Atropine in topical formulations for the management of anterior and posterior segment ocular diseases

ABSTRACT

Introduction

Atropine is an old-known drug which is gaining increasing attention due to the myriad of therapeutic effects it may trigger on eye structures. Nevertheless, novel applications may require more adequate topical formulations.

Areas covered

This review aims to gather the existing knowledge about atropine and its clinical applications in the ophthalmological field when administered topically. Atropine ocular pharmacokinetics is paid a special attention, including recent evidences of the capability of the drug to access to the posterior segment. Ocular bioavailability and systemic bioavailability are counterbalanced. Finally, limitations of traditional dosage forms and potential advantages of under investigation delivery systems are analyzed.

Expert opinion

Mydriasis and cyclopegia have been widely exploited for eye examination, management of anterior segment diseases, and more recently as antidotes of chemical weapons. Improved knowledge on drug receptors and related pathways explains atropine repositioning as an outstanding tool to prevent myopia. The ease with which atropine penetrates ocular tissues is a double edged sword, that is, while it ensures therapeutic levels in the posterior segment, the unspecific distribution causes a wide variety of untoward effects. The design of formulations that can selectively deliver atropine to the target tissue for each specific application is an urgent unmet need.

KEYWORDS:

• Amblyopia
• atropine
• contact lenses
• cyclopegia
• mydriasis
• myopia
• ocular bioavailability
• ocular pharmacokinetics
• systemic bioavailability
• uveitis

Article highlights

• Atropine is a tropane alkaloid that acts as a competitive, non-selective muscarinic acetylcholine receptor antagonist.

• Eye drops are mostly formulated with atropine sulfate, a soluble salt formed by two molecules of atropine and a sulfate ion.

• Atropine is used as mydriatic and cycloplegic agent during eye examinations, for accommodative spasms, and as antidote of chemical weapons.

• Atropine serves as neoadjuvant therapy in inflammatory processes and amblyopia.

• Atropine prevents adhesion of the iris to the anterior lens in cases of floppy iris syndrome.

• In children atropine may prevent the progression of myopia.

• After topical instillation, atropine readily distributes in the anterior chamber and enters in the posterior segment through the periocular-scleral and/or uveal routes.

• Topical administration of atropine sulfate 1% solution provides clinically relevant levels in the posterior segment that last for 72 h.

• Non-productive absorption may lead to atropine blood levels as high as those achieved with intramuscular administration. Systemic absorption is particularly risky for children and elderly patients.

• Myopia control can be improved by combining orthokeratology (OK) lenses with concentrations of topical atropine sulfate in the 0.025% to 0.125% range.

• The design of formulations that can selectively deliver atropine to the target tissue for each specific application is an urgent unmet need.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was funded by MINECO [SAF2017-83118-R], Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia [ED431C 2020/17], and FEDER.