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EMIKA Nemoto, Shota Kojima, Tetsuya Sugiyama, Denan Jin, Shinji Takai, Michiko Maeda, Ryohsuke Kohmoto, Mari Ueki, Hidehiro Oku, Tsunehiko Ikeda; Effects of a multi-kinase inhibitor compared with mitomycin-C on conjunctival scarring in a canine filtration surgery model.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3751.
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© ARVO (1962-2015); The Authors (2016-present)
Regorafenib is a multi-kinase inhibitor of vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, RAF, Tie-2, c-KIT, and RET. The aim of this study was to investigate the effects of regorafenib compared with those of mitomycin-C (MMC) on intraocular pressure (IOP), bleb formation, and conjunctival capillaries in a canine filtration surgery model.
Glaucoma filtration surgery models were created in 12 eyes of 12 beagles. Immediately after surgery, 50 μL of 2% regorafenib solution was instilled to some eyes twice a day for 12 weeks (R group, n=6), while 0.04% MMC was exposed to the sclera of other eyes for 5 minutes during surgery (M group, n=6). IOP and bleb scores were assessed for 12 weeks postoperatively. At 12 weeks, the thickness of the bleb wall was measured using ultrasonic biomicroscopy (UBM) and histological evaluation.
In both groups, IOP reduction and bleb scores were maintained similarly for 12 weeks. UBM showed that bleb walls were significantly thicker in the R group than in the M group (1.05±0.14 mm vs. 0.85±0.12 mm (mean±standard deviation), p=0.04, Mann–Whitney U test). Collagen density and the number of conjunctival capillaries were significantly higher in the R group than in the M group (p=0.02 and 0.01, respectively; Mann–Whitney U test). No significant difference was found in proliferative-cell nuclear antigen-positive, mast, transforming growth factor-β (TGF-β)-positive, or vimentin-positive cells between the two groups. Instillation of regorafenib suppressed fibrosis by inhibiting TGF-β and some cytokines, resulting in prolonged bleb formation and IOP reduction.
Topical regorafenib application maintained bleb formation and IOP reduction by a similar degree to that of MMC exposure, whereas it ameliorated toxicity to conjunctiva. These results suggest that regorafenib is more useful than MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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