Comparing Apples with Apples: Understanding Efficacy in Myopia Management

In this article, Dr Kate Gifford and Jeanne Saw provide the latest evidence-based advice to guide your choices.

Choice is good to have, but psychological research has shown that too much choice can be demotivating – a famous chocolate experiment found choosing between six options resulted in more decisive behaviour than when there were up to 30 choices.¹ Feeling that we hold a large volume of subjective knowledge can also lead to ‘choice overload’, compared to people who feel they are less knowledgeable.² One of the many human thinking paradoxes is ‘the more you learn, the less you know’, called the Dunning-Kruger effect.³

Our confidence in putting changes into practice can follow peaks and troughs as we journey from minimal knowledge to expertise through learning and experience. Figure 1 provides an illustration of the Dunning- Kruger effect, where a little knowledge can go a long way to bolstering confidence (first peak) and then a little more can lead to lack of confidence (subsequent trough). With more time and knowledge, we can reach our strongest levels of confidence and expertise.

In this article, we aim to help you move further along the curve – helping you learn while making the choices simple – bringing you up to date with understanding the latest myopia treatments, and the increasingly varied ways that efficacy is being described.

APPLES, ORANGES, AND BANANAS

In myopia control research and practice, understanding and communicating the efficacy of various treatments is critical. Researchers employ multiple metrics to quantify and describe the effectiveness of interventions aimed at slowing myopia progression. In this article we’ll explore five methods that can be used to describe efficacy: percentage myopia control effect, absolute treatment effect, annualised treatment effect, comparing to prior progression, and comparison to emmetropic eye growth. Each of these methods offer unique insights into how well myopia control strategies perform, but there are cautions in how they may be compared to each other.

As examples, we will primarily reference outcomes from randomised controlled trials (RCTs), which are the gold standard of evidence. Consider the following a knowledge journey where we aim not to push you off the end of the curve in Figure 1, but rather to arm you with understanding, which wraps into confidence and provides you with a simplified approach to understanding efficacy, and communicating it to patients and parents.

Method One: Percentage Myopia Control Effect

This is the most common expression of efficacy, where the reduction in myopia progression measured in a treatment group is compared to the control group. It is calculated as treatment group progression divided by the control group progression, expressed as a percentage. This figure, when subtracted from 100%, gives the percentage slowing acheived by the treatment. This can be represented for both refractive outcomes (D) in axial length growth (mm).

Its advantages are that it provides a standardised and easily understandable measure of treatment effectiveness, for example ‘reducing progression by 52%’. Its disadvantages are that it cannot be used to make comparisons between different treatments investigated in separate studies, as the percentage is unique to one specific study. Factors such as study duration, participant ethnicity, and age can all influence the percentage. Typically, shorter studies show higher percentage efficacy owing to an initial ‘boost’ in treatment in the first six to 12 months. Younger participant groups and studies in Asian children can show lower percentages, due to faster progression of the control group.⁴

Things to watch for: The refractive percentage (dioptres of reduced progression) is typically higher than the axial length percentage (millimetres of reduced elongation) in a study, as refraction is a blunter measure (0.25D steps) compared to axial length (0.01 mm). For this reason, the axial length figures are the key outcomes to look to in evaluating results.⁵

Example: The MiSight 1 day study was a three-year randomised controlled trial (RCT), undertaken in a group of children aged eight to 12 years at outset, with diverse ethnicity of around 55% white (European) and 24% Asian ethnicities. At three years, refractive progression was reduced by 59% and axial elongation by 52% compared to the control group.⁶ The LAMP (low-dose atropine and myopia progression) study, undertaken in Hong Kong Chinese children, showed 67% refractive and 51% axial length efficacy for 0.05% atropine over one year.⁷ On first view, the atropine 0.05% appears to be ‘better’ because of the higher refractive percentage, but the axial length percentages are similar. Also, a threeyear study shows a more robust, sustained effect than a one-year study. We would conclude that these treatments are likely similar, based on their axial length percentage, but the volume of supporting data is stronger for MiSight 1 day.

Take home message: Look at study duration (years), age of participants, and ethnicity of the study group when considering a comparison between treatments.

