Bilateral Fuchs Uveitis Syndrome and Its Association With Multiple Sclerosis

Bilateral Fuchs Uveitis Syndrome and Its Association With Multiple Sclerosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bilateral Fuchs Uveitis Syndrome and Its Association With Multiple Sclerosis Gunes Gumus Kasapoglu, Cigdem Altan, Berru Yargi Ozkocak, Burcu Kemer Atik, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9227016/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose To investigate the prevalence of multiple sclerosis (MS) among bilateral Fuchs uveitis syndrome (FUS) cases and compare their clinical characteristics with unilateral cases. Methods Patients with bilateral FUS (Study group) and unilateral FUS (Control group) were reviewed retrospectively. All patients in the study group underwent fluorescein angiography (FA) and magnetic resonance imaging (MRI) and neurological consultation. Whereas in the control group, patients with posterior segment involvement underwent FA. MRI and neurological consultation were performed on patients with neurological symptoms. The relationship between MS diagnosis and data was evaluated. Results Forty eyes of 20 patients in the study group and 40 eyes of 40 patients in the control group were included. Neurological evaluations revealed that 15% (3/20) of the patients in the study group were diagnosed with MS, whereas neurologic symptoms were observed in one patient in the control group; however, MRI findings did not support a diagnosis of MS. Study group showed a higher prevalence of diffuse keratic precipitates (p < 0.001, χ2 test), while iris nodule subtypes differed between groups, with Busacca nodules predominating in study group and Koeppe nodules in control group (p = 0.019, p = 0.008 respectively, χ2 test). There was no significant difference between MS and non-MS eyes with fundus and FA findings (p > 0.05, χ2 test). Conclusion The frequency of MS disease was found to be higher in bilateral FUS patients than in unilateral FUS cases. MS should be kept in mind in the diagnosis and follow-up of patients with bilateral FUS, and neurological investigations should be carried out when necessary. Bilateral Fuchs uveitis syndrome Fundus Fluorescein angiography Multiple Sclerosis Unilateral Fuchs uveitis syndrome Vitreous condensation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Fuchs' uveitis syndrome (FUS), first described by Ernst Fuchs in 1906, is a chronic, granulomatous ocular condition characterized by predominantly unilateral mild anterior segment inflammation. 1 It accounts for 1–20% of total anterior uveitis cases and is the second most common type of non-infectious uveitis. 2 , 3 The involvement of both eyes has been reported at various rates (0–21%) in the extant literature. 2 , 4 – 6 The diagnosis of FUS is based on clinical findings including, minimal or no ciliary injection, the presence of diffuse medium-sized round or fine-stellate keratic precipitates (KP), low-grade iridocyclitis, the absence of posterior synechiae, diffuse stromal iris atrophy with or without heterochromia, iris nodules, elevated IOP and glaucoma, abnormal vessels in the iris and iridocorneal angle, posterior subcapsular lens opacities, and vitreous opacities or cells. 2 , 3 , 7 , 8 Although posterior segment involvement is rare, chorioretinal scars, sheathing of retinal vessels, epiretinal and preretinal band formation, and peripheral vascular leakage are some of the manifestations that may be observed. 2 , 5 , 6 FUS often remains underdiagnosed and/or misdiagnosed leading to unnecessary investigations and therapy. 5 Treatment is unnecessary in patients with FUS except for symptomatic exacerbations and complications. 9 It is hypothesised that FUS result from a combination of insults or pathogenic mechanisms, including infectious agents, autoimmune diseases, hereditary factors, and sympathetic dysfunction. 7 A multitude of studies have analysed the presence of Rubella RNA or antibodies in the aqueous humour of patients diagnosed with FUS and concluded that patients with FUS have persistent immunoglobulin G (IgG) oligoclonal Rubella antibodies in the affected eye. 10 Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) that is characterized by inflammation, demyelination, and autoimmune mechanisms. The existence of persistent intrathecal oligoclonal immunoglobulin G (IgG) bands (OCBs) and lesional IgG depositions are key features of MS disease pathology. Optic neuritis represents the most prevalent ophthalmic complication observed in patients diagnosed with MS. 11,12 However, uveitis occurs with a higher incidence in this group compared to the general population. 13 , 14 The rarity of documented cases of bilateral FUS may be attributed to the predominantly unilateral presentation of FUS, which could lead to the underrecognition of bilateral cases. Nevertheless, the hypothesis that bilateral FUS might be associated with systemic autoimmune diseases like MS is worth consideration, given the shared autoimmune mechanisms underlying both conditions. 15 Therefore, investigating the possible association between bilateral FUS and MS is essential to better define their pathophysiological interplay and potential shared mechanisms. The present study aims to assess this relationship in the context of the current literature and to address the clinical implications and management of this uncommon association. Materials and Methods This retrospective, comparative study was conducted at a tertiary referral uveitis center between January 2012 and June 2024. The study was approved by the University of Health Sciences Hamidiye Scientific Research Ethics Committee (decision number 2/2 on February 6, 2025) and conducted in accordance with tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal guardians. The study group consisted of patients with bilateral FUS, while the control group included patients with unilateral FUS. Unilateral cases (40 patients) were followed for at least 12 months to exclude delayed bilateral involvement and matched with the bilateral group using propensity score matching method. All patients were diagnosed based on the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria by an experienced specialist (CA). 16 These included the absence of acute inflammatory symptoms, typical KPs (white, stellate, and diffusely distributed), low anterior chamber cell and flare density, absence of posterior synechiae throughout follow-up, and typical iris features such as stromal iris atrophy, flattening of iris crypts, and/or heterochromia. Mild vitreous inflammation consistent with the known clinical spectrum of FUS was permitted. The differential diagnosis of pars planitis and other forms of intermediate uveitis was systematically evaluated based on the SUN classification criteria. 17 , 18 Pars planitis was excluded in all cases due to the predominance of anterior segment findings and the absence of features characteristic of intermediate uveitis such as dense vitritis, snowbanking in the pars plana or inferior vitreous base, recurrent inflammatory exacerbations or the need for long-term systemic immunosuppression. FA findings were interpreted in accordance with the SUN classification, typical anterior segment features and stable clinical course of FUS. The entire diagnostic process was based on clinical evaluation. Invasive diagnostic procedures, such as polymerase chain reaction (PCR) analysis of aqueous or vitreous samples, were not performed, as none of the patients exhibited clinical features suggestive of infectious uveitis. In bilateral FUS cases, a standard uveitis diagnostic panel including complete blood count/biochemistry, acute phase reactants (erythrocyte sedimentation rate, C-reactive protein), syphilis serology, hepatitis markers, and HIV enzyme-linked immunosorbent assay (ELISA), as well as additional laboratory tests if deemed necessary was applied to assess potential systemic associations. Evaluation for MS was performed based on neurological consultation and magnetic resonance imaging (MRI) findings. The diagnosis of MS was established according to neurological clinical findings and relevant diagnostic criteria. The stepwise diagnostic approach used to confirm bilateral FUS and exclude alternative etiologies is summarized in the study flow chart ( Fig. 1 ). Data collection A comprehensive ocular examination was performed for each patient including best-corrected visual acuity (BCVA) via Snellen chart (converted to logMAR), slit-lamp examination, intraocular pressure (IOP) measurement via Goldmann applanation tonometry and dilated fundus examination. Detailed clinical information regarding FUS findings was recorded, including laterality, distribution and characteristics of KPs, iris features, presence of Koeppe/Busacca nodules and heterochromia, presence of abnormal vessels in the iridocorneal angle, lens status, presence of glaucoma, vitreous infiltration, fundus lesions, and if any anterior and posterior segment complications. After pupillary dilation, the aqueous flare was determined in all subjects using the laser flare-cell meter FM-700 (Kowa, Japan). Neurological symptoms, including sensory disturbances, motor deficits, ataxia, bladder dysfunction, dysarthria, vertigo, and cognitive impairment, were systematically evaluated. All patients in the study group underwent fluorescein angiography (FA, Visucam 500, Carl Zeiss Meditec AG, Jena, Germany) and cranial ± cervical MRI with contrast and neurological consultation. Whereas in the control group, patients with posterior segment involvement (intense vitreous inflammation, chorioretinal scar, retinal vascular sheathing, blurred optic disc margins) underwent FA. MRI and neurological consultation were performed in patients with neurological symptoms. Statistical methods Statistical analysis was performed using SPSS Statistics, version 26.0 (SPSS Inc., Chicago, IL, USA). Unilateral FUS patients followed in our clinic were matched according to the propensity scores of bilateral cases and included in the study. The distribution of the variables was assessed using the Kolmogorov–Smirnov and Shapiro–Wilk tests to evaluate normality. Descriptive statistics were presented as frequency (n) and percentage (%), and numerical variables were presented as mean ± standard deviation (SD) or median and interquartile range (IQR). Comparisons between groups were conducted using the Student's t-test for data that meet parametric assumptions, and the Mann–Whitney U test for non-parametric data. The chi-squared test or Fisher’s exact test was employed, as appropriate, to analyze differences in proportions between groups. For correlations involving non-normally distributed or ordinal variables, Spearman's rank correlation coefficient was calculated to assess both the strength and significance of the relationships. p value of < 0.05 was considered statistically significant. To minimize bias due to interocular correlation in bilateral cases, only the right eye of the patients in the study group was included in the visual acuity analysis. This allowed a single-eye comparison for each patient and preserved the assumption of independence between groups. Results A total of 20 patients with bilateral FUS (study group) and 40 patients with unilateral FUS (control group) were included in this study. All unilateral cases were followed for a minimum of 12 months to minimize the risk of delayed contralateral involvement. There was no statistically significant difference in gender distribution in both groups (p = 0.179, χ 2 test ). The mean age in the study group was 40.1 ± 8.9 years and it was 42.2 ± 8.9 years in the control group (p = 0.289, Independent sample t-test ). In the control group, 26 patients exhibited involvement of the right eye, while 14 patients demonstrated involvement of the left eye. The median follow-up period was 36 months (IQR: 20–53) in the study group and 24 months (IQR: 15–59) in the control group (p = 0.633, Mann - Whitney U test). There was no statistically significant difference between the groups in terms of BCVA (p = 0.273, Mann–Whitney U test ). Table 1 presents the demographic and clinical characteristics of the groups. Table 1 Comparison of clinicodemographic features between two groups. Variables The study group (40 eyes of 20 patients) The control group (40 eyes of 40 patients) p -value Age (years) Mean ± SD 40.1 ± 8.9 42.2 ± 8.9 0.289 * Gender N (%) Male 9 (45) 24 (60) 0.179 † Female 11 (55) 16 (40) BCVA** (LogMAR), Median (IQR) Min-max 0.3 (0.1–0.3) 0.00-1.30 0.3 (0.15–0.4) 0.00-1.30 0.273 ‡ IOP at first visit (mmHg), Median (IQR) Min-max 15 (12–17) 10–34 15 (12–20) 7–39 0.229 ‡ Maximum IOP (mmHg) during follow-up, Median (IQR) Min-max 17.5 (15–20) 12–42 20 (16–29) 10–48 0.084 ‡ Aqueous flare values*** (photon counts/ms), Median (IQR) Min-max 13 (8–17) 4–33 9 (8–15) 7–20 0.716 ‡ Slit lamp biomicroscopy KPs (Diffuse stellate KP/medium-sized round granulomatous KP), n 36 / 4 19 / 21 < 0.001/<0.001 † AC cell, n (%) 0 18 (45) 15 (37.5) 0.5 + to 2+ 20 (50) 21 (52.5) 0.496 † 3 + to 4+ 2 (5) 4 (10) Atrophic iris change, n (%) 29 (72.5) 33 (82.5) 0.190 † Heterochromia, N 6 36 < 0.001 † Iris nodule (Busacca/Koeppe), n (%) 11 (27.5) / 8 (20) 3 (7.5) / 18 (45) 0.019/0.008 † Anterior vitreus cell and debris, n (%) 31 (77.5) 33 (82.5) 0.576 † Vitreous condensations and strands, n (%) 29 (72.5) 24 (60) 0.123 † Elevated IOP, n (%) 7 (17.5) 14 (35) 0.075 † Cup/Disc ratio, Median (IQR) Min-max 0.3 (0.3–0.4) 0.2–0.8 0.4 (0.3–0.6) 0.1–0.9 0.098 ‡ Glaucoma surgery history, n (%) 7 (17.5) 13 (22.5) 0.222 † Lens status n (%) Cataract/lens opacity 14 (35) 15 (37.5) 0.816/ 0.011/0.003 † Pseudophakia 9 (22.5) 20 (50) No significant cataract 17 (42.5) 5 (12.5) (AC = anterior chamber, BCVA = best-corrected visual acuity, IOP = intraocular pressure, KP = keratic precipitates, n=number of eyes) N= number of patients, n=number of eyes * Independent sample t-test † χ 2 test ‡ Mann - Whitney U test ** BCVA values were analyzed using the right eye in the study group to avoid interocular correlation. *** Values in the study group were calculated based on both eyes Significant result are shown in bold type. When comparing both groups, floaters were the most frequently reported symptom observed in 40% of the study group and 37.5% of the control group. Blurred vision was reported by 35% of the study group and 32.5% of the control group. Ocular discomfort was present in 25% of the study group and 30% of the control group. Among the patients with blurred vision, 10 of 40 eyes in the study group and 11 of 40 eyes in the control group had cataract. Glaucoma was observed in 4 eyes in the study group and 3 eyes in the control group, while epiretinal membrane was detected in 4 eyes in both groups. There was no statistically significant difference between the groups in terms of these symptoms and findings (p > 0.05 for all comparisons, χ 2 test ). The aqueous flare values of the study and control groups were not significantly different (p = 0.716, Mann - Whitney U test). Heterochromia was significantly more frequent in the control group ( p < 0.001 , χ 2 test) . There were also differences in the subtypes of iris nodules between the groups. Busacca nodules were more common in the study group, whereas Koeppe nodules were more common in the control group (Busacca nodules: p = 0.019 ; Koeppe nodules: p = 0.008 , χ 2 test ) ( Fig. 2 ) . In the control group, FA was performed in eight cases with dense vitreous condensation. Fundus examination identified tent-shaped vitreous opacities in three of them (7.5%). FA evaluation showed blockage patterns due to vitreous opacities in two patients and optic disc hyperfluorescence accompanied by peripheral retinal vascular leakage in one patient. This patient with optic disc hyperfluorescence had a history of FUS diagnosed ten years earlier and was further evaluated due to ongoing neurological symptoms. Cranial MRI revealed no demyelinating plaques consistent with MS, and the diagnosis was therefore radiologically excluded. Nevertheless, the patient remains under neurological follow-up due to persistent clinical findings. In the study group, all patients underwent FA ( Figs. 3 , 4 and 5 ) . Patients were referred to a neurologist with MRI. The fundus examination and FA findings of bilateral FUS patients with and without MS, as well as unilateral FUS patients, are summarized in Table 2 . No statistically significant differences were observed between eyes with and without multiple sclerosis for any fundus or angiographic parameters. Table 2 Distribution of posterior segment and FA findings by MS diagnosis in FUS. Findings MS Non-MS p -value Bilateral FUS (3 patients) (n%) Bilateral FUS (17 patients) (n%) Unilateral FUS (40 patients) (n%) Dense vitreous condensation 4 (67%) 12 (35%) 17 (43%) 0.536* Tent-shaped vitreous bands 1 (17%) 2 (6%) 3 (8%) 1.000* Band-shaped vitreous opacities 1 (17%) 2 (6%) - 0.792* Peripheral chorioretinal scar - 1 (3%) - Optic disc hyperfluorescence (FA) 4 (67%) 3 (9%) 1 (3%) 0.134* Peripheral vascular leakage (FA) 3 (50%) 1 (3%) 1 (3%) 0.147* Blockage due to vitreous opacities (FA) 3 (50%) 7 (21%) 2 (5%) 1.000* N= number of patients, n=number of eyes * χ 2 test MRI of patients in the study group revealed active demyelinating plaques in three patients, bilateral periventricular linear ischaemic gliotic lesions in one patient, and partial empty sella syndrome in another. Cerebrospinal fluid (CSF) analysis was performed in three patients with bilateral FUS manifestations, revealing OCB positivity in all three cases, further supporting the diagnosis of demyelinating disease. Based on clinical, radiological, and laboratory findings, MS was diagnosed in three patients (15%) within the study group. Additionally, one patient whose daughter had been diagnosed with MS underwent detailed evaluation; however, MS was excluded, and the patient remains under observation. Treatment regimens in the study group varied, with one patient receiving fingolimod, another treated with glatiramer acetate, and a third prescribed mycophenolate mofetil. Discussion The diagnosis of FUS is based on the clinical manifestations. 