<p>Neuro-ophthalmic Complications of Immune Checkpoint Inhibitors: A Systematic Review</p>

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.

Anti-PD-1 sintilimab-induced bilateral optic neuropathy in non-small cell lung cancer: A case report and literature review

“…Although sintilimab has shown a potent efficacy in the treatment of tumors with manageable toxicity profiles, the side effects of sintilimab, including pneumonitis, anemia, diarrhea, colitis, hepatitis, nephritis, endocrinologic, hematologic, dermatologic, and other irAEs are inescapable ( 13 , 19 , 26 ). As the usage of sintilimab increases, some rare side effects have been documented, among them being neuro-ophthalmic complications of ICIs ( 12 , 19 , 27 ).…”

“…The relatively rare ophthalmic irAEs have been only reported in less than 5% of patients treated with anti-PD-1 antibody-containing regimens ( 15 ). The optic neuritis was the fifth most common ICI-related ocular adverse event in lung cancer, and most of the patients with ocular irAEs other than ophthalmoplegia could be relieved after drug withdrawal and glucocorticoid treatment ( 17 , 27 ). Optic neuritis is one of the ophthalmic emergencies and may lead to permanent vision damage if left inappropriately treated ( 16 ).…”

Toxic and Nutritional Optic Neuropathies—An Updated Mini-Review

“…Cases of optic neuritis as an adverse event of immune checkpoint inhibitor (ICI) ingestion have also been reported, most commonly with ipilimumab, a CTLA-4 inhibitor. Further, ICIs such as PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab or durvalumab) might cause optic neuropathy [ 123 , 124 ].…”

Neuro-ophthalmic manifestations of cancer: a narrative review

“…Combination therapy results in the highest incidence of adverse events, and is typically higher with the CTLA4 inhibitor ipilimumab (138). In terms of ophthalmic complications, however, a recent systematic review identified pembrolizumab as the most common cause of a neuro-ophthalmic complication (32.1%) (139).…”