Johnson & Johnson Vision myopia research showcased at ARVO 2023

The Association for Research in Vision and Ophthalmology (ARVO) 2023 meeting was held in New Orleans, Louisiana USA from 23 to 27 April 2023. Attracting over 10,000 eye and vision scientists, Johnson & Johnson Vision showcased five posters of their latest myopia research over the course of this conference. Here's the lowdown on this latest work. 

The image above shows lead authors on this latest research, from left: Xu Cheng, Noel Brennan, Monica Jong, Mark Bullimore and Alex Nixon.

Authors: Monica Jong^1,2, Noel A. Brennan¹, Xu Cheng¹, Mark A. Bullimore³

1. Johnson and Johnson Vision, Jacksonville, Florida, United States
2. School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia
3. University of Houston, Houston, Texas, United States

Myopia progression calculators are a useful communication tool when explaining prognosis to parents. The authors compare the Brien Holden Vision Institute (BHVI) Myopia Calculator with MyAppia for its 3-year progression for baseline values of 8 or 11 years, -1.00 or -4.00D and Asian or White. They also compared the differences in the final refraction based on slowing progression by 50%. The BHVI calculator tended to overemphasize the difference between Asian and white children, showing a 2x higher rate of progression in Asians whilst the evidence is suggesting closer to 30%. The BHVI calculator overestimates myopia control efficacy in both younger patients and Asians, whilst for MyAppia it was in younger patients.

Purpose: A number of tools are available for predicting future progression of myopia, an important part of clinical practice. Here we compare the Brien Holden Vision Institute (BHVI) Myopia Calculator with MyAppia.

Methods: The BHVI calculator allows input of a child's age, ethnicity (Asian or white), and current prescription. The free online version of MyAppia uses just age and current prescription. We determined 3-year progression for baseline values of 8 or 11 years, -1.00 or -4.00 D, and Asian or White. We also extracted the slowing of progression (efficacy) based on an input of 50% slowing.

Results: The table shows the results from both calculators. The BHVI calculator shows a faster rate in Asians (by nearly a factor of 2) and slightly slower progression in higher myopes. In contrast, with MyAppia, progression is independent of age and baseline myopia and similar to that derived from the BHVI Calculator for Asian children. Inputting a 50% slowing produces the expected result. Unfortunately, in absolute terms, the 3-year efficacy varies by a factor of three from 0.35 to 1.18 D, when the evidence base indicates that treatment efficacy expressed in D or mm is largely independent of age, ethnicity, and myopia level. Also, a 3-year slowing of over a diopter is at odds with published data.

Conclusions: The BHVI calculator may overemphasize the difference in progression between Asians and whites-meta-analysis suggests the difference is closer to 30%. Both calculators exaggerate myopia control efficacy in younger patients and, for the BHVI calculator, in Asians when compared to the evidence base. It remains unclear whether Asians in the Western world progress at a similar rate to those in Asia.

Authors: Alex Nixon¹, Jie Xu¹, Noel A. Brennan¹, Robert Morlock², Xu Cheng¹

1. Johnson and Johnson Vision, Jacksonville, Florida, United States
2. Henry Ford Health System, Detroit, Michigan, United States

Though myopic progression can occur through the teenage years, most soft contact lens myopia control studies have been on children younger than 12 years old. The authors compared the subjective visual experiences between two groups of children: 7-12 years old and 13-17 years old. Three test lenses were two prototype MC SCLs with noncoaxial ring-focus designs (for enhancing efficacy [EE] and enhancing vision [EV]) and one dual-focus (DF) design. They found that older children were more judgemental of the quality of vision in the early periods of wear, noticing a difference on survey in both EE and DF designs, but not the EV design. Read about efficacy of these designs in THIS review. The designs were not directly compared to each other. The authors concluded that extra thought should be given when considering myopia control in older children who tend to be more critical of their vision quality and are less likely to progress rapidly.

Purpose: Soft contact lenses for myopia control (MC) are often evaluated in younger children (≤12 years), but meaningful myopia progression can occur during the teenage years. We performed post-hoc analysis of a prospective clinical study in myopic children to learn about subjective vision experience in soft contact lenses for MC by age.

