Immature white blood cells infiltrate the retina, and, when they accumulate, nodular masses may be seen. The retinal vessels usually are packed with immature leukocytes. Capillary nonperfusion may result due to massive accumulation of cells. Diffuse infiltration of the iris and the ciliary body is commonly seen. The infiltrates are usually denser near the sphincter and the base of the iris. The trabecular meshwork may be clogged with leukemic cells leading to glaucoma.

Histopathological studies indicate that leukemic infiltration in the orbit most often was mild and diffuse as opposed to massive and tumorous. A chloroma of the orbit is composed of immature granulocyte cells, which contain large amounts of the enzyme myeloperoxidase, giving the tumor a greenish hue on gross examination. Because of the poorly differentiated nature of this tumor on histological examination and often unremarkable CBC, it may be misdiagnosed as a lymphoma.

Histological diagnosis of lymphoma in a rapidly growing orbital mass of a child is unlikely because orbital lymphomas in children are quite rare.

 

Treatment

Medical Care

The treatment of leukemia is in constant flux, evolving and changing rapidly over the past few years. Most treatment protocols use systemic chemotherapy with or without radiotherapy. The basic strategy is to eliminate all detectable disease by using cytotoxic agents. To attain this goal, 3 phases are typically used, as follows: remission induction phase, consolidation phase, and maintenance therapy phase.

Chemotherapeutic agents are chosen that interfere with cell division. Tumor cells usually divide more rapidly than host cells, making them more vulnerable to the effects of chemotherapy. Primary treatment will be under the direction of a medical oncologist, radiation oncologist, and primary care physician. Although a general treatment plan will be outlined, the ophthalmologist does not prescribe or manage such treatment.

The initial treatment of ALL uses various combinations of vincristine, prednisone, and L-asparaginase until a complete remission is obtained.

Maintenance therapy with mercaptopurine is continued for 2-3 years following remission.

Use of intrathecal methotrexate with or without cranial irradiation to cover the CNS varies from facility to facility.

Daunorubicin, cytarabine, and thioguanine currently are used to obtain induction and remission of AML.

Maintenance therapy for 8 months may lengthen remission. Once relapse has occurred, AML generally is curable only by bone marrow transplantation.

Presently, treatment of CLL is palliative.

CML is characterized by a leukocytosis greater than 100,000 cells. Emergent treatment with leukopheresis sometimes is necessary when leukostastic complications are present. Otherwise, busulfan or hydroxyurea may control WBC counts. During the chronic phase, treatment is palliative.

When CML converts to the blastic phase, approximately one third of cases behave as ALL and respond to treatment with vincristine and prednisone. The remaining two thirds resemble AML but respond poorly to AML therapy.

Allogeneic bone marrow transplant is the only curative therapy for CML. However, it carries a high early mortality rate.

Leukemic retinopathy usually is not treated directly. As the hematological parameters normalize with systemic treatment, many of the ophthalmic signs resolve. There are reports that leukopheresis for hyperviscosity also may alleviate intraocular manifestations and improve visual acuity.[20]

When definite intraocular leukemic infiltrates fail to respond to systemic chemotherapy, direct radiation therapy is recommended.

Relapse, manifested by anterior segment involvement, should be treated by radiation. In certain cases, subconjunctival chemotherapeutic agents have been injected.

Optic nerve head infiltration in patients with ALL is an emergency and requires prompt radiation therapy to try to salvage some vision.

Consultations

A multidisciplinary approach is required in the treatment of a leukemic patient. Routine ophthalmic evaluation should be considered at the time of diagnosis because ocular lesions can be asymptomatic.

 

Guidelines

Guidelines Summary

Ophthalmic involvement in patients with leukemia is common. Virtually all parts of the eye may become involved. Ophthalmic examination of patients with leukemia is important, as ocular involvement may be a sign of relapse. Earlier diagnosis may allow earlier treatment.

 

Follow-up

Complications

Ocular complications

Posterior segment complications from bone marrow transplants were seen in 13% of patients. Among the complications seen were vitreous hemorrhage, infectious retinitis, cotton-wool spots, and retinal detachment.

Radiation retinopathy has been reported to occur in patients undergoing bone marrow transplant and high-dose chemotherapy and who received low-dose teletherapy. High-dose chemotherapy may lower the threshold for radiation retinopathy.

Ocular ischemia evidenced by optic disc and retinal neovascularization may lead to tractional retinal detachment following chemotherapy and radiation therapy.

Dry eye, keratitis, and cataracts may be sequelae of external beam radiation therapy with 3000-4000 rads. However, as little as 1150 rads may cause lenticular opacities.

In one study, 82 ALL survivors and 15 AML survivors were followed for an average of 3 years. All of the AML survivors had a normal ocular examination. Cataracts developed in 52% of ALL survivors. However, only 1 patient suffered significant visual dysfunction as a result of ALL or its treatment.[21]

Prognosis

Leukemic retinopathy usually is seen in patients who show a relapse and does not imply a bad prognosis.

Leukemic infiltration portends a poor prognosis and usually is associated with CNS involvement.

Optic nerve head infiltration is associated with CNS disease and a poor prognosis.

Prognosis of ALL is age dependent. Children have a much better outlook than adults. See Mortality/Morbidity.

Patient Education

For patient education resources, see the Cancer Center and Leukemia.

 

Questions & Answers

Overview

What is chronic myelogenous leukemia (CML)?

What is chronic lymphocytic leukemia (CLL)?

What is leukemia?

What is acute lymphocytic leukemia (ALL)?

What is acute myelogenous leukemia (AML)?

What is the pathophysiology of leukemias?

What is the prevalence of leukemias in the US?

What is the global prevalence of leukemias?

What are the survival and mortality rates of leukemias?

What are the racial predilections of leukemias?

What are the sexual predilections of leukemias?

Which age groups have the highest prevalence of leukemias?

What is the prognosis of leukemias?

Presentation

When do ocular symptoms of leukemia typically present?

What are the posterior segment ocular findings characteristic of leukemia?

What are the ocular findings characteristic of direct infiltration of leukemia?

What are the ocular findings characteristic of leukemic retinopathy?

Which anterior segment ocular findings are characteristic of leukemia?

Which ocular orbital findings are characteristic of leukemia?

What causes leukemia?

DDX

What are the differential diagnoses for Ophthalmologic Manifestations of Leukemias?

Workup

What is the role of CBC count in the workup of leukemia?

What is the role of bone marrow aspiration in the workup of leukemia?

What is the role of immunophenotyping in the workup of leukemia?

What is the role of histochemical stains in the workup of leukemia?

What is the role of chromosomal analysis in the workup of leukemia?

What is the role of imaging studies in the workup of leukemia?

Which histologic findings are characteristic of leukemia?

Treatment

How are leukemias treated?

How are the ophthalmologic manifestations of leukemias treated?

When is an ophthalmic evaluation indicated in the treatment of leukemia?

Guidelines

How common are ophthalmologic manifestations of leukemia?

Follow-up

What are the possible ocular complications of leukemia treatments?

What is the prognosis of ophthalmologic leukemia?