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Wenzheng Hu, Donnicia James, Vernard Woodley, Chintan Patel, Anish Kurian, Matthew S Lawrence; Persistent leaking in long term follow-up in the primate model of DL-2-aminoadipic acid-induced retinal neovascularization and vascular leakage. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5483.
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To characterize the long term retinal vascular changes resulting from intravitreal (IVT) injection of DL-2-aminoadipic acid (DLAAA) in the green monkey. The effect of anti-vascular endothelial growth factor (anti-VEGF) treatment on the induced retinal vascular leakage was also evaluated to validate the model for repeated dosing and screening of candidate compounds.
Adult St. Kitts green monkeys (Chlorocebus sabaeus) that had previously received an IVT injection of 5 mg DLAAA and developed various degree of retinal vascular leakage were included in the study. Ophthalmic examinations including slit lamp biomicroscopy, color fundus photography (CFP), fluorescein angiography (FA) and optical coherence tomography (OCT) were conducted up to 18 months. The area and fluorescence intensity of retinal vascular leakage were quantified from the 1 and 3 minute angiograms by Amira software. The retinal histopathologic change following long term leakage and the effect of IVT aflibercept were evaluated in representative eyes with various degree of retinal pathology.
The area and fluorescence intensity of retinal vascular leakage was remained between Month 4 and Month 8 fluorescein angiograms. By Month 18 the leakage persisted in all eyes, however, a reduced lesion area size and fluorescence intensity was observed. CFP and OCT demonstrated a similar retinal phenotype and morphological pattern between Month 8 and Month 18. The results of ongoing anti-VEGF efficacy and histopathology evaluations will provide additional insight into the persisting nature of the DLAAA model.
DLAAA-induced retinal neovascularization and leakage persists through 18 months in the green monkey. The retinal phenotype is stable in the observation period up to 18 months, supporting the application of DLAAA-induced retinal vascular leakage as a primate model for efficacy evaluations of candidate therapeutics targeting retinal vascular leakage, including those with long duration of effect.
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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