Peer Review History

Original SubmissionJuly 6, 2024
Decision Letter - Ayman Elnahry, Editor

PONE-D-24-26615

The Influence of UV-Visible Light, Microwave Radiation, Argon Laser, Heating and Aging Process on Silicone Oil Utilized as Intravitreal Implants: Experimental Exposure with Clinical Correlation

PLOS ONE

Dear Dr. Al-Dwairi,

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.

Please submit your revised manuscript by Dec 19 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Ayman Elnahry

Academic Editor

PLOS ONE

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2. Thank you for stating the following financial disclosure:

“The authors would like to acknowledge Jordan University of Science and Technology for supporting the research projects validated by the Deanship of Scientific Research (Funding ID: 20230529)”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

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Additional Editor Comments:

The manuscript idea is novel but the manuscript is poorly written. It needs to be significantly shortened and repetitive statements removed. The English language needs extensive editing, perhaps using a professional service. Limitations of the study such as sample size and lack of statistical analysis should be mentioned and recommendations for future studies stated. Please respond fully to reviewers’ criticism/comments. Discussion section which is mentioned as “Conclusions” is very short and relevant literature needs to be discussed. The value of having SO in foldable capsular vitreous body can be briefly discussed.

[Note: HTML markup is below. Please do not edit.]

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: Partly

Reviewer #2: Yes

Reviewer #3: Partly

**********

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

Reviewer #1: N/A

Reviewer #2: N/A

Reviewer #3: No

**********

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

**********

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: No

Reviewer #2: Yes

Reviewer #3: No

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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: Running title: Silicone oil under different condition

- I would suggest to add an “s” to condition.

- A thorough English Editing is compulsory.

Page 4. Line 75

Many hypotheses could explain the incompletely understood mechanism of emulsification of SO.

- Rephrase this sentence because it is not clear

Page 6 line 115: Aging factors.

The Authors should explain in detail how this aging process has been done and what are the aging factors.

Page 10 line 224-226; The Authors attested that: To simulate the SO inside the eye while considering the aging factor, we mixed SO with BSS and aqueous humor.

- Unfortunately, I do not agree with this postulation as in the vitreous chamber after surgery a lot of inflammatory cytokines and pro inflammatory factors can be released. Think only to the blood elements that can be released into the vitreous chamber.

Page 17 lines 368-372; The Authors attested: The FTIR spectra of SO under thermal treatment, U.V. irradiation (long and short), microwave irradiation, visible irradiation, and aging exhibit identical spectra for untreated SO, indicating that there are no broken bonds and; therefore, no significant emulsification occurred. Additionally, the optical absorbance and the viscosity of SO under these parameters remain almost the same as the control sample, with slight changes, indicating that the optical properties and viscosity are stable under these parameters.

- I do agree with this statement from physical point of view, but unfortunately in the vitreous chamber there are also al lot of biological components that must be considered before make any conclusion.

ABSTRACT.

The Authors also concluded that : “ It was concluded that the patient's samples treated with argon laser exposure exhibited more emulsification than the other two, which had a lower duration of SO within the eyes.”

- So what the Authors suggest? To avoid laser when SO is in the vitreous chamber or an early removal after laser?

Page 18 Line 379-381

The Author attested: Finally, four patients, two of whom were treated with laser exposure and the other two patients who were untreated with laser irradiation, were compared to validate the previous results. It can be concluded that the patients' samples that were treated with laser exposure exhibited more emulsification than the other two patients who were not treated with a lower duration of SO within the eyes.

- This effect could also be related to the interaction with inflammatory cytokines released after laser treatment. These considerations must be considered from the Authors. Not only physics but biological interactions of SO.

Did the Authors measure the proteins concentration in removed SOs?

Reviewer #2: Novel study combining in vivo and in vitro studies using advanced technology. The authors need to acknowledge that it is difficult to confirm based on single case the effect of silicone oil emulsification. For example, the eye that had argon Laser showed the most difference as concluded by the authors, but this eye could have had PVR or inflammation, more activity of the patient, more sun exposure or less complete oil fill, etc..These variables (inflammation, more activity of the patient, more sun exposure or less complete oil fill) need to be mentioned as drawbacks of the study besides the small number of patients. Otherwise this is a good start for larger studies.

