Two experts in neuro-ophthalmology discuss the advances in the identification and treatment of patients presenting with optic neuritis.
Robert Sergott, MD
The treatment of patients with multiple sclerosis (MS) often spans a multidisciplinary care team to adequately manage the disease’s wide spectrum of symptoms and complications—such as the inflammation of the optic nerve, leading to optic neuritis and neuromyelitis optica (NMO).
Literature suggests that approximately half of patients receiving a diagnosis of MS will present with optic neuritis as the first sign of relapsing-remitting MS, whereas those with primary progressive MS are less likely to present with optic neuritis. A key identifier for neuro-ophthalmologists is pain accompanying eye movement, as well as swelling and other evidence of inflammation in the eye and optic nerve.
In a recent NeurologyLive® Peers & Perspectives series titled “Management of Optic Neuritis,” a pair of specialists in neuro-ophthalmology discussed the diagnosis, management, and treatment of these patients, including discussion on therapeutic advances and anti-myelin oligodendrocyte glycoprotein (MOG) disease.
Treatment and Patient Identification
Although physicians treating optic neuritis had previously been quite limited in what they had available to treat the symptom, there are now nearly 2 dozen treatments to utilize. Robert Sergott, MD, chief of neuro-ophthalmology at Wills Eye Hospital in Philadelphia, Pennsylvania, noted that some patients are still treated with injectable therapy, such as glatiramer acetate or interferon, but many are also treated with oral medications and intravenous infusions.
“While we can prevent a lot of relapses now, where MS therapy needs to move to is how we repair damage,” he said. That area, he added, will be the focus for the next decade in therapeutic development. Advancements in therapy over the past 20 years have shifted what happens in the management of acute optic neuritis—particularly the spectrum of disease with NMO.
“It used to be we would lump all inflammatory optic neuropathy together that looked somewhat like MS,” Rod Foroozan, MD, a neuro-ophthalmologist and associate professor at Baylor College of Medicine in Houston, Texas, said. “We now know that there are some variants and there’s a spectrum of disease. In the early to mid-2000s, a blood test became available for neuromyelitis optica,” Foroozan recalled, noting the discovery of a circulating IgG autoantibody reported in patients with NMO that was absent in those with MS, “which is an antibody to aquaporin 4, and that was a game changer because we could now define—by pathophysiology and identify with a blood test—those patients who were going to be at risk for a more progressive disease.”
Prior to the blood test becoming available, the general belief was that NMO was a variation of MS, despite the fact that the conditions differ greatly both diagnostically and therapeutically. In fact, Foroozan pointed out, some patients treated for NMO will not have an adequate response to traditional therapy for MS. Additionally, physicians were originally taught to only point to NMO if both optic nerves were involved.
Relatively soon after the identification of this antibody to aquaporin 4, physicians began to notice that individuals with more severe optic nerve involvement, poor vision bilaterality, simultaneous involvement, or longer stretches of enhancement of the optic nerve—extending into the optic chiasma, for example— differed immunologically in how inflammation occurred. Sergott noted that patients who do not improve with steroids often lead him to be very suspicious of NMO. In these cases, plasmapheresis can be used and has been with dramatic success.
“NMO is a vicious disease. It’s just not a little worse demyelination,” Sergott said. “Beautiful work by Claudia Lucchinetti, MD, from Mayo Clinic has shown that this is a vasculitis that has special preference for the optic nerve, the retina, an area of the brain near the start of the spinal cord called the medulla, the area postrema, and for long segments of the spinal cord.”
Sergott noted that every patient in question should receive an NMO titer and an anti-MOG titer. He pointed to potential identifying symptoms, including uncontrollable hiccups caused by inflammation in the area postrema in the medulla and, rarely, long-lasting itching, which can present prior to vision loss.
As for imaging, Sergott and Foroozan explained that patients with optic neuritis require imaging in the spinal cord—both cervical and thoracic—to find asymptomatic lesions that stretch over several segments of the cord.
“There are patients who will have what’s called seronegative NMO,” Sergott said. “That is, the blood test will be negative, but they’ll have these clinical features or the neuroradiological features, and that’s still NMO.”
MOG and Neuromyelitis Optica
Foroozan explained that research on MOG revealed that a group of patients with optic neuritis were very responsive to steroids. These patients were found to be MOG antibody positive. In his experience, about one-third of pediatric patients who develop optic neuritis will have MOG antibodies present.
“Exactly what their role is in the pathogenesis of optic neuritis is not clear, but it is a marker in a group of patients, and that includes pediatric patients who develop optic neuritis,” Foroozan said. “And they can signify in older patients a risk for recurrent optic neuritis or what was previously termed CRION, for chronic relapsing idiopathic optic neuritis. Now we have a spectrum of disease that initially was only considered to be MS and now it has branched into at least 2 other forms, MOG and NMO.”
Sergott noted that a common tip-off for MOG disease is swelling on fundoscopic examination when the patient is unable to see, identifiable as optic nerve swelling and hemorrhages. He and Foroozan agreed that admitting these patients quickly is often best to acquire the proper imaging and see response. The pair explained that after between 3 and 5 days of intravenous steroids, if there is no improvement, it is justifiable to conduct plasmapheresis.
“Especially for the pediatric cases routinely admitted, 1 of the things I’ll look for is an early response to treatment,” Foroozan said. “We talked about a lack of response as being a marker maybe for NMO. One of the things that we’ll see with MOG is a very rapid response. If you’re getting a visual recovery within 24 to 48 hours with IV steroids, I’m very suspicious for MOG.”
Additionally, he added, with MOG there is this tendency for a perineural enhancement pattern to appear on MRI. When there is enhancement of the optic nerve extending into the orbital fat or around the optic nerve sheath, instead of just the nerve itself, that can be a strong indicator of MOG, or at least another type of inflammatory optic neuropathy.
“When I was in medical school, before we had MRI and before we had a lot of things, we thought MS was a rare disease,” Sergott said. “That is not true, and that happened because of MRI. Anytime we get better technology, we become better clinicians and can more precisely treat patients. The teaching, 5 years ago, was that NMO and anti-MOG were rare. I think they’re common.”