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International Ophthalmology

, Volume 35, Issue 2, pp 221–227 | Cite as

Subconjunctival and/or intrastromal bevacizumab injections as preconditioning therapy to promote corneal graft survival

  • Romina Fasciani
  • Luigi Mosca
  • Maria Ilaria Giannico
  • Simone Antonio Ambrogio
  • Emilio Balestrazzi
Original Paper

Abstract

The purpose of this study is to investigate whether subconjunctival and/or intrastromal Bevacizumab injections could help to prevent graft failure in high-risk keratoplasties. Twenty seven eyes of 27 patients, affected by high immune rejection risk and corneal neovascularization, were involved in this prospective interventional case–control series (case group: 14 eyes and control group: 13 eyes). Case group was submitted to a cycle of three subconjunctival and/or intrastromal injections of 5 mg/0.2 ml Bevacizumab. After a mean period of 6.36 months ± 3.38 SD from the last injection, all patients underwent keratoplasty. An adjunctive injection was performed intraoperatively at the end of the surgical procedure. Control group did not receive any Bevacizumab injection, but directly underwent keratoplasty. Each patient was submitted to a complete eye examination and corneal confocal microscopy. The absence of immune rejection signs in the graft, at clinical and confocal microscopy examination, was considered as main outcome measure. All cases showed less ocular inflammation and activity of vessels. No side effects were detected after the injection procedure. No corneal graft rejection was seen during the follow-up (mean 26.1 months ± 5.7 SD) in the case group. Six eyes of the control group showed graft rejection 3.8 months ± 1.4 SD after keratoplasty. As a conclusion, Bevacizumab injection may represent a preconditioning treatment to improve prognosis in high-risk corneal transplantation. The procedure seems to be safe and it may help to reduce the inflammatory stimulus that plays a key role in corneal graft rejection.

Keywords

Graft rejection Keratoplasty Bevacizumab Corneal neovascularization Anti-VEGF 

Notes

Funding/Support

None.

Financial Disclosure

None.

