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Progress and Control of Myopia by Light Environments

Jiang, Xiaoyan, M.D.; Kurihara, Toshihide, M.D., Ph.D.; Torii, Hidemasa, M.D., Ph.D.; Tsubota, Kazuo, M.D., Ph.D.

doi: 10.1097/ICL.0000000000000548
Review Article

Abstract: During the past 30 years, the prevalence rate of myopia has been increased dramatically. Myopia has become one of the leading causes of vision loss in some countries, whereas the mechanism of the main pathological change in myopia is still largely unknown. Although several studies showed genetic background influences the phenotype of myopia to some extent, the sudden increase of morbidity cannot be explained by genetics only. The change in lifestyle results in tremendous change in the light environment, which can be considered to play an important role in the onset and progression of myopia. The difference between indoor and outdoor light environments such as intensity and wavelength of modern electronic lighting equipment may be a cue for myopia control as environmental factors. In this review, we discuss the relationship between myopia and light environment focusing on the basic and clinical studies.

Laboratory of Photobiology (X.J., K.T., H.T.), Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; and Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan (T.K., H.T., K.T.).

Address correspondence to Kazuo Tsubota, M.D., Ph.D and Toshihide Kurihara, M.D., Ph.D, Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; e-mail:

The design of the mouse eyeglass has been applied for a patent (Application no. 201741349).

Supported by Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to T. Kurihara. This work is also supported by the grant for myopia research from Tsubota Laboratory, Inc. (Tokyo, Japan).

Accepted July 09, 2018

Myopia, or nearsightedness, is a state of refractive error characterized by the axial length elongation of the eyeball. In general, those with spherical equivalent refraction value less than −0.5 diopters (D) are diagnosed as myopic, and less than −6.0 D or axial length longer than 26.0 mm may be defined as having high myopia.1,2 Although eyeglasses, contact lenses, or refractive surgery can correct the refractive error by modifying the focus onto the retina, the shape of the eyeball remains abnormal. Continual progression of myopia may result in severe deformation of sclera, choroid, and retina increasing the risk of glaucoma, retinal detachment, retinochoroidal atrophy, cataracts, choroidal neovascularization, and optic neuropathy.3,4 To date, several interventions have been confirmed to have therapeutic effects for myopia control in clinical studies. Moderate- and high-dose atropine eye drops showed suppressive effects on both axial elongation and refraction change.5–11 Optical corrections, such as peripheral defocus, bifocal, and multifocal contact or spectacle lenses, and orthokeratology have shown a range of therapeutic efficacy.12

The prevalence of myopia has been growing dramatically in the past 50 years.13 In East Asia, 80% to 90% are myopic in some young adult populations.14 Macular degeneration caused by myopia has become a frequent cause of irreversible vision loss in certain communities.15–18 It was estimated that the global prevalence of myopia would be almost 50%, and one out of ten would be high myopia by the year of 2050.19 The causes of this myopia pandemic are still largely unknown.20 One possible explanation is a shift in the amount of time people spend outdoors.21–23 People tend to spend more time indoors nowadays instead of staying outside, which is in parallel with the increasing prevalence of myopia. Indeed, cross-sectional data showed people spent more time outdoor have lower odds of myopia.24–29 Longitudinal data in cohorts across different locations and races showed that outdoor activity may prevent the onset of myopia,30–33 whereas the effect for those who are already myopic remains controversial.26,33–38 Protective factors and mechanisms are open to debate. Differences in the level of physical activities30,39,40 and serum vitamin D41 between outdoor and indoor activities seem to have little association with myopia. The involvement of other factors such as the viewing distance42–46 and the accommodation response47 is still controversial. Meanwhile, the difference in light environment between indoor and outdoor activities drew much of researchers' attention and several clinical trials, and basic studies have shown some relevance with myopia.1,2,24,30,48–55 In this article, we will discuss the evidence and possibilities of controlling myopia through light environments.

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In 2008, Rose et al.24 showed that there was a lower odds ratio of myopia with increased outdoor time independent of the level of near-work activity (Fig. 1) and suggested the high light intensity in outdoor environment could be the key. Compared with several hundreds lux of light indoor, the brightness outside reaches 10,000 to 100,000 lux in a sunny day.33 Animal studies confirmed that high ambient lighting has protective effect on several species of form-deprivation myopia (FDM) animal model including chicks,51,56,57 mice,50 and monkeys.54 A well-supported hypothesis is that bright light increases the synthesis and the release of dopamine in the retina58 that may affect both physiological and myopic eye growth.59–61 The role of dopamine in myopia development has been confirmed in various animal studies. The level of dopamine or its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the retina or vitreous was reduced by experimental myopia inducement in chicks,61–63 guinea pigs,64 and nonhuman primates.60 Increasing dopamine level65,66 or the administration of nonselective dopamine agonists such as apomorphine (APO) and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide showed suppressive effects in animal models of FDM.67–71 It needs to be mentioned that changes of dopamine, DOPAC, and the effect of APO in lens-induced myopia (LIM) animal models are inconsistent across species.63,69,72,73 Interestingly, the effect of high-intensity light on LIM animal models is also controversial.54,55,74 Bright light showed protective effect on FDM, but not on LIM in monkey.54,74 In LIM chicks, full compensation to minus lens still occurred under bright light, although the progression slowed down.52 These findings indicate that FDM and LIM may induce myopic states with different pathways.

