Inhibitory effects of bevacizumab on filtering bleb scarring following trabeculectomy in rabbits

Abstract

Background The primary reason to trabeculectomy failure is fibrosis of conjunctiva and episclera because of progressive fibroblast proliferation and collagen deposition of the filtration bleb.Conventional methods of inhibiting bleb scarring was intraoperative application of mitomycin C (MMC), but many complications occured after surgery.Researches showed that bevacizumab was an antifibrotic agent, and whether it can suppress scarring of filtering bleb after trabeculectomy is concerned. Objective The aim of this study was to evaluate the antifibrotic efficacy of bevacizumab after trabeculectomy in rabbits. Methods Forty New Zealand rabbits were randomly divided into four groups.Trabeculectomy was performed on the right eyes of each rabbits.The rabbits received subconjunctival injection of 0.05 ml bevacizumab (25 mg/ml) at the end of operation in the bevacizumab single injection group.The same dose of bevacizumab was respectively injected at the end of operation as well as 3 days and 7 days after operation in the bevacizumab repitition injection group, and 0.05 ml normal saline solution was used in the same way in the normal saline group.In the MMC group, MMC cotton patch with 0.2 mg/ml was placed under the Tenon caplsule and scleral flap for 3 minutes during operation.The intraocular pressure (IOP), bleb area and shape were evaluated during the 28-day period.The animals were sacrificed on postoperative day 14 and 28, respectively for the histopathologic examination of bleb.The expression of CD31 in the bleb was detected by immunohistochemistry for the calculation of microvessels.All experiments were performed in accordance with the ethics code for animal experimentation and approved by the Institutional Review Board of Tianjin Eye Hospital. Results No significant difference was found in the postoperative IOP among the groups (F=0.88, P=0.47). Compared with the bevacizumab single injection group, MMC group and normal saline group, the shape of bleb was higher and much diffuse with sparse vessels 7 days after operation in the bevacizumab repitition injection group.The survival time of bleb was 27 days, 19 days and 13 days in the bevacizumab repitition injection group, the bevacizumab single injection group, MMC group and normal saline group, respectively.The percentage of collagen deposition area was (49.18±1.54)%, (26.41±1.23)%, (50.68±1.87)% and (70.63±1.81)% at day 14 postoperative in the bevacizumab single injection group, bevacizumab repitition injection group, MMC group and normal saline group, respectively, with the largest area in the normal saline group, and percentage of collagen deposition area was significantly reduced in the bevacizumab repitition injection group compared with the bevacizumab single injection group (all at P<0.05). The percentage of collagen deposition area was (66.82±1.53)% at day 28 postoperative in the bevacizumab repitition injection group, while complete scarring was seen in other 3 groups.The number of microvessels was least at postoperative day 14 in the bevacizumab repitition injection group compared with the bevacizumab single injection group, MMC group and normal saline group (all at P<0.05). The number of microvessels was more in postoperative day 28 in the bevacizumab repitition injection group (3.51±0.31) compared with other groups (all at P<0.05). Conclusions Subconjunctival injection of bevacizumab following trabeculectomy can improve the successful rate of surgery by remaining the survival time of filtering bleb, inhibiting the bleb scarring in rabbits. Key words: Antibodies, monoclonal, humanized; Bevacizumab; Conjunctiva/pathology; Disease models, animal; Fibrosis/prevention c Glaucoma/surgery; Trabeculectomy; Wound healing/drug effects