Skip to main content

Advertisement

SpringerLink
Log in

Anti-VEGF Therapies and Blood Pressure: More Than Meets the Eye

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

“Wet” (also called neovascular) age-related macular degeneration (AMD) is a chronic progressive disease characterized by leakage of fluid or blood from choroidal neovascularization. It remains the leading cause of blindness in the developed world. Vascular endothelial growth factor (VEGF), which plays a key role in the pathogenesis of retinal neovascularization and vessel leakage leading to central vision loss, has emerged as a potential target in the treatment of wet AMD. Importantly, large-scale clinical trials have demonstrated that intravitreal VEGF antagonism prevents vision loss and may even improve visual acuity in patients with neovascular AMD. Because VEGF and its downstream mediator nitric oxide have a well-established cardioprotective role, however, it can be argued that the beneficial effects of VEGF antagonism in the eye may come at the cost of adverse systemic effects, particularly myocardial infarction and stroke.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gunn MR: Ophthalmoscopic evidence of (1) arterial changes associated with chronic renal diseases and (2) of increased arterial tension. Trans Ophthalmol Soc U K 1892, 12:124–125.

    Google Scholar 

  2. •• DellaCroce JT, Vitale AT: Hypertension and the eye. Curr Opin Ophthalmol 2008, 19:493–498. This is an excellent review of hypertension and ocular disease.

    Article  PubMed  Google Scholar 

  3. •• Wong TY, Mitchell P: The eye in hypertension. Lancet 2007, 369:425–435. This is another excellent review of hypertension and ocular disease.

    Article  PubMed  Google Scholar 

  4. Friedman DS, O’Colmain BJ, Munoz B, et al.: Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004, 122:564–572.

    Article  PubMed  Google Scholar 

  5. Lüscher TF, Vanhoutte PM: The Endothelium: Modulator of Cardiovascular Function. Boca Raton, FL: CRC Press; 1990.

    Google Scholar 

  6. Zachary I: Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am J Physiol Cell Physiol 2001, 280:C1375–C1386.

    CAS  PubMed  Google Scholar 

  7. Senger DR, Galli SJ, Dvorak AM, et al.: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983, 219:983–985.

    Article  CAS  PubMed  Google Scholar 

  8. Carmeliet P, Ferreira V, Breier G, et al.: Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996, 380:435–439.

    Article  CAS  PubMed  Google Scholar 

  9. Ferrara N, Carver-Moore K, Chen H, et al.: Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996, 380:439–442.

    Article  CAS  PubMed  Google Scholar 

  10. de Jong PT: Age-related macular degeneration. N Engl J Med 2006, 355:1474–1485.

    Article  PubMed  Google Scholar 

  11. • Jager RD, Mieler WF, Miller JW: Age-related macular degeneration. N Engl J Med 2008, 358:2606–2617. This article reviews the pathophysiology of AMD.

    Article  CAS  PubMed  Google Scholar 

  12. Kahn HA, Leibowitz HM, Ganley JP, et al.: The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study. Am J Epidemiol 1977, 106:33–41.

    CAS  PubMed  Google Scholar 

  13. Goldberg J, Flowerdew G, Smith E, et al.: Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol 1988, 128:700–710.

    CAS  PubMed  Google Scholar 

  14. Vingerling JR, Dielemans I, Bots ML, et al.: Age-related macular degeneration is associated with atherosclerosis. The Rotterdam Study. Am J Epidemiol 1995, 142:404–409.

    CAS  PubMed  Google Scholar 

  15. Wong TY, Tikellis G, Sun C, et al.: Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology 2007, 114:86–91.

    Article  PubMed  Google Scholar 

  16. Wong TY, Klein R, Sun C, et al.: Age-related macular degeneration and risk for stroke. Ann Intern Med 2006, 145:98–106.

    PubMed  Google Scholar 

  17. Duan Y, Mo J, Klein R, et al.: Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans. Ophthalmology 2007, 114:732–737.

    Article  PubMed  Google Scholar 

  18. • Tan JS, Wang JJ, Liew G, et al.: Age-related macular degeneration and mortality from cardiovascular disease or stroke. Br J Ophthalmol 2008, 92:509–512. This study found an association between AMD and cardiovascular events.

