Articles

The Fundus Refraction Offset is emerging as a promising indicator for a more personalised assessment of myopia, by far the most common refractive defect in the world. In established diagnostic practice, myopia risk assessment has so far been based on parameters such as the spherical equivalent and the axial length of the eye. The Fundus Refraction Offset represents an innovative approach that offers the opportunity to better understand the individual risk factors that contribute to the progression of myopia. In this article, we explore how the Fundus Refraction Offset could redefine myopia risk management strategies, opening new frontiers in prevention and treatment.

Characteristics and epidemiology

Myopia is a refractive defect whereby light rays are focused in front of the retina. Vision is therefore blurred at a distance and sharper up close.

The term myopia is derived from a Greek word meaning 'half-closed eye', as the myopic subject tends to squint in an attempt to focus images on the retina. Vision is therefore blurred at a distance and sharper up close.

Myopia generally arises and progresses due to excessive elongation of the eyeball and has an increasing incidence worldwide.

Today we speak, in fact, of a 'myopic epidemic', which can be seen as the result of a natural process of evolutionary adaptation of the species to the new, highly educated and technological lifestyle.

According to a 2024 study published in the British Journal of Ophthalmology, myopia affects more than one third of children and adolescents worldwide and it is estimated that, by 2050, more than 740 million young people will be affected by this refractive defect.

The percentage of myopic young people rose from 24% in 1990-2000 to 25% between 2001 and 2010, to 30% between 2011 and 2019, and to 36% between 2020 and 2023.

Causes and course

Myopia usually arises in childhood, but progresses over the years and it is not uncommon to go from the simple to the degenerative form.

It is a multifactorial disease, which has biological differences linked to gender, but whose causes are innumerable and not all of them are yet known.

Genetic, epigenetic, environmental and hormonal factors are, in fact, involved in the onset and evolution of the defect itself, which is the result of a genetic-environmental combination.

Environmental factors are indeed very relevant, but they have a combined action with that of the factors hereditary e constitutional. The proof of the genetic-environment combination lies in the fact that this visual defect is often detected with similar characteristics among members of the same family.

Myopia can be considered a predominantly female refractive defect, as cases more than double among women in adulthood. Hormones therefore have their influence and myopia is expected to particularly affect the womenwith a prevalence of 42% compared to 37.5% for men in 2050.

Diffusion in Italy and the World

Based on geographical incidence, myopia can be divided into three blocks: Asian countries with an incidence of 80/90%, the Europe-US block with an incidence of 30%, and Africa with an incidence of 10%. The cause of the lower incidence of myopia in African populations can be found in a lower genetic predisposition, a lower level of education, and an outdoor lifestyle combined with a healthy diet rich in fruit and vegetables.

As far as Italy is concerned, based on data collected by the'Osservatorio Vista, born from the partnership of Censis, Fondazione Bietti and Fondazione OneSight EssilorLuxottica Italia, one Italian in four is short-sighted for a total of 15 million people.

By 2050, it is predicted that about 50% of the population will be nearsighted, partly because economic conditions strongly affect vision care with 45.8% of nearsighted people foregoing eyeglass replacement and 37.4% foregoing eye examinations.

In recent years, a link has been hypothesised between the increase in myopia in adulthood and prolonged work at the video screen, which is a characteristic of the current working style and has experienced an upsurge in the years of the COVID-19 pandemic.

Classification of myopia

Anatomically, the main causes of myopia can be:

1. an excessive elongation of the eyeball, which occurs in conjunction with physical growth and causes the axial myopiawhich is the most common form;

2. excessive curvature of the cornea, which is the cause of the refractive myopia, o a curvature of the anterior surface of the crystalline lens greater than normal, for which one speaks of myopia from accommodative spasm;

3. increased refractive power of the crystalline lens, when the eyeball has a normal shape but the natural lens of the eye is too 'powerful'. One speaks in this case of index myopia. This condition arises, for example, in the case of cataracts, when opacification of the crystalline lens increases its refractive index.

Myopia usually arises at school age and, as it is a refractive defect due to the size of the bulb, tends to increase during growth. It generally stabilises around the age of 25-30 years.

Depending on the number of diopters, myopia is considered:

• slight, up to 4 dioptres
• media, up to 9 dioptres
• high, over 9 dioptres

In a fortunately limited percentage of cases, this visual defect presents itself in the form of degenerative myopiawhich begins at around 2-3 years of age and worsens with growth, following a process of retinal degeneration, which can lead to visual acuity values as low as -30 diopters.

Correction of myopia

Myopia is generally corrected by the use of negative concave lenses, which bring the focus back to the retina. The lenses can be either contact lenses or spectacle-mounted. Myopia correction can also be carried out with surgical techniques (usually via laser) that modify the curvature of the cornea, decreasing its refractive power and compensating for myopia.

You can also surgically implanting phakic lenseswhich are corrective intraocular lenses, but involve retaining the natural lens or, in the case of cataract surgery, replacing the natural lens with a graduated intraocular lens (IOL).

Fundus Refraction Offset

The Fundus Refraction Offset is a new approach that aims to assess the risk of myopia in a more individualised manner. In contrast to traditional parameters, this new approach makes it possible to detect particular conditions of the individual patient's ocular fundus.

