Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review

Objective: To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.

Methods and analysis: Retrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Case 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed.

Conclusions: Immune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.