4 , 5 , 19 – 21 FUS is generally considered to be a unilateral disease, however, bilateral involvement has been reported in some cases. 2 , 5 , 15 The existence of cases involving both eyes may necessitate further investigation of the underlying mechanisms and possible systemic relationships. The findings of this study indicate that bilateral FUS may have distinct clinical and immunopathological characteristics, possibly linking it to autoimmune mechanisms similar to those observed in MS. 15,22 In the present study, the aim was to highlight the clinicodemographic differences in bilateral FUS cases and their potential association with MS. Given the observed association, clinicians should remain aware of potential systemic comorbidities to facilitate timely recognition and appropriate referral when clinically indicated. Norrsell et al. identified bilateral FUS in 6% of patients diagnosed with FUS (3 out of 54) and observed that these cases were evident from the onset. Additionally, they emphasized that bilateral involvement was associated with a higher risk of complications, particularly glaucoma and vitreoretinal abnormalities, and often led to a delayed diagnosis. 22 In this study, no difference was found between the groups in terms of glaucoma presence, IOP, aqueous flare and significant lens opacity. This difference may be related to patient selection, duration of follow-up and characteristics of presentation to the centre and suggests that bilateral involvement alone does not necessarily imply a more severe ocular course. The biomicroscopic findings, including the presence of KPs, heterochromia and iris nodules, exhibited significant disparities between the study and the control groups. This finding suggests that not only the degree of inflammation but also the nature of the inflammatory response may be different in bilateral FUS. However, further studies are required to determine whether there is a definite difference in the clinical severity of the disease. Previous studies have consistently demonstrated frequent vitreous involvement in FUS. Tugal-Tutkun et al. 2 reported vitreous cells or debris in 71.8% and vitreous condensation in 48.6% of patients, while Bouchenaki et al. 5 described vitritis in 97.4% of cases. Similarly, Yang et al. observed vitreous opacities in 73.8% of Chinese patients with FUS. 4 In this study, vitreous condensation and opacities were observed more frequently in the study group but no statistically significant difference was found. This suggests that vitreous involvement is a common disease feature rather than a distinguishing feature of bilateral FUS. The association between pars planitis and MS has previously been reported. 23 Symptomatic intraocular inflammation is uncommon in patients with MS, with an overall prevalence of approximately 1%, and most frequently presents as intermediate uveitis characterized by peripheral retinal vascular involvement detectable on FA. 24,25 Typical angiographic findings include peripheral venous leakage or staining, while clinical examination may reveal features such as snowballs, snowbanking-related exudates, and peripheral periphlebitis. 26 In our study, although MS appeared to be more frequently associated with bilateral FUS, the clinical examination and FA findings were not consistent with MS-related uveitis or pars planitis. While some posterior segment and FA features may overlap, our findings indicate that MS is not the primary cause of ocular inflammation in bilateral FUS cases, but rather represents a concomitant systemic condition, possibly reflecting a shared immune-mediated susceptibility. In contrast to MS-associated intermediate uveitis, which typically demonstrates peripheral venous leakage on FA, FUS is more commonly characterized by optic disc hyperfluorescence and late-phase peripheral retinal capillary leakage. 27 Consequently, although this partial overlap in angiographic features may lead to diagnostic confusion, particularly in bilateral cases. FA findings alone should not be used as a screening tool for MS. Instead, neurological evaluation should be guided by systemic symptoms and the overall clinical context. The pathogenetic relationship between uveitis and MS has not yet been fully elucidated. However, human leukocyte antigen (HLA) class II alleles such as HLA-DR15 and HLA-DR51 have been implicated in MS-associated uveitis, particularly intermediate uveitis, suggesting a shared immunogenetic susceptibility between intraocular inflammation and central nervous system (CNS) involvement. 28 , 29 In addition, infectious agents have been proposed as potential triggers capable of initiating autoimmune responses affecting both the eye and the CNS in genetically or immunologically susceptible individuals. 14 Viral factors, especially rubella virus, have been strongly associated with the pathogenesis of FUS, while chronic intrathecal antiviral immune activation -reflected by the MRZ reaction- is a well-recognized feature of MS. 30–33 Brichová et al. reported that bilateral FUS is more frequently associated with systemic diseases; however, detailed data regarding systemic conditions other than MS were not provided. 15 In the present study, the increased prevalence of MS in patients with bilateral FUS supports the hypothesis that shared autoimmune and virus-triggered immune mechanisms may contribute to this clinical phenotype, consistent with growing evidence on the role of autoimmunity in non-infectious uveitis. 34 This study is one of the limited number of study in the literature comparing the prevalence of MS in patients with bilateral and unilateral FUS. In the study by Brichová et al. the prevalence of MS in bilateral FUS patients was reported as 18% and this rate was found to be significantly higher compared to unilateral cases. 15 Similarly, in our study, MS was diagnosed in 15% of bilateral FUS patients. In contrast, MS was suspected in only one patient in the unilateral FUS group and this diagnosis was excluded for the time being after neurological evaluations. This finding suggests that bilateral FUS may be a warning clinical sign for underlying systemic autoimmune diseases. The retrospective design of the study, the fact that it was single-centre, the lack of systematic autoimmune and infectious screening in all patients and the lack of aqueous humour analyses are important limitations. However, the relatively high number of bilateral FUS cases and the comparative analysis with the unilateral group are the strengths of the study. In conclusion, the frequency of MS disease was found to be higher in bilateral FUS patients than in unilateral FUS cases. The association with MS should be kept in mind in the diagnosis and follow-up of patients diagnosed with bilateral FUS, and neurological examination and consultations should be performed when necessary. Prospective studies are needed to elucidate the immunopathological mechanisms underlying this relationship. Declarations Author contribution statement GGK, BYO and CA contributed to the study design. GGK reviewed the medical records and collected data. GGK performed the statistical analysis. GGK, CA, BYO, BKA and BB examined all patients. GGK wrote the main manuscript. BYO and CA performed critical revision of the manuscript. All authors read and approved the final manuscript. Disclosure Statement: The authors report there are no competing interests to declare. Funding: The authors received no financial support for this study. 