Research supports inclusion of optic nerve in McDonald criteria for MS

Add would help improve diagnostic accuracy in MS, new study says

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Adding optic nerve damage — reflected by a thinning of the nerve layer in the eye’s retina — to the existing diagnostic criteria for multiple sclerosis (MS) was found to enhance diagnostic accuracy among people who had a single, MS-like event, according to a new study.

The study “demonstrated for the first time that diagnosis of multiple sclerosis (MS) can be significantly improved by additionally measuring the thickness of retinal layers in the eye,” researchers said in a press release

As such, the scientists believe their findings support the inclusion of the optic nerve in the next revision of the McDonald criteria, considered the gold standard for diagnosing MS.

“We have identified a new biomarker for MS diagnosis, namely the retinal layer thickness, which can be likened to a window to the brain,” said Gabriel Bsteh, MD, PhD, of the Medical University Vienna, in Austria, and the study’s first author.

The study, “Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for MS,” was published in Neurology.

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Optic nerve inflammation often is first sign of MS

A definitive diagnosis of MS relies on the McDonald criteria, a set of clinical and laboratory guidelines for confirming that an individual has the neurodegenerative disease.

To be considered MS, there must be evidence of damage to the central nervous system (CNS) — the brain and spinal cord — that appears in multiple areas at varying points in time. Such damage across different areas is known as dissemination in space, or DIS, while occurrences at varying timepoints is called dissemination in time.

In terms of the first criterion, there must be damage in at least two of four distinct CNS areas, which include three brain regions — the periventricular, juxtacortical/cortical, and infratentorial — and the spinal cord.

It has been suggested in recent years that the optic nerve should be added to this list. A bundle of nerve fibers running between the retina and the brain, the optic nerve is critical for transmitting signals to the brain that enable vision.

Inflammation of the optic nerve, known as optic neuritis, is a common manifestation of MS — and is the first presentation of the disease in about 1 in 4 people.

While scientists have argued for inclusion of the optic nerve in the DIS criteria, the most recent update to the McDonald criteria in 2017 did not incorporate it, deeming the evidence insufficient.

Now, a team led by researchers at the Medical University Vienna further investigated the diagnostic utility of adding optic nerve damage to the diagnostic criteria.

The analysis involved 267 patients with clinically isolated syndrome (CIS) — those who had experienced a first demyelinating event, or the initial presentation of symptoms attributed to neurological damage consistent with MS, but had not been formally diagnosed with MS.

Not all people who experience a demyelinating event will go on to develop MS. For those who do, the event is often considered their first relapse.

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Adding optic nerve damage to criteria could mean sooner treatment

A technique called optical coherence tomography or OCT was used to track these individuals’ retinal nerve layer thickness — an indicator of optic nerve health — over a period of more than five years. OCT is a well-established imaging tool used to evaluate eye diseases.

A second clinical attack was observed in 100 patients (37.5%) after a mean of 14.8 months. One of the factors associated with an increased risk of a second attack was optic nerve involvement as the sole presentation. Specifically, the risk was about nine times higher. Additionally, the more regions that were affected, the higher was the risk of experiencing a second relapse.

The team then compared the risk of a second attack in terms of standard DIS diagnostic criteria (the four CNS regions) compared with a modified criteria, called DIS-OCT. That criteria dictated that a person must have involvement of at least two of five regions, including the four standard ones and the optic nerve.

The risk of a second attack was elevated about 2.5 times in patients who met standard DIS criteria compared with those who did not. In comparison, the risk was about 3.6 times higher in patients meeting DIS-OCT criteria. That difference was not statistically significant from the DIS criteria.

Still, DIS-OCT, “seemed slightly more accurate and more sensitive,” according to the researchers.

If we use optical coherence tomography alongside the current criteria to diagnose MS, we obtain significantly more accurate results at a much earlier stage. This means we can initiate treatment measures sooner, which considerably improves the long-term prognosis for patients.

Specifically, the diagnostic accuracy was 81% compared with 66% using the traditional metrics. Sensitivity, or the criteria’s true-positive rate, was also greater with the addition of OCT measures (84% vs. 78%), while the true-negative rate was similar for both criteria.

“If we use optical coherence tomography alongside the current criteria to diagnose MS, we obtain significantly more accurate results at a much earlier stage,” Bsteh said. “This means we can initiate treatment measures sooner, which considerably improves the long-term prognosis for patients.”

Importantly, the scientists emphasized that, as with other diagnostic criteria, optic nerve involvement can also occur in other conditions, and other plausible alternative diagnoses should always be ruled out.

The team also noted that, while there are a few ways to assess for optic nerve involvement, OCT is an easy, noninvasive, and inexpensive way to do so, and thus is “an attractive option.”

Overall, “this provides additional evidence arguing in favor of inclusion of the optic nerve in the upcoming revision of the McDonald criteria and, thus, establishing OCT within the spectrum of routine MS diagnostics,” the researchers wrote.