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Vitreous VEGF clearance is increased after vitrectomy.

Susan S Lee1, Corine Ghosn, Zhiling Yu

  • 1Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA. susansle@usc.edu

Investigative Ophthalmology & Visual Science
|December 19, 2009
PubMed
Summary

Pars plana vitrectomy (PPV) accelerates vascular endothelial growth factor (VEGF) clearance from the vitreous. This enhanced VEGF removal may contribute to reduced macular thickness in patients with diabetic macular edema.

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Area of Science:

  • Ophthalmology
  • Vitreoretinal Surgery
  • Molecular Biology

Background:

  • Diabetic macular edema (ME) is a leading cause of vision loss.
  • Pars plana vitrectomy (PPV) has shown potential in reducing macular thickness and improving visual acuity in ME patients.
  • The underlying mechanisms for PPV's efficacy, particularly concerning vitreous fluid dynamics and growth factor concentrations, require further elucidation.

Purpose of the Study:

  • To investigate the effect of PPV on the clearance rate of vascular endothelial growth factor (VEGF) from the vitreous.
  • To test the hypothesis that PPV accelerates VEGF clearance and reduces its concentration in the vitreous.
  • To determine the pharmacokinetic parameters of VEGF in rabbit eyes with and without PPV.

Main Methods:

  • Bilateral 25-gauge PPV was performed in one group of rabbits; the other group served as controls with intact vitreous.
  • Intravitreal injections of human VEGF (hVEGF(165)) were administered to both groups.
  • Vitreous VEGF levels were measured using enzyme-linked immunosorbent assay at various time points up to 7 days post-injection.
  • Pharmacokinetic parameters, including half-life and clearance, were analyzed using a noncompartmental approach.

Main Results:

  • Vitreous VEGF levels decreased significantly faster in eyes that underwent PPV compared to control eyes.
  • The vitreous half-life of VEGF was approximately 10 times shorter in the PPV group than in the no-PPV group.
  • Mean VEGF clearance was increased, and the mean area under the curve (AUC) was decreased in eyes following PPV.

Conclusions:

  • PPV significantly enhances the clearance of VEGF from the vitreous.
  • The accelerated removal of VEGF post-PPV may partially explain the observed improvements in macular thickness for patients with diabetic ME.
  • Surprisingly, VEGF exhibited a short half-life (<3 hours) even in normal rabbit eyes, suggesting inherent rapid clearance mechanisms in the posterior segment of the eye.