Dexamethasone-Eluting Contact Lenses Inhibit VEGF-Induced Retinal Vascular Leakage in a Rabbit Model

Abstract

Purpose : Contact lenses are being increasing explored for ocular drug delivery due to an interest in the pursuit of higher efficiency and better patience compliance than eye drops. They may also be an option to replace intravitreal injection to deliver drugs to the back of the eye. The goal of the experiment is to evaluate the efficacy of dexamethasone-eluting contact lenses (Dex-CL) on Vascular Endothelial Growth Factor (VEGF)-induced retinal vascular leakage in a rabbit model and to compare the efficacy to intravitreal dexamethasone injection (IVT-Dex).

Methods : Retinal vascular leakage was induced by injecting human VEGF-165 (500 ng in 0.05 ml) into the right eye of New Zealand pigmented rabbits using 5 experimental groups (n = 4/group): 1) No Treatment, 2) a single IVT-Dex (400 µg in 100 µl), 3) Dex-CL, 4) topical Dex sodium phosphate drops (0.1 %, 8 drops a day), 5) Vehicle contact lenses without dexamethasone. Retinal vascular leakage was analyzed on day 0 for baseline and after 2 days using fluorescein angiography (FA) and scanning ocular fluorophotometery (SOF). After imaging at 2 days, the animals were euthanized and eye tissue extracted. Two masked retina experts graded late-phase FA on a standardized scale from 0-2 (0=no evidence of leakage, 1=mild to moderate leakage not obscuring the vascular pattern, 2=severe leakage obscuring the individual capillaries). SOF gives the fluorescein concentration along the optical axis from retina to cornea. The AUC of the curve gives the total fluorescein concentration. The baseline (day 0) fluorescein concentration was subtracted from day 2 concentration to give change in fluorescein concentration.

Results : Dex-CL and IVT-Dex had lower FA grading score and fluorescein concentration in the eye than the No Treatment group and Vehicle Lens group demonstrating effective inhibition of retinal vascular leakage (table 1).

Conclusions : The Dex-CL effectively inhibited VEGF-induced retinal leakage similar to the efficacy of intravitreal dexamethasone injection. Contact lens drug delivery may be an option for treating conditions in the back of the eye such as Diabetic Macular Edema and Retinal Vein Occlusions.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

FA grading and fluorescein concentration. Data shown as median (Interquartile range)