Juvenile myopia progression, risk factors and interventions

Abstract

The development and progression of early onset myopia is actively being investigated. While myopia is often considered a benign condition it should be considered a public health problem for its visual, quality of life, and economic consequences. Nearly half of the visually impaired population in the world has uncorrected refractive errors, with myopia a high percent of that group. Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status.

Genetic and environmental factors contribute to the onset and progression of myopia. Twin studies have supported genetic factors and research continues to identify myopia genetic loci. While multiple myopia genetic loci have been identified establishing myopia as a common complex disorder, there is not yet a genetic model explaining myopia progression in populations.

Environmental factors include near work, education levels, urban compared to rural location, and time spent outdoors. In this field of study where there continues to be etiology controversies, there is recent agreement that children who spend more time outdoors are less likely to become myopic.

Worldwide population studies, some completed and some in progress, with a common protocol are gathering both genetic and environmental cohort data of great value. There have been rapid population changes in prevalence rates supporting an environmental influence.

Interventions to prevent juvenile myopia progression include pharmacologic agents, glasses and contact lenses. Pharmacological interventions over 1–2 year trials have shown benefits. Peripheral vision defocus has been found to affect the emmetropization process and may be affected by wearing glasses or contacts. Accommodation accuracy also has been implicated in myopia progression.

Further research will aim to assess both the role and interaction of environmental influences and genetic factors.

Introduction

The prevalence rate for myopia, an extremely common eye disorder worldwide, rose over the past three decades in the United States from 25% to 41%⁵⁰ and has risen to 70–90% in some Asian countries.^22,43 Higher myopia, over six diopters, is also increasing⁵⁰ and is associated with an increased lifelong risk of rhegmatogenous retinal detachment, glaucoma, and myopic degeneration.²⁷ The cost each year in the United States for optometric examinations, optical and surgical refractive corrections is several billion dollars.¹⁷ Worldwide there are 153 million visually impaired persons due to uncorrected refractive errors accounting for 49% of all visually impaired persons.⁴⁰ Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status.³⁸ Understanding the risk factors and interventions for the most common form of myopia, juvenile myopia is the aim of this review.

Juvenile myopia

Most studies classify over 60% of myopia as early onset also called juvenile or school myopia, occurring between 9 and 11 years of age with progression throughout the early teenage years.¹¹ There is agreement that both genetic and environmental factors contribute to the onset and progression of myopia. One variable predicting the future onset of myopia is a cycloplegic auto refraction of 0.75 diopter or less of hyperopia at a mean age of 8.6 years which has been shown to have a sensitivity of 87% and specificity of 73% in predicting future myopia.⁵⁷

While prevalence studies may look at the same age group, their protocols can differ making comparisons difficult. Starting with a year 2000 report,²⁶ many population studies around the world are using a common protocol. The Sydney Myopia Study³⁴ uses a protocol common with six studies starting with the Refractive Error Study in Children (RESC) in 2000. However, there are also 13 myopia prevalence studies in similar age groups that have different protocols for determining prevalence of myopia.³⁴

The prevalence of myopia reported for 6 year old children varies from 0.6% in Oman²³ to 29% in Singapore.⁴⁴ The prevalence in Oman for 6 year old children was 0.6%, but the definition of myopia was more than −1.0 diopter when most studies use −0.5 diopter. The prevalence of myopia among pre-school children at King Abdulaziz Medical City, Riyadh, Saudi Arabia is 2.5%.¹

The visual system has an active process of emmetropization that involves defocus detection and a coordinated growth of the refractive components toward emmetropia with active structural changes.^54,39 It is amazing how well emmetropization works and understanding what occurs when this process fails is the target of the research.³⁰ In the first three years of life the cornea and lens change to counterbalance an approximately 20 diopter increase in axial length of the growing eye.⁴⁷ Between ages 3 and 13 the lens and or cornea need to adjust about 3 diopters to maintain emmetropia.

