Abstract
Purpose:
Glaucoma filtration surgery (GFS) frequently leads to surgical failure due to excessive postoperative wound healing. We previously showed that bevacizumab was able to improve surgical outcome in a rabbit model of GFS. However, the most optimal route of administration of bevacizumab is still unknown. Therefore, the current study was designed to investigate the effect on postoperative scarring of a single subconjunctival, intracameral or intravitreal injection of bevacizumab.
Methods:
The effect of bevacizumab (AvastinTM, Genentech) was investigated in a mouse model of GFS in C75Bl/6 mice. Immediately after surgery, mice were divided in 3 groups (n=10 per group) and received a subconjunctival (SC), intracameral (IC) or intravitreal (IV) injection. In all groups, one eye was injected with bevacizumab (1 µl; 25 µg) and the other eye was used as a negative control and received an injection of NaCl (1 µl; 0.9%). Treatment outcome was studied by clinical investigation of bleb area and bleb survival every other day. Mice were killed on postoperative day 14 and immunohistological analysis of angiogenesis (CD31) and collagen deposition (Sirius Red) were performed.
Results:
In the mouse model of GFS, treatment using a SC, IC, IV injection of bevacizumab significantly improved surgical outcome by increasing bleb area with 53 ± 5 % (P<0.001); with 45 ± 3 % (P=0.004) and with 49 ± 4 % (P<0.001), respectively, compared to negative control. Bleb survival improved only after SC injection compared to NaCl (P=0.04); all blebs survived until day 14 after SC bevacizumab injection, whereas only 62.5% of the NaCl treated eyes survived (P=0.04). No significant effects on bleb survival were seen after IC and IV injection. In all groups, blood vessel density was significantly reduced after bevacizumab treatment at 14 days after surgery with 36 ± 4% (P<0.001); with 31 ± 1% (P<0.001) and with 34 ± 4% (P<0.001), respectively. All administration routes of bevacizumab significantly diminished collagen deposition with 27 ± 4 % (P<0.001); with 27 ± 1 % (P<0.001) and with 27 ± 2 % (P<0.001), respectively, compared to negative control.
Conclusions:
This study shows that a subconjunctival injection of bevacizumab had the largest effect on surgical outcome compared to intracameral and intravitreal injection.
Keywords: 765 wound healing