Ocular surface disease associated with immune checkpoint inhibitor therapy

Abstract

Immune-related adverse events (irAEs) is a term used to describe the various toxicities associated with immune checkpoint inhibitor (ICI) use. As this class of cancer immunotherapy grows, the diversity of documented irAEs also continues to expand. Ocular toxicities secondary to ICI use are relatively rare, with dry eye and uveitis as the most frequently reported ocular side effects. This article specifically investigates the relationship between ocular surface disease and ICI therapy through a review of the existing literature. Dry eye disease (DED), conjunctivitis, and keratitis were the most commonly reported irAEs affecting the ocular surface across the 29 studies reviewed. Keratoplasty graft rejection was also described in two case reports. Our review of eight clinical trials found the incidence of DED, the most common ocular surface irAE, to range from 1 to 4%. Nearly all cases of ocular surface irAEs were graded as mild or moderate in severity and were often self-limited or controlled with conservative treatment. Duration of checkpoint inhibitor use prior to onset of ocular surface side effects varied widely, ranging from days to months. Ocular surface toxicities associated with checkpoint immunotherapy appear to be under-reported and under-investigated. Further work remains to be done to investigate the full breadth of ocular surface pathologies and the molecular mechanisms by which these toxicities occur.

Keywords: Conjunctivitis; Dry eye disease; Immune checkpoint inhibitor; Immune related adverse event; Keratitis; Ocular rosacea; Ocular surface disease; T cell.