·Standard and Specification·
Expert consensus on a repeated low-level red-light therapy as an alternative treatment for childhood myopia (2022)
Expert workgroup of expert consensus on repeated low-level red-light as an alternative treatment for childhood myopia (2022)
Corresponding authors: Xu Xun, Email:drxuxun@sjtu.edu.cn; He Mingguang, Email: mingguang_he@yahoo.com
[Abstract] [View PDF in English] [View PDF in Chinese] [Read Full Text]
A repeated low-level red-light (RLRL) therapy has been adopted in research and practice for a nationwide control of childhood myopia. Preliminary clinical evidence has shown that RLRL has an effect on slowing the progression of myopia. However, sub-optimal applications could become a challenge, including an increased risk of potential adverse reactions owing to a lack of consolidated standards. Accordingly, based on current evidence and an expert consensus, the consensus is based on eight aspects including basic mechanism, eligibility, procedures and dosage, clinical examinations, device and power specification, adverse reactions, use termination, and combined use with other treatments. This expert consensus on a RLRL therapy as an alternative treatment for childhood myopia (2022) was developed, with the aim of standardizing this new clinical procedure.
[Key words] Myopia; Alternative treatment; Repeated low-level red light; Children; Adolescents; Consensus
Fund program: National Key R&D Program of China (2021YFC2702100)
International practice guidelines register: http://www.guidelines-registry.cn/, IPGRP-2022CN323
DOI: 10.3760/cma.j.cn115989-20220616-00279
National surveys have indicated that the prevalence of myopia has reached 52.7% among Chinese children and adolescents aged 6-18 years in 20201. The latest national census estimates that more than 100 million of the Chinese population in this age group has developed myopia. Of note, early onset myopia and high myopia are found to be more prevalent in China2. Ocular complications secondary to high myopia are the main causes of irreversible blindness and severe visual impairment3-4. Therefore, the prevention and control of myopia have been a huge challenge for public health and medical institutions, about which the Chinese government are highly concerned, and it has become a national strategy. Currently, low-concentration atropine eye drops, orthokeratology (OK) lenses, defocusing spectacles, and soft contact lenses are commonly used in clinical practice, which can postpone the progression by 30-80%5-7. However, it should be noted that the long-term use of eye drops and contact devices increases the application difficulties and the risks of adverse events to some extent. There is still much room for research on the prevention and control of onset and progression of myopia.
Studies in China and other countries have confirmed that increased outdoor activities can reduce the incidence of myopia in school-aged children. Compared to the control group, the incidence of myopia was reduced by 20-50% after 1-3 years of intervention. The preventive mechanism of outdoor activities on children’s myopia might be related to light exposure, with a dose-effect relationship found between them 8-14. However, in the real-world environments of schools and families, it is still difficult to implement outdoor activity interventions and ensure effective outdoor light exposure. In addition, current evidence shows that outdoor light has a weak effect on the control of myopia progression in children14-15. Based on the principle of light for the prevention of myopia, a multi-center randomized controlled clinical trial was carried out in China on the control of myopia progression by repeated low-level red-light (RLRL) therapy. This provided a high-level evidence for the effectiveness, safety, and compliance of RLRL therapy in the treatment of myopia 16. Meanwhile, several results of other clinical studies have suggested that the RLRL therapy could delay the rapid progression of myopia in children and adolescents16-20. Through a binocular and repeated red-light irradiation, the RLRL therapy is a non-contact complementation for myopia control in children and adolescents, which shows clear effectiveness and has been widely used in the treatment of children with amblyopia21.
