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Woman reports acute painless vision loss in left eye

One month before presentation, the patient noticed a subtle retro-orbital pain on the left side.

Issue: August 10, 2014

ByKendra A. Klein, MD

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A 64-year-old woman was seen at the ophthalmology clinic with a 1-day history of decreasing vision in her left eye. She reported that throughout the preceding 24 hours, she noted increasingly blurred vision in her left eye at both distance and near. She described the blurred vision as looking through a “veil.” She denied pain, diplopia, photophobia, flashing lights or floaters. She denied constitutional symptoms including headache, weakness, dizziness, weight loss, fevers, jaw claudication, scalp pain, myalgias, arthralgias or rashes.

History

The patient denied having an ocular history and reported that her last routine eye exam was 1 year before presentation. She had a medical history of hypothyroidism, for which she took daily levothyroxine. She denied all other medical conditions, including hypertension, diabetes and cancer, and denied prior surgeries. She was a nonsmoker and denied alcohol or drug use. She was divorced and lived alone with two grown children living locally.

On further questioning, she reported that 1 month before presentation, she began noticing a subtle retro-orbital pain on the left side. She described the pain as a vague, dull pressure sensation that would last approximately 10 minutes and then completely subside. The pain was unrelated to eye movement and occurred approximately three to four times a day. She had no other symptoms at the time. She was seen at a local emergency department and found to have a visual acuity of 20/20 in both eyes. She was sent home with artificial tears. She was set up with a follow-up community ophthalmologist but felt that the pain subsided during this time.

Examination

On initial examination, the patient’s vision was 20/20 in the right eye and hand motions in the left eye. She had a relative afferent pupillary defect in the left eye. IOPs were normal. Confrontation visual fields were full and color vision was normal in the right eye. She had proptosis of approximately 1 mm of the left eye and no restriction of extraocular movements. Anterior segment examination was notable only for moderate nuclear sclerotic cataracts in both eyes. Dilated fundus exam was unremarkable. The optic nerves were pink and the margins were sharp in both eyes.

Visual fields were full in the right eye and globally depressed in the left eye. Optical coherence tomography retinal nerve fiber layer imaging, including ganglion cell analysis, showed no abnormalities. The patient was admitted for further work-up and started on empiric steroids with 1 g of intravenous methylprednisolone.

Physical examination revealed a 3-cm mass on the right breast at the upper outer quadrant. The left breast had a retroareolar mass with inversion of the nipple. The mass was fixed to the underlying chest wall and overlying skin. There were enlarged mobile axillary lymph nodes on both sides. The patient was further questioned about her medical history. At this point, she recalled having discovered a breast lump 10 years prior. Based on outside hospital records, she was subsequently diagnosed with breast cancer and underwent wide local excision with axillary node sampling. She did not require adjuvant chemotherapy or radiation at the time. She was lost to follow-up until 3 years later, at which time a repeat mammogram showed local recurrence. It was recommended that she undergo mastectomy, which she declined. She was started on an aromatase inhibitor and was again lost to follow-up until presentation.

What is your diagnosis?

Rapid painless vision loss

Based on the rapid painless vision loss and given the history of recurrent breast cancer, a complete work-up, including a complete metastatic work-up, was ordered.

Laboratory studies including TSH/free T4, ESR/CRP, RPR/FTA-ABS, ACE, ANA, Lyme C6 antigen and PPD were all negative. MRI of the brain and orbits with gadolinium and fat saturation (Figure 1) showed a heterogeneously enhancing mass overlying the left sphenoid wing extending superiorly and posteriorly to cover the frontal and temporal cortices, with extension into the left cavernous sinus and left orbital apex, causing compression at the orbital apex of the adjacent cortex. Initially, it appeared as if the mass had a dural tail. There was extensive edema and a 6-mm rightward midline shift, with associated uncal herniation and compression of the midbrain. There was also 7-mm tonsillar herniation through the foramen magnum. There was subtle asymmetric proptosis of the left globe with enhancement of the intraconal fat surrounding the optic nerve. Initially, it was believed that these findings could represent an aggressive, atypical meningioma, metastatic disease or metastasis to a pre-existing meningioma.

Figure 1. MRI of the brain and orbits with gadolinium and fat saturation. Right: Axial T1-weighted gadolinium enhanced image shows extension of the mass into the left cavernous sinus and left orbital apex. There is subtle asymmetric proptosis of the left globe with enhancement of the intraconal fat surrounding the optic nerve. Initially, it appeared as if the mass had a dural tail. Left: Axial T2-weighted gadolinium enhanced image shows extensive hyperintensity, representing edema, seen in the periventricular deep subcortical white matter involving the left frontal and temporal lobes with associated mass effect onto the lateral ventricles.

Images: Klein K

Figure 2. CT chest/abdomen/pelvis/cervical spine with oral and rectal contrast. A. A partially calcified soft tissue mass is seen superiorly in the left retroareolar breast, suspicious for local recurrent breast cancer. B. Multiple liver lesions may reflect simple cysts vs. liver metastases. C. Multiple sclerotic lesions throughout the cervical spine involving C2 through C7, concerning for metastatic disease. The vertebral body height is preserved without evidence of acute fracture.

CT imaging of the cervical spine and chest, abdomen and pelvis showed soft tissue masses measuring up to 1.2 cm in the right breast and right axilla. A partially calcified soft tissue mass was seen superiorly in the left retroareolar breast, suspicious for local recurrent breast cancer. Opacities were seen in the anterior right middle lobe of the lung and liver, which could have represented cysts, metastases, or areas of focal inflammation or infections. There were multiple sclerotic lesions noted in the spine, including in the cervical and thoracic vertebral bodies, right and left ribs, pelvis and femoral neck (Figure 2).

