PONE-D-20-09119

Keratoplasty in China: a 5-year review from 2014 to 2018

PLOS ONE

Dear Dr. Shi,

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Yu-Chi Liu, M.D

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

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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: N/A

Reviewer #3: N/A

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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: No

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: No

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: This is a very extensive study with valuable information. The paper is well written. I have the following comments/suggestions to improve the scientific content.

The information of donor cornea preservation is incomplete. The authors should elaborate this aspect by providing specific information about the type of corneal storage medium and describe what is meant by the dry method.

The survey was based on a questionnaire. More details of the methodology of obtaining the information and the questions asked and collection of the responses can be provided.

Reviewer #2: Thank you for the opportunity to review this manuscript. It has the potential to be an important paper, as this is the first time such a comprehensive survey of keratoplasty in China has been attempted.

The current paper is a good draft, but I think there are multiple clarifications that need to be made before it can be published.

Background

1) many readers outside of China will not be familiar with the geography and the classification of provinces in China, so may I suggest that you explain

- how provinces and cities in China are categorised into "tiers"

- if possible, a map to show where the various participating hospitals are located - you may not be able to place all 64 hospitals on the map, but perhaps you can list the hospitals by geographical location?

Methods

2) Some detail needs to be provided on how corneas in China are obtained.

- I understand that use of foreign or imported tissue is highly restricted?

- the use of bio-engineered tissue is very interested, could you elaborate on how these tissues are engineered?

- proportion of fresh, versus frozen, versus bio-engineered tissue would give readers some context

3) a copy of the questionnaire used will be important, and included as an annex. An English translation would be appropriate for most readers.

4) Was there also information collected on graft survival, at least in the first year?

5) Information on the number of surgeries done - lines 276 to 296 - is best summarised in a table rather than written in the text. Similarly with the gender and age distribution.

6) Indications for surgery

- unfortunately, cornea leukoma is a rather rather term, unless there is a specific-definition used by the Chinese Cornea Society? Usually there is an underlying cause - congenital, trauma, infection. Would the authors be able to give further details?

- similarly, cornea perforation is very common, but it would be better to further tell readers if this is due to trauma or infection, ot other causes

- I am surprised bacteria keratitis is such a common indication, but fungal keratitis is not, even though fungal infections are as high as bacterial keratitis in China. Is this practice pattern (meaning that surgery is not done for fungal keratitis), or is it because it is classified under other indications - eg perforations?

7) ALK indications

- curious to see small numbers of corneal perforation - are these patch grafts?

- similarly I see ALK for pseuophakic bullous keratopathy

8) Discussion

- Could the authors comment how the availability of tissue also affects practice patterns?

for example, there could be much more ALK done in China vs the USA because of the lack of healthy fresh tissue for PK and EK

- could authors also comment on what more can be done to improve the CT situation - what this paper shows is that much more CT needs to be done to have any hope of helping the 3 million in China with cornea blindness - is bioengineered cornea a good option? what about training and facilities - 64 hospitals perform transplants, but many are done in smaller units and do much fewer transplants than the top 5 hospitals

Reviewer #3: This paper aims to analyze the trend of corneal transplants in China, focusing in particular on the diffusion of lamellar techniques and surgical indications and to compare the results with the trend in United States (US).

I found the manuscript interesting and original, since few data are available about corneal transplant in China.

I suggests the authors to include the survey as supplemental material.

Moreover, I suggest to include in the discussion the results of similar studies conducted in other countries, in addiction to the US situation.

The sentence at page 21 ,lines 377-328, should be corrected, since only EK surpassed the number of PK in US since 2011 (ALK is still inferior to PK).

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Reviewer #1: Yes: Dr Radhika Tandon, MD, FRCOphth, FRCSEd; Professor of Ophthalmology, Co-Chairperson National Eye Bank, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. Also immediate past president Eye Bank Association of India (EBAI) and immediate past Vice President Association of Eye Banks of Asia (AEBA).

Reviewer #2: No

Reviewer #3: No

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PONE-D-20-09119R1

Survey report on keratoplasty in China: a 5-year review from 2014 to 2018

PLOS ONE

Dear Dr. Shi,

Thank you for submitting your manuscript to PLOS ONE. The reviewers have raised some comments and we would like to 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 Sep 17 2020 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Yu-Chi Liu, M.D

Academic Editor

PLOS ONE

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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: All comments have been addressed

Reviewer #2: (No Response)

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: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: N/A

**********

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: (No Response)

Reviewer #2: Yes

Reviewer #3: 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: (No Response)

Reviewer #2: No

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: The authors have addressed the concerns raised. Minor editorial corrections and language changes are required. For example one-center can be changed to single center. Line 468-471 the sentence "Overall, in China, the geographical ...weak in CT" in the conclusion needs to be re-written as it is not clear.

Reviewer #2: Thank you once again for the opportunity to review this paper, as I was Reviewer 2 for the first submission.

I appreciate that the authors have made some of the amendments as I have suggested, including summarising the data in tables.

Other information that I felt would have made this a more complete paper appears to not be available, based on the methods and on how the questionnaire was designed. I think it is therefore important to include a section of the paper to address the limitations of the study - namely that this was a retrospective study where information is incomplete, diagnoses and classification of indications are not standardised (eg the meaning of cornea leukoma), and that outcome data in terms of graft survival was not obtained.

Reviewer #3: (No Response)

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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: No

Reviewer #2: No

Reviewer #3: No

[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.

Survey report on keratoplasty in China: a 5-year review from 2014 to 2018

PONE-D-20-09119R2

Dear Dr. Shi,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Yu-Chi Liu, M.D

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

**********

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

**********

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

**********

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

**********

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)

**********

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