Comparison of the efficiency of subconjunctival aflibercept ranibizumab and bevacizumab in corneal neovascularization in a rat model
Abstract
Background: Corneal neovascularization (CN) might be a sight-threatening condition via reducing the corneal transparency. One of the most significant proangiogenic factors is vascular endothelial growth factor (VEGF) that is shown to be upregulated in CN. Accordingly, we aimed to evaluate and compare the effectiveness of aflibercept, ranibizumab, and bevacizumab in CN in a rat model.
Material and methods: Twenty-eight male Wistar-Albino rats were administered general anesthesia. 2-mm-diameter central burns were formed on the corneas. Rats were divided into four groups randomly, and one group was administered subconjunctival saline solution as the control group. Subconjunctival aflibercept, bevacizumab, and ranibizumab were applied to the other three groups, respectively. Three rats from each group were randomly selected, and digital photographs of the corneas were taken under general anesthesia. Then, rats were euthanized, and eyes were enucleated one week and one month after the corneal injury. Three enucleated eyes from each group were prepared for histological evaluation with hematoxylin and eosin.
Results: According to the first week results, there was no central CN in all groups except the control group. There was no statistically significant difference in total CN among the groups according to the Kruskal-Wallis test (p = 0.09). The control group had a higher inflammation score than the other groups in the central cornea. On the other hand, the control group had less intense fibrosis than the other groups in the central cornea. In the first month, there was a spontaneous regression in central CN in the control group. There was again no statistical difference among the groups regarding the CN (p = 0.46). There was no inflammation in the central cornea in any groups.
Conclusion: single-dose subconjunctival injection of aflibercept, ranibizumab, and bevacizumab prevents the
central CN and reduces the inflammation.
Keywords: afliberceptbevacizumabcorneal neovascularizationranibizumab
References
- Azar DT. Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2006; 104: 264–302.
- Philipp W, Speicher L, Humpel C. Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci. 2000; 41(9): 2514–2522.
- Nicholas MP, Mysore N. Corneal neovascularization. Exp Eye Res. 2021; 202: 108363.
- Avery RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006; 113(3): 363–372.e5.
- Sarwar S, Clearfield E, Soliman MK, et al. Aflibercept for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2016; 2: CD011346.
- Dursun A, Arici MK, Dursun F, et al. Comparison of the effects of bevacizumab and ranibizumab injection on corneal angiogenesis in an alkali burn induced model. Int J Ophthalmol. 2012; 5(4): 448–451.
- Ahmed A, Berati H, Nalan A, et al. Effect of bevacizumab on corneal neovascularization in experimental rabbit model. Clin Exp Ophthalmol. 2009; 37(7): 730–736.
- Eiger-Moscovich M, Livny E, Sella R, et al. Comparison of Subconjunctival Aflibercept and Betamethasone for the Treatment of Formed Corneal Neovascularization in a Rabbit Model. Ophthalmic Res. 2019; 62(2): 116–122.
- Sener E, Yuksel N, Yildiz DK, et al. The impact of subconjuctivally injected EGF and VEGF inhibitors on experimental corneal neovascularization in rat model. Curr Eye Res. 2011; 36(11): 1005–1013.
- Edelman JL, Castro MR, Wen Y. Correlation of VEGF expression by leukocytes with the growth and regression of blood vessels in the rat cornea. Invest Ophthalmol Vis Sci. 1999; 40(6): 1112–1123.
- Kang S, Chung SK. The effect of subconjuctival combined treatment of bevacizumab and triamcinolone acetonide on corneal neovascularization in rabbits. Cornea. 2010; 29(2): 192–196.
- Ulas B, Altan-Yaycioglu R, Bal N. Comparison of the inhibitory effect of different doses of subconjunctival bevacizumab application in an experimental model of corneal neovascularization. Int J Ophthalmol. 2018; 11(7): 1090–1095.
- Chen WL, Chen YM, Chu HS, et al. Mechanisms controlling the effects of bevacizumab (avastin) on the inhibition of early but not late formed corneal neovascularization. PLoS One. 2014; 9(4): e94205.
- Lin CT, Hu FR, Kuo KT, et al. The different effects of early and late bevacizumab (Avastin) injection on inhibiting corneal neovascularization and conjunctivalization in rabbit limbal insufficiency. Invest Ophthalmol Vis Sci. 2010; 51(12): 6277–6285.
- Kim EK, Kong SJ, Chung SK. Comparative study of ranibizumab and bevacizumab on corneal neovascularization in rabbits. Cornea. 2014; 33(1): 60–64.
- Gal-Or O, Livny E, Sella R, et al. Efficacy of Subconjunctival Aflibercept Versus Bevacizumab for Prevention of Corneal Neovascularization in a Rat Model. Cornea. 2016; 35(7): 991–996.
- Sella R, Gal-Or O, Livny E, et al. Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model. Exp Eye Res. 2016; 146: 224–232.
- Kadar T, Amir A, Cohen L, et al. Anti-VEGF therapy (bevacizumab) for sulfur mustard-induced corneal neovascularization associated with delayed limbal stem cell deficiency in rabbits. Curr Eye Res. 2014; 39(5): 439–450.
- Oh JY, Kim MK, Shin MiS, et al. The anti-inflammatory effect of subconjunctival bevacizumab on chemically burned rat corneas. Curr Eye Res. 2009; 34(2): 85–91.
- Yang L, Kwon J, Popov Y, et al. Vascular endothelial growth factor promotes fibrosis resolution and repair in mice. Gastroenterology. 2014; 146(5): 1339–13350.e1.