A 28-year-old woman with no prior ocular history presented with a 2-day history of bilateral vision loss, noticed initially upon waking and affecting her right eye more than the left. She had a past medical history of triple-negative, right-sided advanced breast cancer that was diagnosed 18 months prior. She initially underwent neoadjuvant chemotherapy with paclitaxel, carboplatin, pembrolizumab, doxorubicin and cyclophosphamide, followed by right-sided mastectomy with axillary lymph node dissection 8 months prior to presentation. A Positron Emission Tomography scan performed at the time of the surgery demonstrated no evidence of metastatic disease, and she was treated with adjuvant localized radiation spread over 15 fractions.

On further history, she endorsed bilateral retrobulbar pain with eye movements. She had no symptoms relating to intracranial hypertension such as headache, pulsatile tinnitus or transient visual obscurations. Physical examination revealed a best-corrected visual acuity of counting fingers at 3 feet OD and 20/80 OS. She had a grade 1 relative afferent pupillary defect OD, and both pupils had sluggish reactions to light. Extraocular movements were full, and she had no other cranial neuropathy, facial weakness, focal motor or sensory deficits, ataxia or meningismus. She had a normal intraocular exam, including no evidence of optic disc edema or pallor. Humphrey 24-2 visual field testing demonstrated bilateral generalized depression (Figure 1). Optical coherence tomography of the macula and peripapillary retinal nerve fiber layer were unremarkable.

Figure 1.

Top: Humphrey 24-2 visual field testing demonstrates bilateral generalized depression with mean deviation values of −26.76 OD and −19.83 OS. Bottom: Optical coherence tomography peripapillary retinal nerve fiber layer values are within the age-controlled range of normal.

Figure 1 Long description

The image contains multiple graphs and visual representations related to retinal nerve fiber layer (RNFL) thickness and neuro-retinal rim thickness for both eyes. The top section features RNFL thickness maps and deviation maps for the right eye (OD) and left eye (OS), with color-coded scales indicating thickness in micrometers. The middle section presents a table comparing various metrics such as average RNFL thickness, RNFL symmetry, rim area, disc area, average cup-to-disc (C/D) ratio, vertical C/D ratio, and cup volume for both eyes. The bottom section includes neuro-retinal rim thickness graphs and extracted horizontal tomograms for both eyes, showing the disc center coordinates. The RNFL thickness maps use a color scale from 0 to 350 micrometers to depict the thickness of the retinal nerve fiber layer around the optic disc. The deviation maps highlight areas of deviation from normal thickness. The neuro-retinal rim thickness graph compares the rim thickness around the optic disc for both eyes, with the green area representing the normal range. The extracted horizontal tomograms provide cross-sectional views of the optic disc. All values are approximated.

At this point, given her bilateral acute vision loss, pain with extraocular eye movements and young female demographic, an urgent contrast-enhanced MRI of the brain and orbits was ordered with a presumptive diagnosis of atypical optic neuritis. MRI revealed bilateral perineural enhancement of the intracanalicular segment of the optic nerves, in keeping with leptomeningeal disease (Figure 2). Intracranially, there were also multiple supratentorial and infratentorial nodular enhancing foci highly concerning metastatic disease. These lesions were new compared to an unremarkable CT head from 9 months prior. MRI spine revealed a linear, thick intradural extra-medullary enhancement layering the thecal sac from L1 to L4, concerning metastatic disease. A lumbar puncture followed, with CSF cytology demonstrating malignant cells with cytopathological features in keeping with breast cancer, confirming the diagnosis of leptomeningeal metastasis. The CSF did not contain oligoclonal bands. Systemic re-staging was performed, which revealed no metastasis outside the central nervous system (CNS). Palliative whole-brain and lumbar spine radiation were then initiated by her oncology team. An inflammatory workup revealed negative serum neuromyelitis optica and myelin oligodendrocyte glycoprotein antibodies, as well as a negative paraneoplastic antibody panel.

Figure 2.

Top: Axial post-contrast T1 fat-saturated magnetic resonance image shows leptomeningeal enhancement along the canalicular segments of the optic nerves (asterisk) and leptomeningeal enhancement along the cerebellar folia (arrows). Bottom: Coronal post-contrast T1 fat-saturated magnetic resonance image shows a right frontal parenchymal enhancing lesion (arrow) and leptomeningeal enhancement about the canalicular segments of the optic nerves (arrowheads).

