Boosting orthokeratology efficacy with repeated low-level red light

Paper title: Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial

Authors: Xiong, Ruilin (1), Wang, Wei (1), Tang, Xianghua (1), He, Meinan (2), Hu, Yin (1), Zhang, Jian (1), Du, Bei (2), Jiang, Yu (3), Zhu, Zhuoting (4), Chen, Yanping (1), Zhang, Shiran (1), Kong, Xiangbin (5), Wei, Ruihua (6), Yang, Xiao (7), He, Mingguang (8).

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, Guangdong, China
2. Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
3. Department of Ophthalmology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
4. Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia
5. Ophthalmology, Department of Surgery, The Second People's Hospital of Foshan, Foshan, Guangdong, China
6. School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong
7. Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Kowloon, Hong Kong
8. Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong

Date: May 2024

Reference: Xiong R, Wang W, Tang X, He M, Hu Y, Zhang J, Du B, Jiang Y, Zhu Z, Chen Y, Zhang S, Kong X, Wei R, Yang X, He M. Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial. Ophthalmology. 2024 May 17: S0161-6420(24)00308-7

[Link to abstract]

Orthokeratology (Ortho-K) uses reverse geometry design gas permeable lenses to temporarily reshape the corneal with overnight wear. This provides myopia management for children via the induced relative myopic peripheral defocus and eliminates the need for daytime optical correction.^1,2 However, some studies have found that 15% of children wearing Ortho-K may still show fast axial progression of 0.36mm or more per year.^3,4 

As an emerging alternative for myopia control, repeated low-level red-light (RLRL) therapy has demonstrated efficacy in slowing axial elongation by 69 and 75% over 1- and 2-year studies respectively, compared to single vision spectacle lenses.^5,6

This randomised, parallel-group study investigated the efficacy and safety of combining RLRL and Ortho-K for myopic children, across 3 hospital sites in China.

Children aged 8-13yrs with cycloplegic spherical equivalent refraction of between -1.00 and -5.00D who had experienced at least 0.5mm axial elongation over the previous year while wearing Ortho-K lenses were recruited to the study;. They were randomised in a 2:1 ratio to receive RLRL therapy for 3 minutes twice daily in addition to wearing Ortho-K lenses (RCO group, n = 31) or to continue with Ortho-K lenses only (orthokeratology group, n = 17).

Adverse events and safety were assessed at each follow-up and questionnaires to assess responses such as discomfort and dry eye, short-term glare and after-images were completed by participants or parents. Serious adverse events were defined as scotoma in the central visual field or sudden visual loss of at least 2 lines.

• The mean axial length growth prior to the trial was 0.060mm/year in the RCO group and 0.61mm/year for the Ortho-K group.
• At 12mths, the adjusted mean axial length changes were ‐0.02mm in the RCO group and 0.27mm in the Ortho‐k group (an adjusted mean difference of -0.29mm). Axial elongation was continuous but slower for the Ortho-K group throughout the study period than in the previous year, but a reduction in axial length was seen in the RCO group during the first 6mths of the study and maintained slower growth in the second 6mths compared to the Ortho-K group and the baseline measurement.
• Adverse responses such as dry eye and tearing following initial RLRL therapy were found to be transient only initially, and were not reported during subsequent RLRL therapy.

Similar findings were noted in both groups for changes in central corneal thickness, aqueous depth and lens thickness and both groups maintained visual quality. However, compared to baseline values, choroidal thickness was seen to increase by 14.2% in the RCO group and decrease by 3.3% in the Ortho-K group.

 Orthokeratology is already popular for myopia control, due to the additional benefit of providing children with correction-free daytime vision. Combining Ortho-K with RLRL appears to offer a safe method of further reducing axial length growth, a key factor in myopia progression, leading to a greater myopia control effect than Ortho-K alone.

1. The participants all experienced 0.5mm axial length growth in the year prior to joining the study, while wearing Ortho-K lenses. This criteria limits the scope of the generalisation to a wider population who will experience varying axial elongation before commencing combined RLRL and Ortho-K therapy.
2. There was a greater control of axial elongation in the RCO combined group during the first 6-mths before this effect reduced, suggesting there may be a time-dependent response and the choroid was found to become thicker with combined RLRL and Ortho-K, but thinner with Ortho-K alone. Further studies with a placebo group could provide evidence of the underlying mechanisms for RLRL enhancing the myopia control effect and the role of the choroid in limiting axial elongation.
3. The study found the combination of RLRL and Ortho-K was well-tolerated, however, longer studies and continuous monitoring are needed to establish a safety profile.

Title: Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial

Authors: Ruilin Xiong; Wei Wang; Xianghua Tang; Meinan He; Yin Hu; Jian Zhang; Bei Du; Yu Jiang; Zhuoting Zhu; Yanping Chen; Shiran Zhang; Xiangbin Kong; Ruihua Wei; Xiao Yang; Mingguang He

Purpose: To investigate the efficacy and safety of repeated low-level red-light (RLRL) therapy combined with orthokeratology among children who, despite undergoing orthokeratology, exhibited an axial elongation of at least 0.50 mm over 1 year.

Methods: Eligible children were 8-13 years of age with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters at the initial orthokeratology fitting examination and had annual axial length (AL) elongation of ≥0.50 mm despite undergoing orthokeratology. Forty-eight children were enrolled from March 2021 through January 2022, and the final follow-up was completed in March 2023.

Children were assigned randomly to the RLRL therapy combined with orthokeratology (RCO) group or to the orthokeratology group in a 2:1 ratio. The orthokeratology group wore orthokeratology lenses for at least 8 hours per night, whereas the RCO group received daily RLRL therapy twice daily for 3 minutes in addition to orthokeratology.

The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 follow-up after randomization using the modified intention-to-treat principle.

Results: Forty-seven children (97.9%) were included in the analysis (30 in the RCO group and 17 in the orthokeratology group). The mean axial elongation rate before the trial was 0.60 mm/year and 0.61 mm/year in the RCO and orthokeratology groups, respectively. After 12 months, the adjusted mean AL changes were -0.02 mm (95% confidence interval [CI], -0.08 to +0.03 mm) in the RCO group and 0.27 mm (95% CI, 0.19-0.34 mm) in the orthokeratology group. The adjusted mean difference in AL change was -0.29 mm (95% CI, -0.44 to -0.14 mm) between the groups. The percentage of children achieving an uncorrected visual acuity of more than 20/25 was similar in the RCO (64.3%) and orthokeratology (65.5%) groups (P = 0.937).

Conclusions: Combining RLRL therapy with orthokeratology may offer a promising approach to optimize axial elongation control among children with myopia. This approach also potentially allows children to achieve satisfactory visual acuity, reducing daytime dependence on corrective eyewear.

[Link to abstract]