Continuing Education Activity

This activity describes the evaluation and management of optic neuritis and details the role of the interprofessional team in managing patients with this condition.

Objectives:

• Describe the presentation of an adult patient with presenting with signs or symptoms consistently with optic neuritis.
• Describe ophthalmic treatment considerations for patients presenting with recent onset optic neuritis.
• Describe long-term systemic health considerations for patients presenting with optic neuritis.
• Explain the importance of collaboration and communication amongst the interdisciplinary team to enhance care coordination and improve outcomes for patients affected by optic neuritis.

Introduction

A healthy optic nerve is a crucial conduit for impulses generated within the layers of the retina to leave the eye. Electrical signals are initiated by the photoreceptors in response to incident light, modified by retinal bipolar cells, and transmitted through the optic nerves to the lateral geniculate bodies. Damage to the nerve fiber layer or optic nerve may compromise the quality of these signals.

The term optic neuritis (ON) is used to describe a variety of conditions affecting the optimal function of the optic nerve. A wide range of conditions, including infections, trauma, vascular insufficiency, metastases, toxins, or nutritional deficiencies, may cause optic neuropathies, but this article focuses on optic neuritis (ON), an inflammatory condition that demyelinates the optic nerve and degrades vision in one or both eyes.

Etiology

The mechanism responsible for acute optic neuritis (ON) has not been definitively identified but it is believed that an autoimmune reaction damages the myelin sheath that encompasses neurons within the optic nerve. Patients with documented autoimmune diseases [1] have a greater propensity for ON and there is a causal relationship between HLA DRB1,[2] HLA-B27[3] and ON. Some studies suggest that viral illnesses, which are known to precipitate auto-immune reactions, may induce ON attacks. ON may be one manifestation of a demyelinating disease that affects several areas of the central nervous system; ON is often the first clinical manifestation of demyelination.

Epidemiology

The annual incidence of new-onset ON has been reported between 0.56 and 5.1 cases per 100,000 [4].  

Risk factors for ON include age (20 to 40 years), sex (female:male = 2:1), and race (Caucasian).

Children infrequently develop bilateral ON but childhood disease is not believed to foreshadow the development of multiple sclerosis [5],[6].

An increased incidence of multiple sclerosis (MS) in temperate climates has been proposed[3],[5]. 

Studies have identified that the northern United States and western Europe have more cases relative to equatorial regions [6].

Pathophysiology

Optic neuritis (ON) is one manifestation of central nervous system inflammation with resultant demyelination. Recurrent episodes of ON indicate a propensity toward developing more generalized diseases [7] including MS, neuromyelitis optica spectrum disorders (NMOSC), and myelin oligodendrocyte glycoprotein-IgG (MOG)[8]. The extent of axonal damage due to optic neuritis (ON) differs according to the causative condition.

Optic neuritis is the initial inflammatory event in 15-20% of patients with MS [9],[10], and half of MS patients will eventually have had at least one ON attack within the prior 15 years (see Image. Optic Neuritis as an Indicator of Multiple Sclerosis). Multiple sclerosis (MS) occurs more commonly in temperate climates [11],[12] with more cases seen in the northern United States and western Europe as opposed to equatorial regions [13]. Oligoclonal bands within the cerebral spinal fluid are pathognomonic for MS.

Optic neuritis related vision loss in patients with NMOSD and MOG is usually more severe and results in larger scotomas. Since both disorders affect the optic nerve, chiasm, and optic tracts, bilateral vision loss is common. Damage often extends longitudinally into the spinal cord in both conditions.

NMOSD is characterized by frequent ON attacks that cause severe bilateral vision loss with little chance of functional improvement. Spinal cord lesions that extend beyond three vertebral segments are typical of NMOSD and debilitating transverse myelitis often limits physical activities. Detection of AQP4-IgG antibodies confirms the diagnosis of NMOSD.

MOG is also associated with significant bilateral visual impairment but marked ON-related papillitis occurs less frequently than with NMOSD. Marked enhancement of the optic nerve, nerve sheath, and periocular tissues is evident with neural imaging studies. Compared to those with NMOSD, patients with MOG are more likely to experience improved visual function after ON and they may have lower spinal cord involvement. Males and females are affected with equal frequencies [14],[15].

History and Physical

Optic neuritis usually presents with the acute onset of monocular eye pain and vision loss in a young adult. Pain is usually associated with eye movements and often precedes loss of vision. Patients often report having had similar events in the same or fellow eye.

The degree of vision impairment may range from near-normal acuity to no light perception [16]. Nearly any visual field defect may be seen on automated visual field testing but central scotomas are most common. Color perception is significantly impaired (red hues are notably desaturated) and contrast sensitivity is diminished. Patients may experience recurring photopsias. Vision loss may be exacerbated after exercise or elevation of body temperature (Uhthoff phenomenon).

