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Management of Macular Hemorrhage pp 23–31Cite as

Subretinal Co-application of rtPA and Bevacizumab for Neovascular AMD with Submacular Hemorrhage

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Abstract

Exudative age-related macular degeneration (AMD) is the most frequent cause of acute submacular hemorrhage (SMH). Without treatment, the formation of a macular scar with poor visual function is the usual outcome. While several surgical treatment approaches have been proposed to date, there is no general consensus regarding optimal treatment of acute SMH. Vitrectomy with subretinal co-application of recombinant tissue plasminogen activator (rtPA) and bevacizumab followed by a gas tamponade is a new approach which has shown promising functional results in clinical studies. The aim of the co-application of rtPA and bevacizumab is to simultaneously displace submacular hemorrhage from the fovea and to reduce choroidal new vessel activity effectively. Experimental laboratory studies have shown that neither rtPA nor rtPA-generated plasmin cleaves or functionally inactivates bevacizumab. The experimental results show that both substances are compatible and may be co-applied in surgery.

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References

  1. Avery RL, Fekrat S, Hawkins BS, et al. Natural history of subfoveal hemorrhage in age-related macular degeneration. Retina. 1996;16:183–9.

    Article  CAS  PubMed  Google Scholar 

  2. Vander JF, Federman JL, Greven C, Slusher MM, Gabel VP. Surgical removal of massive subretinal hemorrhage associated with age-related macular degeneration. Ophthalmology. 1991;98:23–7.

    Article  CAS  PubMed  Google Scholar 

  3. Bressler NM, Bressler SB, Childs AL et al., for Submacular Surgery Trials (SST) Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report No. 13. Ophthalmology. 2004;111:1993–2006.

    Google Scholar 

  4. Lewis H. Intraoperative fibrinolysis of submacular hemorrhage with tissue plasminogen activator and surgical drainage. Am J Ophthalmol. 1994;118:559–68.

    Article  CAS  PubMed  Google Scholar 

  5. Chen CY, Hooper C, Chiu D, Chamberlain M, Karia N, Heriot WJ. Management of submacular hemorrhage with intravitreal injection of tissue plasminogen activator and expansile gas. Retina. 2007;27:321–8.

    Article  PubMed  Google Scholar 

  6. Hesse L, Schmidt J, Kroll P. Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas. Graefes Arch Clin Exp Ophthalmol. 1999;237:273–7.

    Article  CAS  PubMed  Google Scholar 

  7. Handwerger BA, Blodi BA, Chandra SR, Olsen TW, Stevens TS. Treatment of submacular hemorrhage with low-dose intravitreal tissue plasminogen activator injection and pneumatic displacement. Arch Ophthalmol. 2001;119:28–32.

    CAS  PubMed  Google Scholar 

  8. Kamei M, Misono K, Lewis H. A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits. Am J Ophthalmol. 1999;128:739–46.

    Article  CAS  PubMed  Google Scholar 

  9. Takeuchi A, Kricorian G, Yao XY, et al. The rate and source of albumin entry into saline-filled experimental retinal detachments. Invest Ophthalmol Vis Sci. 1994;35:3792–598.

    CAS  PubMed  Google Scholar 

  10. Jackson TL, Antcliff RJ, Hillenkamp J, Marshall J. Human retinal molecular weight exclusion limit and estimate of species variation. Invest Ophthalmol Vis Sci. 2003;44:2141–6.

    Article  PubMed  Google Scholar 

  11. Heiduschka P, Fietz H, Hofmeister S, et al. Penetration of bevacizumab through the retina after intravitreal injection in the monkey. Invest Ophthalmol Vis Sci. 2007;48:2814–23.

    Article  PubMed  Google Scholar 

  12. Haupert CL, BW MC II, Jaffe GJ. Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration. Am J Ophthalmol. 2001;131:208–15.

    Article  CAS  PubMed  Google Scholar 

  13. Olivier S, Chow DR, Packo KH. Subretinal recombinant tissue plasminogen activator injection and pneumatic displacement of thick submacular hemorrhage in age-related macular degeneration. Ophthalmology. 2004;111:1201–8.

    Article  PubMed  Google Scholar 

  14. Hillenkamp J, Surguch V, Framme C, Gabel VP, Sachs HG. Management of submacular hemorrhage with intravitreal versus subretinal injection of recombinant tissue plasminogen activator. Graefes Arch Clin Exp Ophthalmol. 2010;248:5–11.

