Investigation of the Efficacy of Topical and Subconjunctival Bevacizumab in Experimental Corneal Neovascularization in Rabbits

Year 2019, Volume: 3 Issue: 2, 54 - 58, 26.08.2019

Ümit Doğan , Serdal Çelebi Aysel Kükner

Abstract

ABSTRACT

Purpose: To compare the
efficacy of topical and subconjunctival bevacizumab with topical dexamethasone
in the treatment of corneal neovascularization (NV) secondary to chemical burns in
experimental rabbit models.

Materials and Methods: A total of 24 rabbits were used in the study.
Animals were divided into four groups as Control (received topical 0.09% NaCl) (Group 1), topical
dexamethasone (Group 2), subconjunctival bevacizumab (Grup3) and topical
bevacizumab (Group 4). Chemical burns were created with silver nitrate-potassium
nitrate in cornea of the subjects. During the next 10 days, each group was
given the drug (0.09 % NaCl, dexamethasone or bevacizumab). On the 10th day, the
subjects were sacrificed and macroscopic and histopathological evaluation of
corneal neovascularization was performed.

Results: When the number of vessels in the histopathological examination was
evaluated; In Group 2 (5.03 ± 0.42), Group 3 (3.36 ± 0.15) and Group 4 (3.46 ± 0.24), corneal
neovascularization was significantly less than Group 1 (6.76 ± 1.03) (p
<0.05). When the groups except the control group were compared; the
number of vessels was significantly lower in Group 3 and Group 4 than Group 2
(p <0.05).

Conclusion: In this study, both topical and subconjunctival bevacizumab were found to
be more effective than topical dexamethasone in the treatment of corneal NV
secondary to chemical burn.  

Keywords

Bevacizumab, corneal neovascularization, dexamethasone

Tavşanlarda Deneysel Kornea Neovaskülarizasyonunda Topikal ve Subkonjonktival Bevacizumabın Etkinliğinin Araştırılması

Abstract

ÖZ

Amaç: Deneysel tavşan modellerinde oluşturulan kimyasal yanığa sekonder korneal neovaskülarizasyon (NV) tedavisinde topikal ve subkonjonktival bevacizumabın etkinliğini topikal deksametazonla karşılaştırmak.

Araçlar ve Yöntem: Çalışmada toplam 24 adet tavşan kullanıldı. Hayvanlar kontrol (topikal %0.09 NaCl) (Grup 1), topikal deksametazon (Grup 2), subkonjonktival bevacizumab (Grup3) ve topikal bevacizumab (Grup 4) olmak üzere dört gruba ayrıldı. Deneklerin kornealarında gümüş nitratpotasyum nitrat ile kimyasal yanık oluşturuldu. Sonraki 10 gün boyunca her gruba ilgili ilaç uygulandı. Onuncu günde denekler sakrifiye edilip makroskopik ve histopatolojik olarak korneal neovaskülarizasyon değerlendirildi.

Bulgular: Histopatolojik incelemede grupların damar sayıları değerlendirildiğinde; Grup 2 (5.03±0.42), Grup 3 (3.36±0.15) ve Grup 4 (3.46±0.24)’te korneal neovaskülarizasyonda Grup 1 (6.76±1.03)’e göre anlamlı düzeyde az olduğu gözlendi (p<0.05). Kontrol grubu dışındaki gruplar kendi içinde karşılaştırıldığında; damar sayısının Grup 3 ve Grup 4’te Grup 2’ye göre belirgin düzeyde az olduğu gözlendi (p<0.05).

Sonuç: Bu çalışmada kimyasal yanığa sekonder korneal NV tedavisinde hem topikal hem de subkonjonktival bevacizumabın, topikal deksametazondan daha etkili olduğunu gösterilmiştir.

