Devine Intervention

A 30 yo woman presented to the comprehensive ophthalmology clinic with bilateral decreased vision. She had no prior ocular history. Her medical history was notable for breast cancer (diagnosed 1 year prior), treated with radiation, chemotherapy, lumpectomy, and pembrolizumab (completed 8/9 planned infusions). She described progressive vision loss in both eyes over the 2 weeks with light sensitivity, pain with eye movements, and diminished color vision. Her best corrected visual acuity was 20/500 in the right eye and count fingers at 3' in the left eye. No APD. Confrontation visual fields were notable for dense constriction in the right eye and temporal field loss in the left eye. The dilated funduscopic exam was normal. She was sent to the emergency department for an expedited work-up. MRI brain and orbits with and without contrast revealed T2 signal and enhancement along the optic chiasm, tracts, and prechiasmatic optic nerves (radiology images 1-4 ). There was no evidence of demyelinating lesions. Lumbar puncture and CT chest/abdomen/pelvis were unremarkable with no metastatic or systemic inflammatory process identified. A diagnostic procedure was performed.

“Devine Intervention” Letitia Pirau 1, Wayne Cornblath 1, Lindsey De Lott 1, Sangeeta Khanna 1, Tatiana Deveney 1 1 University of Michigan History & Exam: A 30 yo woman presented to the comprehensive ophthalmology clinic with bilateral decreased vision. She had no prior ocular history. Her medical history was notable for breast cancer (diagnosed 1 year prior), treated with radiation, chemotherapy, lumpectomy, and pembrolizumab (completed 8/9 planned infusions). She described progressive vision loss in both eyes over the 2 weeks with light sensitivity, pain with eye movements, and diminished color vision. Her best corrected visual acuity was 20/500 in the right eye and count fingers at 3’ in the left eye. No APD. Confrontation visual fields were notable for dense constriction in the right eye and temporal field loss in the left eye. The dilated funduscopic exam was normal. She was sent to the emergency department for an expedited work-up. MRI brain and orbits with and without contrast revealed T2 signal and enhancement along the optic chiasm, tracts, and prechiasmatic optic nerves (radiology images 1-4 ). There was no evidence of demyelinating lesions. Lumbar puncture and CT chest/abdomen/pelvis were unremarkable with no metastatic or systemic inflammatory process identified. A diagnostic procedure was performed. Financial Disclosures: Letitia Pirau: No; Wayne Cornblath: No; Lindsey De Lott: NIH grant; Sangeeta Khanna: No; Tatiana Deveney: No Grant Support: None. 2024 Annual Meeting Syllabus | 41 “Devine Intervention” Answer Final Diagnosis: Neuromyelitis Optica Spectrum Disorder After Pembrolizumab Treatment (In The Setting of Breast Cancer) Summary of Case: Our patient presented with a rare presentation of neuromyelitis optica spectrum disorder (NMOSD) induced by pembrolizumab treatment. Serum testing confirmed the diagnosis as initial serum AQP4 titer was 1:1000. While AQP-4 antibody testing was pending, she was treated with a 5-day course of methylprednisolone 1g IV daily and discontinued pembrolizumab. However, her visual acuity declined OD to hand motion. Therefore, plasmapheresis (PLEX) was pursued for 7 sessions. Three months post-treatment, her BCVA was 20/20 OU. Her follow-up titer 2 months post-treatment was 1:100. There are several possible explanations for her presentation: 1.) NMO disease unrelated to breast cancer or pembrolizumab, 2) Pembrolizumab induced optic neuritis with false positive NMO, 3) Paraneoplastic optic neuritis related to breast cancer, or 4) Pembrolizumab induced NMOSD. We suspect the last is the most likely explanation given significant recovery and improving titers correlating with the discontinuation of pembrolizumab. There have only been nine reported cases of NNMOSD triggered by an immune checkpoint inhibitor (ICI) (1, 6). ICI monoclonal antibodies target cytotoxic T-lymphocyteassociated