Real-world epidemiology of Uveitis: a retrospective three-tier healthcare facility-based comparison of its causes and visual outcome in Ube-City, Japan

Real-world epidemiology of Uveitis: a retrospective three-tier healthcare facility-based comparison of its causes and visual outcome in Ube-City, Japan | 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 Article Real-world epidemiology of Uveitis: a retrospective three-tier healthcare facility-based comparison of its causes and visual outcome in Ube-City, Japan Ryoji Yanai, Sho-Hei Uchi, Yukiko Kondo, Youichiro Fujitsu, Katsuyoshi Suzuki, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5830111/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Mar, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract This study aimed to conduct a comparative epidemiological survey of uveitis across various healthcare settings and elucidate the clinical characteristics. We conducted a retrospective cross-sectional study in the Ube-City medical region in Yamaguchi prefecture and recruited 268 patients from a university hospital (151 patients), municipal hospitals (51 patients), and private eye clinics (58 patients). Medical records of patients who were newly diagnosed with uveitis between January 2018 and December 2019 in the institutes were included, reviewed, and compared; main outcomes were number of uveitis causes and visual acuity. Panuveitis, which is associated with systemic diseases, such as Vogt–Koyanagi–Harada disease and sarcoidosis, was more prominent in university hospital patients. Conversely, anterior uveitis including traumatic iritis was prominently detected in general hospitals and private eye clinics. The best-corrected visual acuity improved to 1.0 (logMAR = 0); an improvement of 74%, 61%, and 54% was observed in private eye clinic, general hospital, and university hospital patients, respectively. This study identified differences in uveitis presentation and treatment across diverse clinical settings. The results of this study provide valuable real-world data for differentiating the causes of uveitis at university hospitals, general hospitals, and private eye clinics. Health sciences/Health care Health sciences/Medical research community hospitals panuveitis university hospital uveitis visual impairment Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Uveitis is a significant cause of visual impairment worldwide. Its etiology depends on regional, historical, and even genetic backgrounds and includes infectious and noninfectious diseases, such as malignancies. 1 Therefore, epidemiological studies examining uveitis etiology are highly significant. Uveitis has been studied epidemiologically across several regions and time periods. 1 – 4 For example, the Japanese Ocular Inflammation Society (JOIS) has conducted nationwide epidemiologic surveys of uveitis every seven years since 2002. 5 – 7 The survey conducted in 2016 revealed an increase in the incidence of sarcoidosis, Vogt–Koyanagi–Harada disease, and herpetic iritis, whereas Behçet’s disease cases declined. 5 Hence, uveitis, associated with diverse ocular symptoms and systemic complications, is more likely to be definitively diagnosed. However, one of the concerns in the nationwide epidemiologic surveys is that studies on uveitis often focus on university hospitals and uveitis-specialized facilities, not considering the prevalence of mild uveitis from private ophthalmology clinics and community hospitals. This study investigated whether the uveitis etiologies differ between university hospitals, general hospitals, and private eye clinics within the same medical region. We conducted a comparative analysis of real-world data on the causes of uveitis, its characteristics, treatment, and visual prognosis in these healthcare settings. MATERIALS AND METHODS This retrospective cross-sectional study included one university hospital, two general hospitals and three private eye clinics within the Yamaguchi Ube was approved by the review board of each participating institution and adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent. A questionnaire was sent to each hospital to determine the total number of patients attending the uveitis outpatient clinic for the first time at a university hospital, two general hospitals, and three private eye clinics. We retrospectively reviewed the medical records of all newly identified cases of uveitis in the participating institutions from January 1, 2018 to December 31, 2019. Data collected included sex, age at their first visit, diagnosis, anatomic uveitis type, treatment method, visual acuity (first and best), recurrence rate and period from the first visit to remission. The anatomic location of uveitis was surveyed and classified as anterior, intermediate, posterior, and panuveitis per the International Uveitis Study Group definitions. 8 This classification is crucial in determining the underlying etiology of uveitis. As in previous JOIS surveys, each case of uveitis was diagnosed using international, 8 – 11 Japanese 12 or standard diagnostic 13 – 15 guidelines. Patients with uveitis features not fitting a specific category were diagnosed with “unclassified intraocular inflammation.” In this study, uveitis specialists (RY, S-HU, YK, YF, KS, KY, NK), who were members of the JOIS and had over a decade of experience at the Uveitis Clinic in the university hospital, diagnosed, and treated all causes of uveitis. Statistical analysis was performed using the Statistical Package for Prism 10 (GraphPad Software, LCC., Boston, MA, USA). A p -value of < 0.05 indicated statistical significance. RESULTS Our findings (Table 1) indicate that there were no significant differences in the mean age of patients at the initial visit, age distribution, or sex predominance among private eye clinics, general hospitals, and the university hospital. Anatomical localization of uveitis among patients from private eye clinics and general hospitals was similar: 70% and 71% cases were of anterior uveitis, followed by 21% cases of panuveitis; however, the localization in patients from university hospital was significantly different, wherein 48% cases were of panuveitis, followed by 47% cases of anterior uveitis (Fig. 1). Table 2 details the distribution of uveitis etiologies across healthcare settings. In the private eye clinic group (n = 58), 35 patients (60.3%) were diagnosed with a specific etiology. The most frequent diagnoses included acute anterior uveitis (20.7%), traumatic iritis (8.6%), diabetic iritis (6.9%), and Posner–Schlossman (5.2%). In the general hospital group (n = 51), 26 patients (51.0%) received a specific etiologic diagnosis. The most frequent diagnoses included traumatic iritis (11.8%), acute anterior uveitis (7.8%), lens-induced iritis (5.9%), and Vogt–Koyanagi–Harada disease (5.9%). A specific etiologic diagnosis was provided to 82 patients (53%) at the university hospital (n = 151). The most frequent diagnoses included Vogt–Koyanagi–Harada disease (9.9%), sarcoidosis (8.6%), acute anterior uveitis (6.0%), and herpetic iritis (4.6%). The etiologic diagnosis differed between the three healthcare settings; however, granulomatous inflammation was the most prevalent, with no significant differences (Fig. 2). Treatment patterns for uveitis differed across the three healthcare settings. Most patients in the private eye clinic (82%) and general hospital (66%) groups were treated solely with eye drops. In the university hospital group, 59% of patients were treated exclusively with eye drops, while 7% were treated with a combination of eye drops, injections, and systemic treatment (Fig. 3). Nevertheless, the recurrence rates did not differ significantly between the three settings (21%, 10%, and 26%, respectively) and did not correlate with treatment (Fig. 4). The initial and post-treatment best-corrected visual acuity (BCVA) was highest in the private eye clinic group, with 82% of patients having a pretreatment BCVA of 0.2 or better. The percentage of patients whose post-treatment BCVA improved to 1.0 (logMAR = 0) or better was 54%, 61% and 74% in the university hospital, general hospital, and private eye clinic groups, respectively. The visual acuity prognosis was superior in the private eye clinic group, followed by the general hospital group. Patients in the university hospital group exhibited the poorest visual acuity prognosis (Fig. 5). The duration from the first visit to remission was significantly longer for university hospital than general hospitals, but no significant differences were observed in other comparisons (Fig. 6). DISCUSSION This epidemiological survey of uveitis was conducted in diverse healthcare settings within the same region. The clinical characteristics of patients with uveitis at university hospital, general hospitals, and private eye clinics were compared. This study found patients from private eye clinics exhibited a high incidence of anterior uveitis, where over 80% patients were effectively treated solely with eye drops. These patients achieved favorable visual outcomes as well as exhibited the lowest number of poor vision cases at the initial examination and the best post-treatment visual acuity. In contrast, the patients from the university hospital exhibited a high incidence of anterior uveitis as well as three major types of uveitis in Japan: Vogt–Koyanagi–Harada disease, sarcoidosis, and Behçet’s disease. This is consistent with the results of the three recent epidemiological surveys conducted in Japan. 5 – 7 Additionally, a significant number of patients presented with poor vision, with 30% patients exhibiting the highest corrected visual acuity of less than 0.7. Interestingly, only the university hospital encountered cases of neoplastic uveitis (2.6%). The patients with uveitis at the general hospital displayed intermediate characteristics in comparison to those at the private eye clinics and the university hospital. This study demonstrated that the time to remission was significantly longer in university hospital than in general hospitals, but no significant differences were observed in the frequency of undiagnosed cases or the rate of uveitis recurrence across the healthcare facilities examined. Epidemiological studies of uveitis have been conducted at facilities other than university hospitals, such as community healthcare facilities in local communities. 2 , 3 , 5 , 16 – 20 However, no reports have specifically compared the epidemiological findings of uveitis at healthcare facilities of different sizes within the same region. This is the study’s unique strength and the results are highly significant. In accordance with previous reports from Japan, our study observed a high prevalence of Vogt–Koyanagi–Harada disease and sarcoidosis in university hospitals, followed by acute anterior uveitis and herpetic iritis. The observed frequency of uveitis in Behçet’s disease is high in Japan, 21 and it is frequently linked to poor visual outcomes. However, since the introduction of infliximab in 2007, the prognosis for vision has been considerably enhanced and the incidence of Behçet’s disease has decreased. Sonoda et al. reported a frequency of 4.2%, 5 which is consistent with the results of our study (4.0%). Our findings confirm that anterior uveitis is more prevalent among patients with uveitis who present to community hospitals than in those who attend tertiary referral centers, as reported by McCannel et al. 4 From the perspective of general ophthalmology practice, this study offers the assurance that even community-based ophthalmologists who work at general hospitals and private eye clinics can adequately evaluate the etiology and clinical characteristics of uveitis in patients using established diagnostic criteria and recommended tests at a frequency comparable to that of university hospitals or referral centers. 