Clinical Review & Education JAMA Ophthalmology Clinical Challenge Vision Loss and Paresthesias in a Young Man Tavé van Zyl, MD; Thanos D. Papakostas, MD; Lucia Sobrin, MD, MPH A Fundus photograph B Fluorescein angiogram Figure 1. A, Subretinal and retinal pigment epithelial lesions (arrowheads) are visible in the left eye. B, Late staining of the macular lesion. The arrowheads outline the border of the area that was hypofluorescent in the early frames (not shown). The right eye showed similar findings. A young man presented to the emergency department with a 1-day history of vision loss in the left eye. He had experienced eye redness for 1 week, which resolved with use of artificial tears; a mild posterior headache; and paresthesias of the left thumb and index and middle fingers. His medical history was significant for epilepsy as a child, although he had been seizure free for more than 10 years without medication. He had no ocular history, was not taking any medications, and had no known drug allergies. He smoked 2 to 4 packs of cigarettes per day, consumed 1 to 3 alcoholic drinks per day, and denied illicit drug use. He denied recent travel, vaccinations, systemic illnesses, or influenza-like symptoms. Hisbest-correctedvisualacuitywas20/20ODand20/100OS.Amslergridtestingrevealed a central scotoma in the left eye. No afferent papillary defect was apparent. Intraocular pressures were 16 mm Hg OU. Results of the external and anterior segment examinations were unremarkable, and no vitreous inflammation was noted. Figure 1 shows findings of the posterior segment examination. Results of the neurologic examination revealed decreased sensation to light touch, vibration, and temperature in his left upper and lower extremities. jamaophthalmology.com WHAT WOULD YOU DO NEXT? A. Initiate high-dose corticosteroid therapy B. Obtain magnetic resonance imaging of the brain C. Perform a retinal biopsy D. Obtain computed tomography of the chest (Reprinted) JAMA Ophthalmology Published online August 13, 2015 Copyright 2015 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a University of California - San Diego User on 08/17/2015 E1 Clinical Review & Education JAMA Ophthalmology Clinical Challenge Diagnosis Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with presumed associated cerebral vasculitis What To Do Next B. Obtain magnetic resonance imaging of the brain. Classic clinical findings such as bilateral postequatorial creamy gray-yellow placoid lesions at the level of the retinal pigment epithelium demonstrating early blockage and late staining on fluorescein angiography in a young, otherwise healthy patient are often sufficient for establishing a diagnosis of APMPPE. Before considering therapy, however, pertinent associated signs and symptoms should be addressed. This patient described a headache that, in the setting of a prodromal viral illness, has been described with APMPPE and does not always warrant neuroimaging.1 However, the presence of peripheral sensory deficits should prompt urgent magnetic resonance imaging (MRI) with diffusion-weighted imaging and apparent diffusion coefficient sequences to evaluate for signs of cerebral vasculitis. Figure 2. Representative section of magnetic resonance imaging, which demonstrated foci of marked hyperintensity on diffusion-weighted imaging sequences and corresponding hypointensity on apparent diffusion coefficient sequences (inset), consistent with acute stroke. Discussion The rare inflammatory eye disease APMPPE has been associated with multiple systemic conditions, including Wegener disease, systemic lupus erythematosus, and erythema nodosum, although causative relationships have not been established. Central nervous system involvement, ranging in severity from headaches to diffuse cerebral vasculitis, stroke, and death, has also been described, with at least 17 cases of APMPPE-related cerebral stroke reported.2 Optimal therapeutic regimens for APMPPE have not been established because the disease is so rare; however, corticosteroids and immunomodulatory agents are used variably. Some authors3,4 have posited that isolated APMPPE in an otherwise healthy young adult follows a self-limited clinical course and carries an excellent visual prognosis without treatment. Others2,5,6 have reported substantial rates of persistent visual field defects, metamorphopsia, and incomplete visual recovery while remaining equivocal regarding the role of systemic therapy. Several1,7,8 agree that despite the paucity of high-quality clinical evidence, rapid initiation of therapy is justified in patients with central nervous system involvement and that long-term immunomodulatory therapy may be necessary. TheMRIinourpatientrevealedmultiplehyperintensefociondiffusionweightedimagingsequencesandcorrespondinghypointensitiesonapparent diffusion coefficient sequences, consistent with acute stroke (Figure 2). Results of the cerebrospinal fluid sample analysis were normal. Results of the laboratory workup for tuberculosis, sarcoidosis, and syphilis were negative. The patient received a 3-day course of intravenous methylprednisolone sodium succinate (Solu-Medrol); soon after therapy was transitioned to oral prednisone, he developed new symptoms and was found to have new cerebral infarcts. Oral cyclophosphamide was added, and he continued this regimen for 7 months before theprednisonedosewastaperedgradually.Fivemonthsaftertreatment initiation, the patient’s visual acuity was 20/20 OD and 20/25 OS, with no recurrence of the disease. Most patients with APMPPE can expect an excellent overall prognosis. However, physicians of patients who demonstrate any neurologicsignsorsymptomsshouldconsiderpromptneuroimagingbecause delayed treatment of APMPPE-associated cerebral vasculitis can result in substantial morbidity or death. ARTICLE INFORMATION REFERENCES Author Affiliations: Retina and Uveitis Services, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston. 1. Luneau K, Newman NJ, Srivastava S, Biousse V. A case of acute posterior multifocal placoid pigment epitheliopathy with recurrent stroke. J Neuroophthalmol. 2009;29(2):111-118. Corresponding Author: Lucia Sobrin, MD, MPH, Retina and Uveitis Services, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA 02114 (lucia_sobrin@meei.harvard.edu). Published Online: August 13, 2015. doi:10.1001/jamaophthalmol.2015.1935. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Previous Presentation: This paper was presented at the 2015 Meeting of the Atlantic Coast Retina Club; January 8, 2015; Boston, Massachusetts. E2 Patient Outcome 2. Thomas BC, Jacobi C, Korporal M, Becker MD, Wildemann B, Mackensen F. Ocular outcome and frequency of neurological manifestations in patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE). J Ophthalmic Inflamm Infect. 2012;2(3):125-131. 3. Agarwal A, Gass JDM. Gass’ Atlas of Macular Diseases. 5th ed. Edinburgh, Scotland: Elsevier Saunders; 2012. 4. Spencer BR Jr, Kunimoto DY, Patel DR, Dodick DW. Acute multifocal posterior placoid pigment epitheliopathy (AMPPPE) mimicking migraine with aura. Cephalalgia. 2009;29(6):694-698. 5. Fiore T, Iaccheri B, Androudi S, et al. Acute posterior multifocal placoid pigment epitheliopathy. Retina. 2009;29(7):994-1001. 6. Wolf MD, Alward WL, Folk JC. Long-term visual function in acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. 1991;109(6): 800-803. 7. Comu S, Verstraeten T, Rinkoff JS, Busis NA. Neurological manifestations of acute posterior multifocal placoid pigment epitheliopathy. Stroke. 1996;27(5):996-1001. 8. O’Halloran HS, Berger JR, Lee WB, et al. Acute multifocal placoid pigment epitheliopathy and central nervous system involvement. Ophthalmology. 2001;108(5):861-868. JAMA Ophthalmology Published online August 13, 2015 (Reprinted) Copyright 2015 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a University of California - San Diego User on 08/17/2015 jamaophthalmology.com