Predicting myopia control efficacy in the LAMP study

Paper title: Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study

Authors: Bullimore, Mark A (1); Brennan, Noel A (2)

1. University of Houston, College of Optometry, Houston, Texas
2. Johnson & Jonhson Vision, Jacksonville, Florida

Date: July 2023

Reference: Bullimore MA, Brennan NA. Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study. Ophthalmology. 2023 Jul;130(7):771-772

[Link to abstract]

The Low-Concentration Atropine for Myopia Progression (LAMP) clinical study compared the efficacy and safety of varying concentrations of atropine eye drops for myopia control in children. It comprised 4 distinct phases, with Phase 3 results published late 2021.

• During Phase 1, myopic Chinese children randomly received either 0.05, 0.025 or 0.01% concentration atropine or placebo eye drops to use daily for 1 year. A concentration-dose response was found, with 0.05% concentration showing the greatest efficacy over 1yr.¹
• In Phase 2, the placebo group crossed over to receive 0.05% concentration atropine for ethical purposes and all concentration groups were followed for a further year.
• Phase 3 of the LAMP study investigated rebound effects of ceasing treatment from all concentrations. Although rebound effects were found to be concentration-dependent, older age and lower concentration doses were associated with smaller rebound effects for refractive and axial length progression.²
• Phase 4 is expected to follow children who have progressed by 0.50D or more during the washout period and who have resumed atropine use. Results are unpublished to date.

A recent meta-analysis of 80 studies investigating untreated myopia progression rates found an average annual slowing of 15% for AL with age. This slowing rate also held true for East Asian children, despite having greater average progression rates.³

The annual progression rates for spherical equivalent refractive (SER) and axial length (AL) elongation for untreated children in the LAMP study were analysed by Bullimore and Brennan in this review.

• The placebo group in Phase 1 demonstrated untreated AL progression of 0.41mm in 1 year.
• Using a predictive 15% reduction in AL elongation per year from 0.41mm, the suggested AL growth was for 0.35mm and 0.30mm in the subsequent 2^nd and 3^rd years.
• The LAMP study results showed mean AL progression rates for the 3^rd year washout groups of 0.30mm.

Previous studies have shown axial length growth is correlated with refractive error changes in myopes. Bullimore and Brennan suggest that annual predictions of SER reduction in untreated children could also use the same 15% reduction per annum value.

• The LAMP study data showed year 1 untreated progression of -0.81D. Predictive values for years 2 and 3 would be -0.69D and -0.59D, respectively and a cumulative 3-yr progression prediction of -2.08D.
• An alternative method which used the ratio of progression to AL growth gave a value of -1.98D per mm based on -0.81D SER to 0.41mm AL progression for untreated children in year 1. A predicted cumulative 3-yr value was -2.09D.
• When the same method was applied to untreated eyes in Phase 3, they had progressed by -0.61D and experienced AL growth of 0.30mm, which gave the same of -1.99D/mm

Being able to predict AL and SER reductions with age in untreated eyes helps form the basis for predicting myopia management performance.

Within the context of this study, Bullimore and Brennan used their AL/SER ratio to predict 3-yr efficacy of 0.05% atropine to provide 0.5mm (or 1.35D) saving.

• The implications of these calculations suggest low concentration atropine can retain its efficacy longer than a year.

The predictive ratios could be applied in practice alongside AL data to help eyecare practitioners assess an individual’s likely progression pattern, treated or untreated.

The predictive values were based on data from the 1^st and 3^rd years of the LAMP study. Due to the crossover of the placebo group to treatment groups in the 2^nd and 3^rd years, long-term efficacy could not be calculated.

However, the cohort reduced in size over the 3-yr period, meaning some mean values were slightly different and as a result, only the Phase 1 data was used.

• In Phase 1, the placebo group (n = 93) experienced 0.41mm elongation and mean progression of -0.81D.
• In Phase 3, 73 of those children completed the study, giving changed mean progression values of 0.43mm and -0.90D

The authors accept there may be alternative methods to predict progression and that the methodology of the study does not allow for confidence intervals to be calculated.

Title: Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study

Authors: Mark A Bullimore, Noel A Brennan

The 3-year Low-Concentration Atropine for Myopia Progression (LAMP) study has greatly enhanced knowledge of the use of low-concentration atropine for myopia control. 

In year 1, children were randomized to receive 0.05%, 0.025%, or 0.01% atropine, or placebo. 

[Link to abstract]Compared with the placebo, axial elongation was slowed 0.21, 0.12, and 0.05 mm by 0.05%, 0.025%, and 0.01% atropine, respectively. Myopia progression showed a corresponding slowing of 0.54, 0.35, and 0.22 diopters (D).