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Woman referred for pain, decreased vision in left eye
She had a remote history of hearing loss and elevated C-reactive protein.
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A 61-year-old Caucasian woman was referred for neuro-ophthalmology evaluation at Lahey Medical Center for decreased vision associated with pain in the left eye.
History
The patient’s medical history was significant for type 2 diabetes, hypertension, hyperlipidemia, hypothyroidism and a pericardial cyst. She also had an elevated C-reactive protein (CRP) level discovered incidentally 20 years ago, for which work-up by an outside rheumatologist was unrevealing. She had an acute right-sided hearing loss 2 years ago; work-up through an outside otolaryngologist and imaging were also unrevealing. Her ocular history included a mild refractive error. She had no significant family ocular history.
Her symptoms started with pressure around the maxillary and frontal sinuses starting 3 weeks before presentation. She saw an outside ENT who started her on Flonase (fluticasone propionate spray, GlaxoSmithKline) with some relief of her symptoms, but she then noted pain around her orbits. Three days before presentation, she noticed a white-out of the superior visual field in her left eye as well as a reduction in her color vision.
Review of systems was negative for fevers, joint pain, rashes, scalp tenderness and jaw claudication. She also denied paresthesias, numbness, weakness and bowel/bladder abnormalities. There was no history of tick bites or recent travel within or outside the country. She denied any history of sinus or respiratory problems.
Examination
On exam, the patient’s best corrected distance visual acuity was 20/30 in the right eye and 20/40 in the affected left eye. She was noted to have a 2+ afferent pupillary defect in the left eye with color desaturation. Extraocular movements were full bilaterally. Anterior segment exam was significant only for 1+ nuclear sclerotic cataracts bilaterally. Posterior segment exam was also unremarkable. Both discs were pink and sharp with a cup-to-disc ratio of 0.65 (Figure 1).
Images: Moon J, Athappilly G and Romanow JH
What is your diagnosis?
Reduced vision, eye pain
The mildly reduced central vision, positive afferent pupillary defect, reduced color vision and eye pain in the setting of a normal optic nerve head appearance was concerning for a retrobulbar optic neuritis. The differential for optic neuritis can be categorized into infectious, demyelinating and inflammatory causes.
Infectious causes are wide and varied but can include Lyme, syphilis, Cryptococcus, toxoplasmosis, tuberculosis or cytomegalovirus. In addition, spread of sinus infections can cause a retrobulbar optic neuritis, although this is more common in children.
Most commonly, optic neuritis in adults is due to demyelinating disease, specifically multiple sclerosis. This seemed less likely based on the lack of prior neurologic symptoms.
Inflammatory causes of optic neuritis include sarcoidosis, systemic lupus erythematosus or Wegener’s granulomatosis. With the patient’s history of sudden hearing loss and remote history of elevated CRP, the suspicion was high for an inflammatory process.
Diagnosis and management
In the office, an OCT of the macula showed normal retinal anatomy in both eyes. OCT of the retinal nerve fiber layer and ganglion cell layer complex was intact in both eyes. Humphrey visual field testing using the 30-2 SITA Fast protocol showed a superior arcuate defect in the left eye (Figure 2).
MRI of the orbits and brain with and without contrast demonstrated subtle left optic nerve sheath enhancement in the canal (Figure 3). In addition, the patient showed severe, chronic sphenoid sinusitis changes, along with chronic posterior ethmoid mucosal sinus thickening (Figure 4). Interestingly, her maxillary and anterior ethmoid sinuses were clear. There were no other intracranial or demyelinating lesions.
Based on MRI findings, she was referred to see ENT with concern that her acute sinusitis had spread to cause the optic neuritis. ENT took her for emergent bilateral sphenoidectomy. Cultures performed in the operating room grew Staphylococcus aureus with multiple sensitivities. She was started on Augmentin (amoxicillin/clavulanate potassium) as well as oral prednisone with improvement in her vision. She was continued on a prolonged course of prednisone due to subjective vision decline with decreased doses of steroid.