Reviewer #3: I admire the novelty of the idea and the translational value of this work, however, there are some shortcomings that affect the integrity of the conclusions made by the manuscript in its current status:

1. Statistical analysis is needed to prove the physical changes to silicone oil is related to the tested factors and avoid type I error. This is not possible with the current low number of samples. I believe more oil samples are needed to consolidate those observations.

2. More details needed in the study design and more background knowledge. For example, background knowledge on FTIR would be of benefit.

3. I would advise on a more relevant literature review to publications with similar work.

4. The manuscript might as well benefit from language revisions.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

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Revision 1

Academic Editor

PLOS ONE

Dear editor,

My self and the co-authors are pleased to resubmit the manuscript entitled ‘The Influence of UV-Visible Light, Microwave Radiation, Argon Laser, Heating and Aging Process on Silicone Oil Utilized as Intravitreal Implants: Experimental Exposure with Clinical Correlation, ID: PONE-D-24-26615” to be considered for publication in PLOS ONE. The revised manuscript takes into consideration both the editorial and reviewers’ comments. Kindly find below a point-by-point response to those comments, along with an uploaded copy marked with MS track changes indicating changes to the manuscript.

We would like to thank your editorial team and the reviewers for their time and efforts in reviewing our manuscript.

Editorial comments

Thank you so much for your efforts and time in improving this manuscript. Your comments are much appreciated, and the manuscript will be modified accordingly,

1. The manuscript idea is novel but the manuscript is poorly written. It needs to be significantly shortened and repetitive statements removed. The English language needs extensive editing, perhaps using a professional service

Response: Professional English language and scientific editing was performed. Thank you so much.

2. Limitations of the study such as sample size and lack of statistical analysis should be mentioned and recommendations for future studies stated.

Response: Thank you. The small sample size with lack of statistical analysis was added to the limitations. Recommendations were amended to the revised manuscript. Thank you so much.

3. Discussion section which is mentioned as “Conclusions” is very short and relevant literature needs to be discussed. The value of having SO in foldable capsular vitreous body can be briefly discussed.

Response: Thank you so much. The discussion was combined with the results. More relevant literature review was discussed in both sections. In addition, the value of SO in foldable capsular vitreous body was discussed. Thank you so much for efforts in improving the manuscript.

Journal Requirements

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

Response: Thanks so much. It was modified according to the template.

2. Please state what role the funders took in the study.

Response: Thank you so much. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. It was added to the revised manuscript.

3. We note that you have indicated that there are restrictions to data sharing for this study. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

Response: Thank you so much. We have modified the statement into “Data are available upon request from the corresponding author. The data collection sheets used are available in the appendix for use”. In addition, we have uploaded supplementary material for the data.

4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager.

Response: Thank you. We have added the ORCID.

5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

Response: Thank you. We amended the modifications.

Comments from Reviewer #1:

Many thanks for your time and efforts in improving our manuscript. Much appreciated

1. The Running title: Silicone oil under different condition. I would suggest to add an “s” to condition.

Response: Thank you so much. It was modified.

2. A thorough English Editing is compulsory.

Response: Thank you. We have modified the manuscript and extensive language editing was performed.

3. Many hypotheses could explain the incompletely understood mechanism of emulsification of SO. - Rephrase this sentence because it is not clear.

Response: Thank you for your respectful point. It was rephrased and modified in the revised manuscript.

4. age 6 line 115: Aging factors. The Authors should explain in detail how this aging process has been done and what are the aging factors.

Response: Thank you very much for this important point. The aging process means the effect of duration on the emulsification of SO. It was hypothesized that the longer duration of SO in the vitreous cavity may increase the rate of emulsification. Accordingly, to simulate the SO inside the eye while considering the aging factor, we mixed the SO with a balanced salt solution (BSS) and eye aqueous humor. We studied their properties after aging them for 6 and 12 months, respectively. However, this a partial model, as you stated, many inflammatory markers and cytokines may influence the SO emulsification, but technically were difficult to be added to the SO. The required modifications were added to the revised manuscript with more clarifications.