Optic disc swelling is seen on fundoscopy in one-third of patients during the active phase. In the absence of observable papillitis, signs and symptoms of ON are usually sufficient to establish the diagnosis of retrobulbar neuritis.

Bilateral presentation, profound loss of vision, and absence of eye pain prior to vision loss, together with atypical neurologic findings should prompt the search for an alternative etiology. Visual symptoms due to ON tend to resolve over several weeks to months and visual function improves to near-normal levels after six months in the majority of cases. There are, however, instances in which qualitative visual changes persist for the duration of a patient’s life [17], [18].

Evaluation

Clinical evaluation of suspected optic neuritis should include the following:

• Best-corrected visual acuity.
• Automated visual field testing.
• Color vision testing with particular attention to red desaturation.
• Pupillary examination with measurement of a relative afferent pupillary defect (RAPD).

  • Note: A RAPD may not be present with bilateral, symmetric optic nerve involvement.
• Optic nerve examination.
• Optical coherence tomography (OCT) evaluation of the retinal nerve fiber layer (RNFL).

If clinical findings are consistent with ON, additional testing should include:

• Magnetic resonance imaging (MRI) of the brain and orbits with and without contrast to look for demyelinating disease.

  • In the active phase, the affected optic nerve will enhance.
  • Demyelinating lesions within the brain confirm the diagnosis of multiple sclerosis (MS).

    • Optic neuritis with two or more typical lesions (one of which is contrast enhancing) is sufficient to diagnose MS (McDonald criteria)
• Clinical findings suggestive of neuromyelitis optica spectrum disorder (NMOSD) should prompt serum NMO-IgG testing.

Treatment / Management

Visual function will return to near-normal levels over weeks to months whether or not treatment any treatment is initiated. However, visual recovery is hastened when treated with corticosteroid therapy.

Based on the long-term results of the Optic Neuritis Treatment Trial (ONTT), the protocol for treating optic neuritis (ON) is widely accepted throughout the medical community.

• Intravenous methylprednisolone (500-1000mg once daily) for three day
• followed by oral prednisone (1mg/kg once daily) for eleven days.

  • Note that oral prednisone alone was found to increase the rate of recurrent ON attacks.

If lesions characteristic of multiple sclerosis (MS) are evident with magnetic resonance imaging (MRI), then immune-modulating therapies should be considered to delay subsequent attacks.

Differential Diagnosis

The differential diagnosis of optic neuritis includes the following conditions:

• Inflammatory, demyelinating disease (classic)
• • Idiopathic optic neuritis
  • Multiple sclerosis
  • Neuromyelitis optica
  • Myelin oligodendrocyte glycoprotein (MOG) antibody disorder
• Ischemic optic neuropathy
• Autoimmune disorders
• • Systemic lupus erythematosus 
  • Giant cell arteritis
  • Sarcoidosis
  • Behcet’s disease
• Infectious [19]
• • Viral
  • • Herpes simplex1 and 2
    • Varicella-Zoster
    • Cytomegalovirus
    • Less frequent:
    • • Human immunodeficiency, Epstein-Barr, Dengue fever, West Nile, Chikungunya
      • Measles, Mumps, Rubella, Influenza
  • Bacterial
  • • Bartonella henselae (Cat-scratch disease)
    • Treponema pallidum (Syphilis)
    • Borrelia burgdorferi (Lyme disease)
    • Mycobacterium tuberculosis (Tuberculosis)
    • Less frequent:
    • • Rickettsioses, Coxiella burnetti (Q fever), Tropheryma whippleii (Whipple disease)
      • Leptospira, Brucella, Mycobacterium leprae (Leprosy)
  • Fungal
  • • Cryptococcus neoformans (Cryptococcus)
    • Candidiasis
    • Histoplasma capsulatum (Histoplasmosis)
    • Aspergillus fumigatus (Aspergillus)
    • Mucormycosis
  • Parasitic
  • • Toxoplasma gondii (Toxoplasmosis)
    • Toxocara canis (Toxocariasis)
    • Diffuse unilateral subacute necrosis (DUSN)
• Drugs
• • Ethambutol/isoniazid
  • Chloramphenicol, sulfonamides
  • Amiodarone, digitalis
  • Quinine, chloroquine, hydroxychloroquine
  • Methotrexate, vincristine, tamoxifens
• Nutritional/toxic
• • Vitamin B deficiencies, particularly vitamin B12
  • Methanol/alcohol
  • Tobacco
• Compressive optic nerve lesions
• • Most often associated with a slow, subtle onset of signs and symptoms

Pertinent Studies and Ongoing Trials

The standard treatment of acute ON was oral corticosteroids when the collaborative, multicenter Optic Neuritis Treatment Trial (ONTT) [20]sought to clarify the role of corticosteroid therapy. More than 450 patients were enrolled at 15 sites between 1988 and 1991. The average age of enrolled subjects was 32, and most were Caucasian (85%) and female (77%). Subjects were randomized to receive oral prednisone (1 mg/kg daily for two weeks) or intravenous methylprednisolone (250 mg every 6 hours for three days) followed by either oral prednisone for the balance of the two weeks or an oral placebo. 

