Optic neuropathies induced by immune checkpoint inhibitors: A case series and systematic review of the literature

Introduction Immune checkpoint inhibitor (ICI)-related optic neuritis is rare but clinically significant as visual sequelae are reported in around half of affected patients. Materials and methods We retrospectively collected all cases of ICI-related optic neuropathy referred to two tertiary centers. A systematic review of PubMed, Embase, and Medline was conducted following PRISMA guidelines. Cases were classified into: i) optic neuritis, defined by the presence of consistent symptoms (visual loss, dyschromatopsia, afferent pupillary defect) and optic nerve abnormalities on MRI or visual evoked potentials (VEPs); ii) papillitis, defined by any visual disturbance associated with optic disc oedema and absence of optic neuropathy signs on MRI imaging or VEPs. Results Fifty cases were identified. The most common presentation was bilateral, painless visual acuity reduction with papilledema. All optic neuritis cases involved vision loss compared to 60 % of papillitis patients, who also reported scotomas, photopsia, or floaters. Papillitis was frequently associated with uveitis, either isolated or as part of Vogt-Koyanagi-Harada-like syndrome, whereas optic neuritis was more often associated with immune-related neurological toxicities, including neuromyelitis optica spectrum disorder. Despite immunomodulatory treatment, visual deficits persisted in 60 % of cases – rising to nearly 80 % in optic neuritis cases. Seven patients with papillitis and one with optic neuropathy resumed ICIs without recurrence. Conclusions Two distinct patterns of ICI-induced optic neuropathy emerge: papillitis, usually associated with uveitis and Vogt-Koyanagi-Harada syndrome, and optic neuritis, linked to broader immune-related neurological toxicities and poorer outcomes. Our findings suggest that ICIs may be safely reintroduced after full recovery from ICI-related papillitis.