Method Two: Absolute Treatment Effect

This has been proposed as a fairer playing field for efficacy, citing the total dioptres or millimetres reduction in myopia progression rather than a percentage. It has also been described as the ‘cumulative absolute reduction in axial elongation’ (CARE) metric.⁴ It is calculated by subtracting the total refractive progression (D) or axial elongation (mm) in the treatment group from the same in the control group, expressed as an absolute figure. Analysis of studies investigating the same treatment in different ethnicity populations have found this figure to be more robust than percentages, with better consistency.⁸

Things to watch for: Shorter duration studies will show a lower absolute number. Also, control group variability can still influence the absolute effect.⁹

Example: The MiSight 1 day study showed a mean of -0.73D less refractive progression and 0.32 mm less axial elongation in the test group compared to the control group over three years.⁶ The LAMP atropine study showed -0.27D and 0.21 mm less progression over one year.⁷ Both outcomes for MiSight 1 day appear far higher, due to study duration.

Take home message: Look at study duration and consider comparisons across a similar time frame, which leads into method three.

Method Three: Annualised Treatment Effect

Taking the next steps on the absolute treatment effect, we divide the absolute effect by the study duration to provide an annualised value. This can be useful to compare studies of varying duration. A drawback here is that since shorter studies tend to show a higher percentage and absolute effect, due to the initial ‘boost’ observed in efficacy,⁴ the annualised treatment effect of a shorter study may over-estimate the long-term effectiveness of the intervention.

Things to watch for: The ‘best case’ efficacy is typically observed in shorter studies. Evaluating studies with the same duration, or using first year data, provides the most robust comparison. This takes into account the initial ‘boost’ effect when interpreting annualised treatment outcomes.

Example: The DIMS spectacle lens demonstrated 0.34 mm less axial elongation over two years compared to the single vision control.¹⁰ This gives an annualised treatment effect of 0.17 mm. Atropine 0.05% demonstrated 0.21 mm (51%) less progression in one year.⁷ Does this make atropine better than DIMS? Not based on percentages (method one), where DIMS achieved 62%. This makes methods one and three appear conflicting, but when comparing first year data by the annualised method they are similar, since the one-year DIMS efficacy was 0.22 mm.

Take home message: As for method two, evaluation at the same time point (one year) in studies gives the strongest appraisal of comparative efficacy.

Method Four: Comparing to Prior Progression

This approach compares the rate of myopia progression during the treatment period to the rate before treatment in the same individuals. In longer-term studies, this may be done when a control group is switched to the intervention. The advantage of this method is that it translates well to observations of individuals in practice. The disadvantage is that this can overestimate efficacy, as myopia progression typically slows by around 15% per year, with increasing age, even without intervention.⁴

Things to watch for: Efficacy will look much higher by this method, compared to a percentage comparison with a control group in an RCT study.

Example: The MiSight 1 day clinical study recently published six year efficacy data.¹¹ After the initial three-year RCT, participants in the single vision soft contact lens-wearing control group were all switched to MiSight 1 day. During the next three years, the controlto- intervention group showed a significant slowing of myopia progression, from an average of -1.24D / 0.62 mm in the first three years to -0.29D / 0.18 mm in the second three years. Calculating the axial length ‘percentage’ before and after MiSight wear yields 71% efficacy in slowing progression – which seems better than the original 52% in the three-year RCT.⁶ Yet, mathematical modelling showed axial length efficacy compared to an age-matched ‘virtual’ control group was still around 50%. Take home message: Describing slowed progression after treatment makes clinical sense – another metric reported from the study above was that 90% of children showed slower progression once commencing MiSight 1 day wear.¹¹ This is a great sound bite for parents, as they only care about their child and not ‘averages’, but the typically higher percentage should be used with caution in any comparison between treatments.

Method Five: Comparison to Emmetropic Eye Growth

This newer method compares treated myopic eye growth to that of emmetropic eyes, given that some level of eye growth is expected during emmetropisation.¹² If treated eyes show growth rates slowed down to that of age-matched emmetropic eyes (around 0.1 mm/year), the treatment can be considered as highly effective. The advantage of this method is that it can provide age-specific metrics, allowing for more customised goal setting for individuals in practice than efficacy averages. The removal of a ‘physiological growth’ component from outcomes alters the goal posts based on the assumption that some eye growth is ‘normal’ – which is true for emmetropic eyes, but it is unknown if this is the case for myopic eyes where excessive axial length is directly linked to long-term eye health risks.¹³ This is a potential disadvantage of this method.