4 Limited geographical scope is one of the study’s constraints. The Yamaguchi Ube medical region was the sole focus of the data analysis. Nevertheless, the results are indicative of the real-world distribution of uveitis and referral patterns in the region, as the medical facilities in the same region are of varying sizes, with some facilities referring patients and others receiving referrals. In general, private eye clinics may have limited diagnostic equipment; therefore, necessary patient referrals to larger hospitals with more advanced medical facilities are necessary for offering specialized examinations and treatment. The epidemiological survey may have influenced the treatment results. However, this study, a cross-sectional epidemiological survey, was well-suited to capture the reality of uveitis within this region and the data is highly reliable. Although this aspect is a strength of this statistical survey, the results of this study cannot be extrapolated directly to other regions. In the future, the real-world data on uveitis in Japan will be clarified by extrapolating the used research methodology to the cases detected across Japan and conducting epidemiological surveys. For this purpose, it is essential to establish a collaboration with JOIS to spearhead the development of a research plan and further improve the epidemiological surveys conducted every seven years. This study revealed significant variations in the clinical presentation and treatment of uveitis across healthcare facilities within the Yamaguchi Ube medical region. Panuveitis was the predominant type of uveitis among the university hospital patients and a higher proportion of patients were treated systemically. Visual outcomes were better in patients treated at private eye clinics than in those treated at university and general hospitals. Declarations Acknowledgements The authors would like to thank Enago (www.enago.jp) for the English language review. Author contribution Conception and design: Yanai, Uchi, Suzuki, Kumagai, Egawa, Mitamura Analysis and interpretation: Yanai, Uchi, Kondo, Fujitsu, Yoshimura Data collection: Yanai, Uchi, Kondo, Suzuki, Fujitsu, Suzuki, Yoshimura, Kumagai Obtained funding: N/A Overall responsibility: Yanai, Uchi, Egawa, Mitamura Data availability statement Raw data were generated at Tokushima University Graduate School. The derived data supporting the findings of this study are available from the corresponding author upon reasonable request. Funding There are no grants has been supported. Competing interests There are no conflicts of interest to declare. Ethics statement Human subjects were not included in this study. No animal subjects were included in this study. References Joltikov, K. A. & Lobo-Chan, A. M. Epidemiology and risk factors in non-infectious uveitis: A systematic review. Front. Med. (Lausanne) . 8 , 695904 (2021). de-la-Torre, A. et al. Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA). Graefes Arch. Clin. Exp. Ophthalmol. 262 , 2601–2615 (2024). Florez-Esparza, G. et al. Colombian Ocular Inflammatory Diseases Epidemiology Study (COIDES): Prevalence, incidence, and sociodemographic characterization of uveitis in Colombia, 2015–2020. Ocul Immunol. Inflamm. 32 , 1667–1673 (2015). McCannel, C. A. et al. Causes of uveitis in the general practice of ophthalmology. UCLA community-based uveitis study group. Am. J. Ophthalmol. 121 , 35–46 (1996). Sonoda, K. H. et al. Epidemiology of uveitis in Japan: A 2016 retrospective nationwide survey. Jpn J. Ophthalmol. 65 , 184–190 (2021). Ohguro, N., Sonoda, K. H., Takeuchi, M., Matsumura, M. & Mochizuki, M. The 2009 prospective multi-center epidemiologic survey of uveitis in Japan. Jpn J. Ophthalmol. 56 , 432–435 (2012). Goto, H. et al. Epidemiological survey of intraocular inflammation in Japan. Jpn J. Ophthalmol. 51 , 41–44 (2007). Deschenes, J., Murray, P. I., Rao, N. A. & Nussenblatt, R. B. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol. Inflamm. 16 , 1–2 (2008). Read, R. W., Holland, G. N. & Rao, N. A. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: Report of an international committee on nomenclature. Am. J. Ophthalmol. 131 , 647–652 (2001). Jabs, D. A., Nussenblatt, R. B., Rosenbaum, J. T. & Standardization of Uveitis Nomenclature Working Group.. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am. J. Ophthalmol. 140, 509–516 (2005). Chen, E. J. et al. Ocular autoimmune systemic inflammatory infectious study (OASIS) - report 1: Epidemiology and classification. Ocul Immunol. Inflamm. 26 , 732–746 (2018). Takase, H. et al. Development and validation of new diagnostic criteria for acute retinal necrosis. Jpn J. Ophthalmol. 59 , 14–20 (2015). Holland, G. N. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am. J. Ophthalmol. 117 , 663–666 (1994). Petty, R. E. & Southwood, T. R. Classification of childhood arthritis: Divide and conquer. J. Rheumatol. 25 , 1869–1870 (1998). Mandeville, J. T. H., Levinson, R. D. & Holland, G. N. The tubulointerstitial nephritis and uveitis syndrome. Surv. Ophthalmol. 46 , 195–208 (2001). Bechman, K. et al. Incidence of uveitis in patients with axial spondylarthritis treated with biologics or targeted synthetics: A systematic review and network meta-analysis. Arthritis Rheumatol. 76 , 704–714 (2024). Takeuchi, M. et al. Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study. Front. Med. (Lausanne) . 10 , 1095423 (2023). Li, J. Q., Welchowski, T., Schmid, M. & Finger, R. P. Prevalence and incidence of registered severe visual impairment and blindness due to uveitis in Germany. Ocul Immunol. Inflamm. 32 , 735–739 (2023). Suzuki, T. et al. Incidence and changing patterns of uveitis in Central Tokyo. Int. Ophthalmol. 41 , 2377–2388 (2021). Oh, B. L., Lee, J. S., Lee, E. Y., Lee, H. Y. & Yu, H. G. Incidence and risk factors for blindness in uveitis: A nationwide cohort study from 2002 to 2013. Ocul Immunol. Inflamm. 29 , 1040–1044 (2021). Yokoi, H., Goto, H., Sakai, J., Takano, S. & Usui, M. Incidence of uveitis at Tokyo Medical College Hospital. Nippon Ganka Gakkai Zasshi . 99 , 710–714 (1995). Tables Table 1. Patient characteristics Private Eye Clinic (n = 58) General Hospital (n = 51) University Hospital (n = 151) p -value Age (years) Mean ± SD Median Range <20 20–59 ≧60 Sex Male Female 56.1 ± 20.4 61.0 13–89 4 (6.9) 24 (41.4) 30 (51.7) 25 (43.1) 33 (56.9) 59.7 ± 22.2 66.0 12–94 3 (5.9) 19 (37.2) 29 (56.9) 21 (41.2) 30 (58.8) 59.5 ± 20.3 64.0 8–93 10 (6.6) 54 (35.8) 87 (57.6) 60 (39.7) 91 (60.3) 0.4543* 0.8937* 0.1396* 0.2233* 0.8959† *: Kruskal–Wallis test, †: Fisher’s exact test Table 2. Uveitis etiologies Private Eye Clinic Incidence (%) General Hospital Incidence (%) University Hospital Incidence (%) Acute anterior uveitis 20.3 Traumatic iritis 11.8 Vogt–Koyanagi–Harada disease 9.9 Traumatic iritis 8.5 Acute anterior uveitis 7.8 Sarcoidosis 8.6 Diabetic iritis 6.8 Lens-induced uveitis 5.9 Acute anterior uveitis 6.0 Herpetic iritis 5.1 Vogt–Koyanagi–Harada disease 5.9 Herpetic iritis 4.6 Posner–Schlossman 3.4 Fungal endophthalmitis 3.9 CMV iritis 4.0 Sarcoidosis 3.4 Diabetic iritis 3.9 Behçet’s disease 4.0 Varicella-zoster virus (VZV) iritis 3.4 VZV iritis 3.9 VZV iritis 3.3 Fuchs’ uveitis syndrome 3.4 Sarcoidosis 3.9 Malignant disease 2.6 Others 5.1 Others 4.0 Others 9.9 Unclassified 40.7 Unclassified 49.0 Unclassified 47.0 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 15 Mar, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 28 Jan, 2025 Reviews received at journal 26 Jan, 2025 Reviews received at journal 22 Jan, 2025 Reviewers agreed at journal 22 Jan, 2025 Reviewers agreed at journal 21 Jan, 2025 Reviewers invited by journal 20 Jan, 2025 Editor assigned by journal 20 Jan, 2025 Editor invited by journal 20 Jan, 2025 Submission checks completed at journal 17 Jan, 2025 First submitted to journal 14 Jan, 2025 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. 