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Am J Ophthalmol 2006;141(1):212–214. https://doi.org/10.1016/j.ajo.2005.07.078 . Jarius S, Eichhorn P, Franciotta D, Petereit HF, Akman-Demir G, Wick M, et al. The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature. J Neurol. 2017;264(3):453–466. https://doi.org/10.1007/s00415-016-8360-4 Chan NSW, Chee SP, Caspers L, Bodaghi B. Clinical features of CMV-associated anterior uveitis. Ocul Immunol Inflamm. 2018;26(1):107–115. https://doi.org/10.1080/09273948.2017.1394471 Lee RW, Nicholson LB, Sen HN, Chan CC, Wei L, Nussenblatt RB, Dick AD. Autoimmune and autoinflammatory mechanisms in uveitis. Semin Immunopathol. 2014;36(5):581–594. https://doi.org/10.1007/s00281-014-0433-9 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Apr, 2026 Reviews received at journal 20 Apr, 2026 Reviews received at journal 12 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers invited by journal 31 Mar, 2026 Editor assigned by journal 27 Mar, 2026 Submission checks completed at journal 27 Mar, 2026 First submitted to journal 25 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9227016","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":616771362,"identity":"f931ef7f-88d0-438e-8f82-326edafed020","order_by":0,"name":"Gunes Gumus Kasapoglu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYHAD/o8PgCQPHyl6jA1AWthI0WImASIJapGPyD348Mevw9EG5w+kVX7NsZNhY2B++OgGHi2GN/KSjXn7DuduuJFw7LbstmSgw9iMjXPwaZmRYybN2APSwth2W3IbM1ALD5s0AS3mP3+CtJw/zFYsua2esBZ5iRwzBp4fQC0H0tgYP247TFiLAc8bY2nehvTcmTdymKUZtx3nYWMm4Bf59hzDjz/+WOf2nT/D+PHntmp7fvbmh4/x2nIASDC2QTjMPGASj3KwLQ0g8g+Ew/iDgOpRMApGwSgYmQAAIyBKxuKBoFYAAAAASUVORK5CYII=","orcid":"","institution":"Goztepe Prof. Dr. Süleyman Yalçın State Hospital","correspondingAuthor":true,"prefix":"","firstName":"Gunes","middleName":"Gumus","lastName":"Kasapoglu","suffix":""},{"id":616771364,"identity":"61f9fecf-f689-48c0-a0ea-a582034e332b","order_by":1,"name":"Cigdem Altan","email":"","orcid":"","institution":"Beyoglu Goz Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Cigdem","middleName":"","lastName":"Altan","suffix":""},{"id":616771365,"identity":"be2ef1eb-8b71-477d-ae4a-faebefd4f904","order_by":2,"name":"Berru Yargi Ozkocak","email":"","orcid":"","institution":"Beyoglu Goz Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Berru","middleName":"Yargi","lastName":"Ozkocak","suffix":""},{"id":616771367,"identity":"5bf26e0d-64e1-4f63-8ae6-618361636ecb","order_by":3,"name":"Burcu Kemer Atik","email":"","orcid":"","institution":"Beyoglu Goz Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Burcu","middleName":"Kemer","lastName":"Atik","suffix":""},{"id":616771374,"identity":"8b15e085-52ad-4173-aca6-93917b39c631","order_by":4,"name":"Berna Basarir","email":"","orcid":"","institution":"Eye Protection Foundation Bayrampasa Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Berna","middleName":"","lastName":"Basarir","suffix":""}],"badges":[],"createdAt":"2026-03-25 20:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9227016/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9227016/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106402625,"identity":"6cadb06c-6cb7-4e2c-a18e-c65e92516dd2","added_by":"auto","created_at":"2026-04-08 09:12:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":769223,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating the stepwise clinical approach used to establish the diagnosis of bilateral FUS and exclude alternative uveitic entities.\u003c/p\u003e","description":"","filename":"FIGURE1.png","url":"https://assets-eu.researchsquare.com/files/rs-9227016/v1/a217813986dcd08b0447b005.png"},{"id":106189944,"identity":"48012704-559a-416c-a9f5-94bbb7863bdf","added_by":"auto","created_at":"2026-04-05 17:12:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1028723,"visible":true,"origin":"","legend":"\u003cp\u003eAnterior segment photographs of the right and left eyes of a patient with bilateral Fuchs uveitis syndrome (FUS) show Koeppe nodules, fading of iris crypts, and diffuse stellate keratic precipitates, with mild vitreous condensation consistent with typical Fuchs-type vitritis.\u003c/p\u003e","description":"","filename":"FIGURE2.png","url":"https://assets-eu.researchsquare.com/files/rs-9227016/v1/69c1d32843645e6c15cc3007.png"},{"id":106402803,"identity":"2fd5ee30-fba8-4b7f-b005-8724d15dcea4","added_by":"auto","created_at":"2026-04-08 09:12:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":289651,"visible":true,"origin":"","legend":"\u003cp\u003eFA of the patient from the bilateral FUS group without MS: Bilateral peripheral vascular leakage and blockage due to vitreous opacities\u003c/p\u003e","description":"","filename":"FIGURE3.png","url":"https://assets-eu.researchsquare.com/files/rs-9227016/v1/fd9230fda1937a3c00a071ef.png"},{"id":106403026,"identity":"0a4bbe7c-e009-457a-baed-058ef9437c7d","added_by":"auto","created_at":"2026-04-08 09:13:25","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":485395,"visible":true,"origin":"","legend":"\u003cp\u003eFundus photo and FA of one of the patients diagnosed with MS and bilateral\u003cem\u003e \u003c/em\u003eFUS and glaucoma in the left eye. a,b,c: Vitreous opacities in the right eye. d,e,f: FA showing late-phase optic disc hyperfluorescence and peripheral vascular leakage and blockage due to vitreous opacities.\u003c/p\u003e","description":"","filename":"FIGURE4.png","url":"https://assets-eu.researchsquare.com/files/rs-9227016/v1/bbfed88f095094fa897879ba.png"},{"id":106189948,"identity":"e9b20c58-8aa5-4324-94be-a635e4b919eb","added_by":"auto","created_at":"2026-04-05 17:12:35","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":218504,"visible":true,"origin":"","legend":"\u003cp\u003eThe right eye of one of the patients diagnosed with MS. a, b. FA revealed hyperfluorescence in the optic discs and peripheral vascular leakage. (c). Tent-shaped vitritis and vitreous opacities.\u003c/p\u003e","description":"","filename":"FIGURE5.png","url":"https://assets-eu.researchsquare.com/files/rs-9227016/v1/04fbcc6e0c5883cf4eb5f689.png"},{"id":106405640,"identity":"b1c66938-c7a9-4238-b152-b1f20c9f9dad","added_by":"auto","created_at":"2026-04-08 09:28:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3706433,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9227016/v1/0ca8a80e-4636-4df9-ad43-f903d904b635.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBilateral Fuchs Uveitis Syndrome and Its Association With Multiple Sclerosis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFuchs' uveitis syndrome (FUS), first described by Ernst Fuchs in 1906, is a chronic, granulomatous ocular condition characterized by predominantly unilateral mild anterior segment inflammation.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e It accounts for 1\u0026ndash;20% of total anterior uveitis cases and is the second most common type of non-infectious uveitis.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The involvement of both eyes has been reported at various rates (0\u0026ndash;21%) in the extant literature.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe diagnosis of FUS is based on clinical findings including, minimal or no ciliary injection, the presence of diffuse medium-sized round or fine-stellate keratic precipitates (KP), low-grade iridocyclitis, the absence of posterior synechiae, diffuse stromal iris atrophy with or without heterochromia, iris nodules, elevated IOP and glaucoma, abnormal vessels in the iris and iridocorneal angle, posterior subcapsular lens opacities, and vitreous opacities or cells.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Although posterior segment involvement is rare, chorioretinal scars, sheathing of retinal vessels, epiretinal and preretinal band formation, and peripheral vascular leakage are some of the manifestations that may be observed.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e FUS often remains underdiagnosed and/or misdiagnosed leading to unnecessary investigations and therapy.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Treatment is unnecessary in patients with FUS except for symptomatic exacerbations and complications.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e It is hypothesised that FUS result from a combination of insults or pathogenic mechanisms, including infectious agents, autoimmune diseases, hereditary factors, and sympathetic dysfunction.