Combined treatment with bevacizumab and 5-fluorouracil attenuates the postoperative scarring response after experimental glaucoma filtration surgery.
OBJECTIVE
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.
How
Alicia
A
Singapore National Eye Centre, Singapore.
Chua
Jocelyn Leng Leng
JL
Charlton
Amanda
A
Su
Roseline
R
Lim
Marcus
M
Kumar
Rajesh S
RS
Crowston
Jonathan G
JG
Wong
Tina T
TT
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000068258:Bevacizumab; D002921:Cicatrix / Q000378:metabolism / Q000517:prevention & control*; D024042:Collagen Type I / Q000235:genetics; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis / Q000378:metabolism / Q000517:prevention & control; D018463:Filtering Surgery; D005472:Fluorouracil / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000378:metabolism / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014945:Wound Healing / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D024042:Collagen Type I; D005353:Fibronectins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D005472:Fluorouracil