title: Vitreous VEGF clearance is increased after vitrectomy.
abstract: Purpose. Pars plana vitrectomy (PPV) has been reported to reduce macular thickness and improve visual acuity in patients with diabetic macular edema (ME). The hypothesis for the study was that after PPV, clearance is accelerated and VEGF concentrations are reduced. To test this hypothesis, hVEGF(165) injections were performed in rabbit eyes, with and without PPV, and vitreous VEGF levels were measured as a function of time. Methods. The PPV group rabbits had a bilateral 25-gauge PPV, and in the no-PPV group, rabbits had intact vitreous. Intravitreal injections of hVEGF(165) were performed, and the animals were euthanatized at time points up to 7 days. The vitreous was isolated and an enzyme-linked immunosorbent assay was used to measure the VEGF levels. Pharmacokinetic parameters were determined in a noncompartmental analysis approach. Results. Mean vitreous VEGF levels decreased more rapidly in eyes subjected to PPV than in no-PPV eyes. The vitreous VEGF half-life (t([)(1/2)(])) in PPV eyes was 10 times shorter than that in normal eyes. In addition, mean clearance and mean area under the curve (AUC) increased and decreased, respectively, in eyes that underwent PPV. Conclusions. VEGF clearance is increased after PPV. Reducing VEGF concentrations in the vitreous post-PPV may partially explain the improvement in macular thickness in some patients with ME. Unexpectedly, the half-life of VEGF in the vitreous, even in no-PPV eyes, was <3 hours, whereas compounds of similar molecular weight typically have longer vitreous half-lives. The back of the eye may be uniquely adapted with rapid-clearance mechanisms to regulate vitreous VEGF levels. Further study is suggested.
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA. susansle@usc.edu
authors.forename: Susan S
authors.initials: SS
authors.lastname: Lee
authors.forename: Corine
authors.initials: C
authors.lastname: Ghosn
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yu
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Zacharias
authors.forename: Henry
authors.initials: H
authors.lastname: Kao
authors.forename: Carmine
authors.initials: C
authors.lastname: Lanni
authors.forename: Natania
authors.initials: N
authors.lastname: Abdelfattah
authors.forename: Baruch
authors.initials: B
authors.lastname: Kuppermann
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: David Z
authors.initials: DZ
authors.lastname: D'Argenio
authors.forename: James A
authors.initials: JA
authors.lastname: Burke
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Hughes
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
mesh_terms: D000818:Animals; D019540:Area Under Curve; D004797:Enzyme-Linked Immunosorbent Assay; D006207:Half-Life; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000493:pharmacokinetics*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A