Laser-induced Choroidal Neovascularization in the Yucatan Minipig – Characterization of a Novel Model of Neovascular Age-Related Macular Degeneration

Abstract

Purpose : Historically, large animal models of neovascular age-related macular degeneration have been unpredictable, with only 70% of laser-induced choroidal neovascularization (CNV) lesions in non-human primates (NHP) considered clinically relevant. Furthermore, only up to 40% of these CNV lesions are considered ideal, exhibiting Grade IV leakage on fluorescein angiography. This inefficiency leads to excess animal use and high study cost. Previous swine CNV models displayed extensive retinal damage and only minimal choroidal involvement when neovascularization was present. We aimed to create a reproducible, predictable swine model of laser-induced CNV improving efficiency and lowering cost compared to available NHP CNV models.

Methods : Yucatan minipigs were used to optimize laser induction of CNV. Bilaterally, six lesions were created using a 532nm green argon laser under direct visualization with a slit lamp and condensing lens. Follow-up examinations included optical coherence tomography (OCT) and fluorescein angiography (FA) at five day intervals, followed by histopathology at 15 days post-operatively.

Results : Lesions were reliably produced exhibiting rupture of Bruch’s membrane as demonstrated by a focal region of discontinuity of the hyperreflective line representing the retinal pigment epithelium/Bruch’s membrane complex on OCT. These regions showed ingrowth of hyperreflective tissue into the outer retinal layers, as well as hyperfluorescence on FA, both suggestive of fibrovascular proliferation from the choroid into the retina. Histopathological characterization of the lesions supported the in vivo findings with moderate to marked subretinal fibrosis and neovascularization extending from the choroid into the outer nuclear layer. The inner retina was generally unaffected.

Conclusions : The Yucatan minipig is an excellent alternative to other large animal models of neovascular age-related macular degeneration. Similar globe size and retinal anatomy to human patients makes the swine model ideal for characterizing novel investigational molecules targeting proliferative posterior segment disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.