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Uveitis secondary to cancer therapeutics

Cancer cells provide a therapeutic challenge as they impede the immune system and its response to malignancy. Checkpoint inhibitors and targeted therapy provide novel methods for the treatment of these metastases. These use of immunotherapy and targeted therapy is widespread, with indications including metastatic melanoma, squamous cell carcinoma, non-small cell lung cancer, colon cancer, gastric cancer, renal cell carcinoma, Merkel cell carcinoma and urothelial cancer. Checkpoint inhibitors act upon three main receptors or ligands to achieve this goal: cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death protein (PD-1) and programmed death ligand-1 (PD-L1). Additionally, targeted therapies counter the mutations leading to cancer cell proliferation, which include the mitogen-activated protein kinase (MEK) pathway and BRAF enzyme. However, they are known to cause ocular side effects in up to 1% of patients, with uveitis comprising a fraction of these patients. These secondary uveitis manifestations can present with severity ranging from solitary anterior uveitis to panuveitis, sometimes in concert with systemic manifestations such as Vogt-Koyanagi-Harada (VKH)-like syndrome. The uveitis caused by these medications can present both diagnostic and treatment challenges that can complicate patient care. Systemic steroids have demonstrated mixed data regarding the reduction of cancer therapeutic efficacy, and as a result, immunotherapy and targeted therapy are often held when systemic steroids are used for immune-related adverse event (irAE) treatment. Local steroids, although prone to their own set of adverse effects, may therefore be preferable to systemic steroids in the treatment of uveitis secondary to cancer therapeutics. In this review, we provide an overview of uveitis secondary to targeted therapy and immunotherapy, as well as treatment considerations.