McBrien, Neville A.; Morgan, Ian G.; Mutti, Donald O.
Each International Myopia Conference tends to have a hot topic. The 12th International Myopia Conference, held recently at Palm Cove in Far North Queensland, Australia was no exception, with the recent evidence that children who spend more time outdoors are less likely to become myopic as one of the most significant findings reported.
Longitudinal data from the Orinda Longitudinal Study of Myopia have shown that children with the risk factor for myopia of myopic parents, are at only slightly greater risk than children without myopic parents if they spend sufficient time outside. Data from the Sydney Myopia Study data, while cross-sectional in nature, suggest that greater time spent outside can also over-ride the greater risk associated with near work and schooling. These two studies were carried out on populations of school-children who are largely of European origin. The Singapore SCORM Study presented data on this effect in children of Chinese, Malay and Indian origin—suggesting that the effect is likely to be seen in children from all ethnic groups. The agreement between these studies is unusual in the area of the etiology of myopia, which is generally renowned for its controversies, rather than for consensus.
The mechanisms underlying this effect are as yet unclear—but could involve lesser accommodative demands in outdoor environments (despite the considerable evidence that accommodation is not important), pupil constriction in the brighter light typical of outdoor environments resulting in greater depth of focus, or a direct effect of light exposure, perhaps mediated by release of a retinal transmitter such as dopamine, which is known to inhibit eye growth in certain circumstances.
Some important parameters for the effect have already been defined from the human epidemiology. Firstly, protection does not seem to result from a “substitution” effect, in which children replace time spent on reading and writing and other forms of near work with outdoor activities. Secondly, the critical factor seems to be total time outdoors (in daylight hours), rather than sport or physical activity, since indoor sporting activities are not protective, while both active and more passive activities outdoors are. The studies are in rough agreement on the protective exposures—around 2 to 3 hours a day outside of school hours seems to be sufficient to markedly lower the risk of myopia.
Other work presented at the conference dealt with new developments in two symposia that discussed the balance between overall hyperopic (growth-promoting) and myopic (growth-inhibiting) defocus in different natural environments, and the balance between central and peripheral hyperopic and myopic defocus, respectively, and how they might lead to interventions or treatment modalities for myopia.
These two ideas ultimately spring from studies on animal models, which have shown that imposed hyperopic defocus promotes eye growth, while imposed myopic defocus inhibits eye growth. These phenomena appear to have human analogues in the clearance of neonatal hyperopia by accelerated eye growth, and the apparent clearance of the much rarer neonatal myopia. But these processes in humans occur predominantly in the first or second year of life, and later refractive development may predominantly involve other processes, such as reductions in lens power.
It is clear that the interactions between the two forms of defocus are highly non-linear, with small amounts of myopic defocus able to block the effects of much more prolonged hyperopic defocus in a range of ingenious experimental paradigms which involve either sequential or parallel presentation. Wallman has stressed the need to understand how this might work in natural situations.
From a practical perspective, there has been considerable interest in the balance between peripheral and central defocus. Prolate eyes will tend to have peripheral hyperopic defocus when the image is focused at the fovea, which could promote eye growth, whereas oblate eyes will tend to have peripheral myopic defocus, which could inhibit eye growth. This has led to the suggestion that premyopic eyes will tend to be prolate, but most of the recent evidence suggests that premyopic eyes are in fact oblate in shape. Certainly, eyes become relatively more prolate as they become myopic, but that appears to be a consequence, rather than a cause, of the development of myopia.
Nevertheless, animal studies, have shown that peripheral defocus is able to influence the rate of axial eye growth. Even if this is not important for the development of myopia, it is still possible that imposition of peripheral myopic defocus, while leaving central vision corrected, may be able to prevent myopic progression, and even prevent the development of incident myopia. Several groups worldwide, from Hong Kong and Australia to Russia and the United States, are working in this area; reports from these interventions are in prospect in the next few years.
Studies presented on the role of ocular aberrations at the conference increasingly indicate that they do not play any particular role in the etiology of myopia. In fact, they are more likely a consequence to the development of myopia.
Finally, for some on-going controversy, the conference had the perennial issue of nature vs. nurture. Genetic studies are continuing to define localizations of mutations which contribute to early onset high myopias, but as yet there are no well characterized genes identified. Replication of these studies is an important task for the future. So far, these identified mutations does not seem to contribute to ordinary myopia, and the results of a major genetic study on the Singapore cohort, which will no doubt be available for the next meeting, are awaited with interest.
The pathways involved in eye growth control in avian animal models have been characterized to some extent, but at this stage it is not clear that these pathways can be transferred to eye growth control in mammals, let alone humans. Certainly, there is little alignment between what is currently known from animal models, and what has emerged from genetic studies on humans. Experimental models are now available in mice and guinea pigs, and results on these species, which are closer in molecular terms to humans, will hopefully be a high-light of the next conference.
At the same time, it is clear that there are substantial environmental impacts on the development of myopia and that the identification of time outdoors as a protective factor adds considerably to the possible mechanisms that might be involved. Thus, there may even be some form of agreement emerging in this controversial area, based on acceptance of the idea that a high heritability in twin studies, which is uncontested, does not mean tight genetic determination in any way, leaving considerable scope for environmental effects, as well as gene-environment interactions.
The next International Myopia Conference will be held in Tubingen in Germany in 2010. Hopefully, some of the issues discussed at the 12th International Myopia Conference in Australia will have come to fruition, and delivered effective and safe preventive interventions to control incident and progressing myopia, supplementing the use of atropine eye-drops, which despite its problems with side-effects, remains the only consistently effective treatment for myopia in humans.
Neville A. McBrien
Ian G. Morgan
Donald O. Mutti