Two years of red light therapy: safety, efficacy and rebound

Paper title:  Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study

Authors: Ruilin Xiong¹, Zhuoting Zhu^1,2,3 , Yu Jiang,¹ Xiangbin Kong⁴, Jian Zhang¹, Wei Wang¹, Katerina Kiburg², Yixiong Yuan¹ , Yanping Chen¹ , Shiran Zhang¹, Meng Xuan¹ , Junwen Zeng¹, Ian G. Morgan⁵, Mingguang He^1,2,3 

1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of  Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
2. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
3. Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
4. Department of Ophthalmology, Affiliated Foshan Hospital, Southern Medical University, Foshan, China
5. Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia

Date: May 2022

Reference: Xiong R, Zhu Z, Jiang Y, Kong X, Zhang J, Wang W, Kiburg K, Yuan Y, Chen Y, Zhang S, Xuan M, Zeng J, Morgan IG, He M. Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study. Clin Exp Ophthalmol. 2022 Dec;50(9):1013-1024. 

[Link to open access paper]

In this study, the researchers aimed to assess the long-term effectiveness and safety of repeated low-level red-light (RLRL) therapy for controlling myopia over a span of 2 years. The study focused on Chinese children who had initially participated in a one-year randomized controlled trial. The participants were categorized into groups:

• RLRL-RLRL group: participants who continued with repeated low-level red-light (RLRL) therapy from year 1 into year 2 (n=11)
• RLRL-SVS group: Those who stopped RLRL therapy and switched to single-vision spectacle (SVS) in the second year (n=52)
• SVS-SVS group: Participants who either continued wearing SVS without additional RLRL therapy (n=41)
• SVS-RLRL group: Participants who continued wearing SVS and received additional RLRL therapy (n=10)

RLRL therapy involved the use of an at-home desktop light device emitting red light at 650 nm, administered for 3 minutes twice a day, five days a week. Measurements of axial length (AL) and cycloplegic spherical equivalence refraction (SER) were recorded.

The findings revealed that over the 2-year period, continued RLRL therapy demonstrated significant efficacy in slowing myopia progression, with the RLRL-RLRL group exhibiting the smallest axial elongation and SER progression. Specifically, the RLRL-RLRL group showed the least progression in both AL and SER, (0.16mm over two years) followed by SVS-RLRL, RLRL-SVS, and SVS-SVS groups. Over two years, the RLRL-SVS group showed 0.50mm total axial length growth, compared to 0.64mm in the SVS-SVS group, but in the second year the RLRL-SVS group grew significantly faster at 0.42mm compared to 0.28mm in the control group, showing a statistically significant rebound effect. No self-reported adverse events or functional or structural damages were reported, indicating the sustained promise of RLRL therapy in terms of efficacy and safety for myopia control.

The study's outcomes highlight the sustained efficacy of repeated low-level red-light (RLRL) therapy in reducing myopia progression over a 2-year period, suggesting its potential as an effective strategy for managing myopia in pediatric patients, although the numbers in the two year treatment group were very small. The absence of self-reported adverse events, functional, or structural damages associated with RLRL therapy over the 2-year period suggests its safety. This information is pivotal for clinicians when evaluating the risk-benefit profile of interventions for myopia control. 

Furthermore, the rebound effect observed in the study underscores the critical need for continuing treatment in this age group, and continued follow-up after treatment cessation. The children who ceased RLRL treatment after one year were only a mean 11.5 years of age. Atropine and orthokeratology are both myopia interventions that can also exhibit a rebound effect in younger age groups, with mean axial elongation of 0.31mm after 1 year^1,2 and 0.15mm after 7 months³ respectively. In the RLRL-SVS group, cessation of red-light therapy led to a second-year axial elongation of 0.42 mm and a SER progression of -0.91D, indicating a rebound effect compared to 0.28mm and -0.54D in the control group. The study authors suggest that the greater magnitude of rebound in RLRL therapy may be attributed to its higher efficacy or the inherently faster physiological progression observed in the study, aligning with findings from ATOM and LAMP atropine studies.^1-2,4 It is important to advise patients on potential consequences associated with discontinuing RLRL therapy, especially in younger children, and continue follow-up after discontinuation.  

This study is on of the first to examine the long-term effectiveness and safety of RLRL therapy for myopia control over a 2-year period. Limitations include the non-random assignment of participants for continuation or cessation, potentially introducing selection bias. The study also had a smaller number of participants on RLRL therapy, compromising the power to detect group differences and identify risk factors. Future large-scale, well-designed studies are crucial to validate these findings. Additionally, the study focused on Chinese children, and generalizability to other ethnicities needs exploration. Further research is needed to understand RLRL therapy mechanisms, assess efficacy and safety beyond 2 years, and to evaluate factors involved in the rebound effect.