Clinical Case Review of Bilateral Retinal Metastasis

Abstract

Bilateral retinal metastasis is a rare disease that represents less than 1% of ocular metastases. Additionally, the prevalence of ocular metastases overall is only 5% to 10%. It is uncommonly found due to the absence of a lymphatic system in the eye. Ocular metastasis is spread hematogenously and the retina only receives 5% of blood flow, contributing to the rarity of this condition. Retinal metastasis has been reported to mimic symptoms of retinitis which include watery eye discharge, conjunctival injection and pain with ocular movement which leads to a harder diagnosis. Treatment options for retinal metastasis include systemic chemotherapy, intravitreal chemotherapy, and plaque radiotherapy. However, despite treatment, retinal metastasis often has a poor prognosis. This is a case of a 65-year-old woman with a history of breast carcinoma status post mastectomy who initially presented with metastatic infiltration of the lung and liver. However, she later developed an interesting case of retinal metastasis, which presented as symptoms of retinitis and indicated widespread dissemination of an unknown primary neoplasm.

Case Presentation

A 65-year-old woman presented to the emergency department with 1 to 2 weeks of worsening lower abdominal pain and left-sided chest pain. She had a past medical history of left breast carcinoma Stage 1 ER positive, PR positive, and HER2 Neu negative. She underwent left mastectomy in 2014 with left axillary sentinel lymph node biopsy and right prophylactic mastectomy with reconstruction. She was status post 5 years of Arimidex, which she completed in 2019. Patient refused consideration for chemotherapy at that time, and her last follow-up visit showed no evidence of disease.

The patient stated that her chest pain was worse on the left side and increased with deep inspiration and palpation. She also complained of bilateral lower quadrant abdominal pain radiating to her low back. She endorsed nausea with no vomiting, fevers, chills, or diaphoresis. She stated she had been constipated for the past 1 to 2 weeks. She endorsed significant weight loss (100 lbs) over the last year. She reported she smoked for 15 years, 1 pack per day, but quit 15 years ago. She denied alcohol or drug use.

In the emergency department, she was afebrile, saturating 93% on 2 liters nasal cannula. Notable lab values were as follows: white blood cells 8.0 × 10⁹/L, hemoglobin 10.4 g/dL, potassium 3.4 mmol/L, creatinine 0.68 mg/dL, and lipase negative. Electrocardiogram demonstrated normal sinus rhythm. Urinalysis and troponin were negative. CT abdomen and pelvis showed multiple low-density hepatic lesions suggestive of metastatic disease, moderate to large fecal matter, and bilateral hip prosthesis, making interpretation of the film difficult. Chest CT angiogram demonstrated infiltrative consolidation in the left upper lobe with volume loss, likely due to lymphangitis carcinomatosis. There were also scattered lung nodules in the left upper lobe suggestive of left lung neoplasm. Her physical exam was positive for decreased breath sounds on the left side and a palpable left supraclavicular lymph node. She underwent a surgical biopsy of the left supraclavicular lymph node. Labs were significant for elevated CEA (219.4 ng/mL).

On the fourth day of admission, she complained of right eye pain, blurry vision, and pain with eye movement. Physical examination revealed edema, mild proptosis, conjunctival chemosis, and conjunctival injection, worse on the right side than left (Figure 1). Patient was started on bacitracin ointment and ceftriaxone due to concerns of orbital cellulitis. Ophthalmology was consulted, resulting in a fundoscopic exam and assessment suggestive of bilateral metastatic neoplastic lesion in retina of both eyes, more pronounced in the right than the left eye.

Figure 1.

Physical examination revealed edema, mild proptosis, conjunctival chemosis, and conjunctival injection, worse on the right side than the left.

Further imaging studies were obtained. MRI brain was suspicious for calvarial metastatic disease, and nodular thickening was noted along the posterior margin of the globe on the right, measuring up to 7 mm in the long axis dimension, consistent with funduscopic findings (Figure 2). MRI of the abdomen showed multiple nodules in the liver, suggesting metastases and nuclear medicine bone scan of the whole body suggested possible metastases in the hemithorax and bilateral femurs. Surgical pathology of the neoplasm stained positive for cytokeratin 7 and negative for cytokeratin 20. The findings argued against breast or pulmonary origin and favored origin from a gastrointestinal or pancreaticobiliary primary.

Figure 2.

Nodular thickening (red arrow) noted along the posterior margin of the globe on the right, measuring up to 7 mm in the long axis dimension suspicious for calvarial metastatic disease.

After several goals of care discussions, the decision was made by the patient and her family to pursue comfort measures only, and she was discharged home with home hospice. She unfortunately passed away within 2 weeks of discharge.

Discussion

Bilateral retinal metastasis is a rare condition due to the absence of a lymphatic system in the eye. ¹ The most common primary tumors to metastasize to the eye are from breast (47%), lung (21%), and the gastrointestinal tract (4%). ² Furthermore, metastasis of the eye is usually detected in the choroid (88%), iris (9%) and scarcely in the retina (<1%). ² Ocular metastasis is spread hematogenously, with the chorea receiving 85% of blood flow while the retina only receives 5%. Additionally, most are also found to be unilateral. ² Therefore, metastasis to the retina is rare, although tumor emboli have been reported within the lumen of retinal vessels in patients with retinal metastasis. ³ Spread to the retina begins with retinal nerve fiber and ganglion cell layers which are supplied by the retinal central artery. ²

Retinal metastasis has been shown to replicate symptoms of retinitis, as seen in our patient. Multiple cases report symptomatic findings that are similar in nature to viral retinitis.^4,5 Symptoms include watery eye discharge, conjunctival injection, and pain with ocular movement. Often, antimicrobial therapy is initiated to treat the viral symptoms, although, after the failure of treatment, further CT imaging or vitreoretinal biopsy led to the diagnosis of retinal metastasis.^4,5 In some cases, patients may have no other symptoms. ⁶ The survival rate of patients with retinal metastasis is reportedly poor in most cases, further indicating widespread dissemination to organs due to end-stage disease.^3,5

Treatment options for retinal metastasis include systemic chemotherapy, intravitreal chemotherapy, and plaque radiotherapy. In addition, surgical excision or enucleation of the eye may also be considered. ⁵ Complete disappearance of retinal metastasis has been observed only once with the use of chemotherapy in a pediatric case. ⁶ Thus, retinal metastasis is important to include in the differential diagnosis, especially for patients with a history of treated primary cancer.

Conclusion

In conclusion, hematogenous spread to the retina is a rare site of metastasis, especially due to the minimal blood flow received through the retinal central artery. The most common primary source is from the breast and then the lungs. Symptoms of retinal metastasis tend to mimic viral retinitis therefore it is imperative to take retinal metastasis into consideration at the time of treating patients with cancer.