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Subspecialties Retina, Basic & Translational Research, Other

In It for the Long Haul

Mark Bullimore talks about how he and fellow researcher Noel Brennan projected the first year data of the Low-concentration Atropine for Myopia (LAMP) study to predict the three-year efficacy for different concentrations of atropine (1).

Can you outline your work with the three-year LAMP study?

In the first year, researchers randomized children into four different groups – a placebo group and three different concentrations of atropine. At the end of the first year, all of the placebo children were switched to the highest concentration of atropine. So even though researchers have these three-year results, they don't have three years of control data. 

What Noel Brennan and I did was to use the first-year data to project what years two and three would look like for the control group. The original investigators did all of the hard work and collected the data, but we thought it would be nice for them, and also the community, to know what the three-year efficacy was for different concentrations of atropine. 

How did you calculate the data for years two and three? 

We conducted a meta analysis, which we presented at ARVO last year. We identified as many papers as possible – around 80 papers and 200 data points – that had measured and published long-term axial length data in untreated myopic children. From that, our statistical wizards were able to produce an exponential model. One of the features of the model is that East Asian children progress about 35 percent faster. Both East Asian children and non-East Asian children predominantly of European descent slow by 15 percent per year. Basically, we applied that 15 percent slowing to the LAMP data. That's how we were able to extend their one-year data to predict three years’ efficacy.

What were the main findings of the LAMP study?

I’ll speak about the highest concentration: 0.05 percent. Using our model, we were able to estimate that the atropine slowed axial elongation by 0.55 millimeters over three years. We also estimated the slowing of myopia progression in diopters, which was about 1.3 diopters over three years for the highest concentration of atropine. Incidentally, the atropine in the study seemed to be well tolerated by the children. In terms of league tables, this efficacy is among the best that has been published, if not the best three-year efficacy in a randomized clinical trial. It shows that the highest concentration of atropine is highly effective at slowing myopia progression.

Did you face any challenges during the meta-analysis and, if so, how did you overcome them?

When you're applying a model or a prediction to some data, it’s hard to know how good it is. Fortunately, in the LAMP study they had control data in year three, because half of the children who had been treated for the first two years were taken off the drops. The delightful thing was that when we compared our prediction for year three, based on year one, it was very similar for the untreated children in year three – so we have internal validation of our model. We didn’t have time to conduct a meta analysis for myopia progression, so we need to revisit that and see whether we get a similar or slightly different answer. 

Should the results of the LAMP study increase physician confidence in treating myopia patients with low-concentration atropine?

In the UK, in the US, and in many other parts of the world, there is no FDA or EMA-approved formulation for low concentration atropine. At the moment in the US, atropine has to be compounded by a compounding pharmacy. Many ophthalmologists and optometrists use a variety of compounding pharmacies to prescribe atropine for their young patients. The challenge is that these pharmacies are not regulated by the FDA; they have their own somewhat loose regulations at the state level, and they don't have to demonstrate things like stability or even purity of their products. From that point of view, the results of our study can inform clinicians what the efficacy of the drug should be. What’s in the bottle from the compounding pharmacy may or may not be equivalent to that. Hopefully, some time in the near future, we will have an approved formulation of low-concentration atropine that will ensure stability and predicted efficacy.

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  1. M A Bullimore, N A Brennan, “Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study,” Ophthalmology, [Online ahead of print] (2023). PMID: 36842480. 
About the Author
Sarah Healey

Communicating stories in a way that is accessible to all was one of the focal points of my Creative Writing degree. Although writing magical realism is a fun endeavor (and one I still dabble in), getting to the heart of human stories has always been the driving motivator behind my writing. At Texere, I am able to connect with the people behind scientific breakthroughs and share their stories in a way that is impactful and engaging.

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