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Henry F Edelhauser, Rozemarijn S Verhoeven, Brian Burke, Craig B Struble, Samirkumar Rajnikant Patel; Intraocular Distribution and Targeting of Triamcinolone Acetonide Suspension Administered Into the Suprachoroidal Space. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5259.
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© 2017 Association for Research in Vision and Ophthalmology.
To evaluate the intraocular distribution of a triamcinolone acetonide (TA) suspension (CLS1001), 40 mg/mL, after injection into the suprachoroidal space of rabbit eyes.
Ten female New Zealand white rabbits were given bilateral, 100-µL/eye (4-mg/eye) suprachoroidal injections of CLS1001 an injectable triamcinolone acetonide suspension (Clearside Biomedical Inc., Alpharetta GA). The aqueous suspension was formulated at a concentration of 40 mg/mL. Injections were performed using a 33 G 750 µm microneedle. Two animals per time point were euthanized on study days 1 (24 hours postdose), 15, 29, 63, and 91. Blood and ocular tissues (retina, sclera/choroid/RPE, and vitreous humor) were collected using a frozen eye tissue collection procedure. Aqueous humor was collected prior to flash freezing of the globe. Ocular tissues and plasma were analyzed for TA at Tandem Labs (Salt Lake City, UT) using LC/MS/MS.
The total TA mass balance in the ocular tissues analyzed at 24 hours postdose (Day 1) was 98.8% following the suprachoroidal injection of CLS1001. Plasma levels of TA achieved maximum concentration of 4.22 ng/mL at day 1 and decreased until day 63 when TA was no longer detectable. No TA was detected in the aqueous humor throughout the experimental period. There was limited exposure to the vitreous humor following suprachoroidal injection, with maximum mean concentration of 0.281± 0.317 µg/mL on day 15 and cumulative area under the curve (AUC) of only 12.8 µg*day/mL. In contrast, exposure of TA to the Sclera-Choroid-RPE reached maximum mean concentration of 11,600 ± 635 µg/mL on day 1 and a cumulative AUC of 273,000 µg*day/mL. TA was detected in the retina throughout the 91 days and reached maximum mean concentration of 129 ± 142 µg/mL on day 29 and a cumulative AUC of 4,860 µg*day/mL.
Suprachoroidal administration of CLS1001 resulted in localization of TA primarily to the sclera, choroid, and retina. There was limited exposure of TA to the vitreous humor and no TA detected in the aqueous humor indicating limited exposure to the anterior segment of the eye.
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