title: The influence of genetics on response to treatment with ranibizumab (Lucentis) for age-related macular degeneration: the Lucentis Genotype Study (an American Ophthalmological Society thesis).
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) has a complex etiology arising from genetic and environmental influences. This past decade have seen several genes associated with the disease. Variants in five genes have been confirmed to play a major role. The objective of this study was to evaluate whether genes influence treatment response to ranibizumab for neovascular AMD. The hypothesis was that an individual's genetic variation will determine treatment response.
  
  
  METHODS
  The study was a two-site prospective open-label observational study of patients newly diagnosed with exudative (neovascular) AMD receiving intravitreal ranibizumab therapy. Treatment-naïve patients were enrolled at presentation and received monthly "as needed" therapy. Clinical data was collected monthly and DNA extracted. Genotyping was performed using the Illumina (San Diego, California) 660-Quad single-nucleotide polymorphism (SNP) chip. Regression analyses were performed to identify SNPs associated with treatment-response end points.
  
  
  RESULTS
  Sixty-five patients were enrolled. No serious adverse events were recorded. The primary outcome measure was change in ETDRS visual acuity at 12 months. A SNP in the CFH gene was found to be associated with less improvement in visual acuity while receiving ranibizumab therapy. The C3 gene, among others, was associated with reduced thickening and improved retinal architecture. VEGFA, FLT1, and CFH were associated with requiring fewer ranibizumab injections over the 12-month study.
  
  
  CONCLUSIONS
  This study is one of the first prospective pharmacogenetic study of intravitreal ranibizumab. Although preliminary, the results identify a number of putative genetic variants, which will be further examined by replication and functional studies to elucidate the complete pharmacogenetic architecture of therapy for AMD.
authors.affiliation: Divisions of Retina and Ophthalmic Genetics, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Peter James
authors.initials: PJ
authors.lastname: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000209:etiology; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000069579:Ranibizumab; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D014792:Visual Acuity
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D040281:Vascular Endothelial Growth Factor Receptor-1; D000069579:Ranibizumab