Chapter 53 Other optic neuropathies in childhood

Childhood optic neuritis

Childhood optic neuritis presents the ophthalmologist with many difficulties. First, diagnosis may be difficult. Second, the evidence base for our therapeutic decisions is based on adult studies.

Optic neuritis must be distinguished from neuromyelitis optica (NMO) and neuroretinitis. These are separate entities rather than part of the same spectrum and each requires different investigation and treatment.

Pediatric neurologists must be involved in the management of childhood optic neuritis.

Optic neuritis

Although optic neuritis is diagnosed in children using the same clinical criteria as in adults (subacute visual loss, pain with eye movements, visual field defects, and a relative afferent pupil defect), diagnosis may be more difficult. Children find it difficult to articulate the typical history of optic neuritis and may not present until they are profoundly affected. They may complain that it is dark all the time or insist on keeping the house lights on even in daylight because of impaired brightness sense (Fig. 53.1). Perimetry or fields to confrontation often reveal a central scotoma (Fig. 53.2). The abnormal vision and difficulty navigating may be interpreted as poor gait. Input from a pediatric neurologist is important, because transverse myelitis may be the presenting feature of neuromyelitis optica (NMO) – see below. The conversion rate to multiple sclerosis in children is unclear due to a lack of adequately powered long-term studies. However, as with adults, T2 lesions on MRI scan are associated with an increased risk of developing MS.¹^–³

Fig. 53.1 Bilateral optic neuritis. The severely swollen right (a) and left (b) eye of a 7-year-old girl with bilateral optic neuritis. When she presented she was blind: after 6 weeks her acuities were 0.3 right, 0.4 left.

Fig. 53.2 Optic neuritis in a 7-year-old boy. Sudden onset of visual loss to 6/24 acuity right eye, 1/60 left eye. Central scotomas and color vision loss.

Factors that are associated with a reduced risk of developing MS include young age, bilateral optic neuritis, disk swelling (Fig. 53.3), and antecedent infection.

Fig. 53.3 Bilateral optic neuritis. (A) Bilaterally swollen optic disks. (B) Normal optic disks 2 months later. Complete visual recovery. Same patient as in Figure 53.2.

Neuromyelitis optica

Neuromyelitis optica (NMO) or Devic’s disease is a central nervous system inflammatory disorder that predominantly affects the optic nerves and spinal cord. It is a distinct entity, and in about 70% of cases it is associated with an NMO-IgG autoantibody which targets aquaporin-4 channels. AQP4 is expressed in the collecting duct cells in the kidneys and in astrocytes. It is upregulated by direct insult to the central nervous system. Aquaporins are involved in the conduction of water through cell membranes.⁴ The NMO-IgG antibody is not present in MS. Standard MS immunomodulatory treatment may not be effective. Plasmapheresis may be required if immunosuppression is ineffective. The primary goal of therapy is to prevent future attacks.

NMO should be considered in any case with severe bilateral optic neuropathy particularly with evidence of transverse myelitis. Not all of the features of NMO may be present at the first presentation. The term NMO spectrum disorder is used for those cases with some, but not all, of the disease defining features. The remaining diagnostic features may develop over time.

MRI does not usually show the periventricular white matter lesions seen in typical MS. It is important to specifically request imaging of the spinal cord to detect longitudinal myelitis involving ≥three segments (Fig. 53.4).

Fig. 53.4 (A) Optic atrophy and (B) spinal cord changes in a child with relapsing NMO (AQP4) antibody positive, demonstrating high signal lesions within the cervical and lower thoracic regions. The patient has been relapse free for 2 years after commencing treatment with aziothioprine and oral prednisolone.

(Courtesy of Dr Michael Absoud, Clinical Research Fellow and Dr Evangeline Wassmer, Consultant Paediatric Neurologist, Birmingham Childrens Hospital.)

The diagnostic criteria for NMO are summarized in Box 53.1.

The disease is more prevalent in females than males (greater than 4 : 1 ratio). It is more prevalent among the Black, Asian, and Indian populations. In Europe NMO is very rare and the majority of cases are not associated with NMO-IgG autoantibodies.⁵

In the absence of AQP4 antibodies, the disease is more likely to be monophasic and long-term treatment with azothioprine, mycophenolate, or rituximab is usually not required.⁵

Because a diagnosis of NMO is not always established until well after the presenting illness, rescue treatment with plasmapheresis should be considered in all cases of severe optic neuritis refractory to steroids.

Neuroretinitis is usually unilateral, occasionally bilateral. It is an inflammatory disorder characterized by optic disk edema and formation of a macular star (Fig. 53.5). The primary abnormality is inflammation and increased permeability of the optic disk vasculature, causing leakage of fluid into the peripapillary retina.⁶ The cause of this vasculitis is not clear: some cases have an infectious etiology, most commonly Bartonella henselae (cat scratch disease), also syphilis, tuberculosis, Lyme disease, leptospirosis, and toxoplasmosis.⁷

Fig. 53.5 Stages of evolution of fundus changes in neuroretinitis. (A) At presentation the optic disk is swollen and the macula has an opaque appearance. (B) 3 weeks later there is a well-formed macular star. (C) Further resolution leading later to optic atrophy. (D–F) Neuroretinitis in the left with resultant optic atrophy in the fellow eye.

(Picture reproduced with permission of Valerie Purvin Midwest Eye Institute USA. From Journal of Neuro-Ophthalmology 2011; 31: 58–68. Neuroretinitis: Review of the Literature and New Observations.)

Because a macular star can occur in papilledema, symptoms and signs of raised intracranial pressure should be sought and further investigations, including a lumbar puncture and an MRI scan, may be required. Malignant hypertension should also be excluded.

Fluorescein angiography discloses an arteriolar vasculitis on the optic disk. The diagnosis is established by serologic testing, enzyme immunoassays, or indirect immunofluorescence.

The evidence base for treatment is poor and spontaneous recovery is common. Nevertheless most ophthalmologists treat neuroretinitis associated with cat scratch disease with antibiotics.