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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-5830111","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":403505880,"identity":"2695ebb1-bdab-4a2b-999a-cfaf1c368f79","order_by":0,"name":"Ryoji 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1","display":"","copyAsset":false,"role":"figure","size":48945,"visible":true,"origin":"","legend":"\u003cp\u003eAnatomical location of the uveitis\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ep \u003c/em\u003e= 0.0003 Fisher’s exact test\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/186b7a39e46ff415ded69635.png"},{"id":74294732,"identity":"a1a178ca-dff9-4ae0-acec-090e33819e9b","added_by":"auto","created_at":"2025-01-20 17:49:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":32992,"visible":true,"origin":"","legend":"\u003cp\u003eMain etiologic types of uveitis\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/0ce623f08bbcb3f42f05d39d.png"},{"id":74294739,"identity":"fb96a4e4-3cf1-4909-a790-475961e6b7ee","added_by":"auto","created_at":"2025-01-20 17:49:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":54893,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment options for uveitis\u003c/p\u003e","description":"","filename":"Slide3.png","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/020ed855a5498bb2c09fd96f.png"},{"id":74294743,"identity":"38414834-14f6-45e9-965f-f2f7067f15e9","added_by":"auto","created_at":"2025-01-20 17:49:56","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":15708,"visible":true,"origin":"","legend":"\u003cp\u003eUveitis relapse rate\u003c/p\u003e","description":"","filename":"Slide4.png","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/ed5a1fefd8343a754ccdd224.png"},{"id":74294734,"identity":"80cb2c26-86c7-4d37-a207-4520fd494036","added_by":"auto","created_at":"2025-01-20 17:49:55","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":78827,"visible":true,"origin":"","legend":"\u003cp\u003eVisual acuity prognosis at first visit and best-corrected visual acuity during the follow-up period\u003c/p\u003e","description":"","filename":"Slide5.png","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/1ada562cd1e7e35b9a3e7e10.png"},{"id":74294737,"identity":"36616dc0-80a3-47f2-804d-3d1bf75c851d","added_by":"auto","created_at":"2025-01-20 17:49:55","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":19257,"visible":true,"origin":"","legend":"\u003cp\u003eDuration from the first visit to remission\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e*: p \u003c/em\u003e= 0.05 Bonferroni’s multiple comparison test.\u003c/p\u003e","description":"","filename":"Slide6.png","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/6881695344bee0460a4e1ba0.png"},{"id":78688922,"identity":"816ac38d-2846-48ae-8e07-f1a1105158f3","added_by":"auto","created_at":"2025-03-17 16:07:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":805163,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5830111/v1/caa43d6d-cc40-488a-a354-771aa2267177.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Real-world epidemiology of Uveitis: a retrospective three-tier healthcare facility-based comparison of its causes and visual outcome in Ube-City, Japan","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eUveitis is a significant cause of visual impairment worldwide. Its etiology depends on regional, historical, and even genetic backgrounds and includes infectious and noninfectious diseases, such as malignancies.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Therefore, epidemiological studies examining uveitis etiology are highly significant.\u003c/p\u003e \u003cp\u003eUveitis has been studied epidemiologically across several regions and time periods.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e For example, the Japanese Ocular Inflammation Society (JOIS) has conducted nationwide epidemiologic surveys of uveitis every seven years since 2002.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The survey conducted in 2016 revealed an increase in the incidence of sarcoidosis, Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease, and herpetic iritis, whereas Beh\u0026ccedil;et\u0026rsquo;s disease cases declined.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Hence, uveitis, associated with diverse ocular symptoms and systemic complications, is more likely to be definitively diagnosed. However, one of the concerns in the nationwide epidemiologic surveys is that studies on uveitis often focus on university hospitals and uveitis-specialized facilities, not considering the prevalence of mild uveitis from private ophthalmology clinics and community hospitals.\u003c/p\u003e \u003cp\u003eThis study investigated whether the uveitis etiologies differ between university hospitals, general hospitals, and private eye clinics within the same medical region. We conducted a comparative analysis of real-world data on the causes of uveitis, its characteristics, treatment, and visual prognosis in these healthcare settings.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e This retrospective cross-sectional study included one university hospital, two general hospitals and three private eye clinics within the Yamaguchi Ube was approved by the review board of each participating institution and adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent. A questionnaire was sent to each hospital to determine the total number of patients attending the uveitis outpatient clinic for the first time at a university hospital, two general hospitals, and three private eye clinics. We retrospectively reviewed the medical records of all newly identified cases of uveitis in the participating institutions from January 1, 2018 to December 31, 2019. Data collected included sex, age at their first visit, diagnosis, anatomic uveitis type, treatment method, visual acuity (first and best), recurrence rate and period from the first visit to remission. The anatomic location of uveitis was surveyed and classified as anterior, intermediate, posterior, and panuveitis per the International Uveitis Study Group definitions.