Childhood Optic Neuritis 

Updated: Nov 02, 2021
Author: Honey H H Herce, MD; Chief Editor: Edsel B Ing, MD, PhD, MBA, MEd, MPH, MA, FRCSC 

Overview

Practice Essentials

Optic neuritis (ON) is an inflammatory process involving the optic nerve. Optic neuritis may be associated with other neuro-inflammatory syndromes that cause systemic effects.

Pediatric optic neuritis is a rare childhood presentation but can account for 25% of pediatric acute demyelinating syndromes.

Background

In children, most cases of optic neuritis are due to an immune-mediated process. Pediatric optic neuritis can account for 25% of pediatric acute demyelinating syndromes.[3]  Children younger than 10 years usually present with bilateral optic neuritis, whereasile older children usually present with unilateral optic neuritis.[1] These cases of optic neuritis may be associated with a viral or other infection or with immunization. Less commonly, pediatric optic neuritis may be the first manifestation of multiple sclerosis (MS) or part of a more diffuse demyelinating disorder, including acute disseminated encephalomyelitis, neuromyelitis optica (Devic disease), or optic neuritis related to myelin oligodendrocyte glycoprotein (MOG) IgG antibody.[2, 36] Optic neuritis may be related to specific infections, diseases of the adjacent sinuses or orbital structures, and infectious and infiltrative diseases of the brain or meninges that involve the optic nerves. The image below depicts optic disc swelling in a child with bilateral optic neuritis.

Optic disc swelling in the right eye and left eye Optic disc swelling in the right eye and left eye in a child with bilateral optic neuritis.

The following definitions aid in further understanding optic neuritis:

  • Papillitis - Optic neuritis involving the optic disc with disc edema

  • Retrobulbar optic neuritis - Optic neuritis involving the optic nerve behind the globe. The optic disc appearance should be normal in first-time episodes of retrobulbar optic neuritis.

  • Bilateral simultaneous optic neuritis - Optic neuritis in both eyes occurring within 3 weeks of each other

  • Bilateral sequential optic neuritis - Optic neuritis occurring in both optic nerves but separated by a period of more than 3 weeks

  • Neuroretinitis - Inflammatory process involving the optic discs with exudative changes in the nerve fiber layer of the retina producing a partial or complete macular star. In the past, this condition was called Leber idiopathic stellate neuroretinitis, but now a number of underlying causes for this condition are known. Because this condition is not associated with demyelinating disease and does not imply a future risk of MS, the distinction is important.

Pathophysiology

Possible mechanisms of inflammation in immune-mediated optic neuritis are the cross-reaction of viral epitopes and host epitopes and the persistence of a virus in central nervous system (CNS) glial cells. Patients with optic neuritis due to neuromyelitis optica spectrum disorder lack the aquaporin-4 antibody.[1]

Epidemiology

Incidence

The incidence of pediatric optic neuritis in Canadian children is estimated to be 0.2 per 100,0003 Optic neuritis is much less common in children than in adults but is not rare and accounts for approximately a quarter of pediatric acute demyelinating syndromes.4 In one combined series, children comprised 5% of cases. In addition, children may also present with optic neuritis in combination with other inflammatory conditions such as acute disseminated encephalomyelitis or neuromyelitis optica.1

Mortality/Morbidity

Patients with optic neuritis have a good prognosis, but a minority of patients experience persistent visual loss. Patients with neuromyelitis optica generally have a poorer recovery. When optic neuritis is associated with other CNS diseases, the morbidity and mortality of those disorders contribute substantially to the final outcome.

Race

Optic neuritis is more common in whites than in other races.[5]

Sex

In both children and adults, a female predominance exists. Females comprise 60-75% of patients.

Age

Optic neuritis may occur at any age, including in infants younger than 1 year.  The mean age of presentation for pediatric optic neuritis can range from 9-11 years of age.[4]

A comparison of adult optic neuritis and childhood optic neuritis is presented in Table 1. These features are generally true but are not absolute, and they do overlap.