Methods: This was a multi-site, single-masked, 3x3 crossover study with a run-in period. Healthy myopic children from 7 and 17 years old were recruited, balancing the number of children 7-12 years old with those 13-17 years. Subjects initially used a daily disposable (DD) soft contact lens (SCL) with conventional optics (1DAM) for one week, then lens wear sequence was randomized and subjects were fit with one of three MC SCLs for each of three, 2-week periods. There were two senofilcon A prototype MC SCLs with noncoaxial ring-focus designs (for enhancing efficacy [EE] and enhancing vision [EV]) and one omafilcon A dual-focus (DF) design. Subjective vision was assessed using the Pediatric Myopia Control Questionnaire (PMCQ) at the 2-week follow-up. An overall vision item was analyzed using the Pearson chi-square test to assess differences in top two box (T2B, excellent and very good) proportions between the two age groups for each lens type separately.

Results: The intent-to-treat population included 75 participants, with 38 from 7-12 years (mean 10.6 ± 1.05 years) and 37 from 13-17 years (mean 14.7 ± 1.31 years). Patient-reported overall vision by lens type and age is shown in Figure 1. A significant difference in T2B proportions by age was detected for EE (p=0.032) and approached for DF (p=0.053), but there was no significant difference for 1DAM (p=0.252) or EV (p=0.502). Two subjects discontinued due to unsatisfactory vision with a test article, both from the 13-17 age group.

Conclusions: The subjective visual impact of MC SCLs may be perceived differently in younger versus older children, with older children more judgmental of their vision experience, at least during the early period of wear. The subjective visual impact by age was design dependent, and a different balance of vision quality and myopia control efficacy may be prudent in older children to better fit their more critical assessment of vision quality and decreasing average annual rate of myopia progression.

Authors: Xu Cheng¹, Paul Weiss^2,1, Mark A. Bullimore³, Noel A. Brennan¹

1. Johnson and Johnson Vision, Jacksonville, Florida, United States
2. MaxisIT Inc, New Jersey, United States
3. University of Houston, Houston, Texas, United States

Efficacy of myopia control interventions is commonly measured in two ways: using continuous data over the course of the study and determining whether its treatment effect meets a certain threshold in cumulative effect; and/or applying an arbitrary threshold for analysing the odds of progressing a certain value (e.g. 0.50D). The authors applied T-tests, Chi-square tests and Odds Ratio to simulated randomized controlled clinical trials and found that the former outperformed the latter by two statistical methods. This suggests that applying an arbitrary threshold to dichotomize continuous outcomes is insufficient in informing relevant efficacy, and a lesser efficient tool for myopia control clinical trials.

Purpose: Two methods are commonly used to evaluate efficacy of myopia control interventions - 1) using continuous data as they were collected and determining whether the treatment effect size meets a pre-specified target, eg, 0.75 D, and 2) dichotomizing the data by applying an arbitrary cut-off for analysis of odds of progression exceeding an amount, eg, 0.50 D. We consider the implications for myopia control efficacy trials and the efficiency of the approaches in detecting clinically important changes in myopia progression.

Methods: We simulated randomized controlled clinical trials by repeatedly sampling a fixed number of subjects from test and control populations with normally distributed outcomes (changes in refraction and axial length) whose means differed by a fixed effect. Typical progression and Standard Deviation (SD) over time for the control population were estimated from a literature review covering a range of subject ages and races. The empirical power of the clinical trial for detecting a statistically significant difference was computed for a range of effect sizes, progression cut-off values, and sample sizes. Continuous outcomes were assessed by independent sample T-tests and dichotomized outcomes by Chi-square test and Odds Ratio (OR) 95% confidence interval. Significance was determined based on  <0.05 for testing or by an interval failing to cover 1.

Results: Figure 1 presents an example of the output, plotting empirical power for detecting an efficacy over a range of effect sizes (0.25 to 0.75 D) and progression cut-off values (-0.50 to -1.00 D) for sample sizes ranging between 50 and 200 per group after 36 months of treatment. Predictably, T-test consistently outperformed the Chi-square test and OR for any given sample size to detect any efficacy. Dichotomization requires sample size inflation to achieve comparable power to the continuous approach.

Conclusions: Arbitrarily dichotomizing continuous outcome measures for analysis of odds without regard to treatment effect size does not sufficiently inform about clinically relevant efficacy, limits generalizability, and is less efficient in design of a myopia control clinical trial.

Authors: Mark A. Bullimore¹, Noel A. Brennan²

1. College of Optometry, University of Houston, Houston, Texas, United States
2. Johnson & Johnson Vision Care Inc, Jacksonville, Florida, United States

In a previous meta-analysis the authors found that axial length slows by 15% per year amongst untreated myopic children. Applying this figure to children treated with low-dose atropine regardless of concentration accurately the cumulative axial length change after 3 years of treatment, as validated by the LAMP study outcomes. By applying a ratio of -1.99D per mm change, one can predict the degree by which myopia has been slowed after 3 years.

