Acute Zonal Occult Outer Retinopathy Associated With Retrobulbar Optic Neuritis

A 17-year-old girl presented with unilateral retrobulbar optic neuritis as well as bilateral funduscopic findings and outer retinal dysfunction suggestive of acute zonal occult outer retinopathy (AZOOR). Fundus autofluorescence abnormalities, visual field loss, and electroretinographic changes were supportive of bilateral AZOOR. MRI was consistent with the diagnosis of clinically isolated syndrome (CIS), which is defined as a central nervous system demyelinating event that may herald the onset of multiple sclerosis (MS). While AZOOR previously has been linked to MS and demyelinating white matter lesions in the brain, our case seems unique due to concurrent development of AZOOR and retrobulbar optic neuritis as a CIS.

Clinical Observation Acute Zonal Occult Outer Retinopathy Associated With Retrobulbar Optic Neuritis Jay C. Wang, MD, Avni P. Finn, MD, MBA, Lindsay A. Grotting, MD, Lucia Sobrin, MD, MPH Abstract: A 17-year-old girl presented with unilateral retrobulbar optic neuritis as well as bilateral funduscopic findings and outer retinal dysfunction suggestive of acute zonal occult outer retinopathy (AZOOR). Fundus autofluorescence abnormalities, visual field loss, and electroretinographic changes were supportive of bilateral AZOOR. MRI was consistent with the diagnosis of clinically isolated syndrome (CIS), which is defined as a central nervous system demyelinating event that may herald the onset of multiple sclerosis (MS). While AZOOR previously has been linked to MS and demyelinating white matter lesions in the brain, our case seems unique due to concurrent development of AZOOR and retrobulbar optic neuritis as a CIS. Journal of Neuro-Ophthalmology 2017;37:287-290 doi: 10.1097/WNO.0000000000000494 © 2017 by North American Neuro-Ophthalmology Society F irst described in 1992 by Gass (1), acute zonal occult outer retinopathy (AZOOR) is a condition characterized by acute loss of function in certain areas of the outer retina associated with visual field loss and abnormal electroretinogram (ERG) findings. It typically occurs in young women with photopsias and may be unilateral or bilateral. Funduscopic findings range from mild retinal pigmentary changes to large areas of outer retinal degeneration. Vitritis and peripheral phlebitis may be present. It is hypothesized to be an inflammatory condition although the exact mechanism is unknown (2). There are reports of AZOOR associated with demyelinating white matter lesions, transverse myelitis, and clinically confirmed multiple sclerosis (MS) (3,4). It is thought that these entities may share an underlying autoimmune etiology. Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. The authors report no conflicts of interest. Address correspondence to Lucia Sobrin, MD, MPH, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114; E-mail: lucia_sobrin@ meei.harvard.edu Wang et al: J Neuro-Ophthalmol 2017; 37: 287-290 Clinically isolated syndrome (CIS) is characterized as a central nervous system demyelinating event that may eventually develop into MS. Here, we report a case of AZOOR presenting with retrobulbar optic neuritis as a CIS. CASE REPORT A previously healthy 17-year-old girl experienced blurry vision and pain with movement of the left eye over 2 days. She had no visual complaints regarding her right eye and denied photopsias, nyctalopia, and other systemic or neurologic symptoms. There was no family history of nyctalopia or eye or neurologic disease. Visual acuities were 20/20, right eye and counting fingers at 6 inches, left eye, with a left relative afferent pupillary defect. Intraocular pressures were 14 and 13 mm Hg in the right and left eyes, respectively. Extraocular motility was full, and external and anterior segments examinations were normal. Fundus examination revealed a few vitreous cells in the left eye. Localized zonal retinal pigment epithelium changes that were associated with hyperautofluorescence were noted bilaterally (Fig. 1A-D). No optic disc edema was seen on clinical examination although fluorescein angiography showed late staining of the left optic nerve (Fig. 1E, F). Optical coherence tomography showed focal loss of outer retinal segments corresponding to the areas of abnormal autofluorescence (Fig. 1G, H). MRI demonstrated multiple nonenhancing hyperintense periventricular and juxtacortical supratentorial white matter lesions (Fig. 2). Also, there was hyperintensity of the left retrobulbar optic nerve. There was enhancement of the left optic nerve following intravenous contrast. Lumbar puncture did not reveal oligoclonal bands. Angiotensin-converting enzyme, lysozyme, QuantiFERON gold, Lyme serologies, fluorescent treponemal antibody absorption, antinuclear antibody, anti-neutrophil cytoplasmic antibody, and aquaporin-4 antibody were all negative. The patient was treated with 1 g of