Arie Yuko, Miyai Hiroko, Suzuki Ayako, Okabe Takeshi, Takashima Mitsuyo, Takata Mayumi, Kurasawa Takashi, Ito Masaki, Arakawa Reijiro, Ogura Yuichiro, Naito Akira
Sagami Research Laboratories, Wakamoto Pharmaceutical Corporation Ltd., Kanagawa 2580018, Japan.
Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 4678601, Japan.
Int J Ophthalmol. 2020 Dec 18;13(12):1864-1871. doi: 10.18240/ijo.2020.12.04. eCollection 2020.
To compare the differences in kinetics, distribution, and toxicity of triamcinolone acetonide (TA) between the injection methods, sub-Tenon and intravitreal injections in rabbit ocular tissues.
TA was injected into the vitreous or the sub-Tenon in rabbits. For pharmacokinetic study, rabbits were sacrificed periodically and then TA in blood and ocular tissues (retina/choroids, vitreous, and aqueous humor) were measured over 91d. For toxicological study, clinical signs, slit-lamp microscopic examination, ophthalmological test were performed. The eyeballs and surrounding tissues were collected and fixed with glutaraldehyde-formalin solution, and then paraffin embedded for histological investigation.
Higher levels of TA were distributed in the intraocular tissues when injected into the vitreous compared to the sub-Tenon. Conversely, TA level was remarkably lower in the rabbits which received intravitreal TA injections than those treated with sub-Tenon injection throughout the study period in plasma. Optical discharge probably caused by systemic circulation of TA was observed by receiving sub-Tenon TA injection. Meanwhile, technic-associated toxicological ocular symptoms and findings were more frequently observed in intravitreal injection than in sub-Tenon injection.
There are significant differences in kinetics and distribution of TA in vitreous body, aqueous humor and plasma, between the two injection methods. Although further study is needed to explain the species difference between human and rabbit, it is assumed that the difference in the frequency of intraocular pressure elevation and cataract formation by TA between the two injection methods are directly related to the TA concentrations in aqueous humor and vitreous body in each injection methods. Systemic toxicity and technic-associated toxicity are also closely related to kinetics of TA in plasma and each injection method itself, respectively.
比较曲安奈德（TA）在兔眼组织中经Tenon囊下注射和玻璃体腔内注射这两种注射方法在动力学、分布及毒性方面的差异。
将TA注射入兔的玻璃体或Tenon囊下。进行药代动力学研究时，定期处死兔子，在91天内检测血液及眼组织（视网膜/脉络膜、玻璃体和房水）中的TA含量。进行毒理学研究时，观察临床体征、裂隙灯显微镜检查及眼科测试。收集眼球及周围组织，用戊二醛 - 甲醛溶液固定，然后石蜡包埋进行组织学研究。
与Tenon囊下注射相比，玻璃体腔内注射TA时眼内组织中的TA水平更高。相反，在整个研究期间，接受玻璃体腔内TA注射的兔子血浆中的TA水平明显低于接受Tenon囊下注射的兔子。接受Tenon囊下TA注射时观察到可能由TA全身循环引起的视力减退。同时，玻璃体腔内注射比Tenon囊下注射更频繁地观察到与技术相关的毒理学眼部症状和体征。
两种注射方法在玻璃体、房水和血浆中TA的动力学和分布存在显著差异。尽管需要进一步研究来解释人与兔之间的种属差异，但推测两种注射方法中TA引起眼压升高和白内障形成频率的差异与每种注射方法中房水和玻璃体中TA的浓度直接相关。全身毒性和与技术相关的毒性也分别与血浆中TA的动力学和每种注射方法本身密切相关。
