5 years of the Essilor® Stellest® lens - Q&A with Dr. Björn Drobe and Prof. Mark Bullimore

We recently presented the results of the five-year clinical trial of spectacle lenses with highly aspherical lenslets (HAL) at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Seattle. The results demonstrated continued long-term efficacy of the lenses in controlling myopia progression and axial elongation over five years. Essilor® Stellest® lenses are based on the optical design of HAL lenses. The controlled, prospective, randomized clinical trial began in 2018 and was conducted at the Eye Hospital of Wenzhou Medical University in Wenzhou, China with children aged between 8 and 13 years old. 

 To be able to assess the long-term efficacy and whether the lenses would still be effective in slowing down myopia progression in older children, the study was extended first from 2 to 3 years and then onto year 4 and 5 of the clinical trial. The five-year data showed that Essilor® Stellest® lenses slowed myopia progression by 1.75D^*2 and axial elongation by 0.72mm^**2 on average over five years for all subjects, compared to the extrapolated control group. The children who completed the fifth year follow up were aged between 13-18 years by then, so Essilor® Stellest® lenses remained effective in slowing myopia progression in older children, up to 18 years old. It is planned to continue the study for two more years, to gauge the 7-year myopia control efficacy of the lens.  

Research has shown that full-time wear (at least 12 hours per day) should be encouraged for children to potentially maximize myopia control outcomes. The effect of wearing time on myopia control efficacy of spectacle lenses with HAL indicated a dose-response relationship, increasing myopia control efficacy for full-time wearers (at least 12 hours per day)¹, demonstrating that wearing time matters in myopia control. 

 HAL lenses slowed down myopia progression by 0.80D (55%) and axial elongation by 0.35mm (51%), on average, compared to single-vision spectacle lenses¹ over two years. Myopia control efficacy increased with wearing time for HAL lenses, reaching 0.99D (67%) less myopia progression and 0.41mm (60%) less axial elongation on average over two years for full-time wearers, when compared to single vision spectacle lenses¹. This clearly shows that there is greater efficacy when the lenses are worn more than 12 hours per day every day, than when worn less than 12 hours per day. Hence, full-time wear of a myopia control solution such as Essilor® Stellest® lenses should be encouraged for children, to maximize myopia control outcomes.

 Aside from this, a recent publication in Ophthalmic and Physiological Optics journal has shown that after the first and second year, the eye growth of 9 out of 10 children wearing Essilor® Stellest® lenses full time was similar or slower than non-myopic children.³  

A one-year crossover clinical trial led by Brien Holden Vision Institute in collaboration with our R&D team and Hai Yen Care Institute, Vietnam, evaluated the progression of myopia in 119 Vietnamese children wearing HAL lenses versus standard single-vision lenses.  It also allowed us to evaluate whether rebound of myopia progression upon discontinuation was observed. The children were aged 7-13 years, with a myopic prescription between -0.75 to -4.75D and were randomized to wear either HAL lenses or single vision lenses. After 6 months, they crossed over, so the HAL lens group was now wearing single vision lenses for the next 6 months and hence, any rebound effect could be measured. Children were compliant with lens wear; an average of 14 hours per day of lens wear was reported with both lenses. The data was not suggestive of rebound when patients were switched from HAL lenses to single vision lenses.⁴ The efficacy comparisons also confirm that HAL lenses slowed myopia progression compared to single vision lenses.

In the fourth and fifth year of the study, 43 out of 51 children who wore HAL lenses continuously for three years accepted to be followed for two more years and completed the fourth year and fifth year follow-up. For year four and five, there was no control group for ethical reasons, as the new single vision lens group recruited for the third year were given a pair of HAL lenses at the end of the third year. Instead, an extrapolated control group was used for the fourth and fifth years, based on a model proposed by Shamp et al.^1,5 in which mean axial elongation decreases as age increases, by 15.0% per year and a model proposed by Smotherman et al.⁶ in which SER decreases by 9.7% per year on average.  Shamp et al. and Smotherman et al.’s models were applied to the initial control group that participated in the two-year randomized clinical trial.  An average decrease of change in axial length by 15% per year and an average decrease in SER by 9.7% per year was applied to this single vision lens group data from the first two years of the clinical trial.  

 The accuracy of the extrapolated control group was assessed by comparison to the single vision lens group that was matched to the initial control group at the end of the second year. It was found that myopia progression and axial elongation in the extrapolated control group was very comparable to the actual change of axial length and myopia progression during the third year with these real-life recruited age matched controls. Thus, Shamp et al.’s and Smotherman et al.’s models were validated by comparing against the third-year single vision control group. These models proposed by Shamp et al. and Smotherman et al. could be valid options for avoiding placebo control groups if prior change in axial length and myopia progression are available.

