Sjögren Disease and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Sjögren Disease and Myelin Oligodendrocyte Glycoprotein Antibody–Associated Optic Neuritis Aman Mittal, MD, Iyza F. Baig, MD, Arjun G. Merchant, BS, John J. Chen, MD, PhD, Jeanie J. Choi, MD, Alla Goldberg, MD, Ore-Ofe O. Adesina, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 05/04/2022 T he association between optic neuritis and demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein IgG-associated disorder (MOGAD) is well-established; however, few cases have been reported with optic neuritis as a presenting sign of Sjögren disease. Aquaporin-4 (AQP4)-positive NMOSD has been associated with other systemic autoimmune diseases, including systemic lupus erythematosus (SLE) and Sjögren disease, and MOGAD has been identified in patients with SLE. However, no cases of concurrent MOGAD and Sjögren disease have been reported. We report a case of optic neuritis as the initial presentation of Sjögren disease with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies but AQP4-IgG negative. A 32-year-old African American woman with hypertension and well-controlled diabetes experienced left-sided headache and eye pain followed 3 days later by progressive vision loss in the left eye with painful eye movements. She denied a personal or family history of autoimmune disease. On examination, visual acuity (VA) was 20/20 in the right eye and counting fingers at 6 feet in the left eye. Pupil examination was normal in the right eye but sluggishly reactive in the left eye with a left relative afferent pupillary defect (rAPD). Automated perimetry showed a full visual field (VF) in the right eye and complete depression in the left eye. Cranial nerve examination was normal bilaterally. Dilated ophthalmoscopic examination was normal in the right eye and showed left optic disc edema with scattered intraretinal and subretinal hemorrhages throughout the posterior pole without vascular sheathing or vitritis. Fluorescein angiography showed leakage from the optic disc Ruiz Department of Ophthalmology and Visual Science (AM, IFB, AGM, AG, O-OOA), McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth), Houston, Texas; Robert Cizik Eye Clinic (AM, AG, O-OOA), Houston, Texas; Departments of Ophthalmology (JJC) and Neurology (JJC), Mayo Medical School, Rochester, Minnesota; Department of Diagnostic and Interventional Imaging (JC), McGovern Medical School at UTHealth, Houston, Texas; Department of Neurology (O-OOA), McGovern Medical School at UTHealth, Houston, Texas. The authors report no conflicts of interest. Address correspondence to Ore-Ofe O. Adesina, MD, Robert Cizik Eye Clinic, 6400 Fannin Street, Suite 1800, Houston, TX 77030; E-mail: [e-mail] e48 without leakage from the vessels or the areas of retinal hemorrhage (Fig. 1). She was diagnosed with optic neuritis and admitted for inpatient workup. MRI of the orbits demonstrated edema throughout the left optic nerve with longitudinally extensive enhancement involving the entire retrobulbar optic nerve and sheath as well as the intraconal fat (Fig. 2). Scleral flattening with enhancement at the level of the insertion was also seen. No abnormalities were seen in the right optic nerve or on brain or spinal imaging. Cerebrospinal fluid analysis was negative for syphilis, Lyme disease, and abnormal protein synthesis. Serum laboratory test results were remarkable for positive antinuclear antibodies with 1:80 titer and positive anti-Ro and anti-ribonucleoprotein antibodies. She had additional symptoms of xerophthalmia, xerostomia, and fatigue and was diagnosed with Sjögren disease. She received 1-g intravenous methylprednisolone daily for 3 days, then 100-mg oral prednisone for 1 week, with a 4-day taper by 20 mg each day. She experienced rapid improvement of VA to 20/20. Over 3 weeks, her VF deficits resolved in the left eye, with complete resolution of both disc edema and retinal hemorrhages. Over the following year, she developed mild temporal pallor in the left eye with peripapillary retinal nerve fiber layer thinning on optical coherence tomography and had a persistent mild left rAPD. She began hydroxychloroquine for Sjögren disease. She remained stable over the next 4 years. Repeat antiRo and anti-ribonucleoprotein antibodies remained positive. Her Sjögren treatment was successful with stable control of her symptoms and without retinal toxicity. AntiMOG antibody testing was performed once available and was positive with a 1:100 titer. AQP4-IgG serology was negative. She has not experienced any other manifestations of MOGAD nor required any other immunomodulatory or immunosuppressive treatments. Optic neuritis can be associated with MS, NMOSD, and MOGAD. NMOSD is a well-known demyelinating disorder associated with optic neuritis and/or transverse myelitis with AQP4 antibody seropositivity in a majority of cases. MOGAD is a more recently described demyelinating autoimmune disease that presents with inflammatory CNS disease, including acute disseminated encephalomyelitis, optic neuritis, and/or transverse myelitis. It presents more frequently with isolated optic neuritis and can have a monophasic or Mittal et al: J Neuro-Ophthalmol 2021; 41: e48-e50 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Fundus photography. Fundus photograph of the left eye (B) at