title: Ocular Toxicity in Metastatic Melanoma Patients Treated With Mitogen-Activated Protein Kinase Kinase Inhibitors: A Case Series.
abstract: OBJECTIVE
  To report the clinical features and management of mitogen-activated protein kinase kinase inhibitor-associated ocular side effects in 4 patients with advanced melanoma and a review of literature.
  
  
  METHODS
  Interventional case series.
  
  
  METHODS
  Four patients with advanced cutaneous melanoma were treated with a mitogen-activated protein kinase kinase (MEK) inhibitor as single therapy or together with a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor. All patients underwent ophthalmologic examinations at regular intervals or as needed, including visual acuity, intraocular pressure, external eye examination, and funduscopy. When pathologic findings were found, patients underwent visual field examination, optical coherence tomography (OCT), and/or fluorescein angiography. Ocular toxicity was assessed and handled according to the Common Terminology Criteria for Adverse Events.
  
  
  RESULTS
  Ocular adverse events appeared early in the treatment. In 3 patients OCT revealed subfoveal neuroretinal elevation, often asymptomatic, also after discontinuation and re-starting of MEK inhibitor. Vascular injury appeared in 2 patients, in 1 case associated with a visual field defect reduced after discontinuation of the drug and use of systemic therapy. In 1 case an inflammatory reaction was observed in the anterior chamber. Visual symptoms were usually mild and short-lived.
  
  
  CONCLUSIONS
  MEK inhibitor as a single agent or in combination with BRAF inhibitor induces transient retinopathy with time-dependent recurrence and usually mild visual symptoms. Vascular injuries can be observed and their management is essential in clinical practice. It is important to investigate all previous ocular disorders, systemic conditions, and pharmacologic interactions of MEK inhibitor that could facilitate the onset of associated ocular effects.
authors.affiliation: Eye Clinic, University of Bari "Aldo Moro", Bari, Italy. Electronic address: alfred.nir@tiscali.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Niro
authors.affiliation: Department of Medical Oncology, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Strippoli
authors.affiliation: Eye Clinic, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Alessio
authors.affiliation: Eye Clinic, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sborgia
authors.affiliation: Eye Clinic, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Recchimurzo
authors.affiliation: Department of Medical Oncology, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Guida
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000175:diagnosis; D012878:Skin Neoplasms; D041623:Tomography, Optical Coherence; D000096142:Cutaneous Malignant Melanoma
chemical_list: C550600:N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D020929:Mitogen-Activated Protein Kinase Kinases