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Emmetropisation
In early childhood refractive error is widely distributed with the mean refraction being around +3.00D (Figure 1). Emmetropisation is the process of eye development that involves an active matching of the axial length of the eye to the optical power of the cornea and lens. Normally, eye development proceeds from neonatal hypermetropia towards emmetropia, rapidly within the first year12 and then more slowly for the next five to six years. Emmetropisation is visually driven and can be disrupted by environmental factors. Compensatory growth patterns (reduced eye growth with the introduction of positive spectacle lenses and increased eye growth with negative spectacle lenses) have been demonstrated in animals.13
Nature versus nurture
After many years of research there is still no consensus of opinion about whether myopia is caused by genetics, environmental factors, or a combination of the two.15,16,17
Genetics
In a study on monozygotic and dizygotic twins it was suggested that over 80 per cent of the variation in refractive error could be explained by genetic factors.18 A significant link has been found between higher levels of myopia (greater than -6D) and genes present at various loci,19,20 although studies investigating whether some of the same genes are responsible for both high and low myopia have indicated that this is not the case.21 The PAX6 set of genes, which play an important role in various aspects of ocular development, are linked with low myopia.22,23 Several studies have shown that parental myopia is one of the significant risk factors for myopia development.24,25 In particular, the odds of becoming myopic are about six times greater in children with two myopic parents than in children with only one or no myopic parents.22 In the past few weeks a large multi-centre study has identified the first myopia susceptibility gene called RASGRF1.26 The research identified several variations around the RASGRF1 gene, which is associated with eye growth, and seems to be strongly associated with myopia, either preventing it or protecting against it. This study is a major breakthrough and may eventually lead to the development of treatments to prevent or stop myopia progressing.
However, genetics alone cannot explain the sudden increase in myopia prevalence. Evidence of environmental influence comes from a rapid increase in prevalence in certain populations27,28 or in certain population sub-groups.29,30
Environment and near work
The concept that environmental factors, in particular near work, might cause myopia dates back many years.31,32 More recently clinical studies on children have shown an association between myopia and higher levels of nearwork.33,34,15,35 Although near work seems to have an important role to play, the exact mechanism by which near work relates to myopia has remained elusive. Several potential mechanisms have been suggested for myopia development with abnormal accommodative function being a popular hypothesis.
Lag of accommodation
Gwiazda et al36 were the first to suggest that an increased lag of accommodation found in myopes (resulting in hypermetropic retinal defocus) may stimulate axial elongation and therefore myopia progression. This finding of myopes exhibiting an increased lag of accommodation when compared to non-myopes has been replicated in many studies,37,38 although it has been suggested that the increased accommodative lag may be a consequence rather than a cause of myopia.39 Multifocal spectacle lenses have been evaluated as a treatment attempting to arrest myopia development in multiple clinical trials40,41,42,43,44,45 with the rationale being to decrease accommodative lag during near work and thereby reduce hypermetropic retinal blur. The various clinical trials were of limited success with treatment effects being greatest in participants with a high lag of accommodation and near esophoria.46
Dynamic accommodation
Reduced accommodative facility or dynamics of accommodation have been shown to be associated with myopia47,48,49 and myopia progression.50,38 An increased accommodative variability in myopes50,51 that results in retinal defocus during near work could be integrated over time, resulting in axial elongation and hence myopia.52
Sensitivity to blur
This increased variability in accommodation may be related to the low sensitivity to blur exhibited by myopes.53,54,55,56 The reduced sensitivity to blur is associated with a reduced effect of defocusing lenses on visual performance.57 Unlike emmetropes, myopes have significantly different sensitivities to positive and negative lens-induced defocus.58,59 Moreover, myopes are also found to adapt to blur when left uncorrected.60 However, another study by Schmid61 failed to find any significant difference in the blur detection abilities of myopic and non-myopic children, although myopic children showed greater individual variation. Myopes have also been shown to demonstrate significant improvements in blur sensitivity after relatively short periods of blur adaptation.62
Near-work-induced transient myopia
Near-work-induced transient myopia (NITM) refers to a small, transient, near shift in the far point of the eye after a period of sustained near work. The exact mechanism that causes NITM has still to be resolved although biomechanical hysteresis of the crystalline lens, a neuromuscular effect that prevents complete relaxation of the ciliary muscle following near work, and sympathetic inhibitory dysfunction have all been suggested.
In the normal population, the mean magnitude of NITM is typically small (approximately 0.3D) and remains within the depth of focus of the eye, thus producing no perception of blur. Myopes exhibit both larger and longer NITM when compared to emmetropes.63,64 Moreover, this NITM has been shown to be additive selectively in myopes.65 Historically, early onset myopes have been thought to be primarily influenced by genetic factors whereas late onset myopes are susceptible to environmental factors. Interestingly, NITM appears to represent a more global myopic tendency.65 There are several different ways that NITM may cause myopia progression including (a) NITM can affect the steady-state accuracy of accommodation and increase retinal defocus and (b) the incremental retinal defocus theory66 suggests that repeated cycles of incompletely decayed NITM may by myogenic.
Monochromatic aberrations
It has been suggested that optical aberrations may be a cause of some of the accommodative anomalies discussed above.58,59 While some have found myopes to have elevated higher-order aberrations when compared to emmetropes,67,68 others have found no correlation between refractive error group and spherical aberration69 or between refractive error magnitude and total root mean square higher-order error or spherical aberrations.70 Several studies have examined the changes in both spherical aberration and other higher-order aberrations with accommodation with somewhat equivocal results. He et al71 found that ocular aberrations decreased with accommodation in emmetropes, but in myopes aberrations increased or did not change. This suggests that, at near, myopes will have greater amounts of higher-order aberrations than emmetropes. However, Hazel et al72 found that emmetropes and myopes both demonstrated an increase in negative spherical aberration with accommodation. Higher-order optical aberrations may affect the accommodative response by causing a degradation of the retinal image (which extends the depth of field of the eye), by altering the sensitivity to negative defocus73 or by assisting in the detection in the direction of defocus.74
Peripheral refraction
In a study of groups of existing adult ametropes, Millodot75 showed that, at least for field angles up to about 30 degrees, both oblique astigmatic image surfaces in hyperopic eyes along the horizontal meridian tended to show relative peripheral myopia with respect to the axial refraction, whereas in myopic eyes there was relative hypermetropia: in emmetropes the two astigmatic image surfaces tended to lie on opposite sides of the retina (Figure 2). Similar results have been obtained by several subsequent studies.76,77,78 Some of these studies also show differences between the patterns of refraction in different meridians. In addition, Tabernero and Schaeffel79 found that conventional spectacle lenses used to correct myopia induce significant relative hypermetropia in the periphery. Only Calver et al80 found no strong differences between refractive groups. This study used custom-made trial lenses to correct myopia. Recently, a study on over 2,000 eight- to nine-year-old children found little evidence of an influence of peripheral refraction on myopia progression except in a subgroup of children of Asian ethnicity.81 Moreover, Sankaridurg et al82 conducted a clinical trial where participants wore spectacles designed to reduce peripheral hypermetropic retinal defocus. They found that altering field curvature to minimise peripheral hypermetropia made no significant difference to refractive development except in a small subgroup of participants.
The observed differences in peripheral refraction of existing ametropes might either be predictive of future refractive change,83 or they might simply be properties of eyes whose refractive error is already fully developed. Mutti et al,84 in a longitudinal study of almost 1,000 children aged between six and 14 years, found that children who became myopic had more hypermetropic relative peripheral refractive errors than did emmetropes from two years before onset through five years after onset of myopia. The third article in this series will look at evidence for peripheral correction as a means to reducing myopic progression.
Outdoor activity
Recent work has suggested that time spent outdoors has an impact on myopia development and progression.85,86,87 These studies show that children who spent more time in outdoor activities were less likely to develop myopia. This reduction in the chance of becoming myopic with increased outdoor activity occurred even when other risk factors such as quantity of near work, parents with myopia and ethnicity had been accounted for. However, this effect has not been replicated in pre-school children. Low et al88 show that a family history of myopia was the strongest factor associated with myopia in pre-school children, with neither near work nor outdoor activity playing a significant role. The authors suggest that genetic factors may therefore play a more substantial role in the development of early onset myopia than quantity of near work or outdoor activities. ?
? Part 2 will discuss the prevalence of myopia and its impact both medically and sociologically. The final part will consider correction and treatment including details of the latest dual focus treatment lenses.
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? Dr Peter Allen is a principal lecturer and director of clinics at Anglia Ruskin University while Dr Hema Radhakrishnan is a lecturer based at Manchester University