Keywords

Bevacizumab, Deksametazon, Korneal neovaskülarizasyon

References

• 1. Sarah B, Ibtissam H, Mohammed B, Hasna S, Abdeljalil M. Intrastromal Injection of Bevacizumab in the Management of Corneal Neovascularization: About 25 Eyes. J Ophthalmol 2016;2016:6084270.
• 2. Chang JH, Garg NK, Lunde E, Han KY, Jain S, Azar DT. Corneal neovascularization: an anti-VEGF therapy review. Surv Ophthalmol 2012;57(5):415-429.
• 3. Gupta D, Illingworth C. Treatments for corneal neovascularization: a review. Cornea 2011;30(8):927-938.
• 4. Patan S. Vasculogenesis and angiogenesis. Cancer Treat Res 2004;117:3-32.
• 5. Kvanta A. Ocular angiogenesis: the role of growth factors. Acta Ophthalmol Scand 2006;84(3):282-288.
• 6. Xu J, Li Y, Hong J. Progress of anti-vascular endothelial growth factor therapy for ocular neovascular disease: benefits and challenges. Chin Med J (Engl) 2014;127(8):1550-1557.
• 7. 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.
• 8. Stevenson W, Cheng SF, Dastjerdi MH, Ferrari G, Dana R. Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin). Ocul Surf 2012;10(2):67-83.
• 9. Gal-Or O, Livny E, Sella R, Nisgav Y, Weinberger D, Livnat T, Bahar I. Efficacy of Subconjunctival Aflibercept Versus Bevacizumab for Prevention of Corneal Neovascularization in a Rat Model. Cornea 2016;35(7):991-996.
• 10. Kim J, Kim D, Kim ES, Kim MJ, Tchah H. Topically administered bevacizumab had longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in rat corneal neovacularization. Int J Ophthalmol 2013;6(5):588-591.
• 11. Feizi S, Azari AA, Safapour S. Therapeutic approaches for corneal neovascularization. Eye Vis (Lond) 2017;4:28.
• 12. Peebo BB, Fagerholm P, Traneus-Rockert C, Lagali N. Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model. Angiogenesis 2011;14(3):393-405.
• 13. Cheng SF, Dastjerdi MH, Ferrari G, Okanobo A, Bower KS, Ryan DS, Amparo F, Stevenson W, Hamrah P, Nallasamy N, Dana R. Short-term topical bevacizumab in the treatment of stable corneal neovascularization. Am J Ophthalmol 2012;154(6):940-948.e941.
• 14. Bock F, Konig Y, Kruse F, Baier M, Cursiefen C. Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 2008;246(2):281-284.
• 15. You IC, Kang IS, Lee SH, Yoon KC. Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization. Acta Ophthalmol 2009;87(6):653-658.
• 16. Jacobs DS, Lim M, Carrasquillo KG, Rosenthal P. Bevacizumab for corneal neovascularization. Ophthalmology 2009;116(3):592-593; author reply 593-594.
• 17. Yoeruek E, Ziemssen F, Henke-Fahle S, Tatar O, Tura A, Grisanti S, Bartz-Schmidt KU, Szurman P. Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn. Acta Ophthalmol 2008;86(3):322-328.
• 18. Carrasco MA. Subconjunctival bevacizumab for corneal neovascularization in herpetic stromal keratitis. Cornea 2008;27(6):743-745.
• 19. Hasanreisoglu M, Weinberger D, Mimouni K, Luski M, Bourla D, Kramer M, Robinson A, Axer-Siegel R. Intravitreal bevacizumab as an adjunct treatment for neovascular glaucoma. Eur J Ophthalmol 2009;19(4):607-612.
• 20. Barros LF, Belfort R, Jr. The effects of the subconjunctival injection of bevacizumab (Avastin) on angiogenesis in the rat cornea. An Acad Bras Cienc 2007;79(3):389-394.
• 21. Hosseini H, Nejabat M, Mehryar M, Yazdchi T, Sedaghat A, Noori F. Bevacizumab inhibits corneal neovascularization in an alkali burn induced model of corneal angiogenesis. Clin Exp Ophthalmol 2007;35(8):745-748.
• 22. Ahmed A, Berati H, Nalan A, Aylin S. Effect of bevacizumab on corneal neovascularization in experimental rabbit model. Clin Exp Ophthalmol 2009;37(7):730-736.
• 23. Hashemian MN, Moghimi S, Kiumehr S, Riazi M, Amoli FA. Prevention and treatment of corneal neovascularization: comparison of different doses of subconjunctival bevacizumab with corticosteroid in experimental rats. Ophthalmic Res 2009;42(2):90-95.
• 24. Oner V, Kucukerdonmez C, Akova YA, Colak A, Karalezli A. Topical and subconjunctival bevacizumab for corneal neovascularization in an experimental rat model. Ophthalmic Res 2012;48(3):118-123.
• 25. Dastjerdi MH, Sadrai Z, Saban DR, Zhang Q, Dana R. Corneal penetration of topical and subconjunctival bevacizumab. Invest Ophthalmol Vis Sci 2011;52(12):8718-8723.
• 26. Krizova D, Vokrojova M, Liehneova K, Studeny P. Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab. J Ophthalmol 2014;2014:178132.
• 27. Cursiefen C, Wenkel H, Martus P, Langenbucher A, Nguyen NX, Seitz B, Kuchle M, Naumann GO. Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty. Graefes Arch Clin Exp Ophthalmol 2001;239(7):514-521.
• 28. Kim SW, Ha BJ, Kim EK, Tchah H, Kim TI. The effect of topical bevacizumab on corneal neovascularization. Ophthalmology 2008;115(6):e33-38.