RLRL therapy has been used for prevention and control of myopia in several Chinese provinces. The Food and Drug Administration in Jiangsu, Jilin, Hunan, Hainan, and Yunnan has approved the relevant instruments for the adjuvant treatment of myopia. However, the prevention and control of myopia by RLRL therapy is still in the early stages of development. The RLRL instruments produced by different manufacturers have different characteristics. There are still no uniform standards for the indications, specific irradiation time and conditions, operation specifications, outcome evaluation, adverse events of the RLRL therapy, sub-optimal application of the RLRL therapy, and the risk of unreasonable prescription, inappropriate operation, and potential adverse effects are still existing. In order to standardize the application of RLRL therapy in the prevention and control of myopia in children and adolescents, an expert workgroup drafted the “ expert consensus on repeated low-level red-light therapy as an alternative treatment for childhood myopia (2022)”. Based on the published evidence in this field and clinical experience, this consensus is expected to provide guidance for the RLRL therapy in the prevention and control of myopia in children and adolescents.
1 Consensus methodology
According to the application states of RLRL therapy in the prevention and control of myopia in children and adolescents in China, the Shanghai Eye Disease Prevention and Treatment Center organized a nationwide workgroup of expert consensus on RLRL therapy as an adjuvant treatment for childhood myopia from January to March 2022. A total of 38 experts in the fields of fundus disease, optometry, blindness prevention, and public eye health were invited. All the workgroup members participating in the consensus draft met the following criteria: 1) having more than 10 years of related work experience, 2) having senior professional titles, 3) having published high-quality research articles, or being in charge of clinical trials with high-level evidence in the field of ophthalmology.
With respect to the application of RLRL therapy in the adjuvant treatment of myopia in children and adolescents, the consensus workgroup completed an in-depth investigation on its application, and collected, and summarized the key issues in the related processes. Furthermore, the workgroup also fully reviewed and summarized the important published literatures 21-22, and carefully evaluated the available evidence and basis of working principles. After fully scrutinizing and discussing the applicable objects, methods, examination items, adverse events, and discontinuation of RLRL therapy in the control of myopia in children and adolescents, the consensus workgroup drafted and formed the original version of this consensus. Through an online letter review, the original draft was reviewed and revised by all the members of the workgroup in multiple rounds, with 192 discussions and revision opinions received in total. The consensus workgroup carefully considered, sorted, and summarized these opinions, with all the opinions explained. Through partial meetings, the workgroup repeatedly discussed key issues and drafted the final version of this consensus. It took more than six months from inception to the completion of this consensus.
2 Basic principles for the RLRL therapy in the adjuvant treatment of myopia
The principle of RLRL therapy in the adjuvant treatment of myopia has not been fully elucidated. Published clinical trials demonstrated that the choroidal thickness was significantly increased in children and adolescents receiving the RLRL therapy17, which implied that the RLRL ocular irradiation could boost the choroidal blood flow, and subsequently increase the choroidal thickness, microcirculation, and blood supply. The increased choroidal thickness was expected to help mitigate the relative hypoxia in the myopic fundus 23-26, inhibit the excessive elongation of the myopic eye axis, and postpone the development of myopia.
3 Applicable objects of the RLRL therapy in the adjuvant treatment of myopia
3.1 Indications of the RLRL therapy
The RLRL therapy should be prescribed based on the ophthalmologist’s diagnosis and treatment. According to the description of the medical device registration certificate approved for the existing red light irradiation instrument, the RLRL therapy is indicated for myopic children or adolescents aged 3-16 years, especially for those who had rapid myopic progression (≥0.75 D/year). If the patient is insensitive to other anti-myopic treatments, the RLRL therapy should be used with caution under the guidance of a physician in children aged 3-6 years. The RLRL therapy should not be used as a prophylactic treatment in children or adolescents without myopia16-20. If standardized clinical research is planned, an approval should be obtained from the institutional review boards and informed consent should be obtained from the research participants and their guardians. In this case, the upper threshold of the age range and refractive error can be expanded.
