title: Corneal penetration of topical and subconjunctival bevacizumab.
abstract: OBJECTIVE
  To investigate the ability of bevacizumab to penetrate the cornea after topical application or subconjunctival injection.
  
  
  METHODS
  Bevacizumab 1% was topically applied three times a day to the corneas of mice (BALB/c) with intact corneas (n = 14), and with corneal neovascularization (n = 14). Animals were euthanized at 1, 6, 12, and 24 hours, and 2, 4, and 7 days for immunohistochemical analyses. Donkey anti-human IgG labeled with Cy3 was used for bevacizumab immunoreactivity detection. Additionally, one-time topical bevacizumab 1% was tested in corneas with denuded epithelium (n = 16). In another group (n = 16), a single dose of 0.5 mg bevacizumab was injected subconjunctivally. Animals were euthanized at 1, 6, and 24 hours, and 2, 4, 7, 14, and 21 days for immunohistochemical studies.
  
  
  RESULTS
  Bevacizumab was barely detected beyond the very superficial layer of the corneal epithelium in mice with intact corneas even after 7 days of topical administration. Application of bevacizumab in mice with corneal neovascularization; however, showed variable penetration into the corneal stroma. Experimentation with single application of topical bevacizumab in corneas with denuded epithelium or subconjunctivally injected bevacizumab showed intense staining for bevacizumab.
  
  
  CONCLUSIONS
  Topically applied bevacizumab has limited capacity to penetrate the corneas with intact epithelium. However, bevacizumab can penetrate the neovascularized cornea after topical application. This study demonstrates that subconjunctivally injected bevacizumab in eyes with an intact cornea penetrates well into the corneal stroma.
authors: Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
authors: Mohammad H
authors: MH
authors: Dastjerdi
authors: Zahra
authors: Z
authors: Sadrai
authors: Daniel R
authors: DR
authors: Saban
authors: Qiang
authors: Q
authors: Zhang
authors: Reza
authors: R
authors: Dana
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D003228:Conjunctiva / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism; D019573:Epithelium, Corneal / Q000378:metabolism* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D056965:Injections, Intraocular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy*; D009883:Ophthalmic Solutions
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D009883:Ophthalmic Solutions; D016222:Fibroblast Growth Factor 2; D000068258:Bevacizumab