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Simon Dörsam, Shanna Litau, Patrick R Merz, Björn Wängler, Lothar R Schad, Gerd U Auffarth, Elfriede Friedmann, Jorge Chacon-Caldera; Magnetic resonance imaging of anti-VEGF drug diffusion in the human eye. Invest. Ophthalmol. Vis. Sci. 2019;60(11):PB0163. doi: https://doi.org/.
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Today's standard therapy of the most important epidemiological retinal diseases e.g. age-related macular degeneration and macular edema in diabetic retinopathy is the intravitreal anti-VEGF (Vascular Endothelial Growth Factor) monotherapy. It consists of serial injections into the vitreous humor through pars plana. The exact amount and position of the injections relies on empirical knowledge and the treatment often fails. Here we present dynamic MR imaging of the anti-VEGF drug EYLEA® after injection in autopsy eyes to visualize its distribution.
All procedures conformed to HIPAA regulations and the Declaration of Helsinki for research involving human subjects. We performed MRI on two human autopsy eyes (Ethics votum S-134/2018) enucleated within 24h after death and scanned within 48h. Intra ocular pressure was adjusted to normal by injection of ophthalmic viscosurgical device (HEALON, Johnson & Johnson Vision, USA) near the optic nerve before examination. To make the drug visible in the MRI, the syringe was washed out with 2 mg gadolinium before use. The remaining amount was mixed with the drug and used as a stainer. The injection of 2 mg (50 µl) EYLEA® was performed following the instructions for use. For comparison in the second eye 2 mg gadolinium was injected. The eyes were scanned in 50ml centrifugation tubes (Sarstedt, Germany). MRI measurements were acquired simultaneously in a preclinical 9.4T animal scanner (Bruker Biospec 94/20, Ettlingen, Germany) using a Bruker quadrature volumetric transceiver coil 5 min after drug injection. A 2D RARE sequence was used with the parameters: TE/TR=11/618ms, FA=90°, Rare Factor 4, Resolution=200µmx200µm, Slices=24 with 4mm thickness, Averages=3, TA=22m49s.
We obtained whole eye data of drug distribution which diffused inhomogeneously in the vitreous and was visible around the injection site, the middle of the eye and at the bottom near the optic nerve. The interconnected shape of the drug distribution indicates the action of the gravitational force.
The data could be used for treatment planning and outcome predictions. Moreover, vitreous consistency which differs individually with age and disease could also be assessed.
This abstract was presented at the 2019 ARVO Imaging in the Eye Conference, held in Vancouver, Canada, April 26-27, 2019.
Distribution of gadolinium in the first autopsy eye and of anti-VEGF stained with gadolinium in the second autopsy eyes.
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