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Katrin Voelter, Christoph Tappeiner, Karina Klein, Nicole Borel, Deborah Bruetsch, Fernando Laguna Sanz, Simon Pot; The intracameral fibrinolytic capacity and toxicity of Desmoteplase compared to tissue plasminogen activator in a rabbit model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2527.
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© ARVO (1962-2015); The Authors (2016-present)
Tissue plasminogen activator (t-PA), injected intracamerally, is the gold standard to resolve fibrin in the anterior chamber. A drug with better corneal permeability to allow topical application would be desirable. Therefore, Desmoteplase (DSPA) was evaluated as alternative regarding ocular permeation, fibrinolytic efficacy and toxicity after topical and intracameral application.
First, permeation of DSPA (1.4mg/ml) through corneoscleral tissues of different species was evaluated in a diffusion chamber in vitro. Second, fibrin clots were induced in the left anterior chamber of 44 female New Zealand White rabbits, followed by drug application 24 hours (h) after clot induction. DSPA eyedrops (2 mg/ml) were compared to carrier solution in a multiple drop regimen (n=8 per group). Intracameral injections of DSPA (0.6 µg) and t-PA (25 µg) were evaluated for their fibrinolytic efficacy (n=14 per group). Drug efficacy was measured by clot size reduction over 24h. Right eyes served as negative controls. Biocompatibility was evaluated via ophthalmic examinations. Animals were euthanized 48h after clot induction, toxicity was determined histologically. D-dimer levels in aqueous humor were analysed via enzyme-linked immunosorbent assays. Statistical evalution was performed using the Mann-Whitney U Test, ordinal mixed effects and mixed linear models.
DSPA permeated through all tissues ex vivo. In vivo evaluation of topical treatment effect was therefore pursued. No significant differences in clot size reduction at 24h were seen between topically treated groups (Mean +/- SD: 60% +/- 25% (DSPA), 40% +/- 23% (carrier), p=0.2) and between intracameral groups (97% +/- 9% (DSPA), 100% +/- 0% (t-PA), p=0.2) at the tested drug concentrations. While no differences in clinical signs were observed between topical groups, t-PA treated animals demonstrated significantly more symptoms compared to DSPA treated animals. Histologically, no toxic effects were observed in any globe. D-dimer levels were not significantly different between groups and timepoints.
At the tested concentrations, DSPA is a promising fibrinolytic drug with similar fibrinolytic efficacy at 24h post application and fewer side effects than t-PA when injected into the anterior chamber of rabbit eyes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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