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What Is The Mechanism By Which Myopia Develops?

Richard Gallagher in the Ophthalmologist newsletter:

Despite a century of interest in refractive development, the etiology of myopia is still not fully understood. Now, with the prevalence skyrocketing, the search for answers is more urgent than ever.

What is known is that myopia results when an eye is too long for its optical power or optically too powerful for its axial length. The components of the optical system, such as axial length, refracting power of the cornea, and depth of the anterior chamber, must remain in sync as the eye grows to ensure that objects are brought into sharp focus. The hypothesized mechanism by which this is brought about is called emmetropization, a term derived from the Greek emmetros, meaning “well-proportioned” or “fitting”. Identifying aspects of the visual experience that might aid, or hinder, the process of emmetropization provides clues as to why myopia develops. Several factors have been identified; the mechanism du jour is that outdoor light exposure helps maintain emmetropia. Spending too much time indoors, and not enough time outdoors promotes myopia.

There are a couple of mechanistic explanations for this indoor/outdoor light phenomenon. These explanations are not mutually exclusive. One is the huge disparity in the level of light exposure. Outside, light level readings are in the range of 50-100,000 lux; indoors, values are less than 1,000 lux, and mostly closer to 500. Increased exposure to sunlight promotes dopamine neurotransmission in the retina; in animal models, dopamine signaling is associated with an inhibition of axial elongation. Thus, a child exposed to sufficiency of outdoor light is less likely to develop myopia than if he or she spends most of the time indoors.

Another possible mechanism involves peripheral vision. An outdoor vista, such as that experienced at the ocean or in the countryside provides dioptric continuity throughout the visual field: both central and peripheral vision is clear, unblurred. This state may help maintain symmetry of the eyeball, and promote emmetropia. Indoors, dioptric stimuli vary widely across the visual field. Central vision may be focused on a television screen or words on a page, but a wide range of light sources and objects at different distances means that the peripheral retina is likely to be defocused. Studies in animal models indicate that this kind of optically-imposed defocus impacts upon central refractive development: when the periphery of the eye is defocused, refractive errors are more likely to occur. Hence, the child spending his or her time indoors is more inclined to be myopic.

Increased understanding of the factors that influence refractive parameters and how these interactions should lead to more effective treatments to slow myopia progression or to prevent its onset.

Question 3. What factors contribute to susceptibility to myopia?

Nature or nurture? There is clearly a mix of genetic and environmental components involved in the development of myopia, but the contribution of each, and the ingredients that make up that contribution, are still being teased out.

Back in 2005, a meta-analysis of some 300 papers downplayed the role of hereditary factors. It noted distinct variations in prevalence between genetically similar cohorts in different environments: for instance, the high prevalence of myopic Indians in Singapore (70 percent of 18-year-old men), while in India itself the rate was roughly 10 percent. The simplest explanation of such findings is that a massive environmental effect is swamping the genetic influence.

So, was mother right when she said, “Don’t stare at the television too long or your eyes will go square”? No. Despite the folklore of “screens damaging eyes,” which has been passed down the generations in the form of watching TV, playing video games, working with personal computers, to today’s use of smartphones, their impact appears to be minimal. What Mother failed to identify is the crystal-clear relationship between education (and socio-economic status) and myopia prevalence in children. “Education” likely means “more reading,” supporting the idea that “nearwork” is a significant risk factor in myopia. Additionally or alternatively, increased indoor activity means less outdoor activity. As noted above, a strong body of evidence links outdoor activities, such as sports (though not indoor sports) and the amount/duration of sunlight exposure, to reduced risk of myopia in children. Thus, for “environmental factors,” read “lifestyle”; an important distinction when comparing myopia incidence on a global scale.

Environmental factors alone cannot, however, explain why so many individuals within a single family present with myopia; there must be a substantial role for genes. Altogether, an extraordinary 68 genes across all chromosomes have been associated with refractive error, including 20-some recent additions from the international Consortium for Refraction and Myopia (CREAM) and the company 23andMe, who corroborated each other’s findings.

Interestingly, no significant genetic differences between Europeans and Asians were discovered. The bad news is that many of the genes have very slight (though additive) effects, ruling out a simple solution. The rather better news is that they can be mapped onto functional pathways, giving pointers on how to improve our basic understanding and, by extension, our ability to treat this perplexing condition. The pathways include neurotransmission, vitamin A (retinol) metabolism, eye development and remodeling of the extracellular matrix.

Rapid progress is being made on the environmental component too. Randomized clinical trials are underway to more precisely pin down the impact of sunlight, bright light, and/or outdoor exposure; some of these studies use wearable light sensors in place of questionnaires to capture data more rigorously.

The ultimate goal will be to integrate the two streams of information, pinpointing unfavorable combinations of genetic predisposition and environmental factors that are particularly risky for the development of myopia. At that point, improved therapeutic options may come into focus.

Commented by our GURU Neuro-Developmental F.C.O.V.D Dave cook: I liked the mention of variation between central and peripheral vision. When you look at a handheld book Smartphone, your central focus is at the distance of the page or screen, your peripheral vision is completely out of focus. The flat world of the computer screen, TV, and Books all mismatch central and peripheral focus with our eyes relatively unmoving for prolonged periods of time.

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