Can red light therapy delay myopia onset?

Paper title: Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial

Authors: Xiangui He^1,2, Jingjing Wang¹, Zhuoting Zhu^3,4,5, Kaidi Xiang², Xinzi Zhang², Bo Zhang¹, Jun Chen¹, Jinliuxing Yang¹, Linlin Du¹, Chunjin Niu⁶, Mei Leng,⁷ Jiannan Huang¹, Kun Liu², Haidong Zou^1,2, Mingguang He^3,4,5, Xun Xu^1,2 

1. Department of Clinical Research, Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai Vision Health Center and Shanghai Children Myopia Institute, Shanghai, China
2. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Center of Eye Shanghai Key Laboratory of Ocular Fundus Diseases, Engineering Center for Visual Science and Photomedicine, Shanghai, China
3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
4. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
5. Division of Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
6. Department of Ophthalmology Prevention, Changning Center for Disease Control and Prevention, Shanghai, China
7. Department of Teaching and Research, Changning Institute of Education, Shanghai, China

Date: Apr 2023

Reference: He X, Wang J, Zhu Z, Xiang K, Zhang X, Zhang B, Chen J, Yang J, Du L, Niu C, Leng M, Huang J, Liu K, Zou H, He M, Xu X. Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e239612

[Link to open access paper]

In this 12-month randomized clinical trial conducted in Shanghai, China, children aged 6 to 11 years with pre-myopia, defined as a spherical equivalent cycloplegic refractive error (SER) ranging from +0.50 to -0.50D, were investigated for the efficacy and safety of repeated low-level red-light (RLRL) therapy in preventing incident myopia. Among 278 participants, 139 received RLRL therapy (Eyerising), while 139 were in the control group. The trial involved RLRL sessions twice daily for 3 minutes, five days a week, but during the COVID-19 lockdown, some in the intervention group (n=107) faced compliance challenges, impacting the continuity of treatment at home between the 9 and 12-month intervals.

Primary outcome was the 12-mth cumulative myopia incidence rate. This was found to be 61.3% for the control group and 40.8% for the intervention group, giving a relative reduction of 33.4%.

• This reduction was 54.1% for children who had continued with uninterrupted treatment over lockdown (n = 32).

Secondary outcomes included OCT changes and mean changes in SER and AL at 12-mths:

• For SER, mean values were -0.76 and -0.35D for the control and intervention groups respectively, giving a -0.41D (53.9%) reduction. For those able to continue with the RLRL treatment, the mean SER was -0.18D, giving 76.3% reduction.
• Mean AL changes were 0.47 and 0.30mm for the control and intervention groups respectively, representing a 0.17mm (36.2%) reduction. For those who continued treatment, this was 0.24mm, giving 48.9% reduction.
• Mean choroidal thickness changes of 9.2µm and 3.0µm were found for the intervention and control groups respectively, over 12mths. No structural damage was found on OCT scans.

Some children showed hyperopic shifts in SER of >0.25D: the control group showed 24.5% at 6mths and 2.7% at 12mths and the RLRL group showed 51.2% at 6mths and 19.0% at 12mths. Improved efficacy was seen for children with SER values of 0.01 to 0.50D than for those with SER of 0.00 to -0.50D. No significant efficacy differences were found across age groups. 

This study was able to demonstrate reduced myopic shifts of 0.17mm in AL and 0.41D for SER after exposure to repeated low-level red light. For those able to continue therapy uninterrupted (n = 9), there was a greater reduction in myopia incidence.

• The results confirm AL regression seen in another study investigating exposure to RLRL and are comparable to results from a study that measured reduced myopic shift after 1 year of outdoor intervention.^2,3
• The RLRL was well-tolerated by the children. They experienced no glare, flash blindness or after-images that lasted more than 6mins. No functional changes were seen with ongoing OCT reviews.

These findings suggest RLRL may be a safe and effective therapy for myopia prevention in pre-myopic children. Children with SER of 0.01 to 0.50D may receive a greater benefit of RLRL as a pre-emptive measure, regardless of age.