Purpose: 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. Because the year 1 control group in the LAMP Study was switched to treatment in years 2 and 3, long-term efficacy could not be directly calculated.

Methods: Our recent meta-analysis of over 80 studies of axial elongation among untreated myopic children concludes that it slows by an average of 15.0% per year (95% CI of 11.4% to 18.4%). We used this 15% slowing per year to predict axial elongation in years 2 and 3 and the 3-year cumulative absolute reduction in axial elongation for each concentration of atropine. The 3-year slowing of myopia progression was also calculated by applying a ratio of progression to elongation derived from the untreated participants in years 1 and 3.

Results: The 93 children initially assigned to placebo elongated by 0.41 mm in year 1. Applying 15% slowing per year predicts elongation of 0.35 and 0.30 mm in years 2 and 3, respectively, projecting a cumulative untreated 3-year axial elongation of 1.05 mm (Figure 1). The mean axial elongation among the 127 children completing the year-3 washout was also 0.30 mm. The axial elongation for children treated throughout the 3-year study with 0.05%, 0.025%, and 0.01% atropine was 0.50, 0.74 and 0.89 mm, respectively (Figure 1). Thus, the corresponding 3-year cumulative absolute reduction in axial elongation is 0.55, 0.31, and 0.16 mm. The 93 untreated children in year 1 progressed by -0.81 D and elongated by 0.41 mm-a ratio of -1.98 D/mm. Additionally, the 127 untreated children in year 3 progressed by -0.61 D and elongated by 0.30 mm-a ratio of -1.99 D/mm. Applying either of these ratios to the 3-year untreated axial elongation of 1.05 mm gives a 3-year progression of -2.09 D. Comparing this with the mean progression among those treated continuously for 3 years, yields projected 3-year slowing of progression of 1.36, 0.78, and 0.49 D for 0.05%, 0.025%, and 0.01% atropine, respectively.

Conclusions: Applying a 15% annual slowing of axial elongation from a comprehensive meta-analysis allows prediction of the 3-year efficacy of low-concentration atropine in the LAMP Study.

Authors: Carmen Smotherman¹, Noel A. Brennan¹, Xu Cheng¹, Wright Shamp¹, Ryan Butterfield¹, Mark A. Bullimore²

1. Johnson and Johnson Vision, Jacksonville, Florida, United States
2. University of Houston System, Houston, Texas, United States

Myopia growth or progression curves are increasingly referred to in myopia science and practice, yet the variation by age, sex, race and refractive status is yet to be resolved. While large variation was found across the progression range, Asian children were found to progress around 40% faster than non-Asian children, and increasing age contributed a 10% slow down of progression per year. Building on this analysis will help to further characterize expected myopia progression to apply to research and clinical practice settings.

Purpose: With increasing interest in slowing myopia progression, normative data for progression in myopic children provide a valuable clinical reference. Growth curves have been presented but are specific to population and usually include both myopes and non-myopes, limiting their application to myopia control. We conducted a meta-analysis to model refractive error change in myopic children with emphasis on the influence of age and race.

Methods: A comprehensive electronic systematic search was performed using Ovid Medline, EMBASE, Cochrane Central Register of Controlled Trials. To achieve maximum sensitivity of the search strategy, the following terms were used: "myopia" or "myopic" and "child" or "children" and "progression" or "longitudinal" or "follow-up" or "shift" and "refractive error". There were 106 studies with 165 subpopulations and 359 evaluations of the mean refractive error from baseline that met our inclusion criteria. Mean rate of change in refractive error was analyzed using a multivariate linear mixed effects meta-analysis model. All collected covariates were tested for significance (age, race [east Asian or not], and baseline refractive error selected). The model included three levels of random effects to account for all variability. Prediction intervals were calculated to show likely variability across a population.

Results: Only data without missing significant covariates were included in the final model (127 evaluations). The figure shows instantaneous myopia progression (in D/year) as a function of age and race. Mean refractive error progression decreases as age increases (9.7% decrease per year, 95% CI 5.4%-13.9%, P <0.0001) and is greater in Asian children (by 42.2%, 95% CI 18.3%-70.0%, P <0.0001) compared to non-Asians. The estimated prediction intervals show the broad range of progression rates.

Conclusions: To our knowledge, this is the first weighted random effects meta-analysis of refractive error change in myopic children. Interpretation of the data is limited due to the use of aggregated data rather than individual subject data. This analysis sets benchmark values and estimates of the spread of refractive error change for monitoring myopia progression and treatment efficacy.