RESIDENT & FELLOW SECTION Clinical Reasoning: Section Editor A 42-year-old man with sequential Mitchell S.V. Elkind, MD, MS monocular visual loss S. Prasad, MD SECTION 1 Humphrey visual fields of the left eye revealed a H.E. Moss, MD, PhD In April 2005, a 42-year-old African American man dense superior altitudinal defect with a less prom- E.B. Lee, MD, PhD developed insidious, painless visual loss in the left eye inent inferior arcuate defect. The right eye field C.C. Glisson, DO which quickly progressed over several weeks. was full. S.L. Galetta, MD There was no significant medical history. Family He was thought to have idiopathic optic neuritis. history revealed hypertension and diabetes, but no He was treated briefly with oral corticosteroids, but autoimmune disorders, brain tumors, or vision loss. Address correspondence and his vision in the left eye never improved. reprint requests to Dr. Sashank He was a restaurant manager, smoked ½ pack of cig- Prasad, Department of arettes daily, consumed alcohol rarely, and did not Questions for consideration: Neurology, Hospital of the use illicit drugs. University of Pennsylvania, 3W 1. What are the diagnostic considerations for subacute mon- Gates Bldg, 3600 Spruce St., He presented to another institution, where he was ocular visual loss in an adult? Philadelphia, PA 19104 found to have 20/100 acuity, dyschromatopsia, and a 2. What diagnostic workup would you perform? [email protected] relative afferent pupillary defect in the left eye. The left optic nerve head was mildly swollen, without hemorrhage or exudate. GO TO SECTION 2 From the Departments of Neurology (S.P., H.E.M., S.L.G.) and Neuropathology (E.B.L.), Hospital of the University of Pennsylvania, Philadelphia; and Department of Neurology and Ophthalmology (C.C.G.), Michigan State University, East Lansing. Disclosure: The authors report no disclosures. Downloaded from www.neurology.org at UNIV PENNSYLVANIACopyright on © February 2008 by 7, AAN 2010 Enterprises, Inc. e43 SECTION 2 examination (including a nerve that is markedly The differential diagnosis for subacute monocular vi- swollen or atrophic, or retinal abnormalities such as sual loss is broad. Although idiopathic demyelinating hemorrhages, inflammation, or exudates). optic neuritis is a common cause, the differential also includes inflammatory and infectious conditions, Other causes of optic neuropathy. Inflammatory compression, infiltrative or neoplastic processes, he- conditions are an important cause of subacute optic reditary optic neuropathies, glaucoma, retinal disor- neuropathy. In sarcoidosis, optic nerve involvement ders, and ischemic optic neuropathy (table 1). can be accompanied by anterior uveitis or posterior segment vitritis.3 There is progressive visual loss, Optic neuritis. Optic neuritis most often occurs be- which is often steroid-responsive, and significant tween the ages of 20 to 50 and is three times more pain is unusual. Optic neuropathy is also rarely asso- frequent in women.1 Visual loss reaches its nadir ciated with systemic lupus erythematosus and within 7 to 10 days and begins to recover within 1 Sjo¨gren disease. month. Retro-orbital pain, particularly with eye Infectious conditions are another frequent etiology.4 movements, occurs in almost all cases; it may precede Neuroretinitis, in which optic neuropathy coexists the visual loss and typically persists for 1 to 2 weeks.2 with peripapillary or macular exudates, may be due Characteristic findings on examination support the diagnosis of typical optic neuritis. Visual field to cat scratch disease (Bartonella henselae), syphilis defects, such as diffuse field loss or central scotomas, (Treponema pallidum), or Lyme disease (Borrelia are common. In acute optic neuritis, one-third of burgdorferi). Other infectious causes include HIV patients have mild optic disc swelling; the remainder and opportunistic infections, including toxoplasmo- have retrobulbar inflammation and the optic nerve sis, cytomegalovirus, and cryptococcus. Paranasal si- head will appear normal.1 nusitis or mucocele can lead to compressive or Atypical features should prompt a rigorous search inflammatory optic neuropathy. for other causes of monocular visual loss. These “red A variety of compressive mass lesions can cause a flags” include an unusual temporal profile (progres- progressive optic neuropathy. Important causes in- sion beyond 2 weeks, or lack of recovery within 1 clude neoplasm (including optic nerve sheath or skull month), absence of pain, an unusual scotoma (such base meningioma, pituitary adenoma, and cranio- as an altitudinal defect), or an atypical funduscopic pharyngioma), sinus lesions, bony processes (fibrous Table 1 Differential diagnosis for subacute monocular visual loss Condition