Skip to main content
SpringerLink
Log in
Book cover

Corneal Disease pp 71–90Cite as

Antiangiogenic Treatment Options in the Cornea

  • Chapter
  • First Online:

  • 1103 Accesses

Abstract

The cornea uses redundant mechanisms to maintain its evolutionary highly conserved avascular state (“corneal angiogenic privilege”).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Cursiefen C, Chen L, Dana MR, Streilein JW (2003) Corneal lymphangiogenesis: evidence, mechanisms, and implications for corneal transplant immunology. Cornea 22:273–281

    Article  PubMed  Google Scholar 

  2. Streilein JW (2003) Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 3:879–889

    Article  PubMed  CAS  Google Scholar 

  3. Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J, Dana R, Masli S (2011) Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med 208:1083–1092

    Article  PubMed  CAS  Google Scholar 

  4. Cursiefen C, Masli S, Ng TF, Dana MR, Bornstein P, Lawler J, Streilein JW (2004) Roles of thrombospondin-1 and -2 in regulating corneal and iris angiogenesis. Invest Ophthalmol Vis Sci 45:1117–1124

    Article  PubMed  Google Scholar 

  5. Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana MR (2004) Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat Med 10:813–815

    Article  PubMed  CAS  Google Scholar 

  6. Collin HB (1966) Endothelial cell lined lymphatics in the vascularized rabbit cornea. Invest Ophthalmol 5:337–354

    PubMed  CAS  Google Scholar 

  7. Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D’Amore PA, Dana MR, Wiegand SJ, Streilein JW (2004) VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 113:1040–1050

    PubMed  CAS  Google Scholar 

  8. Cursiefen C, Schlotzer-Schrehardt U, Kuchle M, Sorokin L, Breiteneder-Geleff S, Alitalo K, Jackson D (2002) Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin. Invest Ophthalmol Vis Sci 43:2127–2135

    PubMed  Google Scholar 

  9. Cursiefen C, Cao J, Chen L, Liu Y, Maruyama K, Jackson D, Kruse FE, Wiegand SJ, Dana MR, Streilein JW (2004) Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival. Invest Ophthalmol Vis Sci 45:2666–2673

    Article  PubMed  Google Scholar 

  10. Dietrich T, Bock F, Yuen D, Hos D, Bachmann BO, Zahn G, Wiegand S, Chen L, Cursiefen C (2010) Cutting edge: lymphatic vessels, not blood vessels, primarily mediate immune rejections after transplantation. J Immunol 184:535–539

    Article  PubMed  CAS  Google Scholar 

  11. Chang JH, Gabison EE, Kato T, Azar DT (2001) Corneal neovascularization. Curr Opin Ophthalmol 12:242–249

    Article  PubMed  CAS  Google Scholar 

  12. Cursiefen C, Chen L, Saint-Geniez M, Hamrah P, Jin Y, Rashid S, Pytowski B, Persaud K, Wu Y, Streilein JW, Dana R (2006) Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision. Proc Natl Acad Sci USA 103:11405–11410

    Article  PubMed  CAS  Google Scholar 

  13. Regenfuss B, Bock F, Parthasarathy A, Cursiefen C (2008) Corneal (lymph)angiogenesis – from bedside to bench and back: a tribute to Judah Folkman. Lymphat Res Biol 6:191–201

    Article  PubMed  Google Scholar 

  14. Cursiefen C, Ikeda S, Nishina PM, Smith RS, Ikeda A, Jackson D, Mo JS, Chen L, Dana MR, Pytowski B, Kruse FE, Streilein JW (2005) Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling. Am J Pathol 166:1367–1377

    Article  PubMed  CAS  Google Scholar 

  15. Cursiefen C, Wenkel H, Martus P, Langenbucher A, Nguyen NX, Seitz B, Kuchle M, Naumann GO (2001) Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty. Graefes Arch Clin Exp Ophthalmol 239:514–521

    Article  PubMed  CAS  Google Scholar 

  16. Cursiefen C, Rummelt C, Kuchle M (2000) Immunohistochemical localization of vascular endothelial growth factor, transforming growth factor alpha, and transforming growth factor beta1 in human corneas with neovascularization. Cornea 19:526–533

    Article  PubMed  CAS  Google Scholar 

  17. Maguire MG, Stark WJ, Gottsch JD, Stulting RD, Sugar A, Fink NE, Schwartz A (1994) Risk factors for corneal graft failure and rejection in the collaborative corneal transplantation studies. Collaborative Corneal Transplantation Studies Research Group. Ophthalmology 101:1536–1547

    PubMed  CAS  Google Scholar 

  18. Bachmann B, Taylor RS, Cursiefen C (2010) Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based meta-analysis. Ophthalmology 117:1300–1305, e1307

    Article  PubMed  Google Scholar 

  19. Cursiefen C, Martus P, Nguyen NX, Langenbucher A, Seitz B, Kuchle M (2002) Corneal neovascularization after nonmechanical versus mechanical corneal trephination for non-high-risk keratoplasty. Cornea 21:648–652