The neurosurgery team recommended a biopsy of the intracranial mass and tumor debulking. They performed a left frontotemporal craniotomy for partial removal of the brain mass. During the resection, they found the mass to be easily dissected from the dura but firmly attached to the brain parenchyma. The mass was noted to be extremely fibrous and firm. They debulked and sampled the mass but did not remove it entirely. The tumor encased the optic nerve and was left adherent, to be treated with radiation. Fresh tissue from the left frontotemporal mass showed a neoplasm with glandular morphology, consistent with a primary ductal breast adenocarcinoma. Immunochemistry staining of the mass was positive for estrogen receptor (Figure 3).

Figure 3. Biopsy specimen from left frontotemporal mass. Neoplasm with glandular structures lined by minimally atypical cells within a dense fibrotic stroma consistent with ductal breast adenocarcinoma primary. Immunohistochemistry analysis for estrogen receptor shows positive staining.

Differential diagnosis

The differential diagnosis of acute unilateral vision loss and a normal dilated fundus exam includes demyelinating conditions such as retrobulbar optic neuritis and neuromyelitis optica; inflammatory disorders including giant cell arteritis and thyroid eye disease; pituitary apoplexy; vascular abnormalities such as posterior ischemic optic neuropathy and ophthalmic-carotid artery aneurysm; neoplasms such as optic nerve sheath meningioma, optic nerve glioma and metastases; infiltration such as tuberculosis and sarcoidosis; and infections such as Lyme disease and syphilis.

Retrobulbar optic neuritis typically occurs in younger patients and may be associated with periorbital pain worsened by eye movement, and the patient had no spinal cord findings to suggest neuromyelitis optica. Giant cell arteritis must always be considered on the differential diagnosis for acute vision loss in the elderly, but the lack of classic symptoms and normal ESR and CRP argued against this. The patient did not have the characteristic bilateral slowly progressive proptosis and eyelid retraction characteristic of thyroid eye disease. She had no systemic symptoms to suggest lupus, and she had no preceding trauma, surgery or hypotension to suggest posterior ischemic optic neuropathy. There was no anterior chamber or vitreous cell on exam or neuroretinitis, which can be seen in infiltrative and infectious etiologies. In this case, the notable history of breast cancer, the physical exam findings of breast nodules and lymphadenopathy, and the MRI findings in the brain and orbit pointed toward neoplastic-related optic neuropathy, which was confirmed on pathology.

Discussion

Breast cancer is the most common cancer in women in the United States, and it is the second most common cause of cancer-related mortality. Favorable survival outcomes can be achieved with early detection via screening mammography and by use of adjuvant systemic therapy including chemotherapy, hormone therapy and HER2-targeted therapy to eliminate micro-metastases after surgery. Despite these advances, approximately 30% of patients with breast cancer will develop metastases, and up to 10% of patients with breast cancer present with metastatic disease at the time of diagnosis.

Breast cancer is the second most common cause of brain metastases and typically occurs late in the natural history of breast cancer. Up to 10% to 16% of all patients with metastatic disease will develop symptomatic brain metastases, and this increases to 30% when subclinical cases are included. The median time from diagnosis of breast cancer to central nervous system metastases is 33 months.

Patients with brain metastases rarely present solely with a visual disturbance. Rather, the majority of patients present with headache, seizure, or alterations in cognition, mental status or behavior. Brain metastases in breast cancer are associated with estrogen receptor negativity, HER2 overexpression, high tumor grade and large tumor volume of extracranial metastatic disease.

The prognosis for breast cancer patients with brain metastases is poor. Common prognostic markers affecting the survival of patients with brain metastases include age, performance status, systemic tumor burden and breast cancer subtype. Patients with brain metastases treated with palliative care alone have a median survival of 1 to 2 months. In patients treated with whole brain radiotherapy, survival increases to 3 to 4 months. Patients with oligometastatic disease treated with neurosurgical resection and radiosurgery with or without whole brain radiotherapy have an overall survival of approximately 9 to 10 months.

Correct diagnosis of an optic nerve metastasis may be impeded by its low incidence and its clinical and radiologic similarities to other more common optic nerve tumors, such as optic nerve sheath meningiomas. Optic nerve sheath meningiomas constitute one-third of all primary optic nerve tumors, following glioma. Like metastases to the optic nerve, these tumors typically have female predominance and are usually unilateral. Clinical features, such as progressive vision loss and exophthalmos, may be similar in both metastasis and meningioma. Dilated fundus exam may help in differentiation: Metastatic disease progresses so rapidly it will cause no fundus changes or cause acute hemorrhages and vessel thrombosis, whereas meningioma will cause signs of congestion and atrophy from slowly progressive growth.

Interestingly, the risk of developing a meningioma after having breast cancer nearly doubles. Radiologically, optic nerve sheath meningiomas and optic nerve metastases are similar. Features including the characteristic “tram-track” sign or central optic nerve lucency seen on contrast-enhanced CT of an optic nerve sheath meningioma could also be seen in metastatic disease. MRI is potentially more helpful. Optic nerve sheath meningiomas can be isointense or hypointense on T1-weighted imaging and isointense or hyperintense on T2-weighted imaging. Metastatic lesions, on the other hand, are usually isointense or hyperintense on T1-weighted images and hypointense on T2-weighted images. These similarities necessitate tumor biopsy and immunohistochemical examination to ensure an accurate and conclusive diagnosis.

Follow-up

Given the extent of dural-based brain disease and widespread systemic metastases, the patient was scheduled to commence palliative whole brain radiation therapy and palliative radiation therapy to her left hip, where she was found to have extensive sclerotic disease. After the surgical debulking procedure and treatment with intravenous and oral steroids, her vision significantly improved on follow-up examination to 20/25 in both eyes and exam was notable for mild disc pallor in the left eye.