Types Characteristic features Optic neuritis Idiopathic optic neuritis, multiple sclerosis Retro-orbital pain; visual recovery starts within 1 month; normal-appearing optic nerve or mild disc swelling Ischemic optic Arteritis, nonarteritic ischemic optic Typically no pain; disc swelling with nerve fiber neuropathy neuropathy layer hemorrhages Inflammatory Sarcoidosis, systemic lupus erythematosus, Anterior uveitis or posterior segment vitritis optic neuropathy Sjo¨gren syndrome Infectious optic Paranasal sinusitis, cat scratch disease Neuroretinitis (optic disc swelling and retinal neuropathy (Bartonella henselae), syphilis (Treponema exudates) pallidum), Lyme disease (Borrelia burgdorferi), toxoplasmosis, cytomegalovirus, cryptococcus Compression Paranasal mucocele, meningioma (optic nerve Optic disc swelling in intraorbital compression; sheath or skull base), bony compression atrophy in intracanalicular or intracranial (fibrous dysplasia), enlarged extraocular compression; optic nerve head shunt vessels in muscles, aneurysms chronic compression Neoplasm Optic nerve glioma, optic nerve glioblastoma Slowly progressive visual loss multiforme, lymphoma, leukemia, carcinomatous meningitis, metastasis Hereditary Leber hereditary optic neuropathy Circumpapillary telangiectatic microangiopathy, nerve fiber layer pseudoedema Glaucomatous Chronic glaucoma, acute angle closure Elevated intraocular pressure and optic disc glaucoma cupping in chronic glaucoma; excruciating pain and scleral injection in acute angle closure glaucoma Retinal Chronic serous chorioretinopathy (CSR), Macular serous detachment (CSR), retinal retinal artery occlusion (RAO), retinal vein whitening (RAO), retinal hemorrhage and occlusion (RVO), acute idiopathic blind spot engorged veins (RVO), peripapillary pigmentary enlargement syndrome (AIBSE) changes (AIBSE) e44 DownloadedNeurology 71 from October www.neurology.org 21, 2008 at UNIV PENNSYLVANIA on February 7, 2010 Table 2 Diagnostic testing considerations Imaging MRI brain and orbits, optical coherence tomography, fluorescein angiography Serologies NMO-IgG, RPR, titers for Lyme, toxoplasmosis, Bartonella henselae, West Nile virus (WNV), HIV, herpes simplex virus (HSV), angiotensin converting enzyme, antinuclear antibodies, SS-a, SS-b; lumbar puncture for cell counts, protein, glucose, oligoclonal bands, and PCR for Lyme, HSV, WNV Genetic testing Leber hereditary optic neuropathy mitochondrial DNA testing Electrophysiology Visual evoked potentials, electroretinogram dysplasia), enlarged extraocular muscles, or aneu- neuropathy in the appropriate clinical setting include rysms. Primary neoplasms include benign optic nerve nerve fiber hemorrhages, altitudinal visual field loss, glioma in children, and rarely malignant glioblas- moderate to severe disc edema, and the absence of toma in adults. Other neoplastic conditions include pain. Vascular risk factors such as age, hypertension, lymphoma, leukemia, carcinomatous meningitis, diabetes, or hyperlipidemia are often present. More- and optic nerve metastasis. over, most patients with nonarteritic ischemic optic Among the hereditary causes, Leber hereditary neuropathy have the anatomic predisposition of a 5 optic neuropathy is most common. It often becomes small cup to disc ratio. bilateral and the visual impairment is usually severe. There is maternal inheritance, with variable pen- Diagnostic workup. Once the differential diagnosis etrance within families. The condition arises from has been narrowed on the basis of the clinical history mitochondrial DNA mutations that impair cellular and physical examination, an appropriate diagnostic energy stores. Most cases affect men, but the reasons workup is imperative to confirming the correct diag- for this gender asymmetry are unclear. The absence nosis (table 2). of pain in Leber hereditary optic neuropathy can All patients with typical optic neuritis should un- serve as an important distinguishing feature. Find- dergo brain MRI to assess the risk of multiple sclero- ings on examination may include circumpapillary sis. MRI of the orbits may confirm optic nerve telangiectatic microangiopathy and pseudoedema of enhancement in the majority of patients with optic the nerve fiber layer. neuritis and may be helpful to exclude alternative Glaucomatous optic neuropathy is typically easily causes of optic neuropathy.1 Testing for NMO-IgG distinguished from optic neuritis, since it occurs in (neuromyelitis optica anti-aquaporin-4 antibody) is the setting of elevated intraocular pressure and optic useful in patients with recurrent, bilateral, or severe disc cupping. However, angle closure glaucoma may optic neuritis, especially in patients with longitudi- present with painful acute visual loss, resembling the nally