Corneal Penetration of Low-Dose Atropine Eye Drops

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.

Balsam Poplar Buds: Extraction of Potential Phenolic Compounds with Polyethylene Glycol Aqueous Solution, Thermal Sterilization of Extracts and Challenges to Their Application in Topical Ocular Formulations

“…Stability of ophthalmic formulations is a valid aspect and it is important that the physicochemical characteristics of the formulation remain significantly unchanged for the appropriate period of storage or use from the start of manufacture [ 67 ]. The stability of ophthalmic formulations depends on a variety of factors, such as the stability of the active substance, temperature, storage conditions or excipients [ 90 ]. The formulations were stored at room temperature for 30 days after sterilization.…”

Empfehlungen bei progredienter Myopie im Kindes- und Jugendalter. Stellungnahme von DOG, BVA und der Bielschowsky Gesellschaft für Schielforschung und Neuroophthalmologie

“…Allerdings kann auch die Konzentration von 0,05 % mit einer Pupillenerweiterung von 3 mm einhergehen [ 35 ]. Konservierungsmittel haben keinen wesentlichen Einfluss auf die Penetration der Tropfen ins Auge [ 36 ]. Eine asiatische Studie hat keinen Unterschied bezüglich reduzierter Akkommodation und vergrößerten Pupillendurchmessers bei Konzentrationen zwischen 0,01 und 0,02 % gefunden [ 37 ].…”

Efficacy and safety of traditional Chinese medicine decoction in the treatment of adolescent myopia

“…Numerous studies have shown that low-dose (0.01%) atropine is effective in reducing the increase in myopia in adolescents, and topical atropine drops have been used for 150 years to relieve myopia [9–11] . However, long-term use can cause photosensitivity and rebound effects after drug withdrawal due to concentration-dependent side effects, so higher concentrations of atropine drops are still not widely used [12] …”

“…[9][10][11] However, long-term use can cause photosensitivity and rebound effects after drug withdrawal due to concentrationdependent side effects, so higher concentrations of atropine drops are still not widely used. [12] At present, a large number of classic Chinese medicine decoctions have been used in clinical treatment of adolescent myopia, and they have been made into different dosage forms at the same time, with good effects. [13] However, there are many types of traditional Chinese medicine (TCM) decoctions in clinical application, and there is no interactive comparison between them.…”