Vitreous VEGF Clearance is Increased Following Vitrectomy

Abstract

Purpose: : Pars plana vitrectomy (PPV) has been reported to reduce macular thickness in patients with diabetic macular edema (DME). A theoretical mechanism includes improved oxygenation in the vitreous following PPV reduces retinal ischemia and VEGF expression. Another explanation is VEGF clearance from the vitreous cavity is increased following PPV. To test this hypothesis, VEGF injections were done in rabbit eyes, with and without PPV, and vitreous VEGF levels were measured as a function of time.

Methods: : 32 eyes of 16 DB rabbits were used. 8 animals had bilateral complete PPV by a VR surgeon. The injected eyes had 500 ng of hVEGF 165 placed in the mid-vitreous and 2 animals (4 eyes) were euthanized at each time point: baseline (pre-injection), 4 hours, 4 days, 7 days. Vitreous was isolated from each eye and Elisa VEGF quantitation was performed using VEGF Quantikine® Kit SVE00 (R&D Systems, Minneapolis, MN). Pharmacokinetic parameters were calculated using Pharsight WinNonlin® Pro Version 5. 2 (Mountain View, CA).

Results: : Mean vitreous VEGF levels decreased more rapidly in eyes with PPV compared to eyes with no PPV (Table 1). Mean Clearance values and mean AUC values were increased and decreased, respectively, in eyes with PPV (Table 2).

Conclusions: : VEGF clearance is increased following PPV. Reducing VEGF exposure posteriorly may partially explain the improvement in macular thickness in some patients with DME following PPV. Unexpectedly, the clearance of VEGF (MW ~20 KD) from the vitreous, even in non-PPV eyes, was higher than clearance values reported for smaller MW compounds. VEGF sequestration by heparin sulfate proteoglycans in the anterior segment and rapid elimination through aqueous outflow pathways has been previously reported to control pathologic neovascularization. In addition, the back of the eye may be uniquely adapted with rapid clearance mechanisms to regulate vitreous VEGF levels and further study is suggested.

Keywords: vascular endothelial growth factor • retinal neovascularization • vitreous