Healthy man presents with unilateral acute vision loss

There was a hyperemic, swollen optic nerve in the affected eye. A white lesion extended superotemporally from the optic nerve.

Catherine A. Cox

Jordana F. Goren

A 42-year-old man was playing squash when he noted an acute loss of vision in the inferior field of his right eye. He presented to the emergency room at Lahey Clinic 3 hours later. In addition to the visual field loss, the patient also noted some mild pressure behind the right eye. He denied any headaches, floaters or diplopia. A complete review of systems was positive only for nasal congestion associated with body aches 2 weeks before presentation.

The patient’s ocular history was unremarkable. Medical history was notable for a hip replacement for a congenitally dislocated trochanter in 2005. Family history was significant for a maternal aunt with uveitis of unknown etiology. The patient denied any smoking, drinking or use of illicit substances and reported he was monogamous with his wife.

On examination, best corrected visual acuity was 20/20 in both eyes. There was a relative afferent pupillary defect present in the right eye. Extraocular movements were full, IOPs were 10 mm Hg and 13 mm Hg, and anterior segment exam was unremarkable. Dilated fundus exam demonstrated a diffusely swollen and hyperemic optic nerve in the right eye. Extending from the right optic nerve superotemporally was an area of superficial retinal whitening (Figure 1). There was no anterior or posterior segment inflammation. Fluorescein angiography demonstrated leakage around the right optic nerve head without associated vasculitis (Figure 2). The left eye examination was normal.

Ishihara pseudoisochromatic color plate testing showed moderately diminished color vision in the right eye and normal color vision in the left eye. Humphrey visual field testing was significant for a dense inferior altitudinal field defect in the right eye, with a full field in the left eye (Figure 3). Optical coherence tomography revealed an increased retinal nerve fiber layer thickness of the right optic nerve with a normal left optic nerve (Figure 4). Macular OCT scans were normal.

Figure 1. Fundus photography showing a swollen, hyperemic right optic nerve with a white lesion extending from the superotemporal aspect of the right optic nerve. There is a benign nevus by the left inferior arcade. The left eye is unremarkable. Images: Bartolini CE, Athappilly GK

Figure 2. Fluorescein angiography demonstrating leakage of the right optic nerve without evidence of vasculitis.

Figure 3. Humphrey 30-2 visual field tests demonstrating a right inferior altitudinal defect.

Figure 4. OCT revealing increased retinal nerve fiber layer of the right optic nerve.

What is your diagnosis?

Unilateral acute vision loss

The differential diagnosis for a young man with unilateral disc edema includes optic neuritis/neuropathy, non-arteritic ischemic optic neuropathy (NAION), Leber’s hereditary optic neuropathy (LHON) or optic nerve tumors.

Although the patient had an inferior altitudinal field defect as can be seen with NAION, there was no sectoral disc edema and the patient had no risk factors for NAION. The patient recently had an unremarkable physical exam and was checked for diabetes, hypertension and hypercholesterolemia. In addition, the patient was not taking any erectile dysfunction medications. The absence of a central scotoma, telangiectatic vessels or family history made LHON unlikely. Similarly, a compressive optic nerve tumor (meningioma) typically presents with more chronic symptoms, collateral vessels and optic nerve pallor.

Optic neuritis and optic neuropathy were considered because this was a young patient with vision loss associated with ocular pain and an abnormal CBC. To evaluate for infectious, inflammatory and infiltrative causes, the patient underwent additional blood work, CT of the chest and intracranial imaging.

Follow-up

CBC demonstrated low white blood cell count of 3,190 cells/mm³ and low hematocrit of 39.5. ACE levels and lysozyme levels were elevated at 113 U/L (normal range: 9 U/L to 67 U/L) and 31 µg/mL (normal range: 9 µg/mL to 17 µg/mL), respectively. MRI of the brain and orbits did not show a mass lesion, and there was no enhancement of the optic nerve. A chest radiograph revealed prominent hilar adenopathy. A chest CT confirmed the hilar and mediastinal lymphadenopathy and revealed reticulonodular opacities in the upper lung fields bilaterally, more prominent on the right side. This significantly narrowed the differential to include sarcoidosis, lymphoma, primary lung cancer or metastatic disease.

Neurology was consulted and a decision was made to proceed with mediastinal biopsy rather than a spinal tap. A mediastinoscopy was performed with biopsy of mediastinal lymph node tissue that demonstrated confluent non-necrotic granulomas consistent with sarcoidosis. The patient was treated with intravenous methylprednisolone at a dose of 1 g/day for 5 days followed by 60 mg of oral prednisone, which was initially tapered 5 mg/week for 12 weeks until the patient reached a dose of 20 mg of prednisone. The patient noted improvement of his vision and resolution of the ocular discomfort immediately with initiation of steroid therapy.

