Abstract
The fact that outdoor light environment is an important suppressive factor against myopia led us to invent violet light-transmitting eyeglasses (VL glasses) which can transmit violet light (VL), 360–400 nm in wavelength, for the suppression of myopia, and can meanwhile block harmful ultraviolet waves from sunlight. The current study is a double-blinded randomized clinical trial to investigate the myopia-suppressive effect of VL glasses compared to conventional eyeglasses (placebo glasses) that do not transmit VL. The subjects were children aged from 6 to 12 years old, the population in which myopia progression is generally accelerated, and the myopia suppressive effect was followed up for two years in a city in Japan. Periodical ophthalmic examinations, interviews, and measurements of reflection and axial length under mydriasis were performed at the initial visit (the baseline) and at 1, 6, 12, 18, and 24 months. The mean change in axial length in the VL glasses group was significantly smaller than in the placebo glasses group when time for near-work was less than 180 min and when the subjects were limited to those who had never used eyeglasses before this trial (p < 0.01); however, this change was not significant without subgrouping. The suppressive rate for axial elongation in the VL glasses group was 21.4% for two years.
1. Introduction
Myopia is reported to progress due to both genetic and environmental factors [1], but its precise mechanism remains unclear. Only a few safe and secure preventive measures against myopia progression have been established; in addition, the population suffering from myopia has expanded, exceeding one billion people [2].
When myopia progresses and turns into high myopia, the axial length grows and the shape of the eye changes, which may lead to blindness because of sequelae such as myopic maculopathy, glaucoma, and retinal detachment [3,4]. In a domestic epidemiological study, the Tajimi study, it was shown that high myopia accounted for 20% of all myopia cases and ranked first as the cause of WHO-defined blindness [5]. Additionally, it is reported that one diopter suppression of myopia reduces 20% of the possibility of blindness caused by high myopia [6,7]. In order to avoid blindness, prevention of axial elongation and eye deformation is critically important [8]. Therefore, early intervention to prevent myopia progression is highly significant, as it can considerably reduce the risk of sequelae of high myopia, which may lead to blindness.
It is crucial to control environmental factors to suppress the progression of myopia. There are some studies regarding environmental factors in relation to myopia progression, such as the Orinda Study [9], the Singapore Cohort Study of the Risk Factors for Myopia [10], and the Sydney Myopia Study [11,12]. These studies revealed that myopia could be accelerated by urban habitation, long-term near work, higher education, and high intelligence quotient (IQ), while outdoor activities suppressed its development. Two hours or more of daily outdoor activity can reduce the onset rate of myopia, irrespective of whether parents are myopic or not, which is one of its genetic factors [13,14]. There were a couple of major RCTs regarding the correlation of outdoor time with myopia. Cao et al. reported the significance of outdoor time for myopia prevention in their systematic review and meta-analysis, based on randomized controlled trials [15]. According to their report, an additional 20 min of recess outside the classroom could help to slow down the change speed of the refractive error [16]. RCTs conducted in China revealed that 40 min of school outdoor activity was added to the outdoor group, and the changes in both refractive error and axial length were slower than those of the control group [17]. A similar finding in another RCT conducted in Taiwan showed similar results [14]. Though it has been considered that the light that is critical for myopia prevention in an outdoor environment is very high intensity of illumination, even low illumination intensity could have myopia suppressive effects on myopia [18].
Although many researchers have performed investigations to reveal the reason for the effectiveness of outdoor activities on myopia prevention, there are studies focused on a light wavelength that exists in the outdoor environment. The current environment regarding myopia is characterized by ultraviolet-blocking materials such as windows and eyeglasses [19]. Previous studies have revealed that red, green, blue, and violet have the potential to suppress myopia [20,21,22,23,24,25]; among these wavelengths, violet light (VL: 360–400 nm) is the most potent [26]. Conventional eyeglasses do not penetrate the ultraviolet wavelength, but they also cut off VL [19]. VL eyeglasses were invented to solve these issues and this study was performed to verify their effect.
