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David Culp, Samirkumar Rajnikant Patel, Brian C Gilger; Evaluation of Aflibercept in a Laser-Induced Model of Choroidal Neovascularization in Pigs. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1990.
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The purpose of this study was to evaluate and characterize a porcine model of laser induced choroidal neovascularization (CNV) to evaluate therapeutic drug candidates for the treatment of posterior segment diseases, such as macular degeneration.
Choroidal neovascularization complexes were created using an 810 nm diode laser in weanling pigs. Immediately following laser treatment, pigs were given an intravitreal (IVT) injection of aflibercept (2 mg) or balanced salt saline (BSS). Color fundus photography, fluorescein angiography (FA), and retinal optical coherence tomography (OCT), including retinal thickness measurements, were performed on days 14 and 28. Following euthanasia, eye cups were labeled with 4’,6-diamidino-2-phenylindole (nucleus), isolectin IB4 (blood vessels and microglia) and phalloidin (F-actin). The sclera-choroid/RPE complex was flat mounted, 2D fluorescent images were acquired, and the isolectin IB4 signal was used to quantify neovascularization.
The diode laser energy delivered via a laser indirect headset created uniform white laser lesions surrounding the optic nerve. In most pigs, 6 lesions were created. The lesions could be readily observed on fundus photography, optical coherence tomography (OCT), and fluorescein angiography (FA). On evaluation of retinal thickness by OCT, both adjacent to the lesion and the center of the lesion, there was no significant difference between BSS and aflibercept treated eyes at either time point. On FA, at 2 and 4 weeks after laser, eyes treated with aflibercept had significantly smaller mean area of fluorescence compared to BSS eyes (P<0.004). Quantification of neoformed vessels on retinal flat mount tissue revealed that eyes treated with aflibercept had significantly lower isolectin IB4 signal than BSS treated eyes (P=0.0129).
Overall, these results suggest the porcine laser CNV model may be a suitable model to evaluate new drug candidates for CNV. Although color fundus photography and OCT may provide morphologic and descriptive data on the effects of a test article on retinal lesions, these results suggest that FA and retinal flat mount analysis may be the most discerning end points for evaluating test article treatment effect. Furthermore, the time point for these endpoints measurement appears to be as early as 2 weeks after creation of lesions with laser.
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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