Corneal Penetration of Low-Dose Atropine Eye Drops

Henning Austermann,Frank Mußhoff,Frank Schaeffel,Sven Schnichels,Focke Ziemssen,Verena Hund,Ute Mathis

doi:10.3390/jcm10040588

Henning Austermann, Frank Mußhoff + Show 5 more

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https://doi.org/10.3390/jcm10040588

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Abstract

Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid–liquid extraction followed by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10−8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children’s eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

Highlights

According to meta-analyses, Cochrane reviews, and health technology assessments (HTAs), there is a large body of evidence that low-dose (0.01%) atropine is effective in reducing increases in childhood myopia [1,2,3,4,5]
The efficacy of the topical administration of atropine drops to control myopia has been known for almost 150 years [6]
Some very potent muscarinic acetylcholine receptor (mAChR) antagonists (QNB, dicyclomine, scopolamine, tropicamide) showed little effect in the chick model [12], and no link was identified between any mAChR genes and the risk of increased myopia [12]

Summary

Introduction

According to meta-analyses, Cochrane reviews, and health technology assessments (HTAs), there is a large body of evidence that low-dose (0.01%) atropine is effective in reducing increases in childhood myopia [1,2,3,4,5]. The efficacy of the topical administration of atropine drops to control myopia has been known for almost 150 years [6]. In spite of their effectiveness in slowing axial elongation, the use of commercially available and higherconcentration atropine (0.1%, 0.5%, and 1%) is not well-accepted due to concentrationdependent side effects, including light sensitivity, reduced near vision, and a significant rebound effect after discontinuation. Some very potent mAChR antagonists (QNB (quinuclidinyl benzilate), dicyclomine, scopolamine, tropicamide) showed little effect in the chick model [12], and no link was identified between any mAChR genes and the risk of increased myopia [12]

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