    Article  CAS  PubMed  Google Scholar 

  15. Treumer F, Klatt C, Roider J, Hillenkamp J. Subretinal co-application of recombinant tissue plasminogen activator and bevacizumab for neovascular age-related macular degeneration with submacular hemorrhage. Br J Ophthalmol. 2010;94:48–53.

    Article  CAS  PubMed  Google Scholar 

  16. Treumer F, Roider J, Hillenkamp J. Long-term outcome of subretinal co-application of rtPA and bevacizumab followed by repeated intravitreal anti-VEGF injections for neovascular AMD with submacular hemorrhage. Br J Ophthalmol. 2012;96:708–13.

    Article  PubMed  Google Scholar 

  17. Schouten JS, La Heij EC, Webers CA, et al. A systematic review on the effect of bevacizumab in exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2009;247:1–11.

    Article  CAS  PubMed  Google Scholar 

  18. Heimes B, Lommatzsch A, Zeimer M, Gutfleisch M, Spital G, Dietzel M, Pauleikhoff D. Long-term visual course after anti-VEGF therapy for exudative AMD in clinical practice evaluation of the German reinjection scheme. Graefes Arch Clin Exp Ophthalmol. 2010;249:639–44.

    Article  PubMed  Google Scholar 

  19. Dadgostar H, Ventura AA, Chung JY, Sharma S, Kaiser PK. Evaluation of injection frequency and visual acuity outcomes for ranibizumab monotherapy in exudative age-related macular degeneration. Ophthalmology. 2009;116:1740–7.

    Article  PubMed  Google Scholar 

  20. Gerding H, Loukopoulos V, Riese J, Hefner L, Timmermann M. Results of flexible ranibizumab treatment in age-related macular degeneration and search for parameters with impact on outcome. Graefes Arch Clin Exp Ophthalmol. 2011;249:653–62.

    Article  CAS  PubMed  Google Scholar 

  21. Pauleikhoff D, Kirchhof B. Retreatment criteria in anti-VEGF therapy of exudative AMD: critical analysis of present regimes and new morphological definition of “lesion activity”. Graefes Arch Clin Exp Ophthalmol. 2011;249:631–2.

    Article  PubMed  Google Scholar 

  22. Mars WM, Zarnegar R, Michalopoulos GK. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. Am J Pathol. 1993;143:949–858.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Su EJ, Fredriksson L, Geyer M, et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med. 2008;14:731–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Klettner A, Puls S, Treumer F, Roider J, Hillenkamp J. Compatibility of recombinant tissue plasminogen activator (rtPA) and bevacizumab co-applied for neovascular age-related macular degeneration with submacular hemorrhage. Arch Ophthalmol. 2012;130:875–81.

    Article  CAS  PubMed  Google Scholar 

  25. Klettner A, Roider J. Comparison of bevacizumab, ranibizumab, and pegaptanib in vitro: efficiency and possible additional pathways. Invest Ophthalmol Vis Sci. 2008;49:4523–7.

    Article  PubMed  Google Scholar 

  26. Faure C, Macrez R, Vivien D, Sahel JA, Bonnel S. Interaction study between rtPA and bevacizumab. Br J Ophthalmol. 2011;95:743–4.

    Article  PubMed  Google Scholar 

  27. Verheul HM, Lolkema MP, Qian DZ, et al. Platelets take up the monoclonal antibody bevacizumab. Clin Cancer Res. 2007;13:5341–7.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, University Hospital Würzburg, Würzburg, Germany

    Jost Hillenkamp MD

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  1. Jost Hillenkamp MD
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Editors and Affiliations

  1. Augenklinik des Klinikums Ludwigshafen, Ludwigshafen, Germany

    Lars-Olof Hattenbach

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Hillenkamp, J. (2018). Subretinal Co-application of rtPA and Bevacizumab for Neovascular AMD with Submacular Hemorrhage. In: Hattenbach, LO. (eds) Management of Macular Hemorrhage. Springer, Cham. https://doi.org/10.1007/978-3-319-65877-3_4

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  • DOI: https://doi.org/10.1007/978-3-319-65877-3_4

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-65875-9

  • Online ISBN: 978-3-319-65877-3

  • eBook Packages: MedicineMedicine (R0)

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