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Girl referred for visual field defect, ‘heavy’ sensation behind eye
The left optic nerve was mildly edematous and hyperemic superonasally on dilated exam, and OCT revealed a mildly thickened left optic nerve head.
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A 13-year-old girl was referred from an outside ophthalmologist with a complaint of a “gray line going straight through” the visual field in her left eye that began 2 days before presentation. One day before presentation, she began having a “dull, heavy” sensation behind her left eye, with a severity of 8 out of 10, as well as expansion of her visual field defect peripherally, described as “the gray blob spread.”
On presentation, she described her pain as “minimal” but noted her vision still remained very poor. She denied any prior episodes. Review of systems was remarkable for an episode of neck stiffness and headache. Her primary care physician treated the neck stiffness with topical anesthetic for presumed muscle strain, and the neck stiffness and headache resolved within days. She also noted bruising along the vertebrae on her back approximately 1 week before presentation. She denied any fevers, numbness, tingling or weakness.
Her ocular history was significant for myopia in both eyes and soft contact lens wear. Her medical history was remarkable for Lyme disease 2 years prior. Symptoms during the acute episode included neck stiffness, difficulty breathing and a “bulls-eye” rash. She was treated with a complete course of oral doxycycline. Her vaccinations were up to date, and she had no prior surgeries. She lived with her parents, attended junior high school, and denied any use of drugs or alcohol. She was not sexually active and had no recent travel. She reported that she occasionally plays in the woods near her home but had not had any recent camping or hiking trips.
Examination
Uncorrected visual acuity was 20/20 in the right eye and counting fingers at 4 feet with no improvement with pinhole in the left eye. Pupil exam revealed a sluggish left pupil with a 4+ relative afferent pupillary defect. IOPs were normal.
Images: Wright EC, Strominger MB
On confrontation visual fields, the right eye was full and the left eye was grossly constricted and unreliable, given the patient’s count finger visual acuity. She was able to identify 10 of 10 Ishihara color plates in her right eye and 0 of 10 in her left. On red desaturation questioning, she noted that the color red appeared 75% less so in the left eye relative to the right eye.
Extraocular movements were full in both eyes. She had pain with extraocular motility in her left eye. The external exam was normal, and the anterior segment exam by slit lamp was grossly unremarkable. On dilated exam, the left optic nerve appeared mildly edematous and hyperemic superonasally (Figure 1). OCT revealed a mildly thickened left optic nerve head relative to the right optic nerve head (Figure 2). There was mild hyperintensity of the nerve fiber layer and inner retina in the left eye relative to the right eye on OCT of the macula (Figure 3). Ganglion cell analysis by OCT was unremarkable.
What is your diagnosis?
Vision loss
In a young patient with painful vision loss, relative afferent pupillary defect and subtle disc swelling, a diagnosis of optic neuritis is high on the differential. Optic neuritis can be categorized into infectious, autoimmune, demyelinating and idiopathic etiologies.
Infectious causes include Lyme disease, tuberculosis, syphilis and various viral diseases. More common autoimmune causes include sarcoidosis, systemic lupus erythematosus and post-vaccination (measles, mumps, chickenpox). Demyelinating etiologies include multiple sclerosis and neuromyelitis optica.
In a patient with subacute vision loss and relative afferent pupillary defect, tumors of the visual pathway warrant consideration and appropriate imaging. Given the patient’s recent history of bruising along her vertebrae, an infiltrative process such as leukemia remained fairly high on the differential. The patient’s age, history of present illness and family history made Leber hereditary optic neuropathy, ischemic optic neuropathy, and metabolic or toxic optic neuropathies less likely etiologies.
The patient was admitted to the hospital, and a comprehensive work-up was obtained. CBC with differential, CMP, coagulation panel, ANA, ESR, CRP and urinalysis were all within normal limits. Peripheral C6 Lyme titer was elevated at 2.60 (normal range less than 0.90). Western blot testing was positive for Lyme IgM antibodies and negative for Lyme IgG antibodies. Lumbar puncture was negative for oligoclonal bands, NMO antibodies and myelin basic protein. Cerebrospinal fluid (CSF) IgG levels were low; CSF Lyme IgG, IgA and IgM antibodies were negative; and CSF lymphocytes were within normal range. CSF neutrophils, however, were moderately elevated at 36, although there were no organisms seen on Gram stain.
MRI of the brain and orbits with gadolinium revealed enhancement of the pre-chiasmatic left optic nerve, including within the optic canal, and mild enhancement of the intraorbital fat. There was no acute intracranial abnormality, such as hemorrhage or mass (Figure 4).
Given the patient’s elevated level on C6 Lyme ELISA and Lyme IgM by Western blot, moderate elevation of neutrophils in the CSF, and acute optic neuritis, a diagnosis of neuroborreliosis was made. She received intravenous Solu-Medrol (methylprednisolone sodium succinate) 1 g daily for 5 days. When her serum Lyme studies resulted, she was started on intravenous ceftriaxone 1 g daily for 3 days. After 5 days of hospitalization, she was discharged home on an oral prednisone taper and doxycycline 100 mg by mouth twice daily for 14 days.