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e A multitude of studies have analysed the presence of Rubella RNA or antibodies in the aqueous humour of patients diagnosed with FUS and concluded that patients with FUS have persistent immunoglobulin G (IgG) oligoclonal Rubella antibodies in the affected eye.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMultiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) that is characterized by inflammation, demyelination, and autoimmune mechanisms. The existence of persistent intrathecal oligoclonal immunoglobulin G (IgG) bands (OCBs) and lesional IgG depositions are key features of MS disease pathology. Optic neuritis represents the most prevalent ophthalmic complication observed in patients diagnosed with MS.\u003csup\u003e11,12\u003c/sup\u003e However, uveitis occurs with a higher incidence in this group compared to the general population.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe rarity of documented cases of bilateral FUS may be attributed to the predominantly unilateral presentation of FUS, which could lead to the underrecognition of bilateral cases. Nevertheless, the hypothesis that bilateral FUS might be associated with systemic autoimmune diseases like MS is worth consideration, given the shared autoimmune mechanisms underlying both conditions.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTherefore, investigating the possible association between bilateral FUS and MS is essential to better define their pathophysiological interplay and potential shared mechanisms. The present study aims to assess this relationship in the context of the current literature and to address the clinical implications and management of this uncommon association.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis retrospective, comparative study was conducted at a tertiary referral uveitis center between January 2012 and June 2024. The study was approved by the University of Health Sciences Hamidiye Scientific Research Ethics Committee (decision number 2/2 on February 6, 2025) and conducted in accordance with tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legal guardians.\u003c/p\u003e \u003cp\u003eThe study group consisted of patients with bilateral FUS, while the control group included patients with unilateral FUS. Unilateral cases (40 patients) were followed for at least 12 months to exclude delayed bilateral involvement and matched with the bilateral group using propensity score matching method. All patients were diagnosed based on the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria by an experienced specialist (CA).\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e These included the absence of acute inflammatory symptoms, typical KPs (white, stellate, and diffusely distributed), low anterior chamber cell and flare density, absence of posterior synechiae throughout follow-up, and typical iris features such as stromal iris atrophy, flattening of iris crypts, and/or heterochromia. Mild vitreous inflammation consistent with the known clinical spectrum of FUS was permitted.\u003c/p\u003e \u003cp\u003eThe differential diagnosis of pars planitis and other forms of intermediate uveitis was systematically evaluated based on the SUN classification criteria.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Pars planitis was excluded in all cases due to the predominance of anterior segment findings and the absence of features characteristic of intermediate uveitis such as dense vitritis, snowbanking in the pars plana or inferior vitreous base, recurrent inflammatory exacerbations or the need for long-term systemic immunosuppression. FA findings were interpreted in accordance with the SUN classification, typical anterior segment features and stable clinical course of FUS.\u003c/p\u003e \u003cp\u003eThe entire diagnostic process was based on clinical evaluation. Invasive diagnostic procedures, such as polymerase chain reaction (PCR) analysis of aqueous or vitreous samples, were not performed, as none of the patients exhibited clinical features suggestive of infectious uveitis. In bilateral FUS cases, a standard uveitis diagnostic panel including complete blood count/biochemistry, acute phase reactants (erythrocyte sedimentation rate, C-reactive protein), syphilis serology, hepatitis markers, and HIV enzyme-linked immunosorbent assay (ELISA), as well as additional laboratory tests if deemed necessary was applied to assess potential systemic associations.\u003c/p\u003e \u003cp\u003eEvaluation for MS was performed based on neurological consultation and magnetic resonance imaging (MRI) findings. The diagnosis of MS was established according to neurological clinical findings and relevant diagnostic criteria. The stepwise diagnostic approach used to confirm bilateral FUS and exclude alternative etiologies is summarized in the study flow chart \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eA comprehensive ocular examination was performed for each patient including best-corrected visual acuity (BCVA) via Snellen chart (converted to logMAR), slit-lamp examination, intraocular pressure (IOP) measurement via Goldmann applanation tonometry and dilated fundus examination. Detailed clinical information regarding FUS findings was recorded, including laterality, distribution and characteristics of KPs, iris features, presence of Koeppe/Busacca nodules and heterochromia, presence of abnormal vessels in the iridocorneal angle, lens status, presence of glaucoma, vitreous infiltration, fundus lesions, and if any anterior and posterior segment complications. After pupillary dilation, the aqueous flare was determined in all subjects using the laser flare-cell meter FM-700 (Kowa, Japan).\u003c/p\u003e \u003cp\u003eNeurological symptoms, including sensory disturbances, motor deficits, ataxia, bladder dysfunction, dysarthria, vertigo, and cognitive impairment, were systematically evaluated.\u003c/p\u003e \u003cp\u003eAll patients in the study group underwent fluorescein angiography (FA, Visucam 500, Carl Zeiss Meditec AG, Jena, Germany) and cranial\u0026thinsp;\u0026plusmn;\u0026thinsp;cervical MRI with contrast and neurological consultation. Whereas in the control group, patients with posterior segment involvement (intense vitreous inflammation, chorioretinal scar, retinal vascular sheathing, blurred optic disc margins) underwent FA. MRI and neurological consultation were performed in patients with neurological symptoms.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS Statistics, version 26.0 (SPSS Inc., Chicago, IL, USA). Unilateral FUS patients followed in our clinic were matched according to the propensity scores of bilateral cases and included in the study. The distribution of the variables was assessed using the Kolmogorov\u0026ndash;Smirnov and Shapiro\u0026ndash;Wilk tests to evaluate normality. Descriptive statistics were presented as frequency (n) and percentage (%), and numerical variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median and interquartile range (IQR). Comparisons between groups were conducted using the Student's t-test for data that meet parametric assumptions, and the Mann\u0026ndash;Whitney U test for non-parametric data. The chi-squared test or Fisher\u0026rsquo;s exact test was employed, as appropriate, to analyze differences in proportions between groups. For correlations involving non-normally distributed or ordinal variables, Spearman's rank correlation coefficient was calculated to assess both the strength and significance of the relationships. \u003cem\u003ep\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. To minimize bias due to interocular correlation in bilateral cases, only the right eye of the patients in the study group was included in the visual acuity analysis. This allowed a single-eye comparison for each patient and preserved the assumption of independence between groups.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 20 patients with bilateral FUS (study group) and 40 patients with unilateral FUS (control group) were included in this study. All unilateral cases were followed for a minimum of 12 months to minimize the risk of delayed contralateral involvement. There was no statistically significant difference in gender distribution in both groups (p\u0026thinsp;=\u0026thinsp;0.179, \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e \u003cem\u003etest\u003c/em\u003e). The mean age in the study group was 40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9 years and it was 42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9 years in the control group (p\u0026thinsp;=\u0026thinsp;0.289, \u003cem\u003eIndependent sample t-test\u003c/em\u003e). In the control group, 26 patients exhibited involvement of the right eye, while 14 patients demonstrated involvement of the left eye. The median follow-up period was 36 months (IQR: 20\u0026ndash;53) in the study group and 24 months (IQR: 15\u0026ndash;59) in the control group (p\u0026thinsp;=\u0026thinsp;0.633, \u003cem\u003eMann\u003c/em\u003e-\u003cem\u003eWhitney U\u003c/em\u003e test). There was no statistically significant difference between the groups in terms of BCVA (p\u0026thinsp;=\u0026thinsp;0.273, \u003cem\u003eMann\u0026ndash;Whitney U test\u003c/em\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the demographic and clinical characteristics of the groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinicodemographic features between two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe study group (40 eyes of 20 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThe control group (40 eyes of 40 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.289\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eGender N (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.179\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA** (LogMAR), Median (IQR)\u003c/p\u003e \u003cp\u003eMin-max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3 (0.1\u0026ndash;0.3)\u003c/p\u003e \u003cp\u003e0.00-1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3 (0.15\u0026ndash;0.4)\u003c/p\u003e \u003cp\u003e0.00-1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.273\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIOP at first visit (mmHg), Median (IQR)\u003c/p\u003e \u003cp\u003eMin-max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (12\u0026ndash;17)\u003c/p\u003e \u003cp\u003e10\u0026ndash;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (12\u0026ndash;20)\u003c/p\u003e \u003cp\u003e7\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.229\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum IOP (mmHg) during follow-up, Median (IQR)\u003c/p\u003e \u003cp\u003eMin-max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.5 (15\u0026ndash;20)\u003c/p\u003e \u003cp\u003e12\u0026ndash;42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (16\u0026ndash;29)\u003c/p\u003e \u003cp\u003e10\u0026ndash;48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.084\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAqueous flare values*** (photon\u0026nbsp;counts/ms), Median (IQR)\u003c/p\u003e \u003cp\u003eMin-max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (8\u0026ndash;17)\u003c/p\u003e \u003cp\u003e4\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8\u0026ndash;15)\u003c/p\u003e \u003cp\u003e7\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.716\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSlit lamp biomicroscopy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKPs (Diffuse stellate KP/medium-sized round granulomatous KP), n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 / 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 / 21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001/\u0026lt;0.001\u003c/b\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAC cell, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.5\u0026thinsp;+\u0026thinsp;to 2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.496\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026thinsp;+\u0026thinsp;to 4+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophic iris change, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (72.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (82.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.190\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeterochromia, N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIris nodule (Busacca/Koeppe), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (27.5) / 8 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5) / 18 (45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.019/0.008\u003c/b\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnterior vitreus cell and debris, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (77.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (82.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.576\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitreous condensations and strands, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (72.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.123\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated IOP, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCup/Disc ratio, Median (IQR)\u003c/p\u003e \u003cp\u003eMin-max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3 (0.3\u0026ndash;0.4)\u003c/p\u003e \u003cp\u003e0.2\u0026ndash;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4 (0.3\u0026ndash;0.6)\u003c/p\u003e \u003cp\u003e0.1\u0026ndash;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlaucoma surgery history, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.222\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eLens status n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCataract/lens opacity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.816/\u003cb\u003e0.011/0.003\u003c/b\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePseudophakia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo significant cataract\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e(AC\u0026thinsp;=\u0026thinsp;anterior chamber, BCVA\u0026thinsp;=\u0026thinsp;best-corrected visual acuity, IOP\u0026thinsp;=\u0026thinsp;intraocular pressure, KP\u0026thinsp;=\u0026thinsp;keratic precipitates, n=number of eyes)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eN= number of patients, n=number of eyes\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e* \u003cem\u003eIndependent sample t-test\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026dagger; \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e \u003cem\u003etest\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026Dagger; \u003cem\u003eMann\u003c/em\u003e-\u003cem\u003eWhitney U\u003c/em\u003e test\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e** BCVA values were analyzed using the right eye in the study group to avoid interocular correlation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*** Values in the study group were calculated based on both eyes\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eSignificant result are \u003cem\u003eshown\u003c/em\u003e in \u003cb\u003ebold\u003c/b\u003e type.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhen comparing both groups, floaters were the most frequently reported symptom observed in 40% of the study group and 37.5% of the control group. Blurred vision was reported by 35% of the study group and 32.5% of the control group. Ocular discomfort was present in 25% of the study group and 30% of the control group. Among the patients with blurred vision, 10 of 40 eyes in the study group and 11 of 40 eyes in the control group had cataract. Glaucoma was observed in 4 eyes in the study group and 3 eyes in the control group, while epiretinal membrane was detected in 4 eyes in both groups. There was no statistically significant difference between the groups in terms of these symptoms and findings (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all comparisons, \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e \u003cem\u003etest\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eThe aqueous flare values of the study and control groups were not significantly different (p\u0026thinsp;=\u0026thinsp;0.716, \u003cem\u003eMann\u003c/em\u003e-\u003cem\u003eWhitney U\u003c/em\u003e test). Heterochromia was significantly more frequent in the control group (\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e, \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e \u003cem\u003etest)\u003c/em\u003e. There were also differences in the subtypes of iris nodules between the groups. Busacca nodules were more common in the study group, whereas Koeppe nodules were more common in the control group (Busacca nodules: \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.019\u003c/b\u003e; Koeppe nodules: \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.008\u003c/b\u003e, \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e \u003cem\u003etest\u003c/em\u003e) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the control group, FA was performed in eight cases with dense vitreous condensation. Fundus examination identified tent-shaped vitreous opacities in three of them (7.5%). FA evaluation showed blockage patterns due to vitreous opacities in two patients and optic disc hyperfluorescence accompanied by peripheral retinal vascular leakage in one patient. This patient with optic disc hyperfluorescence had a history of FUS diagnosed ten years earlier and was further evaluated due to ongoing neurological symptoms. Cranial MRI revealed no demyelinating plaques consistent with MS, and the diagnosis was therefore radiologically excluded. Nevertheless, the patient remains under neurological follow-up due to persistent clinical findings.