Check Your Assumptions at the Door

A 74-year-old female with metastatic carcinoid tumor presented with acute painless vision loss in the right eye. In the four weeks preceding vision loss she had episodic diplopia. Over the past few days, she noticed a gray shade coming down over her right eye. Her carcinoid tumor was diagnosed in 2019 with brain metastases identified in 2021. She had undergone whole brain radiation and treatment with ipilimumab and nivolumab. Her current medications were nivolumab, gabapentin, and omeprazole. Visual acuity was 20/40 and 20/25 in the right and left eyes, respectively.

“Check Your Assumptions at the Door” Mazin Elsarrag 1, Marielle Mahan 1, Shefali Sood 1, Lakshmi Shree Kulumani Mahadevan 1, Benjamin Osborne 1 1 MedStar Georgetown University Hospital History & Exam: A 74-year-old female with metastatic carcinoid tumor presented with acute painless vision loss in the right eye. In the four weeks preceding vision loss she had episodic diplopia. Over the past few days, she noticed a gray shade coming down over her right eye. Her carcinoid tumor was diagnosed in 2019 with brain metastases identified in 2021. She had undergone whole brain radiation and treatment with ipilimumab and nivolumab. Her current medications were nivolumab, gabapentin, and omeprazole. Visual acuity was 20/40 and 20/25 in the right and left eyes, respectively. Her pupils were equal, round, and reactive to light. Ishihara color testing was decreased to 4/10 in the right and 7/10 in the left. Fundus exam was notable for mild right optic nerve (ON) head elevation, and a normal appearing left nerve. Visual fields revealed a right eye superior altitudinal defect and a homonymous left inferior quadrantanopia. Two days later, her vision decreased to light perception in the right eye. Examination revealed a right relative afferent pupillary defect and a swollen and pale right ONH. Review of systems was notable for jaw claudication but she denied headache and arthralgias. MRI with contrast obtained on the day of presentation revealed enhancement of the right ON and bilateral ON sheaths and stable metastatic brain lesions. There was concern for carcinomatous leptomeningeal spread to the optic nerves. Lumbar puncture cytology was negative. Laboratory results were notable for mildly elevated ESR (43 mm/hr), thrombocytosis, and a normal Creactive protein. The patient was started on intravenous methylprednisolone 1 gram daily. Temporal artery ultrasound (2 days after admission) revealed hypoechoic wall thickening bilaterally. Temporal artery biopsy (3 days after admission) demonstrated severe arteritis. The patient completed 3 days of IV methylprednisolone followed by oral steroids. Nivolumab was discontinued. Her vision remained unchanged one week later. Financial Disclosures: Mazin Elsarrag: No; Marielle Mahan: No; Shefali Sood: No; Lakshmi Shree Kulumani Mahadevan: No; Benjamin Osborne: Dr. Benjamin Osborne is on the speaker bureau for Genentech Roche, the manufacturer of tocilizumab (Actemra). Grant Support: None. 22 | North American Neuro-Ophthalmology Society “Check Your Assumptions at the Door” Answer Final Diagnosis: Arteritic anterior ischemic optic neuropathy secondary to immune checkpoint inhibitor induced giant cell arteritis. Summary of Case: This is a case of atypical biopsy-proven GCA triggered by treatment with nivolumab, an immune checkpoint inhibitor (ICI). The patient’s exam findings of a swollen and pale optic nerve were typical for arteritic anterior ischemic optic neuropathy (AAION), however, given the patient’s painless vision loss, the differential diagnosis included compressive or infiltrative optic neuropathy, non-arteritic anterior ischemic optic neuropathy, and progression of her metastatic disease. There is overlap in both exam and imaging findings of ICI induced optic neuritis and AAION from ICI induced GCA, and these conditions may be difficult to distinguish (3, 4, 5). The mechanism of GCA in these patients is likely related to unregulated immune potentiation and activation (5). There does not appear to be a difference between symptoms or exam findings in patients with ICI associated GCA compared to other patients with GCA (3) The absence of a significantly elevated ESR and lack of headache decreased the initial index of suspicion of giant cell arteritis. A systemic review of the association between inflammatory markers and GCA found that ESR may be normal in 4 to 15% of patients with GCA (1), though the proportion is estimated to be higher in other studies (2). Additionally, patients with underlying malignancy may have elevated ESR/CRP, decreasing the usefulness of these markers in diagnosing ICI-associated GCA unless a baseline is known. Struggle/Dilemma of the Clinical Presentation Description: There were multiple conditions that were felt to be more likely than GCA that could have caused vision loss from optic neuropathy. Additionally, the patient did not have significant headache or temporal artery tenderness, and her ESR was only minimally elevated, decreasing the index of suspicion for GCA. Her MRI findings were also not specific for GCA and initially led us to believe the patient had leptomeningeal carcinomatosis and metastatic disease to the optic nerve. Keywords: Giant cell arteritis, Arteritic ischemic optic neuropathy, Metastatic carcinoma, Optic disc edema References: None provided. Contact Information: Mazin Elsarrag, [e-mail] 2023 Annual Meeting Syllabus | 23