Figure 2 Long description

The top image is an axial post-contrast T1 fat-saturated magnetic resonance image showing leptomeningeal enhancement along the canalicular segments of the optic nerves, marked by asterisks, and along the cerebellar folia, indicated by arrows. The bottom image is a coronal post-contrast T1 fat-saturated magnetic resonance image displaying a right frontal parenchymal enhancing lesion, pointed out by an arrow, and leptomeningeal enhancement around the canalicular segments of the optic nerves, highlighted by arrowheads.

This case highlights a rare presentation of bilateral acute vision loss as the initial symptom of leptomeningeal carcinomatosis from metastatic triple-negative breast cancer. Leptomeningeal carcinomatosis is characterized by infiltration of the pia mater, the arachnoid mater and the subarachnoid space by tumor cells from the primary site. ^{Reference Franzoi and Hortobagyi1} This can result in cranial neuropathies, myelopathy and intracranial hypertension. Leptomeningeal metastasis has been reported in breast cancer, lung carcinoma, malignant lymphoma, leukemia, gastric carcinoma, colorectal carcinoma and malignant melanoma. Several mechanisms of tumor cell invasion to the subarachnoid space are hypothesized including hematogenous spread, direct extension from a parenchymal lesion, direct or venous extension from bone and spread through the lymphatics. ^{Reference Hayat, Ehsan, Selhorst and Manepali2} Cranial nerves such as the optic nerve, abducens nerve, oculomotor nerve, facial nerve, vestibulocochlear nerve and vagus nerve can be affected in leptomeningeal metastasis. Although optic neuropathy is more commonly described in patients with known primary cancers, it is rare for it to manifest as the presenting sign of a metastatic cancer. ^{Reference Susac, Smith and Powell3}

While the acute vision loss and associated retrobulbar pain were suggestive of inflammatory optic neuritis, acute monocular painful vision loss and rapid vision loss associated with headaches from leptomeningeal carcinomatosis-associated optic neuropathy and normal appearing optic nerves at the time of presentation is very rare, and previously reported. ^{Reference McFadzean, Brosnahan, Doyle, Going, Hadley and Lee4} Vascular compromise to the optic nerve in leptomeningeal carcinomatosis has been one of the hypothetical causes of rapid visual loss. ^{Reference McFadzean, Brosnahan, Doyle, Going, Hadley and Lee4} Our patient’s MRI revealed enhancement of the intracanalicular segment of the optic nerves. The optic canal is narrow and fixed in size, making it particularly vulnerable to vascular and possibly to additional compressive insults.

In the literature, there have been many identified reports of unilateral vision loss secondary to metastases to the optic canal. However, acute bilateral vision loss with simultaneous involvement of both optic canals is extremely rare. Previous case series have described vision loss in the second eye weeks to months after the involvement of the first eye. ^{Reference Cantillo, Jain, Singhakowinta and Vaitkevicius5} The rate of vision loss with leptomeningeal carcinomatosis is variable, ranging from sudden-onset near-total vision loss to a gradual, slow progression. Our case is a rare presentation of simultaneous bilateral acute optic neuropathy secondary to leptomeningeal involvement of the optic canals as the first presenting symptom of metastatic disease with rapid, profound visual loss. On history, the patient had no other systemic symptoms at presentation. This case highlights leptomeningeal disease as a potential mimicker of acute atypical optic neuritis in patients with a past medical history of cancer.

The risk of CNS metastasis is higher in patients like ours with a triple-negative subtype of breast cancer (TNBC) and portends a worse prognosis, with a median survival time of 4–6 months. ^{Reference Zimmer6} Notably, TNBC lacks receptors for estrogen and progesterone, with minimal to no human epidermal growth factor receptor 2 (HER2) protein, and is the most aggressive form of breast cancer. Recent research has highlighted that HER2-low tumors (HER2-1+ and HER2-2+) may actually benefit from HER2-targeted therapies, although they have a worse prognosis compared to HER2-0 tumors. ^{Reference Sanomachi, Okuma and Kitadai7} In patients with leptomeningeal carcinomatous from breast cancer, TNBC is 3.5 times more represented than other types of breast cancer. Once CNS metastasis occurs, treatment may involve supplementing systemic chemotherapy with stereotactic radiosurgery or whole-brain palliative radiation, depending on the size and number of metastases. ^{Reference Zimmer6}

In summary, we present a case of a 28-year-old woman with a past history of localized TNBC cancer who developed acute, bilateral simultaneous vision loss and was found to have perineural metastasis involving both optic nerves at the optic canals. Our case highlights how metastatic disease can mimic optic neuritis and should be on the differential diagnosis for acute vision loss in any patient with a prior history of cancer.