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Jeffrey Tran, Caroline Craven, Kathy Wabner, Jenn Schmit, Uday B Kompella, Hans E Grossniklaus, Timothy W Olsen; A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):250.
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© ARVO (1962-2015); The Authors (2016-present)
Delaying the natural progression of pathologic macular aging to maintain sight for the large numbers of individuals affected by age related macular degeneration (AMD). The goal of this in vivo, pre-clinical study is to optimize pharmacodelivery to enhance macular pharmacotherapies by comparing the efficacy of microneedle delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con-1 versus controls on the growth of type 2 choroidal neovascularization (CNV) in the porcine model.
Forty-one pigs were injected either on the day of CNV induction or post-induction day #14 (hI-con1) with either 2.5 mg Ivit bevacizumab (n=9), 1 mg pazopanib (n=9), 300 Ivit mg hI-con1 (n=4), or 1 mg SC pazopanib (n=9), versus 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at postoperative week 2 (11), 3 (8), 4 (11), and 8 (11). Eyes were enucleated and fixed for histology. The size of the type 2 CNV complex was determined by measuring lesion size from histologic sections. Immunostaining for cytotoxic T-cells was performed on the hI-con1 and control eyes.
In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost with the retinal tissue during dissection. Another animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller height measures (90 ± 20 µm) versus controls (180 ± 20 µm; p=0.009), and Ivit pazopanib had smaller maximum CNV height (174 ± 43 µm) compared to SC pazopanib (448 ± 25 µm; p=0.018). The mean lesion size in hI-con-1 treated animals was smaller than controls (p=0.11) although the number of animals was small. Immunostaining did not detect cytotoxic T-cells at the time of enucleation.
Intravitreal pazopanib and hI-con-1 treatments reduced the size of CNV lesions versus controls. The pig model has a near 100% success rate of type 2 CNV induction and is an excellent preclinical model to study and assess CNV growth and therapeutic response.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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