title: Ipilimumab-induced Ocular and Orbital Inflammation--A Case Series and Review of the Literature.
abstract: OBJECTIVE
  Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called "immune-related adverse events" (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy.
  
  
  METHODS
  We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions.
  
  
  RESULTS
  Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy.
  
  
  CONCLUSIONS
  Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae.
authors.affiliation: a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papavasileiou
authors.affiliation: b Department of Neurology , Harvard Medical School, Brigham and Women's Hospital , Boston , Massachusetts , USA.
authors.forename: Sashank
authors.initials: S
authors.lastname: Prasad
authors.affiliation: a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Freitag
authors.affiliation: a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sobrin
authors.affiliation: a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Lobo
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D060908:CTLA-4 Antigen / Q000276:immunology; D003320:Corneal Ulcer / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008875:Middle Aged; D054517:Orbital Cellulitis / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D014605:Uveitis / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005938:Glucocorticoids; D000074324:Ipilimumab
keywords: Autoimmune adverse events; CTLA-4 inhibitors; eye and orbit complications; ipilimumab; melanoma