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Systemic Indications and Ophthalmic Side Effects

Dalvin, Lauren A. MD*,†; Shields, Carol L. MD*; Orloff, Marlana MD; Sato, Takami MD; Shields, Jerry A. MD*

doi: 10.1097/IAE.0000000000002181

Purpose: To review immune checkpoint inhibitor indications and ophthalmic side effects.

Methods: A literature review was performed using a PubMed search for publications between 1990 and 2017.

Results: Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1–24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy.

Conclusion: Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

Checkpoint inhibitors are medications initially used to treat previously incurable cutaneous melanoma metastasis through T-cell immune modulation. These drugs, now used for several malignancies, have associated ocular side effects, especially autoimmune-like inflammatory conditions. With increasing frequency of use, ophthalmologists should be aware of these medications and potential side effects.

*Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota; and

Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, 840 Walnut Street, Suite 1440, Philadelphia, PA 19107; e-mail:

Supported by an unrestricted grant from Research to Prevent Blindness, Inc (L.A.D.), the Heed Ophthalmic Foundation (L.A.D.), and Eye Tumor Research Foundation, Philadelphia, PA (C.L.S., J.A.S.).

None of the authors has any financial/conflicting interests to disclose.

The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. C. L. Shields has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

© 2018 by Ophthalmic Communications Society, Inc.