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Girl experiences progressive vision loss in right eye
The right optic nerve was edematous and hyperemic, and there was a wedge-like extension of fluid from the optic nerve to the macula.
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An otherwise healthy 12-year-old girl was urgently referred from a New Hampshire optometry office to the New England Eye Center in Boston for 3 weeks of decreased visual acuity in the right eye with recent progression. Her initial symptom was pain with eye movement followed by peripheral vision loss that progressed to include central vision. She reported having nausea for the past 2 days but denied headache, fevers, chills, rashes, joint pain, shortness of breath or recent weight change.
Examination
Best corrected visual acuity was hand motions in the right eye and 20/15- in the left eye. The patient was unable to see the Ishihara color plates with her right eye but identified all plates with her left. Her pupils were dilated on arrival, prohibiting observation of pupillary responses. IOP was normal, and extraocular motility was full.
The patient’s slit lamp exam was unremarkable. Her dilated exam revealed an edematous and hyperemic right optic nerve with a wedge-like extension of fluid from the optic nerve to the macula (Figure 1). The veins in the right eye were dilated and tortuous. The left eye was normal. On Cirrus optical coherence tomography (Carl Zeiss Meditec), the patient’s retinal nerve fiber layer measurement was 537 µm in the right eye and 106 µm in the left. High-definition Cirrus OCT imaging of the macula showed photoreceptor and outer nuclear layer disruption nasal to the fovea in the right eye. Some intraretinal fluid was also seen extending from the optic nerve (Figure 2).
Figure 1. Right optic disc edema with hyperemia with some wedge-like extension of fluid into the macula.
Images: Vuong LN, Strominger MB
Figure 2. High-definition OCT of the right macula showing disruption of the photoreceptor and outer nuclear layer nasal to the macula. Some intraretinal fluid is seen nasally, likely tracking from the optic nerve.
On further questioning, the patient revealed that she owned a cat and a dog.
What is your diagnosis?
Optic nerve edema
Infectious sources, including Bartonella and Lyme, are possible diagnoses given the patient’s exposure to cats and her geographic location. However, the patient denied getting scratched by her pet cat or changing the litter. She also did not recall finding any rashes on her body or exhibiting any Lyme-related symptoms. It was also possible that this could be the initial presentation of multiple sclerosis. However, she denied any MS-related symptoms. Other possible diagnoses include compressive or infiltrative lesions or even a rare presentation of Leber’s.
The patient underwent an extensive workup including MRI with and without contrast, MRA, chest X-ray, lumbar puncture, CBC with differential, chemistry, Lyme, Bartonella, VDRL, CMV, EBV, ACE and ANA. MRI showed enhancement of the right optic nerve and optic nerve sheath with no demyelinating lesions (Figure 3). There were no enlarged ventricles. MRV was negative for thrombosis, masses or lesions. All the patient’s lab tests, including those for MS and neuromyelitis optica, were normal, with the exception of Lyme C6 ELISA testing, which came back elevated at 2.50. The Western blot at that time, however, was negative. Given the patient’s geographic location and otherwise negative testing, including VDRL, CMV and EBV, which could cross-react with the Lyme ELISA, the patient was diagnosed with Lyme optic neuritis.
Figure 3. MRI T1 after gadolinium shows enhancement of both the right optic nerve and sheath. No demyelinating lesions or masses were seen.
Figure 4. One month later, the optic nerve swelling and hyperemia have resolved. No pallor is noted.
Figure 5. One month later, there is only residual photoreceptor disruption nasally. There is also some outer nuclear layer thinning seen temporally. The intraretinal fluid is resolved.
Discussion
Lyme disease is caused by the spirochete Borrelia burgdorferi sensu stricto and is transmitted by ticks. The classic associated rash is erythema migrans, or bull’s eye rash. Within days, the spirochete can sequester into any tissue or organ in the body. During the first week, the spirochete is able to pass through the blood-brain barrier, causing meningitis, cranial nerve palsies and radiculoneuritis. Chronic manifestations can present months to years later. The Centers for Disease Control and Prevention recommends testing for Lyme disease using a two-tier test, first with an ELISA test and, if positive, followed by Western blotting to confirm the diagnosis.