\u003c/p\u003e \u003cp\u003eIn the study group, all patients underwent FA \u003cb\u003e(\u003c/b\u003eFigs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Patients were referred to a neurologist with MRI. The fundus examination and FA findings of bilateral FUS patients with and without MS, as well as unilateral FUS patients, are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No statistically significant differences were observed between eyes with and without multiple sclerosis for any fundus or angiographic parameters.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of posterior segment and FA findings by MS diagnosis in FUS.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFindings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNon-MS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBilateral FUS (3 patients) (n%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBilateral FUS (17 patients) (n%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnilateral FUS (40 patients) (n%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDense vitreous condensation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.536*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTent-shaped vitreous bands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBand-shaped vitreous opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.792*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral chorioretinal scar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic disc hyperfluorescence (FA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.134*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral vascular leakage (FA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.147*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlockage due to vitreous opacities (FA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eN= number of patients, n=number of eyes\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e \u003cem\u003etest\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMRI of patients in the study group revealed active demyelinating plaques in three patients, bilateral periventricular linear ischaemic gliotic lesions in one patient, and partial empty sella syndrome in another. Cerebrospinal fluid (CSF) analysis was performed in three patients with bilateral FUS manifestations, revealing OCB positivity in all three cases, further supporting the diagnosis of demyelinating disease. Based on clinical, radiological, and laboratory findings, MS was diagnosed in three patients (15%) within the study group. Additionally, one patient whose daughter had been diagnosed with MS underwent detailed evaluation; however, MS was excluded, and the patient remains under observation.\u003c/p\u003e \u003cp\u003eTreatment regimens in the study group varied, with one patient receiving fingolimod, another treated with glatiramer acetate, and a third prescribed mycophenolate mofetil.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe diagnosis of FUS is based on the clinical manifestations.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e FUS is generally considered to be a unilateral disease, however, bilateral involvement has been reported in some cases.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e The existence of cases involving both eyes may necessitate further investigation of the underlying mechanisms and possible systemic relationships. The findings of this study indicate that bilateral FUS may have distinct clinical and immunopathological characteristics, possibly linking it to autoimmune mechanisms similar to those observed in MS.\u003csup\u003e15,22\u003c/sup\u003e In the present study, the aim was to highlight the clinicodemographic differences in bilateral FUS cases and their potential association with MS. Given the observed association, clinicians should remain aware of potential systemic comorbidities to facilitate timely recognition and appropriate referral when clinically indicated.\u003c/p\u003e \u003cp\u003eNorrsell et al. identified bilateral FUS in 6% of patients diagnosed with FUS (3 out of 54) and observed that these cases were evident from the onset. Additionally, they emphasized that bilateral involvement was associated with a higher risk of complications, particularly glaucoma and vitreoretinal abnormalities, and often led to a delayed diagnosis.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e In this study, no difference was found between the groups in terms of glaucoma presence, IOP, aqueous flare and significant lens opacity. This difference may be related to patient selection, duration of follow-up and characteristics of presentation to the centre and suggests that bilateral involvement alone does not necessarily imply a more severe ocular course.\u003c/p\u003e \u003cp\u003eThe biomicroscopic findings, including the presence of KPs, heterochromia and iris nodules, exhibited significant disparities between the study and the control groups. This finding suggests that not only the degree of inflammation but also the nature of the inflammatory response may be different in bilateral FUS. However, further studies are required to determine whether there is a definite difference in the clinical severity of the disease.\u003c/p\u003e \u003cp\u003ePrevious studies have consistently demonstrated frequent vitreous involvement in FUS. Tugal-Tutkun et al.\u003csup\u003e2\u003c/sup\u003e reported vitreous cells or debris in 71.8% and vitreous condensation in 48.6% of patients, while Bouchenaki et al.\u003csup\u003e5\u003c/sup\u003e described vitritis in 97.4% of cases. Similarly, Yang et al. observed vitreous opacities in 73.8% of Chinese patients with FUS.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e In this study, vitreous condensation and opacities were observed more frequently in the study group but no statistically significant difference was found. This suggests that vitreous involvement is a common disease feature rather than a distinguishing feature of bilateral FUS.\u003c/p\u003e \u003cp\u003eThe association between pars planitis and MS has previously been reported.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Symptomatic intraocular inflammation is uncommon in patients with MS, with an overall prevalence of approximately 1%, and most frequently presents as intermediate uveitis characterized by peripheral retinal vascular involvement detectable on FA.\u003csup\u003e24,25\u003c/sup\u003e Typical angiographic findings include peripheral venous leakage or staining, while clinical examination may reveal features such as snowballs, snowbanking-related exudates, and peripheral periphlebitis.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn our study, although MS appeared to be more frequently associated with bilateral FUS, the clinical examination and FA findings were not consistent with MS-related uveitis or pars planitis. While some posterior segment and FA features may overlap, our findings indicate that MS is not the primary cause of ocular inflammation in bilateral FUS cases, but rather represents a concomitant systemic condition, possibly reflecting a shared immune-mediated susceptibility.\u003c/p\u003e \u003cp\u003eIn contrast to MS-associated intermediate uveitis, which typically demonstrates peripheral venous leakage on FA, FUS is more commonly characterized by optic disc hyperfluorescence and late-phase peripheral retinal capillary leakage.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Consequently, although this partial overlap in angiographic features may lead to diagnostic confusion, particularly in bilateral cases. FA findings alone should not be used as a screening tool for MS. Instead, neurological evaluation should be guided by systemic symptoms and the overall clinical context.