A groundbreaking genetic study has uncovered new insights into why orthokeratology lenses, an innovative treatment increasingly used to slow the progression of myopia in children, work more effectively in some patients than others. This research, representing the largest genome-wide examination of its kind, reveals that the differential response to orthokeratology is linked to specific genetic variants associated with retinal function. The findings herald a new era in personalized myopia management, potentially enabling clinicians to tailor treatments based on a child’s unique genetic profile.
Myopia, or nearsightedness, has emerged as a global epidemic, particularly afflicting populations in East and Southeast Asia. With the prevalence continuing to rise, the demand for effective myopia control measures has intensified. Orthokeratology involves the overnight wearing of specially designed contact lenses that temporarily reshape the cornea, thereby reducing axial elongation—a principal driver of myopia progression. While clinical parameters such as age and initial myopia degree have provided some guidance on who benefits most from orthokeratology, these traditional predictors fall short of fully explaining patient variability.
Increasing evidence points to the retina as a critical player in regulating eye growth and refractive development. This knowledge prompted researchers from Wenzhou Medical University’s National Clinical Research Center for Ocular Diseases, in collaboration with PSI Genomics, to investigate whether genetic differences in retinal-related genes could underpin the varied efficacy of orthokeratology. By analyzing whole-genome sequencing data from 545 children aged 8 to 12 who used orthokeratology lenses for a year, the team sought to untangle the complex genetic factors linked to treatment response.
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The study employed a targeted approach focusing on genes cataloged in the RetNet database, which is known to include genes implicated in inherited retinal diseases. Initial clinical analysis confirmed that older children, those with higher spherical equivalent (SE) refractive errors, and longer baseline axial lengths exhibited better control of myopia progression under orthokeratology treatment. However, these variables alone could not account for the full spectrum of treatment outcomes observed.
Zooming in on genetic data, the researchers selected 60 children at the extremes of treatment response—those with particularly effective control of axial elongation and those with poor results. Strikingly, children benefiting most had a significantly higher number of nonsynonymous mutations—mutations that alter protein structure—in genes related to retinal development and signaling pathways. This implies that retinal genetic architecture may influence how effectively orthokeratology modulates eye growth.
Two genes, in particular, emerged as key influencers: RIMS2 and LCA5. The RIMS2 gene, more frequently mutated in poor responders, encodes a protein associated with synaptic function in rod photoreceptors, influencing contrast sensitivity. Rod photoreceptors play a crucial role in dim lighting but also participate in signaling pathways that regulate eye growth. Conversely, LCA5, enriched in the group with favorable treatment outcomes, is essential for photoreceptor maintenance, specifically in cones, which are vital for color vision and sharp central vision. Variations in this gene suggest enhanced photoreceptor support could underlie better responsiveness to corneal reshaping interventions.
Further fine-mapping identified specific single nucleotide polymorphisms (SNPs) within SLC7A14 (rs36006402) and CLUAP1 (rs2285814) that associate significantly with axial elongation rates during orthokeratology treatment. SLC7A14 is involved in amino acid transport in photoreceptors, while CLUAP1 plays a role in cilia function—both critical in maintaining retinal cellular health and signaling. These findings underscore the sensory retina’s active role in governing eye growth modulation and, by extension, treatment efficacy.
These revelations mark a pioneering implementation of genome-wide genetic profiling to explain individual variability in orthokeratology success, bridging clinical ophthalmology with molecular genetics. The study’s authors highlight the translational potential of this work to usher in precision ophthalmology, where genetic screening may one day guide clinicians in predicting who will benefit from orthokeratology before initiating treatment, thereby optimizing therapeutic outcomes.
Dr. Xinjie Mao, co-corresponding author of the study, emphasized the transformative promise of integrating genetics into myopia management. He noted that children exhibiting rapid eye growth—most at risk for sight-threatening complications later in life—might be monitored more closely or offered alternative interventions if genetic markers predict a less favorable response to orthokeratology. Such a stratified approach would minimize ineffective treatment trials and maximize resource use.
Moreover, these genetic insights could catalyze the design of next-generation orthokeratology lenses or adjunct therapies tailored to the underlying retinal biology. For example, combining low-dose atropine, a pharmacologic agent proven to slow myopia progression, with lens designs informed by a patient’s genetic profile could magnify therapeutic efficacy. This comprehensive strategy would move beyond the conventional one-size-fits-all approach, creating customized treatments that address both corneal biomechanics and retinal signaling.
While the study paves the way for the integration of genetics into clinical eye care, the authors acknowledge the necessity of larger scale, multi-ethnic cohorts to validate the predictive utility of the identified gene variants. Such expansive research will also clarify how these genetic variants interact with environmental factors, such as near-work activities and outdoor exposure, which are known contributors to myopia development.
The implications extend beyond clinical care into public health policy, particularly in countries facing a myopia crisis. Early genetic screening in pediatric populations could identify children at heightened risk for rapid myopia progression who would benefit most from early orthokeratology intervention or alternative strategies. This proactive, genetics-informed framework could play a vital role in curbing the personal and societal burdens of high myopia, including its association with retinal detachment, glaucoma, and macular degeneration.
In summary, this landmark study offers critical evidence that genetic polymorphisms in retinal-related genes significantly affect the success of orthokeratology in controlling myopia progression. By elucidating the molecular underpinnings of treatment variability, it sets the stage for a paradigm shift toward personalized, genetics-driven myopia management in pediatric ophthalmology. The convergence of genomic technologies and clinical practice holds immense promise for mitigating the global myopia epidemic through more effective, targeted interventions.
Subject of Research: Not applicable
Article Title: Associations between RetNet gene polymorphisms and the efficacy of orthokeratology for myopia control: a retrospective clinical study
News Publication Date: 17-Mar-2025
Web References: http://dx.doi.org/10.1186/s40662-025-00426-4
References: DOI: 10.1186/s40662-025-00426-4
Image Credits: Eye and Vision
Keywords: Health and medicine
Tags: axial elongation in myopiachildren’s nearsightedness solutionsclinical predictors of myopia responsecontact lenses for myopia controlEast Asia myopia epidemicgenetic factors in myopia treatmentgenome-wide studies on myopiainnovative treatments for nearsightednessmyopia managementorthokeratology lenses effectivenesspersonalized myopia careretinal function and eye growth