What's in the atropine bottle? Q&A With Professor Mark Bullimore
In this article:
- We have varying optical designs for spectacle and contact lens myopia interventions; how should we consider the same about atropine?
- What should eye care practitioners know about compounded low-concentration atropine?
- How could the formulation of atropine influence patient acceptance and efficacy?
- What would you consider the key features of the ideal atropine drop for myopia?
- The story of topical atropine for myopia control has been a journey from 1% to 0.01% and somewhat back again. What do you think the future holds?
- Further reading
Our Q&A format is designed to explore a particular clinical topic, intervention, product or research paper with an expert. In this interview we asked some key atropine questions of Professor Mark Bullimore, arguably one of the world's thought leaders in myopia; being co-author of landmark papers in the field such as Myopia Control: Why Each Diopter Matters, Efficacy in Myopia Control and The Risks and Benefits of Myopia Control. Professor Bullimore's latest publication explores the characteristics of compounded low-concentration atropine, which is currently the primary method by which eye care practitioners are able to prescribe this treatment for access by their patients. Is what's on the label found in the bottle? What other impacts could there be? Read on to learn more about the present and future of atropine treatment for childhood myopia.
We have varying optical designs for spectacle and contact lens myopia interventions; how should we consider the same about atropine?
Prof. Bullimore: With spectacles and contact lens, there are a variety of designs with varying levels of myopia control efficacy. Considering spectacles, progressive addition lenses have limited efficacy slowing progression by 0.25 D over three years.1 This applies to all myopes, including esophores.2 Flat top bifocals have a mixed history with some clinical trials showing meaningful efficacy,3 while others show modest or no slowing.4 The new generation of designs incorporating peripheral lenslets appear to have robust efficacy.5, 6
Studies have shown that the efficacy of atropine in slowing myopia progression and axial elongation is primarily dependent on its concentration. Higher concentrations of atropine have been shown to be highly effective in slowing myopia progression but result in potentially debilitating mydriasis and cycloplegia.7 Lower concentrations offer meaningful slowing of progression and are well tolerated.8 The choice of concentration is best determined by the eyecare practitioner's assessment of the individual patient.
What should eye care practitioners know about compounded low-concentration atropine?
Prof. Bullimore: In the United States (US), low-concentration atropine can only be obtained through compounding pharmacies and is not FDA-approved to treat myopia. US Food and Drug Administration (FDA)-approved drugs undergo rigorous testing, and manufacturers are required to follow current good manufacturing practices in order to consistently produce high quality products.9 Compounding pharmacies are generally held under the authority of state boards of pharmacy.9, 10
We surveyed 26 pharmacies across 19 US states.11 There were a wide variety of formulation methods, which may affect atropine stability and potency. This includes the source of the active pharmaceutical ingredient, the liquid, the excipients and the preservatives. Similarly, there are a wide variety of storage and beyond-use recommendations. Unlike FDA-approved products, compounded medications are not routinely analyzed. Some pharmacies may employ analytical methods if batches of drug are being compounded, but it is highly unlikely that any assessment of stability is made.
How could the formulation of atropine influence patient acceptance and efficacy?
Prof. Bullimore: Efficacy is influenced by the stability of the formulation. Atropine is relatively unstable as it is susceptible to hydrolysis, and the rate of degradation is influenced by pH and the ingredients used in formulation.12, 13 The degradation products, tropic acid and apoatropine, do not have anticholinergic activity and thus reduce efficacy. Lower concentrations of atropine degrade more rapidly.
Our recent analysis of compounded atropine14 found that the concentration relative to the prescribed concentration was as low as 70% and a quarter of all samples were under the 90% minimum target concentration. There was a significant correlation between higher pH and higher tropic acid concentration. In other words, the more neutral the pH, the greater the degradation. Of course, a lower pH may sting slightly, potentially influencing acceptance.
What would you consider the key features of the ideal atropine drop for myopia?
