Genetic model can help predict risk of MS in optic neuritis patients

A model based on genetic factors could help predict the risk of developing multiple sclerosis (MS) in people with optic neuritis, an eye disorder that can be an early sign of MS, according to new research.

“As a doctor caring for many patients with optic neuritis, I’m excited by the possibility of translating this pilot research into front-line clinical care in the near future,” Tasanee Braithwaite, MD, a co-author of the study detailing the research findings, said in a press release.

Optic neuritis refers to inflammation of the nerves that connect the eyes to the brain, which results in problems with vision. About 20% of people with unexplained optic neuritis will ultimately be diagnosed with MS within five years — and as many as 50% within 15 years.

“Whilst more research is needed, our study provides a strong signal that we could better identify patients at high risk of MS, perhaps enabling these people to have earlier MS treatment in the future,” said Brathwaite, a consultant ophthalmologist at Guy’s and St. Thomas NHS Foundation Trust’s medical eye unit and and adjunct senior lecturer at King’s College London.

“If we could better identify people whose optic neuritis is very unlikely to result from MS, we could treat these people urgently to reduce irreversible vision loss and blindness,” Brathwaite added.

The study, “Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis,” was published in Nature Communications.

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“Currently, 130,000 people live with MS in the U.K., and one in five will have experienced optic neuritis at the start of their MS journey,” said Clare Walton, head of research at the MS Society, a U.K. nonprofit.

Giving MS treatments to at-risk patients with optic neuritis is thought to reduce the chances of future disease. But these therapies often are expensive and carry risks of side effects. Moreover, researchers and clinicians still lack reliable methods to predict MS risk for people with optic neuritis.

Predicting this risk is important because treatment approaches for someone with optic neuritis caused by MS are very different from those for non-MS-related optic neuritis, the experts note. At-risk patients may go permanently blind if they don’t receive an intensive course of steroids as soon as possible.

“Using immunotherapies in people at high risk of MS could significantly delay the onset of the condition, but these drugs come with side effects,” Walton said, adding that “this exciting study opens up the possibility of finding people in which the benefits will outweigh the risks.”

Although the causes of MS aren’t fully understood, it’s increasingly clear that genetic factors play a major role in determining disease risk.

For this study, the researchers analyzed more than 300 MS-associated genetic variants to develop a so-called MS genetic risk score. The team then explored whether the score — which also included information on patients’ age and sex — could help predict the risk of MS for people with optic neuritis.

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“Since the first genome was sequenced three decades ago, we’ve been working towards the promise of being able to use genetics to improve outcomes for individual patients,” said Richard Oram, PhD, a professor at the University of Exeter Medical School and co-author of the study.

“This research is an excellent example of precision genetic diagnosis in practice,” Oram said.

In a first analysis using data from the U.K. Biobank, the scientists identified data for 687 people with optic neuritis. Among them, 142 had a prior or simultaneous MS diagnosis and 545 had no identifiable cause for their condition at the study’s start. Over a median follow-up of 18.4 years, 124 of patients (22.8%) with unexplained optic neuritis were eventually diagnosed with MS.

In statistical models, the researchers showed that the likelihood of MS was higher for patients with a greater genetic risk score. For every one standard deviation increase in genetic risk, the risk of developing MS was increased by 29%.

This research is an excellent example of precision genetic diagnosis in practice.

When the researchers divided the patients into four groups according to genetic risk, they found that 3.6% of patients in the lowest-risk group developed MS over the course of follow-up. In the highest-risk quartile, conversely, 41.2% of patients did.

Further analyses using two other national databases, one from the U.S. and another from Finland, showed consistent results. That provided some validation for the findings, though the researchers noted that all three databases mainly included people of European descent, so further work will be needed to determine if the genetic risk score can also be applied in more diverse populations.

The scientists suggested the genetic risk score could be applied in clinical practice to “facilitate MS follow-up management and guide decisions around performing [diagnostic tests] to seek earlier MS diagnosis and potentially earlier disease-modifying treatment.” More work will be needed to figure out how best to apply the score in a clinical context, they said.