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Girl presents with eye pain and decreased vision
The left pupil was nonreactive to light with a 4+ afferent pupillary defect, and the nerve fiber layer was thinner in the left eye.
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A 15-year-old African-Asian teenager was referred to our office for 3 days of pain and decreased vision in her left eye. She awoke 3 days earlier with mild pain and blurry vision, which progressed over the following 72 hours to severe pain that was worse with eye movement and profound vision loss. She did not have any prior vision problems and had never had an eye exam in the past. She had no medical issues and was on no medication.
Examination
The patient’s vision was 20/20 in the right eye and no light perception in the left eye. The right pupil was round and reactive to light, and the left pupil was nonreactive to light with a 4+ afferent pupillary defect. Extraocular motility and IOP were normal in both eyes. Confrontation visual fields were full in the right eye. Color vision was normal in the right eye by Ishihara color plate testing. Anterior segment examination was unremarkable. Dilated examination was also unremarkable and demonstrated no optic nerve swelling or clinical pallor (Figure 1).
Optical coherence tomography at the time of presentation showed slight asymmetry of the nerve fiber layer, with relative thinning in the left eye, with an average nerve fiber layer thickness of 98 µm and 75 µm in the right eye and left eye, respectively.
Figure 1. Fundus photography of the right eye and left eye at the time of presentation. No optic nerve swelling or pallor was noted clinically at the patient’s initial visit, although fundus photography of the left eye gave the appearance of mild relative pallor compared with the right due to a difference in exposure.
Images: Tawse KL, Hedges TR
What is your diagnosis?
Optic neuropathy, normal fundus
The differential diagnosis for optic neuropathy with a normal fundus is extensive but was narrowed by the reported subacute onset, accompanying pain and degree of vision loss, which together were most suggestive of an inflammatory optic neuropathy.
MRI of the brain and orbits with contrast was normal with no obvious optic nerve enhancement, although the study was limited by artifact from the patient’s braces. The patient was admitted to the hospital, and intravenous methylprednisolone was initiated as empiric treatment for inflammatory optic neuropathy. Cerebrospinal fluid from a lumbar puncture was normal and negative for oligoclonal bands. Angiotensin converting enzyme, lysozyme, RPR, Lyme, and Bartonella tests were negative. Visual evoked potential (VEP) performed at the time of admission showed decreased amplitudes and delay on the left but was normal on the right.
Two days into her hospitalization, the patient was able to count fingers at 1 foot with extreme eccentric fixation. After 3 days of IV methylprednisolone (1 g daily), she was placed on a high-dose prednisone taper and discharged from the hospital. Three weeks after discharge, while still on a moderate dose of prednisone, she returned for follow-up and vision remained very poor at 7/200 with extreme eccentric fixation.
Discussion
Neuromyelitis optica (NMO), also known as Devic’s disease, is a relatively rare idiopathic autoimmune inflammatory disorder of the central nervous system that preferentially affects the optic nerves and spinal cord. Antibodies to aquaporin 4 (AQP4), a water channel densely expressed on astrocytes that form part of the blood-brain barrier, produce an antibody-mediated astrocytopathy that is distinct from demyelinating disorders such as multiple sclerosis (MS). Prevalence has been reported from 0.5 to 4.4 per 100,000 people, with a fairly constant frequency worldwide. However, given a much lower prevalence of MS in Asian cohorts, there is a much higher NMO-MS ratio in these populations, and the diagnosis of NMO should be considered in any patient of Asian descent presenting with symptoms including optic neuritis.
Testing for the anti-AQP4 antibody using immunoassay is highly specific for neuromyelitis optica but has moderate sensitivity; 20% to 30% of patients with the disease will test negative. In such cases, diagnosis is made based on clinical and radiologic features of the disease. MRI of the brain and spinal cord should be performed in all patients suspected of the diagnosis. Long spinal cord lesions as well as a brain MRI showing an absence of characteristic white matter lesions, and thus not meeting the criteria for MS at the disease onset, are supportive criteria for the diagnosis, in addition to optic neuritis and acute myelitis.
Patients with NMO generally have a worse prognosis with poor response to therapy as compared to those with MS. Given the rarity of this disease, no large-scale randomized trials have been conducted evaluating treatment, and high-dose intravenous methylprednisolone remains the standard of care for acute NMO, based on historical evidence when NMO was treated as a variant of MS. However, in refractory cases, the use of plasmapheresis has more recently been described with favorable outcomes in several case series and has been shown to significantly reduce the level of anti-AQP4 antibody circulating in the serum. In terms of maintenance therapy, a variety of immunosuppressive and immunomodulatory agents have been used. Most recently, the use of rituximab, an anti-CD20+ B-cell agent, has shown promising results in patients with NMO, with an 87% reduction in annualized relapse rate over 5 years and 60% of the patients remaining relapse-free over that course of time.
The profound vision loss, absence of other evidence of demyelinating disease on MRI and subacute onset of symptoms in our patient were all suggestive of the diagnosis of NMO. Although the average nerve fiber layer thickness was normal in both eyes on OCT, the relative asymmetry and borderline thinning in the left eye compared with the right eye at the time of presentation may have indicated prior subclinical events. The diagnosis was confirmed by a strongly positive neuromyelitis optica antibody (anti-AQP4 antibody).
Clinical course
Given the persistent poor vision and a repeat VEP that showed no significant objective improvement in optic nerve function, the patient was readmitted to the hospital 3 weeks after discharge for a repeat course of IV steroids. After 3 days of IV methylprednisolone, there was no improvement in the vision in her left eye, and the decision was made to initiate a trial of plasmapheresis. Treatments were scheduled every other day for a total of five treatments. After her third treatment, vision improved to 20/30 in the left eye with return of central fixation. After completion of the full course of plasmapheresis, she was given a single dose of IV rituximab and discharged home.
Two weeks after discharge, the patient’s best corrected visual acuity was 20/25 in the left eye and improved to 20/20 after 2 more weeks. At that time, color vision by pseudochromatic plates was 20/20 in the right eye and 19/20 in the left. Visual field testing showed a full field in the right eye with persistent visual field loss in the left eye (Figure 2). A 2+ afferent pupillary defect remained in the left eye, and OCT confirmed nerve fiber layer loss in the left eye (Figure 3). Funduscopy demonstrated left optic nerve pallor (Figure 4).
Figure 2. Visual field testing 4 weeks after treatment with plasmapheresis showed a remaining predominantly nasal visual field loss in the left eye (a) and a full field in the right eye (b).
Figure 3. Optical coherence tomography 4 weeks after plasmapheresis showed diffuse nerve fiber layer loss in the left eye compared with the right. Average RNFL thickness was 91 µm and 63 µm in the right eye and left eye, respectively.
Figure 4. Dilated fundus exam 4 weeks after completion of treatment demonstrated optic nerve pallor in the left eye.
At the patient’s most recent visit, her vision remained stable and she was doing well on maintenance therapy with periodic infusion of rituximab based on B-cell monitoring with no relapses.