As the human eye grows the lens adds layers of tissue yet thins by stretching in the equatorial plane so that it flattens, thins and loses power to compensate for the increasing axial length and maintains emmetropia.^32,25 When the lens fails to stretch and thin the eye becomes myopic and the eyeball shape becomes more prolate or less oblate. The source of this interruption of equatorial expansion is unknown with one hypothesis being the thickening of the ciliary muscle which is found in myopic children and adults.^35,2

When myopia develops the eye is longer than it is wider (greater anteroposterior length than lateral transverse dimensions). This prolate shape of the eyeball will create a relative hyperopic defocus in the peripheral vision, along the lateral dimensions away from the macula. This peripheral vision refraction is another hypothesis as a potential impact or trigger on the active emmetropization process.³³ Peripheral refraction in the myopic eye becomes relatively more hyperopic (Fig. 1). Local retinal regions can control local eye growth and myopia.⁵² The peripheral refractive state of the eye can affect eye development especially the progression of myopia.⁴⁶ An interesting study found 77% of young entering emmetropic pilots with relative hyperopic defocus in their peripheral refraction developed myopia during their training.¹³ Hyperopic eyes are usually myopic in the periphery adding to the hypothesis that the periphery focus could be a trigger in eye growth. Also being investigated is the increase in the lag of accommodation during near work and the increase in myopia.^4,29

Figure 1.

Emmetropic eye with relative hyperopic defocus in pheriphery.

A 2010 search in PubMed yields over 14,000 citations with many research disciplines working to identify risk factors and potential interventions to help control myopia. Understanding, controlling and treating myopia are also a goal of the World Health Organization, Vision 2020 project.⁵³

Genetic factors

High heritability in myopia suggests that there is a significant genetic component to explain the variance in the population. A high heritability index is found in twin studies varying from 75% to 94%. A recent large sample study of monozygotic and dizygotic twins estimates a heritability index of 77%.²⁴ However, this high index does not preclude an environmental precursor, and has some contestable assumptions (Morgan and Rose). Other genetic evidence pointed to is the prevalence of myopia in children increased with the number of myopic parents from 7.6, 14.9, to 43.6 percent for no, one or two myopic parents.¹⁵ However, it is an interesting observation of low heritability values in parent-offspring correlations when there has been rapid environmental change between generations.²⁸ The Genes in Myopia (GEM) family study calculated the heritability index between 27% and 55%.⁵ In a non twin study heritable factors accounted for 80% of juvenile myopia.³¹

Multiple myopia genetic loci have been identified establishing myopia as a common complex disorder.¹⁴ A recent review of data from the past decade in searching for myopia genes points to axial length and refraction sharing common genes and states that the majority of myopia cases are not likely caused by defects in structural proteins, but in defects involving the control of structural proteins.¹⁶ They conclude in discussing genes and their effects on myopia, “it is hard to show anything but a modest effect on their etiologies. Thus we are still left with the impression that the influence of environment exerts a greater effect than does the concerted action of several genes”.¹⁶

Environmental factors

While we wait for more evidence for genetic determination of refractive error there does exist evidence pointing to environmental risk factors. The increasing prevalence of myopia and high myopia which at times has rapidly changed in Taiwan, Singapore, Hong Kong, Scandinavia, and the United States has been pointed out as likely being environmental.^34,50 In can be difficult to compare prevalence studies if the protocol for sampling, refraction and use of cycloplegia is not standardized. Starting with a year 2000 study there have been population studies in Chile, China, Nepal, Urban India, Rural India, South Africa, and Australia using a common or comparable protocol.³⁴ This common protocol was further advanced in The Sydney Myopia Study which had a stratified random cluster sample a group of children aged 6 and a group aged 12, with a three year interval for reexamination. Data on eye structure and changes over time in this study include using Cyclopentolate use with auto refraction, noncontact biometry including optical coherence tomography. By also gathering data from the parents of the study population the study aimed to assess interactions between genetic and environmental risk factors.³⁴

Urbanization and educational attainment also has some contribution toward myopia development but only explains a small proportion of the variance seen.²⁸ Near work has been identified as a risk factor but with a weak association and difficult to quantify.⁵⁶

Recently data have shown a protective effect of the time spent outdoors in 6–7 year old children.^{31,36,41,18,20} This outdoor protective effect was also reported in 12 year old Sydney children.(Rose et al., 2008b) The time outdoor protective effect has been reported in the United States,^31,18 in Turkey,³⁶ and in Jordan.(Khader et al., 2006) The Orinda longitudinal study found this protective difference precedes the onset of myopia.¹⁸ The reduction in the probability of developing myopia by eighth grade if a child had two myopic parents went from 0.60 if the outdoor time in the third grade was low (0–5 h per week) to 0.20 if the outdoor time is high (>14 h per week).¹⁸ Statisticians have modeled risk factors that include age, gender, ethnicity, school, IQ level, number of books read per week, height, parental myopia and adding time spent outdoors significantly improves the fit of the model.⁹