Most subjects in each cohort recovered visual function in the first 1 to 3 months. Visual improvement occurred more rapidly in subjects treated with intravenous methylprednisolone, but there was no difference in the cohorts receiving oral corticosteroids and placebo. Visual acuity did not fully return in many subjects with initial visual acuities of 20/200 or worse. Visual outcomes at six months were similar in all cohorts but optic neuritis recurred twice as often in subjects who received prednisone. 

At one year there were no differences in visual function (acuity, visual field, color discrimination, and contrast sensitivity) between subjects who received placebo and corticosteroids (VA of 20/40 or better: placebo (95%), intravenous methylprednisolone (94%), and oral prednisone (91%) [21]. Visual recovery [22],[23],[24],[25], visual field results [26],[27], and neurologic consequences of ON [28],[29],[30],[31],[10],[32]have been reported at three years 7864737[33],[34] and 15 years [35],[36].

Diagnostic and treatment guidelines of ON have evolved over time [37],[38],[39],[40]to help physicians differentiate typical ON from the atypical variants associated with more complex neurologic disorders.

Prognosis

The prognosis for patients with ON depends on the underlying etiology.

Short-term: Pain with eye movement usually resolves within days to weeks. Visual acuity and color perception improve over two weeks to three months, and nearly 90% of patients achieve near-normal function by six months. Only 3% of patients have BCVA of 20/200 or worse after 5 years [22].

Long-term: In 15-20% of cases optic neuritis precedes the development of multiple sclerosis [9],[10], and recurrent ON increases the risk of developing MS or neuromyelitis optica spectrum disorders (NMOSD) [7]. Approximately 50% of patients with MS have had at least one ON attack within the prior 15 years.

Pearls and Other Issues

To reduce the potential for visual impairment, neurologic disabilities, and physical limitations, optic neuritis must be recognized quickly and accurately. 

Patients with acute optic neuritis and the following characteristics have a lower risk of developing multiple sclerosis:

• No demyelinating lesions on MRI. 
• Optic disc swelling.
• Male gender.

 Other causes of optic nerve disease should be considered when:

• Vision loss is bilateral, especially in older patients.
• Deterioration in visual due to presumed optic neuritis persists without improvement after five weeks.
• Vision loss is not accompanied by eye pain. 
• Retinal hemorrhage or marked optic disc edema is present.

Enhancing Healthcare Team Outcomes

The management of the patient with optic neuritis (ON) requires the close coordination of a variety of healthcare professionals.  

The initial treatment is managed by a neuro-ophthalmologist or a neurology team familiar with the guidelines derived by the Optic Neuritis Treatment Trial (ONTT).

The probability of developing multiple sclerosis (MS) within 15 years of the initial ON attack is 50%[10].

For patients with MS or at high risk for developing MS, an array of healthcare specialists come together to provide comprehensive care.

The healthcare team provides a wide range of services, some of which are listed below.

A complete team will include a combination of the following providers:

• Neurology team to manage the diagnosis and treatment.

  • Neurologist
  • Advanced practice professionals (APP)

    • Nurse practitioners and advanced practice nurses (NP)
    • Physician assistants (PA)
• Rehabilitation specialists to enhance strength, physical stability, and musculoskeletal function.

  • Physical medicine and rehabilitation (PMR) physician management.
  • Physical therapists (PT) to facilitate strength, balance, range of motion, and alleviate musculoskeletal pain.
  • Occupational therapists (OT) to facilitate activities of daily living skills.
• Medical specialists

  • Mental health specialists

    • Psychiatrists/psychologists to manage mental health concerns.
    • Clinical social workers to provide appropriate resources, advocate for patient rights.
  • Neuro-ophthalmologists to manage visual deficiencies related to neurologic disease.
  • Low vision specialists present aids to ameliorate the barriers inherent to diminished visual function.
  • Urologists/gynecologists
• Pharmacists to provide patient education and monitor the complex medication regimen.
• Primary care providers coordinate overall health status and manage concomitant conditions. 
• Well-being professionals provide lifestyle modifications that benefit nutrition, fitness, and resilience.

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Disclosure: Christian Guier declares no relevant financial relationships with ineligible companies.

Disclosure: Thomas Stokkermans declares no relevant financial relationships with ineligible companies.