Bilateral Optic Neuritis as an Atypical Presentation of Primary Sjögren’s Syndrome (pSS)

Introduction: Primary Sjögren’s syndrome (pSS) is a chronic progressive autoimmune disease that primarily affects exocrine glands with varying symptoms. Here we discuss atypical optic neuritis as an initial presentation of pSS without any sicca symptoms. Case presentation: A 22-year-old woman came to the outpatient clinic with the chief complaint of rapid deteriorating visual acuity that had started one week before—no complaint of the eye or other mucosal dryness. At the initial visit, best corrected visual acuity (BCVA) was hand movement on the right eye and 6/7.5 on the left eye with decreasing color perception. Fundus examination showed bilateral optic nerve head edema. Schirmer test and tear-film break up time were within normal limits. After the initial one gram intravenous methylprednisolone treatment, no significant changes were observed for three consecutive days. Serological investigations revealed raised levels of SS-A native. Improvement happened after being given azathioprine. Conclusion: Optic neuritis may be the initial presentation of Sjögren’s syndrome without sicca symptoms. The presence of a specific antibody, including anti-SSA, is supportive for the diagnosis of such a case.


Introduction
Optic neuritis is an optic nerve inflammation, where the most common cause is idiopathic. However, this disease can also be associated with several conditions such as demyelinating disease, autoimmune disease, infection, and inflammation. Dominant optic neuritis affects a healthy young woman with subacute decreased visual acuity symptoms with unilateral pain. Optic neuritis is the most common optic neuropathy in patients under 50 years of age, and as much as 20% is an early sign of multiple sclerosis (MS). [1] Common complaints of optic neuritis include impaired subacute monocular visual acuity, flashes or flickering lights, discomfort or pain around the eye (90%) on eye movement due to contraction of the eyeball muscle that pulls the optic nerve sheath, headache, visual field disturbances, widening of the blind spots (focal central/altitudinal/ arcuata), impaired color vision (dyschromatopsia), presence of relative afferent pupillary defect (RAPD) and optic disc appears edema in papillitis. [2] Sjogren's syndrome is a chronic progressive autoimmune disease with periductal lymphocytic infiltration in the exocrine secretory glands, especially the salivary and tear glands. This causes dryness of the mucous membranes throughout the body and the appearance of systemic symptoms due to an inflammatory reaction or vasculitis and can be accompanied by neurological disorders. [3] Based on data, the incidence of optic neuritis worldwide is 0.94-2.18 per 100.000 person/year, with 1.62 per 100.000 person/year in Japan. Female predominance was 1:3 in a European cohort study [4] . Clinical manifestations of Sjogren's syndrome include dry eye symptoms, xerostomia, edema of the salivary gland, dry skin, and persistent dry cough. Optic neuritis caused by Sjogren's syndrome is very rare.
According to a retrospective study by Tang and Wei [3] , out of 128 patients treated https://e-journal.unair.ac.id/VSEHJ with optic neuritis, only eight people had Sjogren's syndrome. Of the eight people, only three people with dry eye manifestations, while the others were diagnosed based on the results of the ANA profile test (SS-A and SS-B). [3] According to Shiboski et al. [5] diagnostic criteria for Sjogren's syndrome based on complaints of dry eyes for three months (objectively with Schirmer's test < 5 mm for five minutes), serological results of ANA titer > 1:160 with Anti-Ro-SSA and/or positive anti-La/SSB antibodies and abnormal histological examination (salivary gland biopsy) in the form of mononuclear lymphoid cell infiltration in the salivary glands.
There is no standard treatment for optic neuritis associated with Sjogren's syndrome. However, based on previous literature [6] , administration of highdose methylprednisolone for three days followed by oral prednisone can give good results. In addition, immunosuppressive drugs can also be used. [6] Here we discuss atypical optic neuritis as an initial presentation of primary Sjögren's syndrome (pSS) without any sicca symptoms.

Case presentation
A 22-year-old woman came to the outpatient unit with rapidly deteriorating visual acuity in the right eye one week before being admitted to the hospital. She had blurred vision which was accompanied by eye pain in movement. There was no diplopia, recurrent red eyes, nystagmus, headache, nausea, or vomiting. Seeing black dot, the flash of light and curtain-like vision were denied.
The patient also felt a little blurry in the left eye with no pain on movement. No complaints of burning, gritty, itchy, or dry eyes in both eyes. Dry lips and difficulty chewing were denied. The patient was referred from a regional hospital with suspicion of right eye optic neuritis. There was no trauma, history of wearing glasses, eye surgery, or previous systemic disease. History of treatment with oral methylprednisolone 8 mg every eight hours and artificial tears for three days but no improvement of vision.
The general status of the patient was within normal limit. Ophthalmology examination revealed right eye hand movement visual acuity and the left eye visual acuity was 6/20 pinhole improved to 6/7.5. Intraocular pressure in both eyes was within the normal limit.
Examination of color perception in the right eye could not be evaluated, and the left eye was within normal limit.
Ocular motility in both eyes was good in every direction but accompanied by pain in the right eye movement.   We performed a Schirmer's test that showed a reading of more than 10 mm at the end of five minutes, and the tear film break-up time was ten seconds.
Our patient was consulted to the rheumatology division and diagnosed with Sjogren's syndrome. The patient received Azathioprine 50 mg once daily. One week later, the visual acuity changed to 5/60 on the right eye, with color vision improving to 9/14. On the next visit, visual acuity improved significantly to 5/60 pinhole 5/12, and color perception was 12/14. The posterior segment showed significant changes and became firmly demarcated with normal color. After three months of treatment, the BCVA of the right eye was 5/6.6, the left eye was 5/5, the right and left eyes color perceptions were normal. Fundus examination remained the same with the last visit ( Figure 5). The patient was decreasing the dose of methylprednisolone and continuing azathioprine.

Discussion and conclusions
Sjögren's syndrome is an autoimmune disease that causes exocrine glands throughout the body to die gradually. The lacrimal and salivary glands are the most impacted, causing the most symptoms in the form of the ocular surface and mucosal dryness. This condition can affect the exocrine glands exclusively or as a side effect of other autoimmune diseases. [7], [8], [9] Although very rare, optic neuritis can be an early sign of Sjögren's syndrome in which there is no complaint of dry mouth and dry eye.
In this case, we found a vague case of Sjögren's syndrome associated with bilateral optic neuritis in a young woman.
After detailed history taking, no keratoconjunctivitis sicca nor xerostomia symptoms were found in this patient.
A similar case was also reported by Tang et al. [3] , which observed eight patients with primary Sjogren's syndrome, all were women, and half of the patients had bilateral optic neuritis. All of the patients initially presented with acute blurred vision, just like our patient with negative serum  anti AQP4 antibody titers, so neuromyelitis optic was not taken into consideration. [3] Another study from Sun et al. [6] also reported some cases of Sjogren's syndromerelated optic neuritis. The seven female patients were all between the ages of 8 and 56. Five of the individuals had never been diagnosed with Sjögren's syndrome before. [6] In a case series published by Bak et al. [11] , three out of syndrome-related optic neuropathy is caused by many of these processes. [11] In this case, we made the diagnosis of pSS based on diagnostic criteria of the American Rheumatology Association [5] , including five criteria. Labial Sjögren's syndrome patients in a prior investigation. [12], [13] Patients with visual neuritis caused by primary Sjögren's syndrome may not have any other symptoms. As a result, it is easy to overlook or misinterpret it. There was a diagnostic and therapeutic challenge in this. Misdiagnosis of pSS-associated ON has negative effects. To begin with, it may cause a delay in adequate treatment, as well as unanticipated complications and visual loss. [14] Second, misdiagnosis can lead to incorrect therapy and negative outcomes. Five of seven cases in earlier reports were misdiagnosed as primary ON or other eye disorders. [15], [16] Because the patient had no sicca symptoms, treating pSS is also challenging. There is no standard treatment  Table 1. Visual Evoked Potential examination shows partial demyelinating prechiasma lesion on right visual pathway. gram of methylprednisolone intravenously for three days. Our patient had a methylprednisolone injection followed by a maintenance dosage of prednisone as part of the conventional treatment procedure for optic neuritis, however, no improvement in vision was seen.
It emphasizes Sjögren's syndrome's atypical signs, such as optic neuritis, before major disease-related ocular or oral symptoms. [18], [19], [20] The patient was diagnosed with Sjögren's syndrome and received oral administration of azathioprine which is effective after steroid tapering According to thorough research, most patients with optic neuritis do not follow the expected clinical course. [19] Although further research is not normally required in typical optic neuritis, neuroimaging is necessary to rule out the potential of multiple sclerosis. [20] On the other hand, atypical instances necessitate a more thorough and ongoing assessment. In cases of optic neuritis with an atypical underlying condition, a detailed clinical history, thorough testing, and attentive monitoring are essential.