    Article  CAS  PubMed  Google Scholar 

  19. The Eye Disease Case-Control Study Group: Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 1992, 110:1701–1708.

    Google Scholar 

  20. Delaney WV Jr, Oates RP: Senile macular degeneration: a preliminary study. Ann Ophthalmol 1982, 14:21–24.

    PubMed  Google Scholar 

  21. Klein R, Klein BE, Franke T: The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 1993, 100:406–414.

    CAS  PubMed  Google Scholar 

  22. Maltzman BA, Mulvihill MN, Greenbaum A: Senile macular degeneration and risk factors: a case-control study. Ann Ophthalmol 1979, 11:1197–1201.

    CAS  PubMed  Google Scholar 

  23. Smith W, Mitchell P, Leeder SR, Wang JJ: Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study. Arch Ophthalmol 1998, 116:583–587.

    CAS  PubMed  Google Scholar 

  24. Vinding T: Age-related macular degeneration. An epidemiological study of 1000 elderly individuals. With reference to prevalence, funduscopic findings, visual impairment and risk factors. Acta Ophthalmol Scand Suppl 1995, (217):1–32.

    PubMed  Google Scholar 

  25. Vinding T, Appleyard M, Nyboe J, Jensen G: Risk factor analysis for atrophic and exudative age-related macular degeneration. An epidemiological study of 1000 aged individuals. Acta Ophthalmol (Copenh) 1992, 70:66–72.

    Article  CAS  Google Scholar 

  26. Liew G, Mitchell P: Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2007, 356:747–748; author reply 749–750.

    Google Scholar 

  27. Ferrara N: Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001, 280:C1358–C1366.

    CAS  PubMed  Google Scholar 

  28. Rosenfeld PJ, Brown DM, Heier JS, et al.: Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006, 355:1419–1431.

    Article  CAS  PubMed  Google Scholar 

  29. Brown DM, Kaiser PK, Michels M, et al.: Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006, 355:1432–1444.

    Article  CAS  PubMed  Google Scholar 

  30. Ueta T, Yanagi Y, Tamaki Y, Yamaguchi T: Cerebrovascular accidents in ranibizumab. Ophthalmology 2009, 116:362.

    Article  PubMed  Google Scholar 

  31. European Medicines Agency (EMEA): Ranibizumab (Lucentis): summary of product characteristics. 2007. Available at http://ec.europa.eu/enterprise/pharmaceuticals/register/2007/2007012218294/anx_18294_en.pdf. Accessed December 18, 2009.

  32. Gillies MC, Wong TY: Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2007, 356:748–749, author reply 749–750.

    Google Scholar 

  33. Larsson A, Skoldenberg E, Ericson H: Serum and plasma levels of FGF-2 and VEGF in healthy blood donors. Angiogenesis 2002, 5:107–110.

    Article  CAS  PubMed  Google Scholar 

  34. Wong TY, Liew G, Mitchell P: Clinical update: new treatments for age-related macular degeneration. Lancet 2007, 370:204–206.

    Article  PubMed  Google Scholar 

  35. Michels S, Rosenfeld PJ, Puliafito CA, et al.: Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twelve-week results of an uncontrolled open-label clinical study. Ophthalmology 2005, 112:1035–1047.

    Article  PubMed  Google Scholar 

  36. Rosenfeld PJ, Fung AE, Puliafito CA: Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 2005, 36:336–339.

    PubMed  Google Scholar 

  37. Cleary CA, Jungkim S, Ravikumar K, et al.: Intravitreal bevacizumab in the treatment of neovascular age-related macular degeneration; 6- and 9-month results. Eye 2008, 22:82–86.

    Article  CAS  PubMed  Google Scholar 

  38. Weigert G, Michels S, Sacu S, et al.: Intravitreal bevacizumab (Avastin) therapy versus photodynamic therapy plus intravitreal triamcinolone for neovascular age-related macular degeneration: 6-month results of a prospective, randomised, controlled clinical study. Br J Ophthalmol 2008, 92:356–360.

    Article  CAS  PubMed  Google Scholar 

  39. Algvere PV, Steen B, Seregard S, Kvanta A: A prospective study on intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration of different durations. Acta Ophthalmol 2008, 86:482–489.