Table 1. Comparison of Features of Optic Neuritis in Adults and Children (Open Table in a new window)

Adult Optic Neuritis

Pediatric Optic Neuritis

Unilateral

Often bilateral in children < 10 years[6]

Retrobulbar optic neuritis

Papillitis

Commonly associated with pain on eye movements

Commonly associated with headache

Most often idiopathic

Most often postinfectious or postimmunization

High probability of recurrent inflammatory demyelinating events in the CNS and a diagnosis of MS

Low probability of recurrent demyelinating events and a diagnosis of MS, with the exception of NMO

Prognosis

The prognosis for visual recovery generally is considered good to excellent, regardless of medical treatment, except in cases of neuromyelitis optica (see Medical Care).[4, 7]

Approximately one third of children with optic neuritis present with recurrent symptoms.[1]

Multiple sclerosis

Older children and those with brain MRI abnormalities outside the visual system (viewed using T2-weighted and FLAIR sequences) at presentation are at greater risk for MS.[6] The increased risk for MS in older children may result from a difference in their immune system, hormonal change, or puberty; further research is required. In addition, the risk of evolving multiple sclerosis is probably less in children than in adults, but pediatric optic neuritis is more likely to be an initial manifestation of acute disseminated encephalomyelitis.[7]

Adults with isolated optic neuritis have a substantial risk of developing MS. Approximately 15% of patients with normal MRIs at the time of their optic neuritis develop MS in the next 4 years. However, MRI findings are strongly correlated with risk of recurrence of demyelinating events.[6] Fifty percent of patients whose MRIs demonstrate white matter lesions characteristic of MS at the time of their optic neuritis develop clinically definite MS in the next 4 years.

A large study from the Mayo Clinic with a mean follow-up of 20 years produced a life-table analysis showing 13% of children with optic neuritis had progressed to clinically or laboratory-supported definite MS at 10 years (see Table 2 below). As in adult studies, those patients converting to MS were more likely to do so early; however, the longer the follow-up interval, the more patients there were who developed MS.[6]

A smaller study by Wilejto et al found that 36% of children with optic neuritis developed MS.[8] All who did had abnormalities on the initial MRI, and bilateral cases were more likely to go on to develop MS.

Table 2. Life-Table Analysis of the Risk for Development of MS in Children With an Isolated Attack of Optic Neuritis [9] (Open Table in a new window)

Age

Risk for Development of MS

10 years

13%

20 years

19%

30 years

22%

40 years

26%

Both adults and children with more severe optic disc swelling are less likely to develop MS, and those with both severe optic disc swelling and retinal exudates rarely develop MS.

Patient Education

With Uhthoff symptom, patients who have had demyelinating lesions with recovery often have symptoms return with exercise, exposure to heat (eg, hot baths), or febrile illnesses; a rapid return to baseline occurs when body temperature returns to normal. Warning patients about Uhthoff symptom is important so that they do not think they are having a recurrence.

For excellent patient education resources, see eMedicineHealth's patient education article Multiple Sclerosis.

 

Presentation

History

In general, obtaining an accurate history from children may be difficult. Young children may not notice unilateral visual loss and may not report bilateral visual loss until their behavior indicates visual loss to parents or teachers. A review of systemic symptoms should be aimed at detecting recent vaccinations, infections, or vasculitis.

History of present illness (HPI) findings

Optic neuritis produces a subacute loss of vision, reaching its maximum deficit in a few days to 2-3 weeks. Unilateral optic neuritis may progress to bilateral optic neuritis (< 2 weeks is considered bilateral simultaneous optic neuritis; 2-12 weeks is considered bilateral recurrent optic neuritis).[1] In many cases, recovery is already underway at 2-3 weeks.

Visual symptoms reflect the expected deficit observed in any optic neuropathy, as follows:

  • Loss of visual acuity: Children often experience greater visual acuity deficits. [10]
  • Change in color perception
  • Change in brightness sense
  • Loss of portions of the visual field

Headache is common in children with optic neuritis.

Periorbital pain, especially if it worsens with eye movements, supports a diagnosis of optic neuritis.

Neurologic symptoms may include the following:

  • Prior resolved neurologic symptoms imply a recurrent process, such as MS
  • Ongoing neurologic symptoms may indicate MS, acute disseminated encephalomyelitis, or neuromyelitis optica.

