PONE-D-24-25756Adult male-specific inverse association between dry eye disease and intraocular pressure: KNHANES 2010–2012PLOS ONE

Dear Dr. Kim,

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PLOS ONE

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Additional Editor Comments:

It interests me that your study demonstrates a significant negative association between DED and IOP in Korean males using a large-scale general population epidemiological study. However, overall, there are several areas for improvement. For improvement, in addition to what I mentioned, please respond well to the points discussed below by two reviewers.

[Major comments]

1.In Table 1, it is noticeable that the percentage of DED cases among all subjects is 7.8% overall and 8.6% in urban areas, which appears to be significantly lower compared to the prevalence of DED in Asian countries in DEWSII epidemiology report. This is likely due to the criteria requiring both DED symptoms and a doctor's diagnosis. However, this may result in distortions due to patients' tendencies regarding hospital visits (i.e., whether they visit a hospital with the same degree of DED). This should be included as a limitation in the discussion.

2.In Table 2, there is no relationship between IOP and DED in Models 1 and 2, but there is a significant relationship in Model 3. The difference between Models 2 and 3 lies in the inclusion of family history of glaucoma, diabetes, and hypertension. It would be beneficial to add a detailed analysis of the significance of these differences between the models in the discussion. Additionally, it would be helpful to discuss the necessity of such a complex analysis system and explain the criteria used to classify risk factors into Models 1 to 3.

3.Regarding the sudden change in the percentage of DED cases by survey year in Table 1 (7.1% in 2010, 6.3% in 2011, and a sharp increase to 10.3% in 2012), how can this be explained? Such a drastic change could raise questions about the reliability of the data used in this analysis, so a possible explanation or acknowledgment of limitations is needed. Considering that only 55 out of 19,599 patients were undergoing glaucoma treatment, could this be considered too few, given the general prevalence of glaucoma in Korea? The use of glaucoma medication could be a significant variable in the results. Is there a possibility of insincere responses?

[Minor comments]

4. Lines 74–76: Did they really report that the non-glaucoma group with DED had significantly lower IOP than the non-glaucoma group without DED? Check it out. (PMID: 32811862)

5. It needs to be clearly stated whether the results of the multiple regression are beta values or odds ratios.

6. Tables S5 and S7 show positive values, unlike the other tables. In the text, there is a mention of "lower IOP," yet the title is set as "high IOP." It is necessary to check whether the descriptions, titles, and figures in these tables are accurate and consistent with the other tables.

7. The criteria for high IOP are defined as ">21" in S2 and "≥18" in S3, but there are no criteria listed for Tables 2, S5, and S7. Although line 125 of the paper states that high IOP is defined as">21," why is the criterion of"≥18" used in Table S3? This is very confusing.

8. Figure 2: The survey year and region, which were included in Model 1, are omitted. Please add them.

9. Lines 251–252: Shouldn't "significantly lower" be corrected to "significantly stronger negative correlation"? The meaning could be interpreted entirely oppositely.

10. Line 295: The expression "in vitro mouse study" seems odd. Please check the expression.

11. Lines 337–339: Alcohol leads to a reduction in the production of aqueous humor, which lowers IOP, so this is the opposite mechanism of increasing IOP by Alcohol. A more appropriate reason should be found.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The relevance of reviewed article beyond doubt due to the prevalence of advanced dry eye syndrome. The study of the relationship of dry eye syndrome with various general and ophthalmological parameters (in particular, IOP) is of great interest for attention.

The article is presented in an accessible form and in understandable language. The abstract fully reflects the material presented. The tables are clear. The conclusions correspond to the stated goals.

The statistical methods that were used at each stage of the population study are sufficiently described. This proves the significance of the data analysis results.

During the review of the results, there were some questions that required clarification:

In the “Definition of DED” section of the “Materials and Methods” chapter, it would be worthwhile to describe in more detail which questionnaire is used to determine the definition of DED.

The article found that the presence of diabetes is determined based on several factors (fasting blood glucose levels, current diabetes medications or insulin injections, physician diagnosis). A factor such as fasting blood glucose level was measured separately or only depending on any of the other factors recognized by the authors (for example, fasting blood glucose level + doctor's diagnosis, etc.), or how an independent factor? If this factor was measured as independent did individuals with high fasting glucose levels have this individuals been additional measured glycated hemoglobin or did they have a glucose tolerance test performed?

Reviewer #2: This is an interesting paper that suggests possible relationship between dry eye disease and IOP by analyzing data of large population. I would like to recommend some revision before further consideration.

1. Introduction: Lines 55-79: description regarding IOP seems too long and somewhat distracting. Please make the description more compact.

2. Line 82 : Is there any reason the authors selected the data from KNHANES 2010-2012, as more recent data is available. Please describe the reason in the Discussion.

3. Discussion : sensation of dry eye symptoms can be association with increased systemic inflammatory level and pain modulation in the CNS. Would there be any possible relationship between the inflammation and IOP ? The authors can add some comments/

4. IOP measured with GAT may be affected by corneal hysteresis. Wouldn't there be some relationship between the corneal hysteresis and corneal sensation?

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Reviewer #1: No

Reviewer #2: No

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Adult male-specific inverse association between dry eye disease and intraocular pressure: KNHANES 2010–2012

PONE-D-24-25756R1

Dear Dr. Kim,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Daniel Duck-Jin Hwang

Academic Editor

PLOS ONE

Additional Editor Comments:

The authors have revised and supplemented their manuscript appropriately. Thank you for the diligent revisions made to the manuscript in line with our comments. I truly appreciate your hard work and dedication to improving the manuscript.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: All the issues raised were adequately addressed. I believe now it can be published. Thank you for your effort.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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