The LAMP Study data over three years: 0.05% atropine leads and minimally rebounds

Paper title: Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression Study: Continued Versus Washout: Phase 3 Report

Authors: Jason C Yam, Xiu Juan Zhang, Yuzhou Zhang, Yu Meng Wang, Shu Min Tang, Fen Fen Li, Ka Wai Kam, Simon T Ko, Benjamin H K Yip, Alvin L Young, Clement C Tham, Li Jia Chen, Chi Pui Pang

Author affiliations with Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong and other: see pubmed listing for full detail.

Date: October 2021

Reference:   Ophthalmol 2021; Oct 7:S0161-6420(21)00745-4. [Link to abstract]

This study continued the Low-Concentration Atropine for Myopia Progression (LAMP) Study to three years in total. To overview the findings of all three studies:

1. The one year LAMP study compared 0.05%, 0.025% and 0.01% atropine to a placebo group. The first data of its kind, it showed a concentration dependent response. Both 0.025% and 0.05% had similar, minimal side effect profiles, but 0.05% was most effective, 0.025% next and 0.01% minimally effective in controlling axial elongation compared to the placebo group. [Link to Myopia Profile Science analysis]
2. The two year LAMP study saw the placebo-treated children all switched into 0.05% atropine, while the other treatment groups continued. Over two years, 0.05% was most effective and the children who only had one year of 0.05% treatment showed similar final axial length to those on 0.01% for two years. In the second year, 0.025% and 0.01% did not show a statistically different treatment effect from each other, as they had in the first year. [Link to abstract]
3. The three year LAMP study saw half of the children continue with 0.05%, 0.025% or 0.01% treatment and half ceased, to test for a rebound effect (faster post-treatment progression). Progression was faster in the non-treated groups, and the formerly-0.05% group showed a slightly faster 'rebound' but only by around 0.04mm over one year, considered clinically insignificant. Younger children (6-8 years) were more likely to show greater rebound, but there was no influence of refraction, sex, parental myopia status, outdoor activity or near work activity on progression or the rebound effect in the washout group. Over the whole three years, 0.05% was most effective while 0.025% and 0.01% were not significantly different in total axial length change. The conclusion confirmed 0.05% as most effective over three years.

Atropine 0.05% appears to work best over three years to control axial elongation. Atropine 0.025% was more effective than 0.01% in the first year of the LAMP study, but in the second year they were similar. In the third year, they were all similar. This indicates the clinical value of starting at 0.05% and that it is not advisable to start at a lower concentration with an expectation to potentially increase concentration later. 

This study also showed that the rebound effect from ceasing atropine 0.05% was small, labelled 'clinically insignificant' (0.04mm faster progression over one year), while 0.025% and 0.01% groups didn't experience a 'rebound effect'. This indicates there is likely still value in some form of tapering before atropine cessation, if 0.05% concentration has been used.

The LAMP Study is the only placebo-controlled trial (which it was in the first year) to directly compare these low concentrations of atropine. Over three years, the results showed that 0.05% was most effective in the first and second years, while the greater effect of 0.025% over 0.01% was only found in the first year. Understanding how these concentrations work in other patient demographics would be valuable, as would further definition of long-term treatment strategies beyond three years, especially in older children. 

Title: Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression Study: Continued Versus Washout: Phase 3 Report

Authors: Jason C Yam, Xiu Juan Zhang, Yuzhou Zhang, Yu Meng Wang, Shu Min Tang, Fen Fen Li, Ka Wai Kam, Simon T Ko, Benjamin H K Yip, Alvin L Young, Clement C Tham, Li Jia Chen, Chi Pui Pang

Purpose: (1) To compare the efficacy of continued and stopping treatment for 0.05%, 0.025%, and 0.01% atropine during the third year. (2) To evaluate the efficacy of continued treatment over 3 years. (3) To investigate the rebound phenomenon and its determinants after cessation of treatment.

Design: A randomized, double-masked extended trial.

Participants: A total of 350 of 438 children aged 4 to 12 years originally recruited into the Low-Concentration Atropine for Myopia Progression (LAMP) study.

Methods: At the beginning of the third year, children in each group were randomized at a 1:1 ratio to continued treatment and washout subgroups. Cycloplegic spherical equivalent (SE) refraction and axial length (AL) were measured at 4-month intervals.

Main outcome measures: Changes in SE and AL between groups.

Results: A total of 326 children completed 3 years of follow-up. During the third year, SE progression and AL elongation were faster in the washout subgroups than in the continued treatment groups across all concentrations: -0.68 ± 0.49 diopters (D) versus -0.28 ± 0.42 D (P < 0.001) and 0.33 ± 0.17 mm versus 0.17 ± 0.14 mm (P < 0.001) for the 0.05%; -0.57 ± 0.38 D versus -0.35 ± 0.37 D (P = 0.004) and 0.29 ± 0.14 mm versus 0.20 ± 0.15 mm (P = 0.001) for the 0.025%; -0.56 ± 0.40 D versus -0.38 ± 0.49 D (P = 0.04) and 0.29 ± 0.15 mm versus 0.24 ± 0.18 mm (P = 0.13) for the 0.01%. Over the 3-year period, SE progressions were -0.73 ± 1.04 D, -1.31 ± 0.92 D, and -1.60 ± 1.32 D (P = 0.001) for the 0.05%, 0.025%, and 0.01% groups in the continued treatment subgroups, respectively, and -1.15 ± 1.13 D, -1.47 ± 0.77 D, and -1.81 ± 1.10 D (P = 0.03), respectively, in the washout subgroup. The respective AL elongations were 0.50 ± 0.40 mm, 0.74 ± 0.41 mm, and 0.89 ± 0.53 mm (P < 0.001) for the continued treatment subgroups and 0.70 ± 0.47 mm, 0.82 ± 0.37 mm, and 0.98 ± 0.48 mm (P = 0.04) for the washout subgroup. The rebound SE progressions during washout were concentration dependent, but their differences were clinically small (P = 0.15). Older age and lower concentration were associated with smaller rebound effects in both SE progression (P < 0.001) and AL elongation (P < 0.001).

Conclusions: During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. 0.05% atropine remained the optimal concentration over 3 years in Chinese children. The differences in rebound effects were clinically small across all 3 studied atropine concentrations. Stopping treatment at an older age and lower concentration are associated with a smaller rebound.