PONE-D-23-40090Exposure to air pollutants contributes to an increased rate of neovascular age-related macular degeneration in IsraelPLOS ONE

Dear Dr. Sela,

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: No

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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: AMD is a severe problem related to vision loss. There are many factors which might contribute AMD but age is the most important factor. Here in this article the author is trying to relate AMD with air pollutant. Since air pollution is on the rise and the author has shown how these air pollutant has direct relation with AMD, this kind of study is very important. However the author has not mentioned about the age of the patients. It will be important to see if there are any patient with AMD relatively at young age. It is also interesting to see if the author has any data with AMD and air pollutant in relation to the sex of the patient.

Reviewer #2: I would like to thank you for your efforts on the manuscript entitled “Exposure to air pollutants contributes to an increased rate of neovascular age-related macular degeneration in Israel".

Please see my comments below:

MAJOR COMMENTS

Comment 1

There is very limited patient information available for this study. There is no information on age, sex, smoking status, BMI etc that are major contributing factors for AMD. It is not clear if the statistical data was adjusted based on such information.

Comment 2

Lines 99-101 states that, “Records of patients with neovascular AMD who received intravitreal anti-VEGF injections were retrieved from Assuta Medical Centres’ Eye Clinic, where members of Maccabi Healthcare Services are treated”.

The above statement indicates that the patients included in the study were receiving anti-VEGF therapy. Therefore, it is important to include data/information on the treatment status from routine ocular examinations, as that will significantly influence the data. For example, what percentage of these patients were responding to the therapy and showing improvement etc.

Comment 3

This study is limited to information on area level exposure. It lacks information on individual exposure, which may be affected by personal measures/lifestyle.

Comment 4

Several studies show the correlation of different air pollutants with AMD prevalence. Since this

study aimed to better understand the interactions between air pollution and the development of AMD, it would be more relevant to study the progression of AMD with variations in air pollution (and other factors) over a longer period of time.

Comment 5

The discussion includes a comprehensive compilation of similar studies in other countries. It would be compelling to compare and contrast this study to the other studies to get an insight into the importance of ethnicity in the current analysis.

MINOR COMMENTS

Comment1

Lines 192-193:

“It also surpassed the two standard deviations limits for PM10 and in the negative direction for O3”.

The data shows that PM10 surpassed the two standard deviations limits in both directions, similar to O3. Please correct the above statement with appropriate explanation.

Comment 2

Please include shuffled correlation data for all pollutants.

Comment 3

Lines 224-226:

“To conclude, in these separate analyses, the coefficients of the air pollution gases in

the univariate regression were all positively associated with an increase in the rate of

neovascular age-related macular degeneration”.

The above statement should be rephrased to “increase in the number of neovascular age-related macular degeneration”.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: plos one_AMD.docx

PONE-D-23-40090R1Exposure to air pollutants contributes to increased rate of neovascular age-related macular degeneration in IsraelPLOS ONE

Dear Dr. Sela,

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.

The manuscript has been evaluated by two reviewers, and their comments are available below.

The reviewers have raised a number of major concerns. In particular, they request a clearly outlined rationale for the study and further information on the analysis.

Could you please carefully revise the manuscript to address all comments raised?

Please submit your revised manuscript by Dec 29 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 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: 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-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Helen Howard

Staff 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 #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: Partly

**********

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

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

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: The authors have responded to all the comments to the best of their ability and made corrections wherever needed.

Reviewer #3: This is a very important topic. Faced with the impact of air pollution on health, this article has done a very complete research explanation. However, the following points need to be explained.

Introduction

1.There have been many studies on this topic in the past, and the author should clarify what is innovative or different from previous studies.

Material and Methods

2.Is the air pollution data collected only from 2016 to 2019 sufficient to represent the air pollution exposure of the subjects in this study? Has sensitivity analysis been performed?

3.Are there corrections for personal health or disease factors? For example, diabetes, high blood pressure, frequency of eye use in work or life, UV exposure, etc.?

Results

4.Please improve the quality of figures.

Discussion

5.The same question, whether there are the same or different findings from past studies. What is innovativeness.

6.In addition to exploring the issues of air pollution and health, this study should stand on a higher vantage point and make possible suggestions for policy or health countermeasures.

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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.

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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 #2: No

Reviewer #3: No

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[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.

Exposure to air pollutants contributes to increased rate of neovascular age-related macular degeneration in Israel

PONE-D-23-40090R2

Dear Dr. Hannan,

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,

Der-Chong Tsai, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All concerns raised during review process have been adequately addressed.

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 #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 #3: Yes

**********

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

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 #3: No

**********

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 #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 #3: Thanks for your response. No further comments.

The authors make response to my comments point by point.

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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 #3: No

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