Young children exhibit the highest rate of myopia progression (Mäntyjärvi, 1986) (Figure 8), which normally stabilizes around 16 years of age (Tan et al., 2000). Thus, the ammount of adult myopia is dependent on the age of onset of myopia (greater duration to progress) and the faster progression when younger. Myopia advances at a rate of -0.50DS per year in progressing Caucasian children (Gwiazda et al., 2003; Tan et al, 2000), -0.60DS per year in children from Hong Kong (Fan et al., 2004) and -0.80DS per year in Asian children (Donovan et al., 2012).
Figure 8. Rate of myopic progression in dioptres per year in Finnish 8 and 13 year old (Data from Mäntyjärvi, 1986).
2.1 Genetic risk factors for myopia
A substantial proportion of myopia is inherited (Young et al., 2007). Myopia progression from childhood is a combination of genetic influences, including parental myopia, combined with environmental influences.
Studies comparing monozygotic twins to dizygotic twins show a 84-86% similarity in refraction as well as concordance in refractive components (axial length, corneal curvature, lens power). The remaining 14-16% is due to environmental influences, such as the amount of near work (Hammond et al., 2001). Twin studies use a technique that is based on the comparison of the covariances (or correlations) in monozygotic and dizygotic twin pairs, allowing separation of the observed phenotype variance into additive or dominant genetic components and common or unique environmental components. The concordance of myopia in twins is more likely in genetically identical twins than non-identical twins (Sorsby, 1962). A large cohort study of white twins also reported evidence for a genetic component in adult-onset myopia (Dirani et al., 2008).
Parental myopia (Table 1) is one of the most important influences on the onset of myopia with only 6.3% of children having myopia if neither parent are myopic. This increases to 18.2% if one parent has myopia and to 32.9% if both have (Mutti et al., 2002)
Number of parents with myopia % of children myopic at age 6.7 years % of children myopic at age 12.7 years
0 0.8 7.6
1 2.5 14.8
2 4.2 43.6
Table 1. The prevalence of myopia in children aged 6.7 and 12.7 years with either 0, 1, or 2 myopic parents (Rose et al., 2008)
Axial length is thought to be the greatest determinant of refractive error. Its heritability ranges from 40 to 94% (Hammond et al., 2001; Lyhne et al., 2001; Teikan et al., 1989; Biino et al., 2005) and in a recent whole genome twin study in Australia was 81% (Zhu et al., 2008). Loci on chromosomes 5q (q stands for the long arm of a chromosome), 6, 10 and 11 are implicated in ocular axial length (Zhu et al., 2008).
No specific genes have been identified for juvenile onset myopia. However, there is significant linkage near the PAX6 gene of chromosome 11 and as this is an important gene in eye growth it is suggestive of PAX6 involvement in myopia (Hammond et al., 2004). Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 (q as described above) in Caucasian populations. The mutations reported in myopia are linked to the scleral extracellular matrix (ECM) and linked to structural and metabolic constituents of the sclera (Wojciechowski, 2011). The list of hypothesized candidate genes for myopia is based on our understanding of the pathophysiology of syndromic myopia and it is unclear how ethnic populations will differ (Hornbeak et al., 2009).
The fact that myopia is on the increase suggests that there may be environmental influences driving myopia progression as well as genetic ones (Rose et al., 2002). In a study of Inuit people in the 1960’s on the northern tip of Alaska the prevalence of myopia increased from practically zero in the grandparents (aged over 40) but more than half of the children and grandchildren were myopic. The variable between the three generations was a changing lifestyle in the form of compulsory education. Genetic change would be too slow to cause such a difference between generations (Young, 1969).
2.2 Environmental risk factors for myopia
Twin and epidemiological studies demonstrate the most compelling evidence for an environmental component to the development of myopia (Wong et al., 2000; Hammond et al., 2001). Environmental influences include an increase in the amount of near work due to education, and decreased time spent outside and lower light levels (Chapter 3).