    Article  PubMed  Google Scholar 

  20. Bachmann BO, Bock F, Wiegand SJ, Maruyama K, Dana MR, Kruse FE, Luetjen-Drecoll E, Cursiefen C (2008) Promotion of graft survival by vascular endothelial growth factor a neutralization after high-risk corneal transplantation. Arch Ophthalmol 126:71–77

    Article  PubMed  Google Scholar 

  21. Saharinen P, Tammela T, Karkkainen MJ, Alitalo K (2004) Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation. Trends Immunol 25:387–395

    Article  PubMed  CAS  Google Scholar 

  22. Cursiefen C, Maruyama K, Jackson DG, Streilein JW, Kruse FE (2006) Time course of angiogenesis and lymphangiogenesis after brief corneal inflammation. Cornea 25:443–447

    Article  PubMed  Google Scholar 

  23. Yamagami S, Dana MR (2001) The critical role of lymph nodes in corneal alloimmunization and graft rejection. Invest Ophthalmol Vis Sci 42:1293–1298

    PubMed  CAS  Google Scholar 

  24. Yamagami S, Dana MR, Tsuru T (2002) Draining lymph nodes play an essential role in alloimmunity generated in response to high-risk corneal transplantation. Cornea 21:405–409

    Article  PubMed  Google Scholar 

  25. Dietrich T, Onderka J, Bock F, Kruse FE, Vossmeyer D, Stragies R, Zahn G, Cursiefen C (2007) Inhibition of inflammatory lymphangiogenesis by integrin alpha5 blockade. Am J Pathol 171:361–372

    Article  PubMed  CAS  Google Scholar 

  26. Bock F, Onderka J, Dietrich T, Bachmann B, Pytowski B, Cursiefen C (2008) Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation. Graefes Arch Clin Exp Ophthalmol 246:115–119

    Article  PubMed  CAS  Google Scholar 

  27. Hos D, Saban DR, Bock F, Regenfuss B, Onderka J, Masli S, Cursiefen C (2011) Suppression of inflammatory corneal lymphangiogenesis by application of topical corticosteroids. Arch Ophthalmol 129:445–452

    Article  PubMed  CAS  Google Scholar 

  28. Bock F, Onderka J, Dietrich T, Bachmann B, Kruse FE, Paschke M, Zahn G, Cursiefen C (2007) Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. Invest Ophthalmol Vis Sci 48:2545–2552

    Article  PubMed  Google Scholar 

  29. Bock F, Konig Y, Kruse F, Baier M, Cursiefen C (2008) Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 246:281–284

    Article  PubMed  CAS  Google Scholar 

  30. Cursiefen C, Bock F, Horn FK, Kruse FE, Seitz B, Borderie V, Fruh B, Thiel MA, Wilhelm F, Geudelin B, Descohand I, Steuhl KP, Hahn A, Meller D (2009) GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization: interim results of a randomized phase II trial. Ophthalmology 116:1630–1637

    Article  PubMed  Google Scholar 

  31. Cursiefen C, Hofmann-Rummelt C, Kuchle M, Schlotzer-Schrehardt U (2003) Pericyte recruitment in human corneal angiogenesis: an ultrastructural study with clinicopathological correlation. Br J Ophthalmol 87:101–106

    Article  PubMed  CAS  Google Scholar 

  32. Pillai CT, Dua HS, Hossain P (2000) Fine needle diathermy occlusion of corneal vessels. Invest Ophthalmol Vis Sci 41:2148–2153

    PubMed  CAS  Google Scholar 

  33. Cursiefen C, Colin J, Dana R, Diaz-Llopis M, Faraj L, Garcia-Delpech S, Geerling G, Price F, Remeijer L, Rouse B, Seitz B, Udaondo P, Meller D, Dua H (2012) Consensus statement on indications for anti-angiogenic therapy in the management of corneal diseases associated with neovascularisation: outcome of an expert roundtable. Br J Ophthalmol 96:3–9

    Article  PubMed  Google Scholar 

  34. Koenig Y, Bock F, Kruse FE, Stock K, Cursiefen C (2012) Angioregressive Pretreatment of Mature Corneal Blood Vessels Before Keratoplasty: Fine-Needle Vessel Coagulation Combined With Anti-VEGFs. Cornea Feb 22. [Epub ahead of print]

    Article  PubMed  Google Scholar 

  35. Steven P, Bock F, Hüttmann G, Cursiefen C (2011) Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels. PLoS One 6(10):e26253. Epub 2011 Oct 20

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University of Cologne, Joseph-Stelzmann-Strasse 9, Köln, D-50924, Germany

    Claus Cursiefen M.D., FEBO & Felix Bock

Authors
  1. Claus Cursiefen M.D., FEBO
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Felix Bock
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claus Cursiefen M.D., FEBO .

Editor information

Editors and Affiliations

  1. University Eye Hospital, University of Freiburg, Killianstr. 5, Freiburg, 79106, Germany

    Thomas Reinhard

  2. Moorfields Eye Hospital, City Road 162, London, EC1V 2PD, United Kingdom

    Frank Larkin

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Cursiefen, C., Bock, F. (2013). Antiangiogenic Treatment Options in the Cornea. In: Reinhard, T., Larkin, F. (eds) Corneal Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28747-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-28747-3_5

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-28746-6

  • Online ISBN: 978-3-642-28747-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation