Introduction

Uveitis is an inflammatory condition of the eye that encompasses a variety of etiologies and clinical manifestations, posing a significant burden on pediatric populations. Although less common than in adults, pediatric uveitis accounts for 2–14% of all uveitis cases and often presents unique diagnostic and therapeutic challenges [1,2]. Non-infectious uveitis, particularly associated with systemic conditions like juvenile idiopathic arthritis (JIA), represents the most frequent cause in children, as highlighted in studies conducted globally and in Saudi Arabia [3,4].

The diagnosis of pediatric uveitis can be particularly challenging due to its often-insidious onset and asymptomatic progression in early stages. This silent nature can lead to delayed detection until complications such as cataracts, glaucoma, or visual impairment occur [2,5,6]. Additionally, the limited ability of young children to articulate symptoms further complicates timely diagnosis, making systematic screening crucial in high-risk groups, such as children with ANA-positive JIA [3,6].

Epidemiological data on pediatric uveitis in the Middle East, including Saudi Arabia, remains sparse. The limited studies indicate that idiopathic and JIA-associated uveitis predominates in this region, mirroring global trends [2,4]. These insights underscore region-specific research’s importance in informing clinical management and improving outcomes.

Advances in managing pediatric uveitis have significantly improved outcomes over the past decade. The introduction of biologics, such as TNF inhibitors (e.g., adalimumab), has revolutionized the treatment of refractory cases, providing an effective alternative to traditional immunosuppressants and reducing reliance on corticosteroids [7–9]. Early and aggressive treatment strategies aim to prevent complications and preserve vision, emphasizing the importance of early diagnosis and intervention [6,10–12].

This study assesses the clinical features, complications, and treatment outcomes of pediatric non-infectious uveitis in Saudi Arabia. By analyzing data from two tertiary centers, the study seeks to contribute to the growing body of evidence on the region’s epidemiology and management of pediatric uveitis. Insights from this research are expected to guide future clinical practice and policy development in Saudi Arabia and surrounding countries.

Subjects and methods

Study design, setting, and time frame: A retrospective observational study was done at two centers, King Abdulaziz University Hospital and King Fahd Armed Forces Hospital Jeddah, Saudi Arabia, Patients diagnosed between January 2017 and December 2022 were included in the study. Data extraction and statistical analysis were conducted during 2023.

Data collection

A pre-designed checklist was prepared to collect data about clinical features, laboratory workup, and treatment of these patients at the time of diagnosis (Table 1), three (Table 2), six (Table 3), twelve (Table 4), and twenty-four months after diagnosis (Table 4).

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Table 1. The basic data of the patients at the time of diagnosis.

https://doi.org/10.1371/journal.pone.0350150.t001

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Table 2. The patients’ basic data at the follow-up interval [3 months after diagnosis].

https://doi.org/10.1371/journal.pone.0350150.t002

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Table 3. The patients’ basic data at the follow-up interval [9 Months after diagnosis].

https://doi.org/10.1371/journal.pone.0350150.t003

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Table 4. The patients’ basic data at the follow-up interval [1 year after diagnosis].

https://doi.org/10.1371/journal.pone.0350150.t004

Results

The study included patients with pediatric non-infectious uveitis, of which 66.67% were female and 33.33% were male. The mean age at diagnosis was 8.99 ± 4.17 years (range: 3–18 years). Juvenile idiopathic arthritis (JIA) was the most common etiology, accounting for 52.8% of cases, followed by idiopathic uveitis (25%), Vogt-Koyanagi-Harada disease (19.4%), and psoriatic JIA (2.8%). Most cases (55.6%) involved both eyes.

The ophthalmological examination at diagnosis revealed a mean intraocular pressure (IOP) of 14.11 ± 4.45 mmHg (range: 8–22 mmHg) in the right eye and 15.43 ± 4.35 mmHg (range: 8–20 mmHg) in the left eye. The anterior chamber cell grade averaged +1.82 ± 0.97 (range: + 0.5–3) in the right eye and +2.0 ± 1.31 (range: + 0.5–4) in the left eye. Laboratory findings showed a high prevalence of antinuclear antibody (ANA) positivity (69.44%) among patients, with mean CRP and ESR values of 17.92 ± 29.39 mg/L (range: 0–22) and 5.82 ± 7.60 mm/h (range: 1–91), respectively. Visual acuity was assessed at baseline and during follow-up visits using age-appropriate assessment methods.

