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    Time outdoors and myopia: a case for vitamin D?

    One of the most common stereotypes about the young myope is that he or she is a reader. The Internet age may modify our picture somewhat, but parents and optometrists probably still imagine the young myope reading under the covers at night, although now with a tablet or smartphone instead of a book. But, is reading the problem? Can children read themselves into becoming myopic or needing a stronger prescription? Research funded by the National Eye Institute and conducted over the past 23 years suggests that the answer is no. Avoiding reading or the computer or other near work is not the way to maintain emmetropia or to slow progression.

    The Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) study, conducted by optometrists at 4 sites across the U.S. followed nearly 5,000 children over time to determine what factors were different between those who became myopic and those who remained emmetropic. Study investigators recently reported that myopic children do in fact fit the stereotype and engage in more near work than emmetropic children.The surprising finding was that near work did not cause the myopia. Children who became myopic did no more near work before the onset of myopia than children who remained emmetropic.Once myopic, children’s near work also had no effect on their rate of progression.3

    Nature/nurture?

    If excessive near work does not cause myopia, is it all genetic? Is there any environmental influence on refractive error? CLEERE has shown that time outdoors, not near work, is the behavioral factor that affects the probability that an emmetropic child will develop myopia.

     

     

    Figure 1. Ocular growth might be restricted equatorially if a thick ciliary muscle restricts expansion. The eye would become longer and more myopic. A more normal ciliary muscle might allow for uniform expansion and a shorter, non-myopic axial length. (Photo provided by Donald O. Mutti, OD, PhD.)

     

    More time outdoors lowers the probability of onset, and potentially by a large amount. Emmetropic children with two myopic parents (the largest genetic risk) who spent the lowest amount of time outside (5 hours or less per week) had about a 60% chance of becoming myopic. However, for emmetropic children with two myopic parents who spent 14 hours per week or more outside, the probability of becoming myopic was reduced to 20%. Children with one or even no myopic parents also benefitted from more time outdoors.2

    The great indoors

    One might wonder whether more time outdoors is just less time reading, but this tradeoff behavior does not seem to be happening. The effect of time outdoors is independent of near work with no evidence of a negative correlation between them.Oddly, the evidence from CLEERE also shows that more time outdoors does not affect the rate of progression of myopia.The benefit seems to occur only in emmetropic children, suggesting mechanisms that lead to myopia onset may be different than those related to progression of myopia.

    The next wave of research seeks to understand the mechanism by which time outdoors lowers the chances of becoming myopic. Some have suggested that increased physical activity while outside may be important, but careful measurement of activity levels by survey or by objective sensors in studies from Australia, Singapore, and England do not offer strong support for this idea.4-6 

    Seeing the light

    A more widely accepted hypothesis is that the brighter light outdoors stimulates release of dopamine from the retina that inhibits the growth of the eye.However, not all myopia in animal experiments is inhibited by light. Myopia from form deprivation, when the eye is deprived of high-contrast vision, seems the most sensitive to the effects of light.7,8 Myopia induced by lenses, where the eye grows longer to compensate for hyperopic defocus imposed by minus lenses, is not inhibited by light in recent studies on research monkeys.This difference is important because lens-induced myopia is far more relevant to human myopia than form deprivation. The other problem is that bright light should have a general inhibitory effect on eye growth, should inhibit ocular elongation both before and after myopia onset, but that does not seem to happen. As mentioned earlier, time outdoors lowers the risk of onset, but does not seem to affect myopia progression.3

     

    The vitamin D factor

    Another effect of spending more time outdoors is greater cutaneous production of vitamin D from exposure to ultraviolet (UV) light. Myopes spend less time outdoors, but even adjusted for this factor, they had 20% lower levels of vitamin D in their blood than non-myopes according to a recent report.10 CLEERE examined genetic variations within the vitamin D receptor gene (VDR) and the group-specific component (Gc, vitamin D-binding protein) gene, finding 4 significant variations in Caucasians related to myopia less severe than −4.00 D.11 These variants explained 12-18% of the total variation in the sample, a very high percentage compared to the 2.9-3.4% of the variance explained by the many polymorphisms related to myopia identified in recent genome-wide association studies.12,13

    How might vitamin D help prevent the onset of myopia? Results from CLEERE show that emmetropic axial elongation is nicely matched by compensatory decreases in crystalline lens power and thickness. The crystalline lens thins, flattens, and loses power to maintain emmetropia, probably through a process of simple mechanical stretch provided by the connection between the growing eye, ciliary muscle, zonules, and lens. The onset of myopia is characterized by the sudden cessation of this stretch.14 The growth of the eye essentially becomes disconnected from changes in the crystalline lens. When that connection is broken, all axial elongation translates into negative diopters of myopia (Figure 1). We hypothesize that this disconnect occurs because of changes in the ciliary muscle. When stretched, smooth muscles in other parts of the body, such as blood vessels or the bladder, tends to hypertrophy, resulting in altered structural properties.15,16 A thick ciliary muscle might act like a restraining O-ring, preventing a growing eye from stretching the crystalline lens.

    If hypertrophy of the ciliary muscle plays a role in the onset of myopia—a large “if” at this stage—vitamin D might help. Vitamin D improves bladder function during obstructive disease in both rats and humans where muscle wall stretch produces hypertrophy and impaired contraction.17,18 Increased vitamin D levels might have a similar beneficial effect on ocular ciliary muscle. A more pliant ciliary ring might preserve the stretch on the crystalline lens during growth and may prevent or delay the onset of myopia. Vitamin D would not affect the growth of the eye directly, perhaps explaining why more time outdoors does not affect the rate of progression once myopia has occurred.