To help measure the relative roles of the environment and genes it is valuable to examine the prevalence of similar ethnicity in a population that migrates to a different environment. This was done in comparing the prevalence and risk factors in 6 and 7 year old children of Chinese ethnicity in Sydney and Singapore. The prevalence of myopia in the Chinese children was 3.3% in Sydney and 29.1% in Singapore yet the children in Sydney read significantly more books and had more total time in near activities. The most significant factor between the two sites was much more time on outdoor activities in Sydney.⁴² Measuring the prevalence rates in Caucasian and Chinese students in local and international schools in Hong Kong found both an effect of the different genetic background and an effect of the Hong Kong environment.²¹ Indians show a very low prevalence of myopia in India, however, the prevalence of myopia in Indians in Singapore is high.⁵⁵ Park and Congdon³⁷ argue that many of the prevalence studies in the literature have “significant shortcomings” chiefly due to lack of longitudinal data. Morgan and Rose²⁸ feel there is enough environmental evidence that in high pressure environments with intensive mass-education systems in highly urbanized environments, almost everyone could become myopic.

Interventions

Interventions to control juvenile myopia progression have included pharmaceutical agents, bifocal and Progressive lens glasses, and rigid gas permeable contact lenses. In a review of myopia trials to retard myopia progression in 2002 it was felt there was insufficient evidence to support any interventions.⁴⁴

Animal studies show myopic defocus produced by positive lenses reduce axial length increase.⁵⁸ Yet, a two year controlled prospective study on myopic children aged 9–14 who were under corrected by approximately +0.75 diopter showed an enhanced rather than an inhibited myopia development in axial length and thus more myopia.⁸

In a randomized masked 2 year trial giving myopic children atropine in one eye the treated eye progressed 0.38 diopters and the untreated eye progressed 1.20 diopters.⁷ This difference in myopia progression of −0.92 D was also accompanied by a reduced axial elongation of 0.40 mm. No serious adverse events related to atropine were reported. However, this difference narrowed one year after the atropine was stopped.⁴⁹ This atropine study group also reports embarking on a new randomized clinical trial using three different atropine concentrations with bilateral treatment for more than two years with a post treatment monitoring to evaluate long term comparative myopia control effects of the treatment.⁷ There have been two studies using Pirenzepine gel, in the United States,⁴⁵ and, in Asia,⁴⁸ showing a nearly 50% reduction in progression when used twice a day.

Rigid contact lenses have been reported to slow myopia progression but had not been studied in a controlled randomized trial until 2003. Rigid gas permeable contact lenses were found to have only a mild nonsignificant protective effect.¹⁹ A more recent two year study of forty, 8–11 year old children given corneal reshaping contact lenses during sleep reported slowed eye growth compared to the matched soft contact wearing children.⁵¹

Two randomized trials of Progressive addition lens showed a very small protective effect of wearing the progressive glasses.^10,12 However, recently in a two year study, three randomized groups of children wearing single vision glasses, bifocals, or bifocals with base in prism progressed after two years 1.55 D, 0.96 D, and 0.70 D, respectively.⁶

Baseline data for the Study of Theories about Myopia Progression (STAMP) have recently been reported.³ This 2-year, double-masked, randomized trial will look at Progressive addition lenses compared to single vision glasses and myopia progression and also look at peripheral refraction, accommodative response and convergence, crystalline lens radii of curvature, axial dimensions, intraocular pressure, corneal curvature and thickness, as well as near work and outdoor activity assessment. The STAMP study will gather complete biometric data at 6 month intervals. The STAMP baseline data found that indeed the myopic children did have a peripheral hyperopic defocus similar to other reports along the lateral meridian of the eye and a new finding was a myopic defocus along the vertical peripheral meridian of the eye.(Fig. 2)

Figure 2.

Mean (SD) and relative peripheral refractions in the Study of Theories about Myopia Progression (STAMP) baseline data.

Conclusion

Genetic studies are actively continuing, but to date have not yet identified a genetic pathway for familial risk of myopia. The emmetropization process continues to be investigated looking for risk factors, such as peripheral vision defocus and accommodative lag, contributing to juvenile myopia progression. Pharmacologic treatments have reduced myopia progression but more studies including longer follow up are needed. Recent epidemiological studies have identified the time spent outdoors to be protective of the development of myopia. Much progress has been made in the past decade both in epidemiological studies as well as in clinical trials leading to new questions requiring more research.