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e This classification is crucial in determining the underlying etiology of uveitis. As in previous JOIS surveys, each case of uveitis was diagnosed using international,\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Japanese\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e or standard diagnostic\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e guidelines. Patients with uveitis features not fitting a specific category were diagnosed with \u0026ldquo;unclassified intraocular inflammation.\u0026rdquo; In this study, uveitis specialists (RY, S-HU, YK, YF, KS, KY, NK), who were members of the JOIS and had over a decade of experience at the Uveitis Clinic in the university hospital, diagnosed, and treated all causes of uveitis. Statistical analysis was performed using the Statistical Package for Prism 10 (GraphPad Software, LCC., Boston, MA, USA). A \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 indicated statistical significance.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOur findings (Table 1) indicate that there were no significant differences in the mean age of patients at the initial visit, age distribution, or sex predominance among private eye clinics, general hospitals, and the university hospital. Anatomical localization of uveitis among patients from private eye clinics and general hospitals was similar: 70% and 71% cases were of anterior uveitis, followed by 21% cases of panuveitis; however, the localization\u0026nbsp;in patients from university hospital was significantly different, wherein 48% cases were of panuveitis, followed by 47% cases of anterior uveitis (Fig. 1).\u003c/p\u003e\n\u003cp\u003eTable 2 details the distribution of uveitis etiologies across healthcare settings. In the private eye clinic group (n = 58), 35 patients (60.3%) were diagnosed with a specific etiology. The most frequent diagnoses included acute anterior uveitis (20.7%), traumatic iritis (8.6%), diabetic iritis (6.9%), and Posner\u0026ndash;Schlossman (5.2%). In the general hospital group (n = 51), 26 patients (51.0%) received a specific etiologic diagnosis. The most frequent diagnoses included traumatic iritis (11.8%), acute anterior uveitis (7.8%), lens-induced iritis (5.9%), and Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease (5.9%). A specific etiologic diagnosis was provided to 82 patients (53%) at the university hospital (n = 151). The most frequent diagnoses included Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease (9.9%), sarcoidosis (8.6%), acute anterior uveitis (6.0%),\u0026nbsp;and herpetic iritis (4.6%). The etiologic diagnosis differed between the three healthcare settings; however, granulomatous inflammation was the most prevalent, with no significant differences (Fig. 2).\u003c/p\u003e\n\u003cp\u003eTreatment patterns for uveitis differed across the three healthcare settings. Most patients in the private eye clinic (82%) and general hospital (66%) groups were treated solely with eye drops. In the university hospital group, 59% of patients were treated exclusively with eye drops, while 7% were treated with a combination of eye drops, injections, and systemic treatment (Fig. 3). Nevertheless, the recurrence rates did not differ significantly between the three settings (21%, 10%, and 26%, respectively) and did not correlate with treatment (Fig. 4). The initial and post-treatment best-corrected visual acuity (BCVA) was highest in the private eye clinic group, with 82% of patients having a pretreatment BCVA of 0.2 or better. The percentage of patients whose post-treatment BCVA improved to 1.0 (logMAR = 0) or better was 54%, 61% and 74% in the university hospital, general hospital, and private eye clinic groups, respectively. The visual acuity prognosis was superior in the private eye clinic group, followed by the general hospital group. Patients in the university hospital group exhibited the poorest visual acuity prognosis (Fig. 5). The duration from the first visit to remission was significantly longer for university hospital than general hospitals, but no significant differences were observed in other comparisons (Fig. 6).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis epidemiological survey of uveitis was conducted in diverse healthcare settings within the same region. The clinical characteristics of patients with uveitis at university hospital, general hospitals, and private eye clinics were compared. This study found patients from private eye clinics exhibited a high incidence of anterior uveitis, where over 80% patients were effectively treated solely with eye drops. These patients achieved favorable visual outcomes as well as exhibited the lowest number of poor vision cases at the initial examination and the best post-treatment visual acuity. In contrast, the patients from the university hospital exhibited a high incidence of anterior uveitis as well as three major types of uveitis in Japan: Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease, sarcoidosis, and Beh\u0026ccedil;et\u0026rsquo;s disease. This is consistent with the results of the three recent epidemiological surveys conducted in Japan.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Additionally, a significant number of patients presented with poor vision, with 30% patients exhibiting the highest corrected visual acuity of less than 0.7. Interestingly, only the university hospital encountered cases of neoplastic uveitis (2.6%). The patients with uveitis at the general hospital displayed intermediate characteristics in comparison to those at the private eye clinics and the university hospital. This study demonstrated that the time to remission was significantly longer in university hospital than in general hospitals, but no significant differences were observed in the frequency of undiagnosed cases or the rate of uveitis recurrence across the healthcare facilities examined.