PONE-D-20-06442

Repeatability of measuring the vessel density in patients with retinal vein occlusion: an optical coherence tomography angiography study.

PLOS ONE

Dear DR. Kim,

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Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: Comments for the Authors: PONE-D-20-06442

1) General comments

The authors assessed the repeatability of the vessel density measurements by the OCTA, however, the authors did not clarify what have been investigated so far and what kind of unsolved research questions are going to be tested in the study. Also, the flow of the sentences is usually off and hard to understand the sales point of the manuscript.

Specific comments:

- Abstract: Please spell out several abbreviations (e.g. SD-OCTA, VD, CV etc.) at their first appearance in the abstract.

- Abstract: lease specify what the full VD means.

- Abstract: The terms "group 1" and "group 2" were suddenly come up in the Results. Please define those in the Methods properly.

- Introduction: The authors should reconsider the flow of sentences in the introduction, which do not sound well and hard to understand. For example, the introduction said that RVO were classified into two categories.., but this information is not related to the following sentence and would be redundant.

- Introduction: The authors stated OCTA has provided many benefits though there are many limitations in FA - however, the authors did not explain what are the "many benefits" of OCTA and not only pros but also their cons should be explained.

- Introduction: What is the sale point of the study? - Could not find any new information/investigations from the study. What is the strong point of the study, which has not been investigated?

- Introduction: The authors did not put appropriate citations throughout the introduction section. Please cite previous paper which support what the authors stated.

- Methods: Please provide the diagnosing criteria for RVO - did the atuhors use FA or just an OCTA?

- Methods: Methods: Did the authors choose one eye per patient or sometimes both eyes? If both eyes were used, specific stat models such as GLM/ GEE should be considered to employ.

- Methods: Demographics should be also shown by CMT category, i.e., <400 and >400 groups.

Reviewer #2: The manuscript by Dr. Kim et al investigated the repeatability of vessel density measurement in RVO patients and explore its related factor. It found that in eyes with macular edema, the repeatability is poor. Generally it is interesting, but further revisions are needed.

1. Please clarify how the sample size be calculated. This study only repeated the scan twice. Why didn't you scan more times?

2.This study found that macular edema is a risk factor of poor repeatability, it also give some explaination in the discussion. I would like to suggest the author to quantifiy segmentation error in their images and report the repeatability after manual correction of segmentation.

3. This study only reported the results of vessel density. The metrics of foveal avascular zone are also important paramters on OCTA. Please also investigate the repeatability of FAZ metrics.

4. The study subjects are mixed of CRVO and BRVO. There are also different region of BRVO. It would be interesting to investigate whether the repeatability is different between the region involved and not involved.

Reviewer #3: The authors present an assessment of OCTA repeatability in retinal vein occlusion.

The authors also report a linear regression analysis of clinical and anatomical parameters affecting VD repeatibility and demonstrate how the increase of macular volume reduce the accuracy of the examination.

Our group recently published an angio-OCT study to evaluate Papillary Vessel Density Changes after Intravitreal Anti-VEGF Injections in Central Retinal Vein Occlusion (J Clin Med. 2019 Oct 6;8(10). pii: E1636. doi: 10.3390/jcm8101636). We believe that the peripapillary area might be a region of interest to study microvascular changes when significant macular edema is present. I think it would be interesting to add a comment on this subject.

In the conclusions section it would be more appropriate to specify that there is a correlation between the entity of macular edema and the repeatability of VD measurement rather than stating that the repeatability is "poor when eyes were associated with macular edema".

Minor corrections:

Page 13 line line 120: typos thickness

Page 15 line 220 lower instead of low

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Reviewer #1: No

Reviewer #2: Yes: Haoyu Chen

Reviewer #3: Yes: Michele Nicolai

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Repeatability of measuring the vessel density in patients with retinal vein occlusion: an optical coherence tomography angiography study.

PONE-D-20-06442R1

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.

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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

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 #2: Yes

Reviewer #3: Yes

**********

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

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 #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 #2: Yes

Reviewer #3: 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 #2: (No Response)

Reviewer #3: The authors have addressed the comments. The English appears correct. The conclusion is now more in accordance with the findings of the study. I think the study provides interesting data on the repeatability of OCTA assessment in patients with macular edema correlated to RVO.

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Reviewer #2: No

Reviewer #3: No