Discussion
Lyme disease is a vector-borne illness and is endemic in the northeastern United States. It results from transmission of a bacterial species of the spirochete class, Borrelia burgdorferi, by the Ixodes tick. For the diagnosis of early disseminated and late disease, the CDC recommends a two-tiered approach consisting of initial ELISA followed by confirmatory IgG and IgM Western blots. The C6 peptide is a highly antigenic Borrelia membrane protein for which ELISA testing has 99% specificity. This is a drastic improvement from previous ELISA tests that typically yielded false positive results approximately 20% of the time. Additionally, the C6 Lyme ELISA is highly sensitive, detecting nearly twice as many patients with early Lyme disease as compared with Western blot testing. Lyme Western blot testing is typically ordered in C6 Lyme ELISA-positive patients in order to gain more information regarding the chronicity of the infection because IgG levels are not detectable until 4 weeks after the onset of symptoms.
Neuroborreliosis results from invasion by the vector of the cerebral or spinal meninges and occurs in only 4% to 15% of infected children. Neuroborreliosis may manifest as cranial neuritis, radiculitis, encephalitis, myelitis or demyelinating lesions. Optic neuropathy is a rare manifestation of neuroborreliosis, and the relationship between Lyme disease and retrobulbar optic neuritis has been debated due, in part, to a lack of uniform diagnostic criterion as well as varying infectious strains in different regions of the United States and world.
Diagnostic criteria of Lyme optic neuritis is widely debated in the literature, but most commonly is based on clinical history and symptoms and the presence of serum IgM and IgG antibodies to B. burgdorferi by either ELISA or Western blot. CSF analysis should be considered, but false negatives for Lyme titers are not uncommon. The intrathecal anti-Borrelia antibody index has a sensitivity ranging from 55% to 80% and a specificity greater than 95%, and it is a necessary diagnostic criterion for neuroborreliosis in Europe but not in the United States.
The most recent literature review of patients with retrobulbar optic neuritis and Lyme disease was published in 2007 by Krim and colleagues, who cited 14 previously reported patients as well as their own case report. Krim and colleagues cited Sibony’s diagnostic criterion for Lyme optic neuritis and noted that among the 15 cases reported, only their own patient satisfied these stringent criterion:
“According to Sibony’s recommendations, strong evidence of optic neuritis associated with active Lyme disease requires the following elements: optic neuritis, endemic exposure, negative VDRL, exclusion of multiple sclerosis and a positive serum titer (ELISA or indirect fluorescent antibody), in association with at least one of the following: (1) encephalitis or meningitis with CSF pleocytosis, intrathecal antibody production or CSF PCR positive for Borrelia burgdorferi DNA and a positive serum or CSF Western blot; (2) recent signs of Lyme disease, such as facial nerve palsy, arthritis or radiculoneuritis, with positive serum ELISA confirmed by Western blot; and (3) recent physician diagnosed erythema migrans.”
Treatment of neuroborreliosis, and in this case retrobulbar optic neuritis, consists of intravenous antibiotics (typically ceftriaxone) for 3 to 5 days followed by 2 weeks of doxycycline 100 mg by mouth twice daily. Typically, depending on the degree of inflammation, patients will also require intravenous Solu-Medrol for 3 to 5 days, followed by an oral prednisone taper. Appropriate Lyme serologies and follow-up MRI should be obtained to follow the course and resolution of the infection.
Follow-up
Within 1 week of diagnosis, the patient’s visual acuity in her left eye had returned to 20/20. At 1-month follow-up, she was 20/15 in each eye, and her relative afferent pupillary defect, mild optic nerve head edema and hyperemia had resolved. Two months after her hospitalization, the patient had a repeat MRI of her brain and orbits that revealed mild asymmetric atrophy and interval resolution of the abnormal enhancement of the left optic nerve, compatible with sequelae of an episode of prior optic neuritis. At this time, she still had no evidence of demyelinating disease on MRI of her brain and spine.
- References:
- Blanc F, et al. Neurology. 2007;doi:10.1212/01.wnl.0000269672.17807.e0.
- Blanc F, et al. J Neurol Sci. 2010;doi:10.1016/j.jns.2010.05.009.
- Jacobson DM. Neurology. 2007;doi:0.1212/WNL.61.8.1162.
- Krim E, et al. J Neurol Neurosurg Psychiatry. 2007;doi:10.1136/jnnp.2006.113761.
- Lesser RL. Am J Med. 1995;doi:10.1016/S0002-9343(99)80045-X.
- verhey LH, et al. Handb Clin Neurol. 2013;doi:10.1016/B978-0-444-52910-7.00020-9.
- For more information:
- Emily C. Wright, MD, and Mitchell B. Strominger, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Kristen E. Dunbar, MD, and Kendra Klein, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.