Physical

Decreased visual acuity: Visual acuity is not the most sensitive indicator of optic nerve injury and may be normal; however, most children with optic neuritis have some loss of visual acuity. Occasionally, patients with optic neuritis have severe loss of vision that includes no light perception.[1]

Dyschromatopsia: A deficit in color vision is a more sensitive indicator of optic nerve injury, and, when checked, a deficit is expected that is out of proportion to any loss of visual acuity. Patients report red color desaturation.[1]

Afferent pupil defect: In unilateral cases of optic neuritis, an afferent pupil defect should be present. In bilateral cases of optic neuritis, this sign is less reliable unless the 2 nerves are asymmetrically affected.

Subjective light brightness difference between the 2 eyes is also common in asymmetric or unilateral cases of optic neuritis.

Visual field defects occur from a few hours to days, reaching maximum loss within several days.[1] . The most common visual field defect is a central or cecocentral scotoma, which occurs in 50% of children who are able to undergo formal visual field testing.[4, 23]

Papillitis: In contrast to adults with optic neuritis, in whom 65% of cases are retrobulbar, optic disc swelling may be seen in up to 73% of children with optic neuritis.[4]

Causes

See the list below:

  • Immune mediated

    • In children, as many as 85% of cases of optic neuritis are associated with a recent immunization or an infection, usually a viral infection.

    • Optic neuritis can be associated with a preceding nonviral infection, such as pertussis, infectious mononucleosis, toxoplasmosis, or brucella.

    • Common history: Flu-like illness preceding the onset of vision loss by a week

  • Multiple sclerosis 

  • Neuromyelitis optica, or Devic disease (inflammation of the optic nerve and spinal cord)

  • Myelin Oligodendrocyte Glycoprotein (MOG-IgG+) Seropositive Demyelinating Disease

  • Acute disseminated encephalomyelitis: Monophasic illness with multifocal involvement of the CNS, which could include the optic nerve

  • Idiopathic

  • Lyme disease in endemic areas

  • Specific meningeal infections and infiltrations involving the optic nerves, including cryptococcus, tuberculosis, and sarcoidosis

  • Vasculitis, such as systemic lupus erythematosus

  • Syphilis

  • Leukemia

  • Associated with bee and wasp stings

  • Several cases of optic neuritis have been seen in patients on anti-tumor necrosis factor (anti-TNF) drugs.

  • Causes of neuroretinitis

    • Following a viral syndrome

    • Cat scratch disease

    • Toxoplasmosis

    • Toxocariasis and helminths (The finding of a discrete white inflammatory mass overlying the optic disc is suggestive of toxocariasis and helminths.)

    • Lyme disease, usually stage 2

    • Syphilis, especially secondary syphilis as part of a meningitis

Physical Examination

Visual Acuity

Table 3. Visual Acuity on Examination in Children with Optic Neuritis (Open Table in a new window)

Percentage (%) Visual Acuity
20 20/40 or better at presentation
20 20/50 - 20/190
60 20/200 or worse

Fundus examination

In children, most cases (60%-70%) of optic neuritis involve the optic disc with disc edema (as shown below), as compared to 35% in adults. In addition, most children present with optic nerve pallor.

Optic disc swelling in the right eye and left eye Optic disc swelling in the right eye and left eye in a child with bilateral optic neuritis.

Most pediatric optic neuritis cases result from anterior optic neuritis, in contrast with retrobulbar optic neuritis, which is common in adults. In retrobulbar optic neuritis, the optic disc should be normal. Atrophy of the disc implies a prior episode of optic neuritis or another more chronic process, such as an optic nerve glioma, a craniopharyngioma, or other compressive process.

If macular edema or a macular star (as shown below) is associated, a diagnosis of neuroretinitis rather than optic neuritis should be made.

Neuroretinitis in the right eye of an adolescent w Neuroretinitis in the right eye of an adolescent with cat scratch disease. The optic nerve is swollen, and a deposition of yellowish exudate in the nerve fiber layer of the macula produces a macular star.

