Safety analysis of repeated low-level red light therapy on cone mosaic and microvasculature by adaptive optics scanning laser ophthalmoscopy

PURPOSE: Despite the growing use of repeated low-level red light (RLRL) therapy for myopic children, its safety remains controversial. This study aimed to analyze macular cone morphology and retinal microvascular hemodynamics using adaptive optics scanning laser ophthalmoscopy (AOSLO) to evaluate retinal microstructural impacts. DESIGN: Cross-sectional study. METHODS: Three groups were recruited: Myopia-RLRL (20 eyes; ≥8 months treatment), Myopia-Untreated (32 eyes), and Non-Myopic (14 eyes). RLRL therapy was administered using a 650 nm laser at 0.29 mW, twice daily for 3 min per session. AOSLO was used to assess cone morphology (density, spacing, regularity, dispersion) and retinal microvasculature parameters (vessel diameter, lumen diameter, blood flow velocity). RESULTS: Cone density was higher in the Non-Myopic group (45,649 ± 5092/mm²) compared to the Myopia-Untreated group (40,202 ± 7365/mm², P = 0.013), with no significant difference versus the Myopia-RLRL group (41,274 ± 6228/mm², P = 0.627). Cone spacing was enlarged in myopic groups relative to non-myopic (P < 0.05). Cone dispersion was lower in the Myopia-RLRL group (16.47 ± 2.43%) than in the Myopia-Untreated (17.36 ± 2.14%, P = 0.030) and Non-Myopic (17.80 ± 2.25%, P = 0.024) groups. No significant intergroup differences were found in cone regularity or microvasculature. Cone density positively correlated with spherical equivalent refraction (r = 0.541) and negatively with axial length (r=-0.594; both P < 0.001). CONCLUSIONS: After 8 months of RLRL therapy, there was no significant loss of cone density or issues with retinal microvasculature. Assessment of retinal arteriole and venule diameters and flow velocity also showed no significant differences. The reduced cone dispersion in the RLRL group suggests potential photobiomodulation effects on photoreceptor organization, indicating the therapy's safety and potential benefits.