Things to watch for: This method typically results in higher percentages than the standard percentage myopia control effect of method one.

Example: An analysis of the MiSight 1 day RCT data showed mean three-year absolute eye growth of 0.30 mm. An age-matched cohort of emmetropes was calculated to have 0.24 mm axial elongation over three years. This represents eye growth slowed to almost ‘normal / physiological’ rates; if this is a reasonable goal of myopia control, the treated growth was slowed to 80% of the emmetropic eye growth rate.¹² Another recent paper computed the same for highly aspherical lenslet spectacle lenses, which showed 0.34 mm (50%) less axial elongation in the two-year RCT, and 0.41 mm (60%) for a subset wearing their spectacles full time. In this subset, eye growth rates were similar or slower than those of non-myopic children in around 90% of full-time wearers.¹³

Take home message: This metric arguably provides more concrete numbers on efficacy for parents and patients, but when making comparisons between treatments, be aware that these percentages will be higher than in the standard percentage efficacy expressed in all RCTs.

USING EFFICACY METRICS IN PRACTICE

What matters most in understanding efficacy in myopia management is being able to select a treatment and explain it to patients and their parents or carers. While the knowledge journey to this point may seem complex, the punch line is simple: no treatment shows clear superiority, with many treatments being apparently similar.^4,15 This means you can prescribe based on what’s available to you, and what best suits the patient: compliance and full-time wear is key to achieving best outcomes. It makes sense to consider effective optical treatments first, as they offer the dual benefit of myopia correction as well as myopia control.

There are various ways to clinically explain efficacy – a simplified approach based on the vast data available in RCTs is using percentage categories. This is a variation on method one, where instead of directly comparing the numbers, treatments are grouped into two simple categories of those showing efficacy of at least 50% (based on axial length, the more accurate measure) – which can be described as ‘slowing progression by at least half ’ – and those showing efficacy around 33%, described as ‘slowing progression by about a third’. These metrics are easy to communicate and are evidence-based, using categorical comparison of all RCTs published with at least one year of data.

This is the clinical translation advocated in the Managing Myopia Guidelines Infographics, a communication tool which is free to download and available in 20 languages from MyopiaProfile.com. Figure 2 shows one of the four panels of the patientfacing infographic, which helps to guide evidence-based discussions on treatment options. The take home message here is that a number of treatments fit the ‘best’ category of slowing progression by at least half (>50%): atropine 0.05%; MiSight 1 day soft contact lenses and orthokeratology; and DIMS, highly aspherical lenslet and diffusion optics technology spectacle lenses.^{6-7,10-11,14,16-17} All but the latter are available in Australia and New Zealand.

CONCLUSION

The expanding array of myopia control treatments, and various ways in which their efficacy is being reported in scientific literature, can push the clinician into a knowledge-valley of despair (as per Figure 1), especially when different metrics are used. The important awareness is that several metrics do exist, though with similar comparative outcomes where many treatments show similar effectiveness. While the learning journey continues in myopia management, the numerous options for patients and clear benefits of treatment are clear.

Dr Kate Gifford is an internationally renowned clinician-scientist optometrist and peer educator, and a Visiting Research Fellow at Queensland University of Technology, in Brisbane. She holds a PhD in contact lens optics in myopia, four professional fellowships, has written in over 100 peer reviewed and professional publications, and has presented more than 200 conference lectures. Dr Gifford is the Chair of the Clinical Management Guidelines Committee of the International Myopia Institute. In 2016 she co-founded Myopia Profile with Dr Paul Gifford; the world-leading educational platform on childhood myopia management. After 13 years of clinical practice ownership, she now works full time on Myopia Profile.

Jeanne Saw is a clinical optometrist based in Brisbane. She has worked as a research assistant with leading vision scientists and has a keen interest in myopia control and professional education. As Manager, Professional Affairs and Partnerships at Myopia Profile, Ms Saw works closely with Dr Gifford in developing content and strategy, and in working with industry partners. She also writes for the clinical domain of MyopiaProfile. com, and the My Kids Vision website.

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