Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration

Pharmacogenomics. 2012 Jul;13(9):1037-53. doi: 10.2217/pgs.12.77.


Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Blood Vessels / growth & development
  • Blood Vessels / pathology
  • Complement Factor H / genetics
  • Genetic Association Studies
  • Humans
  • Neovascularization, Pathologic* / drug therapy
  • Neovascularization, Pathologic* / genetics
  • Neovascularization, Pathologic* / pathology
  • Photochemotherapy
  • Polymorphism, Single Nucleotide
  • Porphyrins / administration & dosage*
  • Precision Medicine
  • Vascular Endothelial Growth Factor A / genetics
  • Verteporfin
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / genetics
  • Wet Macular Degeneration / pathology


  • Angiogenesis Inhibitors
  • Porphyrins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Verteporfin
  • Complement Factor H