Immunotherapy and Direct Acting Anti-Cancer Agent Associated-Uveitis

Abstract

Background: Immunotherapies and targeted anti-cancer agents upregulate the immune responses through cell surface receptor binding and altering intracellular signaling pathways. While these medications have shown a survival benefit and decreased disease burdens for several types of malignancies, immune-related adverse effects can develop with use. This review focuses on the clinical manifestations and treatment of uveitis with each class of immunotherapy agents. Methods: A comprehensive literature search was conducted using search terms checkpoint inhibitors, mitogen-activated kinase cascade inhibitors, B-RAF serine/threonine kinase inhibitors, epidermal growth factor receptor inhibitors, indoleamine 2,3-deoxygenase 1 inhibitors, and mirvetuximab. For each drug class, the mechanisms of action, associated reports of uveitis, and treatment strategies for ocular adverse effects were described. Results: The percentage of patients that develop uveitis varies by the drug class, with the highest percentage seen in BRAF inhibitors. The mechanisms by which immunotherapeutic drugs cause uveitis are ill-defined, leading to gaps in current literature on the subject. Most commonly, uveitis secondary to immunotherapy manifests as iritis, intermediate uveitis, or Vogt-Koyanagi-Harada-like disease. The incidence of immunotherapy-induced uveitis is rare, but can result in vision loss from macular edema, subretinal fluid, or optic nerve inflammation. Treatment options generally include topical, intravitreal, or oral corticosteroids. Dose holds or modifications may be required, with cessation of the immunotherapy as a last-line treatment. Conclusion: Future research is needed to elucidate the mechanisms by which immunotherapies and targeted cancer agents cause uveitis. Coordination of care between ophthalmologists and oncologists is needed to schedule screening and follow-up exams in addition to patient education on home symptom monitoring.