Ophthalmic Manifestations of Neuromyelitis Optica Spectrum Disorder (NMOSD) - A Complete Guide

Introduction:

Several autoimmune conditions affecting the human body are considered to cause varied manifestations in different parts of the body. Ophthalmic manifestations are very common in individuals with autoimmune diseases. One such rare debilitating autoimmune spectrum disorder is the Neuromyelitis Optica Spectrum Disorder (NMOSD), and the clinical features noted in the eyes in this disorder are prominent and must be managed as soon as possible.

What Is Neuromyelitis Optica Spectrum Disorder (NMOSD)?

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic autoimmune spectrum disorder mainly affecting the central nervous system. The most commonly involved organs are the optic nerve and spinal cord. The pathogenesis of neuromyelitis optica spectrum disorder is the production of antibodies against astrocytes (nervous system cells). The antibodies primarily focus on destroying aquaporin-4 (AQP4), a water channel protein found in astrocytes.

When antibodies are produced against aquaporin proteins, they bind together and activate the complement system in the body. The immune response escalates. The resultant reaction is destruction of the involved astrocytes, demyelination (loss of myelin sheath that surrounds the nerve fibers), and damage to the involved cranial nerves. In some patients, the antibodies involved in the causation of this spectrum disorder are also considered to be myelin oligodendrocyte glycoprotein antibodies. However, extensive study is required to confirm this causative factor.

What Are the Ophthalmic Manifestations of Neuromyelitis Optica Spectrum Disorder?

Clinical manifestations in the ocular system are a very significant part of NMOSD. This is because the optic nerves are highly vulnerable to attack by aquaporin-4 antibodies due to the higher number of aquaporin-4 water channels in them. The common ophthalmic manifestations noted in patients affected by neuromyelitis optica spectrum disorder are:

• Optic Neuritis: Optic neuritis is the most important and hallmark manifestation of NMOSD. The involvement of the optic nerve occurs on both sides (bilateral optic neuritis), unlike multiple sclerosis, where optic neuritis occurs only on one involved side. Optic neuritis in NMOSD patients also causes bulging of the optic disk. The associated clinical features are:

• Severe loss of vision can occur suddenly or gradually (segment-wise) over time.

• Intense pain in the periorbital region. Patients with NMOSD often complain of exaggerated periorbital pain following any kind of eye movement.

• Reading fine details accurately will be challenging for patients with impaired vision in the center of the visual field (central scotoma). This occurs secondary to damage and inflammation of the optic nerve and the retina.

• Ischemic damage to the optic nerve also results in altitudinal field defects in patients with NMOSD (loss of visual acuity in the upper or lower half of the visual field).

• Deficits in differentiating colors (dyschromatopsia), particularly red desaturation, are noted in patients with NMOSD.

Other Ophthalmic Manifestations:

The involvement of the optic nerve is the primary clinical manifestation of NMOSD. However, a broad spectrum of ophthalmic manifestations can also be noted secondary to the involvement of other central nervous system structures. Such ophthalmic features include:

• Rapid eye movements that occur involuntarily due to the affected brainstem are frequent in NMOSD patients.

• Double vision is noted when cranial nerves are affected by the AQP-4 antibodies.

• Coordinated movement of both eyes becomes nearly impossible (conjugate gaze palsies) due to lesions affecting the brainstem and cranial nerves.

• Cortical visual disturbances may arise from demyelinating lesions in the brain's visual pathways.

• Defects in the pupils will also be noted in NMOSD patients.

How to Diagnose Ophthalmic Manifestations of Neuromyelitis Optica Spectrum Disorder?

The involvement of the optic nerve and associated manifestations in the eyes are the first noticeable symptoms of NMOSD. Hence, evaluating the ocular system can help diagnose and prompt treatment of this condition.

• The history-taking step is important to determine the time of incidence of various ophthalmic symptoms in the patients. Clinical features will be evaluated through physical examination. During physical examination, the involvement of the bilateral side optic nerve should be noted as it is a vital distinguishing feature to differentiate NMOSD from multiple sclerosis.

• An ophthalmic examination will check the visual acuity (degree of vision loss in both eyes) and color vision integrity. Visual acuity levels below 20/200 indicate complete blindness due to optic nerve atrophy. A fundoscopic examination will indicate a damaged and atrophic optic nerve due to an antibody attack in NMOSD.

• An MRI of the ocular system will be performed to confirm the involvement of optic nerves and inflammation on both sides. T2 weighted images or T1 weighted images with contrast are ideal for viewing the optic system in NMOSD. The optic nerve sheath will appear hypointense, and both eyes will have hyperintense lesions. Abnormal signals from the optic chiasm during MRI imaging are characteristic of NMOSD. Along with these features, hyperintense lesions will be seen on the spinal cord (indicating longitudinal transverse myelitis), which confirms the diagnostic features of NMOSD.

• One of the core characteristics of the diagnostic criteria for NMOSD is the confirmation of AQP-4 IgG antibodies in the serum of the affected patients. The serological test done is the AQP-4 IgG antibody test. Testing for MOG-IgG antibodies is equally essential in the diagnostic process of NMOSD, especially in AQP4-IgG-negative patients, as it identifies a different subset of NMOSD with distinct clinical features.

• Optical coherence tomography is a great modality for visualizing the thickness of the retinal nerve fiber layer. If the layer is very thin, it clearly indicates chronic damage to the retina secondary to optic neuritis in NMOSD.

• Demyelination and the severity of axonal damage incurred to the optic nerve can be elicited through the visually evoked potential test, which indicates a delay in the conduction process in the optic nerve.

How to Treat Ophthalmic Manifestations of Neuromyelitis Optica Spectrum Disorder?

The objective of treating ophthalmic manifestations is to manage acute illness and inflammation, prevent relapse, and preserve visual integrity.

• For acute flare-ups of optic neuritis and associated features, high-dose intravenous administration of corticosteroids is done.

• For patients with NMOSD who do not respond to steroid therapy or there is a relapse, plasma exchange to remove the AQP-4 antibodies is the treatment option.

• The long-term plan for managing NMOSD is immunosuppressive therapy with drugs like Azathioprine, Rituximab, or Mycophenolate mofetil.

• Rehabilitation for vision loss patients is necessary.

Conclusion:

Ophthalmic manifestations, particularly optic neuritis, are central to the clinical presentation of NMOSD. Recognizing the distinct features of NMOSD-associated optic neuritis, such as its severity, bilaterality, and high recurrence rate, is vital for differentiating it from other optic neuropathies. In reality, advanced research and clinical vigilance can only improve the understanding of NMOSD and help manage the associated clinical manifestations.