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Epidemiology
Clinical science
Factors influencing myopia stabilisation in young myopic adult Singaporeans
Free
  1. Li Lian Foo1,2,3,
  2. Chuen-Seng Tan4,
  3. Brennan Noel5,
  4. Hla M Htoon2,
  5. Raymond P Najjar2,3,6,
  6. Biten Kathrani5,
  7. Charumathi Sabanayagam2,3,
  8. Seang-Mei Saw2,3,4
  1. 1 Singapore National Eye Centre, Singapore
  2. 2 Singapore Eye Research Institute, Singapore
  3. 3 Duke-NUS Medical School, National University of Singapore, Singapore
  4. 4 National University Singapore Saw Swee Hock School of Public Health, Singapore
  5. 5 Johnson & Johnson Vision, Jacksonville, Florida, USA
  6. 6 Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  1. Correspondence to Dr Seang-Mei Saw, Singapore Eye Research Institute, Singapore, Singapore; ephssm{at}nus.edu.sg

Abstract

Purpose To evaluate factors influencing stabilisation of myopia in the Singapore Cohort of Risk factors for Myopia.

Methods We evaluated the longitudinal natural history of 424 myopic participants from 1999 to 2022. The outcome was the change in myopia from the adolescence follow-up visit (aged 12–19 years) to the adulthood follow-up visit (aged 26–33 years). Association of predictive factors, including baseline spherical error, gender, ethnicity, parental myopia, time outdoor, near work and age at adolescence, was examined with the dichotomous outcome of adult myopia progression (≤ −1.00 dioptres (D) over 10 years) using multiple logistic regression and progression in linear regression models.

Results For the primary outcome, the mean rate of progression of the outcome was found to be −0.04±0.09 D per year from the adolescent to the adulthood follow-up visits. 82.3% (95% CI 78.3% to 85.8%) had myopia stabilisation, with progression of less than 1.00 D over 10 years while 61.3% (95% CI 56.5% to 66.0%) of the subjects had progression of less than 0.50 D. In logistic regression models, both male gender (p=0.035) and non-Chinese ethnicity (p=0.032) were more likely to achieve myopia stabilisation while in linear multivariate regression models, males had a significantly slower degree of myopia progression (p=0.021).

Conclusion 5 in 6 Singaporean young adults had myopia stabilisation. Male gender is 2 times and non-Chinese ethnicities are 2.5 times more likely to achieve myopia stabilisation. However, a proportion of myopes continue to exhibit a clinically significant degree of progression in adulthood.

  • Epidemiology

Data availability statement

Data are available on reasonable request.

https://doi.org/10.1136/bjo-2023-323680

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • Myopia stabilisation was found to be associated with ethnicity, gender, parental myopia and severity of myopia in various non-Asian cohorts. There is currently a lack of longitudinal studies elucidating the potential associations of myopia stabilisation in Asian cohorts.

    WHAT THIS STUDY ADDS

    • Five in six adolescents and young Asian adults had myopia stabilisation with less than 1.00 D of myopia progression over a 10-year period. Male gender is 2 times and non-Chinese in ethnicity are 2.5 times more likely to achieve myopia stabilisation, regardless of age, parental myopia, childhood refractive error and environmental risk factors.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • Early termination of myopia control treatment could be considered in low-risk individuals for myopia progression.

    Introduction

    Myopia, defined by a refractive error of −0.50 dioptres (D) or worse,1 is becoming a global public health concern. Fast myopia progression in childhood can be addressed through interventions such as atropine eye-drops and optical devices (eg, myopic defocus spectacles and contact lenses).2 However, there is currently no consensus among eye care professionals with regard to the age to terminate treatment, duration of treatment and the type or combination of myopia control interventions to use. Although randomised control trials were typically performed on younger children of up to 13 years of age,3–5 myopia control treatments may or may not be efficacious in older individuals in adolescence and young adulthood.6

    The identification of factors influencing myopia progression during teenage years into young adulthood could guide myopia management and risk profiling. It was estimated that the mean age for myopia stabilisation was 15.6±4.2 years, based on the US-based Correction of Myopia Evaluation Trial (COMET) with stabilisation age being strongly dependent on ethnicity.7 In the Drentse Refractive Error and Myopia (DREAM) Study from the Netherlands, the refractive error of children with childhood myopia at 10 years generally stabilised after age 15 years. However, in children with myopia worse than or equal to −5 D, myopia may continue to progress up to a rate of −0.25 D per year until the age of 21 years.8 In the Raine study from Australia, although it was found that 52.2% of the 20-year subjects had a stable refraction in both eyes over the 8 years, around one-third of them had myopic progression (change in 0.50D in at least one eye).9 Female gender and parental myopia were also found to be associated with continual myopia progression from 20 to 28 years.9 However, there is currently a lack in longitudinal studies elucidating the potential associations of myopia stabilisation, particularly in Asian cohorts.

