PONE-D-22-27465Health-related quality of life of daily-life-affected benign essential blepharospasm: multi-center observational studyPLOS ONE

Dear Dr. Hirunwiwatkul,

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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Academic Editor

PLOS ONE

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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

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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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: The authors reported an interesting study about quality of like in patients with benign essential blepharospasm (BEB). I have some comments to the authors:

- In the methods the authors should specify that the diagnosis of BEB was made in accordance with the recent criteria. Here the paper that should be included:

Defazio G, et al. Diagnostic criteria for blepharospasm: A multicenter international study. Parkinsonism Relat Disord. 2021 Oct;91:109-114. doi: 10.1016/j.parkreldis.2021.09.004. Epub 2021 Sep 8. PMID: 34583301; PMCID: PMC9048224.

- Please specify whether all the patients had focal dystonia. The phenomenon of spread in BEB is a frequent condition, so it would be better if the authors expanded this point in the methods. There are several studies on the topic that might be helpful:

Berman BD, et al. Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study. J Neurol Neurosurg Psychiatry. 2020 Mar;91(3):314-320. doi: 10.1136/jnnp-2019-321794. Epub 2019 Dec 17. PMID: 31848221; PMCID: PMC7024047.

Ercoli T, et al. Spread of segmental/multifocal idiopathic adult-onset dystonia to a third body site. Parkinsonism Relat Disord. 2021 Jun;87:70-74. doi: 10.1016/j.parkreldis.2021.04.022. Epub 2021 May 12. PMID: 33991781.

- Among the strengths of the study, the author may also add that the Jankovic rating scale is one of the best tool to assess BEB, as recently reported in this recent international study:

Defazio G, et al. Measurement Properties of Clinical Scales Rating the Severity of Blepharospasm: A Multicenter Observational Study. Mov Disord Clin Pract. 2022 Aug 15;9(7):949-955. doi: 10.1002/mdc3.13530. PMID: 36247913; PMCID: PMC9547140.

- The results should better organize adding the p value in the text and the findings from the statistic.

- “In our study, the female to male ratio was higher than previous studies.” Please expand this point.

Reviewer #2: The authors present data about quality of life of Thai patients with blepharospasm treated with

Botulinum toxin type A. The manuscript might have important clinical message and may be of great

interest to the readers who are interested in this specific topic.

However, I do believe that the manuscript would benefit from a second round of major revisions in order to

improve it before being considered for publication. Below are some recommendations:

Q1. Line 63: “Most of the patients had bilateral involvement (96.9%)”

Please discuss why you consider few patients with unilateral involvement as having blepharospasm rather

than hemifacial spasm taking into account that all more accepted definitions describe blepharospasm as a

bilateral disturb.

Q2. Line 97-98 : “We evaluated 98 HRQOL in Thai patients who had daily-life-affected BEB before and

after…”

What do you mean by “daily-life-affected” when you consider a disease with continuous symtpoms like

blepharospasm? Do you refer to more severe forms of BEB? Please specify

Q3. Lines 107-108 “Inclusion criteria were daily-life-affected BEB patients who had Jankovic rating scale

(JRS) of at least 3 in both severity and frequency scores graded…”

Please provide a brief sentence on the scoring graduation of the Jankovic rating scale (for istance : The JRS

ranges from 0 to 8 points (sum score) and includes 2 categories:… etc etc). Moreover, a score of at least 3

for both severity and frequency on the Jankovic rating scale is relatively high as compared to those present

in several case series from the literature (see works by Jankovic J, et al. 10.1002/mds.22368; and Jankovic

J, et al. 10.1002/mds.23658), where Mean JRS sum score was less than 6 despite of a disease duration of

more than 6 years (5.05 ± 4.25 years in the present study). It would be of great interest to report which

rate of patients from the 14 centers across Thailand reached a Jankovic rating scale total score more than 6.

Had all patients higher severity scores? why was the severity of the blepharospasm in this study population

higher than that of the general population (as you stated – line 243)? The blepharospasm is a disorder

almost exclusively managed in tertiary centers worldwide and this should not be a reason why the severity

scores are so high in BEB patients in this study. Consider this in the discussion.

Q.4 Line 130: “Both versions of the Thai questionnaires were validated in previous studies”.

please report reference of the previous studies were a the Thai version of the 25-item National Eye

Institute visual function questionnaire (NEI VFQ-25) was validated.

Q5. Line 179: “Table 1: Demographic data of patients with daily-life-affected BEB”

Please specify in the table that JRS scores refer to baseline state.

Q6. Lines 221-222-223 : “Duration of action analyzed by Kaplan-Meier estimates, 50% of participants

reported the beginning of recurrent BEB symptoms at 10 weeks after the treatment.”

Please give sense to the first part of the sentence.

