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Pharmacokinetic profile of intraocular aflibercept in patients receiving intravitreal aflibercept therapy for neovascular age-related macular degeneration

Session Details

Session Title: Quick Fire Free Paper 4

Session Date/Time: Sunday 14/09/2014 | 08:00-10:00

Paper Time: 08:15

Venue: Boulevard B

First Author: : C.H.Meyer SWITZERLAND

Co Author(s): :    C. Chan   Z. Liu   T.U. Krohne        

Abstract Details

Purpose:

There is a lack of studies on intraocular pharmacokinetics of aflibercept in human eyes. This study investigates the pharmacokinetics after intravitreal injections of 2.0 mg aflibercept for treatment of exudative AMD in patients.

Setting:

Pallas Clinic, Aarau

Methods:

A short 27-gauge needle connected to a tuberculin syringe with a plunger was used to retrieve 0.10 to 0.25 mL of aqueous via a limbal paracentesis immediately prior to each intravitreal 2.0 mg aflibercept injection for treatment of neovascular AMD. A syringe with specimen was immediately capped, taped, and placed in a freezer at -80-degree centigrade. Batches of specimens frozen in dry ice were shipped to University of Bonn for analysis. Each specimen was diluted in phosphate buffered saline (PBS) for enzyme-link immunosorbent assay (ELISA) for analysis of vascular endothelial growth factor (VEGF) and free-aflibercept levels, after appropriate calibration.

Results:

Twenty-nine specimens were retrieved from 11 patients (8 women, 3 men). Ages ranged from 76 to 89 (mean: 83.1). The best-spectacle corrected visual acuity ranged from 20/25 to 20/500 (median: 20/60). All but one eye had PCIOL. The interval from last injection to specimen retrieval ranged from 0 to 69 days (median: 37.5 days). Only 3 naïve eyes had VEGF levels ≥ 9 pg/mL (9,26, and 74 pg/mL). Marked VEGF suppression was noted for all non-naïve eyes up till 69 days from last injection, with VEGF levels ≤ 10 pg/mL in 23 specimens, and between 10 and 20 pg/ml in 3 specimens (obtained ≥ 50 days). Results are consistent with mathematical model predicting suppression of intraocular VEGF level for 72 days after a single aflibercept injection (M Stewart). This is in contrast to 27-38 days for bevacizumab and 36.4 days (Muether et al) for ranibizumab in VEGF-binding after a single injection.

Conclusions:

A single Intravitreal injection of 2.0 mg aflibercept results in marked VEGF suppression for at least 70 days. Further investigation will detect the upper boundary in duration of suppression. This information is highly relevant for clinicians treating patients with neovascular AMD.

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