\u003c/p\u003e \u003cp\u003eEpidemiological studies of uveitis have been conducted at facilities other than university hospitals, such as community healthcare facilities in local communities.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e However, no reports have specifically compared the epidemiological findings of uveitis at healthcare facilities of different sizes within the same region. This is the study\u0026rsquo;s unique strength and the results are highly significant. In accordance with previous reports from Japan, our study observed a high prevalence of Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease and sarcoidosis in university hospitals, followed by acute anterior uveitis and herpetic iritis. The observed frequency of uveitis in Beh\u0026ccedil;et\u0026rsquo;s disease is high in Japan,\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e and it is frequently linked to poor visual outcomes. However, since the introduction of infliximab in 2007, the prognosis for vision has been considerably enhanced and the incidence of Beh\u0026ccedil;et\u0026rsquo;s disease has decreased. Sonoda et al. reported a frequency of 4.2%,\u003csup\u003e5\u003c/sup\u003e which is consistent with the results of our study (4.0%).\u003c/p\u003e \u003cp\u003eOur findings confirm that anterior uveitis is more prevalent among patients with uveitis who present to community hospitals than in those who attend tertiary referral centers, as reported by McCannel et al.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e From the perspective of general ophthalmology practice, this study offers the assurance that even community-based ophthalmologists who work at general hospitals and private eye clinics can adequately evaluate the etiology and clinical characteristics of uveitis in patients using established diagnostic criteria and recommended tests at a frequency comparable to that of university hospitals or referral centers.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eLimited geographical scope is one of the study\u0026rsquo;s constraints. The Yamaguchi Ube medical region was the sole focus of the data analysis. Nevertheless, the results are indicative of the real-world distribution of uveitis and referral patterns in the region, as the medical facilities in the same region are of varying sizes, with some facilities referring patients and others receiving referrals. In general, private eye clinics may have limited diagnostic equipment; therefore, necessary patient referrals to larger hospitals with more advanced medical facilities are necessary for offering specialized examinations and treatment. The epidemiological survey may have influenced the treatment results. However, this study, a cross-sectional epidemiological survey, was well-suited to capture the reality of uveitis within this region and the data is highly reliable. Although this aspect is a strength of this statistical survey, the results of this study cannot be extrapolated directly to other regions.\u003c/p\u003e \u003cp\u003eIn the future, the real-world data on uveitis in Japan will be clarified by extrapolating the used research methodology to the cases detected across Japan and conducting epidemiological surveys. For this purpose, it is essential to establish a collaboration with JOIS to spearhead the development of a research plan and further improve the epidemiological surveys conducted every seven years.\u003c/p\u003e \u003cp\u003eThis study revealed significant variations in the clinical presentation and treatment of uveitis across healthcare facilities within the Yamaguchi Ube medical region. Panuveitis was the predominant type of uveitis among the university hospital patients and a higher proportion of patients were treated systemically. Visual outcomes were better in patients treated at private eye clinics than in those treated at university and general hospitals.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Enago (www.enago.jp) for the English language review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: Yanai, Uchi, Suzuki, Kumagai, Egawa, Mitamura\u003c/p\u003e\n\u003cp\u003eAnalysis and interpretation: Yanai, Uchi, Kondo, Fujitsu, Yoshimura\u003c/p\u003e\n\u003cp\u003eData collection: Yanai, Uchi, Kondo, Suzuki, Fujitsu, Suzuki, Yoshimura, Kumagai\u003c/p\u003e\n\u003cp\u003eObtained funding: N/A\u003c/p\u003e\n\u003cp\u003eOverall responsibility: Yanai, Uchi, Egawa, Mitamura\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRaw data were generated at Tokushima University Graduate School. The derived data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no grants has been supported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHuman subjects were not included in this study.\u003c/p\u003e\n\u003cp\u003eNo animal subjects were included in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJoltikov, K. A. \u0026amp; Lobo-Chan, A. M. Epidemiology and risk factors in non-infectious uveitis: A systematic review. \u003cem\u003eFront. Med. (Lausanne)\u003c/em\u003e. \u003cb\u003e8\u003c/b\u003e, 695904 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede-la-Torre, A. et al. Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA). \u003cem\u003eGraefes Arch. Clin. Exp. Ophthalmol.\u003c/em\u003e \u003cb\u003e262\u003c/b\u003e, 2601\u0026ndash;2615 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlorez-Esparza, G. et al. Colombian Ocular Inflammatory Diseases Epidemiology Study (COIDES): Prevalence, incidence, and sociodemographic characterization of uveitis in Colombia, 2015\u0026ndash;2020. \u003cem\u003eOcul Immunol. Inflamm.\u003c/em\u003e \u003cb\u003e32\u003c/b\u003e, 1667\u0026ndash;1673 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCannel, C. A. et al. Causes of uveitis in the general practice of ophthalmology. UCLA community-based uveitis study group. \u003cem\u003eAm. J. Ophthalmol.\u003c/em\u003e \u003cb\u003e121\u003c/b\u003e, 35\u0026ndash;46 (1996).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSonoda, K. H. et al. Epidemiology of uveitis in Japan: A 2016 retrospective nationwide survey. \u003cem\u003eJpn J. Ophthalmol.\u003c/em\u003e \u003cb\u003e65\u003c/b\u003e, 184\u0026ndash;190 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhguro, N., Sonoda, K. H., Takeuchi, M., Matsumura, M. \u0026amp; Mochizuki, M. The 2009 prospective multi-center epidemiologic survey of uveitis in Japan. \u003cem\u003eJpn J. Ophthalmol.