Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits...

To compare ocular pharmacokinetics (PK), systemic absorption, and injectability of triamcinolone acetonide (TA) suprachoroidal (SC) and intravitreal (IVT) suspensions. New Zealand White (NZW) rabbits received a bilateral injection of 4 mg TA injectable suspension, TRI (TRIESENCE ^®; Alcon) through either microneedle-based SC or standard IVT injection. Another group of NZW rabbits received a bilateral SC injection (4 mg) of either TRI or a proprietary TA suspension for SC use, CLS-TA (Clearside Biomedical). Blood and ocular tissues were analyzed for TA over 3 months. Separately, injectability of TRI and CLS-TA through a proprietary SC delivery system (SCS Microinjector^®; Clearside Biomedical) was compared using microinjector syringe-plunger glide force measurement. Suprachoroidal delivery of TRI, compared with IVT-TRI, resulted in ∼12-fold higher exposure in the retinal pigment epithelium-choroid-sclera, and comparable exposure in the retina. Conversely, SC-TRI, compared to IVT-TRI, resulted in 460-, 34-, and 22-fold lower exposure in the lens, iris-ciliary body, and vitreous humor, and negligible exposure in the aqueous humor. SC injection of either CLS-TA or TRI resulted in comparable and sustained ocular TA levels. Plasma TA levels were generally undetectable in both studies. A significantly greater and more variable glide force was measured for TRI vs. CLS-TA. Suprachoroidal delivery of TA enabled high and durable TA levels targeted to the chorioretina with limited anterior segment exposure. SC delivery of either CLS-TA or TRI resulted in comparable ocular PK profiles with low systemic exposure; however, CLS-TA required lower and less variable glide force than TRI, potentiating more consistent, controlled administration.