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Tine Van Bergen, Karolien Hollanders, Davine Sijnave, Sarah Van de Velde, Evelien Vandewalle, Lieve Moons, Ingeborg Stalmans; Complementary effects of bevacizumab and MMC in the improvement of surgical outcome after glaucoma filtration surgery. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4774. doi: https://doi.org/.
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Mitomycin-C (MMC) serves as the gold standard to reduce scar formation. It has impacted the success rate of glaucoma filtration surgery (GFS), but carries a risk of vision threatening complications. Antifibrotic agents, such as bevacizumab, also can improve surgical outcome. In this study, we first compared the effect of MMC versus bevacizumab on the surgical outcome of GFS. Secondly, we investigated the complementary effects of MMC and anti-VEGF therapy.
The effect of bevacizumab and MMC on surgical outcome was investigated in a mouse model of GFS. Immediately after surgery, mice were allocated into three groups (n=5/group). The 1st group received a subconjunctival (SC) injection of bevacizumab (1 µl; 25 µg); the 2nd group was treated during surgery with MMC (sponge soaked with MMC 0.02% for 2 minutes). Group 3 received a combination of MMC and a SC bevacizumab injection. Treatment outcome was studied by clinical investigation of bleb area every other day. (Immuno)stainings were performed to study angiogenesis (CD31) and fibrosis (Sirius Red) on postoperative day 14. Vascular endothelial growth factor (VEGF) levels after MMC treatment were measured in rabbit aqueous humor (AH) samples by ELISA.
SC injection of bevacizumab and MMC application were equally effective in improving surgical outcome. In both groups, bleb area was improved with 53 ± 4% (P=0.17) and blood vessel density (37 ± 4 %; P=0.44) and fibrosis (22 ± 3%; P=0.88) were equally reduced after both treatments. Remarkably, one day after surgery, VEGF levels were significantly increased with 97 ± 4 % in the AH of MMC-treated eyes (P=0.04). As compared to MMC monotherapy, combination of MMC and bevacizumab was able to increase bleb area with 18 ± 6% (P=0.02) by an additional reduction of angiogenesis (54 ± 4%; P=0.002) and fibrosis (32 ± 5%; P=0.01).
This study elucidates the potential benefit of bevacizumab to improve glaucoma surgery, in combination with the currently used antimitotic agents. Our data indeed suggest that bevacizumab together with MMC may have complementary effects, due to upregulation of VEGF after MMC treatment.
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