Introduction: This study analyzed the effectiveness of 650-nm red-light feeding instruments in the control of myopia. Methods: In this study, 164 school-aged participants diagnosed with myopia in the city of Shenzhen were enrolled in a red-light feeding instrument study. Of these, 41 were enrolled in the mild-to-moderate myopia group that received red-light feeding (RLMM group), 65 were enrolled in the mild-to-moderate myopia group that received single-vision spectacle treatment (SVSMM group), and 58 were included in the severe myopia group that received red-light feeding (RLS group). Results: After the baseline values of the three groups were matched, the right eye data were used for statistical analysis. The average return visit time of each group was 60.42 days, and changes in the observation indexes before treatment and after follow-up treatment were compared. As the primary outcome, the axial length changes in the right eye of the SVSMM group (0.08 ± 0.40 mm), the RLMM group (−0.03 ± 0.11 mm), and the RLS group (−0.07 ± 0.11 mm) were compared and showed a statistical result of p < 0.001. Conclusion: The study results verified that red light had a noticeable effect on the control of myopia and that low-level red-light therapy played a vital role in the treatment of severe myopia.

© 2023 The Author(s). Published by S. Karger AG, Basel

Introduction

Currently, myopia is one of the most common diseases among teenagers [1]. It is a condition in which the spherical equivalent refractive (SER) error of an eye is ≤−0.50 diopter (D) when ocular accommodation is relaxed. The number of young people with myopia in Asia has reached 80%. Myopia has also gradually become the sixth most common disease endangering human health [2]. If left untreated, the condition can lead to a deterioration in vision and several potential adverse complications, such as retinal detachment, glaucoma, macular hemorrhage, macular split, and even blindness in severe cases [3, 4]. These complications are more likely to occur in people with severe myopia and those who have an eye SER of ≤−6.0 D. This severe myopia is also called high myopia. Currently, methods for controlling the progression of myopia can be divided into the following categories: establishing myopia files, outdoor sports intervention [5], medication, optical treatments, including orthokeratology (OK), specially designed soft contact lenses, myopia control glasses, and surgical treatment [6].

Clinical research has demonstrated that low-level laser therapy (LLLT) has an effect within the fields of dermatology, orthopedics, and neurology [7–11]. In ophthalmology, LLLT was also effective in amblyopia in the early stage [12]. In recent years, it has been found that red-light therapy can control and slow down the progression of myopia [13–15], and a number of clinical studies have shown that LLLT seems to be a new direction for myopia control [13–18]. This method is relatively quick and safe, has achieved good results in children aged 3–16 years old, and causes no serious adverse reactions [19]. Therefore, it is a good supplement to the current treatment of myopia.

In current clinical studies, it was found that the irradiation of short-wavelength and low-level red light could cause the axial length (AL) of the eye to shorten [13, 15, 18] and increase in choroidal thickness [20]. Some scholars believe that, in a similar process, the amount of dopamine in the eye increases through natural light to alleviate eye hypoxia [21, 22]. Others have found that red light affects a variety of biochemical mechanisms, such as adenosine triphosphate factor and fibrogenesis [23–26].

The technology behind using red-light feeding instruments for the control of myopia is, however, still subject to ongoing research. The current study was conducted involving school-aged individuals who had been diagnosed with myopia (6–18 years old) in Shenzhen, China. Treatment using red-light feeding instruments was delivered, and its therapeutic effect and safety were analyzed. The results provide data and information for future research regarding the treatment of myopia using red light.

Materials and MethodsStudy Participants

This study was a prospective non-randomized controlled trial. All of the participants were patients with myopia from the Pediatric Ophthalmology Clinic of Shenzhen Eye Hospital. All data were collected as of April 2019 through December 2019.

Existing data included the first screenings for the participants, which were recorded from the optometry clinic’s medical records. The screenings included an eye examination, past medical history, family history, current myopia prevention, and control methods. The parents of school-aged individuals who met the criteria were consulted by telephone about their willingness to participate in this research. If they agreed, the parents contacted the outpatient clinic for further screening.