Optic nerve abnormalities include papillitis (acute stage) and optic nerve pallor (chronic stage).[1]

Complications

The reported rates of visual recovery after optic neuritis in children vary in the literature depending on follow-up time and criteria for good vision. Most authors have found good visual recovery in 70%-85% of children following optic neuritis.[4, 8, 11]  

 

DDx

Diagnostic Considerations

Childhood optic neuritis is marked by heterogeneity. It may occur as a monophasic illness, recurrent isolated optic neuritis, and recurrent optic neuritis in the context of multifocal inflammatory CNS disease.

Neuromyelitis optica (Devic disease)

Formal diagnostic criteria for neuromyelitis optica are as follows: absolute criteria and one major supportive criterion or two minor supportive criteria.

Absolute criteria include the following:

  • Optic neuritis

  • Acute myelitis

  • No clinical disease outside the optic nerves and spinal cord

Major supportive criteria include the following:

  • Negative brain MRI at disease onset

  • Spinal cord MRI with T2 signal abnormality extending over 3 or more vertebral segments

  • Cerebrospinal fluid (CSF) pleocytosis greater than 50 WBC/mm3 or greater than 5 neutrophils/mm3

Minor supportive criteria include the following:

  • Bilateral optic neuritis

  • Severe optic neuritis with fixed visual acuity worse than 20/200 in at least one eye

  • Severe, fixed, attack-related weakness in one or more limbs

Since there may be a delay between the optic neuritis and the myelitis, and since the treatment will be different, suspicion for neuromyelitis optica should prompt laboratory study for NMO (neuromyelitis optica) antibody.

Myelin Oligodendrocyte Glycoprotein (MOG-IgG+) Seropositive Demyelinating Disease

Myelin Oligodendrocyte Glycoprotein Serepositive Demyelinating disease (MOG IgG+) is a recently discovered cause of optic neuritis.  The disease phenotype associated with MOG seropositivity is still being studied. Patient presentation for optic neuritis has been found to have a bimodal distribution with younger patients less than 9 years of age exhibiting MOG-IgG in association with ADEM and older children with clinically isolated optic neuritis or NMO-SD phenotype. [36, 37]

Differential Diagnoses

  • Chronic Relapsing Inflammatory Optic Neuropathy

  • Craniopharyngioma

  • Diabetic Papillopathy

  • Leber Hereditary Optic Neuropathy

  • Medication Related

    eg, nivolumab

  • Multiple Sclerosis

  • Neuroretinitis

    Due to infectious causes (Bartonella, Syphilis, Lyme, Toxoplasma, Toxocara) or idiopathic causes

  • NMO Spectrum Disorder

  • Optic nerve or optic nerve sheath tumor

    Due to glioma or meningioma

  • Papilledema

    Due to increased intracranial hypertension (idiopathic intracranial hypertension, meningitis, intracranial mass lesion, hydrocephalus, or venous thrombosis)

  • Pituitary Adenoma

  • Systemic Lupus Erythematosus

 

Workup

Approach Considerations

Visual acuity, color vision, afferent pupillary defect (if visual loss is asymmetrical), and confrontation fields should be documented. Perimetry and optical coherence tomography (OCT) of the optic nerve should be performed whenever feasible. Visual evoked potentials may be helpful.

Exclude infectious, genetic, or neoplastic processes.

Laboratory Studies

Systemic laboratory studies can be performed directed by features in the history and physical examination consistent with other non–immune-mediated causes of optic neuritis.

Neuromyelitis optica (NMO) antibody in serum (anti aquaporin-4 immunoglobulin) helps establish a diagnosis of neuromyelitis optica, although a spectrum of diseases may have this antibody. Testing for myelin oligodendrocyte glycoprotein may be helpful, as the disease course in patients with this spectrum of NMO may be relatively benign.

Myelin Oligodendrocyte Glycoprotein (MOG-IgG+) antibody testing in the serum helps establish a diagnosis of Myelin Oligodendrocyte Glycoprotein (MOG-IgG+) Seropositive Demyelinating Disease.  This can be helpful in both the diagnosis and prognosis of the patient.[36, 37]

Lumbar puncture with measurement of opening pressure excludes papilledema secondary to intracranial hypertension.

Cerebrospinal fluid (CSF) studies may indicate the presence of a simultaneous meningitis or encephalitis, but a mild lymphocytic pleocytosis may be present with optic neuritis.

