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

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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.

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References

  1. Chang Jin-Hong, Garg Nitin K, Lunde Elisa et al (2012) Corneal neovascularization: an anti-VEGF therapy review. Surv Ophtahalmol 57(5):415–429

    Article  Google Scholar 

  2. Awadein A (2007) Subconjunctival bevacizumab for vascularized rejected corneal grafts. J Cataract Refract Surg 33:1991–1993

    Article  PubMed  Google Scholar 

  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):760–764

    Article  PubMed  Google Scholar 

  4. Panda A, Vanathi M, Kumar A, Dash Y, Priya S (2007) Corneal graft rejection. Surv Ophthalmol 52(4):375–396

    Article  PubMed  Google Scholar 

  5. Vassileva PI, Hergeldzhieva TG (2009) Avastin use in high risk corneal transplantation. Graefes Arch Clin Exp Ophthalmol 247:1701–1706

    Article  CAS  PubMed  Google Scholar 

  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 39:18–22

    CAS  PubMed  Google Scholar 

  7. Niederkorn JY (2007) Immune mechanisms of corneal allograft rejection. Curr Eye Res 32:1005–1016

    Article  CAS  PubMed  Google Scholar 

  8. Pleyer U, Schlickeiser S (2009) The taming of the shrew? The immunology of corneal transplantation. Acta Ophthalmol 87:488–497

    Article  CAS  PubMed  Google Scholar 

  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):912–916

    Article  PubMed  Google Scholar 

  10. Alessio G, L’Abbate M, Boscia F et al (2010) Excimer laser-assisted keratoplasty and the corneal endothelium. Am J Ophthalmol 150:88–96

    Article  PubMed  Google Scholar 

  11. Joussen AM, Kruse FE, Volcker HE et al (1999) Topical application of methotrexate for inhibition of corneal angiogenesis. Graefes Arch Clin Exp Ophthalmol 237:920–927

    Article  CAS  PubMed  Google Scholar 

  12. Lipman RM, Epstein RJ, Hendricks RL (1992) Suppression of corneal neovascularization with cyclosporine. Arch Ophthalmol 110:405–407

    Article  CAS  PubMed  Google Scholar 

  13. D’Amato RJ, Loughnan MS, Flynn E et al (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91:4082–4085

    Article  PubMed Central  PubMed  Google Scholar 

  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 70:419–428

    Article  CAS  PubMed  Google Scholar 

  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 82:557–563

    Article  CAS  PubMed  Google Scholar 

  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 40:1112–1123

    CAS  PubMed  Google Scholar 

  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):934–944

    Article  Google Scholar 

  18. Symes RJ, Poole TRG (2010) Corneal graft surgery combined with subconjunctival bevacizumab (Avastin). Cornea 29:691–693

    PubMed  Google Scholar 

  19. Acar BT, Halili E, Acar S (2013) The effect of different doses of subconjunctival bevacizumab injection on corneal neovascularization. Int Ophthalmol 33(5):507–513

    Article  PubMed  Google Scholar 

  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 97:28–32

    Article  PubMed  Google Scholar 

  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):67–83

    Article  PubMed Central  PubMed  Google Scholar 

  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 127

    Chapter  Google Scholar 

  23. Breier G, Albrecht U, Sterrer S et al (1992) Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532

    CAS  PubMed  Google Scholar 

  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):2411–2417

    Article  PubMed Central  PubMed  Google Scholar 

  25. Niederer LR, Sherwin T, McGhee CNJ (2007) In vivo confocal microscopy of subepithelial infiltrates in human corneal transplant rejection. Cornea 26:501–504

    Article  PubMed  Google Scholar 

  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 113:1040–1050

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Traversi C, Nuti E, Bovone C (2009) Principi di immunologia. Newsletter S.I.TRA.C. No 3, 1–2 Oct 2009

  28. Cursiefen C, Küchle M (1998) Naumann GOH: angiogenesis in corneal diseases: histopathologic evaluation of 254 human corneal buttons with neovascularisation. Cornea 17:611–613

    Article  CAS  PubMed  Google Scholar 

  29. Rama P, Insacco C (2009). Rigetto nel trapianto di cornea perforante. Newsletter S.I.TRA.C.No 3, 3–4 Oct 2009

  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 2009

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Authors and Affiliations

  1. Ophthalmology Department, A. Gemelli Policlinic, Catholic University of “Sacro Cuore”, Largo A. Gemelli 8, 00168, Rome, Italy

    Romina Fasciani, Luigi Mosca, Maria Ilaria Giannico, Simone Antonio Ambrogio & Emilio Balestrazzi

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  1. Romina Fasciani
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  2. Luigi Mosca
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  3. Maria Ilaria Giannico
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  4. Simone Antonio Ambrogio
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  5. Emilio Balestrazzi
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Correspondence to Romina Fasciani.

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Fasciani, R., Mosca, L., Giannico, M.I. et al. Subconjunctival and/or intrastromal bevacizumab injections as preconditioning therapy to promote corneal graft survival. Int Ophthalmol 35, 221–227 (2015). https://doi.org/10.1007/s10792-014-9938-4

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  • DOI: https://doi.org/10.1007/s10792-014-9938-4

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