Q7. the General health item and composite score of the 25-item National Eye Institute visual function

questionnaire (NEI VFQ-25) are first described in the results and discussion. It would be better to introduce

them in the methods firstly. In particular, unlike the other scores, Composite scores increase after

treatment, so it should be better defined in methods section.

Q8. Figures:

most Y-X graphs’ legends are almost unreadable. Please increase graphs’ quality or limit the number of

graphs/figures in order to increase size (fig. 4 is a good solution)

Q9. Statistical analysis and results:

It would be more appropriate to specify coefficient and significance values when comparing pre and posttreatment data (both in text and tables)

Reviewer #3: This research is an accurate description of demographic and clinical features of BEB in Thailand. Authors show with adeguate statistical tools how quality of life improves after treatment with botulinum toxin. Authors used different and validated scales with reliable results.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PONE-D-22-27465R1Health-related quality of life of daily-life-affected benign essential blepharospasm: multi-center observational studyPLOS ONE

Dear Dr. Hirunwiwatkul,

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.

==============================

ACADEMIC EDITOR: I received positive evaluation from our eminent referees. There are still some minor comments that needs to be addressed (see below). A further revision of your english writing style is needed. 

==============================

Please submit your revised manuscript by Mar 19 2023 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,

Tommaso Martino, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

​

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Academic Editor Comments:

In addition to the comments of our eminent referees, please consider the following:

- Line 63: add p-values.

- Line 77: change "depends of multifactor" with "are multifactorial".

- Line 78: change "another" with "one of".

- Line 86: change "that" with "whose".

- Line 108: remove the sentence from "we would like..." to "... then the". Start with inclusion and exclusion criteria, which should be reported in a more systematic way.

- Line 121: change "was pregnant" with "were pregnant".

- Line 125: explain what is the most common "standard routine" used in your centers.

- Line 178 and 185: change "underlying diseases" with "comorbid diseases" or "comorbidity".

- Line 188: I would not say "significant number" if the percentage is 12.5%.

- Line 190: what do you mean by "transportation cost"? And why is it reported?

- Line 196-198: acronyms should be listed in alphabetical order.

- Line 203-205: why are you reporting the predicted scores using the linear mixed model? What is the meaning to give to the predicted scores, compared to the actual scores? Similarly for the other reported scores (line 219, etc.)

- Line 214: remove the opening parenthesis.

- Line 257-262: move the paragraph from "a recent multicenter..." to "... and specificity [27]" in the limitations section of the article.

- Line 262-291: move the sentences after the discussion of your results. The discussion section should be focused on the results of YOUR paper, and then a comparison with previous literature.

- Line 318: start a new paragraph when reporting the strength and limitations of your paper. Another limitation is the fact that some interview (how many?) were performed by remote, due to COVID19 pandemia.

- In the introduction it is said that the treatment with BTX-A is not covered by your health system. How do you treated the patients included in your study? Do they payed the treatment? This could also be a selection bias, that should be included in the limitations section.

Tommaso Martino, 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: All comments have been addressed

Reviewer #3: 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 #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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: No

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: Yes

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 #1: The authors have addressed all the points, and they have strengthen the manuscript.

Reviewer #2: The authors aswered to most of the comments. However, I have further recommendations in order to get acceptable english language. Please check the following sentences:

1. line 86: “Blepharospasm is one of focal dystonias that symptoms commonly spread to…”

2. lines 114-115 : “We use the JRS, worldwide for clinical research and easy to use [21], for assess the severity and frequency of the blepharospasm”

3. line 288 : “Male and female patients might aware of the…”

4. lines 301-302 : “Mental health and difficulties with vision activities in near, distance and peripheral had effects…”

5. line 316: “BTXA treatment is useful for decreased physical severity…”

6. lines 320-322 : “The large 320 network of cooperation from participating neuro321

ophthalmologists and neuro-medicine units to deploy both generic and visual-specific

322 questionnaires allowed for broader data collection however, this study did have some limitations”

Moreover, Martino et al., 2012 and Weiss et al.,2006 references are reported twice in refercences list. (9-30 and 8 – 29 , respectively); Yang et al., 2021 reference is reported three times (5-7-12);

Reviewer #3: I did non ask for revision of the previous version, the revised version is still accurate and I can confirm that the current version of the manuscript is worthy of publication.

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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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[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.

Health-related quality of life of daily-life-affected benign essential blepharospasm: multi-center observational study

PONE-D-22-27465R2

Dear Dr. Hirunwiwatkul,

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.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tommaso Martino, M.D.

Academic Editor

PLOS ONE

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

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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

**********

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

Reviewer #1: Yes

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 #1: No

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 #1: Yes

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 #1: I have no further comments to this manuscript.

Reviewer #2: (No Response)

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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

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