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

Caberry W Yu; Matthew Yau; Natalie Mezey; Ishraq Joarder; Jonathan A Micieli

doi:10.2147/EB.S277760

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

Eye Brain. 2020 Nov 3:12:139-167. doi: 10.2147/EB.S277760. eCollection 2020.

Authors

Caberry W Yu¹, Matthew Yau², Natalie Mezey¹, Ishraq Joarder³, Jonathan A Micieli^{4

5}

Affiliations

¹ Faculty of Medicine, Queen's University, Kingston, Canada.
² Faculty of Medicine, University of Toronto, Toronto, Canada.
³ Faculty of Science, University of Toronto, Scarborough, Ontario, Canada.
⁴ Department of Ophthalmology and Vision Sciences and Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.
⁵ Kensington Vision and Research Centre, Toronto, Canada.

Abstract

Objective: 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: CTLA-4 inhibitors; PD-1 inhibitors; PD-L1 inhibitors; cancer immunotherapy; immune checkpoint inhibitors.

Publication types

Review

Grants and funding

There is no funding to report.