title: Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn.
abstract: OBJECTIVE
  That vascular endothelial growth factor (VEGF) plays a major role in inflammatory angiogenesis has been well established. This pilot study was designed to evaluate experimental treatment with bevacizumab eyedrops in corneal neovascularization induced by alkali burn. The feasibility of topical administration, corneal cell viability and corneal penetration were investigated in an animal model.
  
  
  METHODS
  Eighteen chinchilla bastard rabbit corneas injured with 1 m NaOH were divided into three groups: untreated, early and late treatment groups. Eyedrops of bevacizumab solution (25 mg/ml) were administered five times daily. Clinical examination under stereoscopic microscope was performed to evaluate corneal opacity, neovascularization, vessel size and oedema. Histopathology was analysed for vessel density and apoptotic reaction. Additionally, intracameral bevacizumab concentration was measured with enzyme-linked immunosorbent assay (ELISA) after repeated topical applications.
  
  
  RESULTS
  A fast increase in aqueous bevacizumab concentration was achieved when the solution was instilled every minute onto a healthy eye surface. As well as clear anti-angiogenic effects, anti-fibrotic effects were also seen after corneal burn, maintaining corneal transparency. Early treatment of actively growing vessels showed a significantly better outcome, although apoptosis of pre-existing vessels could also be induced by the late treatment. No specific toxicity was seen regarding epithelium, keratocytes or endothelium.
  
  
  CONCLUSIONS
  The data from this pilot study suggest that bevacizumab eyedrops can sufficiently penetrate the corneal stroma and anterior chamber. When administered soon after alkali burn, bevacizumab seems to significantly reduce corneal damage. Combinations of established treatment regimens with topical bevacizumab might be considered in severe injuries with otherwise devastating prognoses.
authors.affiliation: Department of Ophthalmology, Eberhard-Karls University Tübingen, Germany.
authors.forename: Efdal
authors.initials: E
authors.lastname: Yoeruek
authors.forename: Focke
authors.initials: F
authors.lastname: Ziemssen
authors.forename: Sigrid
authors.initials: S
authors.lastname: Henke-Fahle
authors.forename: Olcay
authors.initials: O
authors.lastname: Tatar
authors.forename: Aysegül
authors.initials: A
authors.lastname: Tura
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Karl U
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Peter
authors.initials: P
authors.lastname: Szurman
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002057:Burns, Chemical / Q000150:complications*; D002470:Cell Survival; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D005240:Feasibility Studies; D005260:Female; D007150:Immunohistochemistry; D009883:Ophthalmic Solutions; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009883:Ophthalmic Solutions; D000068258:Bevacizumab