Myopia affects approximately 70 million Americans.1 It is associated with potentially sight-threatening side effects, and it costs the United States up to $4.6 billion every year.2-4
Finding a treatment that slows the progression of myopia or even prevents its onset will have a dramatic affect on individual patients lives and society in general. While researchers have compiled considerable information about myopia over the past several years, controversy regarding its primary cause still exists.
We can broadly categorize potential causes of myopia and myopia progression into two theories: genetic or environmental. Through animal and human trials, researchers have gathered evidence for and against each theory. So far, however, no single study has proven either theory correct. Most likely, no study will provide definitive evidence that one theory alone can fully explain how people become myopic.
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A young, myopic patient participates in a myopia control clinical trial. |
Genetics vs. Environment
Evidence of a genetic etiology includes the high heritability (approximately 0.90) of myopia.5-7 Monozygotic twins also have higher heritability than dizygotic twins, and the refractive error of twins is highly correlated.5-10
Furthermore, research has shown that emmetropic children who have two myopic parents have longer eyes than emmetropic children who have one myopic parent and that children who have one myopic parent have longer eyes than children who have no myopic parents.11 Researchers have also found that parental history of myopia at school entry has excellent sensitivity (0.90) for predicting the future onset of myopia and is associated with higher rates of myopia progression in children.12,13
These findings all indicate a strong propensity for myopia to be passed from one generation to the next. However, no single gene has been mapped for high myopia or moderate myopia.14-20 Perhaps, this is because multiple gene loci are involved in myopia development and progression.
Some of these factors suggest that the tendency for myopia is passed from generation to generation. However, it is difficult to separate the effects of genes from similar environments because siblings are typically raised in similar environments in which similar factors, such as near visual activities, may affect myopia progression.
Evidence for an environmental cause of myopia includes the possibility of an epidemic of myopia in specific populations.21-23 Francis Young, Ph.D., was among the first to report this phenomenon.24 He and his colleagues reported a refractive error correlation equivalent to zero between parents and children in an Eskimo population, while siblings had a refractive error correlation of approximately 0.5.23 The Eskimo parents and grandparents had nearly no myopia, yet approximately three out of five children were nearsighted.
The authors concluded that this was due to the recent onset of formalized education, which engaged children in more reading and led to the development of myopia. This sudden increase in the prevalence of myopia in Eskimos and similar trends in Asia are difficult to explain by genetics alone because it has been reported to occur within one or two generations.25-28
Confounding Factors
It is unclear whether there truly is an epidemic of myopia or whether confounding factors suggest a sudden rise in the prevalence of myopia. For example, changes in the ethnic profile of a particular area may explain changes in the prevalence of myopia. One study found that the prevalence of myopia in a northern California community doubled over 30 yearsa finding that researchers attribute to an influx of Asian-American children in the area.29
Similarly, changes in the age distribution of a particular area could explain a sudden increase in the prevalence of myopia. Cross-sectional studies show that the prevalence of myopia is approximately two times greater for people in their 40s than people in their 70s.30, 31 If a community was suddenly infused with a younger population, it may appear that the mean refractive error of the community could change dramatically. In reality, though, the younger age distribution of the population could explain the apparent shift in myopia prevalence. A difference in age could explain the difference in the prevalence of myopia between generations of Eskimos in Dr. Youngs cross-sectional study.23
The possibility of an epidemic of myopia is stirring. Even so, we must not draw unwarranted conclusions without more rigorous examinations of potential causes of sudden reported increases in the prevalence of myopia.
Current Therapies
Many current therapies are geared toward alleviating potential environmental effects on myopia progression. One current theory is that accommodative lag experienced by young children leads to myopic eye growth due to light focusing posteriorly on the retina. Indeed, several animal studies show that hyperopic blur detected within the eye results in faster axial elongation and myopic development.32-34
Controversy exists regarding the onset of accommodative error in young, incipient myopes. Jane Gwiazda, Ph.D., and colleagues found that increased accommodative lag occurs prior to the onset of myopia, while Donald Mutti, O.D., and colleagues contend that increased accommodative lag occurs before myopia onset.35,36 If the latter is true, then accommodative lag does not explain the onset of myopia but is a result of myopia onset.