    The Singapore Cohort of Risk factors for Myopia (SCORM) cohort is a retrospective population-based study whereby children from grades 1 to 3 (aged 7–11 years) were recruited from three Singapore schools (n=1979) with the methodology described previously.10–12 The aim of this study is to evaluate the factors influencing myopia progression in adulthood in the SCORM 23-year cohort.

    Methods

    Study design

    Four hundred and twenty-four subjects of the SCORM cohort who were myopic and attended at the 2007 visit were included in this study. At baseline, children were excluded if they had serious medical conditions, syndrome-associated myopia, a history of refractive surgery or any other eye disorders. All subjects included in this study attended childhood baseline visit (1999–2001), adolescence follow-up (2007) visit and the adulthood follow-up (2016–2022) visit.

    Eye measurements

    Cycloplegic refraction was performed at every visit. After the instillation of one drop of 0.5% proparacaine, cycloplegia was achieved with 3 drops of 1% cyclopentolate instilled at 5 min intervals. After an interval of at least 30 min after the last eye-drop, cycloplegic autorefraction was performed with a table-mounted autorefractor (model RK5; Canon, Japan). Five measurements were performed per eye (all readings <0.25 D apart) and total mean was used for analysis. Spherical equivalent (SE) for each eye was calculated as sphere power plus half cylinder power.

    Questionnaires

    Questionnaires translated and validated in different languages (English, Chinese and Malay) were administered to parents by a trained interviewer at the childhood baseline visit (1999–2001). The questionnaires included demographic data (age, ethnicity, gender) as well as environmental risk factors (books read per week, and time spent outdoors (hours per week)) and parental risk factors (mother’s education level and number of parents with myopia).11 Parents were considered myopic if they were wearing corrective lenses for distance vision. Time spent outdoors in adolescence follow-up visit (2007) and adulthood follow-up visit (2016–2022) were recorded separately for weekdays and weekends using an adapted version of the Sydney Myopia Study questionnaire and was defined as the sum of outdoor leisure and outdoor sporting activities.13

    Statistical analysis

    Statistical analyses were performed on 424 subjects who attended all three visits with the change in myopic refractive error from the adolescence follow-up visit to the adulthood follow-up visit as the outcome. Refraction was determined by cycloplegic autorefraction for all visits. The more myopic eye (worse eye) of each subject at the adult follow-up visit was chosen for analysis. Predictive factors from the childhood baseline follow-up visit (baseline SE, parental myopia, time outdoor and near work) and adolescence follow-up visit (age in 2007) were analysed as continuous variables with gender and ethnicity as categorical variables. We examined the association of predictive factors for adult myopia progression using multiple logistic regression models with ORs and their 95% CIs as well as adult SE progression (D/year) using multiple linear regression models with regression coefficients and their 95% CIs using the manual backward stepwise approaches. Myopia progression was defined as worsening in myopia of at least 1.00 D or more over 10 years (with myopia progression corresponding to≤−1.00 D) and is calculated by

    Embedded Image

    Confounders considered were based on a priori knowledge from the literature and the fit of the model. The final multivariable model was determined with backward manual stepwise selection, starting with the full model and identifying a single confounder with the least significant p value (if p>0.05) to exit the model at each step. Instead of an automated process, a manual exclusion and inclusion of confounders were made as the decision for the final model considered both model fits and evidence from the literature. Receiver operating characteristic curve and area under the curve (AUC) associated with logistic regression model for SE stabilisation was used to assess the model’s predictive performance. A two-sided p value that was less than 0.05 was considered statistically significant. IBM SPSS Statistics for Windows (V.24.0) and Stata (V.16) were used to perform the analyses.

