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Marina Hovakimyan, Stefan Siewert, Wolfram Schmidt, Katrin Sternberg, Thomas Reske, Oliver Stachs, Rudolf Guthoff, Andreas Wree, Martin Witt, Klaus-Peter Schmitz, Reto Allemann; Development of an Experimental Drug Eluting Suprachoroidal Microstent as Glaucoma Drainage Device. Trans. Vis. Sci. Tech. 2015;4(3):14. doi: 10.1167/tvst.4.3.14.
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© ARVO (1962-2015); The Authors (2016-present)
A novel glaucoma drainage device (GDD) with local drug delivery (LDD) system was created and characterized for safety and effectiveness after implantation into the suprachoroidal space (SCS) of rabbit eyes.
Thin films of two different polymers, Poly(3-hydroxybutyrate) (P(3HB)) and Poly(4-hydroxybutyrate) (P(4HB)), containing the drugs mitomycin C (MitC) or paclitaxel (PTX) were attached to silicone-tubes to create LDD devices. The release kinetics of these drugs were explored in vitro using high performance liquid chromatography (HPLC). Twenty-four New Zealand white rabbits, randomly divided into eight groups, were implanted with different kinds of microstents into SCS. The intraocular pressure (IOP) was monitored noninvasively. After 6 weeks, rabbits were sacrificed and enucleated eyes were used for anterior segment optical coherence tomography (OCT), micro magnetic resonance imaging (MRI), and histology.
In vitro, faster drug release from both polymers was observed for MitC compared to PTX. Comparing polymers, the release from P(3HB) matrix was slower for both drugs. MRI and OCT showed all implants maintained a proper location. An effective IOP reduction was observed for up to 6 weeks in eyes with microstents combined with a drug-releasing LDD system. Overall, the surrounding tissue revealed mild-to-moderate inflammation. No pronounced fibrosis was observed in any of the groups. However, both drugs caused damage to the neighboring retina.
The suprachoroidal microstent reduced IOP with mild inflammation in rabbit eyes. To avoid negative effects on the retina, it is necessary to identify novel drugs with less cytotoxicity. Future studies are needed to explore the fibrotic process over the long-term.
The presented data serve as a proof of principle study for the concept of a suprachoroidal drug eluting microstent. Future device improvements will be focused on the design of LDD systems and the use of specific anti-inflammatory or antifibrotic agents with less cytotoxicity compared to MitC or PTX. Long-term animal studies using a reliable glaucoma model will be a further step towards clinical application and improvement of surgical glaucoma therapy.
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