Can low-concentration atropine delay myopia onset in pre-myopic children?

Paper title: Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children. The LAMP2 Randomized Clinical Trial

Authors: Jason C Yam (1,2,3,4,5,6), Xiu Juan Zhang (1,6), Yuzhou Zhang (1), Benjamin H K Yip (7), Fangyao Tang (1), Emily S Wong (1,2,5), Christine H T Bui (1), Ka Wai Kam (1,3), Mandy P H Ng (1), Simon T Ko (1,5), Wilson W K Yip (1,3), Alvin L Young (1,3), Clement C Tham (1,2,3,4,5,6), Li Jia Chen (1,3,4,6), Chi Pui Pang (1,4,6)

1. Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
2. Hong Kong Eye Hospital, Hong Kong.
3. Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong.
4. Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
5. Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong.
6. Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, China.
7. Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.

Date: February 2023

Reference:  Yam JC, Zhang XJ, Zhang Y, Yip BHK, Tang F, Wong ES, Bui CHT, Kam KW, Ng MPH, Ko ST, Yip WWK, Young AL, Tham CC, Chen LJ, Pang CP. Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial. JAMA. 2023 Feb 14;329(6):472-481. [Link to abstract]

High myopia is associated with greater risks of myopia-related complications. The earlier the onset of myopia, the greater the risk of high myopia later in life.^1-4   Lifestyle changes such as spending more time outdoors have been found to delay the onset of myopia for some children.^5,6,7

The Low-Concentration Atropine for Myopia Prevention (LAMP2) study aimed to evaluate the efficacy of 0.05% and 0.01% atropine for delaying myopia onset in children. This randomised, double-masked, placebo-controlled trial was conducted at the Chinese University of Hong Kong Eye Centre.

Non-myopic healthy children aged 4 to 9yrs who had cycloplegia-confirmed spherical equivalent refraction between 0.00 and +1.00D and astigmatism no more than 1.00DC were recruited. They randomly received either 0.05% atropine (n = 160), 0.01% atropine (n = 159) or saline placebo eyedrops (n = 155) to use nightly for 2yrs.

The primary outcomes were the number of children who experienced a fast myopic shift of at least 1D and a cumulative incidence of myopia of at least -0.50D in either eye, over 2yrs.

Of the original 474 participants, 353 (74.5%) completed the trial, with a mean age of 6.8yrs. After 2yrs, the cumulative myopia incidence was found to be:

• 28.4% for the 0.05% atropine group
• 45.9% for the 0.01% group
• 53% for the placebo group

When compared to the 0.01% atropine and placebo groups, 0.05% atropine gave a significantly lower myopia incidence over 2yrs by 17.5% and 24.6%, respectively.

The percentages of children with a fast myopic shift were:

• 25% for the 0.05% atropine group
• 45.1% for the 0.01% group
• 53.9% for the placebo group

Compared to the 0.01% atropine and placebo groups, 0.05% atropine gave reduced myopic shift of 20.1% and 28.9%, respectively. No statistically significant difference was found between 0.01% atropine and placebo groups for 2-yr cumulative myopic incidence (7.1%) or for percentage of fast progressors (8.8%)

Secondary outcomes of changes in spherical equivalent error and axial lengths were found to be -0.46D, -0.84D and -1.01D and 0.48mm, 0.63mm and 0.70mm for the 0.05% group, 0.01% group and placebo group, respectively. The 0.05% atropine was shown to decrease myopic shift and axial elongation compared to the 0.01% atropine and the placebo.

Best-corrected distance and near acuity was no different between the three groups, being around 6/6 or 20/20 equivalent. Pupil size was around 0.5mm larger in the 0.05% group and 0.5mm larger in the 0.01% group compared to the placebo group.

Photophobia was the most common adverse effect found with the drops: 18.9% found light sensitivity with 0.01% atropine. There were similar responses for the 0.05% atropine and placebo with 12.9% and 12.2% respectively.

1. Children with pre-myopia were identified by their young age (4-9 years) and cycloplegic spherical equivalent refraction between 0.00 and +1.00D.
2. Atropine 0.01% was not effective to delay myopia onset, but atropine 0.05% reduced onset by around half over two years. It was safe and well tolerated, with similar rates of photophobia in placebo, 0.01% and 0.05% groups.

Low-concentration 0.05% atropine could be an extra strategy for use alongside lifestyle adjustments, such as increased time outdoors, to slow refractive changes and axial elongation before the onset of myopia, in children identified as at-risk pre-myopes.

Although 0.05% atropine compared favourably to 0.01% concentration for pre-myopic children in this study, further research to replicate this study is needed to understand:

• If 0.05% atropine can provide the same results for children of different ages, ethnicities and locations. In this study, all children were of Chinese ancestry and attended a single study site.
• Around 25% of children dropped out, across the groups. If faster progressors dropped out, the results may not indicate the true efficacy for both concentrations for delaying myopia onset.
• If there are safety implications for long-term atropine use (an extended trial was planned to evaluate effects over a longer time)
• How pre-myopes who could benefit from a delaying effect may be identified, when they may not present for eye examinations before myopia onset

Part of the study coincided with COVID-19 which has since been associated with increased myopic risk with children⁸ - this could have potentially decreased the efficacy of the atropine.

Title: Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children. The LAMP2 Randomized Clinical Trial

Authors: Jason C Yam, Xiu Juan Zhang, Yuzhou Zhang, Benjamin H K Yip, Fangyao Tang, Emily S Wong, Christine H T Bui, Ka Wai Kam, Mandy P H Ng, Simon T Ko, Wilson W K Yip, Alvin L Young, Clement C Tham , Li Jia Chen, Chi Pui Pang

Purpose: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia.

Methods: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than −1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022.

Participants were assigned at random to the 0.05%atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years.

Results: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least −0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D).

Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05%atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0%(61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05%atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95%CI,12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95%CI,16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05%atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95%CI,5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95%CI,8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05%atropine group, 18.9% in the 0.01% atropine group, and 12.2%in the placebo group in the second year.

Conclusions: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety.

[Link to abstract]