Varying treatment efficacy for low-dose atropine in Europe

Paper title: Myopia outcome study of atropine in children: Two-year result of daily 0.01% atropine in a European population

Authors: Loughman, James (1); Kobia-Acquah, Emmanuel (1); Lingham, Gareth (1,2); Butler, John (1,3); Loskutova, Ekaterina (1); Mackey, David A (2,4,5); Lee, Samantha S Y (2); Flitcroft, Damiel I (1,6)

1. Centre for Eye Research Ireland, School of Physics, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland.
2. Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Perth, Western Australia, Australia.
3. School of Mathematical Sciences, Technological University Dublin, Dublin, Ireland.
4. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
5. School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
6. Department of Ophthalmology, Children's Health Ireland at Temple Street Hospital, Dublin, Ireland.

Date: Sep 2023

Reference: Loughman J, Kobia-Acquah E, Lingham G, Butler J, Loskutova E, Mackey DA, Lee SSY, Flitcroft DI. Myopia outcome study of atropine in children: Two-year result of daily 0.01% atropine in a European population. Acta Ophthalmol. 2023 Sep 11

[Link to open access paper]

Previous studies into atropine efficacy and safety to date have been conducted mainly in South and East Asia, where the prevalence and rate of myopia progression is typically greater.^1-7 The Myopia Outcome Study of Atropine in Children (MOSAIC) was a double-masked randomised study which explored the efficacy, safety and acceptability of 0.01% atropine over 2 years for myopia progression in 250 predominantly white, European children.

Children aged between 6 to 16yrs, with myopia of -0.50D or greater, were recruited to the study at a research centre in Dublin, Ireland. They were randomly assigned to receive either 0.01% atropine (n = 167) or placebo drops (n = 83) to use nightly for 2yrs. Spherical equivalent refractive error (SER) was measured by cycloplegic auto-refraction at baseline, as was axial length. Repeat examinations were planned for 6-monthly intervals. The primary outcome was change in SER at 24-mths. Secondary outcomes were safety, acceptability of drops and change in axial length (AL).

Due to COVID-19 lockdowns and social distancing needs occurring during the study period, the first 6-mth visit was cancelled and the 12-mth visit excluded near and accommodation tests in order to maintain distancing.

At 18mths, myopia progression was significantly lower in the treatment group (0.12D effect). However, at 24mths, SER changes were not significantly different between the 0.01% atropine and placebo groups (0.10D effect). The treatment effect was also found to be no different for having low or high myopia at baseline, although there was an increased effect for white, rather than non-white children. Axial length growth was lower for the atropine group at 18 and 24mths (0.06 and 0.07mm, respectively) versus placebo group. It was also lower for older children (11yr or older) and white children but not for younger or non-white children. There were no significant adverse responses to 0.01% atropine use or differences in distance and near acuity or accommodative amplitude function between the groups. 

Although this study was unable to show reduced SER with 0.01% atropine over 2yrs, they found that axial length growth was reduced by 0.07mm in the treatment group; furthermore, 0.01% atropine was well-tolerated with no significant adverse responses, which supports its use in children.

The greatest treatment effect was seen for white rather than non-white children. This adds to the findings from the WA-ATOM study from Australia where 0.01% atropine had greater efficacy for white children for reducing myopia progression and axial length. This may be related to iris colour, where greater effects were seen for lighter eyes, particularly blue.  

The treatment efficacy of 0.01% atropine in the MOSAIC study appeared to vary due to ethnicity, eye colour and COVID-19 restrictions which occurred during the study period. Sub-groups were analysed for the effect of COVID-19. The low COVID impact group comprised one-third of participants recruited after the harshest COVID-19 restrictions lifted and schools re-opened. 

• At baseline they were younger and had shorter mean axial lengths, compared to the high COVID impact group.
• Despite showing the fastest progression compared to the high COVID impact group, they also showed the greatest treatment effect with SER and AL differences of 0.37D and -0.17mm, respectively, compared to the low COVID impact placebo group.
• However, approximately two-thirds of the study participants were older (11 to16yrs). Progression is thought to be slower for this age group which may explain the lower progression rates for the placebo group.

Further studies will confirm optimal atropine dosage for both Asian and non-Asian children, how much the environment impacts on progression rates and treatment efficacy and the need of balancing the environment alongside the treatment. The results of the MOSAIC study can provide added data to investigations into atropine efficacy for managing myopia in children.

Title: Myopia outcome study of atropine in children: Two-year result of daily 0.01% atropine in a European population

Authors: James Loughman, Emmanuel Kobia-Acquah, Gareth Lingham, John Butler, Ekaterina Loskutova, David A Mackey, Samantha S Y Lee, Daniel I Flitcroft

Purpose: The Myopia Outcome Study of Atropine in Children (MOSAIC) is an investigator-led, double-masked, randomized controlled trial investigating the efficacy and safety of 0.01% atropine eye drops for managing myopia progression in a predominantly White, European population.

Methods: Children aged 6-16 years with myopia were randomly allocated 2:1 to nightly 0.01% atropine or placebo eye drops in both eyes for 2 years. The primary outcome was cycloplegic spherical equivalent (SE) progression at 24 months. Secondary outcomes included axial length (AL) change, safety and acceptability. Linear mixed models with random intercepts were used for statistical analyses.

Results: Of 250 participants enrolled, 204 (81.6%) completed the 24-month visit (136 (81.4%) treatment, 68 (81.9%) placebo). Baseline characteristics, drop-out and adverse event rates were similar between treatment and control groups. At 24 months, SE change was not significantly different between 0.01% atropine and placebo groups (effect = 0.10 D, p = 0.07), but AL growth was lower in the 0.01% atropine group, compared to the placebo group (-0.07 mm, p = 0.007). Significant treatment effects on SE (0.14 D, p = 0.049) and AL (-0.11 mm, p = 0.002) were observed in children of White, but not non-White (SE = 0.05 D, p = 0.89; AL = 0.008 mm, p = 0.93), ethnicity at 24 months. A larger treatment effect was observed in subjects least affected by COVID-19 restrictions (SE difference = 0.37 D, p = 0.005; AL difference = -0.17 mm, p = 0.001).

Conclusions: Atropine 0.01% was safe, well-tolerated and effective in slowing axial elongation in this European population. Treatment efficacy varied by ethnicity and eye colour, and potentially by degree of COVID-19 public health restriction exposure during trial participation.

[Link to open access paper]