Background To study how clinical and genetic factors control the effectiveness of orthokeratology lenses in myopia. Methods In this study, we conducted a retrospective clinical study of 545 children aged from 8 to 12 years with myopia who were wearing orthokeratology lenses for one year and performed whole-genome sequencing (WGS) for 60 participants in two groups, one with rapid axial length progression of larger than 0.33 mm and the other with slow axial length progression of less than 0.09 mm. Genes in the RetNet database were used to screen candidate genes that may contribute to the effectiveness of orthokeratology lenses in controlling myopia. Results We found that children with a greater baseline eye axial length, greater spherical equivalent (SE) and greater age had better myopia control with orthokeratology. We observed a significant excess of nonsynonymous variants among those with slow myopia progression, which were prominently enriched in retinal disease related genes. We subsequently identified RIMS2 (OR=0.01, p=0.0075) and LCA5 (OR=6.96, p=0.0080) harboring an excess number of nonsynonymous variants in patients with slow progression of high myopia. Two intronic common variants rs36006402 in SLC7A14 and rs2285814 in CLUAP1 were strongly associated with axial length growth. Together, our finding identified novel genes associated with the effectiveness of orthokeratology lenses therapy in myopic children and provide insight into the genetic mechanism of orthokeratology treatment. Conclusion The effectiveness of orthokeratology lenses treatment involved interindividual variability in controlling axial length growth in myopic eyes. The efficacy increased when patients carried more nonsynonymous variants in retinal disease-related gene sets. Our data will serve as a well-founded reference for genetic counseling and better management of patients who choose orthokeratology lenses to control myopia.

The authors have declared no competing interest.

This study did not receive any funding

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Ethics committee of Wenzhou Eye and Vision Hospital gave ethical approval for this work

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All data produced in the present study are available upon reasonable request to the authors