    Discovering that spending more time outdoors reduces the risk of the onset of myopia represents a major advance in our understanding of refractive error. But, we need to figure out what’s so good about more time outdoors—exercise, brighter light, vitamin D synthesis, or some combination. Being outside is a common behavior that can be influenced to have a beneficial effect, not only on the eye, but also on risk factors for other diseases in children, such as obesity and diabetes. Caution should be used before making any sweeping recommendation about children spending more time outdoors. UV light outdoors has known, harmful effects on the skin and the eye. More light or more dietary vitamin D?

    Once we find the answer, children might be able to come out from under the covers and use their tablets or smartphones without parents telling them to stop ruining their eyes.ODT

     

    References

    1. Jones-Jordan LA, Mitchell GL, Cotter SA, Kleinstein RN, Manny RE, Mutti DO, et al. Visual Activity before and after the onset of juvenile myopia. Invest Ophthalmol Vis Sci 2011;52:1841-1850.

    2. Jones LA, Sinnott LT, Mutti DO, Mitchell GL, Moeschberger ML, Zadnik K. Parental history of myopia, sports and outdoor activities, and future myopia. Invest Ophthalmol Vis Sci 2007;48:3524-3532.

    3. Jones-Jordan LA, Sinnott LT, Cotter SA, Kleinstein RN, Manny RE, Mutti DO, et al. Time outdoors, visual activity, and myopia progression in juvenile-onset myopes. Invest Ophthalmol Vis Sci 2012;53:7169-7175.

    4. Rose KA, Morgan IG, Ip J, Kifley A, Huynh S, Smith W, et al. Outdoor activity reduces the prevalence of myopia in children. Ophthalmology 2008;115:1279-1285.

    5. Dirani M, Tong L, Gazzard G, Zhang X, Chia A, Young TL, et al. Outdoor activity and myopia in Singapore teenage children. Br J Ophthalmol 2009;93:997-1000.

    6. Guggenheim JA, Northstone K, McMahon G, Ness AR, Deere K, Mattocks C, et al. Time outdoors and physical activity as predictors of incident myopia in childhood: a prospective cohort study. Invest Ophthalmol Vis Sci 2012;53:2856-2865.

    7. Ashby R, Ohlendorf A, Schaeffel F. The effect of ambient illuminance on the development of deprivation myopia in chicks. Invest Ophthalmol Vis Sci 2009;50:5348-5354.

    8. Smith EL, 3rd, Hung LF, Huang J. Protective effects of high ambient lighting on the development of form-deprivation myopia in rhesus monkeys. Invest Ophthalmol Vis Sci 2012;53:421-428.

    9. Smith EL, 3rd, Hung LF, Arumugam B, Huang J. Negative lens-induced myopia in infant monkeys: effects of high ambient lighting. Invest Ophthalmol Vis Sci 2013;54:2959-2969.

    10. Mutti DO, Marks AR. Blood levels of vitamin D in teens and young adults with myopia. Optom Vis Sci 2011;88:377-382.

    11. Mutti DO, Cooper ME, Dragan E, Jones-Jordan LA, Bailey MD, Marazita ML, et al. Vitamin D receptor (VDR) and group-specific component (GC, vitamin D binding protein) polymorphisms in myopia. Invest Ophthalmol Vis Sci 2011;52:3818-3824.

    12. Verhoeven VJ, Hysi PG, Wojciechowski R, Fan Q, Guggenheim JA, Hohn R, et al. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat Genet 2013;45:314-318.

    13. Kiefer AK, Tung JY, Do CB, Hinds DA, Mountain JL, Francke U, et al. Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia. PLoS Genet 2013;9:e1003299.

    14. Mutti DO, Mitchell GL, Sinnott LT, Jones-Jordan LA, Moeschberger ML, Cotter SA, et al. Corneal and crystalline lens dimensions before and after myopia onset. Optom Vis Sci 2012;89:251-262.

    15. Christ GJ, Andersson KE. Rho-kinase and effects of Rho-kinase inhibition on the lower urinary tract. Neurourol Urodyn 2007;26:948-954.

    16. Ren J, Albinsson S, Hellstrand P. Distinct effects of voltage- and store-dependent calcium influx on stretch-induced differentiation and growth in vascular smooth muscle. J Biol Chem 2010;285:31829-31839.

    17. Dallosso HM, McGrother CW, Matthews RJ, Donaldson MM. Nutrient composition of the diet and the development of overactive bladder: a longitudinal study in women. Neurourol Urodyn 2004;23:204-210.

    18. Schroder A, Colli E, Maggi M, Andersson KE. Effects of a vitamin D(3) analogue in a rat model of bladder outlet obstruction. BJU Int 2006;98:637-642.

     

    Author Info

    Donald O. Mutti, OD, PhD, received his Doctor of Optometry degree in 1982 from the School of Optometry at the University of California, Berkeley, and his PhD in physiological optics from UC Berkeley in 1992. Dr. Mutti joined The Ohio State University College of Optometry faculty in 1999 and is currently the E.F. Wildermuth Foundation Professor in Optometry. He is a co-investigator on the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) study, and was the principal investigator of the Berkeley Infant Biometry Study (BIBS).

    Take-Home Message

    The CLEERE study followed approximately 5,000 children over time to determine what factors were different between those who became myopic and those who remained emmetropic. Study investigators recently reported that myopic children engage in more near work than emmetropic children, although near work did not cause the myopia. It appears, however, that time spent outdoors lowers the risk of becoming myopic.

     

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