Combined treatment with bevacizumab and 5-fluorouracil attenuates the postoperative scarring response after experimental glaucoma filtration surgery

Invest Ophthalmol Vis Sci. 2010 Feb;51(2):928-32. doi: 10.1167/iovs.09-3949. Epub 2009 Sep 24.

Abstract

Purpose: This study evaluated the use of combined bevacizumab with 5-fluorouracil (5-FU) on postoperative scarring and bleb survival after experimental glaucoma filtration surgery in comparison to the agents alone.

Methods: Filtration surgery was performed on 26 female New Zealand White rabbits. The rabbits were allocated to one of four treatments: 5-FU combined with bevacizumab, 5-FU alone, bevacizumab alone, or phosphate buffered saline (PBS). The subconjunctival injections were administered immediate postoperatively and weekly for 3 weeks. Clinical assessment and bleb photography were performed. Histologic staining determined the presence of subconjunctvial fibrosis and mRNA expression of collagen I and fibronectin in the tissue was quantified.

Results: Bevacizumab in combination with 5-FU resulted in a greater antifibrotic effect compared with monotherapy with 5-FU or bevacizumab alone, as evidenced by the attenuation in fibronectin and mature collagen I expression and deposition (P < 0.05). In addition, this was associated with a 100% bleb survival at day 28 in the combined treatment group compared with monotherapy (50% bevacizumab [P < 0.05] and 25% 5-FU [P < 0.001]). Conjunctival vascularity significantly reduced with bevacizumab treatment both alone and in combination with 5-FU.

Conclusions: The results provide compelling evidence that combined bevacizumab and 5-FU offers superior antifibrotic effect over monotherapy in a model of glaucoma filtration surgery, while prolonging bleb survival at the same time. A synergistic effect is suggested to be present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic / administration & dosage
  • Bevacizumab
  • Cicatrix / metabolism
  • Cicatrix / prevention & control*
  • Collagen Type I / genetics
  • Conjunctiva / drug effects
  • Conjunctiva / metabolism
  • Conjunctiva / pathology
  • Drug Therapy, Combination
  • Female
  • Fibronectins / genetics
  • Fibrosis / metabolism
  • Fibrosis / prevention & control
  • Filtering Surgery*
  • Fluorouracil / administration & dosage*
  • Postoperative Complications / metabolism
  • Postoperative Complications / prevention & control*
  • RNA, Messenger / metabolism
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Wound Healing / drug effects*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • Collagen Type I
  • Fibronectins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Fluorouracil