The inclusion criteria were as follows: participants 6–18 years old with myopia, with a corrected visual acuity of 1.0 or more after rapid optometry (tropicamide eye drops), and good fixation in both eyes. The intraocular pressure (IOP) of both eyes was 10–21 mm Hg, and the difference in IOP between the two eyes was less than 5 mm Hg. The exclusion criteria were as follows: the presence of strabismus, amblyopia, glaucoma, severe pathological myopia, and/or a history of ocular trauma or ocular surgery. The study was conducted in line with the principles of the Helsinki Declaration and was approved by the Ethics Committee of Shenzhen Eye Hospital in 2019.

A total of 210 school-aged participants were expected to participate in the trial. According to the SER error, the participants were divided into a mild-to-moderate myopia group (SER = ≤−0.5 D to >−6.0 D) and a severe myopia group (SER = ≤−6.0 D). Among the 140 participants in the mild-to-moderate myopia group, some were randomly assigned to the red-light feeding (RLMM) group (n = 70) and others were assigned to the single-vision spectacle (SVSMM) group (n = 70). Then, 70 participants in the severe myopia group were treated with red-light feeding (RLS group) and were recruited independently for further analysis. Some of the participants dropped out during follow-up, and others in the SVSMM group had to be treated with atropine. Atropine treatment leads to pupil dilation and more light being admitted into the retina; as such, these participants were treated separately to ensure their safety. In total, 164 participants completed the study (Fig. 1). Among them, 41 were part of the RLMM group (average age, 8.62 ± 2.11 years), 65 were in the SVSMM group (average age, 8.37 ± 2.66 years), and 58 were in the RLS group (average age, 8.59 ± 3.57 years). The average age of the three groups was essentially the same.

Fig. 1.

Flow chart showing the grouping number of myopia study.

The red-light feeding instrument in the experimental group was the Eyerising single-wavelength 650-nm red-light therapeutic instrument (the safety of which passed a quality inspection by the China Optical Radiation Safety and Quality Supervision and the Inspection Center of Optoelectronic Products and had a medical device registration certificate issued by the People’s Republic of China). The laser power used was 2 ± 0.5 mW. The participants in the RLMM and RLS groups received treatment using the instrument at home twice a day for 3 min each session, 5 days a week; after each treatment, they closed their eyes and rested for 2 min. The entire process was supervised by the patients’ parents. The interval between two sessions of treatment was more than 4 h, and strong light in the room was avoided while the instrument was in use to avoid impacting the efficacy of the treatment. In addition to the red-light feeding instrument, all the participants in the study were required to wear full-correction distance vision glasses with single-vision spectacle lenses. The senior optometrist of Shenzhen Eye Hospital provided the SVSMM group with the corresponding degree of framed glasses, based on the patients’ optometry results, and there were no specific requirements for the brand and style of these. The participants in the SVSMM group wore the glasses every day and did not use other preventative or control treatments.

Aside from notifying the pediatric ophthalmologist responsible for the participants’ follow-up care, neither the optometry technician who examined the participants nor the outpatient physician was aware of the results. The study participants with myopia were also unaware of their examination results compared with previous data. A return visit was conducted 60 days after undergoing the red-light treatment, and the participants’ parents were informed 1 week in advance to make the follow-up appointment. The initial and follow-up examinations included visual acuity chart tests (far-and-near standard visual acuity table GB II 533-2011), an optometry examination (conducted by a senior optometry technician, national professional qualification level 1), a semi-automatic IOP measurement (Canon TX-20 Full Auto Tonometer), a slit-lamp examination (Haag-Streit BQ 900, Switzerland), an examination with a fundus wide-angle scanning laser ophthalmoscope (Panoramic Ophthalmoscope Daytona P200T), and optic AL and corneal curvature examinations (IOLMaster 700 Zeiss). Due to the coronavirus disease 2019 (COVID-19), the participants’ return visit time could not be controlled; for most participants, this was 30 and 90 days following treatment, and the average return visit time was 60.42 ± 35.49 days.