5. Page 10 line 224-226; The Authors attested that: To simulate the SO inside the eye while considering the aging factor, we mixed SO with BSS and aqueous humor.

- Unfortunately, I do not agree with this postulation as in the vitreous chamber after surgery a lot of inflammatory cytokines and pro inflammatory factors can be released. Think only to the blood elements that can be released into the vitreous chamber.

Response: Thank you very much for this valid point. As aforementioned comment, we have tried to stimulate the aging or time factor as much as possible, however, it would be difficult to extract the exact vitreous inflammatory markers and add them to the SO. We mix the SO with BSS and aqueous. The aqueous was extracted at the time of SO removal in order to resemble the vitreous with its inflammatory components as much as possible. Accordingly, we have tried a partial model to stimulate the process. We have clarified this point and added to the limitations. Thank you so much.

6. Page 17 lines 368-372; The Authors attested: The FTIR spectra of SO under thermal treatment, U.V. irradiation (long and short), microwave irradiation, visible irradiation, and aging exhibit identical spectra for untreated SO, indicating that there are no broken bonds and; therefore, no significant emulsification occurred. Additionally, the optical absorbance and the viscosity of SO under these parameters remain almost the same as the control sample, with slight changes, indicating that. the optical properties and viscosity are stable under these parameters.

- I do agree with this statement from physical point of view, but unfortunately in the vitreous chamber there are also al lot of biological components that must be considered before make any conclusion.

Response: Thank you for this point. Yes, we agree with your point, accordingly, we have modified the Conclusions and amended your point regarding the biological effects.

7. The Authors also concluded that : “ It was concluded that the patient's samples treated with argon laser exposure exhibited more emulsification than the other two, which had a lower duration of SO within the eyes.”

- So what the Authors suggest? To avoid laser when SO is in the vitreous chamber or an early removal after laser?.

Response: Thank so much this valid comment. In certain circumstances the additional postoperative laser in unavoidable. However, out suggested educational purpose is to perform adequate and comprehensive endo-laser treatment during the pars plana vitrectomy and before SO implantation. We have amended this education point.

8. The Author attested: Finally, four patients, two of whom were treated with laser exposure and the other two patients who were untreated with laser irradiation, were compared to validate the previous results. It can be concluded that the patients' samples that were treated with laser exposure exhibited more emulsification than the other two patients who were not treated with a lower duration of SO within the eyes.

- This effect could also be related to the interaction with inflammatory cytokines released after laser treatment. These considerations must be considered from the Authors. Not only physics but biological interactions of SO.

Did the Authors measure the proteins concentration in removed SOs?.

Response: Thank you very very much. The conclusion was made from the experimental in-vitro exposure of naïve unused SO sample to the green argon laser. However, you suggestion is very important and cannot be avoided. The biological factors may have critical effects on SO emulsification. We have tried to approach the biological effect by mixing the SO with aqueous extracted at the time of SO removal. The protein was not measured as the size of the SO was too small to perform enough physical and biological tests. We have amended this point to the limitations and modified the revised manuscript.

Comments from Reviewer #2:

Thank you for efforts in reviewing our manuscript.

1. Novel study combining in vivo and in vitro studies using advanced technology. The authors need to acknowledge that it is difficult to confirm based on single case the effect of silicone oil emulsification. For example, the eye that had argon Laser showed the most difference as concluded by the authors, but this eye could have had PVR or inflammation, more activity of the patient, more sun exposure or less complete oil fill, etc..These variables (inflammation, more activity of the patient, more sun exposure or less complete oil fill) need to be mentioned as drawbacks of the study besides the small number of patients. Otherwise this is a good start for larger studies.

Response: Thank you so much for your encouraging and respectful comment. We agree with your that important biological and environmental factors should be taken into consideration. Actually, some eyes that needed postoperative laser were more active and complicated eyes. However, the findings of in-vitro change of SO characteristics after exposure of unused SO sample to argon laser supported this suggestion. These drawbacks were added to the limitations. Thank you again and again.

Comments from Reviewer #3:

Thank you for efforts in reviewing our manuscript. Your comments and points are much appreciated and encouraging to us.

