title: Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child.
abstract: OBJECTIVE
  To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165.
  
  
  METHODS
  A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF.
  
  
  RESULTS
  Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection.
  
  
  CONCLUSIONS
  These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.
authors: 1] Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK [2] Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford, UK.
authors: E H
authors: EH
authors: Shao
authors: Kingston Hospital NHS Foundation Trust, Galsworthy Road, Kingston-upon-Thames, Surrey, UK.
authors: V
authors: V
authors: Sivagnanavel
authors: Kingston Hospital NHS Foundation Trust, Galsworthy Road, Kingston-upon-Thames, Surrey, UK.
authors: A
authors: A
authors: Dabbagh
authors: Kingston Hospital NHS Foundation Trust, Galsworthy Road, Kingston-upon-Thames, Surrey, UK.
authors: R
authors: R
authors: Dave
authors: Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
authors: S
authors: S
authors: Tempest-Roe
authors: Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
authors: F W K
authors: FW
authors: Tam
authors: 1] Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK [2] Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford, UK.
authors: S R
authors: SR
authors: Taylor
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D002829:Choroid / Q000293:injuries*; D020256:Choroidal Neovascularization / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D000069579:Ranibizumab / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab
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