Bilateral optic neuropathy in Krukenberg tumor treated with FOLFOX plus nivolumab: a case report

A combination of FOLFOX and nivolumab is a first-line treatment for HER2-negative advanced gastric cancer, significantly improving survival. However, this regimen is associated with potential neurotoxicity. 5-Fluorouracil and oxaliplatin in FOLFOX have been linked to optic neuropathy, whereas nivolumab, an immune checkpoint inhibitor, may cause immune-related optic neuropathy. Although FOLFOX plus nivolumab provides considerable survival benefits, careful monitoring for ocular complications is essential. We report a case of bilateral optic neuropathy in a patient who received FOLFOX plus nivolumab. Despite discontinuation of chemotherapy and treated with high-dose corticosteroid pulse therapy, the patient's symptoms did not improve.

A 48-year-old woman with a Krukenberg tumor developed progressive bilateral visual impairment during treatment with FOLFOX plus nivolumab. Her ophthalmologic history included branch retinal vein occlusion in the right eye but no systemic diseases. She presented with bilateral central scotomas and visual field defects. On examination, best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/25 in the left eye, with bilateral optic disc swelling and hemorrhage. Fluorescein angiography confirmed optic disc leakage, and a visual evoked potential (VEP) test indicated axonal loss. Brain magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) ruled out metastatic disease, and autoimmune markers were negative. High-dose intravenous methylprednisolone was administered, and chemotherapy was discontinued. Despite initial stabilization, vision deteriorated, ultimately progressing to light perception in both eyes. Repeated steroid pulse therapy failed to improve outcomes.

This case highlights the potential for severe bilateral optic neuropathy associated with FOLFOX plus nivolumab, leading to irreversible vision loss. These findings suggest that close ophthalmologic monitoring is warranted in patients receiving FOLFOX plus nivolumab for early recognition of bilateral visual impairment. Further research is needed to elucidate the mechanisms and identify agents responsible for the development of optic neuropathy.