Data Analysis

Statistical analysis was conducted using the SPSS Statistics (v.23.0; IBM Co., Armonk, NY, USA) software program. Only data derived from the right eye were used in the analysis. The measurement data were compared between the two groups. If the data obeyed normal distribution, t tests were used. If the data did not obey normal distribution, a Wilcoxon rank-sum test was used. For comparison among the groups, the data obeyed normal distribution and homogeneity of variance, based on an analysis of variance. If there were differences between the groups, a pairwise comparison, following the use of a Tukey test, was applied. For data that did not obey a normal distribution or where the variance was uneven, a Kruskal-Wallis test was conducted. For cases where there were differences between the groups, a Nemenyi test was used for the pairwise comparison. If p < 0.05, the hypothesis test was considered to be statistically significant.

Results

This study, conducted in Shenzhen, China, indicated that myopia progression was largely slowed and controlled in school-aged participants after they received red-light feeding instrument treatment. To ensure the accuracy of this non-randomized trial, the patients in the RLMM and RLS groups only received red-light feeding treatment and glasses treatment. This meant that those who underwent other methods of slowing and controlling myopia progression, such as atropine or OK, were excluded from the experimental results. A total of 173 patients were enrolled; however, due to loss of contact, changes in the methods of slowing and controlling myopia progression, and other unavoidable issues, the final experimental sample included 164 cases. The sample included 80 males and 84 females. The average age was 8.54 ± 2.82 years, and the average SER was −5.11 ± 3.80 D. There were 99 cases in the experimental group, divided into mild-to-moderate and severe myopia groups, with 41 and 58 cases, respectively, and 65 in the single-vision spectacle group. The difference between the left and right eyes was not statistically significant; accordingly, this statistical analysis used data derived from the right eye of the participants. The baseline comparison for the RLS, SVSMM, and RLMM groups is shown in Table 1 (age, AL, AL/CR, spherical lens, astigmatism, and SER).

1. The main outcome concerns the changes in AL and refraction (the equivalent spherical, spherical, and columnar lenses) in the RLS, SVSMM, and RLMM groups after follow-up examination. Compared with the SVSMM group (0.08 ± 0.40 mm), there was a significant difference in the change in AL between the RLS (−0.07 ± 0.11 mm) and the RLMM (−0.03 ± 0.11 mm) groups (p < 0.001). The AL change in the RLS group was significantly higher than in the RLMM group (p < 0.001) (see Table 2).

2. Compared with the spherical lens growth of the SVSMM group (0.09 ± 2.84 D), the spherical lens growth of the RLMM group (0.07 ± 0.29 D; p = 0.006) was significantly different. According to the spherical degree change among the groups, the change in the RLS group (0.05 ± 0.40 D) was less than that in the RLMM group (0.07 ± 0.29 D) but not more obvious. However, there was no significant difference in the cylindrical lens change and SE change between the three groups (see Table 2).

3. For different ages and different eyeball sizes, only changes in the AL and the SER were insufficient for evaluating the controlling effect on myopia. The AL/CR growth [27–29] values of the participants in the treatment groups were analyzed and compared with the AL/CR growth values of the SVSMM group (0.04 ± 0.14) to reflect the growth of the entire AL more accurately. There was a significant difference between the growth values of the RLMM (−0.01 ± 0.02) and RLS group (−0.02 ± 0.05), respectively; the control effect on the RLS group was more obvious (see Table 2).

4. For further analysis, the RLMM and RLS groups were divided into two subgroups based on their AL, i.e., an AL of >24 and ≤24 mm. The results showed that the AL change of the >24 mm group (−0.19 ± 0.13 mm) was significantly greater than that of the ≤24 mm group (−0.02 ± 0.07 mm) after using the red-light feeding instrument (see Table 3). There was no significant difference in baseline average age between the two groups (the AL ≤24 mm group vs. the AL >24 mm group; 8.29 ± 2.76 vs. 8.74 ± 2.94, p = 0.472). This showed that the use of the red-light feeding instrument was more effective for people with a longer AL. Next, the participants were divided into two groups according to their age (6–12 and 13–18 years) to observe the therapeutic effect of various indexes of the eye on younger and older age groups. The baseline average values of the SER and the AL in the young group were −5.14 ± 3.61 D and 24.89 ± 1.37 mm, while those in the old group were −6.69 ± 3.97 D and 25.50 ± 1.99 mm; however, there was no statistically significant change in the AL and the SER in the two groups after treatment.