3.2 Contraindications for RLRL ocular irradiation
The RLRL therapy is contraindicated in patients with a history of photosensitivity, macular disease, moderate-to-severe dry eye, corneal disease, cataract, vitreoretinal disease, infectious conjunctivitis, uveitis, optic nerve damage, congenital optic nerve dysplasia, or other eye diseases, to avoid serious ocular tissue damage, exacerbation of inflammation, or recurrence. In addition, it is also not recommended to use the RLRL therapy in children or adolescents with autoimmune diseases (such as lupus erythematosus, dermatomyositis, Sjogren’s syndrome, etc.), systemic diseases (such as hypertension, lupus erythematosus, albinism, etc.), other diseases (history of convulsions, tics, incomplete development of the central nervous system, psoriasis, epilepsy, and mental and psychological diseases, etc.). In addition, children or adolescents using low-concentration atropine eye drops for myopia or other cycloplegic agents for optometry examinations should not receive RLRL irradiation.
4 Methods and dosages of RLRL ocular irradiation
The RLRL irradiation should be used for natural pupils. According to previous clinical research, the frequency of RLRL ocular irradiation should not exceed twice a day. Each RLRL irradiation should not exceed 3 min, and the interval between two irradiations should be at least 4 h 16-20. Considering that a 75% compliance of the “twice a day and five days a week” treatment protocol led to approximately 87.7% delay in the progression of myopia16, the weekly exposure to the RLRL irradiation should not exceed 5 days if the frequency of RLRL therapy is set to be twice a day. The frequency of the dose of the RLRL therapy should be determined based on the principle of effective control of myopia progression (for example, the growth of the eye axis in children aged 6-12 years is less than 0.25 mm per year or the growth of myopia is less than 0.50D per year). The effectiveness of individualized intermittent RLRL therapy on the control of myopia in children and adolescents can be observed through standardized clinical research. The RLRL therapy should involve specific steps and protocols in myopia control. To ensure that the frequency and duration are within the instructed ranges of frequency and dose, the treatment parameters should be appropriately set in the RLRL instruments.
5 Ocular examinations and irradiation frequency
Irradiated eyes should be examined regularly before and during the RLRL therapy. The examination items include visual acuity (uncorrected visual acuity, best corrected visual acuity), color vision, intraocular pressure, eye position, anterior segment structure under a slit-lamp, refraction, axial length, corneal curvature, fundus photography, macular optical coherence tomography (OCT), and choroidal thickness. If possible, the following items should also be added: adjustive and collective function, tertiary vision function (simultaneous, fusion, stereoscopic vision), tear film break-up time, tear secretion test, contrast sensitivity, macular optical coherence tomography angiography (OCTA), central visual field, microvisual field, and multifocal electroretinography ( ERG). The first follow-up should be scheduled within the first month after the RLRL therapy, and then at least once every three months. During the RLRL therapy, patients should be aware of the duration of after-image responses (colored aperture after RLRL irradiation) and other adverse events.
6 Instrument selection and power
The RLRL therapy should use instruments that have obtained Category II medical device registration certificate from the Food and Drug Administration. The range of indications should include adjuvant treatment for myopia. According to regulations on the supervision and management of medical devices, the product manual should indicate the properties, wavelength, and power of the light source. The safety and effectiveness of the RLRL instruments should be supported by data and evidence from basic and clinical research.
In published clinical trials, the power of the light source is 2.0+/-0.5mW in most RLRL instruments16,18-20, which should be used under 2mW, and the output power based on approval documents specified by the Food and Drug Administration. According to the national standard (GB 7247.1-2021), the RLRL therapy should be performed in the natural state of the pupil, and intraocular power (light power entering the pupil) should be no more than 0.39mW28. There is no direct relationship between the laser output power and intraocular power, which can be calculated using the power density and pupil diameter measured at the eyepiece position. For example, the power density at the eyepiece is 2 mW/cm2, pupil diameter is 4 mm, and light power entering the pupil is 0.25 mW. To ensure that the RLRL power meets the corresponding standards, manufacturers should regularly examine and calibrate the power of the instrument during the RLRL therapy.
