Clinical Patterns and Factors Contributing to Ophthalmic and Otologic Events Associated With Immune Checkpoint Inhibitors: A Narrative Review

Immune checkpoint inhibitors, which are a type of cancer immunotherapy, have been associated with the development of adverse events related to an overactive immune system caused by the effect of this type of therapy. It affects a wide range of organs, including the ear and eye. Ophthalmic toxicity related to immune checkpoint inhibitors usually occurs bilaterally. Corneal toxicity (mainly dry eye disease) and uveitis are the most commonly reported patterns of toxicity. Other patterns of involvement include optic neuritis, serous retinal detachment, keratitis, ophthalmoplegia, and ocular myasthenia, but are not limited to them. Potential factors contributing to the development of toxicity are age, previous history of ocular immune disease, type, doses, and duration of treatment, and race. Ototoxicity is also reported in the literature, usually manifesting as bilateral, symmetrical/asymmetrical hearing loss. Ear toxicity presenting as ear fullness, tinnitus, and vertigo has also been mentioned in the literature. Hearing loss is often associated with word/speech recognition. An audiogram usually shows a pattern of sensorineural hearing loss. Otitis media has also been reported to be a potential cause of ear toxicity. Immune checkpoint inhibitor toxicity was present more commonly when used along with other anti-neoplastic agents. Ear toxicity, which presumably results from damage to the melanocytes in the ear, often presents with other melanocytotic manifestations, like uveitis and vitiligo. According to the literature, some agents (ipilimumab, nivolumab, atezolizumab, and pembrolizumab) were more commonly associated with toxic effects on the eye and ear and more when combined with each other.