Table 1.

Baseline characteristics of study group

Age, yearAL, mmAL/CRSpherical lens (D)Astigmatism lens (D)SE (D)Interval daySVSMM (N = 65)8.37±2.6624.29±1.213.15±0.11−1.88±2.17−0.98±1.25−2.32±2.6465.14±45.49RLMM (N = 41)8.62±2.1124.28±1.043.14±0.12−2.13±2.30−1.24±0.93−3.20±2.8260.42±35.65p valuep = 0.8402p = 0.9531p = 0.8301p = 0.8331p = 0.5781p = 0.5381p = 0.32*RLS (N = 58)8.59±3.5725.68±1.573.31±0.21−6.61±2.84−2.10±1.35−7.93±2.9567.26±30.21p valuep = 0.71*p < 0.001*p < 0.001*p < 0.001*p < 0.001*p < 0.001*p = 0.47*Table 2.

Measured value change of study group

SVSMM (N = 65)RLS (N = 58)RLMM (N = 41)p valueAL change, mm0.08±0.40−0.07±0.11−0.03±0.11<0.001*AL/CR change0.04±0.14−0.02±0.05−0.01±0.02<0.001*Spherical lens (D) change0.09±2.840.05±0.400.07±0.290.006*Astigmatism lens (D) change−0.13±0.740.03±0.17−0.01±0.270.998*SE (D) Change−0.26±1.910.06±0.300.06±0.370.456*Table 3.AL subgroupsAGE, yearAL change, mmAL/CR changeSE change (D)≤24 mm (n = 38)8.29±2.76−0.02±0.07−0.01±0.030.12±0.25>24 mm (n = 61)8.74±2.94−0.19±0.13−0.01±0.020.04±0.38p value*0.4720.0070.5870.071AGE subgroupsAL, mmSER (D)AL change, mmAL/CR changeSE change (D)6∼12 years old (n = 58)24.89±1.37−5.14±3.610.07±0.22−0.01±0.020.05±0.3613∼18 years old (n = 41)25.50±1.99−6.69±3.970.05±0.37−0.03±0.050.12±0.33p value*0.220.2670.4320.1040.067Discussion

Myopia remains a major health problem. To address its control, this study evaluated a potentially effective treatment in the form of red-light therapy. The AL growth and SER correlated with the severity of myopia; accordingly, once AL growth and SER can be controlled, controlling myopia will also be more achievable. This study’s results showed that, compared with an increase in the AL growth in the SVSMM group (0.08 ± 0.40 mm), the growth of AL among the participants in the RLMM and RLS groups slowed (−0.03 ± 0.11 mm and −0.07 ± 0.11 mm, respectively). The same outcome was observed regarding the growth of spherical lenses, which was consistent with the findings of existing studies [13, 15].

This study and other existing research confirmed that red light played a role in controlling myopia [15]. The present study also verified that red light had an obvious effect on the control of eye axial growth (see Table 2). This may have been related to the overall situation of the eyeball wall. Existing studies have found that the choroidal thickness of patients will increase after red-light irradiation [20], which may be caused by the effect of red light on the metabolic processes of choroidal cells. This is likely to play a role, to varying degrees, at all layers of the overall eyeball wall and is subsequently reflected in changes in the AL. This study’s results indicated that red light played a more significant role in severe cases of myopia, which suggests that these may be related. This presents a significant advantage compared with the limitations of OK when considering the severity of myopia.

Red-light treatment represents a new approach to the slowing down and control of progressive myopia in school-aged individuals for whom the condition is severe. However, the results of this study found no significant correlation between the efficacy of red light in the control of myopia and age. This indicated that, regardless of age, red-light feeding instruments can be effectively used in the control of myopia. This result is, however, inconsistent with existing studies that show that the therapeutic effect in older age groups will be more pronounced [14], which may be a result of the different timings of follow-up and the severity of myopia, and this study does not use multivariate analysis, which may be affected by confounding factors.

Compared with traditional correction of ametropia using lenses, red-light therapy can delay the progression of myopia and prevent mild myopia from becoming more severe, which appears to be more noticeable compared with the current treatments of atropine and OK. Current research indicates the effect of red-light treatment on myopia control is superior to that of OK [13] in the short term; however, the long-term effects of red-light instrument feeding remain unclear.