7 Adverse events
According to the published literature, there are no reports of ocular functional and structural damage within the 1-year research period of the RLRL irradiation in adjuvant myopia treatment16. Therefore, whether long-term RLRL irradiation causes ocular structural and functional damage remains unknown. In view of the safety of related interventions, examinations about some sensitive parameters like macular OCT (including choroidal thickness) and mERG should be added in further follow-up studies, to ensure the safety of the irradiated eyes to the greatest extent. An after-image response may occur during the RLRL eye irradiation process, and some children and adolescents cannot tolerate long-lasting after-images. According to the current practical experience, patients with after-images lasting for more than 6 min should receive close attention. If a prolonged after-image repeatedly appears in the irradiated eye, the duration of the after-image should be recorded. Related examinations of fundus function and structure (such as ERG, macular OCTA, visual field, and macular OCT, etc.) should be conducted under the guidance of a professional doctor. The irradiation frequency or dosage should be adjusted, and the RLRL therapy should be stopped if necessary. In addition, there have been cases of RLRL intolerance due to eyelid skin allergy and red light glare. As for rare cases with prolonged after-images, fractured ellipsoid bands, or central dark spots (approximately 1 in 20,000 based on preliminary estimation), the RLRL therapy should be terminated in time and medical consultation should be sought in this situation; whether it is related to RLRL irradiation requires further research. The above situations are summarized based on personal experiences and suggestions of the workgroup members, who have not been involved in the published research. At present, there are few reports of adverse events following the RLRL irradiation. Whether long-term RLRL therapy produces cumulative retinal structural damage or leads to functional changes in retinal electrophysiology, visual field, contrast sensitivity, and color vision has not been reported, and long-term observation and research are still required in further studies.
8 Treatment termination
In the process of adjuvant myopia treatment, the RLRL therapy should be discontinued if there are any abnormalities, including long-lasting after-images, short-term severe loss of visual acuity, persistent halo, scotoma, any retinal structural damage or retinal electrophysiology, visual field, contrast sensitivity, or color vision changes. In addition, the doctor should instruct the patient to stop the treatment and seek timely consultation if there is any discomfort in the eye. As for ineffective RLRL therapy and patients with unsatisfactory effectiveness (myopia increases rapidly by 0.75 diopters/year) 27, the treatment protocol should be adjusted based on the doctors’ judgement. After rapid progression of myopia in children and adolescents, it can be discontinued. When considering discontinuation, the dosage of RLRL irradiation can be gradually reduced. The ocular axial length should be examined after the first and third months of discontinuation, and the follow-up period should be no less than half a year29.
9 Problems in combined application with other methods
Regarding the combined application of the RLRL therapy and other treatments, the workgroup members suggested that: (1) Outdoor activities: the RLRL therapy cannot replace outdoor activities, and outdoor activities have a positive effect on preventing myopia in children and adolescents, and promoting general physical and mental health 8-11,14,30. The RLRL therapy can be performed simultaneously as an outdoor intervention to control myopia. (2) Low-concentration atropine eye drops: As atropine eye drops have a certain pupil dilation effect, the dosage of red light entering the eye could be uncontrollable after the use of atropine. The combination of the two therapies is not recommended according to the available evidence. (3) Orthokeratology lenses, mono-focal spectacles, defocus-designed spectacles, and soft/hard contact lenses: As the use of these glasses does not theoretically cause a change in the RLRL irradiation dosage, these therapies could be used in combination. However, combined use should be conducted under the guidance of medical specialists. The contact lenses should be removed before the RLRL irradiation.
10 Summary
This consensus is based on eight aspects: basic principles, applicable objects, methods and dosages, examination items and frequency, instrument selection and power, adverse events, treatment termination, and combined application of other treatments of RLRL therapy in the control of myopia progression. According to the available clinical research evidence, myopia treatment by the RLRL ocular irradiation has a certain effect within a 1-year range, and is expected to be a new adjuvant treatment for the prevention and control of myopia in children and adolescents. However, the mid- and long-term effectiveness and safety of the RLRL therapy require further investigation. Its effective threshold, optimal dosage, regression or rebound of myopia after RLRL discontinuation, safety threshold, and mechanism need to be determined and elucidated. In current research and practice, the indications for the RLRL ocular irradiation should be carefully controlled. To ensure the eye health and safety of children and adolescents in the first place, changes in ocular parameters should be closely monitored during follow-up.