Discussion
According to previous reports, VL has an effect on suppressing myopia progression [19,26,30]. Based on this research, the application of instruments that could distinguish the effective light to prevent myopia progression from harmful lights to protect the eyes was attempted. The VL glasses, which actually transmit VL and block detrimental constituent such as UV, were invented in our laboratory and were expected to exert potency in clinical situations. This 2-year randomized controlled study was designed to investigate the effectiveness of VL glasses in suppressing the progression of myopia, and it revealed that the mean change in axial length in the VL glasses group was significantly smaller than that in the placebo glasses group when time for near-work was less than 180 min and when the subjects were limited to those who had never used eyeglasses before this trial (p < 0.01). This is the first randomized controlled study of VL glasses that reflects their potency. However, this study could not attain statistical significance when no limitation regarding near-work time and eyeglasses histories of the subjects was applied. Because VL transmitting eyeglasses do not exert their effect until they transmit VL in an outdoor environment, it was inappropriate to perform analysis while including the cases who did not have enough time for outdoor activity; therefore, PPS was performed. Nevertheless, since there were unexpectedly many unregistered cases, and those of protocol deviation such as shortage of outdoor activity time, VL glasses were merely found to have a tendency to be effective, but they did not reach statistical significance, even by PPS. The subgroup analysis limited to the group with no history of eyeglasses before this study, and with less than 180 min of near-work time, eventually revealed that VL glasses significantly suppressed axial elongation. The suppressive rate of axial elongation in the VL glasses group for two years was 21.4%, which could be considered meaningful to some extent.
The reason why limiting the subjects with no history of wearing eyeglasses led to the result being significant regarding axial elongation was sought. This study also revealed that the speed of myopia progression in the subgroup that had already worn conventional eyeglasses was actually fast; this result is possibly due to genetic background and the development of myopia at the early stage of life (Table 3 and Table 4). The excessive burden of near-work accelerates myopia progression and may cause attenuation of the effect of VL glasses. In addition, during a period of blocking VL transmission by wearing conventional eyeglasses, myopia progression could be facilitated.
As a prerequisite for a human study, there have been some reports concerning animal experimental models. Exposure to long-wavelength red light developed hyperopic responses in Rhesus monkeys and tree shrews [21,35], whereas red light was, in contrast, demonstrated to induce myopia response in chicks [22]. Meanwhile, short-wavelength light exposure led to hyperopia in chickens, fish and guinea pigs [22,23,25,36]. Furthermore, lens-induced myopia (LIM) models in chicks, mice and guinea pigs showed suppression of axial elongation and myopic shift of refractive error when exposed to VL [19,24,26,37]. Among visible lights, VL was the most effective wavelength for suppressing myopia progression in LIM [26].
VL is characteristic of the shortest wavelength and adjacent to ultraviolet waves. Because of this fact, it has often been considered whether VL is detrimental to the eyes. In this study, we did not find any adverse events during the two-years period through this study by regular examinations, including ocular surface, cataracts, allergy, and the fundus (Table S2). When VL glasses are worn, the amount of VL reaching the eye is more than that when conventional eyeglasses are worn. Furthermore, the amount of VL transmitted when VL glasses are worn is less than that when no glasses are worn. This fact may have contributed to no adverse effects being observed.
To date, there have been many types of eyeglasses sold to the public. In order to study the pure effectiveness of VL glasses, the subjects were limited to children who had never worn eyeglasses. Moreover, at the baseline, near-work time in the VL group was less than that in the placebo group, as shown in Table 1; it is well known that near-work time is an important factor for the progression of myopia. Therefore, subgroup analysis was performed and was limited to a group in which near-work time was less than 180 min. As a result, axial elongation was suppressed in the VL glasses group unless the time for near-work exceeded 180 min. The suppressive rate of the axial elongation with VL glasses for 2 years was 21.4% (Figure 3A). While this value does not surpass the suppressive rate of axial elongation with orthokeratology, multifocal contact lenses, or the defocus incorporated multiple segments (DIMS) eyeglasses [38,39], it is competitive with other methodologies such as progressive addition lenses (PAL), radial refractive gradient lenses, and positively aspherized PAL. The suppressive rate of axial elongation in PAL was 0–16%, that in radial refractive gradient lenses was not statistically significant, and that in positively aspherized PAL was 12% [31,40,41]. Additionally, the suppressive rate of axial elongation with 0.01% atropine drops, one of the current major standard remedies for myopia suppression, is reported to be 12% in Low-Concentration Atropine for Myopia Progression (LAMP) and 18% in Atropine for the Treatment of Myopia in Japan (ATOM-J) studies [42,43]. VL glasses, the suppressive rate of which is 21.4% under the limited condition regarding near-work time and the history of eyeglasses use, are demonstrated to be barely superior to atropine eye drops as a preventive measure against myopia progression.
