**Background:** Myopia is a growing global public health problem, with prevalence projected to reach ~50% (4.8 billion people) by 2050. Current interventions such as atropine, orthokeratology, and multifocal lenses have limited efficacy (30-60%) and side effects. Repeated low-level red-light (RLRL) therapy has emerged as a novel approach, leveraging photobiomodulation (PBM) to influence cellular bioenergetics. This review synthesizes evidence on RLRL's mechanisms, clinical efficacy, and safety for myopia control.
**Methods:** The authors conducted a narrative review of the literature, covering preclinical studies (animal models including chicks, guinea pigs, tree shrews, mice, and monkeys) and clinical trials (primarily from China). Key clinical trials summarized include randomized controlled trials (RCTs) by Jiang et al. (2022, 12 months, n=264), Dong et al. (2022, 6 months, n=111), Chen et al. (2022, 12 months, n=62), and Tian et al. (2022, 6 months, n=224), as well as a post-trial follow-up by Xiong et al. (2022, 24 months, n=199). The review also discusses mechanistic studies on cytochrome c oxidase (CCO), dopamine (DA), nitric oxide (NO), and choroidal changes.
**Key Results:** Clinical trials consistently demonstrate that RLRL therapy significantly reduces axial elongation and spherical equivalent refraction (SER) progression compared to controls. For example, Jiang et al. reported adjusted 12-month axial elongation of 0.13 mm (95% CI: 0.09-0.17 mm) in the RLRL group vs. 0.38 mm (0.34-0.42 mm) in the single-vision spectacle (SVS) group, with SER progression of -0.20 D (-0.29 to -0.11 D) vs. -0.79 D (-0.88 to -0.69 D). Dong et al. found mean 6-month SER change of 0.06 ± 0.30 D in RLRL vs. -0.11 ± 0.33 D in sham control, and axial length (AL) increase of 0.02 ± 0.11 mm vs. 0.13 ± 0.10 mm. Chen et al. reported RLRL was more effective than 0.01% atropine, with 1-year AL change of 0.08 mm vs. 0.33 mm. Xiong et al. showed continued RLRL over 2 years sustained efficacy (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79 D) with a modest rebound after cessation. Wang et al. (2023, retrospective, n=434) found that 26.50% of children had AL shortening ≥0.05 mm/year, with mean AL change of -0.142 mm/year. No severe adverse events (e.g., vision loss, structural damage) were reported across studies. Mechanistically, RLRL is proposed to act via CCO activation, increasing ATP production, enhancing DA and NO release, improving choroidal blood flow, and promoting scleral remodeling through TGFβ/Smad signaling.
**Clinical Implications:** RLRL therapy represents a promising, non-invasive, and well-tolerated intervention for myopia control in children, with efficacy comparable or superior to low-dose atropine and other optical methods. The therapy appears to induce choroidal thickening and, in some cases, axial shortening, suggesting effects on posterior segment structures. However, limitations include short follow-up durations (mostly 6-12 months), lack of masking in some trials, potential rebound after cessation, and generalizability primarily to Chinese children. Long-term safety, optimal treatment parameters (wavelength, power, duration, frequency), and efficacy in high myopia or for preventing myopia onset remain to be established. Comparative studies with other treatments (e.g., atropine, DIMS lenses) are needed.