PONE-D-23-27793Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitisPLOS ONE

Dear Dr. Tagami,

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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: Partly

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

Reviewer #1: No

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: No

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 authors demonstrated that relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis. The manuscript contains many grammatical errors. In addition, the purpose of the study is ambiguous. The methods for counting vitreous cells are not clear. Major revision must be necessary.

1. Line 25-26. Purpose of this study is ambiguous. Is the purpose may be to clarify the relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis?

2. Line 56. “and acute anterior uveitis (5.5%),” should be “and acute anterior uveitis (5.5%) [2].”

3. Line 58. “represented over half of case, thus Diagnosis and treatment of” should be “represented over one-third of cases, thus diagnosis and treatment of”.

4. Line 62. “Widefield OCT angiography (WOCTA)” should be “Widefield OCT (WOCT)”.

5. Line 66-67. “the relationship between uveitis and IL-6 level and several functions of IL-6 have been identified” should be “relationship between uveitis and IL-6 levels in aqueous humor and significant roles of IL-6 in non-infectious uveitis have been identified”.

6. Line 69. “increased in uveitis” should be “increased in the aqueous humor in patients with uveitis”.

7. Line99-100. Please describe the details of multiplex PCR. What kinds of pathogens did you examine? Did you examine fugus or toxoplasma DNA? It is necessary to include references related to multiplex PCR.

8. Line 104-115. I cannot understand the meaning of Figure 1A, 1B, 1C, 1D, 1E and 1F. Where is the area of “through the macula (Figure 1A)”, “upper vitreous cavity around the equatorial region (Figure 1B)” and “lower vitreous cavity (Figure 1C)”? How to determine the position of the equator in a WOCT image?

9. Line 131-133. What is the area for counting cells in vitreous cavity in a WOCT image? (for example, 13mm x 5mm)

10. Line 140-142. If you defined “posterior vitreous area” as described here, the area for counting the number of cells varies greatly depending on the height of the PVD, and this is not fair for evaluation of the severity of inflammation in the vitreous cavity.

11. Line 150-151. The methods for “counting by software” should be described. References for the methods for “counting by software” are necessary.

12. Line 167-168. In flow cytometry analyses, it is common to separate cell fractions (erythrocytes, lymphocytes, monocytes, and granulocytes) using forward scatter and side scatter at first. Which cell fraction did you gate on?

13. Line 194-202. Numbers of cells in Group 1 (manual counting) and Group 2 (software-based counting) were quite different and more numbers of cells was counted by manual counting. Why is there such a big difference between manual counting and software-based counting?

14. Line 268. “Correlation with IL-6 value” should be “Correlation with IL-6 levels and changing of visual acuity”.

15. Line 277. “Fig 4. We compared visual acuity between preoperatively and 3 months postoperatively“ should be “Fig 4. Comparisons of IL-6 levels among three groups depending on improvement or deterioration of visual acuity”.

16. Line 283-291. The finding that there is a correlation between the number of cells in WOCT and CD56-positive cells in FACS is clearly due to the fact that one case of ARN had an exceptionally high number of CD56-positive cells. ARN is infectious uveitis, and the other eight cases are non-infectious. If you want to claim that there is a correlation between the cell count in WOCT and CD56-positive cells in FACS, you should exclude one case of ARN from the analysis.

17. Line 311-313. IL-6 may be mainly produced by T cells, B cells and monocytes/macrophages in the eyes with uveitis.

18. Line 329. “OCT is an important tool in ophthalmology” should be “OCT is an important tool in clinical practice in ophthalmology”.

19. Line 332. “Papers” should be “Articles”.

20. Line 337. “We evaluated WOCT findings” should be “In this study, we evaluated WOCT findings”.

21. Line 337-340. The methods for binarization of WOCT image and the methods for counting vitreous cells should be described in Materials and Methods section.

22. Line 368. “WOCTA” should be “WOCT”.

Reviewer #2: 3.11.2023

In this manuscript, the authors described “Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis”. The study will be very useful for the literature. The report is an interesting study, but it needed some suggestions for publication.

Here are the concerns for the authors;

Generally;

1. Keywords should be ordered alphabetical.

2. Grammar should be checked.

3. Abstract structure should be the same as described in the journal.

4. The inclusion and exclusion criteria determined for the study should be clearly stated in the materials and methods.

5. The findings given in the table should not be repeated in the text in the results section.

6. The units of evaluated parameters should be given clearly. For example, pg/mL for IL-6 value.

7. The % of demographic characteristics should also be given in Table 1.

8. The spelling features of Tables 1 and 2 are not the same.

9. All p values should be written in italic.

10. The resolution of the figures is low and should be corrected.

11. Citations should be corrected according to the journal instructions.

12. The lot number of kits should be stated.

13. The brand and model numbers of the devices used in the study should be stated.

14. What does the word “patiene” in Table 1 mean?

15. Significance levels of p values should be stated below the tables.

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Reviewer #1: Yes: Toshikatsu Kaburaki

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Rev_Relationship between vitreous interleukin-6 levels and vitreous particles findings on.docx

PONE-D-23-27793R1Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitisPLOS ONE

Dear Dr. Tagami,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Feb 11 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-emailutm_source=authorlettersutm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Jiro Kogo

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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)

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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

**********

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

**********

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

**********

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: The authors demonstrated that relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis. The manuscript was well revised according to the reviewers’ suggestions. However, a few mistakes were remained to be corrected.

1. Line 204, line 353 and Fig 5. CD3 was examined in line 356 and Fig 5, whereas CD9 was examined in line 204. CD3 may be correct.

2. Line 344. In Table 4, there were no cases with ARN, thus “ARN acute retinal necrosis” should be erased.

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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: Yes: Toshikatsu Kaburaki

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis

PONE-D-23-27793R2

Dear Dr. Tagami

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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PLOS ONE