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Wenqiang Liu, Anessa Puskar Tawakol, Kayla M. Rudeen, William F. Mieler, Jennifer J. Kang-Mieler; Treatment Efficacy and Biocompatibility of a Biodegradable Aflibercept-Loaded Microsphere-Hydrogel Drug Delivery System. Trans. Vis. Sci. Tech. 2020;9(11):13. doi: https://doi.org/10.1167/tvst.9.11.13.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the in vivo treatment efficacy and biocompatibility of a biodegradable aflibercept-loaded microsphere-hydrogel drug delivery system (DDS) in a laser-induced choroidal neovascularization (CNV) rat model.
Two weeks after CNV induction, animals were randomly assigned into four experimental groups: (1) no treatment, (2) single intravitreal (IVT) injection of blank DDS, (3) bimonthly bolus IVT aflibercept injections, and (4) single IVT injection of aflibercept-DDS. CNV lesion sizes were monitored longitudinally using fluorescence angiography and multi-Otsu thresholding for 6 months. For safety and biocompatibility assessment, an additional three non-CNV animals received a blank DDS injection. Electroretinogram, intraocular pressure, and clinical ophthalmoscopic examinations were performed.
The average lesion areas at week 0 (treatment intervention) were (1) 8693 ± 628 µm2 for no treatment, (2) 8261 ± 709 µm2 for blank DDS, (3) 10,368 ± 885 µm2 for bolus, and (4) 10,306 ± 1212 µm2 for aflibercept-DDS. For the nontreated groups, CNV lesion size increased by week 2 and remained increased throughout the study. The treated groups exhibited CNV size reduction after week 2 and remained for 6 months. At week 22, the average percent changes in CNV lesion area were +38.87% ± 7.08%, +34.19% ± 9.93%, –25.95% ± 3.51%, and –32.69% ± 5.40% for the above corresponding groups. No signs of chronic inflammation and other ocular abnormalities were found.
The aflibercept-DDS was effective in treating CNV lesions for 6 months and is safe, well tolerated, and biocompatible.
The proposed DDS is a promising system to reduce IVT injection frequency for anti–vascular endothelial growth factor treatment.
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