methylprednisolone intravenously for 5 days followed by 287 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 1. Wide-field fundus photography. A. Right eye: retinal pigment epithelium changes are seen along the superior arcade. B. Left eye: bone spicules are present inferotemporally with areas of vascular sheathing above and below the arcades. Fundus autofluorescence demonstrates zonal hyperautofluorescence around the superior arcade in the right eye (C) and inferiorly in the left eye (D). Late-phase fluorescein angiography shows optic disc staining in the left eye and no evidence of perivascular leakage in either eye (E, F). Optical coherence tomography demonstrates loss of the outer retina in the superior macula of the right eye (G) and inferotemporal macula of the left eye (H) corresponding to the areas of abnormal fundus autofluorescence. 288 Wang et al: J Neuro-Ophthalmol 2017; 37: 287-290 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 2. A. Coronal T2 MRI reveals hyperintensity of the left optic nerve (arrow). Axial FLAIR images demonstrate juxtacortical (B) and periventricular (C) white matter lesions. a taper of oral prednisone starting at 80 mg daily. One week after initial presentation, the patient's visual acuity had improved to 20/25, left eye, with resolution of pain. An ERG showed reduced full-field photopic and scotopic amplitudes, and multifocal ERG revealed localized depressed sensitivity corresponding to the locations of abnormal autofluorescence. Kinetic visual fields demonstrated focal constriction superonasally in the left eye, also corresponding to an area of abnormal autofluorescence. DISCUSSION Many aspects of our patient's presentation were consistent with the classic findings of retrobulbar optic neuritis, including the appropriate demographic (young woman), decreased vision in 1 eye, relative afferent pupillary defect in the affected eye, pain with eye movement, absence of optic disc edema, and abnormal signal of the affected optic nerve on MRI. Our patient also had multiple periventricular white matter lesions. However, since these lesions were not contrast enhancing, the patient was diagnosed with CIS rather than clinically confirmed MS (5). Despite the presence of a contrast-enhancing optic nerve in our patient, this lesion is specifically excluded as per the McDonald criteria (6). In addition, the absence of oligoclonal bands in our patient halves her risk for developing MS compared with a patient with CIS and positive oligoclonal bands (7). The retinal findings in both eyes raised the possibility of posterior uveitis. Appropriate laboratory studies excluded infectious or inflammatory causes of uveitis, such as Lyme disease, sarcoidosis, tuberculosis, and syphilis. The possibility of an atypical inherited pigmentary retinopathy was considered, but there was no family history to support this. The zonal distribution of retinal pigment epithelial changes and associated hyperautofluorescence seen in both eyes were suggestive of AZOOR. Multifocal ERG and kinetic visual fields demonstrated reduced photopic and scotopic Wang et al: J Neuro-Ophthalmol 2017; 37: 287-290 amplitudes with focal constriction of visual field in the left eye corresponding to the zone of damaged outer retina, all consistent with the diagnosis of AZOOR (8,9). Treatment of optic neuritis with intravenous steroids does hasten visual recovery, but it does not alter the final visual outcome (10), whereas steroid pulse therapy has been shown to improve visual acuity in AZOOR (11). Initiation of intravenous steroid therapy rapidly improved our patient's vision. AZOOR has been reported to be associated with a case of clinically confirmed MS (3) and a case of acute relapsing- remitting cervical myelitis with numerous intracranial white matter abnormalities on MRI, although these were not further characterized (4). One long-term follow-up study of AZOOR found autoimmune diseases present in 28% of patients, including relapsing transverse myelopathy in 8% (12). We are unaware of other reports of retrobulbar optic neuritis developing concurrently with AZOOR. Both AZOOR and demyelinating disease share certain clinical features including preponderance in young women, a relapsing course followed by gradual progression, may occur following viral illness, in association with other autoimmune disorders and possible autoimmune etiology (2). STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Jay Wang, Avni Finn, and Lindsay Grotting; b. Acquisition of data: Jay Wang and Avni Patel; c. Analysis and interpretation of data: Jay Wang, Avni Finn, Lindsay Grotting, and Lucia Sobrin. Category 2: a. Drafting the manuscript: Jay Wang; b. Revising it for intellectual content: Jay Wang, Avni Finn, Lindsay Grotting, and Lucia Sobrin. Category 3: a. Final approval of the completed manuscript: Lucia Sobrin. 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