Axial Shortening Effects of Repeated Low-level Red-light Therapy in Children with High Myopia: A Multicenter Randomized Controlled Trial

To evaluate the effectiveness and safety of repeated low-level red-light (RLRL) in delaying the progression of high myopes with -6.00 diopters (D) or worse. Multicenter, randomized, parallel-group, single-blind clinical trial. A total of 202 high myopic children aged 7 to 12 years with cycloplegia spherical equivalent (SE) refraction ≤-6.00 D, astigmatism less than 2.50 D, and anisometropia of 1.50 D or less were enrolled from March 2022 to December 2022. Follow-up was completed in December 2023. Eligible participants were randomly allocated to the intervention (RLRL + single vision spectacle) or the control group (single vision spectacle). The RLRL treatment was administered every day for 3 minutes, twice a day, with an interval of at least 4 hours. The primary outcome was the change in axial length (AL) at 12 months compared with baseline. Secondary outcomes included changes in SE, changes in choroidal thickness (ChT), and changes in retinal thickness (RT) in different circle sectors. Outcomes were analyzed by means of intention-to-treat and per-protocol methods. After 12 months of treatment, AL and SE changes were -0.11 ± 0.25 mm and 0.18 ± 0.63 D for the RLRL group and 0.32 ± 0.09 mm and -0.80 ± 0.42 D for the control group, respectively. Axial shortening >0.05 mm was 59% in the RLRL and 0% in the control group at 12 months. ChT and RT from a single center were analyzed. In the RLRL group, ChT was thickened in all sectors at 12 months. RT was increased in parafoveal and perifoveal circles. In the control group, all sectors of ChT and only perifoveal RT were significantly thinner at 12 months. The multivariate linear regression model revealed significant correlations between changes in the ChT central foveal circle and RT perifoveal circle at 1 month and AL changes at 12 months. No fundus structure changes, afterimage exceeding 6 minutes, or best-corrected visual acuity decrease were reported. RLRL could effectively shorten the AL and inhibit the progression of myopia in high myopic patients with -6.00 D or worse. AL shortening is sustained over 12 months of treatment. These observed changes appeared to be associated with increases in ChT and RT.