Influence of ocular volume and lens status on pharmacokinetics and duration of action of intravitreal vascular endothelial growth factor inhibitors

Retina. 2015 Jan;35(1):69-74. doi: 10.1097/IAE.0000000000000265.

Abstract

Purpose: To assess the effects of ocular axial length, refraction, and lens status on pharmacokinetics and duration of action of the vascular endothelial growth factor (VEGF) inhibitors ranibizumab and bevacizumab after intravitreal injection in humans.

Methods: In 119 eyes of 119 patients, aqueous humor was sampled at different time points after intravitreal injection of ranibizumab or bevacizumab, and either drug or VEGF concentrations were measured by enzyme-linked immunosorbent assays and Luminex multiplex bead technology, respectively. Relative deviation of the measured drug concentrations from the time-corrected mean values was calculated (n = 41). Repetitive VEGF measurements were preformed to identify the duration of complete suppression of ocular VEGF activity for individual eyes (n = 78). In addition, axial length, spherical equivalent refraction, and lens status were determined.

Results: For neither ranibizumab nor bevacizumab, a correlation between ocular pharmacokinetics (as measured by relative deviation of drug concentration from the mean) and axial length was detected in phakic eyes (Spearman's correlation coefficient, r = 0.084; P = 0.600). Similarly, the duration of action of intravitreal ranibizumab (as measured by VEGF suppression time) did not correlate with spherical equivalent refraction in phakic eyes (Spearman's correlation coefficient, r = 0.164; P = 0.301) and was not different between phakic and pseudophakic eyes (P = 0.694; Mann-Whitney U test).

Conclusion: The results indicate that ocular volume and lens status have no relevant impact on ocular pharmacokinetics and duration of action of VEGF-inhibitory drugs and may, thus, be excluded as factors accounting for the high interindividual variability in morphologic and functional responses to intravitreal anti-VEGF therapy.

MeSH terms

  • Angiogenesis Inhibitors / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Aqueous Humor / metabolism*
  • Axial Length, Eye / anatomy & histology*
  • Bevacizumab
  • Biological Availability
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intravitreal Injections
  • Lens, Crystalline / physiology*
  • Macular Edema / drug therapy
  • Macular Edema / metabolism
  • Male
  • Middle Aged
  • Ranibizumab
  • Refraction, Ocular / physiology
  • Retinal Diseases / drug therapy
  • Retinal Diseases / metabolism*
  • Retinal Vein Occlusion / drug therapy
  • Retinal Vein Occlusion / metabolism
  • Time Factors
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Wet Macular Degeneration / drug therapy
  • Wet Macular Degeneration / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Ranibizumab