Skip to main content
SpringerLink
Log in

Current and Emerging Therapies for Ocular Neovascularisation

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Ocular neovascularisation (ONV) is a pathological feature of many human blinding diseases. Here, we review current pharmacological therapies for these disorders and highlight emerging therapies in clinical trial for ONV. Finally, we discuss desirable characteristics of future ONV therapies, including innovative strategies for novel delivery to the back of the eye.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

Institutional subscriptions

Similar content being viewed by others

References

  1. Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358:2606–2617

    Article  PubMed  CAS  Google Scholar 

  2. Cheung N, Mitchell P, Wong TY (2010) Diabetic retinopathy. Lancet 376:124–136

    Article  PubMed  Google Scholar 

  3. European ophthalmics pharmaceuticals market (2010) Frost & Sullivan report M4AC-52 Web. 08 Oct. 2013

    Google Scholar 

  4. U.S. retinal therapeutics market (2011) Frost & Sullivan report N85D-52. Web. 08 Oct. 2013

    Google Scholar 

  5. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431

    Article  PubMed  CAS  Google Scholar 

  6. The CATT Research Group (2011) Ranibizumab and Bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364:1897–1908

    Article  PubMed Central  Google Scholar 

  7. Heier JS, Brown DM, Chong V, Korobelnik J-F, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U (2012) Intravitreal Aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548

    Article  PubMed  Google Scholar 

  8. Huang J, Li X, Li M, Li S, Xiao W, Chen X, Cai M, Wu Q, Luo D, Tang S, Luo Y (2012) Effects of intravitreal injection of KH902, a vascular endothelial growth factor receptor decoy, on the retinas of streptozotocin-induced diabetic rats. Diabetes Obes Metab 14:644–653

    Article  PubMed  CAS  Google Scholar 

  9. Lukason M, DuFresne E, Rubin H, Pechan P, Li Q, Kim I, Kiss S, Flaxel C, Collins M, Miller J, Hauswirth W, MacLachlan T, Wadsworth S, Scaria A (2011) Inhibition of choroidal neovascularization in a nonhuman primate model by intravitreal administration of an AAV2 vector expressing a novel anti-vegf molecule. Mol Ther 19:260–265

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Neurotech (2012) NT-503 VEGF-Antagonist. http://www.neurotechusa.com/VEGF-Antagonist.html. Accessed 08 Oct 2013

  11. Klein RJ, Zeiss C, Chew EY, Tsai J-Y, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308:385–389

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Ophthotech Corp (2013) ARC1905- Anti-C5 Aptamer. http://www.ophthotech.com/product-candidates/arc1905/. Accessed 08 Oct 2013

  13. Binley K, Widdowson P, Kelleher M, de Belin J, Loader J, Ferrige G, Carlucci M, Esapa M, Chipchase D, Angell-Manning D, Ellis S, Mitrophanous K, Miskin J, Bantseev V, Nork T, Miller P, Naylor S (2012) Safety and biodistribution of an equine infectious anemia virus-based gene therapy, RetinoStat(®), for age-related macular degeneration. Hum Gene Ther 23:980–989

    Article  PubMed  CAS  Google Scholar 

  14. Rasmussen H, Chu K, Campochiaro P, Gehlbach P, Haller J, Handa J, Nguyen Q, Sung J (2001) Clinical protocol. An open-label, phase I, single administration dose-escalation study of ADGVPEDF.11D (ADPEDF) in neovascular age-related macular degeneration (AMD). Hum Gene Ther 12:2029–2032

    PubMed  CAS  Google Scholar 

  15. Cloutier F, Lawrence M, Goody R, Lamoureux S, Al-Mahmood S, Colin S, Ferry A, Conduzorgues J-P, Hadri A, Cursiefen C, Udaondo P, Viaud E, Thorin E, Chemtob S (2012) Antiangiogenic activity of aganirsen in nonhuman primate and rodent models of retinal neovascular disease after topical administration. Invest Ophthalmol Vis Sci 53:1195–1203

    Article  PubMed  CAS  Google Scholar 

  16. Kim S, Bell K, Mousa SA, Varner JA (2000) Regulation of angiogenesis in vivo by ligation of integrin α5β1 with the central cell-binding domain of fibronectin. Am J Pathol 156:1345–1362

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Ramakrishnan V, Bhaskar V, Law D, Wong M, DuBridge R, Breinberg D, O’Hara C, Powers D, Liu G, Grove J, Hevezi P, Cass K, Watson S, Evangelista F, Powers R, Finck B, Wills M, Caras I, Fang Y, McDonald D, Johnson D, Murray R, Jeffry U (2006) Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent. J Exp Ther Oncol 5:273–286