At 2-month follow-up, the patient reported 70% return of vision in the aforementioned right inferior visual field defect. Central vision remained 20/20, and he had further improvement of his color vision. Dilated fundus exam showed resolution of the optic disc edema and reduction in size of the cotton wool spot in the right eye. Humphrey visual field 30-2 showed improvement in the right inferior visual field defect (Figure 5). OCT was significant for decreased thickening of the retinal nerve fiber layer.

Figure 5. Humphrey 30-2 visual fields demonstrating gradual improvement of the right inferior altitudinal field defect. Left visual field is within normal limits.

Discussion

Sarcoidosis is an idiopathic granulomatous multisystem disease that affects the lungs, skin, lymph nodes, liver, brain and eyes. It is characterized histologically by noncaseating epithelioid granulomas. There is some evidence that environmental exposure in genetically susceptible hosts may be responsible for the formation of sarcoid granulomas; however, the exact cause remains elusive. It most often presents in the second to fourth decade of life and is more prevalent in African-Americans and Scandinavians.

Ophthalmic disease occurs in 22% to 60% of these patients, most commonly in the form of uveitis. Anterior segment findings frequently seen with sarcoidosis include conjunctival nodules, keratoconjunctivitis sicca, band keratopathy, mutton fat keratic precipitates, iris nodules, posterior synechiae, cataract and glaucoma. Common posterior segment findings include vitritis in the form of “snowballs” or “string of pearls,” periphlebitis in the form of “candle wax drippings” and yellow-white chorioretinal peripheral lesions.

Less frequently, in 5% to 15% of cases, neurological involvement occurs and includes cranial or peripheral neuropathies, meningeal disease, hydrocephalus, parenchymal disease, vasculitis, encephalopathy and seizures. Cranial neuropathy is the most frequent neurological manifestation, with the facial nerve followed by the optic nerve being the most commonly affected.

If the optic nerve is involved, patients present with symptoms of acute or progressively worsening visual loss that may or may not be accompanied by eye pain or pressure. Rarely, a sarcoid granuloma will be visualized at the optic disc. Thus, it is important for ophthalmologists to remember sarcoidosis in the differential diagnosis when a patient presents with symptoms and signs suggesting optic neuritis or optic neuropathy, as in this case.

Diagnosis of neurosarcoidosis is difficult, owing to its nonspecific and extensive symptomatology. Definitive diagnosis is generally made with a biopsy showing noncaseating granulomas and a compatible clinical picture with response to treatment. MRI of the brain and orbits may reveal thickening or enhancement of the optic nerve or other structures in the brain in close to 80% of neurosarcoidosis cases. The diagnostic accuracy of cerebrospinal ACE levels for neurosarcoidosis is not well established and therefore cannot replace tissue diagnosis. Although it has a low sensitivity (25% to 44%), the high specificity (94% to 95%) may make it useful in the evaluation of patients suspected of having neurosarcoidosis.

Supporting evidence includes elevated levels of serum ACE, lysozyme and calcium as well as a chest radiograph or CT showing lymphadenopathy or parenchymal disease. 18F-FDG PET/CT scans may be useful to identify alternative diagnostic biopsy sites in cases with isolated optic neuropathy, as the optic nerve is a not a site easily amenable to surgical intervention.

If a patient has pulmonary involvement, however, chest radiograph is a great screening test, revealing 90% of sarcoidosis cases. CT of the chest should be performed when chest radiograph findings are equivocal. Interestingly, 90% of patients with sarcoidosis will develop pulmonary involvement at some point in the course of their disease.

The main treatment modality for neurosarcoidosis is corticosteroids, although there are no large randomized clinical studies evaluating this treatment. The dosing regimen varies on clinical presentation, but most reports advocate the initial use of high-dose glucocorticoids followed by maintenance therapy of 0.5 mg/kg/day to 1 mg/kg/day of oral prednisone with a slow taper. Adjunctive treatment with immunomodulatory agents such as methotrexate, cyclosporine and mycophenolate mofetil may also have a long-term beneficial effect. TNF-alpha inhibitors and thalidomide have been reported to show benefit in a few case studies. Adjunctive treatment also may be needed in patients who cannot tolerate or do not respond to adequate steroid doses.

Conclusion

In summary, a 42-year-old previously healthy man presented with sudden onset of right-sided inferior visual field loss with a swollen optic nerve and cotton wool spot in the right eye on clinical exam. Diagnostic studies, which included a chest CT, ACE levels and lysozyme levels, suggested the diagnosis of sarcoidosis, which was confirmed by biopsy of an enlarged mediastinal lymph node.

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• Claudia E. Bartolini, MD, and Geetha K. Athappilly, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Catherine A. Cox, MD, and Jordana F. Goren, MD, MS. Drs. Cox and Goren can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.