Genetic Influences and Treatment Response in Myopia

Orthokeratology lenses have become an increasingly popular strategy to slow myopic progression, yet substantial interindividual variability in their effectiveness remains. A recent study investigated both clinical and genetic determinants influencing the success of orthokeratology in controlling axial length (AL) elongation among children with myopia. This retrospective study included 545 children aged 8 to 12 who wore orthokeratology lenses for one year. It revealed that older age, higher baseline axial length, and greater baseline spherical equivalent (SE) refractive error were associated with better control of AL growth. Specifically, older children with higher degrees of myopia at baseline experienced less axial elongation, a finding that aligns with previous reports suggesting that natural age-related slowing of eye growth may augment the lens effect, and that eyes with longer initial AL might have already entered a slower phase of elongation. These insights underscore the importance of carefully selecting candidates for orthokeratology and considering adjunctive strategies—such as low-dose atropine—in younger or less myopic patients to achieve optimal control.

In addition to clinical predictors, this study provided the first genetic exploration into differential orthokeratology outcomes by leveraging whole-genome sequencing (WGS) on a subset of 60 participants. By comparing 30 children with well-controlled myopia progression (annual AL growth ≤0.09 mm) to 30 children with poor control (annual AL growth ≥0.33 mm), researchers identified significant enrichment of nonsynonymous variants in genes related to retinal disease (cataloged in the RetNet database) among those with slower myopia progression. Notably, variants in the genes RIMS2 and LCA5 were strongly implicated. RIMS2, predominantly expressed in retinal rod cells and critical for synaptic function, was associated with reduced effectiveness of orthokeratology, while LCA5 variants appeared to support better control of axial elongation. These findings suggest that genetic differences influencing retinal signaling and photoreceptor integrity could modulate the retina’s response to peripheral defocus induced by orthokeratology lenses.

Moreover, single-nucleotide polymorphism (SNP) analysis identified two intronic variants with significant associations: rs36006402 in SLC7A14, linked to decreased AL growth, and rs2285814 in CLUAP1, linked to increased AL growth. Both genes play roles in retinal development and photoreceptor maintenance, supporting the hypothesis that the retina’s ability to process contrast and focus cues may underlie differences in treatment response. While these results are intriguing, the authors acknowledge limitations, including a relatively small genetic sample size and a one-year follow-up period, emphasizing the need for larger, prospective studies to validate these genetic associations and explore longer-term outcomes.

Taken together, this study advances the understanding of why orthokeratology lenses work more effectively in some children than others by highlighting both phenotypic factors—such as age, baseline axial length, and SE—and novel genetic contributors tied to retinal structure and function. This emerging evidence could ultimately inform more personalized treatment strategies for myopia control, guiding clinicians in identifying which patients might benefit most from orthokeratology alone versus those who may require combined therapeutic approaches. It also opens the door to genetic counseling considerations for families considering orthokeratology, underscoring the potential of integrating genomic data into routine ophthalmic care to better manage myopia’s long-term risks.