Case number: 136

The disc hides the answer

Author: Lucas Viana

This 44 year-old woman presents with recurrent visual loss in the right eye, in the setting of hypertension and T-cell acute lymphoblastic leukemia diagnosed in 2005, successfully treated with chemotherapy.

She had recurrence of leukemia in June 2015 and was again treated with chemotherapy, including 8 preventive intrathecal injections as part of the treatment protocol. She developed fever with neutropenia in December 2015, and was found to have an infected central venous catheter, which was eventually removed. Lumbar puncture didn’t show leukemic cells in the cerebrospinal fluid. Ten days later, she developed pain OD, with decreased vision OD the next day. She was diagnosed with right optic neuritis and treated with high dose intravenous steroids for 5 days followed by oral prednisone, with complete resolution of visual symptoms. Her last preventive intrathecal injection was given 3 days after onset of visual symptoms.

She noted painless decreased vision OD 1 month later. Vision was 20/60 OD and 20/25 OS, with color 8.5/10 OD and 10/10 OS. She had a right relative afferent pupil defect. Her fundus findings are shown below.

case136_OD1 case136_OS1

MRI showed subtle enhancement of the right optic nerve.

The next day vision was 20/200 OD and 20/20 OS, with color 1/10 OD and 10/10 OS. Confrontation visual field showed a central visual field defect OD and normal visual field OS. There was a right relative afferent pupil defect and similar fundus findings. Macular OCT is shown.

Roldan, Andrea

She was treated with high dose intravenous steroids for 3 days followed by oral prednisone. Five days later vision was 20/40 OD and 20/20 OS, with color 9/10 OD and 10/10 OS, improvement of the visual field defect OD and resolution of macular edema OD in the OCT. Lumbar puncture didn’t show leukemic cells in the cerebrospinal fluid.

She presented 1 week later with subacute decreased vision OD. She was again treated with pulse intravenous steroids, without improvement. MRI showed bilateral lacrimal gland enlargement with diffuse enhancement. Vision was NLP OD and 20/20 OS. There was a right relative afferent pupil defect and the rest of the examination OS remained normal. Fundus findings are shown.

case136_OD2 case136_OS2

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View Diagnosis

Leukemic infiltration of the optic nerve and retina

Fundus findings in the right eye during the second episode of decreased vision were consistent with venous stasis retinopathy, supported by OCT showing macular edema. Given her background, ocular infiltration by leukemia was the most likely diagnosis. However, cerebrospinal fluid was consistently negative for leukemic cells. Moreover, she was treated with preventive intrathecal chemotherapy prior to the initial episode of vision loss. The hematology team was reluctant to perform further treatment without confirmation of recurrence. Diagnostic vitrectomy was performed after the third episode of vision loss, with dry aspiration of vitreous samples followed by completion of vitrectomy and aspiration of the lesion emerging from the optic disc. Infection was ruled out by PCR in both samples, and cultures were eventually negative. Flow cytometry of the optic disc lesion showed 87.6% necrosis and 12.4% precursor-T cells, which was later confirmed by PCR showing T-cell receptor gene rearrangement. Systemic recurrence of leukemia was diagnosed soon after the ocular involvement was confirmed, and the patient died 4 months later.

Ocular involvement in leukemia was initially described by Liebreich in 1861, and is associated with a lower survival rate. It is the third most frequent extramedullary site of recurrence. Several ocular structures may be involved, with retinal hemorrhages representing the most common finding (1). Retinal involvement can also manifest as venous stasis retinopathy. Leukemic optic neuropathy is rare, and represents a visual emergency. This complication can occur even in remission, and has been increasing in frequency in recent years due to more effective chemotherapeutic treatments (2). The optic nerve is considered a sanctuary site, and leukemic infiltration may represent residual tumor not effectively treated by chemotherapy. One theory states that leukemic cells at the optic canal may act as a barrier that interrupts the smooth flow of cerebrospinal fluid, preventing access of chemotherapeutic agents to some portions of the optic nerve. Focal radiation therapy reduces the number of leukemic cells in the optic canal, which improves the flow of cerebrospinal fluid around the optic nerve, and allows more effective action of cytotoxic drugs (3). Flow cytometry of cerebrospinal fluid may assess in diagnosis, although it may be negative for leukemic cells despite optic nerve infiltration. A recent article describes optic nerve sheath biopsy as a safe and effective method to confirm leukemic optic nerve infiltration (4).


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