PONE-D-22-03740Choriocapillaris flow deficit in a pachychoroid spectrum disease using en face optical coherence tomography angiography averagingPLOS ONE

Dear Dr. Ooto,

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- https://link.springer.com/article/10.1007/s00417-019-04399-8

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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: Major comments

Authors investigated the choriocapillaris changes associated with pachychoroid pigment epitheliopathy (PPE) in comparison with healthy eyes. Authors found that the blood flow area of the choriocapillaris decreased diffusely within the macular area in PPE eyes compared to control eyes, and the choriocapillaris flow deficit was not necessarily related to pachyvessel location.

This study shows that choriocapillaris changes in PPE eyes were not directly caused by the pachyvessels. This is an interesting finding.

The definition of pachyvessel is not clear. Authors stated that “Pachyvessels were defined as dilated choroidal venous veins that continuously extended from the dilated vortex vein, could be distinguished by their relatively larger caliber in comparison with other choroidal veins in other quadrants, and showed asymmetry of upper and lower vortex veins.” This is a subjective and vague definition, and it is difficult for other researchers to follow this study. This part should be stated in the limitation section.

In addition, this study does not pay attention to the distance between pachyvessel and PRE. Because PRE abnormality, PRE detachment, or choroidal neovascularization tend to occur on or near the site where this distance is very small, this distance is an important factor when evaluating PPE. This may be why there was no significant difference in Table 3. If authors ignored this parameter, this part also should be stated in the limitation section.

Minor comments

Eye of PPE were fellow eyes of CSC or normal eyes? Please add information of the patients of PPE.

Table 2 and Table 3: “p values adjusted for age and sex.”

Was this comparison possible using un-paired t-test, as stated in the Method.

Table 3: Please add the information of choroidal thickness.

Reviewer #2: Thank you for inviting me to review the manuscript entitled, "Choriocapillaris flow deficit in a pachychoroid spectrum disease using en face optical coherence tomography angiography averaging."

Comments:

1. This study included the eyes with PPE and nornal control eyes. However, the detailed information about the contralateral eyes were not provided. In terms of PPE, the contralateral eyes had no abnormalities or only PPE? If so, performing dye angiography sounds ethically problematic. Were there any exudative abnormalities in the contralateral eyes, such as CSC, PNV, pr PCV? In terms of nornal control eyes, were there any ocular diseases in the contralateral eyes? Furthermore, the status of contralateral eyes affected the results?

2. Please demonstrate more information about the systemic conditions that might influence the results (i.e, hypertension and diabetes) should be mentioned. Otherwise, some comments should be included as the limitation of the study.

End of comments.

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Reviewer #1: No

Reviewer #2: No

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Choriocapillaris flow deficit in a pachychoroid spectrum disease using en face optical coherence tomography angiography averaging

PONE-D-22-03740R1

Dear Dr. Ooto,

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,

Ireneusz Grulkowski, PhD

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 #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 #2: Yes

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

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 #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 #2: 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 #2: Thank you for allowing me to review the manuscript. The authors have adequately addressed my comments raised in a previous round of review.

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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 #2: No

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