PONE-D-22-32461Light and Electron Microscopic Features of Preclinical Pseudoexfoliation SyndromePLOS ONE

Dear Dr. Suwan,

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.

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Kind regards,

Sanjoy Bhattacharya

Academic Editor

PLOS ONE

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Additional Editor Comments:

All three learned reviewers have requested minor revision that can be done by incorporating appropriate changes in the manuscript

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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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: Clear and concise paper.

I wish the paper included more information on pPEX findings (P, D, C, W), e.g., some background information and if available, proposed etiology. Why were they specifically chosen? Why were they different than Mardin et al.? If possible, please add information and clarify.

Inclusion/exclusion criteria and methods are well-described.

Minor suggestion and correction:

-Simplify the opening sentence (lines 62-65). Stylistically, it is a bit convoluted and not easy to follow.

-Correct to show* (line 186).

Reviewer #2: Overall, this is an interesting subject and the paper is well-written. The study design is well done, and the introduction provides a thorough background for the study. The pictures provides very helpful additional information and context for the study.

The authors should clarify why only a portion of the samples were sent for TEM analysis (34 samples), and how those specific samples were chosen. The authors should also clarify if any differences were found between the results of the two thicknesses and staining methods (thin samples with toluidine blue, and ultrathin samples with uranyl acetate and lead citrate) used for the samples undergoing TEM analysis.

It would be helpful if the authors could elaborate on the clinical significance of their findings, that pPEX is not associated with PXM and is significantly associated with TEX.

Reviewer #3: The study evaluated the ultrastructural alterations of the anterior capsules in patients with signs of preclinical pseudoexfoliation syndrome using histological analyses with light microscopy and transmission electron microscopy in 34 pPEX patients and 62 controls undergoing cataract surgeries in Thailand. The manuscript is well-written with clear logics. The presented data was self-explaining and easy to follow. The authors explained the possible reasons leading to the different outcomes of this study compared to several published reports. The findings here could contribute to the diverse clinical studies in identifying the subclinical features related to PEX diagnosis. The study could be strengthened in a few ways.

1. The introduction justified the importance to diagnose PEX in its early stage. It will be more helpful to add more information about the prevalence of PEX worldwide and the percentage of PEX patients developing elevated IOP and glaucoma eventually. This could help readers understand the different stages of the disease - PEX.

2. TEX diagnosis has been a major finding in this study. However, its diagnosis criteria needs to be detailed in the methods section. Is it necessary to remove any patients with clear clinical signs of TEX in the first place of study enrollment?

3. It has been more than two years after the initial study. Is it possible to check whether any of the study patients has developed clinical symptoms of PEX, especially the one case with TEM alterations?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Light and Electron Microscopic Features of Preclinical Pseudoexfoliation Syndrome

PONE-D-22-32461R1

Dear Dr. Suwan,

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,

Sanjoy Bhattacharya

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

Reviewer #2: All comments have been addressed

Reviewer #3: 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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: All comments were addressed in the text. The paper is well-written, and the figures clearly demonstrate the pPEX features.

Reviewer #2: The reviewer comments have adequately been addressed in this revised submission for this manuscript.

Reviewer #3: The authors have addressed all the comments from last round. The quality of the manuscript has been improved. No additional 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

Reviewer #2: No

Reviewer #3: No

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