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Editors Selection IGR 11-4

Surgical Treatment: Anti-VEGF in wound modulation

Comment by Malik Kahook on:

48416 The role of different VEGF isoforms in scar formation after glaucoma filtration surgery, Van Bergen T; Vandewalle E; Van de Veire S et al., Experimental Eye Research, 2011; 93: 689-699

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The use of anti-vascular endothelial growth factor (VEGF) agents, such as bevacizumab and ranibizumab, for treating neovascular diseases of the eye is well known. The utility of these agents as wound modulators after glaucoma filtration surgery has also received wide attention. Van Bergen et al. (2129) highlight the science behind the use of anti-VEGF agents to address fibroblast proliferation and scar formation. The study was designed to 'elucidate the differential roles of VEGF isoforms in scar formation after trabeculectomy' and they found different isoforms of VEGF have selective effects on endothelial cells and Tenon's fibroblast cells. Specifically VEGF 121 and VEGF 189 were noted to cause fibroblast proliferation, while VEGF 121 and 165 led to endothelial cell proliferation. Use of pegaptanib (Macugen), a selective VEGF 165 blocking agent, inhibited endothelial cell proliferation as expected but had little effects on fibroblast cells. In-vivo testing of pegaptanib in a rabbit model of filtration surgery resulted in reduction of angiogenesis with little effect on fibrosis, findings which were in line with the in-vitro data. A closer look at the in-vivo data reveals, as noted by the authors, that there were no differences in the IOP between treatment and control groups. Furthermore, the analyses of bleb characteristics did not concretely show any advantage for the treatment groups that could be considered clinically significant. Bleb survival was enhanced in the repeat injection group, but this could have been due to the mechanical effects of subconjunctival injections every two days for the first two weeks. It would be of interest to have also included a group of rabbits treated with a single intravitreal injection, resulting in longer-term exposure of the bleb to anti-VEGF effects, rather than the use of anterior chamber and repeated subconjunctival injections of pegaptanib. While level of vascularity was influenced by use of pegaptanib, this alone does not appear sufficient to support the routine use of this specific agent as standalone wound modulators in humans. The study does however support the need for further investigation of anti-VEGF agents that target multiple isoforms of VEGF as part of a combination approach to wound modulation. Such an approach could ultimately replace mitomycin C as the primary anti-fibrotic used in filtration surgery and might eventually lead to safer and more efficacious surgical results for glaucoma patients.

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