Elsevier

Survey of Ophthalmology

Volume 65, Issue 2, March–April 2020, Pages 272-277
Survey of Ophthalmology

Clinical challenges
A lot of nerve

https://doi.org/10.1016/j.survophthal.2019.04.005Get rights and content

Abstract

A 71-year-old woman with a history of acute lymphoblastic leukemia presented with unilateral optic disc edema. Laboratory evaluations for infectious, inflammatory, and neoplastic etiologies were negative. Magnetic resonance imaging of the orbits with and without contrast demonstrated enhancement and thickening of the right optic nerve with mild stranding of the intraconal fat. She underwent three large-volume lumbar punctures, all of which were negative for malignancy. An optic nerve biopsy was ultimately performed, demonstrating malignant cells on immunohistochemical staining. This case illustrates a rare case of biopsy-proven leukemic infiltration of the optic nerve head as the presenting sign of leukemic relapse despite a negative systemic workup. Leukemic infiltration should be considered in the differential diagnosis for cases of acquired disc edema, especially in patients with a past medical history of leukemia.

Section snippets

Case presentation

A 71-year-old woman presented with two weeks of several episodes of transient vision loss in the right eye lasting 5 seconds associated with right-sided scalp tenderness, right-sided headache, and pain with eye movements. Her past medical history included Philadelphia chromosome-positive lymphoblastic leukemia in remission for three years, currently on dasatinib maintenance therapy and treatment for hypertension, osteoporosis, and depression. Her past ocular history included moderate myopia,

Comments by Drs. Srinivasan and Murchison

The list of differential diagnosis for unilateral optic disc edema is long and illustrious. A careful history and examination often provide important clues to the underlying diagnosis. Timely diagnosis and management in these cases has not just visual but systemic implications as well.

The causes of unilateral optic nerve head edema can be broadly divided into the following categories: vascular (arteritic vs nonarteritic anterior ischemic optic neuropathy), inflammatory (typical vs atypical

Comments by Drs. Srinivasan and Murchison

For possible GCA, laboratory evaluation should be performed and include complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein. Elevated C-reactive protein is more sensitive than ESR for detection of GCA as a small percentage of patients with biopsy-proven GCA have normal ESR.14 Thrombocytosis can also be a useful feature that complements ESR and C-reactive protein.2

Also, in this patient, with the history of leukemia, an infiltrative optic neuropathy must be

Case report (continued)

Initial laboratory evaluation revealed an ESR of 23 mm/hr and C-reactive protein of 0.29 mg/L. MRI of the orbits with and without contrast demonstrated enhancement and thickening of the right optic nerve with mild stranding of the intraconal fat (Fig. 3). She was admitted to the hospital for an expedited workup for presumed atypical optic neuritis.

Subsequent laboratory testing was negative for syphilis, tuberculosis, sarcoidosis, and Lyme disease. Antinuclear antibodies were positive with a

Comments by Drs. Srinivasan and Murchison (continued)

An optic neuritis pattern on MRI combined with lack of sustained improvement with steroids rules out an inflammatory etiology. The CSF findings, though not conclusive, cannot be ignored, especially in a patient with a history of leukemia. Our diagnosis at this point is leukemic infiltration of the optic nerve, unless proved otherwise. Although not common, there have been reports of isolated leukemia recurrence in the optic nerve, especially in patients with acute lymphoblastic leukemia. In

Case report (continued)

She developed a new relative afferent pupillary defect in the right eye, submacular fluid, scattered retinal dot-blot hemorrhages, and delayed arterial to venous transit on fluorescein angiography, consistent with a CRVO (Fig. 4). Repeat MRI revealed continued right optic nerve enhancement, right superior ophthalmic vein enlargement, and significant right orbital apex congestion. She underwent a third large-volume lumbar puncture which was negative for cytologic malignancy. Peripheral blood

Comments by Drs. Srinivasan and Murchison (continued)

In addition to optic neuropathy, this patient has also developed CRVO. This rapidly progressive clinical picture is consistent with malignancy. With systemic testing being negative, optic nerve biopsy is the only option that can help establish diagnosis at this point; however, there are risks associated with the procedure, including complete loss of vision in the affected eye, which should be clearly explained to the patient. Also, with prior steroid administration, the biopsy results may not

Case report (concluded)

Despite the unexceptional CSF studies and lack of other CNS involvement, there was high concern for leukemic infiltration, and she underwent biopsy of the right optic nerve. Pathology demonstrated clusters of B-lymphoblasts expressing CD10 and CD79 (Fig. 6) and the immunophenotype of her peripheral blood performed three years prior. She was subsequently treated with methotrexate, dasatinib, and rituximab for CNS leukemic relapse. Her eye pain resolved over the next few weeks. Optical coherence

Discussion

Leukemic infiltration of the optic nerve is rare, but has been documented in several case reports as the first sign of lymphoblastic leukemia or leukemic relapse.2, 13, 14, 15 Optic nerve involvement is regarded as equivalent to CNS infiltration, which can occur in 5-11% of patients who have attained remission of leukemia.3, 8 Systemic chemotherapy has poor CNS penetration, and furthermore, intrathecal chemotherapy may poorly penetrate the optic nerves due to poor CSF flow in the optic canal.14

Methods of literature search

The MEDLINE database was used for the literature review using the following search terms: “optic nerve infiltration”, “optic nerve leukemia”, “optic nerve biopsy”, “central retinal vein occlusion and leukemia”, “central nervous system malignancy and lumbar puncture”, “lumbar puncture sensitivity in leukemia”, “central nervous system leukemia relapse”, and “dasatinib optic neuropathy.” Articles were limited to English only. There were no date exclusions.

Acknowledgments

The authors would like to thank Dr. Mays El-Dairi (Department of Neuro-ophthalmology, Duke Eye Center) and Dr. Alan Proia (Department of Pathology, Duke Eye Center) for their clinical expertise in the diagnosis and management of this patient.

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Financial Interest Statement: The authors have no financial disclosures.

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