The mean time between systemic disease diagnosis and uveitis onset was 24.09 ± 36.74 months (range: 0–132 months), whereas the mean time between uveitis onset and systemic disease diagnosis was 1.33 ± 4 months (range: 0–12 months). At diagnosis, most patients with uveitis received topical prednisolone acetate 1% (91.67%), cyclopentolate (36.11%), adalimumab (22.22%), and oral prednisolone (19.44%), while treatments for systemic disease primarily involved methotrexate (50%), prednisolone (25%), and adalimumab (22.22%) (Table 1). Over the 2-year follow-up period (Tables 2–5), a significant number of patients experienced persistent or recurrent uveitis, with most requiring an increase in local corticosteroid therapy rather than an escalation of systemic treatments. Complications observed included anterior or posterior synechiae (13.89%), cataracts (8.3%), band keratopathy (5.56%), macular edema (2.78%), and secondary glaucoma (2.78%).

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Table 5. The basic data of the patients at the interval of follow-up [2 years after diagnosis].

https://doi.org/10.1371/journal.pone.0350150.t005

Discussion

Pediatric non-infectious uveitis presents significant challenges in diagnosis, management, and long-term outcomes, as highlighted by this study conducted in a pediatric population in Saudi Arabia. Juvenile idiopathic arthritis (JIA) was identified as the most common etiology (52.8%), followed by idiopathic causes (25%), aligning with global trends that emphasize JIA as a leading cause of pediatric uveitis [5,6]. Anterior uveitis predominated in 75% of cases, reflecting similarities with international cohorts [7,13–16]. The high rate of antinuclear antibody (ANA) positivity (69.44%) underscores its value as a biomarker for JIA-associated uveitis and the necessity of routine ANA testing in high-risk populations [5]. Treatment strategies predominantly included corticosteroids and immunomodulatory agents such as methotrexate and adalimumab, with biological therapies like TNF inhibitors proving effective in refractory cases [8,10,11,17,18]. Encouragingly, 86.11% of patients achieved remission after two years of treatment, a rate comparable or even slightly higher to global reports, highlighting the efficacy of current therapeutic approaches when systematically applied [8,9,17,18]. However, complications such as synechiae (13.89%), cataracts (8.33%), and band keratopathy (5.56%) occurred, although at relatively lower rates compared to historical cohorts, reflecting improvements in diagnosis and treatment [12–16]. Delayed diagnosis, often due to the asymptomatic nature of anterior uveitis, remains a critical challenge, emphasizing the need for systematic screening programs for ANA-positive JIA patients [5,13–16]. The relatively higher proportion of VKH disease observed in this cohort may reflect regional genetic predisposition and ethnic variations reported in Middle Eastern populations. Future research should explore the role of emerging therapies such as JAK inhibitors and IL-6 inhibitors and further incorporate biomarkers and advanced imaging techniques to refine diagnostic and therapeutic strategies [8–11,19,20]. These findings underscore the importance of timely intervention, tailored treatments, and continued efforts to optimize outcomes for pediatric uveitis patients. Biologic therapies, particularly TNF inhibitors such as adalimumab, were used in a subset of patients with refractory disease and appeared to contribute to improved disease control. However, given the retrospective design and relatively small sample size, these findings should be interpreted cautiously, and further prospective studies are required to evaluate their long-term effectiveness

Conclusion

This study reinforces the significance of JIA and idiopathic causes as leading etiologies of pediatric uveitis in Saudi Arabia, highlighting the efficacy of biologic therapies in achieving remission and minimizing complications. Continued efforts to improve early diagnosis, patient adherence, and access to advanced therapies will be essential in optimizing outcomes for children with uveitis. Moreover, encouraging a multidisciplinary approach as joint clinics to ensure proper management of the patients

Supporting information

Acknowledgments

Declaration of AI assistance: The authors declare that artificial intelligence-based linguistic tools were used solely to enhance the manuscript’s clarity and quality of the English language. All research ideas, study design, statistical analyses, results, and discussions presented in this paper are entirely authentic and the original work of the authors. The use of AI was limited to linguistic refinement and did not contribute to the conceptualization or scientific content of the manuscript.