A 33-year-old woman was diagnosed with acute B-lymphoblastic leukemia (BCR/ABL-P190+) in 2019 and underwent allogeneic hematopoietic stem cell transplantation (HSCT) following three cycles of chemotherapy. Post-transplant, she received immunosuppressive therapy to prevent graft-versus-host disease, and the leukemia entered complete remission. In 2021, she presented with rapid loss of visual acuity and eye pain in both eyes for 10 days. Her visual acuity was 20/200 in the right eye (RE) and light perception in the left eye (LE). The pupillary light reflex was weaker than normal bilaterally. Ophthalmoscopy revealed bilateral optic disc edema and tortuous retinal vessels. Automated visual field testing identified blind spot enlargement with a ring scotoma in RE, and the LE could not be examined because of low vision. MRI showed demyelination of the cerebral white matter and thickening of the bilateral optic nerves without enhancement (Fig. 1). Hematologic and cerebrospinal fluid tests for infectious and inflammatory etiologies were negative results (including AQP4 antibodies, MOG antibodies, CRMP5 antibodies, etc.). There were no signs of CNS involvement other than the optic nerve. She declined an optic nerve biopsy. Suspecting isolated ocular relapse of leukemia causing bilateral optic neuritis, she received an intrathecal injection of dexamethasone (5 mg), which alleviated ocular pain but did not improve vision. She refused further treatment and was subsequently treated at another hospital for optic neuritis with high-dose methylprednisolone pulse therapy, which restored vision to 20/20 in both eyes. Subsequently, she had an intermittent visual loss, which was restored each time after hormone therapy at other hospitals. Her leukemia remained in remission during the period.

leukemic occult infiltrative optic neuropathy phase. A. Orbital MRI showed bilateral thickening of the optic nerves. B. Fundus photography revealed bilateral optic disc edema. C. Optical coherence tomography indicated bilateral optic disc edema. D. Automated visual field testing (24 − 2 SITA Fast pattern deviation) demonstrated blind spot enlargement with a ring scotoma in RE

By January 2023, she noticed vision loss and hormone therapy was ineffective. The corrected visual acuity was 20/400 in RE and 20/25 in LE, with a relative afferent papillary defect in RE. Ophthalmoscopy revealed a pale optic disc and thin arteries. The visual evoked potential (VEP) showed prolonged P100 latency bilaterally, a normal P100 amplitude, and reduced amplitude on LE compared with RE. CSF examination remained unremarkable. However, she found hormone therapy was ineffective. Six months later, she presented to our hospital with visual acuity of light perception in RE and 20/40 in LE. MRI showed bilateral thickening and enhancement of the optic nerves and cerebral white matter, with abnormal signals and soft meninges. CSF analysis remained normal. Her right optic nerve appeared atrophied. VEP revealed no waveform in RE, while LE showed near-normal P-VEP latency and reduced amplitude at high spatial frequencies. She was diagnosed with isolated ocular relapse and leukemic infiltrative optic neuropathy. Orbital radiotherapy was recommended, but she did not perform it. She received intrathecal injections of chemotherapeutic agents (cytarabine 30 mg, methotrexate 10 mg and dexamethasone 5 mg) and her vision stabilized. She then underwent regular intrathecal injections with no improvement in vision in both eyes.

In early 2024, the patient returned for right eye proptosis with pain for 10 days. The visual acuity was no light perception in RE and 20/40 in LE. On examination, RE protruded markedly with RAPD+. The proptosis was 22 mm in RE and 19 mm in LE. MRI showed bilateral optic nerve infiltration, prominent on the right side, and multiple abnormal signals with nodular enhancement in both cerebral hemispheres (Fig. 2). The CSF contained 41.3% abnormal primitive cells, some suspicious tumor cells on pathology. She was diagnosed with the progression of leukemic infiltrative optic neuropathy. Three weeks later, her vision in both eyes decreased to no light perception. On fundus examination, the optic discs in both eyes were elevated, hemorrhages were visible in the right retina and the optic nerve was atrophied in LE (Fig. 2). Several months later, she died of leukemic multisystem involvement.

leukemic infiltrative optic neuropathy phase. A. Orbital MRI showed bilateral optic nerve infiltration, more prominent on the right side. B. Fundus photography revealed the optic discs in both eyes were elevated, hemorrhages were visible in the right retina and the optic nerve was atrophied in LE. C. Optical coherence tomography indicated the disappearance of optic disc edema bilaterally and decreased blood vessels in the left optic disc compared to the previous examination. D. Automated visual field testing (24 − 2 SITA Fast total deviation) demonstrated a tubular visual field in both eyes (out of the MD threshold)