    Results

    Our study comprised 424 myopic subjects aged between 12 and 19 years (mean±SD, 14.6±1.2 years) in the adolescence follow-up visit, and 26–33 years (28.6±1.2 years) in the adulthood follow-up visit. Overall, 46.2% of subjects were males and 83.3% were Chinese and 35.6%, 40.3% and 24.1% had 0, 1 and 2 parents with myopia, respectively. The outcome was determined from these two visits with a mean follow-up duration of 12.0±2.0 years. 82.3% (95% CI 78.3% to 85.8%) of subjects had myopia stabilisation, with progression of less than 1.00 D over 10 years, while 61.3% (95% CI 56.5% to 66.0%) of the subjects had progression of less than 0.50 D. The mean rate of progression was found to be −0.04±0.09 D per year, with −0.03±0.08 D per year in males and −0.05±0.09 D per year in females (p<0.001) (figure 1).

    Figure 1
    Figure 1

    Box plot of change in SE per year in from adolescence to adulthood (D/year) by gender (N=424). SE, spherical equivalent.

    In the logistic regression analysis, both female gender and Chinese ethnicity were found to be at higher risk of myopia progression. The OR for gender and ethnicity are 1.72 (95% CI 1.04 to 2.86; p=0.035) and 2.52 (95% CI 1.08 to 5.89; p=0.032), respectively, in the multivariable model comprising age (2007), gender, ethnicity, parental myopia and time outdoors (baseline) (table 1). In linear regression analysis, female gender was also found to have greater degree of myopia progression with significant regression coefficient of −0.020 D/year (95% CI −0.037 to −0.003; p=0.021) in the multivariable model (table 1). 84.2% of males had myopia stabilisation compared with 75.0% in females over 10 years (p=0.020).

    View this table:
    Table 1

    Association of key risk factors for adult myopia progression (lack of stabilisation)

    Prediction models using AUC for SE stabilisation yielded suboptimal results with an AUC of only 0.62 in the model comprising age (2007), gender, ethnicity, parental myopia and time outdoor (baseline) as predictors.

    When comparing the baseline characteristics of the 424 subjects included in our analysis with the 1555 subjects lost to follow-up, we observed no significant differences in age (7.9±0.9 vs 7.8±0.5 years; p=0.32), gender (46.7% vs 51.6% males; p=0.071) and parental myopia (35.6%, 40.3%, 24.1% vs 39.7%, 39.0%, 21.2% with 0, 1, 2 parents with myopia, respectively; p=0.24). However, we did find significant differences of Chinese race and other races (83.3%, 17.7% vs 72.4%, 27.6%; p<0.001) and baseline SE (−0.79±1.8 vs -0.30±1.6 D; p<0.001).

    Discussion

    In this study, we evaluated the factors that predict stabilisation of myopia from childhood to young adulthood. Myopia may continue to progress in young adulthood with progression of −0.04±0.09 D per year from the adolescence to young adult years. However, 82.3% had myopia progression stabilisation with myopia progression of less than 1.00 D progression over 10 years while 61.3% of the subjects had stabilisation with less than 0.50 D progression. We found that non-Chinese males had a higher likelihood of adult myopia stabilisation regardless of age, parental myopia as well as childhood refractive error and environmental risk factors. Females had higher odds of myopia progression (OR=1.7) and degree of myopia progression (regression coefficient of −0.020 D/year). The borderline significance of age as a risk factor for adult myopia progression in our study may be attributed to a relatively small sample size leading to reduced statistical power. There may also be residual confounding.