Prof. Bullimore: Sterility is a key feature. This can be achieved by preservatives, but this may be a cause for concern, given that a child will likely use the drops for several years. The long-term effects of chemicals such as BAK on a child's cornea are unknown. High levels of BAK could cause irritation and can be toxic to the ocular surface.15 Allergic reactions are known to occur with chronic use of BAK-preserved ophthalmic medications.15, 16 An attractive alternative is a preservative-free single dose.
The story of topical atropine for myopia control has been a journey from 1% to 0.01% and somewhat back again. What do you think the future holds?
Prof. Bullimore: The book on atropine for myopia control is still in early draft form. We know that 1% works best, but that it is unacceptable to most children. The chronic pupil dilation presents its own challenges for long-term retinal health. We have some early, quality data on delaying onset with low concentration atropine, but only on Chinese children. Indeed, the bulk of the published research in the field is on East Asians. Atropine does not correct myopia, so optical therapies have something of an advantage. We need to know how best to combine atropine with the optical therapies that work well. Finally, an atropine-eluting soft contact lens may be an attractive option. In the meantime, practitioners need to ask themselves and their compounding pharmacies, "what's in the bottle?"14
Meet the Authors:
About Professor Mark Bullimore
Professor Bullimore is an internationally renowned scientist, speaker, and educator based in Boulder, Colorado. He received his Optometry degree and PhD in Vision Science from Aston University in Birmingham, England. He spent most of his career at the Ohio State University and the University of California at Berkeley and is now Adjunct Professor at the University of Houston. His expertise in myopia, contact lenses, low vision, presbyopia, and refractive surgery means that he is consultant for a number of ophthalmic, surgical, and pharmaceutical companies. He has co-authored over 100 peer-reviewed scientific articles including several modern classics in the field of myopia control.
This content is brought to you thanks to unrestricted educational grant from
- Gwiazda J, Hyman L, Hussein M, et al. A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci 2003;44:1492-500.
- Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator G. Progressive-addition lenses versus single-vision lenses for slowing progression of myopia in children with high accommodative lag and near esophoria. Invest Ophthalmol Vis Sci 2011;52:2749-57.
- Cheng D, Woo GC, Drobe B, Schmid KL. Effect of bifocal and prismatic bifocal spectacles on myopia progression in children: three-year results of a randomized clinical trial. JAMA ophthalmology 2014;132:258-64.
- Fulk GW, Cyert LA, Parker DE. A randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria. Optom Vis Sci 2000;77:395-401.
- Lam CSY, Tang WC, Tse DY, et al. Defocus Incorporated Multiple Segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial. Br J Ophthalmol 2020;104:363-8.
- Bao J, Huang Y, Li X, et al. Spectacle Lenses With Aspherical Lenslets for Myopia Control vs Single-Vision Spectacle Lenses: A Randomized Clinical Trial. JAMA ophthalmology 2022;140:472-8.
- Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the treatment of childhood myopia. Ophthalmology 2006;113:2285-91.
- Yam JC, Jiang Y, Tang SM, et al. Low-Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control. Ophthalmology 2019;126:113-24.
- Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs R D 2013;13:1-8.
- Watson CJ, Whitledge JD, Siani AM, Burns MM. Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors. J Med Toxicol 2021;17:197-217.
- Richdale K, Tomiyama ES, Novack GD, Bullimore MA. Compounding of Low-Concentration Atropine for Myopia Control. Eye Contact Lens 2022;48:489-92.
- Austermann H, Schaeffel F, Mathis U, et al. Corneal Penetration of Low-Dose Atropine Eye Drops. J Clin Med 2021;10.
- Lund W, Waaler T. The kinetics of atropine and apoatropine in aqueous solutions. Acta Chem Scand 1968;22:3085-97.
- Richdale K, Skidmore KV, Tomiyama ES, Bullimore MA. Compounded 0.01% Atropine-What's in the Bottle? Eye Contact Lens 2023: https://doi.org/10.1097/icl.0000000000000990.
- Baudouin C, Labbe A, Liang H, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res 2010;29:312-34.
- Keller N, Moore D, Carper D, Longwell A. Increased corneal permeability induced by the dual effects of transient tear film acidification and exposure to benzalkonium chloride. Experimental eye research 1980;30:203-10.
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