The patient then presented urgently 1 month after the surgery with significant left-sided eye pain and decreased vision in the left eye. At this point she was on 20 mg of prednisone as well as Augmentin. On exam her vision decreased to 20/80 in the left eye. She also had a left afferent pupillary defect, reduced color vision and an inferotemporal field defect on confrontation. The anterior and posterior segment exams remained unremarkable.
She was admitted to the medicine service for further work-up and management as her current symptoms did not seem to be due to optic neuritis from an infectious sinus process. More concerning was a potential inflammatory process such as Wegener’s granulomatosis, for which rheumatology was consulted. An infectious work-up, including QuantiFERON Gold, Lyme antibody screen, Treponema pallidum antibody and CMV, was negative. Aquaporin-4 antibody for neuromyelitis optica was negative as well. Chest CT revealed multiple cavitary basilar pulmonary nodules. Pulmonary was consulted and did not feel the lesions appeared infectious or neoplastic but recommended an IR-guided biopsy, which unfortunately yielded insufficient cellular material for analysis.
Cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) came back positive with high anti-PR3 antibody levels. She was also found to have elevated total complement levels. The ANA screen, which detects antibodies to SSA, SSB, SCL-70 and ds-DNA, among others, was negative.
Conclusion
The patient’s history of this acute episode of optic neuritis, cavitating pulmonary nodules, sinus disease and episode of hearing loss in the setting of a positive c-ANCA with high PR3 antibodies was consistent with the diagnosis of granulomatosis with polyangiitis.
She was started on IV steroids immediately upon admission to the hospital for suspected inflammatory cause of optic neuritis. She was given 3 days of IV steroids before being transitioned to oral steroids. With the Solu-Medrol (methylprednisolone sodium succinate), the patient experienced immediate improvement in her symptoms both subjectively and objectively. On discharge the patient’s vision in the left eye was 20/20 with return of color vision. Her visual field defect on confrontation improved, and her pain had resolved completely.
With the diagnosis of granulomatosis with polyangiitis, she was started on rituximab therapy by the rheumatologist in addition to the oral steroids. Her urinalysis showed mild proteinuria, but fortunately she has not developed any signs of kidney disease. Her vision has remained at baseline with no recurrent symptoms, and she continues to be followed closely by rheumatology and pulmonary.
Discussion
Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is a form of vasculitis that affects small and medium-sized vessels. It commonly affects the upper respiratory tract, lungs and kidneys, but it can affect almost any organ. Lung disease develops in 85% of patients, and kidney disease develops in about 80%. Additionally, GPA has been known to cause otitis with hearing loss, as was seen in our patient.
Sinonasal disease is also a common manifestation of GPA, occurring in 85% of patients. Over time continued granulomatous inflammation can lead to septal perforation or the classic “saddle nose” deformity. S. aureus is the most common organism seen in sinus disease due to GPA. However, it is also the most common organism in secondary infection of chronic sinusitis, so it is not always easy to differentiate; secondary infection is commonly seen in areas of nasal crusting in chronic sinusitis.
Non-specific laboratory values seen in GPA include anemia, elevated ESR and elevated CRP. A more specific value is antineutrophil cytoplasmic antibodies (ANCA), which have been found to be positive in 80% to 90% of patients with GPA. More specifically, the antibody targets cytoplasmic proteinase 3 (PR3) in 80% of patients. However, ANCA titers do not correspond to level of disease and do not predict recurrence.
Ocular manifestation is also fairly common in GPA. The incidence varies between 50% to 60%, depending on the study. Occasionally ocular symptoms can be the initial presenting sign of GPA, occurring in up to 17% of patients. Scleritis is the most commonly seen ophthalmic complication. Other complications include space-occupying orbital lesions, conjunctivitis, episcleritis, peripheral ulcerative keratitis, uveitis and retinitis. Optic neuritis tends to be rare.
Only a few studies have reported vision loss due to optic neuritis as a complication of GPA. One study notes that it is possible that some of the cases reported as ischemic optic neuropathy in GPA may have been undertreated optic neuritis complicated by a vascular infarction. In all four of the cases, there was pulmonary involvement. All of the patients recovered vision after receiving high-dose corticosteroid therapy.
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- For more information:
- Jessica Moon, MD, Geetha Athappilly, MD, and John H. Romanow, MD, can be reached at the 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 the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.