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Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in
Emika Nemoto1, Shota Kojima1, Tetsuya Sugiyama1
1Department of Ophthalmology, Osaka Medical College, Takatsuki-City, Osaka 569-8686, Japan.
Abstract:
Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.
Insights
Regorafenib eye drops may offer a superior alternative to mitomycin-C for glaucoma surgery. This multi-kinase inhibitor promotes thicker, less ischemic blebs, potentially improving outcomes in filtration surgery.
Area of Science:
- Ophthalmology
- Glaucoma Research
- Drug Development
Background:
- Age-related macular degeneration (AMD) treatment is an emerging application for regorafenib.
- Glaucoma filtration surgery aims to reduce intraocular pressure (IOP) but can be limited by bleb morphology and vascularization.
- Investigating novel agents to enhance glaucoma surgery outcomes is crucial.
Purpose of the Study:
- To evaluate the efficacy of regorafenib eye drops in a canine glaucoma filtration surgery model.
- To assess the impact of regorafenib on intraocular pressure (IOP), bleb formation, and conjunctival tissue.
- To compare regorafenib with mitomycin-C (MMC) as a surgical adjunct.
Main Methods:
- Glaucoma filtration surgery was performed on 24 canine eyes.
- Experiment 1: Regorafenib or vehicle eyedrops applied post-surgery for 4 weeks.
- Experiment 2: Regorafenib or MMC applied intraoperatively and regorafenib eyedrops for 12 weeks.
Main Results:
- Regorafenib significantly reduced IOP and increased bleb scores in Experiment 1.
- Regorafenib treatment led to reduced subconjunctival tissue proliferation and vascularization.
- In Experiment 2, regorafenib produced thicker, more vascularized blebs compared to MMC, with no significant difference in IOP reduction.
Conclusions:
- Regorafenib eye drops show potential for improving glaucoma filtration surgery outcomes.
- The drug may enhance bleb quality by promoting thicker, less ischemic conjunctival tissue.
- Regorafenib could be a promising alternative to mitomycin-C in glaucoma surgery.