2.2.1 The effect of intensive near work on the development of myopia
Intensive near work has been linked to myopia. Children are spending an ever-increasing amount of time reading, studying and using computers and smartphones. This is especially so in East Asia where children spend most time studying due to high pressure and value put on educational performance. The average 15 year old in Shanghai now spends 14 hours per week on homework, compared with 5 hours in the United Kingdom and 6 hours in the United States of America (Salinas 2014).
Academic achievement and myopia have been linked (Sperduto et al., 1983; Rosenfield and Gilmartin, 1990). Only 18.9% of emmetropes who begin manual labour are likely to become myopic, compared with students doing much more near work 48.8% of whom are likely to become myopic (Hepson et al., 2001). 81.3% of Jewish boys attending an Orthodox school in Israel, where there is much more intensive near work (studying religious texts), are myopic compared to only 27.4% in students in other Israeli secular schools (Zylbermann et al., 1993) (Figure 9). A higher rate of myopia is present in children in academically selective schools in Singapore (Quek et al., 2004). Myopia is more prevalent in both children (Saw et al., 2007) and adults who have completed longer years of education and achieved higher qualifications (Au Eong et al., 1993). Intensive near work also has an effect on emmetropic adults as 39% of clinical microbiologists become myopic (perhaps due to proximal accommodation) and stable myopes also progress (McBrien et al., 1997). Myopia is rare amongst certain occupational groups such as fisherman and farmers who spend an increased amount of time in the great outdoors with their work and a reduced time reading (Tscherning, 1883). Figure 9. A frequency ditribution of refractive error for 4 different Isralis student populations (Zylbermann et al., 1993).
Accurate accommodation is critical for inhibiting myopia progression by reducing defocus and so axial elongation. Children engaging in near work with an accommodation insufficiency resulting in retinal defocus are more likely to become myopic (Gwiazda et al., 1993). Hyperopic blur due to a lag of accommodation, similar to the emmetropisation process, results in axial elongation (Figure 10) because the image is formed behind the retina and so axial length increases to grow towards the clear image.
Figure 10. Diagram to illustrate hyperopic blur and axial elongation (from www.divaportal.org/smash/get/diva2:349998/FULLTEXT01.pdf).
Animal studies demonstrate that increased retinal defocus is a factor in myopia pathogenesis (Norton, 1999; Wildsoet, 1997). Monkeys exhibit axial growth when negative lenses (causing hyperopic defocus) are inserted in front of the eye, which stops when the lens is removed. Conversely, hyperopic monkeys who had a positive lens inducing myopic blur had little axial growth but when the lens was removed the eye began the emmetropisation process and began to grow (Hung et al., 1995).
2.2.2 The effect of peripheral defocus on the development of myopia.
Clear vision at the fovea has long been considered the key factor in the emmetropisation process. However, recent studies suggest it is in fact the peripheral retina that plays the strongest role in regulating eye growth. In infant monkeys, photocoagulation of the fovea had little effect on the emmetropization process, suggesting that foveal input is not necessary (Smith et al., 2005). In monkeys in whom a hemisphere of blur was induced via a negative lens in front of the eye, caused hyperopic blur which resulted in half of the eye elongating (Smith et al., 2009). The half of the eye with no lens did not grow. If plus or minus lenses are placed in front of the eye, different levels of chemical mediators (dopamine) are released into the retina, affecting eye growth (Wallman et al., 2004).
In humans, emmetropic or hyperopic pilots who later progressed into myopia had hyperopic peripheral refractions and those who remained hyperopic or emmetropic had relatively myopic peripheral refractions (Hoogerheide et al., 1971). Thus, peripheral defocus might be responsible for myopia progression (Wallman et al., 2004; Collins, 1995; Charmann, 2005, 2005, 2010; Seidmann, 2002).
With modern lens designs the central fovea is in focus, but the peripheral retina has hyperopic defocus (Line et al., 2010), which could be inducing peripheral axis elongation and increased myopia. This hyperopic peripheral blur is significantly higher in moderate myopia compared to low myopia.
Clearly the effect of light is an environmental risk factor involved in myopia progression and this will be discussed in the following chapter, chapter 3 (Appendix 1 shows the methodology from which the papers were researche on this subject).