A neurologist shares his warning about recurrent optic neuritis attacks and NMOSD

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic disorder which causes inflammation of the central nervous system (CNS). While patients may go through long periods of remission, acute attacks can cause ongoing vision problems and permanent sight loss, said Friedemann Paul, MD, PhD, head of the research group in clinical neuroimmunology at the NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Charité – Universitätsmedizin, Berlin, Germany.

Hattie Hayes: NMOSD presents with a diverse array of symptoms. Can you tell me about the ocular manifestations?

Friedemann Paul, MD, PhD: NMOSD can significantly impact patients’ well-being, especially due to ocular effects, which can be severe and lasting. These effects primarily stem from inflammation of the optic nerve, known as optic neuritis, which can lead to acute vision loss, ranging from blurred vision to total blindness.

Many patients also experience eye movement-related pain, which can be sharp and severe, especially during an acute optic neuritis attack. Persistent eye pain can interfere with concentration and can cause discomfort in everyday activities. It can also contribute to overall fatigue. In some cases, patients report increased sensitivity to light, making it difficult to be in brightly lit environments,further isolating them from social or professional settings. Overall, the ocular effects of NMOSD have a deep impact on patients’ quality of life (QoL), influencing functional abilities and emotional health.

HH: What advice do you have for ophthalmologists to help them recognise signs of NMOSD?

FP: Ophthalmologists should be alert to optic neuritis as a possible early sign of NMOSD, especially if it affects both eyes or presents in recurrent episodes. Severe, treatment-resistant vision loss, painful eye movements and symptoms like motor weakness, sensory issues or myelitis history should prompt immediate neurology referrals for further evaluation.

The presence of aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies is highly specific to NMOSD and can differentiate it from other conditions, including multiple sclerosis (MS). Therefore, early AQP4-IgG testing in patients with suspected optic neuritis is encouraged, as it can expedite diagnosis and lead to targeted treatments that prevent NMOSD relapses, preserving vision and neurological function. As NMOSD has severe optic and CNS manifestations, collaboration between ophthalmologists and neurologists is critical.

HH: What mechanisms make inebilizumab a suitable therapy for patients with NMOSD?

FP: Inebilizumab is an approved treatment for adults with NMOSD who test positive for anti-AQP4 antibodies, offering proven clinical efficacy and an established safety profile. NMOSD is primarily driven by B-cell activity, with autoantibodies targeting and damaging AQP4 protein found in the CNS. Inebilizumab works by binding to CD19-positive B cells, inducing their destruction, and effectively depleting a broad range of B cells, including the plasmablasts and plasma cells, responsible for producing AQP4-IgG. Inebilizumab is indicated as monotherapy for the treatment of adult patients with AQP4-IgG-positive NMOSD, with a twice-yearly dosing schedule following two initial start-up doses, which can be a good fit for patients’ lifestyles.

In the N-MOmentum trial, inebilizumab demonstrated significant efficacy–83% of patients treated with inebilizumab for 4 or more years remained attack free. Additionally, patients experienced fewer new CNS lesions, reduced hospitalisations and no worsening of disability over time. The ability of inebilizumab to reduce relapses complements a multidisciplinary approach because it allows each specialist to focus on maintaining and enhancing patient health, addressing both immediate and chronic aspects of NMOSD.

HH: Does the relationship between the chronic disease and acute attacks challenge our current understanding of NMOSD?

FP: The post hoc analysis presented at the 40th European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) showed that inebilizumab provided sustained improvements in pain levels, QoL and Expanded Disability Status Scale (EDSS) and Fatigue Severity Scale (FSS) scores, independent of recovery from acute attacks.

Notably, 89% of patients with initially poor QoL showed improvement after three years of treatment and 78% of the patients who reported pain at the start of the trial reported improvement after treatment. These findings suggest inebilizumab offers benefits beyond reducing acute attack frequency.

This challenges the traditional approach to addressing NMOSD, which has historically focused on managing acute attacks to prevent disability. The continuous improvement in chronic symptoms highlights NMOSD as a disease with ongoing activity, even in the absence of attacks. These insights underscore the need for treatment strategies that address both acute and chronic elements of NMOSD to improve overall patient outcomes.

HH: What do you wish more patients or clinicians understood about ocular health and the CNS?

FP: Patients may not realise that vision problems can result from inflammation in the optic nerve, a part of the CNS. Understanding this connection could help them recognize early signs of vision changes as potential indicators of a broader neurological condition rather than isolated eye issues. Prompt recognition of visual disturbances (e.g., blurred vision, pain during eye movement) is essential, as early recognition and treatment can limit optic nerve damage.

Recurrent optic neuritis in NMOSD can significantly increase the risk of vision loss with each attack, making it essential to prioritise therapies that reduce relapse frequency. By focusing on treatments that target and reduce B-cell activity, patients may benefit from a reduced frequency of debilitating attacks, leading to more stable and long-term visual outcomes.

NMOSD often affects the optic nerves and spinal cord more intensely than other parts of the CNS, with more severe and less reversible damage than in conditions like MS. Clinicians recognising this pattern can guide patients to better monitoring and targeted early interventions.

NMOSD symptoms can overlap with MS, but treatments differ significantly. Misdiagnosis can lead to suboptimal care, so it is essential for clinicians to be aware of NMOSD-specific signs like longitudinally extensive transverse myelitis, unilateral or bilateral optic neuritis, and the AQP4-antibody profile.

Understanding these dimensions of NMOSD can empower patients and clinicians to adopt a more comprehensive, proactive approach to managing the condition, addressing both acute and chronic aspects of ocular and neurological health.

NMOSD poses severe risks, as a single attack can lead to permanent disability and significantly impact QoL. Early, accurate diagnosis is critical, with AQP4 antibody testing essential to distinguishing NMOSD from similar conditions like MS and myelin oligodendrocyte glycoprotein antibody-associated disease. Raising awareness among health care professionals, particularly ophthalmologists who often are the first line of care to spot NMOSD symptoms, can improve early detection and timely intervention.

Friedemann Paul, MD, PhD | E: friedemann.paul@charite.de

Paul is head of the research group in clinical neuroimmunology at the NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Charité – Universitätsmedizin, Berlin, Germany.