CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects
Abstract
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.
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Of these six patients, only two showed TRAb positivity, and the GO diagnosis in the four others could be reconsidered as ICPi-induced orbitopathy rather than Graves' disease.
“Of these six patients only two showed TRAb positivity, and we could reconsider the GO diagnosis in the four others because it may represent ICPi-induced orbitopathy rather than Graves’ disease [45].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [45]
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Thompson, J. A., Schneider, B. J., Brahmer, J., Andrews, S., Armand, P., Bhatia, S., Budde, L. E., Costa, L., Davies, M., Dunnington, D., et al. (2019) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2019.0013 · Cited by 570 · see citing works
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- Authors
- Dalvin, L. A., Shields, C. L., Orloff, M., Sato, T., & Shields, J. A.
- Affiliations
- Mayo Clinic (US)
- Thomas Jefferson University (US)
- Corresponding author
- Dalvin, Lauren A.
- Shields, Carol L.
- Shields, Jerry A.
- Venue
- Retina
- Published
- 2018-06
- Volume
- 38
- Issue
- 6
- Pages
- 1063-1078
- ISSN
- 0275-004X (ISSN-L)
- OpenAlex
- W2918950605
- Cited by
- 336
- References
- 161
- Citations by year
- 2026: 18 · 2025: 40 · 2024: 42 · 2023: 38 · 2022: 44 · 2021: 50 · 2020: 59 · 2019: 41 · 2018: 4
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Retina (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- immune checkpoint inhibitors, immune-related adverse events, uveitis, dry eye, myasthenia gravis, keratitis, optic neuropathy, serous retinal detachment, neuroretinitis, CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 inhibitors, ocular inflammation, corticosteroid therapy
- MeSH terms
- Antineoplastic Agents, Immunological, Eye Diseases, Humans, Immunotherapy, Orbital Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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