Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues
Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues
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DOI：
10.18240/ijo.2020.12.04
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发表时间：
2020-12-18
影响因子：
1.4
通讯作者：
Naito, Akira
中科院分区：
文献类型：
--
作者：
Arie, Yuko;Miyai, Hiroko;Naito, Akira
目的：目的：比较曲安奈德（TA）眼内注射方法、Tenon下注射和玻璃体内注射在兔眼组织中的动力学、分布和毒性的差异。在药代动力学研究中，定期处死家兔，然后在91 d内测量血液和眼组织（视网膜/脉络膜、玻璃体和房水）中的TA。对于毒理学研究，进行了临床体征、裂隙灯显微镜检查、眼科检查。取眼球及周围组织，用戊二醛-福尔马林溶液固定，石蜡包埋后进行组织学观察。结果：注射到玻璃体内时，TA在眼内组织中的分布高于眼球筋膜下组织。相反，在整个研究期间，接受玻璃体内TA注射的兔血浆中TA水平显著低于接受Tenon下注射的兔。Tenon下注射TA可观察到可能由TA体循环引起的光放电。同时，技术相关的毒理学眼部症状和调查结果更频繁地观察到在玻璃体内注射比在sub-Tenon injection.CONCLUSION：有显着差异的动力学和TA在玻璃体，房水和血浆中的分布，两种注射方法之间。尽管需要进一步研究来解释人和兔之间的种属差异，但假设两种注射方法之间TA引起的眼内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的TA浓度直接相关。全身毒性和技术相关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。
AIM: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.