    Article  CAS  PubMed  Google Scholar 

  40. Arias L, Caminal JM, Casas L, et al.: A study comparing two protocols of treatment with intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Br J Ophthalmol 2008, 92:1636–1641.

    Article  CAS  PubMed  Google Scholar 

  41. Azad RV, Khan MA, Chanana B, Azad S: Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to age-related macular degeneration in an Indian population. Jpn J Ophthalmol 2008, 52:52–56.

    Article  CAS  PubMed  Google Scholar 

  42. Bashshur ZF, Haddad ZA, Schakal AR, et al.: Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: the second year of a prospective study. Am J Ophthalmol 2009, 148:59.e1–65.e1.

    Google Scholar 

  43. Costagliola C, Semeraro F, Cipollone U, et al.: Changes in neovascular choroidal morphology after intravitreal bevacizumab injection: prospective trial on 156 eyes throughout 12-month follow-up. Graefes Arch Clin Exp Ophthalmol 2009, 247:1031–1037.

    Article  CAS  PubMed  Google Scholar 

  44. Geitzenauer W, Michels S, Prager F, et al.: Comparison of 2.5 mg/kg and 5 mg/kg systemic bevacizumab in neovascular age-related macular degeneration: twenty-four week results of an uncontrolled, prospective cohort study. Retina 2008, 28:1375–1386.

    Article  PubMed  Google Scholar 

  45. Moshfeghi AA, Rosenfeld PJ, Puliafito CA, et al.: Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twenty-four-week results of an uncontrolled open-label clinical study. Ophthalmology 2006, 113:2002.e1–2002.e12.

  46. Ferrara N, Hillan KJ, Novotny W: Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 2005, 333:328–335.

    Article  CAS  PubMed  Google Scholar 

  47. Algvere PV, Kvanta A, Seregard S: Shall we use Avastin or Lucentis for ocular neovascularization? Acta Ophthalmol 2008, 86:352–355.

    Article  CAS  PubMed  Google Scholar 

  48. •• 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. This article presents a systematic review of the effect of bevacizumab on AMD.

    Article  CAS  PubMed  Google Scholar 

  49. Comparison of AMD Treatments Trials (CATT): Lucentis - Avastin Trial. National Eye Institute, 2008. http://www.nei.nih.gov/catt/.

  50. A randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation. University of Bristol, 2009. http://cteu.bris.ac.uk/trials/ivan/.

  51. Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335–2342.

    Article  CAS  PubMed  Google Scholar 

  52. Gragoudas ES, Adamis AP, Cunningham ET Jr, et al.: Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004, 351:2805–2816.

    Article  CAS  PubMed  Google Scholar 

  53. Heier JS, Boyer DS, Ciulla TA, et al.: Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study. Arch Ophthalmol 2006, 124:1532–1542.

    Article  CAS  PubMed  Google Scholar 

  54. Fung AE, Lalwani GA, Rosenfeld PJ, et al.: An optical coherence tomography–guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007, 143:566–583.

    Article  CAS  PubMed  Google Scholar 

  55. Lalwani GA, Rosenfeld PJ, Fung AE, et al.: A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol 2009, 148:43.e1–58.e1.

    Google Scholar 

Download references

Disclosure

Dr. Ruschitzka has been a speaker for Pfizer and Novartis and has received honoraria from these companies. No other potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Cardiovascular Center Cardiology, University Hospital, Rämistrasse 100, Zürich, 8091, Switzerland

    Frank Enseleit & Frank Ruschitzka

  2. Department of Ophthalmology, Triemli Hospital Zürich, Birmensdorferstrasse 497, Zürich, 8063, Switzerland

    Stephan Michels

Authors
  1. Frank Enseleit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan Michels
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank Ruschitzka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank Ruschitzka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Enseleit, F., Michels, S. & Ruschitzka, F. Anti-VEGF Therapies and Blood Pressure: More Than Meets the Eye. Current Science Inc 12, 33–38 (2010). https://doi.org/10.1007/s11906-009-0082-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-009-0082-x

Keywords

Search

Navigation