title: Corneal verticillata after dual anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor 2 therapy (vandetanib) for anaplastic astrocytoma.
abstract: OBJECTIVE
  To describe a patient with a history of epithelial basement membrane dystrophy who developed symptomatic corneal verticillata after vandetanib therapy for anaplastic astrocytoma.
  
  
  METHODS
  Retrospective interventional case report.
  
  
  RESULTS
  A 48-year-old female patient with a history of anaplastic astrocytoma status post resection, external beam radiation, and chemotherapy presented with glare symptoms, decreased contrast sensitivity, and increased lacrimation after approximately 12 months of therapy with the anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor, vandetanib. Ophthalmic examination revealed diffuse corneal verticillata and fine subepithelial opacities. Schirmer 1 testing was normal bilaterally. Therapy with carboxymethylcellulose, 5% sodium chloride ointment, and a decrease in the dose of vandetanib led to an improvement in the patient's ophthalmic symptoms despite persistence of the corneal findings. The patient remained under surveillance for tumor recurrence.
  
  
  CONCLUSIONS
  Vandetanib (ZD6474), a protein tyrosine kinase inhibitor with dual anti-EGFR and anti-vascular endothelial growth factor receptor 2 action, may have contributed to the formation of corneal verticillata in our patient. Inhibition of EGFR, which is involved with corneal epithelial cell migration and wound healing, may play a role in the pathogenesis underlying corneal vortex keratopathy and ocular surface conditions with significant epithelial turnover.
authors.affiliation: National Eye Institute and daggerNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Yeh
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
authors.forename: Janine A
authors.initials: JA
authors.lastname: Smith
mesh_terms: D001254:Astrocytoma / Q000188:drug therapy* / Q000601:surgery; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000601:surgery; D002480:Cellulase / Q000627:therapeutic use; D003316:Corneal Diseases / Q000139:chemically induced* / Q000473:pathology; D003318:Corneal Opacity / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009824:Ointments; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012965:Sodium Chloride / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D009824:Ointments; D010880:Piperidines; D011799:Quinazolines; D012965:Sodium Chloride; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2; D002480:Cellulase; C019826:carboxymethylcellulase; C452423:vandetanib