Bifocal spectacles. These decrease the accommodative demand for young children and, as a result, the accommodative error they experience. However, three recently completed randomized clinical trials show little to no treatment effect by bifocal spectacle lenses, indicating that accommodative lag plays a minor, if any, role in increased myopic progression in children.37-39 (See Annual Myopia Progression Rates During Recently Completed Bifocal Myopia Control Clinical Trials, above.)
An auxiliary study is examining the potential treatment effect of bifocal spectacles for a subset of children who have low myopia, high accommodative lag and nearpoint esophoria.40 Results from this study will help elucidate the role of accommodative error in myopia development.
Undercorrection of myopia is similar to wearing a bifocal and should lead to decreased accommodative effort and improved near vision. This would result in decreased myopia progression. However, a randomized trial found that undercorrection of myopia actually increased the progression.41 Treatment of accommodative error, the most commonly hypothesized environmental cause of myopia development, has not yet proven to be fruitful, but other environmental theories have been proposed.
In other studies, researchers evaluated specific receptors in the retina for myopia control using pirenzepinea selective muscarinic antagonist reported to minimally affect accommodation. They found that pirenzepine reduced axial eye growth in lens-induced refractive errors of animals.55-57 Randomized clinical trials in humans have proven that application of the ophthalmic gel slows the progression of myopia in children.58,59 In both studies, myopia progression was reduced to nearly half that of the control subjects after one year. About one in 10 subjects withdrew from the study due to side effects of the drug. Still, all subjects fully recovered from any ill effects they exhibited. The FDA has not approved this treatment, so it is not available in the United States.
Elevated intraocular pressure is another factor that researchers have investigated as a possible contributor to myopia. One hypothesis: Higher IOP, perhaps in combination with a weaker scleral shell, leads to increased globe expansion and greater axial elongation.60-62 A study of chicks showed that timolol maleate lowers IOP but does not slow the growth of the eyes. One study in humans showed that IOP-lowering agents are unsuccessful at slowing the progression of nearsightedness in children.63
Animal models of blur-driven myopia development have shown that brief periods of unrestricted vision can greatly decrease or eliminate myopic eye growth.64,65 This finding indicates that a blur-driven cause of myopia development must be relatively constant and would argue against accommodative error as a cause for myopia development. Higher-order aberrations lead to sustained minute levels of blur on the retina and are currently being examined as a potential initiator for myopia development.66,67
An animal model of myopia indicates that the midperipheral portion of the retina may play a stronger role in eye growth regulation than the central retina, so patients may experience clear vision while benefiting from slowed eye growth as images focus in front of the peripheral retina.70 Determining potential causes of myopia, such as higher order aberrations leading to myopic eye growth (discussed previously), may lead to future treatments for myopia progression.
Neither genetic nor environmental factors alone explain the onset or progression of myopia. However, environmental and genetic causes may play integrated roles in the development of myopia.
For example, a subset of children may carry specific genes that make them susceptible to the effects of accommodative error. These children will become myopic if they exhibit an accommodative lag to near stimuli, while children who are not genetically susceptible will remain emmetropic, even when they exhibit a large accommodative lag while reading. To determine whether this may be true, scientists have searched for a gene-environment interaction, but no such interaction has been reported to date.
Although two distinct camps exist regarding the cause of myopia development and progression, it is likely that a combination of the two general causes will partially explain how people become nearsighted.
Dr. Walline is an Assistant Professor at the Ohio State University (OSU) College of Optometry. He served as chairman of the Contact Lens and Myopia Progression (CLAMP) Studya randomized clinical trial to examine the effects of gas permeable contact lens wear on myopia progression in children. He currently is the principal investigator of the Adolescent and Child Health Initiative to Encourage Vision Empowerment (ACHIEVE) Studya randomized clinical trial to investigate the effects of contact lens wear on nearsighted childrens self-perception, and is conducting the Corneal Reshaping and Yearly Observation of Nearsightedness (CRAYON) Study to examine the effects of corneal reshaping contact lenses on myopia progression in children.
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