Imaging Studies

MRI of the brain and orbits with contrast should be performed. The MRI should exclude extrinsic compressive lesions.

Enhancement of the optic nerve in the orbit or the intracranial segment of the optic nerve or of the chiasm is helpful in confirming the diagnosis. Some enlargement of the optic nerve is present in optic neuritis, and a diagnosis of optic nerve glioma should not be made unless the clinical course dictates reconsideration of the diagnosis of optic neuritis.

Meningeal enhancement suggests some form of infectious or noninfectious meningitis and may merit additional workup and different therapy.

Changes in the CNS white matter may confirm other neurologic involvement found on physical examination, may affect the prognosis of MS in the future, or may indicate the presence of acute disseminated encephalomyelitis. One third of children with optic neuritis will have asymptomatic white matter lesions of the brain as compared to one half of adults with optic neuritis.

The images below depict characteristics relevant to a diagnosis of optic neuritis.

T1 contrast enhanced axial section of an MRI of th T1 contrast enhanced axial section of an MRI of the orbital optic nerve of a child with optic neuritis on the left side. The arrows point to the left optic nerve that enhances along its entire orbital course.
T1 contrast enhanced coronal section of the MRI of T1 contrast enhanced coronal section of the MRI of the orbital optic nerve. The arrow points to the enhancing left optic nerve.
T1 contrast enhanced axial section of an MRI of th T1 contrast enhanced axial section of an MRI of the intracranial optic nerves. Enhancement of both optic nerves is seen. The arrow indicates the left optic nerve.
T1 contrast enhanced coronal section of the MRI sh T1 contrast enhanced coronal section of the MRI showing the optic nerves that both enhance. The arrow points to the left optic nerve.
T2 axial section of an MRI through the cerebral he T2 axial section of an MRI through the cerebral hemisphere of a boy with bilateral optic neuritis. Note high-signal abnormalities in the cerebral white matter that are most prominent in the posterior hemispheres. This is suspicious for mild acute disseminated leukoencephalitis.

To either diagnose or exclude neuromyelitis optica (Devic disease), an MRI of the spinal cord with contrast is necessary if symptoms and signs consistent with a spinal cord process are present.

Other Tests

Optical coherence tomography (OCT) is often used to assess neuronal injury, including retinal nerve fiber layer (RNFL) thickness. Pediatric patients with MS have been reported to have a 10%-20% thinner RNFL layer.[1]

 

Treatment

Approach Considerations

Optic neuritis may be a primary manifestation of an underlying disorder such as MS or a system autoimmune condition. Recurrence of ON occurs in approximately one third of patients.[1]

The prognosis for visual recovery is excellent in adults with or without medical therapy, as found in the Optic Neuritis Treatment Trial (ONTT).[12] The first pilot study of pediatric optic neuritis was launched in 2016, a 4-year study of children aged 3-15 years with acute optic neuritis in one or both eyes.[10] Data are not yet available from this trial.

Oral corticosteroids should not be used in treatment, as data from the Optic Neuritis Treatment Trial indicate that they increase the risk for optic neuritis relapse.[10]

Medical Care

The established treatment for children with optic neuritis is intravenous methylprednisolone 30 mg/kg per day (maximum 1 g daily) for 3-5 days. While steroids are not expected to change the medical outcome of an optic neuritis episode, they increase the speed of recovery to baseline.[1]

No prospective study of the prognosis for visual recovery in children is available; most, but not all, studies of children have found that visual recovery is good. Specifically, studies have indicated good recovery of high-contrast visual acuity in children.[1] In children with optic neuritis, pulse steroids may speed recovery from 7 weeks to 2 weeks. This may be valuable to avoid psychosocial challenges, including the need to make up schoolwork, or affect other tasks because of visual limitations.[1]

Treatment of the initial event in neuromyelitis optica, whether it is optic neuritis or myelitis, also uses high-dose intravenous steroids, but refractory cases are common and other therapies may be needed. Currently, plasma exchange (PLEX) is favored in those cases, but intravenous immune globulin (IVIG) has also been used.[11, 37]  For (MOG-IgG+) Seropositive Demyelinating Disease, current first-line treatment includes either intravenous corticosteroids, IVIG, or PLEX at the discretion of their managing team, however further data is needed on which method helps prevent relapse.[37]

The equivalent doses of 4 commonly used drugs to treat optic neuritis are provided in Table 4.