According to feedback from participants who had been enrolled in this study, the main adverse reaction to the red-light feeding instrument was an afterimage [30]. Afterimage is a visual physiological phenomenon that does not immediately disappear after visual stimulation stops but instead fades gradually. This adverse phenomenon can be alleviated by a short period of eye-closing and rest; with the progression of treatment, this adverse phenomenon does not appear to worsen. At present, no other adverse reactions have been noted. Red-light control of myopia will not cause short-term organic damage to patients; regardless, the long-term adverse reactions of the treatment have yet to be studied and reported. Compared with Kent’s 670-nm red light for reducing retinopathy of prematurity [26], the red-light control therapy used in the current study is very safe. Future studies can explore the adverse reactions of long-term treatment, as well as the best treatment wavelength.

In the future, large, multicenter samples and long-term follow-up studies are needed to confirm the safety of red-light therapy. It is still controversial as to whether atropine and mydriasis can be combined with red-light therapy. Some scholars believe that the amount of light input will be increased following mydriasis and will result in increased afterimage reactions. Uncontrollable adverse reactions may also occur for an extended time following treatment. However, others believe that at a safe dosage, pupil dilation will not cause adverse reactions, and even with atropine treatment, it will form a superposition effect to enhance the effect of myopia control. This study adhered to the principle of safety first, and, as such, all of the participants who were treated with atropine were excluded from this research. The latest treatment guidelines do not recommend combining these two treatments for myopia control without current evidence-based medicine to ensure their safety [19].

There were some limitations to this study. First, because most of the patients were school-aged, following the outbreak of COVID-19, most of them were required to engage in online education at home, and the long-term use of electronic screens can accelerate AL growth. Additionally, COVID-19 also led to a loss in the follow-up rate of the study. Second, the red-light feeding equipment used in this study was a fixed-power device; accordingly, variation in treatment time and light power was limited. Third, the Eyerising single-wavelength 650-nm red-light therapeutic instrument employed in this study was unavailable for completing follow-up evaluations of the patients after they had completed the treatment. Thus, it is unclear whether a rebound effect occurred, and if so, the extent of rebound after discontinuation of treatment was similar to that with atropine. Fourth, the average follow-up time of this study was less than 60 days, which is relatively short, resulting in lack of observation of longer term effects. Fifth, a non-red-light treatment group for severe myopia should be added to this study to compare the control effect with the RLS group, so that a more rigorous comparison can be made, while the comparison between the SVSMM group and the RLS group was not rigorous enough. Finally, in this study, choroidal thickness and other structural parameters could not be assessed and additional ocular parameters should be included for better evaluation.

Conclusion

The study results verified that red light had an obvious effect on slowing and controlling the progression of myopia and that low-level red-light therapy played a more vital role in severe myopia, which provides a certain reference value for the applicable population and safety of red-light treatment. In the future, more long-term studies are required to verify the long-term control, rebound effect, and long-term safety of red-light treatment.

Acknowledgments

We are particularly grateful to all the people who have given us help on our article.

Statement of Ethics

This controlled trial was approved by the Ethics Committee of the Shenzhen Eye Hospital (No. 20191021-04) and registered in the Chinese Clinical Trial Register website (https://www.chictr.org.cn/, ChiCTR2000032172). For participants under the age of 18 years, written informed consent was obtained from their parents.

Conflict of Interest Statement

The authors declare that they have no competing interests.

Funding Sources

This study was funded by the International Science and Technology Cooperation Research Project of Shenzhen Science and Technology Innovation Committee (GJHZ20190821113401670), Sanming Project of Medicine in Shenzhen (SZSM201812090), and Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (No. SZGSP014).

Author Contributions

Acquisition of data: Zheng-Yang Tao. Analysis and interpretation of the data, statistical analysis, and writing of the manuscript: Zhi-Hong Lin. Obtaining financing and conception and design of the research: Hong-Wei Deng. Critical revision of the manuscript for intellectual content: Ze-Feng Kang. All authors read and approved the final draft.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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