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Arthur Driscoll, Charles D Blizzard, Ankita Desai, Taylor Dickman, Michael Bassett, Douglas Molla, William Cowe, Jennifer Wittbold, Amar Sawhney; A Toxicological Evaluation of a Single Dose, 90 Day Sustained Release Travoprost Punctum Plug in Canines. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1993.
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© ARVO (1962-2015); The Authors (2016-present)
Pre-clinically evaluate the ocular and systemic toxicity of the Travoprost Punctum Plug (OTX-TP3) following insertion over a 90 day period in dogs.
OTX-TP3 is a biodegradable hydrogel matrix containing encapsulated travoprost. Upon insertion into the canaliculus, the hydrogel swells to conform to the space enabling plug retention & travoprost release over 90 days. The hydrogel is conjugated with fluorescein to aid visualization. Baseline ophthalmic exams & clinical pathology were conducted. OTX-TP3 was inserted into the vertical canaliculus bilaterally in 16 beagles; a control group (n=16) received a placebo punctum plug & contralaterally a sham insertion procedure. Dosing was ensured (95+%) by replacing lost plugs &/or extending the dosing period. Ophthalmic examinations were performed periodically (slit lamp biomicroscopy, fluorescein staining, fundoscopy, and tonometry). Plasma & tear fluid were collected. Canines were sacrificed at approximately Day 91 of dosing or Day 121 (30 day recovery period) & complete necropsies conducted. Histology was assessed on ocular tissues and nasal turbinates. The study followed FDA 21 CFR, Part 58 GLP for Non Clinical Laboratory Studies.
Punctum plugs were well tolerated overall during the study. A high incidence of punctum plug retention was observed. Systemically, there were no test article-related effects. Posterior segment ophthalmic examinations were similar for all eyes. Consistent with travoprost ocular drops, anterior segment exam findings were limited to mild redness & congestion in the conjunctiva of test article eyes; this was not noted at recovery & not considered adverse. There were no test article related macroscopic observations. All microscopic findings, such as cell infiltration & dilation of the canaliculi, were related to expansion of canalicular tissue from the plugs & resolved during the recovery period. Lack of detectable travoprost in plasma indicated no systemic exposure, while travoprost in tear fluid demonstrated local delivery throughout the dosing period.
The presence OTX-TP3 in the puncta were well tolerated. Results showed no systemic toxicity. A single OTX-TP3 dose demonstrated local drug delivery throughout the course of the study. Clinically, a biodegradable, single dose of sustained release travoprost may offer higher therapy compliance and more convenient alternative to eye drops.
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