Abstract
Purpose :
Although immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, their use is limited by non-specific inflammatory events that occur distant from the neoplastic site. To better understand the adverse reactions of these agents involving the ocular posterior segment, we sought to summarize and categorize postulated mechanisms of ICI-mediated retinal and choroidal inflammation.
Methods :
We reviewed selected literature describing immune-mediated retinal and choroidal adverse reactions associated with systemic ICI therapy. By drawing parallels with ICI-associated findings in other organ systems, we synthesized and categorized the likely pathogenic mechanisms underlying the various chorioretinal adverse immune reactions.
Results :
ICI-induced posterior segment adverse reactions can be categorized into three major mechanisms of unintended, targeted inflammation. In Type 1 reactions, T cell activation by ICIs can result in cross-reactivity of anti-tumor T cells with ocular tissues (Type 1a) or expansion of eye-specific T cells in predisposed individuals (Type 1b), leading to ocular inflammation that mimics known uveitic conditions. In Type 2 reactions, non-specific ocular or systemic inflammation exacerbated by ICI use can cause retinal vasculitis through a ”bystander” mechanism, potentially resulting in vision-threatening vascular occlusions. In Type 3 reactions, ICI use can prompt autoantibody-antibody mediated inflammation and/or exacerbation of paraneoplastic processes likely related to T cell driven expansion of B cell populations.
Conclusions :
Although relatively uncommon, posterior segment inflammatory disorders associated with ICI therapy may be vision-threatening if not identified and treated appropriately. We propose that the pathogenic mechanisms underlying these chorioretinopathies fall into three major categories involving inadvertent T cell mediated inflammation. Visual prognosis with appropriate treatment is generally favorable, but some reactions, such as longstanding exudative retinal detachment and ICI-induced occlusive retinal vasculitis, can result in permanent visual defects.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.