\u003c/em\u003e \u003cb\u003e56\u003c/b\u003e, 432\u0026ndash;435 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoto, H. et al. Epidemiological survey of intraocular inflammation in Japan. \u003cem\u003eJpn J. Ophthalmol.\u003c/em\u003e \u003cb\u003e51\u003c/b\u003e, 41\u0026ndash;44 (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeschenes, J., Murray, P. I., Rao, N. A. \u0026amp; Nussenblatt, R. B. International Uveitis Study Group (IUSG): clinical classification of uveitis. \u003cem\u003eOcul Immunol. Inflamm.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e, 1\u0026ndash;2 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRead, R. W., Holland, G. N. \u0026amp; Rao, N. A. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: Report of an international committee on nomenclature. \u003cem\u003eAm. J. Ophthalmol.\u003c/em\u003e \u003cb\u003e131\u003c/b\u003e, 647\u0026ndash;652 (2001).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJabs, D. A., Nussenblatt, R. B., Rosenbaum, J. T. \u0026amp; Standardization of Uveitis Nomenclature Working Group.. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. \u003cem\u003eAm. J. Ophthalmol.\u003c/em\u003e 140, 509\u0026ndash;516 (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen, E. J. et al. Ocular autoimmune systemic inflammatory infectious study (OASIS) - report 1: Epidemiology and classification. \u003cem\u003eOcul Immunol. Inflamm.\u003c/em\u003e \u003cb\u003e26\u003c/b\u003e, 732\u0026ndash;746 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakase, H. et al. Development and validation of new diagnostic criteria for acute retinal necrosis. \u003cem\u003eJpn J. Ophthalmol.\u003c/em\u003e \u003cb\u003e59\u003c/b\u003e, 14\u0026ndash;20 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolland, G. N. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. \u003cem\u003eAm. J. Ophthalmol.\u003c/em\u003e \u003cb\u003e117\u003c/b\u003e, 663\u0026ndash;666 (1994).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePetty, R. E. \u0026amp; Southwood, T. R. Classification of childhood arthritis: Divide and conquer. \u003cem\u003eJ. Rheumatol.\u003c/em\u003e \u003cb\u003e25\u003c/b\u003e, 1869\u0026ndash;1870 (1998).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMandeville, J. T. H., Levinson, R. D. \u0026amp; Holland, G. N. The tubulointerstitial nephritis and uveitis syndrome. \u003cem\u003eSurv. Ophthalmol.\u003c/em\u003e \u003cb\u003e46\u003c/b\u003e, 195\u0026ndash;208 (2001).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBechman, K. et al. Incidence of uveitis in patients with axial spondylarthritis treated with biologics or targeted synthetics: A systematic review and network meta-analysis. \u003cem\u003eArthritis Rheumatol.\u003c/em\u003e \u003cb\u003e76\u003c/b\u003e, 704\u0026ndash;714 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakeuchi, M. et al. Ten-year follow-up of infliximab treatment for uveitis in Beh\u0026ccedil;et disease patients: A multicenter retrospective study. \u003cem\u003eFront. Med. (Lausanne)\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e, 1095423 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi, J. Q., Welchowski, T., Schmid, M. \u0026amp; Finger, R. P. Prevalence and incidence of registered severe visual impairment and blindness due to uveitis in Germany. \u003cem\u003eOcul Immunol. Inflamm.\u003c/em\u003e \u003cb\u003e32\u003c/b\u003e, 735\u0026ndash;739 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuzuki, T. et al. Incidence and changing patterns of uveitis in Central Tokyo. \u003cem\u003eInt. Ophthalmol.\u003c/em\u003e \u003cb\u003e41\u003c/b\u003e, 2377\u0026ndash;2388 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOh, B. L., Lee, J. S., Lee, E. Y., Lee, H. Y. \u0026amp; Yu, H. G. Incidence and risk factors for blindness in uveitis: A nationwide cohort study from 2002 to 2013. \u003cem\u003eOcul Immunol. Inflamm.\u003c/em\u003e \u003cb\u003e29\u003c/b\u003e, 1040\u0026ndash;1044 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYokoi, H., Goto, H., Sakai, J., Takano, S. \u0026amp; Usui, M. Incidence of uveitis at Tokyo Medical College Hospital. \u003cem\u003eNippon Ganka Gakkai Zasshi\u003c/em\u003e. \u003cb\u003e99\u003c/b\u003e, 710\u0026ndash;714 (1995).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Patient characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrivate Eye Clinic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 58)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGeneral Hospital\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 51)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUniversity Hospital\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 151)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;20\u003c/p\u003e\n \u003cp\u003e20\u0026ndash;59\u003c/p\u003e\n \u003cp\u003e≧60\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56.1 \u0026plusmn; 20.4\u003c/p\u003e\n \u003cp\u003e61.0\u003c/p\u003e\n \u003cp\u003e13\u0026ndash;89\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (6.9)\u003c/p\u003e\n \u003cp\u003e24 (41.4)\u003c/p\u003e\n \u003cp\u003e30 (51.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (43.1)\u003c/p\u003e\n \u003cp\u003e33 (56.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59.7 \u0026plusmn; 22.2\u003c/p\u003e\n \u003cp\u003e66.0\u003c/p\u003e\n \u003cp\u003e12\u0026ndash;94\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (5.9)\u003c/p\u003e\n \u003cp\u003e19 (37.2)\u003c/p\u003e\n \u003cp\u003e29 (56.9)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (41.2)\u003c/p\u003e\n \u003cp\u003e30 (58.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59.5 \u0026plusmn; 20.3\u003c/p\u003e\n \u003cp\u003e64.0\u003c/p\u003e\n \u003cp\u003e8\u0026ndash;93\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (6.6)\u003c/p\u003e\n \u003cp\u003e54 (35.8)\u003c/p\u003e\n \u003cp\u003e87 (57.6)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60 (39.7)\u003c/p\u003e\n \u003cp\u003e91 (60.