1. Statistical analysis is needed to prove the physical changes to silicone oil is related to the tested factors and avoid type I error. This is not possible with the current low number of samples. I believe more oil samples are needed to consolidate those observations.

Response: Thank you very much. Yes, we agree with your respectful comment. The cause for the small sample size the preciosity of extracted SO samples along with high-cost tests. However, we are working on a much larger sample size. This point was amended in the limitations. Thank you so much.

2. More details needed in the study design and more background knowledge. For example, background knowledge on FTIR would be of benefit.

Response: Thank you so much for your meaningful point. We have amended more background knowledge in the Methods.

3. I would advise on a more relevant literature review to publications with similar work.

Response: Thank you so much. We have elaborated more in the Discussion with more literature reviews.

4. The manuscript might as well benefit from language revisions.

Response: Thank you very much. Extensive language revisions were made. Thank you again.

Again, we thank the editor and reviewers for their constructive comments. We hope that we have sufficiently addressed their concerns.

Sincerely,

Authors

Attachments
Attachment
Submitted filename: Response_letter_final.docx
Decision Letter - Ayman Elnahry, Editor

PONE-D-24-26615R1The Influence of UV-visible light, microwave radiation, argon laser, heating and aging process on silicone oil utilized as intravitreal implants: Experimental exposure with clinical correlationPLOS ONE

Dear Dr. Al-Dwairi,

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.

Please submit your revised manuscript by Jan 02 2025 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,

Ayman Elnahry

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 Editor Comments:

Thanks for submitting your revised manuscript.

Unfortunately professional English language editing was not performed. The English language still needs extensive editing and correction of spelling mistakes. For example, one of your subtitles reads “partients and design”. I suggest to use a professional English language editor to improve the style of the manuscript.

[Note: HTML markup is below. Please do not edit.]

[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.

Revision 2

Academic Editor

PLOS ONE

Dear editor,

My self and the co-authors are pleased to resubmit the revised version of the manuscript entitled ‘The influence of UV-visible light, microwave radiation, argon laser, and heating and aging processes on silicone oil utilized as intravitreal implants: Experimental exposure with clinical correlation, ID: PONE-D-24-26615R1” to be considered for publication in PLOS ONE. The revised manuscript takes into consideration all editorial comments. Kindly find below a point-by-point response to those comments, along with an uploaded copy marked with MS track changes indicating changes to the manuscript.

Again and again, many thanks for our respectful editor and the editorial staff for their efforts. Your efforts are much appreciated and valuable and will be kept in heart

Editorial comments

Thank you so much for your efforts and time in improving this manuscript.

“Thanks for submitting your revised manuscript. Unfortunately professional English language editing was not performed. The English language still needs extensive editing and correction of spelling mistakes. For example, one of your subtitles reads “partients and design”. I suggest to use a professional English language editor to improve the style of the manuscript.”

Response: Thank you so much for your efforts and the comments. We have sent the manuscript for a professional English language editing service and we have uploaded the certificate. Thank you again

Journal Requirements

1. 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.

Response: Thanks so much. We have revised and modified the reference list. Furthermore, to cooperate with your efforts, we have included two references lists, one without software and one arranged with the software.

Again, we thank the editor and reviewers for their constructive comments. We hope that we have sufficiently addressed their concerns.

Sincerely,

Authors

Attachments
Attachment
Submitted filename: Response_letter_final.docx
Decision Letter - Ayman Elnahry, Editor

The influence of UV-visible light, microwave radiation, argon laser, and heating and aging processes on silicone oil utilized as intravitreal implants: Experimental exposure with clinical correlation

PONE-D-24-26615R2

Dear Dr. Al-Dwairi,

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,

Ayman Elnahry

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I thank the authors for completing the requested revisions.

Reviewers' comments:

Formally Accepted
Acceptance Letter - Ayman Elnahry, Editor

PONE-D-24-26615R2

PLOS ONE

Dear Dr. Al-Dwairi,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

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PLOS ONE Editorial Office Staff

on behalf of

Dr. Ayman Elnahry

Academic Editor

PLOS ONE

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