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The epidemiology of uveitis: comparison of its causes and visual outcomes between three-tiered medical facilities in…

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 newly diagnosed with uveitis between January 2018 and December 2019 in the institutes were included, reviewed, and compared. The main outcomes included the number of uveitis causes, treatment methods, 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 data for differentiating the causes of uveitis at university hospitals, general hospitals, and private eye clinics.

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 malignancies1. Therefore, epidemiological studies examining uveitis etiology are highly significant.

Uveitis has been studied epidemiologically across several regions and periods1,2,3,4,5,6. For example, the Japanese Ocular Inflammation Society (JOIS) has conducted nationwide epidemiologic surveys of uveitis every seven years since 20027,8,9. 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 declined7. 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. McCannel et al. and Sakai et al. reported that data from facilities managing referral cases may not accurately reflect the actual status of uveitis in the community4,5.

This study investigated whether the uveitis etiologies differ between university hospitals, general hospitals, and private eye clinics within the same medical region. Building on our understanding of the Japanese healthcare system, we present an epidemiological comparison of uveitis across three distinct medical facilities: a primary care facility (private eye clinic), a secondary care facility (general hospital), and a tertiary care center (university hospital). The Japanese healthcare system is systematically organized into multiple tiers, comprising primary, secondary, tertiary, and advanced medical care services. We conducted a comparative analysis of 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. The study 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 definitions10. This classification is crucial in determining the underlying etiology of uveitis. As in previous JOIS surveys, each case of uveitis was diagnosed using international10,11,12,13, Japanese14, or standard diagnostic15,16,17 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). Fisher’s exact test was used to analyze age, anatomical locations, and uveitis relapse rate. The Kruskal–Wallis test was employed to analyze sex, while Bonferroni’s multiple comparison test was conducted following Bartlett’s test. A p-value of < 0.05 indicated statistical significance.

Results

Our findings (Table 1) indicate 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 the university hospital was significantly different, wherein 48% cases were of panuveitis, followed by 47% cases of anterior uveitis (Fig. 1).

Table 1 Patient characteristics.

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Fig. 1

figure 1

Anatomical location of uveitis. p = 0.0003 Fisher’s exact test.

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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).

Table 2 Uveitis etiologies.

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Fig. 2

figure 2

Main etiologic types of uveitis.

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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 the university hospital than general hospitals, but no significant differences were observed in other comparisons (Fig. 6).

Fig. 3

figure 3

Treatment options for uveitis.

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Fig. 4

figure 4

Uveitis relapse rate.

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Fig. 5

figure 5

Visual acuity prognosis at the first visit and best-corrected visual acuity during the follow-up period.

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Fig. 6

figure 6

Duration from the first visit to remission. *: p = 0.05. Bonferroni’s multiple comparison test was performed after Bartlett’s test.

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Discussion

This epidemiological survey of uveitis was conducted in diverse healthcare settings within the same region. The clinical characteristics of patients with uveitis at a 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% of patients were effectively treated solely with eye drops. These patients achieved favorable visual outcomes and 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 and three major types of uveitis in Japan: Vogt–Koyanagi–Harada disease, sarcoidosis, and Behçet’s disease. This is consistent with findings from the three recent epidemiological surveys conducted in Japan7,8,9. Additionally, a significant number of patients presented with poor vision, with 30% 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 compared to those at the private eye clinics and the university hospital. This study demonstrated that the time to remission was significantly longer in the 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. Systemic treatments, such as immunosuppressants, immune modulators, and biologics administered at university hospitals, may contribute to the recurrence rate. Further research is planned to investigate the impact of these systemic treatments on recurrence.

Epidemiological studies of uveitis have been conducted at facilities other than university hospitals, such as community healthcare facilities in local communities2,3,6,7,18,19,20,21,22. 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 Japan23, 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%7, 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 centers4,5 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 centers4,5.

The study findings indicated that anterior uveitis is the most common form of uveitis observed in ophthalmology clinics and general hospitals. Moreover, a significant proportion of patients can be effectively managed with topical ocular medications alone. During the medical interview, it is important to inquire about any history of trauma, herpes, or shingles, as these factors are part of the etiology of anterior uveitis. By leveraging this information, healthcare providers can expedite diagnosis and initiate treatment at an ophthalmology clinic or general hospital. However, given that these facilities also manage patients with conditions such as sarcoidosis and Vogt-Koyanagi-Harada disease, it is crucial to perform pupil dilation and a thorough fundus examination in all cases.

The 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 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, 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.

The data on the anatomical diagnosis and etiology of uveitis in this study are consistent with reports from university hospitals and tertiary centers in Japan and China24,25. Notably, the etiology of uveitis in this study closely resembles the findings reported by Hayashi et al., with sarcoidosis accounting for 9.1%, Vogt-Koyanagi-Harada disease for 8.3%, and acute anterior uveitis for 5.7%24. A national epidemiological study in China, which analyzed uveitis cases using a national database with a different research design, showed discrepancies when compared to our study. In that study, Vogt-Koyanagi-Harada disease accounted for 12.7%, Behçet’s disease at 8.7%, ankylosing spondylitis for 5.0%, and juvenile idiopathic arthritis for 1.2%26. These discrepancies may be attributed to differences in research design, even when studying similar populations and geographical regions.

This limitations of this study include its retrospective design, restriction to a single geographical medical region, potential impact of referral patterns on observed differences in uveitis presentation and outcomes, and the study period from 2018 to 2019. While we cannot rule out potential bias, we aimed to analyze the most recent pre-COVID-19 data to minimize the impact of incomplete medical records or selection bias resulting from restrictions on medical consultations during the 2020 pandemic. Therefore, we reviewed the medical records of all newly identified cases of uveitis across participating institutions from January 1, 2018, to December 31, 2019.

In the future, the data on uveitis in Japan will be clarified by extrapolating the research methodology used 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 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.

Data availability

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.

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

There are no grants supporting this study.

Author information

Authors and Affiliations

Department of Ophthalmology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, Tokushima, 770-8503, Japan

Ryoji Yanai, Mariko Egawa & Yoshinori Mitamura

Department of Ophthalmology, Yamaguchi University Hospital, Ube, Yamaguchi, Japan

Ryoji Yanai & Sho-Hei Uchi

Department of Ophthalmology, Ube-Kohsan Central Hospital, Ube, Yamaguchi, Japan

Yukiko Kondo

Fujitsu Eye Clinic, Ube, Yamaguchi, Japan

Youichiro Fujitsu

Suzuki Eye Clinic, Ube, Yamaguchi, Japan

Katsuyoshi Suzuki

Ogori Daiichi General Hospital, Yamaguchi, Yamaguchi, Japan

Keiko Yoshimura

Kumagai Eye Clinic, Ube, Yamaguchi, Japan

Naoki Kumagai

Authors

Ryoji Yanai

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