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.4543*\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.8937*\u003c/p\u003e\n \u003cp\u003e0.1396*\u003c/p\u003e\n \u003cp\u003e0.2233*\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.8959\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*: Kruskal\u0026ndash;Wallis test, \u0026dagger;: Fisher\u0026rsquo;s exact test\u003c/p\u003e\n\u003cp\u003eTable 2. Uveitis etiologies\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrivate Eye Clinic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncidence (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGeneral Hospital\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncidence (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUniversity Hospital\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncidence (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eAcute anterior uveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e20.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eTraumatic iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eVogt\u0026ndash;Koyanagi\u0026ndash;Harada disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eTraumatic iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eAcute anterior uveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eSarcoidosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eDiabetic iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eLens-induced uveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eAcute anterior uveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eHerpetic iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eVogt\u0026ndash;Koyanagi\u0026ndash;Harada disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eHerpetic iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003ePosner\u0026ndash;Schlossman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eFungal endophthalmitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eCMV iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eSarcoidosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eDiabetic iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eBeh\u0026ccedil;et\u0026rsquo;s disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eVaricella-zoster virus (VZV) iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eVZV iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eVZV iritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eFuchs\u0026rsquo; uveitis syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eSarcoidosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eMalignant disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eUnclassified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e40.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.2646%;\"\u003e\n \u003cp\u003eUnclassified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e49.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.3028%;\"\u003e\n \u003cp\u003eUnclassified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.3766%;\"\u003e\n \u003cp\u003e47.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"community hospitals, panuveitis, university hospital, uveitis, visual impairment","lastPublishedDoi":"10.21203/rs.3.rs-5830111/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5830111/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to conduct a comparative epidemiological survey of uveitis across various healthcare settings and elucidate the clinical characteristics. We conducted a retrospective cross-sectional study in the Ube-City medical region in Yamaguchi prefecture and recruited 268 patients from a university hospital (151 patients), municipal hospitals (51 patients), and private eye clinics (58 patients). Medical records of patients who were newly diagnosed with uveitis between January 2018 and December 2019 in the institutes were included, reviewed, and compared; main outcomes were number of uveitis causes and visual acuity. Panuveitis, which is associated with systemic diseases, such as Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease and sarcoidosis, was more prominent in university hospital patients. Conversely, anterior uveitis including traumatic iritis was prominently detected in general hospitals and private eye clinics. The best-corrected visual acuity improved to 1.0 (logMAR\u0026thinsp;=\u0026thinsp;0); an improvement of 74%, 61%, and 54% was observed in private eye clinic, general hospital, and university hospital patients, respectively. This study identified differences in uveitis presentation and treatment across diverse clinical settings. The results of this study provide valuable real-world data for differentiating the causes of uveitis at university hospitals, general hospitals, and private eye clinics.\u003c/p\u003e","manuscriptTitle":"Real-world epidemiology of Uveitis: a retrospective three-tier healthcare facility-based comparison of its causes and visual outcome in Ube-City, Japan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-20 17:49:50","doi":"10.21203/rs.3.rs-5830111/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-28T09:17:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-26T10:40:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-23T03:03:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162096792572748968300917383282331584789","date":"2025-01-23T00:45:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"307617206154202553919743214692740145032","date":"2025-01-22T02:13:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-20T23:59:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-20T11:57:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-01-20T11:17:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-17T11:56:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-01-14T23:50:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"db955c4a-46e1-46a9-8a64-e31e17b2a895","owner":[],"postedDate":"January 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":43022076,"name":"Health sciences/Health care"},{"id":43022077,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-03-17T16:00:20+00:00","versionOfRecord":{"articleIdentity":"rs-5830111","link":"https://doi.org/10.1038/s41598-025-93223-x","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-03-15 15:57:16","publishedOnDateReadable":"March 15th, 2025"},"versionCreatedAt":"2025-01-20 17:49:50","video":"","vorDoi":"10.1038/s41598-025-93223-x","vorDoiUrl":"https://doi.org/10.1038/s41598-025-93223-x","workflowStages":[]},"version":"v1","identity":"rs-5830111","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5830111","identity":"rs-5830111","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}