Not all -4.00 Ds are created equal. Meet the myopia biomarker that new research says knows the difference.
Researchers have developed a novel biomarker that may help eye care providers better assess individual risk for myopia progression and complications beyond traditional measurements.1
A research team from the University of Edinburgh have introduced a new metric called fundus refraction offset (FRO), which quantifies the mismatch between an eye’s fundus appearance and what would be expected for its refractive error.1
According to the JAMA Ophthalmology article, spherical equivalent refraction (SER) and axial length (AL) have long been the standard measurements for assessing myopia. However, these on-axis metrics are limited in capturing individual differences in posterior segment anatomy, which may explain why patients with similar refractive errors can have vastly different outcomes.1
READ MORE: Tech, Clinical Trials and Rethinking Myopia Management With EssilorLuxottica
How FRO works
The group used data from 45,180 healthy eyes in the UK Biobank to train a deep learning model to predict SER from fundus photographs. Unlike previous studies that focused on improving prediction accuracy, this study specifically utilized prediction errors as a meaningful biomarker.1
FRO was calculated as the difference between predicted and actual SER. A negative FRO indicates a more myopic-looking fundus than typical for an eye with the same SER, while a positive FRO suggests a more hyperopic-looking fundus.1
Key findings
The study found that FRO was independently associated with posterior segment anatomical features, even among eyes with similar SER or AL:
- A more negative FRO was associated with lower macular thickness (0.64 μm reduction per -1.00 D FRO)
- Similar findings were observed in an external validation dataset of younger adults (Caledonian cohort), with a 2.45 μm reduction in macular thickness per -1.00 D FRO
- FRO was also associated with decreased choroidal vascularity index, suggesting reduced choroidal perfusion in eyes with more negative FRO values1
These associations remained significant after controlling for SER, AL, age, sex and race.1
READ MORE: WSPOS Myopia Consensus Statement 2025: What Practitioners Need to Know
Clinical implications
“FRO reflects the individual-level mismatch between SER (or AL) and the anatomical severity of ametropia,” the researchers wrote. “This may have prognostic relevance for personalized risk prediction of myopia and its complications.”1
Zhang et al. from the University of Hong Kong, in an accompanying invited commentary, noted that FRO “highlights structural heterogeneity not captured by conventional on-axis metrics, suggesting potential utility for risk stratification, treatment monitoring or surgical planning in myopia management.”2
Future directions
While the initial findings are promising, Zhang et al. raised several important questions that need to be addressed before FRO can be implemented in clinical practice:
- Whether baseline FRO can predict future myopia progression or complications in prospective studies
- How well FRO performs across different ethnic populations and age groups
- Establishing clinical thresholds for high-risk FRO values
- How to integrate FRO with existing metrics and potentially genetic markers2
READ MORE: Outsmarting Myopia
Additionally, the researchers suggest that longitudinal studies are needed to validate FRO’s prognostic potential for predicting myopia progression and complications. As they note in their conclusion, “A promising future direction is to explore whether baseline FRO is independently associated with the risks of future myopic complications, beyond the influence of baseline myopia severity and other potential covariates.”1
As myopia prevalence continues to rise globally, tools that enable more personalized risk assessment could help clinicians better target interventions and monitoring strategies for those at highest risk of vision-threatening complications.
Editor’s Note: This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore.
References
- Yii F, MacCormick IJC, Strang N, Bernabeu MO, MacGillivray T. Fundus Refraction Offset as an Individualized Myopia Biomarker. JAMA Ophthalmol. 2025:e251513. [Epub ahead of print.]
- Zhang XJ, Lai CHY, Shih KC. Beyond Spherical Equivalent and Axial Length in Myopia. JAMA Ophthalmol. 2025 Jun 5. [Epub ahead of print.]