    PubMed  CAS  Google Scholar 

  18. Zahn G, Vossmeyer D, Stragies R, Wills M, Wong C, Löffler K, Adamis A, Knolle J (2009) Preclinical evaluation of the novel small-molecule integrin Î ± 5β1 inhibitor jsm6427 in monkey and rabbit models of choroidal neovascularization. Arch Ophthalmol 127:1329–1335

    Article  PubMed  CAS  Google Scholar 

  19. Caballero S, Sengupta N, Binghaman DP, Timmers A, Romano C, Grant MB (2007) Oral Administration of AL-39324 Can Both Suppress and Cause Regression of Vascular Lesion Volume in Experimental Choroidal Neovascularization. ARVO Meeting Abstracts 48:1470

    Google Scholar 

  20. Doukas J, Mahesh S, Umeda N, Kachi S, Akiyama H, Yokoi K, Cao J, Chen Z, Dellamary L, Tam B, Racanelli-Layton A, Hood J, Martin M, Noronha G, Soll R, Campochiaro PA (2008) Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. J Cell Physiol 216:29–37

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Maier P, Unsoeld A, Junker B, Martin G, Drevs J, Hansen L, Agostini H (2005) Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice. Graefes Arch Clin Exp Ophthalmol 243:593–600

    Article  PubMed  CAS  Google Scholar 

  22. Takahashi K, Saishin Y, Saishin Y, King AG, Levin R, Campochiaro PA (2009) Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib. Arch Ophthalmol 127:494–499

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Kiernan DF, Mieler WF. Intraocular corticosteroids for posterior segment disease: 2012 update. Expert Opin Pharmacother. 2012; 13:1679–1694.

    Article  PubMed  CAS  Google Scholar 

  24. Comparison of Ranibizumab monotherapy and Ranibizumab combination therapies in recurrent or persistent choroidal neovascularization secondary to age-related macular degeneration. NCT01162746 http://www.ClinicalTrials.gov. Accessed 08 Oct 2013

  25. Aiello L, Vignati L, Sheetz M, Zhi X, Girach A, Davis M, Wolka A, Shahri N, Milton R, PKC-DRS Group, PKC-DRS2 Group (2011) Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the protein kinase C β inhibitor-diabetic retinopathy study and the protein kinase C β inhibitor-diabetic retinopathy study 2. Retina 31:2084–2094

    Article  PubMed  CAS  Google Scholar 

  26. Liang Z, Brooks J, Willard M, Liang K, Yoon Y, Kang S, Shim H. CXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway. Biochem Biophys Res Commun. 2007; 359:716–722.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Connolly B, Desai A, Garcia C, Thomas E, Gast M (2006) Squalamine lactate for exudative age-related macular degeneration. Ophthalmol Clin North Am 19:381–391

    PubMed  Google Scholar 

  28. Kiuchi K, Matsuoka M, Wu JC, Lima eSR, Kengatharan M, Verghese M, Ueno S, Yokoi K, Khu NH, Cooke JP, Campochiaro PA (2008) Mecamylamine suppresses basal and nicotine-stimulated choroidal neovascularization. Invest Ophthalmol Vis Sci 49:1705–1711

    Article  PubMed Central  PubMed  Google Scholar 

  29. Cohen MP, Hud E, Wu V-Y, Shearman CW (2008) Amelioration of diabetes-associated abnormalities in the vitreous fluid by an inhibitor of albumin glycation. Invest Ophthalmol Vis Sci 49:5089–5093

    Article  PubMed  Google Scholar 

  30. Nambu H, Nambu R, Melia M, Campochiaro PA (2003) Combretastatin A-4 phosphate suppresses development and induces regression of choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3650–3655

    Article  PubMed  Google Scholar 

  31. Jo N, Mailhos C, Ju M, Cheung E, Bradley J, Nishijima K, Robinson GS, Adamis AP, Shima DT (2006) Inhibition of Platelet-Derived Growth Factor B Signaling Enhances the Efficacy of Anti-Vascular Endothelial Growth Factor Therapy in Multiple Models of Ocular Neovascularization. Am J Pathol 168:2036–2053.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Ophthotech Corp (2012) Ophthotech’s novel anti-PDGF combination agent fovista demonstrated superior efficacy over lucentis monotherapy in large controlled wet AMD trial. http://www.ophthotech.com/. Accessed 08 Oct 2013

  33. Iconic Therapeutics (2010) hI-con1. http://www.iconictherapeutics.com/. Accessed 08 Oct 2013

Download references

Author information

Authors and Affiliations

  1. School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland

    Alison L. Reynolds & Breandán N. Kennedy

  2. The Vision Clinic, Circular Road, Kilkenny, Ireland

    David Kent

  3. Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA

    David Kent

Authors
  1. Alison L. Reynolds
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Kent
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Breandán N. Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alison L. Reynolds .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media, LLC

About this paper

Cite this paper

Reynolds, A., Kent, D., Kennedy, B. (2014). Current and Emerging Therapies for Ocular Neovascularisation. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_100

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_100

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation