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Tine Van Bergen, Evelien Vandewalle, Lieve K M Moons, Ingeborg Stalmans; Bevacizumab enhances the antifibrotic effect of MMC and allows to reduce its exposure time to improve safety. Invest. Ophthalmol. Vis. Sci. 2014;55(13):824.
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We already showed that mitomycin-C (MMC) together with bevacizumab can improve the success rate of glaucoma filtration surgery (GFS). However, the ideal concentration and exposure time of MMC in combination with the VEGF inhibitor is still unknown. The purpose of this study was to determine whether reducing the exposure time and/or dose of MMC in combination with bevacizumab could improve surgical outcome with a lower incidence of side effects.
Before performing GFS, mice were divided in different groups (n=10/group). In the 1st group, a surgical sponge soaked in MMC was applied to one eye, whereas the other eye received a NaCl sponge. The second group of mice received a MMC sponge in either eye, and a subconjunctival (SC) injection of bevacizumab (1 µl, 25 µg) or NaCl. In the 3rd group, NaCl (sponge as well as SC injection) was compared to the combination of MMC and bevacizumab. Surgical sponges soaked in MMC 0.02% and 0.01% were investigated and exposed to the sclera for 1 or 2 minutes. Treatment outcome was studied by clinical investigation of the bleb every other day and by checking collagen deposition at day 34 after surgery (Sirius Red).
Administration of bevacizumab combined with 1 or 2 minutes of MMC 0.02% both improved bleb area and survival, as compared to MMC 0.02% alone (P<0.001), with no significant differences between both conditions (P>0.05). Moreover, analysis of Sirius Red on postoperative day 34 showed a similar decrease in fibrosis after 1 and 2 minute administration (both with 21%; P=0.84). Importantly, 25 % of the eyes treated for 2 minutes with MMC showed corneal toxicity, whereas this was not the case after 1 minute of administration. The combination of bevacizumab and 1 minute exposure of MMC 0.01% also significantly improved surgical outcome (P<0.001 versus 1 min MMC 0.01%). However, these results were significantly worse than those with MMC 0.02% (P<0.001). These data suggest that halving the concentration and administration time of MMC in combination with bevacizumab is not as effective as the higher dose/administration time.
This study demonstrates that adjunctive bevacizumab allows to reduce the administration time of MMC 0.02%, thereby eliminating its toxic effects on the corneal epithelium while maintaining the beneficial effects on surgical outcome.
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