Introduction

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, accounting for more than 30% of cases, with 400–500 new children diagnosed annually in the UK. Combination chemotherapy for acute leukemia in children is highly effective; thus, serious ocular involvement is much less common than it was, and routine ophthalmic surveillance is usually unnecessary. Five-year survival rates of over 80% are usual for ALL and up to 60% for acute myeloid leukemia (AML). The majority of treatment failures are due to recurrent leukemia, and treatment-related deaths have become less common with improved supportive care.

Several clinical and biologic criteria adversely affect prognosis and treatment regimens: age (infants under 1 year and children over 10 years suffer higher relapse rates), high presenting white blood cell count, slow response to initial therapy, and chromosomal changes within the leukemic cells. This approach has closed the gap in treatment success rates originally identified between the subgroups of patients.

Almost all children are treated initially with chemotherapy; bone marrow transplantation is reserved for the around 10% of children with initial very poor prognosis, or following relapse. AML accounts for 5% of children’s cancers, with only 60–70 new cases in children in the UK each year; treatment is very intensive over 5 or 6 months. Chemotherapy is increasingly effective, and bone marrow transplantation less common. Outcome of therapy correlates with chromosomal changes in the leukemic cells and response to initial treatment which are used to divide children into subgroups in a manner similar to those for acute lymphoblastic disease.

Common sites of disease at presentation are bone marrow, blood, lymph nodes, liver, and spleen. The eye is the only site where the leukemic involvement of nerves and blood vessels can be directly observed and it may act as a “sanctuary” for leukemic cells against chemotherapy. Eye complications may occasionally be the major residual disability¹ but serious eye involvement is unusual.² Ophthalmic manifestations may be dramatic, requiring prompt diagnosis and treatment and are more a feature of relapse than of initial presentation. The ocular manifestations of acute leukemia are divided into direct (infiltration of the anterior segment, the orbit, or the CNS) and indirect (secondary to hematologic changes such as hyperviscosity, anemia, thrombocytopenia, and immunosuppression).³

Orbital leukemia is a small, but significant cause of proptosis in children⁴ and is more likely to be found in uncontrolled disease, in the first decade and with AML. It is associated with higher mortality. Orbital presentation may occur without eye involvement and it may be the only manifestation, especially in AML. Myeloid leukemia may present as an isolated solid tumor mass (granulocytic sarcoma) at a variety of sites, including the orbit (Fig. 64.1). A greenish tinge to the tissue mass led to the term chloroma: this appearance may be due to myeloperoxidase or altered blood products.

Fig. 64.1 “Chloroma” due to myeloid leukemia.

Orbital involvement in leukemia may be due to bone or soft tissue infiltration, tumor formation, or hemorrhage; the lacrimal gland, or lacrimal drainage apparatus may be primarily involved, with a more benign diagnosis. Children with orbital involvement present with proptosis, chemosis, and, rarely, muscle involvement; these may occur early in the disease. Exposure keratitis may occur. It may be difficult to differentiate between primary leukemic infiltration and complications such as hemorrhage or opportunistic infection; a biopsy may be necessary.⁵ A biopsy should be from the center of the abnormal area, not from the periphery where secondary inflammatory changes may occur. Review of the blood count and blood film by a pediatric oncologist, and a thorough clinical assessment prior to biopsy, together with a bone marrow examination at the time of biopsy, are important steps.

Lids

The lids are usually only involved as a part of orbital infiltration, but can be due to direct leukemic infiltration.⁴

Conjunctiva

The conjunctiva may be involved by hemorrhage (Fig. 64.2), infiltration (Fig. 64.3), or hyperviscosity, when the vessels are tortuous or comma-shaped. Conjunctival mass formation, though rare, can be the presenting sign in acute leukemia.³

Fig. 64.2 Conjunctival hemorrhages and infiltration in acute lymphoblastic leukemia.

Fig. 64.3 Conjunctival infiltration with leukemic cells (ALL).

Cornea and sclera

Being avascular, the cornea is not often involved in the leukemias, but it may be involved in herpes simplex or zoster in the immune-compromised child, or by other inflammatory disease. Corneal ulcers may be the presenting sign in acute leukemia⁶ and perilimbal infiltrates have been described in acute monocytic leukemia.⁷

Lens

Cataracts occur frequently in patients who have had total body irradiation, related to the total dose and to the rate and fractionation of administration.⁸ The use of steroids to treat graft-versus-host disease may cause or exacerbate cataracts.

Anterior chamber, iris and intraocular pressure

Most reported cases have been of relapse in ALL (Fig. 64.4) but, rarely, children present with a leukemic hyphema or hypopyon. In ALL, anterior segment relapse accounts for up to 2% of all relapses; it is very rare in AML.^4,9

Fig. 64.4 Anterior chamber relapse (ALL).

The infiltration is most likely to be blood-borne rather than CNS related⁹ and the relatively frequent occurrence of isolated anterior segment relapse supports the concept of the eye as a sanctuary site.¹⁰ Because of the blood–eye barrier, chemotherapeutic agents do not penetrate the eye so well as at many other sites, allowing leukemic cells to survive, causing signs and symptoms after chemotherapy has stopped. Symptoms include redness, watering, photophobia, pain, and visual loss. The parents may notice changes in the shape or reactions of the pupil or in the color and appearance of the iris (Fig. 64.5). Leukemia accounts for 5% of pediatric uveitis³.

Fig. 64.5 Anisocoria and mild heterochromia (ALL).

Clinical findings are variable with iritis and hypopyon being the most common. Ciliary injection, keratic precipitates, anterior chamber cells, and flare are frequent. Posterior synechiae are unusual, but a grayish hypopyon streaked with blood is common.

Secondary glaucoma is common and is associated with corneal edema, pain, and redness.

The iris may be thickened diffusely (Fig. 64.6) or in the form of one or more nodules or a mass of variable size; the thickening of the iris obliterates the iris crypts and may give a rather featureless iris. The iris may also be thinned with loss of pigment (Fig. 64.7). The iris color may be changed, usually by a brownish discoloration. Rubeosis may occur. It is often the failure of standard treatment for uveitis that draws the ophthalmologist’s attention to the underlying leukemia. If in diagnostic doubt, perform anterior chamber paracentesis and iridectomy:⁹ a paracentesis alone may not be sufficient to give an accurate diagnosis. Pathologic studies show leukemic infiltration of the iris and trabecular meshwork,⁴ and the hypopyon consists of leukemic cells, necrotic tissue, and proteinaceous exudate. Leukemic cells may be difficult to find. Patients with glaucoma have leukemic obstruction of the outflow channels and episcleral vessels.

Fig. 64.6 Iris relapse with heterochromia, infiltrated left iris, and sluggish pupil reactions.

Fig. 64.7 Same patient as in Figure 65.6. After treatment with 2500 cGy there is iris transilluminance. The right eye had become affected.

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