Cited by 336Cancer Immunotherapy and BiomarkersDrug-Induced Ocular ToxicityOcular Diseases and Behçet’s Syndrome

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects

Dalvin, Lauren A., Shields, Carol L., Orloff, Marlana, Sato, Takami, Shields, Jerry A.·2018·Retina

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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Crossref · 10.1097/iae.0000000000002181

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161 of 161 references verified0 citation errors · 0 not checkable

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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].”

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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

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