Ocular manifestation of Lyme disease can present as conjunctivitis, keratitis, iritis, choroiditis, neuroretinitis or endophthalmitis. Disc edema associated with Lyme disease is believed to be secondary to either elevated intracranial pressure or direct inflammation of the optic nerve.
Given the rarity of this disease process, only a few cases of Lyme-related optic neuritis have been reported. Two of four pediatric cases presented by Rothermel et al were of children presenting with optic neuritis as either the initial presentation of Lyme disease or as a recurrence of previously treated Lyme. All other tests, including MS, were negative. Krim at al reported one case of Lyme-related retrobulbar optic neuritis. In both reports, the patients improved when treated with intravenous ceftriaxone. Interestingly, Blanc et al reported one case of a patient who first developed right eye optic neuritis of unknown etiology and never received treatment. Nine months later, the patient developed optic neuritis in the fellow eye that prompted further workup, which revealed positive Lyme disease and negative workup for MS and neuromyelitis optica. The patient received IV ceftriaxone and experienced improvement in vision in both eyes. Jacobson et al reported four patients with unilateral optic neuritis believed to be related to Lyme. His findings prompted him to recommend that all patients with unilateral optic neuritis in endemic areas should be checked for Lyme, regardless of other Lyme symptoms.
Sibony et al conducted a retrospective study of 440 patients with optic neuritis and available serology testing to determine how common Lyme optic neuritis was. They identified 25 patients with optic neuritis who had positive Lyme ELISA and negative syphilis results. Of those 25 patients, only one patient likely had Lyme-related optic neuritis based on serology testing and symptoms. The remaining patients did not have enough additional findings to support the diagnosis. This prompted the authors to perform a literature review that found that many published case reports on Lyme optic neuritis did not actually meet the diagnosis according to the CDC guidelines by also checking Western blots following a positive ELISA test. In addition, Sibony et al found that not all patients were tested for syphilis, which can cross-react with the Lyme ELISA test. In 2003, Jacobson provided an update on the four patients he reported on in 1999. Two patients were eventually diagnosed with MS, prompting Jacobson to revise his recommendation that Lyme testing is not beneficial unless the patient has other symptoms, lest it lead to a misdiagnosis, especially if antigens are indeed present, but the Lyme may be sequestered in other parts of the body.
Treatment
Our patient was immediately started on 1 g daily of Solu-Medrol (methylprednisolone, Pfizer) for 3 days upon admission. When her Lyme C6 ELISA was found to be positive on hospital day 2, she was started on a 3-week course of IV ceftriaxone. On hospital day 4, the patient subjectively felt her vision was improving, although her BCVA remained hand motions in the right eye. Her right optic nerve was still edematous and hyperemic.
One month later, BCVA in the right eye was 20/20-. The right afferent pupillary defect was still present, and the patient identified 8 out of 11 Ishihara color plates. On dilated examination, the disc edema appeared to have resolved (Figure 4). Retinal nerve fiber layer measurement improved to 153 µm, down from 537 µm. In comparison to her left eye at 107 µm, however, the optic disc was still slightly swollen. Repeat Lyme C6 ELISA testing was still positive, but the Western blot results were still negative. At her 3-month follow-up, the patient’s BCVA was 20/15- in the right eye with only a residual small temporal black spot in her visual field. The afferent pupillary defect was resolved, and color testing was full in both eyes. Repeat retinal nerve fiber layer measurement was decreased and thin at 85 µm. Repeat high-definition OCT of the macula revealed residual nasal photoreceptor disruption and outer nuclear layer thinning (Figure 5).
Despite only having a positive Lyme C6 and negative Western blot, our patient was diagnosed with Lyme-related optic neuritis because the rest of her workup, including MS, neuromyelitis optica and possible cross-reacting processes such as syphilis, CMV and EBV, was negative, and she experienced improvement after she received IV ceftriaxone. It is possible that the patient’s C6 ELISA was much more sensitive than the Western blot. In a study comparing the Western blot and the C6 Lyme ELISA from 52 characterized specimens, Mogilyansky et al found four samples to be C6 ELISA positive but with negative Western blots. Those four patient who provided those specimens, in fact, had clinically and microbiologically confirmed Lyme disease.