Table 4. Equivalent Doses of Commonly Used Corticosteroid Medications (Open Table in a new window)

Corticosteroid Drug

Approximate Equivalent Dose

Prednisone

5 mg

Prednisolone

5 mg

Methylprednisolone

4 mg

Dexamethasone

0.75 mg

See related CME at Optic Neuritis: Diagnosis, Treatment, and Prognosis.

Consultations

The management of a child with optic neuritis is a combined effort by the ophthalmologist and the neurologist. Ophthalmologic input is required to distinguish between optic neuritis and neuroretinitis and to monitor visual response. Neurologic input is required to evaluate possible generalized CNS involvement and to make appropriate decisions and recommendations based on the future risk of MS. An immunologist should also be consulted for children with underlying immunologic pathology.

Children taking etanercept or other tumor necrosis factor (TNF) inhibitors should be reevaluated by their rheumatologists.

Long-Term Monitoring

Children who do develop MS may be more likely to develop disability at a younger age. Monitoring patients who had no associated neurologic signs or symptoms at the time of their optic neuritis will allow early diagnosis. Treatment of those patients for early onset MS with the disease modifying agents that are used in adults may be an option.

If optic neuritis is a suspected first manifestation of an underlying disorder, prophylactic treatment must be dictated by the causative disorder. For example, with rheumatologic disorders, steroids and long-term immunotherapy may prevent the recurrence of optic neuritis or other inflammatory CNS events.

Recurrence of optic neuritis during or shortly after the discontinuation of steroids indicates a steroid-dependent optic neuritis and requires reevaluation and a more prolonged taper of corticosteroids.

Further Outpatient Care

Outpatient follow-up care should include monitoring both visual recovery and recovery from neurologic or systemic disorders that were associated with optic neuritis.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Corticosteroids

Class Summary

A widely used group of drugs. They have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli. GI tract absorption is approximately 85% of intravenously administered doses. Corticosteroids are well tolerated. A brief course of steroids is not expected to produce significant adrenal complications. Many physicians prescribe an H2 blocker to prevent GI tract distress.

Methylprednisolone (Medrol, Adlone, Medralone injection)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Prednisone (Meticorten, Orasone, Deltasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

 

Questions & Answers

Overview

What is childhood optic neuritis?

What is the pathophysiology of childhood optic neuritis?

What is the prevalence of childhood optic neuritis?

What is the morbidity associated with childhood optic neuritis?

What are the racial predilections of childhood optic neuritis?

What are the sexual predilections of childhood optic neuritis?

How do the clinical features of optic neuritis vary between adults and children?

What is the prognosis of childhood optic neuritis?

How does childhood optic neuritis affect the risk for development of multiple sclerosis?

What is included in patient education about childhood optic neuritis?

Presentation

Which clinical history findings are characteristic of childhood optic neuritis?

Which physical findings are characteristic of childhood optic neuritis?

What causes childhood optic neuritis?

What is the visual acuity on examination in childhood optic neuritis?

Which fundus exam findings suggest childhood optic neuritis?

What is the visual prognosis after childhood optic neuritis?

DDX

Which conditions are included in the differential diagnoses of childhood optic neuritis?

What are the differential diagnoses for Childhood Optic Neuritis?

Workup

What is the workup approach for childhood optic neuritis?

What is the role of lab testing in the workup of childhood optic neuritis?

What is the role of imaging studies in the workup of childhood optic neuritis?

What is the role of optical coherence tomography (OCT) in the workup of childhood optic neuritis?

Treatment

How is childhood optic neuritis treated?

Which specialist consultations are beneficial to patients with childhood optic neuritis?

What is included in the long-term monitoring of childhood optic neuritis?

What is included in outpatient follow-up care for childhood optic neuritis?

Medications

What are the goals of drug treatment for childhood optic neuritis?

Which medications in the drug class Corticosteroids are used in the treatment of Childhood Optic Neuritis?