FIG. 1

FIG. 1

The underlying mechanism of dopamine pathway, especially the involvement of dopamine receptors with myopia, is still under debate. Two families of dopamine receptors exist in the retina: D1-like receptors (D1R and D5R) and D2-like receptors (D2R and D4R).75,76 D2-like receptors are generally considered to be more important in myopia. D2R agonist quinpirole inhibited FDM in chicks and mimicked the protective effect of short-period normal vision during FDM inducement.77,78 D2R antagonists canceled the protective effect of APO,79 although D2R antagonist alone had no effect on normal eye growth.77 However, the role of D2-like receptors seemed to be swaying with different pharmacological manipulations such as the dosage,76,80 administration method,68,81 and perhaps species.67,81 The protective effect of dopamine induced by bright light might also be related with D2R,52 whereas one recent report also showed the involvement of D1R.50 Although further studies are needed to reveal the complex relationship of the light environment and myopia development, dopamine is a strong candidate contributing to the protective effect of bright light at least in experimental light conditions.

Another big difference between outdoor light environment and indoor manufactural light sources is the distribution of wavelength.1,2 Sunlight has smooth continuous spectral distribution across a wide range of wavelength. The typical indoor light sources such as fluorescent light or light-emitting diode have some wavelength regions that are very strong while some regions are even missing.1 According to results of animal experiments, wavelengths affected the refractive development and eye growth independently from intensity.82,83 However, effects of wavelength on refraction were different among species. In guinea pigs, compared with broad-band white light, exposure to blue light produced more hyperopia in naked eyes and suppressed axial elongation in LIM, whereas green light induced myopic tendency. Positive lenses no longer induced hyperopia under red light.83–85 The situation is similar with chicks, which could be more hyperopic in blue light than in red light.86,87 By contrast, opposite results were found in tree shrews: steady red light produced substantial hyperopia while blue flicker produced myopia.88,89 Red light also did not necessarily promote myopia development in rhesus monkeys.90 These varieties of phenotypes across the species are hard to be interpreted.

The retina might be able to detect the longitudinal chromatic aberration (LCA, the physical phenomenon that shorter wavelengths focused closer to the lens than longer wavelengths) and use it as the clue for emmetropization.86,91–93 Gawne et al. argued that LCA might be considered as either a target or a cue of the ocular elongation in a manner dependent on context. In the former condition, the eye would grow longer to match the focus of long wavelength and vice versa. In the latter condition, long wavelength would be the signal to tell the eye that it is already long enough to catch the focus, so the growth should be stopped.88 However, the theoretical effects based on LCA were far below phenotypical value obtained from those experiments.83,91 Further research is necessary to explore the mechanisms of wavelength effect in the eye growth.

Besides the distributions, ranges of wavelength are also different: indoor light sources do not emit light under 400 nm, and most of the glass windows block the wavelength under 400 nm as well. This implies that indoor light environments rarely contain ultraviolet-C (UVC, ∼280 nm), UVB (280∼315 nm), UVA (315∼360 nm), and violet light (VL, 360∼400 nm).1 Recently, our group reported that VL, the shortest part of visible light wavelength, had a protective effect against myopia in chicks and human.1,2 This finding might provide a new strategy on controlling myopia pandemic in the world.

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Violet light is the shortest wavelength in the visible light: 360 nm∼400 nm (Commission internationale de l'éclairage [CIE]). Violet light exists abundantly in the sunlight outside while rarely been detected in the indoor light environments. Daily using artificial light sources emit no wavelength under 400 nm. The sunlight through the window rarely contains VL; most of the modern window glass cut the light of wavelength under 400 nm because of the concern for the health risk caused by UV (Fig. 2).1 This is also the case in almost all the eyeglasses and some contact lenses indicating that the eyeball rarely exposed to VL with commonly used optical correction devices even in outdoor environment.1

FIG. 2

FIG. 2

We consider that this over protection from UV and the lack of VL in artificial light are possible reasons for the myopia boom worldwide. Our group reported that VL had protective effect on myopia in chicks.94 Retrospective studies in human also showed that VL suppressed the progression of both school-aged myopia and adult high myopia (Fig. 3).1,2 Whether LCA contributed to VL effect is still unknown. Our group showed that VL could induce the upregulation of myopia protective gene early growth response protein 1 (EGR-1) in the chick retina, which showed that VL might prevent myopia through pathways independent to other wavelengths. The mechanism behind VL for myopia control must not be simple, and more works still need to be performed. Recently, we have established a highly efficient myopia murine model (Fig. 4).95 The protocol induces robust myopic phenotype in mice using transparent lenses that the light can pass through without changing physical property. Combined with genetic manipulation, we believe the mechanism of myopia and the relationship between light and myopia could be unveiled by using this model.

FIG. 3

FIG. 3

FIG. 4

FIG. 4

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Until the ideal pharmacological targets being found, we believe that manipulating light environment is the most practical way to prevent myopia. Although whether there is a threshold of daily outdoor light exposure for preventing myopia is still under debate,96,97 evidence has shown that less than 40 min per day of outdoor light exposure may be a risk factor to faster axial eye growth in children.96 Generally, approximately 2 hours of outdoor light exposure per day is recommended.96,98 There is a lack of concordance between areas with short hours of sunlight and areas of high myopia prevalence.99,100 Therefore, more data are required to prove the VL hypothesis described above. Currently, we have started a clinical trial to test the effect of artificial VL source on preventing myopia in human. We hope our research on VL could extend the potential and feasibility of using light environment to prevent myopia.

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Myopia; Light environments; Life style; Violet light

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