Orthokeratology and retinal risk: a new dimension in myopia control

The prevalence of myopia is on the rise worldwide, with a surge in development during the recent decades. It is currently estimated to affect up to one-third of the global population, with an even higher prevalence among the younger generations and in East Asian countries. Current projections estimate a prevalence of nearly half the global population by 2050 (1). This raises concerns due to the potential ocular health implications associated with the development of myopia. The risk of conditions such as myopic macular degeneration, open-angle glaucoma, and retinal detachment increases in correlation with the degree of myopia and can result in severe visual complications (2). It is therefore vital to identify potential children at risk of myopic progression and intervene early.

Over the past decade, an increasing amount of research and evidence are built around preventative measures to dampen the myopic progression and thereby the resulting complications, rather than solely focusing on benign refractory correction. Several variables, including demographic and environmental factors such as age of onset, baseline refractive error, parental myopia, near-work, and time spent outdoors, have been established as risk factors (3-5). While these factors remain clinically relevant, they provide limited insight into the biological mechanisms driving axial elongation, a key factor to improve more personalized preventative measurements. In recent years, evidence has accumulated that the retina plays an active role in regulating eye growth, acting as both a sensor and effector in response to visual stimuli such as defocus and contrast gradients (6,7). Experimental studies and animal models have demonstrated that the retinal neurons are able to detect focus and defocus, and in a physiological complex association with the retinal pigment epithelium and choroid can initiate signaling pathways that regulate ocular growth (8,9).

Additionally, previous electrophysiological studies indicate that children with myopia, and those who later develop myopia, exhibit reduced central inner retinal responses on multifocal electroretinography (mfERG) compared with emmetropic peers (10,11).

Current treatment strategies for controlling myopic progression

Several different treatment options are currently implemented to reduce myopic progression in children. They are generally divided into two main subgroups of regimens—pharmacological and optical management. Pharmacological treatment is mainly based upon the use of topical atropine in various dosing regimens ranging from high- to low-dose and has been widely used through many years despite being debated in pediatric ophthalmology due to current evidence showing variable efficacy in reducing myopic progression in children and potential adverse events. The current evidence does, however, point towards a decrease in myopic progression with few adverse events using low-dose atropine (12-15), but also a potential myopic rebound after stopping the treatment (16).

Optical regimens currently consist of different types of lenses such as single vision (SV) lenses, multifocal lenses, defocus lenses, highly aspherical lenslets (HAL), and orthokeratology (OK) lenses. The primary mechanism of action by the subgroup of optical treatments utilizing myopic defocus is thought to be related to the aforementioned retinal regulation of eye growth by implementing a myopic defocus on the mid-peripheral retina while maintaining refractive correction on the central retina. Current data indicate overall reduced myopic progression by these interventions compared to controls (15,17,18).

OK lenses are rigid gas-permeable lenses worn overnight to temporarily reshape the corneal topography in order to change refractive power throughout the day, hence eliminating the need for additional refractive correction. Studies show promising results in halting myopic progression (15,19,20). There also appears to be increasing evidence of a synergistic effect of combining a pharmacological and optical treatment regimen to reduce myopic progression even further (18,21,22).

Another more novel treatment modality is repeated low-level red light (RLRL) therapy that aims to reduce axial elongation by repeated exposure of red wavelength light onto the retina. This is thought to enhance choroidal and retinal blood flow and ultimately limit axial elongation. Studies have shown a reduction in myopic progression, but also potential adverse events (23,24). Current consensus warrants further research due to non-standardized protocols and potential risks associated with the treatment (25).

Central inner retinal response as a prognostic biomarker?

The recently published study by Choi et al. further expands existing evidence reinforcing an association between retinal electrophysiology and axial elongation in myopic children. Here, the group enrolled 91 myopic children aged 8–12 years in a randomized, single-blind, parallel-controlled trial that randomized the patients into either treatment with SV lenses or OK lenses. At baseline, retinal function was evaluated using global-flash mfERG (MOFO mfERG). Patients were evaluated at 6-month intervals up to 24 months of follow-up with measurements of axial elongation.

In their study, they demonstrate, as previously established, an association between a weak inner central retinal response on mfERG and risk of myopic progression. Their results demonstrated this to be true despite treatment with SV lenses. However, no significant difference was observed in the arm treated with OK lenses, indicating that OK lenses could eliminate a reduced inner central retinal response as a risk factor for myopic progression in children (26).

Similarly, prior work by the same research group demonstrated a significant interaction between baseline retinal electrophysiology and atropine response; children with weaker retinal responses benefited more, while those with stronger baseline retinal function showed little benefit. Instead, their analysis surprisingly demonstrated a potential accelerated myopic progression using low-dose atropine, suggesting that atropine treatment in the wrong population could potentially worsen myopic progression (27).

Their new study provides additional important insights and considerations in myopia treatment going forward. Their findings, in addition to previous results, indicate promising effects of an optical regimen, specifically OK lenses, in preventing myopic progression by utilizing mfERG measurement to stratify patients into the best possible individual treatment plan. While this is notable, certain aspects of the study should be considered. First, a total of 70 patients completed the follow-up out of the 91 enrolled patients, with a larger percentage of dropouts in the SV group, potentially increasing the risk of attrition bias. At the same time, this makes the subgroup at 24-month follow-up smaller, which increases the spread in the endpoint data. In addition to that, certain visits were delayed due to the coronavirus disease 2019 (COVID-19) pandemic, and they adjusted for this in their analysis by dividing axial elongation by time and interpolating to 12- and 24-month follow-up, respectively. This, however, assumes linear growth over time that does not necessarily translate correspondingly to real-world data. Second, it is not common practice in general pediatric ophthalmology to routinely use mfERG for the assessment of children. Some practical and logistical challenges therefore have to be considered to transfer these results into clinical practice going forward.

Additionally, to improve the generalizability of these findings, further research in non-Asian populations is required to determine whether the same associations are applicable worldwide. A previous study has shown differences in response to treatment regimens when comparing East Asian and European populations (28). The underlying mechanisms of this phenomenon remain unclear, as few studies have examined this issue, and the majority of research on myopic progression has been conducted on an Asian population.

Conclusions

The recent study by Choi et al. provides further evidence that a weak inner central retinal response, as measured by mfERG, is a risk factor for more rapid axial elongation and myopic progression. The results also suggest that OK lenses may be an effective intervention for myopia control regardless of baseline retinal function, thereby diminishing the influence of this electrophysiological risk factor. When considered alongside previous studies, these findings reinforce the role of OK as a robust and effective treatment intervention in pediatric myopia control.

It represents another step toward precision-based approaches in pediatric eye care. The findings do, however, need to be practically possible to implement in an ophthalmic clinical setting as a key personalized variable, as the use of ERG in pediatric ophthalmology is not widely implemented or available as a routine examination. Additional research in non-Asian populations is also warranted to determine whether the findings are applicable worldwide.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article has undergone external peer review.

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0141/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0141/coif). L.J.C. reports roles in AbbVie (research grant, and speaker honorarium), Bayer (speaker honorarium, and advisory board), and Roche (research grant, and advisory board). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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