When Vision Blurs, Genetics May Bring Clarity: Predicting Multiple Sclerosis from a Single Eye Episode
Imagine waking up one morning with blurred vision in one eye, pain when moving it, and colors seeming dimmer than usual. This sudden inflammation of the optic nerve—called optic neuritis (ON)—is one of the scariest experiences for young adults. For about half of these patients, this episode is not an isolated event but the first sign of multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system.
The problem? At the first presentation, clinicians can’t easily tell who will go on to develop MS and who will not. The stakes are high: patients at high risk might benefit from early MS-modifying therapy, while those at low risk might need urgent immunosuppressive treatment to preserve their vision from other inflammatory diseases.
Until now, that crucial distinction relied mostly on MRI scans and follow-up—but not on genetics.
The Study: Can Our Genes Reveal What the MRI Can’t Yet Show?
A paper in Nature Communications by Pavel Loginovic, Tasanee Braithwaite, Richard Oram, and colleagues takes a major step toward solving this clinical dilemma. The researchers asked:
Can a person’s genetic risk score for MS help predict who will develop MS after an episode of optic neuritis?
To find out, they turned to the UK Biobank, a massive health and genetics database of nearly half a million participants, and two additional datasets from Geisinger (USA) and FinnGen (Finland) to test whether their findings held true in other populations.
Building a Genetic Compass: The MS Genetic Risk Score (MS-GRS)
The team constructed an MS Genetic Risk Score (MS-GRS) using data from the International Multiple Sclerosis Genetics Consortium (IMSGC), which identified over 200 genetic loci associated with MS. These include genes involved in immune system regulation, particularly within the HLA region on chromosome 6.
Each genetic variant contributes a tiny bit to MS risk. By aggregating hundreds of these variants—weighted by their individual effects—the researchers produced a single composite genetic score reflecting an individual’s inherited susceptibility to MS.
They then combined this MS-GRS with simple demographic factors—age and sex—to see if it could help predict who among patients with optic neuritis would later develop MS.
What They Found: Genetics Adds Predictive Power
From 483,506 participants, the researchers identified:
2,369 cases of MS
687 cases of optic neuritis (ON)
Of those with ON, about 23% later developed MS—closely matching the known long-term risk seen in clinical practice.
1. The Higher the MS-GRS, the Higher the Risk
For every one standard deviation increase in MS-GRS, the hazard of developing MS after ON rose by 1.3-fold (95% CI 1.07–1.55, P < 0.01).
Participants were divided into quartiles of predicted MS risk based on the model:
Lowest risk quartile: ~4% developed MS
Highest risk quartile: ~41% developed MS
That’s a tenfold difference—just from combining genetics, age, and sex.
2. Validation Across Populations
The model held up when tested in two independent cohorts:
Geisinger (USA): 17% developed MS after ON
FinnGen (Finland): 38% developed MS after ON
Despite differences in population genetics and follow-up time, the predictive trend was remarkably consistent.
Why This Matters: Toward Precision Neurology
In everyday clinical practice, patients with optic neuritis face an anxious waiting period before definitive answers emerge from MRI or lab tests. This research suggests that a genetic risk test—calculated from a saliva or blood sample—could soon become part of the diagnostic toolkit to guide early decisions.
For instance:
A high MS-GRS might prompt earlier MRI follow-up, lumbar puncture, or consideration of disease-modifying therapy.
A low MS-GRS might justify aggressive corticosteroid treatment aimed at preserving vision, if an alternative immune disorder is suspected.
This is not science fiction—the authors even built a prototype online tool, MS Predictor, to demonstrate how such a model could be used in the clinic.
Limitations and Next Steps
Like all pioneering studies, this one has caveats.
The UK Biobank primarily includes participants of European ancestry, limiting generalizability.
Some optic neuritis diagnoses relied on medical codes rather than imaging confirmation.
Key factors like Epstein–Barr virus exposure, vitamin D status, or MRI lesion data were incomplete.
Nevertheless, the model’s successful replication in two large, independent datasets lends strong support to its robustness.
The next frontier? Prospective clinical validation—testing how this genetic model performs in real-time, as patients are diagnosed. Integrating genetic risk into acute care could redefine the early management of demyelinating disease.
A Glimpse Into a Predictive Future
Multiple sclerosis has long been known as a disease with unpredictable onset and course. This study shifts the paradigm: by weaving genetics into clinical prediction, neurologists may soon see the future more clearly—sometimes quite literally through the eyes.
As precision medicine advances, the once fuzzy boundary between “risk” and “disease” begins to sharpen. For patients who first present with blurred vision, genetics might offer not only answers but also hope.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Loginovic P., Wang F., Li J., Ferrat L., Mirshahi U.L., Rao H.S., et al. (2024). Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis. Nature Communications, 15, 1415. https://doi.org/10.1038/s41467-024-44917-9