The efficacy of different myopia control modalities can be evaluated in terms of myopia progression in dioptres or axial elongation in millimetres. Axial length is preferred due to its greater precision and because refractive error cannot be accurately assessed during orthokeratology and can be influenced by atropine. 

 At present, there are different metrics for presenting efficacy of a myopia control treatment. Percentages should be avoided because they are very dependent on the age and race of the  participants. Brennan et al. recognized that the optimal way to express efficacy observed with   myopia control solutions is Cumulative Absolute Reduction in axial Elongation (CARE).⁷ This is  reported by most clinical trials and is a simple and clear metric. 

 CARE provides relevant insights into the success of myopia control solutions by evaluating the actual reduction in axial elongation over time. Moreover, unlike other metrics, such as percentages, CARE is unaffected by age and ethnicity, so values from one study can be applied to other populations. For Essilor® Stellest® lenses, the CARE value is 0.49 mm over three years, higher than any other optical treatment, and 0.72 mm over 5 years, placing it among the most effective options.

Last year we published a paper identifying some of the challenges of conducting conventional randomized clinical trials of myopia control.⁸ For example, we have to ask ourselves whether it's ethical to withhold myopia control treatment from children ⁹ for the duration of a three-year trial. Likewise, there are practical challenges of recruiting and retaining children when myopia control modalities are becoming available. 

We proposed a number of solutions including non-inferiority trials where an approved drug or device is used as a control.⁸ Here all children receive some form of treatment. Two other potential solutions were the creation of a virtual control group based on our meta-analysis where age and ethnicity are accounted for. The challenge here is that any cohort of children recruited for a study may show differences from historical cohorts because of the setting and potential recruitment biases. A preferred approach is to recruit a control group for a short period of time, perhaps one or two years, and after that time, put them on treatment. The control group data can then be extrapolated to future years assuming a slowing of axial elongation of 15% per year.

A number of papers have successfully leveraged this approach. For example, we examined the three-year data from the LAMP study¹⁰ where there were only one year of control data.¹¹ By applying the 15% slowing per year, we were able to extrapolate the control group to three years and thus estimate the three-year efficacy of the three different concentrations of atropine. Likewise, the investigators of the MiSight dual-focus contact lens were able to estimate the six-year efficacy of the lens by taking three years of data on control subjects wearing single vision soft contact lenses and extrapolating their axial elongation through six years.⁹ In summary, this approach offers a solution to the ethical challenge of withholding treatment for several years.

It is important to recruit a robust sample size and to carefully randomize the children to either treated or control groups. If randomization is not performed, this can lead to bias as parents may elect to choose the treatment or single vision spectacles based on unknown factors. It is also important to recruit and retain a meaningful number of control subjects. We know from recent clinical trials that any withdrawal of some subjects may lead to bias as those withdrawing may have above average rates of progression, leaving the retained subjects with a lower rate of progression, again leading to bias.¹² A final concern is that the parents of control group children may seek myopia management options outside of the study.

We performed several studies with HAL lenses to observe their impact on other factors such as choroidal thickness, corneal astigmatism, peripheral and central eye elongation, and more. For example, we conducted a study based on the two-year randomized clinical trial with HAL lenses, to explore the changes in cylinder power and corneal astigmatism in myopic children wearing HAL lenses and to compare these findings with myopic children wearing single-vision lenses (SVL). 

 In this study, a total of 103 eyes in 52 children from the HAL group and 98 eyes in 49 children from the SVL group completed all examinations and were included in the analysis. The HAL group demonstrated significantly slower myopia progression and change in axial length, compared to the SVL group. The study concluded that after two years, wearing HAL lenses had no significant impact on cylinder power and corneal astigmatism compared to single vision lenses.¹³

 In addition to this, we also conducted another study to examine the effect of wearing HAL lenses for three years and whether switching from single-vision lenses to HAL lenses exhibited any changes in choroidal thickness. The key outcomes from the study were that during the third year, children who consistently wore or switched to wearing HAL lenses demonstrated significantly less choroidal thinning compared to children wearing single vision lenses.¹⁴ 

 Aside from this, we also wanted to explore the effect of HAL lenses on the peripheral eye length changes in Chinese myopic children. We presented an abstract at ARVO on this study as well. We observed that HAL lenses were effective in slowing down both central and peripheral eye elongation. Similar elongation rates were observed in children wearing HAL lenses, thus preventing the eyeball from growing towards a more oval shape.¹⁵