Disclaimer: This article mainly consists of expert opinions and suggestions that provide guidance for clinical research and medical services. This article should not be considered a standard that must be followed in all situations. This article has no economic interest related to the manufacturers and resellers of relevant instruments.
Members of the expert workgroup:
Writing experts
Xu Xun Shanghai Eye Disease Prevention and Treatment Center, First People’s Hospital Affiliated to Shanghai Jiaotong University, National Eye Disease Clinical Research Center
He Mingguang Zhongshan Ophthalmology Center Sun Yat-sen University, State Key Laboratory of Ophthalmology, University of Melbourne
He Xiangui Shanghai Eye Disease Prevention and Treatment Center, First People’s Hospital Affiliated to Shanghai Jiaotong University, National Eye Disease Clinical Research Center
Experts participating in the consensus draft
(Sorted by last name, in no particular order)
Ma Jun Institute of Child and Adolescent Health of Peking University
Wang Xiaojuan The First Peoples’ Hospital of Xuzhou
Wang Yusheng Xijing Hospital, Air Force Medical University
Wang Kai Peking University People’s Hospital
Wen Feng Zhongshan Ophthalmology Center, Sun Yat-Sen University
Shi Lei The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
Bi Hongsheng Eye Institute of Shandong University of Traditional Chinese Medicine
Bi Yanlong Tongji Hospital Affiliated with Tongji University School of Medicine
Lyu Hongbin Affiliated Hospital of Southwest Medical University
Zhu Jianfeng Shanghai Eye Disease Prevention and Treatment Center
Zhu Yihua The First Affiliated Hospital of Fujian Medical University
Zhuang Wenjuan People’s Hospital of Ningxia Hui Autonomous Region
Liu Longqian West China Hospital, Sichuan University
Liu Yong First Affiliated Hospital of Chinese People’s Liberation Army General Hospital
Xu Yan Shanghai Eye Disease Prevention and Treatment Center
Du Chixin The First Affiliated Hospital, College of Medicine, Zhejiang University
Li Li Beijing Children’s Hospital, Capital Medical University
Yang Xiao Zhongshan Ophthalmology Center, Sun Yat-Sen University
Wu Xixi The First Affiliated Hospital of Guangxi University of Chinese Medicine
Zou Haidong Shanghai First People’s Hospital, Affiliated Shanghai Jiaotong University
Zhang Mingzhi Shantou International Eye Center
Lu Fang West China Hospital, Sichuan University
Chen Zhi Eye and Ear Nose and Throat Hospital, Fudan University
Yi Hong Chongqing General Hospital
Yi Jinglin Affiliated Eye Hospital of Nanchang University, Nanchang University
Zhou Xiyuan The Second Affiliated Hospital of Chongqing Medical University
Zhou Lei Ningbo Eye Hospital
Zhong Hua The First Affiliated Hospital of Kunming Medical University
Rong Weining People’s Hospital of Ningxia Hui Autonomous Region
Tao Fangbiao School of Public Health, Anhui Medical University
Tao Liming The Second Affiliated Hospital of Anhui Medical University
Zeng Junwen Zhongshan Ophthalmology Center, Sun Yat-Sen University
Tan Xingping Eye Center of Xiangya Hospital, Central South University
Pan Chenwei School of Public Health, Medical College of Soochow University
Wei Ruihua Tianjin Medical University Eye Hospital
Conflict of interest Professor He Mingguang is the inventor of the relevant red light technology patent (CN110237432A). Professor He Mingguang is also the director and stock holder of Suzhou Xuanjia Optoelectronics Technology Co. Ltd. and Eyerising International Pty Ltd.
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