Although this study suggests RLRL is a safe and effective treatment, the results can only be applied to the red-light wavelength and power intensity produced by the particular device used.

• Further studies will confirm tolerance and safety over longer periods, the efficacy of other wavelengths, an optimal intervention dose and if rebound is likely once stopped. The underlying mechanisms of RLRL intervention therapy also need to be fully established.

The authors discussed the greatest efficacy being seen for children with SER between +0.01 and +0.5D, rather than for SER between 0.00 and -0.50D. However, the IMI has categorised pre-myopic refractive states in children as being +0.75D or less and more than -0.50D.⁴

• This may mean RLRL was offered too late to some children in the study to be fully effective. Instead, RLRL therapy could be introduced as an early prophylactic measure for pre-myopes who have a higher risk of developing myopia.

Title: Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial

Authors: He, Xiangui, PhD; Wang, Jingjing, PhD; Zhu, Zhuoting, PhD; Xiang, Kaidi, MD; Zhang, Xinzi, MD; Zhang, Bo, MS; Chen, Jun, PhD; Yang, Jinliuxing, PhD; Du, Linlin, MPH; Niu, Chunjin, BS; Leng, Mei, BS; Huang, Jiannan, PhD; Liu, Kun, MD; Zou, Haidong, MD; He, Mingguang, PhD; Xu, Xun, MD

Purpose: To assess the efficacy and safety of a repeated low-level red-light (RLRL) intervention in preventing incident myopia among children with premyopia.

Methods: This was a 12-month, parallel-group, school-based randomized clinical trial conducted in 10 primary schools in Shanghai, China. A total of 139 children with premyopia (defined as cycloplegic spherical equivalence refraction [SER] of -0.50 to 0.50 diopter [D] in the more myopic eye and having at least 1 parent with SER ≤-3.00 D) in grades 1 to 4 were enrolled between April 1, 2021, and June 30, 2021; the trial was completed August 31, 2022. Children were randomly assigned to 2 groups after grade stratification. Children in the intervention group received RLRL therapy twice per day, 5 days per week, with each session lasting 3 minutes. The intervention was conducted at school during semesters and at home during winter and summer vacations. Children in the control group continued usual activities.

Results: The primary outcome was the 12-month incidence rate of myopia (defined as SER ≤-0.50 D). Secondary outcomes included the changes in SER, axial length, vision function, and optical coherence tomography scan results over 12 months. Data from the more myopic eyes were analyzed. Outcomes were analyzed by means of an intention-to-treat method and per-protocol method. The intention-to-treat analysis included participants in both groups at baseline, while the per-protocol analysis included participants in the control group and those in the intervention group who were able to continue the intervention without interruption by the COVID-19 pandemic.

There were 139 children (mean [SD] age, 8.3 [1.1] years; 71 boys [51.1%]) in the intervention group and 139 children (mean [SD] age, 8.3 [1.1] years; 68 boys [48.9%]) in the control group. The 12-month incidence of myopia was 40.8% (49 of 120) in the intervention group and 61.3% (68 of 111) in the control group, a relative 33.4% reduction in incidence. For children in the intervention group who did not have treatment interruption secondary to the COVID-19 pandemic, the incidence was 28.1% (9 of 32), a relative 54.1% reduction in incidence. The RLRL intervention significantly reduced the myopic shifts in terms of axial length and SER compared with the control group (mean [SD] axial length, 0.30 [0.27] mm vs 0.47 [0.25] mm; difference, 0.17 mm [95% CI, 0.11-0.23 mm]; mean [SD] SER, -0.35 [0.54] D vs -0.76 [0.60] D; difference, -0.41 D [95% CI, -0.56 to -0.26 D]). No visual acuity or structural damage was noted on optical coherence tomography scans in the intervention group.

Conclusions: In this randomized clinical trial, RLRL therapy was a novel and effective intervention for myopia prevention, with good user acceptability and up to 54.1% reduction in incident myopia within 12 months among children with premyopia.

[Link to open access paper]