initial presentation demonstrated left optic disc edema with associated peripapillary radial folds and scattered intraretinal and subretinal hemorrhages without vascular sheathing. The right eye (A) was normal. relapsing course. Optic neuritis attacks in patients with MOGAD can be severe, and MRI frequently shows perineural enhancement associated with optic neuritis, similar to our case (1). MOGAD patients, however, often respond well to initial treatment with steroids. Although recurrences do occur, long-term visual outcomes are favorable, with substantial recovery after attacks in most patients (1). Our patient presented with optic neuritis with positive anti-MOG and Sjögren antibodies. Although uncommon, Sjögren antibodies and SLE have been described in association with AQP4-IgG-positive NMOSD. Patients with AQP4-IgG-positive NMOSD initially present more frequently with transverse myelitis than optic neuritis and have a more severe course and worse prognosis of myelopathy and vision. It is proposed that anti-AQP4 antibodies may target common epitopes between AQP4 in the CNS and AQP5 in the salivary glands. In addition, vasculopathy from systemic autoimmune disease may disrupt the blood–brain barrier and potentiate the effects of anti-AQP4 antibodies (2). An association between MOGAD and SLE has been suggested, but to a lesser degree than the association of AQP4-IgG-positive NMOSD with SLE or Sjögren antibodies, in part due to the improved specificity of MOG assays over time (3,4). As with NMOSD, vasculopathy and perivascular demyelination are believed to be contributing factors (3). Before 2004, when the NMO antibody was first identified, the prevalent theory was that the systematic disorder (SLE, Sjögren disease, etc.) caused the neurological syndrome. We now understand better that they reflect dysimmunity with more than one target (systemic and neurological) (5,6). Javed et al (7) also had a few patients with longitudinally extensive myelitis, with positive biopsies and negative serology; it is possible that these patients were antiMOG–positive eventually. Review of the literature shows that optic neuritis associated with Sjögren disease has a highly variable clinical presentation. When present, optic neuritis may be the initial manifestation of Sjögren disease, with acute or insidious onset and development of chronic optic nerve atrophy. Cases report frequent relapses and bilateral involvement, prompting further investigation into the role of demyelinating diseases (8). Although NMOSD has been demonstrated as a coexisting disease with Sjögren disease, no previous cases of anti-MOG optic neuritis have been reported in the setting of Sjögren disease. Our patient presented with intraretinal and subretinal hemorrhages, which have only rarely been described in patients with MOGAD. Her clinical course was benign, and the initial presence of intraretinal and subretinal hemorrhages provided an initial clue that this case is not a typical presentation of optic neuritis, illustrating the need to obtain AQP4 and anti-MOG testing in any atypical optic neuritis. FIG. 2. MRI. Axial T2 precontrast MRI of the orbits showing hyperintensity and expansion of the left optic nerve and nerve sheath, along with flattening of the globe at the nerve insertion (A). Coronal T1 postcontrast MRI of the orbits with fat suppression showing enhancement of the left optic nerve and nerve sheath (B). Mittal et al: J Neuro-Ophthalmol 2021; 41: e48-e50 e49 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Fluorescein angiography demonstrated delayed arteriovenous transit, indicating venous stasis from severe optic disc edema. Although our patient did have hypertension and diabetes, these were well-controlled, and she did not have retinopathy in the fellow eye or other signs of vasculitis, suggesting her hemorrhages were due to venous stasis retinopathy associated with anti-MOG–related optic neuritis. She responded well to an initial 3-day high-dose steroid treatment and a short course of oral steroids and is taking hydroxychloroquine for treatment of her Sjögren disease. She experienced good visual recovery, characteristic of anti-MOG optic neuritis, and has remained relapse-free after 4 years. We present the first case of anti-MOG–positive optic neuritis in a patient with Sjögren disease. Testing for the presence of these and other autoimmune diseases in anti-MOG–positive patients should be considered. Additional cases of antiMOG–positive optic neuritis associated with systemic autoimmune disease will help to determine whether management and prognosis differ in the presence of autoimmune disease. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: O.-O. O. Adesina, A. Goldberg, and J. Choi, Chen; b. Acquisition of data: A. Mittal, I. F. Baig, and A. G. Merchant; c. Analysis and interpretation of data: O.-O. O. Adesina, A. Goldberg, J. Choi, J. J. Chen, A. Mittal, I. F. Baig, and A. G. Merchant. Category 2: a. Drafting the manuscript: A. Mittal, I. F. Baig, and A. G. Merchant; b. Revising it for intellectual content: O.-O. O. Adesina, A. Goldberg, J. Choi, and J. J. Chen. Category 3: a. Final approval of the completed manuscript: O.-O. O. Adesina, A. Goldberg, J. Choi, J. J. Chen, A. Mittal, I. F. Baig, and A. G. Merchant. e50 REFERENCES 1. 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