Low dose atropine is often used for myopia control in children. How commonly will patients complain of side effects, such as photophobia, allergy or blurry vision at near? BL presents a patient who experienced blurry vision after using 0.01% atropine once, and subsequently refused to use it. This led to significant fear and misconception on the part of the parent. How should a case like this be managed?
Possible causes for these effects as suggested by the community are:
- Inaccurate dilution of atropine: atropine drops are compounded manually, and variability in the active ingredient potency and stability is possible.1 See our blog Complications in Atropine Compounding for more detail.
- Instilling excessive number of drops of atropine
- Hypersensitivity to atropine leading to excessive response
Investigating these potential causes are important in successfully managing this patient.
What does the research say?
Effect of low-concentration atropine on pupil size
- The ATOM22 and LAMP3 studies, mainly comprised Southeast Asian and East Asian children respectively, reported only minor pupil dilation with 0.01% atropine of 0.8mm and 0.5mm respectively.
- A group of German school children experienced on average 1mm of pupil dilation after use of 0.01% atropine.4
- Liang and Williams5 reported that visual performance and the resolution of images on the retina are affected when the pupil is large (>7.3mm).
Therefore, this suggests that if a child has large pupils to begin with, minor pupil dilation after low-dose atropine instillation may potentially impact distance and near vision due to the change of image resolution.
Effect of low-concentration atropine on accommodation
- In the LAMP study,3 0.01% atropine only reduced accommodative amplitude by 0.3D, while 0.025% and 0.05% reduced amplitude (amps) by 2D.
- In the ATOM2 study,2 0.01% atropine reduced amps by about 4-5D, but 0.1% and 0.5% dramatically reduced amps from around 16D at baseline to 4-6D after two years, which impacted near acuity.
- Accommodation amps decreased by 1.5D in Japanese children using 0.01% atropine.6 However, subjective symptoms were not reported.
- Another study on Chinese children using 0.01% atropine found it did not affect monocular or binocular amps, or accommodative facility tested with +/-2.00 lenses.7
Children normally have good accommodation, so a minor decrease in accommodation amplitude would not typically affect their near vision. However in some children, atropine's side effects could be enough to cause a problem with binocular vision and hence it should be comprehensively assessed in children on atropine treatment, especially if they are experiencing problems with near vision. Optical support may be needed, as determined by their BV status, such as a near add in spectacles.
What else should be considered?
Iris colour. Many atropine studies involve children of East Asian heritage; it is expected that side effects may be more pronounced in Caucasian children with lighter iris pigmentation. This could be true for the individual, although Gong et al’s meta-analysis of efficacy versus side effects in low dose atropine8 suggests that difference in response between Asian and Caucasian children was minimal. Instead, increase side effects were linked to higher concentrations of atropine.
Incorrect dispensing. A key consideration is a pharmacy dispensing error. In Australia, a number of cases were reported in 2018 and 2019 where 1% atropine was dispensed to children where 0.01% atropine had been prescribed. In response, Optometry Australia recommended that atropine prescriptions include the specific note 'MUST BE COMPOUNDED' to avoid this dispensing error.
Number of drops used. Clinical advice would be to instill one drop in each eye, nightly, in atropine treatment. Interestingly, the ATOM22 and LAMP3 studies do not mention if children were told to instill one or two drops. Generally, the pre-corneal ocular volume is only around 20 uL while dropper bottles can deliver 25-70 uL per drop,9 so one drop should be enough to deliver the medication. Multiple drops could increase the concentration of the medication absorbing into the eye.
Take home messages:
- Ensure your prescription is written clearly and legibly to reduce the potential for dispensing error. It is also prudent to write 'MUST BE COMPOUNDED' on the prescription to ensure the non-commercially available, low concentrations of atropine are correctly compounded.
- When a patient experiences adverse effects with 0.01% atropine use, the first port of call is to ensure that they have been dispensed correctly and are instilling the correct dosage. Just one drop is needed, but patients and parents should be counselled that some 'overflow' of eyedrop onto the eyelid and skin may occur due to drop volume, and this does not mean multiple drops are required to achieve therapeutic dose.
- Side effects of atropine are concentration and dose dependent, so it is important to inform patients and their parents of potential symptoms and ensure regular follow up in the initial stage of management, especially when prescribing at higher concentrations. The International Myopia Institute Clinical Management Guidelines recommends follow up after 4-7 days of atropine commencement, then again at 1 month, 3 months and 6 monthly thereafter.
- Guderman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs in R&D. 2013; 13:1-8 (link)
- 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;123(2):391-9. (link)
- Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. 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(1):113-124 (link)
- Joachimsen L, Böhringer D, Gross NJ, Reich M, Stifter J, Reinhard T, Lagrèze WA. A pilot study on the efficacy and safety of 0.01% atropine in German schoolchildren with progressive myopia. Ophthalmology and Therapy. 2019 Sep 1;8(3):427-33. (link)
- Liang J, Williams DR. Aberrations and retinal image quality of the normal human eye. JOSA A. 1997;14(11):2873-83. (link)
- Nishiyama Y, Moriyama M, Fukamachi M, Uchida A, Miyaushiro H, Kurata A, Tokoro T, Ohno-Matsui K. Side effects of low dose atropine. Nippon Ganka Gakkai Zasshi. 2015;119(11):812-6. (link)
- Wang Y, Yao J, Qu, X. Atropine 0.01% for the Control of Myopia in Chinese Children: Effect on Accommodation Functions and Pupil Size. J Ophthalmol 2020:7525180. (link)
- Gong Q, Liu L, Janowski M. Efficacy vs. side effects of atropine in myopia: a meta-analysis. Investigative Ophthalmology & Visual Science. June 2017; 58:2388 (link)
- Van Santvliet L, Ludwig A. Determinants of eye drop size. Surv Ophthalmol. 2004;49(2):197-213. (link)