References

  1. 1.
    Chang Jin-Hong, Garg Nitin K, Lunde Elisa et al (2012) Corneal neovascularization: an anti-VEGF therapy review. Surv Ophtahalmol 57(5):415–429CrossRefGoogle Scholar
  2. 2.
    Awadein A (2007) Subconjunctival bevacizumab for vascularized rejected corneal grafts. J Cataract Refract Surg 33:1991–1993CrossRefPubMedGoogle Scholar
  3. 3.
    Patel HY, Ormonde S, Brookes NH et al (2011) The New Zeland National Eye Bank: survival and visual outcome 1 year after penetrating keratoplasty. Cornea 30(7):760–764CrossRefPubMedGoogle Scholar
  4. 4.
    Panda A, Vanathi M, Kumar A, Dash Y, Priya S (2007) Corneal graft rejection. Surv Ophthalmol 52(4):375–396CrossRefPubMedGoogle Scholar
  5. 5.
    Vassileva PI, Hergeldzhieva TG (2009) Avastin use in high risk corneal transplantation. Graefes Arch Clin Exp Ophthalmol 247:1701–1706CrossRefPubMedGoogle Scholar
  6. 6.
    Amano S, Rohan R, Kuroki M et al (1998) Requirement for vascular endothelial growth factor in wound and inflammation related corneal neovascularization. Invest Ophthalmol Vis Sci 39:18–22PubMedGoogle Scholar
  7. 7.
    Niederkorn JY (2007) Immune mechanisms of corneal allograft rejection. Curr Eye Res 32:1005–1016CrossRefPubMedGoogle Scholar
  8. 8.
    Pleyer U, Schlickeiser S (2009) The taming of the shrew? The immunology of corneal transplantation. Acta Ophthalmol 87:488–497CrossRefPubMedGoogle Scholar
  9. 9.
    Mosca L, Fasciani R, Mosca L et al (2011) Graft rejection after Femtosecond-assisted deep anterior lamellar keratoplasty: report of 3 cases. Cornea 30(8):912–916CrossRefPubMedGoogle Scholar
  10. 10.
    Alessio G, L’Abbate M, Boscia F et al (2010) Excimer laser-assisted keratoplasty and the corneal endothelium. Am J Ophthalmol 150:88–96CrossRefPubMedGoogle Scholar
  11. 11.
    Joussen AM, Kruse FE, Volcker HE et al (1999) Topical application of methotrexate for inhibition of corneal angiogenesis. Graefes Arch Clin Exp Ophthalmol 237:920–927CrossRefPubMedGoogle Scholar
  12. 12.
    Lipman RM, Epstein RJ, Hendricks RL (1992) Suppression of corneal neovascularization with cyclosporine. Arch Ophthalmol 110:405–407CrossRefPubMedGoogle Scholar
  13. 13.
    D’Amato RJ, Loughnan MS, Flynn E et al (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91:4082–4085CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Kvanta A, Sarman S, Fagerholm P et al (2000) Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation associated corneal neovascularization. Exp Eye Res 70:419–428CrossRefPubMedGoogle Scholar
  15. 15.
    Gan L, Fagerholm P, Palmblad J (2004) Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing. Acta Ophthalmol Scand 82:557–563CrossRefPubMedGoogle Scholar
  16. 16.
    Edelman JL, Castro MR, Wen Y (1999) Correlation of VEGF expression by leukocytes with the growth and regression of blood vessels in the rat cornea. Invest Ophthalmol Vis Sci 40:1112–1123PubMedGoogle Scholar
  17. 17.
    Benayoun Y, Adenis JP, Casse G et al (2012) Effects of subconjunctival bevacizumab on corneal neovascularization: results of a prospective study. Cornea 31(8):934–944CrossRefGoogle Scholar
  18. 18.
    Symes RJ, Poole TRG (2010) Corneal graft surgery combined with subconjunctival bevacizumab (Avastin). Cornea 29:691–693PubMedGoogle Scholar
  19. 19.
    Acar BT, Halili E, Acar S (2013) The effect of different doses of subconjunctival bevacizumab injection on corneal neovascularization. Int Ophthalmol 33(5):507–513CrossRefPubMedGoogle Scholar
  20. 20.
    Petsoglou C, Balaggan KS, Dart JKG et al (2013) Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomized placebo-controlled double-masked trial. Br J Ophthalmol 97:28–32CrossRefPubMedGoogle Scholar
  21. 21.
    Stevenson W, Cheng SF, Dastjerdi MH et al (2012) Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin). Ocul Surf 10(2):67–83CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Ferrara N, Leung DW, Phillips HS (1991) Molecular characterization and distribution of vascular endothelial growth factor. In: Muller EE, MacLeod RB (eds) Neuroendocrine Perspectives. Springer-Verlag, New York, p 127CrossRefGoogle Scholar
  23. 23.
    Breier G, Albrecht U, Sterrer S et al (1992) Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532PubMedGoogle Scholar
  24. 24.
    Dastjerdi NH, Saban DN, Okanobo A et al (2010) Effects of topical and subconjunctival bevacizumab in high-risk corneal transplant survival. Invest Ophthalmol Vis Sci 51(5):2411–2417CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Niederer LR, Sherwin T, McGhee CNJ (2007) In vivo confocal microscopy of subepithelial infiltrates in human corneal transplant rejection. Cornea 26:501–504CrossRefPubMedGoogle Scholar
  26. 26.
    Cursiefen C, Chen Lu, Borges LP et al (2004) VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophages recruitment. J Clin Invest 113:1040–1050CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Traversi C, Nuti E, Bovone C (2009) Principi di immunologia. Newsletter S.I.TRA.C. No 3, 1–2 Oct 2009Google Scholar
  28. 28.
    Cursiefen C, Küchle M (1998) Naumann GOH: angiogenesis in corneal diseases: histopathologic evaluation of 254 human corneal buttons with neovascularisation. Cornea 17:611–613CrossRefPubMedGoogle Scholar
  29. 29.
    Rama P, Insacco C (2009). Rigetto nel trapianto di cornea perforante. Newsletter S.I.TRA.C.No 3, 3–4 Oct 2009Google Scholar
  30. 30.
    Fontana L, Parente G, Tassinari G (2009). Reazioni di rigetto dopo cheratoplastica lamellare anteriore profonda, aspetti clinici. Newsletter S.I.TRA.C.No 3, 3 Oct 2009Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Romina Fasciani
    • 1
  • Luigi Mosca
    • 1
  • Maria Ilaria Giannico
    • 1
  • Simone Antonio Ambrogio
    • 1
  • Emilio Balestrazzi
    • 1
  1. 1.Ophthalmology DepartmentA. Gemelli Policlinic, Catholic University of “Sacro Cuore”RomeItaly

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