title: Long-term alterations of systemic vascular endothelial growth factor levels in patients treated with ranibizumab for age-related macular degeneration.
abstract: OBJECTIVE
  To analyze long-term changes of systemic vascular endothelial growth factor (VEGF) levels in patients treated with ranibizumab for neovascular age-related macular degeneration.
  
  
  METHODS
  Sixty-one patients with neovascular age-related macular degeneration and 68 age-matched controls were included in the study. Patients were treated with ranibizumab on a pro re nata regimen. Plasma samples were collected before initiation of treatment and after 1 year (30 patients) or 2 years (31 patients) of treatment. Vascular endothelial growth factor was measured by Luminex microbead analysis.
  
  
  RESULTS
  At baseline, patients with neovascular age-related macular degeneration and controls did not differ significantly in VEGF levels (P = 0.062). There was a significant decline in systemic VEGF levels of 39.5% after 1 year (34.2 ± 17.2 pg/mL to 20.7 ± 14.0 pg/mL; P = 7.50 × 10(-5)) and of 46.7% after 2 years (40.4 ± 24.1 pg/mL to 21.5 ± 23.3 pg/mL; P = 2.48 × 10(-4)) of treatment. Patients with persistent activity of choroidal neovascularization showed a significantly smaller decrease of plasma VEGF levels than patients with dry intervals despite the higher number of injections (P = 0.048).
  
  
  CONCLUSIONS
  In addition to immediate effects limited to days if not hours, ranibizumab also leads to long-term alterations of systemic VEGF to subnormal levels. Patients with persistent choroidal neovascularization activity showed a less pronounced VEGF decrease. Therefore, VEGF levels might be a useful marker for treatment response.
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Enders
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Muether
authors.forename: Manuel
authors.initials: M
authors.lastname: Hermann
authors.forename: Tina
authors.initials: T
authors.lastname: Ristau
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D011446:Prospective Studies; D000069579:Ranibizumab; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D057135:Wet Macular Degeneration / Q000097:blood / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab