INTRODUCTION:

Based on the data from American Optometric Association, (2014) people nowadays are having different kinds of vision problems viz. accommodative dysfunction, amblyopia, astigmatism, blepharitis, cataract, chalazion, color vision deficiency, computer vision syndrome, conjunctivitis, convergence insufficiency, corneal abrasion, diabetic retinopathy, dry eye, floaters and spots, glaucoma, hordeolum, hyperopia, keratitis, keratoconus, learning-related vision problems, macular degeneration, myopia, nystagmus, ocular allergies, ocular hypertension, ocular migraine, pinquecula, presbyopia, pterygium, ptosis, retinal detachment, retinitis pigmentosa, retinoblastoma, strabismus, subconjunctival hemorrhage, uveitis, etc,.

Received on 16.07.2015 Modified on 24.07.2015

Research J. Pharm. and Tech. 8(9): Sept, 2015; Page 1307-1311

DOI: 10.5958/0974-360X.2015.00236.X

Myopia (short-sightedness or near-sightedness) is often regarded as a benign disorder, because vision can be corrected with glasses, contact lenses, and refractive surgery. Nevertheless, myopia has emerged as a major public health concern for three reasons: first, in developed countries in east and Southeast Asia, such as Singapore, China, Taiwan, Hong Kong, Japan, and Korea, the prevalence of myopia has rapidly increased in the past 50–60 years [1, 2]. In urban areas in these countries, 80–90% of children completing high school are now myopic, whereas 10–20% can have high myopia [3]. These changes are not restricted to urbanised east Asia, since the prevalence of myopia is also increasing in North America[4], albeit more slowly, and probably in Europe as well. Second, the WHO recognizes that myopia, if not fully corrected (uncorrected or under-corrected refractive error) is a major cause of visual impairment [5]. Finally, people with high myopia are at a substantially increased risk of potentially blinding myopic pathologies, which are not prevented by optical correction[6].

Centuries ago, dedicated monastic scribes or cloistered seamstresses might have blamed failing eyesight on their particular type of near-focus “close work.” By the late twentieth century, such blame was expanded to include “close leisure,” such as countless hours spent study, sitting in front of the television, and most recently squinting at high-resolution monitors on everything from gaming consoles to cell phones.

Changes in the prevalence of myopia in the three major ethnic groups in Singapore and Malaysia [7].

However, despite ongoing attempts to tie these close behaviors to the onset of nearsightedness, or myopia, researchers have not come up with convincing results. On the other hand, a rapidly growing body of research on certain populations in East Asia is yielding strong evidence linking diminishing levels of exposure to outdoor light with a prevalence of myopia that is approaching epidemic proportions [8-10].

Myopia is an optical condition where distant objects are focused in front of the retina so that vision for distance is blurred, but near vision is normal. Myopia is measured by the power in diopters of the concave lens needed to focus the light onto the retina [11]. There is significant evidence that many people inherit nearsightedness, or at least the tendency to develop nearsightedness. If one or both parents are nearsighted, there is an increased chance their children will be nearsighted. Even though the tendency to develop nearsightedness may be inherited, its actual development may be affected by how a person uses his or her eyes. Individuals who spend considerable time reading, working at a computer, or doing other intense close visual work may be more likely to develop nearsightedness [12].

Genetic and environmental influences and myopia

50 years ago, myopia was believed to be genetic, with only minor environmental influences [13]. However, results from experimental studies, including in primates, support the evidence of environmental factors from human epidemiology. These studies show that changes in visual experience by fitting of diffusers or both positive and negative lenses over the eyes can generate signals that promote eye growth, leading to myopia, as well as signals that slow eye growth [14].

These models are relevant to human myopia, since children with eyelid ptosis or corneal opacities can develop myopia [15], whereas the use of negative power lenses can mimic the near work exposures that might be important in human myopia. Paradigms that slow eye growth, such as removal of the diffusers used to induce myopia or fitting of positive-powered lenses, are important because slowing eye growth would prevent the onset of myopia and slow progression. These animal models have given important insights into human myopia, which will be covered in other sections of this review.

Another important issue is that human myopia is aetiologically heterogeneous. As of Oct 4, 2011, the Online Mendelian Inheritance in Man (OMIM) database listed 261 genetic disorders in which myopia is one of the symptoms. The list includes the syndromic high myopias, in which high myopia is associated with other symptoms that define the disease, such as connective tissue disorders (e.g., Marfan and Stickler syndromes), and complete and incomplete congenital stationary night blindness. In the non-syndromic high myopias, the predominant clinical feature is high, familial, early-onset myopia, whereas myopia that appears during the middle childhood years is commonly known as school myopia.

It is now generally agreed that major genetic contributions to high myopia exist, although these might be reduced in younger cohorts given the increasing prevalence of acquired high myopia in East Asia. By contrast, it increasingly seems that school myopia is multifactorial, possibly involving a large number of genes of small effect, and major environmental factors.

i) Environmental risk factors for myopia

The importance of environmental risk factors is strongly supported by experimentation with animals and by the rapid changes in the prevalence of myopia. Associations of myopia with years of schooling and school results have been consistently reported [1].

