As the only commonly prescribed pharmacological intervention for childhood myopia, atropine therapy is distinct from optical interventions such as orthokeratology and soft multifocal lenses both conceptually and practically. So where does low-dose atropine, which is an off-label offering in the United States, fit into a myopia management protocol?

How Does Atropine Work?

Atropine is a competitive, reversible muscarinic acetylcholine receptor antagonist that demonstrates nonselective actions in ocular tissues ranging from the lacrimal gland to the trabecular meshwork (Mitchelson, 2012). Effects on the iris sphincter and ciliary muscle yield the strong cycloplegic and mydriatic effects eyecare practitioners associate with atropine (Qu et al, 2006).

In recent years, a growing body of evidence has emerged to support the notion that atropine therapy slows the progression of myopia in children. While the associated mechanism is not yet clear, it does not appear that the effect is related to accommodation; in fact, atropine has been shown to slow myopia progression in chicks, who do not have muscarinic ciliary muscle receptors (Galvis et al, 2016).

A more recent study suggested that choroidal thickening induced by atropine may be a possible mechanism of slowing of myopia progression, but research is ongoing (Ye et al, 2020).

Prescribing Atropine Therapy

The Atropine in the Treatment of Myopia (ATOM) and Low-Concentration Atropine for Myopia Progression (LAMP) studies showed nightly instillation of atropine in concentrations ranging from 0.01% to 1% can result in slowing of myopia progression over a period of one year or more (Chia et al, 2016; Yam et al, 2022). However, the latest evidence suggests higher concentrations, such as 0.05% or more, may be more effective than lower concentrations (Yam et al, 2022).

When prescribing atropine, it is important to realize that all concentrations of atropine result in some cycloplegia and mydriasis; however, the frequency and magnitude of symptoms are dose-dependent (Chia et al, 2012).

Furthermore, discontinuing atropine tends to result in a “rebound period” whereby axial elongation is increased—this effect may be more pronounced with higher concentrations of atropine and in younger children (Chia et al, 2012, Yam et al, 2022).

While they are unlikely with topical atropine instillation, it is also important to recall potential systemic anticholinergic side effects, including increased body temperature, constipation, and altered mental status (Mitchelson, 2012).

Atropine in Practice

One key benefit of atropine therapy is the ability to treat patients who are unable or unwilling to pursue orthokeratology or soft multifocal lenses, for example, patients who have high astigmatism and those who cannot master application and removal of contact lenses. On the other hand, drawbacks of atropine therapy include the difficulty of gauging compliance as well as the expense of compounded atropine (which is in addition to materials and professional fees).

I start most atropine therapy patients on 0.025% every evening and follow up one to two weeks after beginning treatment, then once every six months. In addition to subjective complaints such as photophobia or blurred near vision, at minimum, consider measuring pupil size, accommodative amplitude, and phorias in patients undergoing atropine therapy. If subjective symptoms are noted, first clarify whether the symptoms are simply noticeable or bothersome; in the event that symptoms are disruptive, decrease the concentration of atropine until you find the maximum dosage the patient can tolerate.

Combination Therapy

Combined therapy with low-dose atropine and optical interventions is an ongoing area of research and preliminary results indicate combination therapy may have an additive effect compared to optical or pharmacological monotherapy (Wan et al, 2018). Particularly for patients whose myopia is progressing quickly or those at greatest risk for high myopia, it may be wise to consider prescribing low-dose atropine alongside orthokeratology or soft multifocals. CLS

References

1. Mitchelson F. Muscarinic receptor agonists and antagonists: effects on ocular function. Handb Exp Pharmacol. 2012;(208):263-298.
2. Qu J, Zhou X, Xie R, et al. The presence of m1 to m5 receptors in human sclera: evidence of the sclera as a potential site of action for muscarinic receptor antagonists. Curr Eye Res. 2006 Jul-Aug;31:587-597.
3. Galvis V, et al. Topical Atropine in the Control of Myopia. Med Hypothesis Discov Innov Ophthalmol. 2016 Fall;5:78-88.
4. Ye L, Shi Y, Yin Y, et al. Effects of atropine treatment on choroidal thickness in myopic children. Invest Ophthalmol Vis Sci. 2020 Dec 1;61:15.
5. Chia A, Chua W-H, Cheung Y-B, et al. Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses. Ophthalmology. 2012 Feb;119:347-354.
6. Chia A, Lu QS, Tan D. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops. Ophthalmology. 2016 Feb;123:391-399.
7. Yam JC, Zhang XJ, Zhang Y, et al. Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report. Ophthalmology. 2022 Mar;129:308-321.
8. Wan L, Wie C-C, Chen CS, et al. The synergistic effects of orthokeratology and atropine in slowing the progression of myopia. J Clin Med. 2018 Sep 7;7:259.