The penetration and distribution of topical atropine in animal ocular tissues

Abstract

Purpose: To conduct a multi-tissue investigation on the penetration and distribution of topical atropine in myopia treatment, and determine if atropine is detectable in the untreated contralateral eye after uniocular instillation. Methods: Nine mature New Zealand white rabbits were evenly divided into three groups. Each group was killed at 5, 24 and 72 hr, respectively, following uniocular instillation of 0.05 ml of 1% atropine. Tissues were sampled after enucleation: conjunctiva, sclera, cornea, iris, ciliary body, lens, retina, aqueous, and vitreous humors. The assay for atropine was performed using liquid chromatography-mass spectrometry (LC-MS), and molecular tissue distribution was illustrated using matrix-assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS) via an independent experiment on murine eyes. Results: At 5 hr, the highest (mean AE SEM) concentration of atropine was detected in the conjunctiva (19.05 AE 5.57 ng/mg, p < 0.05) with a concentration gradient established anteriorly to posteriorly, as supported by MALDI-IMS. At 24 hr, preferential binding of atropine to posterior ocular tissues occurred, demonstrating a reversal of the initial concentration gradient. Atropine has good ocular bioavailability with concentrations of two magnitudes higher than its binding affinity in most tissues at 3 days. Crossing-over of atropine to the untreated eye occurred within 5 hr post-administration. Conclusion: Both transcorneal and transconjunctival-scleral routes are key in atropine absorption. Posterior ocular tissues could be important sites of action by atropine in myopic reduction. In uniocular atropine trials, cross-over effects on the placebo eye should be adjusted to enhance results reliability. Combining the use of LC-MS and MALDI-IMS can be a viable approach in the study of the ocular pharmacokinetics of atropine.

Stability of Ophthalmic Atropine Solutions for Child Myopia Control

“…In the human body, atropine metabolism produces small (3%) amounts of tropic acid [ 58 ] and atropine is mostly excreted unchanged in the urines. During ophthalmic administrations in rabbits, it has been shown that atropine has good ocular bioavailability via both transcorneal and transconjunctival-scleral routes [ 59 ]. Unfortunately and to the best of our knowledge, atropine metabolism in the eye has not been studied despite there being a clear incentive to do so, like for other drugs [ 60 ].…”

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

“…Based on the drug concentration ranges observed for the dorsal and ventral cornea (1.03-9.45 μg/g), if protein binding is similar to serum, voriconazole is expected to be above the target MIC for up to 48 h, which is of significance for the treatment of keratomycosis [35,36]. The maintenance of voriconazole concentrations in ranges from 1.04-14.22 μg/g in the sclera is of importance, since transcleral drug diffusion is very efficient in allowing drug molecules to reach the cornea [37]. Our data showed significant individual variation in voriconazole concentrations, both in tissues as in tears, therefore, in some individuals, therapeutic concentrations might not be reached in tissues other than the cornea.…”

Effects of Monocular Atropinization on Refractive Error and Eye Growth in Infant New World Monkeys

“…In the rabbit, topical atropine reaches the vitreous and also retina, 32 so it is possible that some of the effects of atropine we observed arose from scleral or retinal effects. It is possible that the atropinized eyes became amblyopic.…”