-->PONE-D-25-54205-->-->Clinical Characteristics, Management, and Outcomes of Pediatric Non-Infectious Uveitis: A Multicenter Study in Saudi Arabia-->-->PLOS One

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Reviewer #1: Partly

Reviewer #2: Partly

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: The manuscript reports a retrospective multicenter observational study describing the clinical characteristics, management strategies, and outcomes of pediatric non-infectious uveitis from two tertiary centers in Saudi Arabia. The manuscript is generally well written and clinically coherent, but there are many important concerns.

Methods

- Inclusion and exclusion criteria are too broadly defined. There is no case definitiion standards. The authors should clearly state uveitis diagnostic and grading criteria.

- Definition of outcomes is not identified. Some terms such as remission, recurrence, and persistence should be identified and clarified

- No explanation of missing data handling is identified. The authors should state how missing or incomplete follow-up data were handled.

Results

- Visual acuity should be reported both at iniitial and final visit.

- Some data were reported in Tables (1-5). However, I cannot find them.

- Small sample size (n=36) limits robustness. The authors should report the confidence intervals for important outcomes.

Discussion

- Discussion largely reiterates known global trends. Regional access disparities should be mentioned.

- The authors over-interpreted biologic therapy effectiveness. They should downtone this part or add evidence.

- The authors should reflect their limitations (such as small sample size, retrospective data, and so on) in this study.

Reviewer #2: This retrospective observational study aims to describe the clinical features and outcomes of pediatric non-infectious uveitis in 36 patients across two medical centers in Saudi Arabia. The authors report that Juvenile Idiopathic Arthritis (JIA) is the most common etiology (52.8%) and that 86.11% of patients achieved remission over a 2-year follow-up.

While epidemiological data from this region is valuable, the manuscript in its current form suffers from severe internal inconsistencies regarding basic demographic data and study timelines. Furthermore, the sample size (n=36) collected over what appears to be a 6-year period from two major tertiary centers is surprisingly low, raising questions about case ascertainment and selection bias. These fundamental errors must be addressed before the scientific merit of the work can be fully assessed.

Major Comments

1. Critical Data Inconsistencies (Reliability of Results)

The manuscript contains major contradictions between the Abstract and the Main Text that make it impossible to interpret the study population accurately.

• Discrepancy in Patient Age:

o The Abstract states the mean age at diagnosis was 3.99 ± 4.17 years.

o The Results section states the mean age at diagnosis was 8.99 ± 4.17 years.

o Impact: This is a massive 5-year difference in a pediatric cohort. A mean age of 4 years implies a predominance of early-onset JIA, whereas 9 years allows for different etiologies (e.g., HLA-B27 associated uveitis, VKH). The authors must clarify which dataset is correct.

• Discrepancy in Study Duration:

o The Abstract defines the study period as January 2017 to December 2023 (7 years).

o The Methods section states the study was done "from 25 March 2023 to 31 December 2023".

o Impact: It is likely the dates in the Methods refer to the data collection window, not the patient inclusion period. However, stating the study was "done" in 2023 confuses the retrospective nature of the cohort. If the inclusion period was indeed 7 years (2017–2023), the identification of only 36 patients across two major centers suggests significant under-reporting or strict exclusion criteria that are not defined.

2. Sample Size and Generalizability

• The study includes only 36 patients. Given this is a "multicenter" study involving King Abdulaziz University Hospital and King Fahd Armed Forces Hospital over a potential 7-year period, this averages to roughly 2.5 cases per center per year.

• This low yield raises concerns about the sensitivity of the case identification methods. Were patients identified via ICD codes, pharmacy records, or a uveitis registry? The method "a pre-designed checklist was prepared" does not explain how the cases were initially identified in the system.

3. Ambiguity in Treatment and Outcomes

• Remission Definition: The authors state that 86.11% achieved remission. However, "remission" is not defined in the Methods. Does this strictly follow the SUN (Standardization of Uveitis Nomenclature) criteria (e.g., drug-free remission vs. remission on medication)? Without a clear definition, this high success rate is difficult to interpret.

• Visual Acuity Reporting: The results mention visual acuity outcomes improved but provide no quantitative data (e.g., mean LogMAR change, proportion with vision loss). Given the mean age might be as young as 3.99 years, reporting visual acuity is challenging; the methods must specify how vision was assessed in pre-verbal children (e.g., Fix and Follow vs. Snellen).

4. Statistical Reporting

• Standard Deviations: The age is reported as 3.99 ± 4.17 years. A standard deviation larger than the mean in this context suggests a non-normal distribution (skewed data). It would be more appropriate to report the Median and Interquartile Range (IQR) rather than Mean/SD for age and duration of disease.

Minor Comments

• Formatting/Typos: There are visible formatting errors in the text, such as "$3.99\pm4$ 4.17 years" and "$8.99+4.17$ years". These appear to be LaTeX or equation editor artifacts that were not cleaned up.

• VKH Prevalence: The finding that Vogt-Koyanagi-Harada (VKH) disease accounts for 19.4% of pediatric cases is notable and significantly higher than many Western cohorts. This warrants more discussion regarding the genetic predisposition in the Saudi population.

• Ethical Statement: The manuscript states "Data was collected retrospectively... so no consent was collected". While standard, the Methods section should explicitly state that the IRB waived the requirement for informed consent, rather than just stating it wasn't collected.

Conclusion

The manuscript presents data on an under-represented population in the uveitis literature. However, the contradictory data regarding patient age (Abstract vs. Results) is a major quality control failure that casts doubt on the accuracy of the entire dataset. This, combined with the confusing study dates and small sample size, makes the manuscript unsuitable for publication in its current state. Major revisions are required to correct these errors and clarify the methodology.

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Reviewer #1: No

Reviewer #2: No

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Clinical Characteristics, Management, and Outcomes of Pediatric Non-Infectious Uveitis: A Multicenter Study in Saudi Arabia

PONE-D-25-54205R1

Dear Dr. Nashawi,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Georges M.G.M. Verjans, MSc, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

The comments of the reviewers have been carefully addressed and the manuscript revised satisfactory.

Reviewers' comments:

Not shared.