The rise in myopia prevalence in urban East Asia might therefore be plausibly associated with the increasing intensity of education. Moreover, East Asian countries with high myopia now dominate international rankings of educational performance, according to the Organisation for Economic Co-operation and Development (OECD) Programme for International Student Assessment.

Increased accommodation due to intensive near work, such as reading and writing, could mediate the association of myopia with schooling, but epidemiological support for this idea is not strong. Although Saw and colleagues[16] showed that Singaporean children who read more than two books per week were more likely to have higher myopia than those who read less, the Sydney Myopia Study showed that near work per se was a weak factor, but that children who read continuously or at a close distance were more likely to be myopic [17], Results from the US Orinda Longitudinal Study of Myopia[18] showed weak albeit significant effects of increased hours of near work, and the authors of this study argued that the evidence did not support a significant effect of near work [19].

This evidence, combined with evidence from experiments in animals that accommodation is not important [20], led to the idea that sub-optimum accommodation during near work (accommodative lag), which leads to hyperopic defocus on the retina, might be more important. The ability of hyperopic defocus to promote eye growth in animals supports this hypothesis. Myopes are known to show greater accommodative lag than emmetropes [21] but the crucial test is whether high accommodative lag appears before or after the onset of myopia. The literature is divided on this point [22, 23], which means that, although the associations between education and myopia are strong and consistent, the biological link between schooling and myopia is not clear.

Recent epidemiological surveys have shown that increased amounts of time outdoors protect against the development of myopia, minimising the increased risk of myopia associated with near work [24] or with having myopic parents [25] The protective effect seems to be associated with total time outdoors, rather than with specific engagement in sport [24] Results from a comparative study [26] of children of Chinese ancestry from Singapore and Sydney showed that the only environmental factor that correlated with the much higher prevalence of myopia in Singapore was time spent outdoors.

Rose and colleagues [24] postulated that increased light intensity outdoors might protect from myopia because of increased release of the retinal transmitter dopamine, which is known to reduce eye growth in experimental myopia [27]. The protective effect of bright light has been replicated in animal experiments with UV-free light [28], including in primates [29], and the protective effect can be blocked by the dopamine antagonist spiperone, giving substantial support to this hypothesis [30]. A role for vitamin D has been suggested, but has not obtained significant experimental support [31] although vitamin D receptor polymorphisms have been reported to be associated with myopia [32].

ii) Genetic risk factors for myopia

One key indicator of a genetic basis is familial clustering. In the case of myopia, sibling risk ratios are generally high, and even higher for high myopia [33]. However, families share environments as well as genes, and sibling similarities in postulated myopigenic environmental factors are often higher than the sibling risk for myopia itself [34].

Heritability values for myopia in twin studies have generally been high [35]. Although apparently less ambiguous, twin heritability analysis depends on the common environment assumption that monozygotic and dizygotic twin are similarly concordant in environments [36], and is specific to a given population at a given time. The significant heritability values obtained with both approaches validate the search for genetic factors, but lower heritability values have generally been obtained in broader familial studies, and even lower values in studies of whole populations [37].

A consistent finding is that children with myopic parents have a higher prevalence of myopia [19, 38, 39] but the relative risk varies substantially, and is lower in locations in which the prevalence of myopia is high, such as in east Asia. No consistent relation with number of myopic parents exists. At this stage, the impact of parental myopia might be evidence of genetic effects. Differences in family behaviour associated with myopic parents seem less likely, but cannot be excluded at this time.

Several recent reviews [22, 40, 41] have extensively covered genetic analysis in human myopia. A list of genes reported to be associated with myopia is provided in the appendix. For the syndromic high myopias, a common feature is the participation of genes involved in scleral extracellular matrix (ECM). For the non-syndromic high myopias, a large number of chromosomal localisations have been reported (MYP1–MYP17), but few specific genes have been identified. The one exception seems to be MYP16, in which mutations in CTNND2 (cadherin-associated protein) have been identified and replicated [42]. Although many issues with replication exist, Wojciechowski has shown that many of the mutations reported form a coherent nexus of linked structural and metabolic constituents of the ECM.

Substantial progress has occurred in understanding the genetic basis of congenital stationary night blindness, in which myopia is a common feature. The OMIM database identified mutations in several genes that affect photoreceptor and ON-bipolar cell function implicated in this disease, with substantial allelic heterogeneity since 20 mutations have been identified in one of the genes [43].

Work on the genetic basis of high myopia has therefore defined two clusters of mutations—one in the outer retina affecting the function of photoreceptors and ON-bipolar cells, and one in the sclera affecting scleral ECM composition and metabolism. Of the many characterised, only a few seem to be involved in variation in more moderate levels of myopia [44-46]. These clusters do not include all the genes that have been associated with high myopia. At present, the very low number of defined and replicated genotypic contributions to variation in refractive error in the range of school myopia account for only a small proportion of the variation [47]. Thus, school myopia is faced with a mismatch between the high heritability defined in twin studies and defined associated allelic variations - a common problem in complex disease genetics now known as missing heritability [48]. Further research in this area will undoubtedly continue, but with existing knowledge, the contribution that genetic analysis can make to the prediction of susceptibility to school myopia seems to be poor. Future research is needed to identify specific modifiable lifestyle factors and genetic markers for myopia. This will enable preventive measures such as health education to be instituted.

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