Neuro-ophthalmic Complications of Immune Checkpoint Inhibitors: A Systematic Review

Abstract

Caberry W Yu,1 Matthew Yau,2 Natalie Mezey,1 Ishraq Joarder,3 Jonathan A Micieli4,5 1Faculty of Medicine, Queen’s University, Kingston, Canada; 2Faculty of Medicine, University of Toronto, Toronto, Canada; 3Faculty of Science, University of Toronto, Scarborough, Ontario, Canada; 4Department of Ophthalmology and Vision Sciences and Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada; 5Kensington Vision and Research Centre, Toronto, CanadaCorrespondence: Jonathan A MicieliKensington Vision and Research Centre, 340 College Street, Suite 501, Toronto, Ontario M5T 3A9, CanadaTel [phone]Fax [phone]Email [email protected]: Immune checkpoint inhibitors (ICIs) are novel cancer therapies that may be associated with immune-related adverse events (IRAEs) and come to the attention of neuro-ophthalmologists. This systematic review aims to synthesize the reported ICI-associated IRAEs relevant to neuro-ophthalmologists to help in the diagnosis and management of these conditions.Methods: A systematic review of the literature indexed by MEDLINE, Embase, CENTRAL, and Web of Science databases was searched from inception to May 2020. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Primary studies on ICIs and neuro-ophthalmic complications were included. Outcomes included number of cases and incidence of neuro-ophthalmic IRAEs.Results: Neuro-ophthalmic complications of ICIs occurred in 0.46% of patients undergoing ICI and may affect the afferent and efferent visual systems. Afferent complications include optic neuritis (12.8%), neuroretinitis (0.9%), and giant cell arteritis (3.7%). Efferent complications include myasthenia gravis (MG) (45.0%), thyroid-like eye disease (11.9%), orbital myositis (13.8%), general myositis with ptosis (7.3%), internuclear ophthalmoplegia (0.9%), opsoclonus-myoclonus-ataxia syndrome (0.9%), and oculomotor nerve palsy (0.9%). Pembrolizumab was the most common causative agent for neuro-ophthalmic complications (32.1%). Mortality was highest for MG (19.8%). Most patients (79.8%) experienced improvement or complete resolution of neuro-ophthalmic symptoms due to cessation of ICI and immunosuppression with systemic corticosteroids.Conclusion: While incidence of neuro-ophthalmic IRAEs is low, clinicians involved in the care of cancer patients must be aware of their presentation to facilitate prompt recognition and management. Collaboration between oncology and neuro-ophthalmology teams is required to effectively manage patients and reduce morbidity and mortality.Keywords: immune checkpoint inhibitors, cancer immunotherapy, CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 inhibitors

Keywords

• immune checkpoint inhibitors
• cancer immunotherapy
• ctla-4 inhibitors
• pd-1 inhibitors
• pd-l1 inhibitors