Efficacy of repeated low-level red light therapy for high myopia control

Paper title: Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial

Authors: Xu, Yan (1); Cui, Lipu (2,3); Kong, Miao (4); Li, Qian (5); Feng, Xueliang (4); Feng, Kehong (6); Zhu, Huang (7); Cui, Hongping (5); Shi, Caiping (8); Zhang, Jian (9,10,11)^; Zou, Haidong (1,2,3,12,13,14) 

1. Shanghai Eye Diseases Prevention &Treatment Center/ Shanghai Eye Hospital, School of Medicine, Tongji University, Shanghai, China
2. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3. Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China
4. Shanxi Eye Hospital, Taiyuan, Shanxi, China
5. Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
6. Children's Hospital of Soochow University, Suzhou, Jiangsu, China
7. Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
8. Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
9. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Chin
10. Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
11. Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou, China
12. Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
13. Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
14. National Clinical Research Center for Eye Diseases, Shanghai, China

Date: June 2024

References: Xu Y, Cui L, Kong M, Li Q, Feng X, Feng K, Zhu H, Cui H, Shi C, Zhang J, Zou H. Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial. Ophthalmology. 2024 Jun 6:S0161-6420(24)00318-X.  [Link to open access paper]

Several studies have already investigated the role of repeated low-level red light (RLRL) therapy in myopia management.^1-5 This prospective, multi-site, randomised clinical trial evaluated the safety of the Eyerising International desktop device for RLRL therapy (wavelength 650nm), and its efficacy in limiting myopia progression in highly myopic children and teenagers.

The participants were aged 6 to 16yrs with healthy eyes, spherical equivalent refraction (SER) of -4.00D myopia or higher in at least one eye, astigmatism less than 2D and no previous experience of any myopia control therapies. They were randomised in a 1:1 ratio to either the RLRL plus single vision spectacle lens intervention group (n = 97) or the single vision spectacle only control group (n = 95).

The intervention group participants were asked to use the device twice daily for 3min sessions for a year with at least 4hrs between sessions. The device recorded the date and time of use to aid compliance monitoring. Of the original 192 participants, 173 completed the 12mths (treatment group, n = 90 and control group, n = 83). Overall, 188 were included in the intention to treat analyses. 

• The mean ages were 10.4yrs and 11.2yrs for the intervention and control groups, respectively. There were no differences between the groups at baseline for corrected and uncorrected best visual acuities, AL, SER or intra-ocular pressure (IOP). Mean myopia was -5.88D and 25.93mm in the treatment group. 
• There was an 84% compliance rate for the RLRL group. 
• After 12mths, the adjusted mean change in AL was -0.06mm and 0.34mm in the treatment and control groups, respectively, with a mean difference of 0.41mm. Over half of the treatment group (53.3%) demonstrated axial length reduction beyond the instrument’s margin of error of >0.05mm at 12mths. Children aged 6-11yrs showed more axial length growth compared to 12-16yr olds. 
• The adjusted mean change in SER at 12mths was +0.11D and -0.75D for the treatment and control groups, respectively, with a mean difference of -0.86D.

No severe adverse responses were reported, such as structural damage within the eyes, sudden vision loss of 2 lines or more, scotoma, glare or after-images lasting more than 5mins. One child in the RLRL group reported conjunctivitis.

These results confirm findings from the first published RCT on RLRL, by Jiang et al,¹ although the results here appear to be stronger in this high myopia cohort. In that first published RCT in children with -1.00 to -5.00D of myopia (mean myopia -2.49D, 24.54mm and mean age 10.4 years), the control group progressed 0.38mm and -0.79D in one year compared to 0.13mm and -0.20D in the treatment group.¹ In this study (similar mean age, but myopia -5.88D and 25.93mm), the control group progressed similarly but the treatment group showed mean reduction in myopia of -0.06mm and +0.11D compared to their baseline. 

In this study, there was a higher compliance rate in daily device use (84% vs 75%) and apparent higher efficacy, suggesting both a dose-dependent effect and a potentially stronger result for high myopes with RLRL therapy.

Highly myopic eyes can be at greater risk of fundus damage, with decreased retinal and choroidal thickness, and recent studies have found that scleral hypoxia may be a prerequisite to myopia development and scleral remodelling.^6-8

It has been hypothesised that RLRL exposure may increase blood flow to the fundus, subsequently increasing scleral collagen levels and decreasing scleral hypoxia.¹ Increased choroidal thickening was noted in this and other studies of RLRL, which does not fully account for the degree of axial shortening found, implying that other factors may play a role in axial length shortening. In this study, the authors suggested that choroidal thickening may instead indicate an inflammatory response to repeated red light laser exposure. Currently, there is little data regarding the precise power levels received at the retina when using the Eyerising RLRL device or what impact repeated exposure may have on the retinal tissue, although no structural fundus damage was seen on OCT images available in this study. 

Further studies are needed to determine optimal treatment duration and frequency, monitor structural changes in the retina, establish the underlying mechanisms and long-term safety of RLRL therapy and if rebound effects occur when treatment is stopped.

Title: Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial

Authors: Yan Xu, Lipu Cui, Miao Kong , Qian Li, Xueliang Feng, Kehong Feng, Huang Zhu, Hongping Cui, Caiping Shi, Jian Zhang, Haidong Zou

Purpose: To assess the effectiveness and safety of repeated low-level red light (RLRL), which is a newly available treatment for myopia control in children and adolescents with high myopia.

Methods: Between February 2021 and April 2022, 192 children aged 6 to 16 years were enrolled. Each child had at least 1 eye with myopia of cycloplegic spherical equivalent refraction (SER) at least -4.0 diopters (D), astigmatism of ≤2.0 D, anisometropia of ≤3.0 D, and best-corrected visual acuity (BCVA) of 0.2 logarithm of the minimum angle of resolution or better. Follow-up was completed by April 2023.

Participants were randomly assigned at a 1:1 ratio to intervention (RLRL treatment plus single-vision spectacles) or control (single-vision spectacles) groups. The RLRL treatment was administered for 3 minutes per session, twice daily with a minimum interval of 4 hours, 7 days per week.

The primary outcome and key secondary outcome were changes in axial length (AL) and cycloplegic SER measured at baseline and the 12-month follow-up visit. Participants who had at least 1 post-randomization follow-up visit were analyzed for treatment efficacy.

Results:  Among 192 randomized participants, 188 (97.91%) were included in the analyses (96 in the RLRL group and 92 in the control group). After 12 months, the adjusted mean change in AL was -0.06 mm (95% confidence interval [CI], -0.10 to -0.02 mm) and 0.34 mm (95% CI, 0.30 to 0.39 mm) in the intervention and control groups, respectively. A total of 48 participants (53.3%) in the intervention group were still experiencing axial shortening >0.05 mm at the 12-month follow-up. The mean SER change after 12 months was 0.11 D (95% CI, 0.02to 0.19 D) and -0.75 D (95% CI, -0.88 to -0.62 D) in the intervention and control groups, respectively.

Conclusions: Repeated low-level red light demonstrates stronger treatment efficacy among those with high myopia, with 53.3% experiencing substantial axial shortening. Repeated low-level red light provides an excellent solution for the management of high myopia progression, a significant challenge in ophthalmology practice.

[Link to open access paper]