\u003c/p\u003e \u003cp\u003eThe pathogenetic relationship between uveitis and MS has not yet been fully elucidated. However, human leukocyte antigen (HLA) class II alleles such as HLA-DR15 and HLA-DR51 have been implicated in MS-associated uveitis, particularly intermediate uveitis, suggesting a shared immunogenetic susceptibility between intraocular inflammation and central nervous system (CNS) involvement.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e In addition, infectious agents have been proposed as potential triggers capable of initiating autoimmune responses affecting both the eye and the CNS in genetically or immunologically susceptible individuals. \u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eViral factors, especially rubella virus, have been strongly associated with the pathogenesis of FUS, while chronic intrathecal antiviral immune activation -reflected by the MRZ reaction- is a well-recognized feature of MS.\u003csup\u003e30\u0026ndash;33\u003c/sup\u003e Brichov\u0026aacute; et al. reported that bilateral FUS is more frequently associated with systemic diseases; however, detailed data regarding systemic conditions other than MS were not provided.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In the present study, the increased prevalence of MS in patients with bilateral FUS supports the hypothesis that shared autoimmune and virus-triggered immune mechanisms may contribute to this clinical phenotype, consistent with growing evidence on the role of autoimmunity in non-infectious uveitis.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study is one of the limited number of study in the literature comparing the prevalence of MS in patients with bilateral and unilateral FUS. In the study by Brichov\u0026aacute; et al. the prevalence of MS in bilateral FUS patients was reported as 18% and this rate was found to be significantly higher compared to unilateral cases.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Similarly, in our study, MS was diagnosed in 15% of bilateral FUS patients. In contrast, MS was suspected in only one patient in the unilateral FUS group and this diagnosis was excluded for the time being after neurological evaluations. This finding suggests that bilateral FUS may be a warning clinical sign for underlying systemic autoimmune diseases.\u003c/p\u003e \u003cp\u003eThe retrospective design of the study, the fact that it was single-centre, the lack of systematic autoimmune and infectious screening in all patients and the lack of aqueous humour analyses are important limitations. However, the relatively high number of bilateral FUS cases and the comparative analysis with the unilateral group are the strengths of the study.\u003c/p\u003e \u003cp\u003eIn conclusion, the frequency of MS disease was found to be higher in bilateral FUS patients than in unilateral FUS cases. The association with MS should be kept in mind in the diagnosis and follow-up of patients diagnosed with bilateral FUS, and neurological examination and consultations should be performed when necessary. Prospective studies are needed to elucidate the immunopathological mechanisms underlying this relationship.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGGK, BYO and CA contributed to the study design. GGK reviewed the medical records and collected data. GGK performed the statistical analysis. GGK, CA, BYO, BKA and BB examined all patients. GGK wrote the main manuscript. BYO and CA performed critical revision of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u0026nbsp;Statement:\u003c/strong\u003e The authors report there are no competing interests to declare.\u003c/p\u003e\n\u003ch2\u003e\u0026nbsp;\u003c/h2\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThe authors received no financial support for this study.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eG.G.K., B.Y.O. and C.A. contributed to the study design. G.G.K. reviewed the medical records and collected data. G.G.K. performed the statistical analysis. G.G.K., C.A., B.Y.O., B.K.A. and B.B. examined all patients. G.G.K. wrote the main manuscript. B.Y.O. and C.A. performed critical revision of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements:\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFuchs E. Ueber komplikationen der heterochromie. Ophthalmologica 1906;15:191\u0026ndash;212. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000290570\u003c/span\u003e\u003cspan address=\"10.1159/000290570\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTugal-Tutkun I, Guney-Tefekli E, Kamaci-Duman F, Corum I. A cross-sectional and longitudinal study of Fuchs uveitis syndrome in Turkish patients. 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Semin Immunopathol. 2014;36(5):581\u0026ndash;594. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00281-014-0433-9\u003c/span\u003e\u003cspan address=\"10.1007/s00281-014-0433-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Bilateral Fuchs uveitis syndrome, Fundus Fluorescein angiography, Multiple Sclerosis, Unilateral Fuchs uveitis syndrome, Vitreous condensation","lastPublishedDoi":"10.21203/rs.3.rs-9227016/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9227016/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate the prevalence of multiple sclerosis (MS) among bilateral Fuchs uveitis syndrome (FUS) cases and compare their clinical characteristics with unilateral cases.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with bilateral FUS (Study group) and unilateral FUS (Control group) were reviewed retrospectively. All patients in the study group underwent fluorescein angiography (FA) and magnetic resonance imaging (MRI) and neurological consultation. Whereas in the control group, patients with posterior segment involvement underwent FA. MRI and neurological consultation were performed on patients with neurological symptoms. The relationship between MS diagnosis and data was evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eForty eyes of 20 patients in the study group and 40 eyes of 40 patients in the control group were included. Neurological evaluations revealed that 15% (3/20) of the patients in the study group were diagnosed with MS, whereas neurologic symptoms were observed in one patient in the control group; however, MRI findings did not support a diagnosis of MS. Study group showed a higher prevalence of diffuse keratic precipitates (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, χ2 test), while iris nodule subtypes differed between groups, with Busacca nodules predominating in study group and Koeppe nodules in control group (p\u0026thinsp;=\u0026thinsp;0.019, p\u0026thinsp;=\u0026thinsp;0.008 respectively, χ2 test). There was no significant difference between MS and non-MS eyes with fundus and FA findings (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, χ2 test).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe frequency of MS disease was found to be higher in bilateral FUS patients than in unilateral FUS cases. MS should be kept in mind in the diagnosis and follow-up of patients with bilateral FUS, and neurological investigations should be carried out when necessary.\u003c/p\u003e","manuscriptTitle":"Bilateral Fuchs Uveitis Syndrome and Its Association With Multiple Sclerosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-05 17:12:31","doi":"10.21203/rs.3.rs-9227016/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-21T11:29:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-20T04:48:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-12T15:11:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"38516524157481761279880270707247154907","date":"2026-04-02T14:21:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88022121752491568425108899602565980803","date":"2026-04-02T06:14:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-31T09:02:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-27T06:28:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-27T06:27:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2026-03-25T20:40:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3f5c7940-6721-4e47-b5c1-806b9e8fbc82","owner":[],"postedDate":"April 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-10T14:25:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-05 17:12:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9227016","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9227016","identity":"rs-9227016","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}