Innovations and advantages compared to standard parameters

In the case of axial myopia, due to the excessive elongation of the eyeball, the myopic eye is exposed to the risk of possible serious complications such as myopic macular degeneration, which can lead to choroidal neovascularisation, abnormalities of the vitreoretinal interface including possible peripheral retinal tears or retinal detachments, and the occurrence of glaucoma

The two parameters used in traditional myopia diagnostics are thespherical refractive equivalent (SER) and the axial lengthwhich remain two clinically fundamental diagnostic elements, but which have important limitations in detecting individual differences in the anatomy of the posterior segment of the eye in myopic patients.

Hence the need to identify new biomarkers that can specifically signal this anatomical component of risk.

This gave rise to the idea of a metrics model based on deep learning, which associates the anatomical aspect of the ocular fundus with the axial refractive profile in quantitative terms. This is a very innovative concept that seems likely to lead to promising results in terms of early diagnosis of myopia progression and its possible complications.

Biomarkers of fundus abnormalities

In order to develop a metric based on the Fundus Refraction Offset, a cross-sectional, population-based study was carried out to associate the data from photographs of the ocular fundus with the parameters measured with optical coherence tomography (OCT).

Data from 45,180 healthy eyes from the UK Biobank from 2009-2010 were examined. Fundus photographs obtained from one sub-grouping (70%) were used to train a deep learning model to predict the refractive spherical equivalent, with the aim of obtaining a model that could capture non-pathological changes in the ocular fundus in the range of -15.50 D to 9.25 D. The resulting model was applied to the remaining sub-grouping to derive the Fundus Refractive Offset of each eye.

The Fundus Refractive Offset was also calculated for 152 right eyes on an external dataset (Caledonian cohort, 2023-2024) by combining axial length and depth-enhanced OCT images.

How it is calculated

Unlike previous studies based on deep learning that aimed to improve diagnostic accuracy with a more accurate measurement of refractive spherical equivalent or long-term visual acuity, the FRO-based approach focuses on retinal structural changes.

The Fundus Refractive Offset (FRO) is in fact calculated as the deviation of the actual refractive spherical equivalent from the expected spherical equivalent based on the fundus image.

A negative Fundus Refractive Offset value indicates an ocular fundus with a more myopic appearance than would be typical for an eye with the same spherical equivalent.

By correlating the Fundus Refractive Offset with indices of macular thickness or choroidal vascularisation, it was possible to show that eyes with a similar axis metric profile had large differences in the posterior segment profile. In particular, a more negative Fundus Refractive Offset (indicating a fundus with a myopic appearance) was associated with a lower macular thickness and a lower index of choroidal vascularisation.

These associations persisted even after spherical equivalent and axial length adjustments, demonstrating that the Fundus Refractive Offset can be a biomarker for stratifying anatomical risk between eyes with a similar axial refractive profile.

From a structural point of view, thinning of the choroid and retinal atrophy are markers of possible complications of myopia and, therefore, the Fundus Refractive Offset has the potential to identify eyes at higher risk, much earlier than routinely used parameters.

Perspectives of the new biomarker

The Fundus Refractive Offset undoubtedly has great potential with regard to the stratification of the risk of progression or complications of myopia, precisely because of its ability to identify structural alterations of the ocular fundus that are not detected by the spherical equivalent or the uncorrected visual acuity measurement.

Its use can also be envisaged in monitoring the results of corrective interventions, with glasses or contact lenses, that are used from time to time and especially in planning a surgical correction of myopia.

The fact that the Fundus Refractive Offset is based on photographs of the ocular fundus, which do not require invasive diagnostic procedures or particularly expensive equipment, makes its future inclusion in routine clinical practice conceivable.

However, it is very important that certain issues are addressed first:

1. Evaluations on multi-ethnic and longitudinal cohorts of patients in terms of gender and age
2. Unambiguous determination of clinically significant thresholds
3. Training of personnel trained in the use of the new technology.

Horizons of Research and Clinical Practice

Despite the challenges, there are many opportunities for future research in the field of Fundus Refraction Offset.

• Technological developmentmeasurement instruments can be improved and made more sensitive.
• Clinical studiesNew study protocols will have to be promoted to confirm the significance of the new biomarker.
• Integration into diagnosticsClinical practices will have to be adapted to include this biomarker.

These lines of development could lead to significant advances in myopia management, positioning the Fundus Refraction Offset as an indispensable tool.

• Yii F, MacCormick IJC, Strang N, Bernabeu MO, MacGillivray T. Fundus Refraction Offset as an Individualized Myopia Biomarker. JAMA Ophthalmol. 2025 Jul 1;143(7):597-606. doi: 10.1001/jamaophthalmol.2025.1513. PMID: 40471629; PMCID: PMC12142477.
• Yii F, MacCormick IJC, Strang N, Bernabeu MO, MacGillivray T. Fundus Refraction Offset as a Personalized Biomarker for 12-Year Risk of Retinal Detachment. Invest Ophthalmol Vis Sci. 2025 Jul 1;66(9):1. doi: 10.1167/iovs.66.9.1. PMID: 40590806; PMCID: PMC12227021.
• Zhang XJ, Lai CHY, Shih KC. Beyond Spherical Equivalent and Axial Length in Myopia. JAMA Ophthalmol. 2025 Jul 1;143(7):606-607. doi: 10.1001/jamaophthalmol.2025.1622. PMID: 40471619