protein-4 or programmed-cell-death receptor-1 to inhibit T lymphocytes (2, 3)-- possibly secondary to “unmasking of a predetermined paraneoplastic condition” related to the underlying cancer (2). Symptoms generally occur about 2-16 weeks after treatment but may occur as far out as 1 year (4). With a prednisone taper, she had a complete recovery after completing PLEX. In contrast, the previously reported cases in the Hirano et. al. review were associated with only partial recovery with steroids and PLEX (1). Based on prior literature on neurologic manifestations of ICI toxicity (meningitis, myasthenia gravis, myositis, peripheral neuropathy) guidelines suggest prompt discontinuation of the immunotherapy, as well as steroids (8). Case reports on pembrolizumab-induced optic neuropathy have documented the use of long-term treatments including rituximab, infliximab, IVIG, and mycophenolate (9). Struggle/Dilemma of the Clinical Presentation Description: Given the rare incidence of NMOSD secondary to ICI, it was unknown what was the best long-term treatment strategy. Prior cases have used rituximab for further immunosuppression after high-dose corticosteroids. In this case, due to her improving AQ4+ titers and clinical recovery, the decision was made with neuro-immunology to observe after receiving plasmapheresis. Keywords: Optic chiasm, Optic neuritis, Magnetic resonance imaging (MRI) References: Hirano, S., Kojima, A., Nakayama, Y., Takeda, T., Kishimoto, T., Takahashi, T., Kuwabara, S., & Mori, M. (2022). A case report of neuromyelitis optica spectrum disorder induced by pembrolizumab treatment for lung adenocarcinoma: A clinical and immunohistochemical study. BMC Neurology, 22(1). https://doi.org/10.1186/s12883-022-02987-6, Nasralla, S., & Abboud, H. (2020). Is neuromyelitis optica without AQP4-IGG a T-cell-mediated disease? insights from checkpoint inhibitor immune-related adverse events. Multiple Sclerosis and Related Disorders, 46, 102451. https://doi.org/10.1016/j.msard.2020.102451, Wilson, R., Menassa, D. A., Davies, A. J., Michael, S., Hester, J., Kuker, W., Collins, G. P., Cossins, J., Beeson, D., Steven, N., Maddison, P., Rinaldi, S., Jacob, S., & Irani, S. R. (2018). Seronegative antibody-mediated neurology after immune checkpoint inhibitors. Annals of Clinical and Translational Neurology, 5(5), 640– 645. https://doi.org/10.1002/acn3.547. Vargas Pivato de Almeida, D. (2022). Neurological toxic effects associated with treatment with immune checkpoint inhibitors—are we really safer now? JAMA Network Open, 5(4). https://doi.org/10.1001/jamanetworkopen.2022.7731 Wingerchuk DM;Banwell B;Bennett JL;Cabre P;Carroll W;Chitnis T;de Seze J;Fujihara K;Greenberg B;Jacob A;Jarius S;Lana-Peixoto M;Levy M;Simon JH;Tenembaum S;Traboulsee AL;Waters P;Wellik KE;Weinshenker BG; ; (n.d.). International consensus diagnostic criteria for Neuromyelitis Optica Spectrum Disorders. Neurology. https://pubmed.ncbi.nlm.nih.gov/26092914/ Yu, C. W., Yau, M., Mezey, N., Joarder, I., & Micieli, J. A. (2020, November 3). Neuro-ophthalmic complications of immune checkpoint inhibitors: A systematic review. Eye and brain. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648547/ Carrillo, P., Gorría, T., Santana, D., Sepulveda, M., Aldecoa, I., Gonzalez-Farré, B., Sanfeliu, E., Mension, E., Cebrecos, I., Martínez-Saez, O., Alonso, I., & Saiz, A. (2022). Aquaporin-4-positive triple-negative breast cancer presenting with paraneoplastic neuromyelitis Optica Spectrum disorder. Biomedicine Hub, 7(1), 11–16. https://doi.org/10.1159/000521578 Haanen J;Obeid M;Spain L;Carbonnel F;Wang Y;Robert C;Lyon AR;Wick W;Kostine M;Peters S;Jordan K;Larkin J; ; (n.d.). Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology. https://pubmed.ncbi.nlm.nih.gov/36270461/ Daetwyler, E., Zippelius, A., Meyer, P., & Läubli, H. (2023). Pembrolizumabinduced optic neuropathy – A case report. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1171981 Contact Information: Letitia Pirau, [e-mail] 42 | North American Neuro-Ophthalmology Society