PONE-D-22-21223Sex differences in the association between oxidative stress markers and optic nerve head blood flow in normal-tension glaucomaPLOS ONE

Dear Dr. Nakazawa,

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 Both reviewers found the MS of interest and suggested minor revisions. We look forward to the revised version 

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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: This work investigates the role of oxidative stress / antioxidant potential and optic nerve head perfusion parameters in normal tension glaucoma. The manuscript is well written, with interesting data for the scientific community but some revision is needed.

1) Lines 128-130: exclusion criteria “a history of high IOP (higher than 22 mmHg, as measured with Goldmann applanation tonometry) on the test day”. explain why patients with IOP of 22 mmHg were included, since this characterizes open angle glaucoma. Also, briefly explain why high myopia patients were excluded.

2) Line 154: “Measurements of ocular blood flow” This paragraph does not provide methods for measurement of ocular blood flow. Please review.

3) Lines 256-257 and 384-386: Authors state that ß value was very small / low. What criteria authors used to classify a ß value as very small/low? Other associations on the manuscript had similar ß value, but that information was not highlighted.

4) Lines 300-301: authors state no significant association between dROMs and OBF were found. However, authors also report a negative correlation between dROMs and FAI-T in females (rs=-0.18, p=0.036). Please review the statement.

5) Lines 305-306: If authors present previously published data showing that dROMs levels might not directly reflect local ocular oxidative stress, please explain why dROMs was used as oxidative stress marker in this study in the first place.

6) The main findings are related to BAP (antioxidant potential) and not dROMs (oxidative stress marker). BAP is not a direct oxidative stress marker, instead it reflects the systemic antioxidant potential by reducing ferric oxide to ferrous oxide. Therefore, the TITLE and ABSTRACT should be reworded to give less emphasis to “oxidative stress markers”.

Reviewer #2: This is a very interesting study investigating and reporting on the association of ocular blood flow parameters with oxidative stress markers in patients with normal tension glaucoma. More specifically, the study focuses on differences in these correlations that are observed between genders. The authors managed to present a sound and thoroughly organized study and relate their findings very well to previous studies. However, the following points need to be taken into consideration.

Abstract: The investigation of sex differences regarding the association of ocular blood flow with oxidative stress should also be mentioned in the purpose of the study.

The methods and results presented in the abstract should precisely reflect the investigations and outcomes of the present study. In particular, the authors should additionally refer to the outcomes regarding the correlation of MBR-T to d-ROMs, the other oxidative stress marker. A possible association of pulse-waveform parameters with oxidative stress markers and other clinical parameters was also investigated in the present study and should be mentioned both in methods and results of the abstract.

Line 44: The authors had better replace “MBR-T” with “mean blur rate in the tissue area of the optic nerve head (MBR-T)”, since the abbreviation has not been explained earlier.

Line 52: MBR-T was significantly correlated with disc area, too. The text should be changed accordingly.

Line 132: It is advisable that the authors explain why high myopia is included in the exclusion criteria.

Line 154: The title should be changed in order to correspond to the text that follows.

Line 167: The authors should further explain in more detail what the parameter “mean blur rate” exactly indicates.

Lines 171-172: References should be provided.

Table 2: Explanations for the abbreviations “BOS-T”, “BOT-T” should also be included in the caption of the table.

Lines 206, 212: Statical should be changed to statistical.

Line 228: FAI-T was significantly correlated with disc area too. The text should be changed accordingly.

Line 230: cpRNFLT was significantly correlated to FAI-T both in males and females. The text should also be changed accordingly.

Tables 3 and 4: The statistical method that was used for the presented analysis should be mentioned at the title of each table, i.e. spearman’s correlation coefficient and multivariate linear-mixed effect models, respectively. Furthermore, explanation for the abbreviation “AU” should be included in the caption of the tables.

Figure S1: A caption should be provided.

I would like to look at a revised version of the manuscript.

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Reviewer #1: No

Reviewer #2: No

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Sex differences in the association between systemic oxidative stress status and optic nerve head blood flow in normal-tension glaucoma

PONE-D-22-21223R1

Dear Dr. Nakazawa,

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,

Demetrios G. Vavvas

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: 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

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

Reviewer #1: 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

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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

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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: Authors have adequately addressed all reviewers comments. The manuscript has improved overall. I have no further comments.

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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

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