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Yong Li, Joanna Marie Busoy, Ben Alfyan Achirn Zaman, Jay Ji-Ye Wei, Wanjin Hong, Tien Yin Wong; Preclinical safety assessment of novel pharmaceuticals following intravitreal biologics in rabbits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5169.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreal injections of anti-angiogenic drugs have become a dominant approach to restore sight in the blindness of the angiogenic and neovascular diseases. However, the intravitreal biologics is often complicated by immunogenicity and inflammation. The purpose of this study was to evaluate safety and tolerability of a novel anti-angiogenic small peptide (SIPRAD 0276) after a single intravitreal (IVT) injection in naïve Dutch-Belted (DB) rabbits.
4 DB rabbits were randomly divided into 2 groups (each group, n=2). The small peptide of SIPRAD 0276 was formulated in a fixed volume (50 µl), and concentrations ranged from 0.2 to 5mg per eye in single-dose. Ocular inflammation was evaluated in preclinical observation by one ophthalmologist using slit lamp for anterior segment screen. Standard grading from 0-4 was applied according to the Standardization of Uveitis Nomenclature (SUN) grading scheme. Retinal toxicity was determined by the profile of fundus photographic images, fluorescein angiography (FA) and optical coherence tomography (OCT). All imaging and intraocular pressure (IOP) measurements were performed at baseline and scheduled time points over 4 weeks in conscious animals that were manually restrained.
No anterior segment inflammation was observed at the low dose group (n=2) of 0.2mg/eye. The eyes were received with high dose of 5mg/eye (n=2) which showed an slight uveitic reaction (aqueous flare of 1+ to 2+ and 0.5+ for 1–5 cells per field) peaked at 3 days after the injection, and slowly resolved by 2 to 3 weeks subsequently. There was no significant change in IOP or retinal toxic effects were identified such as vitreous clouding, retinal cloudy or edema by fundus photography, OCT as well as FA during the study period in any of the eyes.
A single intravitreal administration of anti-angiogenic small peptide included an early onset uveitic reaction in a dose-dependent fashion by slit-lamp examinations in DB rabbits.
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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