    Our findings were consistent with previously reported studies. In the 8-year Raine Study examining young adults from 20 to 28 years, 52.2% had stabilisation of myopia with myopia progression (≤ −0.50 D in at least 1 eye) continuing for more than one-third of adults at a rate of −0.04 D per year.9 This study also found that the risks of myopia progression were greater in female subjects (OR=1.8).9 However, the disparity in the racial composition of our study subjects and those in the Raine Study as well as the difference in recruitment methods (hospital based vs population based) could account for the lack of significance in our findings regarding parental myopia as a risk factor. At present, the key driving factors for this finding are unclear and other factors including environmental or hormonal, particularly during pregnancy, require further exploration.14 15 In the diverse ethnicity COMET study, comprising 47% Caucasian, 26% African American, 15% Hispanic, 8% Asian and 5% mixed, the mean age at myopia stabilisation was 15.6±4.2 years with ethnicity significantly influencing the age of stabilisation (p=0.02). African Americans were the youngest (mean 13.82 years) at stabilisation,7 further emphasising the role of genetic influence in myopia stabilisation, similar to our findings where ethnicity play a role in predicting stabilisation.16 The DREAM study also found that myopia generally stabilised after age 15 years except for those with magnitude of myopia ≤−5 D in a European population.8 This difference once again reinforces the role of various ethnic genetic compositions in determining the onset of myopia stabilisation, in comparison with our Asian cohort comprising largely Chinese population.16 Our results are clinically relevant as there is currently no consensus among eye care professionals with regard to the age to terminate treatment, duration of treatment and the form of myopia control interventions to use. Latest treatments for myopia include optical devices in the form of defocus spectacle lenses5 17 and daily disposable soft contact lenses.3 18 Although randomised control trials were typically performed on younger children of up to 13 years of age,3–5 myopia control treatment may also be efficacious in older children and adolescents.6 Since one in six adolescents were found to have continued progression of at least 1 D or more, myopia control interventions might be beneficial in minimising the risk of developing high myopia through limiting ongoing myopia progression. However, these interventions may not be suitable for all and can potentially introduce side effects.19 20 Eye care professionals would need to exercise judgement and weigh in on the risks and benefits of initiating or continuing treatment on a case-by-case basis.

    From early adulthood, individuals may opt for refractive surgery to reduce their dependence on spectacles and contact lenses. Laser in situ keratomileusis (LASIK) has been around for more than two decades and is one of the most commonly performed refractive surgeries to correct myopia globally.21 Despite technological advances, post-LASIK regression (residual myopia of 0.25 D or greater) is still frequently observed and has significant implications for the long-term visual performance and quality of life of patients.22 The exact mechanism that leads to regression is yet to be elucidated with several factors postulated to be involved, including compensatory epithelial hyperplasia,23 biomechanics changes24 and forward shift of both the anterior and posterior corneal surfaces.25 26 Our study suggests that myopia progression in young adulthood could also contribute to the residual myopic outcome for post refractive surgery individuals, with potential myopia progression of at least 1.00 D or more with time. However, further works would be required to investigate the progression in axial length to validate this finding.

    The strength of our study was the school-based, longitudinal design with long duration of follow-up. However, our study had several limitations. We were limited by lost to follow-up secondary to the lengthy follow-up duration. Participants who attended the last follow-up visit in adulthood were significantly different in terms of race and SE at baseline from those who did not attend, thereby introducing a lost to follow up bias. Furthermore, the absence of genetic data prevents us from assessing its impact on the stabilisation of adult myopia.Nevertheless, the results from this study could serve as the precursor for studying myopia stabilisation in early adulthood, thereby guiding myopia control treatment and refractive surgery management. Future studies, investigating different populations with larger sample size, longer follow-up duration and axial length elongation, may be more elucidative.

    Conclusion

    In conclusion, our study showed that five in six adolescents and young adults had myopia stabilisation with less than 1.00 D of myopia progression over a 10-year period. Male gender is 2 times and non-Chinese in ethnicity are 2.5 times more likely to achieve myopia stabilisation, regardless of age, parental myopia, childhood refractive error and environmental risk factors. Early termination of myopia control treatment could be considered in these low-risk individuals for myopia progression. However, a proportion of myopes continue to exhibit a clinically significant degree of progression into the adult years.

    Data availability statement

    Data are available on reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    The study obtained ethics approval from the Centralised Institutional Review Boards of the Singapore Health Services (2016/2215) and was conducted in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from the parents in childhood baseline and adolescence follow-up visits and from the subjects themselves in visit 3 after the nature of the study was explained.

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    Footnotes

    • X @Ray_Najjar

    • Correction notice This article has been updated since it was first published. An additional affiliation has been added for Raymond P Najjar.

    • Contributors LLF, C-ST, BN, HMH, RPN, BK, CS and S-MS conceptualised the manuscript, researched its contents, wrote the manuscript and edited all revisions. S-MS is guarantor.

    • Funding This work is supported by National Medical Research Council Individual Research Grant (NMRC/0975/2005) and National Medical Research Council Center Grant (NMRC/CG/C010A/2017_SERI).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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